Effect of new type extrusion modification technology on supramolecular structure and in vitro glycemic release characteristics of starches with various estimated glycemic indices.
Nowadays, the highly effective modified technology to starch with various digestibility is gaining interest in food science. Here, the interactions between glycemic release characteristics and fine supramolecular structure of cassava (ECS), potato (EPS), jackfruit seed (EJFSS), maize (EMS), wheat (EWS), and rice starches (ERS) prepared with improved extrusion modification technology (IEMS) were investigated. The crystalline structures of all extruded cooking starches changed from the A-type to V-type. IEMS-treated cassava, potato, and rice starches had broken α-1.6-glycosidic amylopectin (long chains). The others sheared α-1.4-glycosidic amylopectin. The molecular weight, medium and long chain counts, and relative crystallinity decreased, whereas the number of amylopectin short chains increased. The glycemic index (GI) and digestive speed rate constant (k) of ECS, EPS, EJFSS, and EWS were improved compared to those of raw starch. Although EMS and ERS had degraded molecular structures, their particle morphology changed from looser polyhedral to more compact with less enzymolysis channels due to the rearrangement of side chain clusters of amylopectin, leading to enzyme resistance. The starch characteristics of IEMS-treated samples significantly differed. EPS had the highest amylose content, medium chains, long chains, and molecular weight but lowest GI, relative crystallinity, and k. ERS showed the opposite results. Thus, IEMS may affect starches with different GIs to varying degrees. In this investigation, we provide a basis for wider applications of conventional crop starch in the food industry corresponding to different nutrition audience.


Age- and sex-differences in the nitric oxide synthase expression and dopamine concentration in the murine model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
Parkinson's disease (PD) is an age- and sex-related neurodegenerative disorder of unknown aetiology. The involvement of nitric oxide synthase (NOS) in the etiopathogenesis of PD is quite well documented. We decided to examine changes in dopamine (DA) levels as well as iNOS, nNOS, eNOS mRNA and protein expression in the striatum of C57BL male and female (2- and 12-month old) mice in the course of PD-related neurodegeneration induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The significantly decreased level of DA was previously observed in male than in female, irrespective of age. In young mice the recovery of DA was significantly greater in female compared to male mice. On the contrary, both in male and female old animals the low concentration of DA was extended up to 21 days post MPTP injection. The increases in iNOS protein expression post MPTP intoxication occurred more rapidly in male (young and old) than in female mice. The pattern of changes in iNOS protein expression was also different in young versus aged mice. nNOS protein expression increased earlier in young male than young female mice. No changes were observed in eNOS expression. In conclusion, our results support the hypothesis of the involvement of iNOS and nNOS, but not eNOS in neurodegenerative processes. Our findings suggest that age- and sex-differences in DA concentration and iNOS expression as well as sex-differences of nNOS expression after intoxication may depend on the increased susceptibility of males as well as older animals to toxic effect of MPTP and aggravated process of recovery in old brains.


Asbestos-related radiographic findings among household contacts of workers exposed to Libby vermiculite: impact of workers' personal hygiene practices.
To explore the potential impact of worker hygiene by determining the prevalence of radiographic changes consistent with asbestos exposure among household contacts of workers exposed to Libby vermiculite that contained amphibole fibers. Workers and household contacts had chest radiographs and completed questionnaires regarding hygiene and potential exposure pathways. Participants included 191 household contacts of 118 workers. One household contact (0.5%) had localized pleural thickening, and three (1.6%) had irregular opacities at profusion category 1/0 or greater. Worker radiographs demonstrated pleural changes in 45% and irregular opacities at profusion category 1/0 or greater in 8%. Libby vermiculite-exposed workers demonstrated an elevated prevalence of pleural and interstitial chest radiographic changes. There was, however, no increased prevalence of similar changes among household contacts, likely because of personal hygiene measures taken by the majority of workers.


Pattern formation of the cone mosaic in the zebrafish retina: a cell rearrangement model.
In fish retinas, cone photoreceptor cells are arranged in two-dimensional regular patterns, called cone mosaics. In the zebrafish retina, four subtypes of cone cells, which are maximally sensitive to different wavelengths of light, appear in quasi-periodic patterns. The pattern formation mechanism is unknown. Here, I develop a mathematical model to examine whether cell adhesion can explain the formation of the zebrafish mosaic. I assume that the movement of differentiated cells is responsible for generating the pattern, and that the movement rate is modified by cell adhesion. The pattern is formed if the magnitudes of cell adhesion between cell types are chosen appropriately. I determine the conditions of cell adhesion for generating the pattern. I also compare this cell rearrangement model with a previously studied model in which the pattern is formed by transitions of cell fate. The condition for obtaining the focal pattern is looser in the cell rearrangement model than in the fate transition model.


[Biointegration properties of eyelid weight implants made of various materials (experimental study)].
Palpebral eyelid weight implants are currently considered as the gold standard method for lagophthalmos correction. Manufactured from different precious metals, they have both benefits and drawbacks. The article presents the results of an experimental morphological study of biointegration of different eyelid weight implants used for correction of paralytic lagophthalmos. To investigate biointegration properties of implants made of gold, platinum and platinum-gold alloy. The study enrolled 4 Chinchilla rabbits (8 eyelids). Palpebral implants manufactured of gold, platinum and platinum-gold alloy were placed into the eyelids of the experimental animals. The morphological examination was performed 1 and 6 months after the implantation using paraffin sections. Light microscopy revealed that the implant beds were surrounded by pronounced fibrovascular capsule of uneven thickness over the whole follow-up. The capsule formed after the placement of an implant made of gold and platinum alloy was more loose. However, the emerging connective tissue bridges of the capsule contributed to its immobilization in the tissues and lower risk of extrusion. No signs of an inflammatory and/or allergic reaction were observed in any of the cases. The obtained results show that implants made of a 90/10% platinum-gold alloy and 999.9 fine platinum have similar biointegration in terms of morphological features during 6 months of the follow-up period.


[Treatment of behavioral disorders in dementia with risperidone in psychogeriatric out-patients].
The atypical neuroleptic drug risperidone has been approved for the treatment of behavioural and psychological symptoms of dementia for more than three years in Germany. To assess the efficacy and tolerability of risperidone in general practice two open-label prospective studies were performed. In 7142 patients with dementia the treatment course with risperidone was examined over 6 resp. 8 weeks. Efficacy was evaluated by assessing the target symptoms agitation, aggression, sleep-wake-cycle disturbances, social withdrawal, suspiciousness, and delusion. Furthermore, the global impression was rated by the physician and the caregiver at the end of the study. The tolerability of risperidone was documented by monitoring blood pressure, heart rate, bodyweight, and adverse events. 6170 patients complied with the inclusion criteria for analysis. Risperidone achieved statistically significant improvements of behavioural symptoms at an average dose of 1,5 mg/d (90% of patients received < or = 2 mg/d). 92% of the patients showed a favourable treatment response as defined by a > or = 30% improvement of the total score of the target symptoms. This improvement was already apparent 2 and 3 weeks after the start of treatment, respectively. A subgroup analysis demonstrated statistically significant improvements of target symptoms with risperidone also in patients who had been pre-treated with other neuroleptics. The global impression of physician and caregiver was positive in over 90% of patients. Adverse events were seen in 309 of 6170 patients (5,7%). Risperidone was highly effective and well tolerated in the treatment of behavioural disturbances in dementia under routine conditions of general practice.


Androgens, progestins, and glucocorticoids induce follicle-stimulating hormone beta-subunit gene expression at the level of the gonadotrope.
FSH is produced by the pituitary gonadotrope to regulate gametogenesis. Steroid hormones, including androgens, progestins, and glucocorticoids, have all been shown to stimulate expression of the FSHbeta subunit in primary pituitary cells and rodent models. Understanding the molecular mechanisms of steroid induction of FSHbeta has been difficult due to the heterogeneity of the anterior pituitary. Immortalized LbetaT2 cells are a model of a mature gonadotrope cell and express the endogenous steroid receptor for each of the three hormones. Transient transfection of each receptor, along with ligand treatment, stimulates the mouse FSHbeta promoter, but induction is severely diminished using receptors that lack the ability to bind DNA, indicating that induction is likely through direct DNA binding. All three steroid hormones act within the first 500 bp of the FSHbeta promoter where six putative hormone response elements exist. The -381 site is critical for FSHbeta induction by all three steroid hormones, whereas the -197 and -139 sites contribute to maximal induction. Interestingly, the -273 and -230 sites are also necessary for androgen and progestin induction of FSHbeta, but not for glucocorticoid induction. Additionally, we find that all three receptors bind the endogenous FSHbeta promoter, in vivo, and specifically bind the -381 site in vitro, suggesting that the binding of the receptors to this element is critical for the induction of FSHbeta by these 3-keto steroid hormones. Our data indicate that androgens, glucocorticoids, and progestins act via their receptors to directly activate FSHbeta gene expression in the pituitary gonadotrope.


Blast colony-forming cells in myelodysplastic syndrome: decreased potential to generate erythroid precursors.
In vitro colony-forming abilities of highly purified primitive hematopoietic cells in eight cases of myelodysplastic syndrome (MDS) were studied using the blast cell colony assay. Blast cell colony formation from seven normal bone marrow (NBM) samples was studied in parallel. Blast cell colonies were formed in 7/8 cases of MDS, the numbers not significantly differing from those generated by NBM. In contrast the more mature hematopoietic progenitors (granulocyte-erythroid-macrophage-megakaryocyte colony-forming unit, CFU-GEMM; erythroid burst-forming units, BFU-E; granulocyte colony-forming units, CFU-G; eosinophilic colony-forming units, CFU-Eo) were severely depressed in numbers in MDS marrow. After replating of blast cell colonies in secondary cultures, colonies were obtained in 5/8 MDS cases. A marked difference was evident in the composition of the secondary colonies between MDS and normal marrow. Whereas secondary colonies derived from normal blast cell colonies consisted of about 45% of erythroid cells, MDS blast colonies generated mainly colonies of the granulocytic-monocytic lineage and no erythroid colonies. The normal quantitative level of CFU-blast progenitors in MDS in the context of their impaired ability to generate lineage specific progeny upon secondary plating suggests that the incompetence of maturation of MDS may reside in the CFU-blast progenitor cell being incapable of properly responding to growth factor stimulation.


[Clinical outcomes of total arterial off-pump coronary revascularization in patients with left ventricular dysfunction].
Objective: To compare the advantages and disadvantages of total arterial revascularization (TAR) and conventional off-pump coronary artery bypass (OPCAB) grafting in patients with left ventricular dysfunction (LVD). Methods: Between January 2008 and March 2015, 76 patients who were scheduled to undergo selective OPCAB were selected for cardiac surgery in Zhongshan Hospital, Fudan University. The left ventricular ejection fraction of enrolled patients was less than 35%. Among those patients, 38 patients in TAR group underwent total arterial OPCAB with bilateral internal mammary artery, left and/or right radial artery, and another 38 patients in control group underwent conventional OPCAB with left internal mammary artery and great saphenous vein. The clinical data of all patients were collected. The follow-up was performed within 36 months. Results: There was no significant difference in preoperative clinical data between the two groups (all P>0.05). Additionally, there was no significant difference in the application rate of internal mammary artery, positive inotropic drugs and intra-aortic balloon pump (IABP) use between the two groups (all P>0.05). The operation time of TAR group was longer than that of control group [(278.3±31.2) min vs (196.7±19.1) min, P<0.01]. There was no significant difference in perioperative mortality between the two groups (5.3% vs 7.9%, P=0.64). The volume of operative drainage and blood transfusion in TAR group increased significantly at 24 hours after operation [(895.0±236.2) ml vs (585.4±172.5) ml, (656.3±84.4) ml vs (433.3±62.9) ml, both P<0.01]. There was no significant difference in perioperative complications such as heart, kidney and lung failure between the two groups (all P>0.05). At 12 months after operation, there were no significant differences in survival rate, cardiac death rate, angina recurrence, myocardial infarction, re-treatment rate of revascularization, re-hospitalization rate from cardiac insufficiency, graft patency rate, cardiac function and echocardiographic data between the two groups (all P>0.05). From 24 to 36 months after operation, all the above indexes in TAR group were better than those in control group except for echocardiographic data (all P<0.05). Conclusions: For LVD patients, the early clinical efficacy of the two surgical methods is similar, but for the long-term outcomes, the whole arterial OPCAB operation is obviously superior. However, the shortcomings of total arterial OPCAB are that operative drainage and the use of blood products increased significantly after operation.


Energetic factors and seasonal changes in ovarian function in women from rural Poland.
Female mammals can optimize their fitness by temporal suppression of reproductive function in response to unfavorable environmental conditions. Since reproduction is energetically demanding for a human female, ovarian function is expected to be sensitive to factors influencing energy availability and metabolism. Dieting and exercise in women from industrial countries, and low-calorie diet and workload in women from developing countries, are often associated with ovarian suppression. This study shows that in Polish rural women seasonal changes in workload correlate with seasonal changes in indices of ovarian function (progesterone measured in saliva samples collected daily for six menstrual cycles for each subject). Mean levels of energy expenditure of the most work demanding weeks of the summer exceeded mean levels of energy expenditure during winter by 37%. Energy intake in this population was sufficient throughout the year. During the summer, when physical work was most intense, low values of progesterone levels were observed (178.2 pmol/L in July and 182.2 pmol/L in August), indicating ovarian suppression. Mean progesterone levels rose to 234.6 pmol/L in October when levels of energy expenditure were lower due to cessation of harvest-related activities. As indicated by several causal models tested through path analysis, energy expenditure was the only variable responsible for suppressed progesterone levels during the summer. Variables describing the nutritional status and energy balance did not correlate significantly with progesterone levels; neither body weight nor body fat or seasonal changes of these variables seem to influence ovarian function in this population. Thus work-related energy expenditure does not need to lead to negative energy balance in order to cause suppression of reproductive function in women.


New guidance on imaging tests for a range of chest pain scenarios.
New recommendations from the American College of Cardiology and the American College of Radiology offer guidance to emergency providers on which imaging tests to use in 20 different clinical scenarios involving chest pain. For each clinical scenario, an expert panel rated the appropriateness of a range of imaging modalities as rarely appropriate (R), may be appropriate (M), or appropriate (A). The guidelines are constructed to flow from the clinician's judgment as to the probable cause of the chest pain. The recommendations for each clinical scenario are condensed into tables that can be fashioned into notecards or a smartphone app for quick reference. Developers note that the guidelines will need to be revisited when high-sensitivity troponin tests are approved for use in the United States, as these newer-generation blood tests may negate the need for many imaging tests when patients present with chest pain.


Study of the causes and the results of treatment in infertile couples at Thammasat Hospital between 1999-2004.
To study the type, cause, pregnancy rate, and pregnancy outcome of infertile couple in Fertility Clinic of Thammasat Hospital, Thammasat University. The retrospective study was performed by reviewing the data of infertile couples attending the Fertility Clinic of Thammasat Hospital from 1999 until 2004. The data included age, type of infertility, duration, causes, treatments, and results of treatment of the infertile couples and excluded the data from the cancellation treatment cycles. One thousand seventy two infertile couples revealed 61.8% of primary infertility, 35.6% ofsecondary infertility, and 2.5% of incomplete data record. The overall duration of infertility was mostly between 1-4 years in 58.3%. The age of 65.9% of female partners and 61.2% of male partners were between 30-39 years. The causes of infertility were found in both partners (55.6%), only in male partners (19.4%), only in female partners (17.5%), in unexplained cause (4.7%), and in incomplete data group (2.8%). The causes of female infertility were endometriosis, tubal, ovulatory, uterine, endocrinnological, pelvic factors, and unexplained causes were found in 25.6%, 12.4%, 11.8%, 9.1%, 9.0%, 1.7%, and 25.7% of cases respectively. The causes of male infertility were terato, oligoasthenoterato, asthenoterato, astheno, oligoterato, oligo, asthenooligo, azoospermia, and unexplained causes found in 25.4%, 14.4%, 12%, 2.0%, 1.0%, 0.4%, 0.3%, 4.5%, and 24.2%, respectively. The pregnancy rate of IUI was 14.8% of which 95.5% succeeded in three attempts, where those of IVF, ICSI and ICSI- PESA were 32.3%, 28.0%, and 35.3%, respectively. The outcomes of pregnancy from IUI were 71.6% singleton, 1.5% twins, 1.5% triplets, 19.4% abortion, and 6.0% ectopic pregnancy. The outcomes of pregnancy from IVF were 30% singleton, 20% twins, 40% abortion, and 10% ectopic pregnancy. The outcomes of pregnancy from ICSI were 56.5% singleton, 17.4% twins, 13% triplets, and 13% abortion. Finally, the outcomes of pregnancy from ICSI-PESA were 66.7% singleton, 16.7% twins, and 16.7% abortion. Primary infertility cases were more common than secondary infertility cases. More than half of the infertile couples causes were from both male and female partners. The causes of male and female factors were similar to other reports, such as abnormal semen analysis, endometriosis, tubal factor and ovulatory factor The pregnancy rate and pregnancy outcome of IUI, IVF and ICSI were comparable with the other reports.


Mast cells and biogenic amines in radiation-induced pulmonary fibrosis.
Sprague-Dawley rats were exposed to a single X-ray dose of 30 Gy over the lungs and examined at 1-wk intervals during the following 3 to 8 wk. Mast cells were counted after specific staining with toluidine blue at a low pH and the mast-cell amines, histamine (Hi) and serotonin (5-HT), were measured using high-performance liquid chromatography. Irradiation induced pneumonitis followed by pulmonary mast-cell hyperplasia and progressive fibrosis 4 to 8 wk after irradiation. By week 4, immature-looking mast cells with a few granules started to appear, followed by a gradual increase in mast cells that reached very high levels after 8 wk, up to 40 to 200 times the normal. The pulmonary Hi and 5-HT content increased concomitantly from 6 and 1 micrograms/g to a maximum of 200 and 18 micrograms/g, respectively. These high levels of amine content and mast-cell densities greatly exceed those of any normal tissue. There was a strong correlation between the Hi and 5-HT content in both normal (r = 0.87) and irradiated (r = 0.93) lung tissue, as well as between the mast-cell density and amine content after irradiation (r = 0.86), thereby indicating that both amines derived from mast cells. The Hi/5-HT quotients were much lower in both normal and irradiated lung tissue (5 and 9, respectively) than in other tissues where these amines are stored in mast cells, or in isolated peritoneal mast cells (43). This relatively higher 5-HT content in pulmonary mast cells suggests that this amine performs a specific function in the lung.


Cinacalcet administration by gastrostomy tube in a child receiving peritoneal dialysis.
A 2-year-old male with chronic kidney disease with secondary hyperparathyroidism developed hypercalcemia while receiving calcitriol, without achieving a serum parathyroid hormone concentration within the goal range. Cinacalcet 15 mg (1.2 mg/kg), crushed and administered via gastrostomy tube, was added to the patient's therapy. This therapy was effective in achieving targeted laboratory parameters in our patient despite instructions in the prescribing information that cinacalcet should always be taken whole.


Estimating Model-Based Oral Reading Fluency: A Bayesian Approach.
Oral reading fluency (ORF), used by teachers and school districts across the country to screen and progress monitor at-risk readers, has been documented as a good indicator of reading comprehension and overall reading competence. In traditional ORF administration, students are given one minute to read a grade-level passage, after which the assessor calculates the words correct per minute (WCPM) fluency score by subtracting the number of incorrectly read words from the total number of words read aloud. As part of a larger effort to develop an improved ORF assessment system, this study expands on and demonstrates the performance of a new model-based estimate of WCPM based on a recently developed latent-variable psychometric model of speed and accuracy for ORF data. The proposed method was applied to a data set collected from 58 fourth-grade students who read four passages (a total of 260 words). The proposed model-based WCPM scores were also evaluated through a simulation study with respect to sample size and number of passages read.


Vitrification of preimplantation stages of mouse embryos.
Three vitrification solutions (VS) namely VS1 (5.5 mol ethylene glycol l-1 and 2.5 mol glycerol l-1), VS11 (6.0 mol ethylene glycol l-1 and 1.8 mol glycerol l-1) and VS14 (5.5 mol ethylene glycol l-1 and 1 mol sucrose l-1) were tested for cryopreservation by vitrification of all developmental stages of mouse preimplantation embryos. In these experiments all preparative work was at room temperature (25 degrees C). VS1 was toxic to embryos at and earlier than the eight-cell stage, whereas VS11 was toxic to the four-cell and earlier stages. VS14 was the least toxic VS. All three VS resulted in good viability of vitrified Swiss Outbred day-4 embryos (morulae, early blastocysts and blastocysts) in vitro and vitrification with VS14 resulted in no loss of viability in all preimplantation stage Swiss Outbred embryos except one-cell embryos. One-cell F1 embryos were vitrified successfully with VS14 and VS1. The minimal equilibration time essential for successful vitrification of embryos suggests that concentration of the intracellular solutes by dehydration has a major role in establishing conditions conducive to intracellular vitrification. Studies in vitro suggested that sucrose dilution was not necessary in the removal of cryoprotectant from vitrified eight-cell and day-4 mouse embryos but, in contrast, development of vitrified day-4 embryos in vivo was better when the VS was diluted with sucrose.(ABSTRACT TRUNCATED AT 250 WORDS)


Application of flow cytometry to monitor antibody levels in ABO incompatible kidney transplantation.
Current methods of measuring ABO antibody levels based on the hemagglutination (HA) titers have the disadvantages of relatively poor reproducibility and do not offer fine discrimination of antibody concentration. We therefore developed a simple and rapid method of measuring ABO antibody levels using flow cytometry (FC). For validation, we analyzed plasma samples from 79 blood donors. Both IgM and IgG were detected and measured with IgG essentially restricted blood group O donors. Forty-two successive samples were collected from a patient with blood group O undergoing antibody removal and subsequent transplantation from a group A2 donor and tested by both HA and FC. Changes in IgG measured by FC (relative median fluorescence) correlated well with HA titers and importantly rejection episodes were preempted by a rising relative median fluorescence. The method allowed quantitative discrimination in the range of antibody levels relevant to ABO incompatible transplantation and has the advantages over HA of objective measurement and reproducibility.


EndoS, a novel secreted protein from Streptococcus pyogenes with endoglycosidase activity on human IgG.
Streptococcus pyogenes is an important human pathogen that selectively interacts with proteins involved in the humoral defense system, such as immunoglobulins and complement factors. In this report we show that S.pyogenes has the ability to hydrolyze the chitobiose core of the asparagine-linked glycan on immuno globulin G (IgG) when bacteria are grown in the presence of human plasma. This activity is associated with the secretion of a novel 108 kDa protein denoted EndoS. EndoS has endoglycosidase activity on purified soluble IgG as well as IgG bound to the bacterial surface. EndoS is required for the activity on IgG, as an isogenic EndoS mutant could not hydrolyze the glycan on IgG. In addition, we show that the secreted streptococcal cysteine proteinase SpeB cleaves IgG in the hinge region in a papain-like manner. This is the first example of an endoglycosidase produced by a bacterial pathogen that selectively hydrolyzes human IgG, and reveals a novel mechanism which may contribute to S.pyogenes pathogenesis.


Rogers v Commissioner: denouement of an important right-to-refuse-treatment case.
After almost 9 years of passage through various courts, the right-to-refuse-treatment case of Rogers v Commissioner of Mental Health has reached its final resolution in Massachusetts. The author outlines the substantive rulings of this decision in contemporary context, its importance for clinicians in general, and its implications for practice. He proposes that the case presents many problematic elements that could possibly impede good clinical care.


Frank H. Netter, M.D. (1906-1991): the artist and his legacy.
The renowned medical illustrator Frank H. Netter, M.D., was born on 25 April 1906 in Brooklyn, NY, and died on 17 September 1991 in New York, NY, at the age of 85. In his professional career, Dr. Netter painted over 4,000 medical illustrations, many of which became the center pieces of over 250 issues of Clinical Symposia and were compiled in the 13 volume set of The CIBA Collection of Medical Illustrations. Two years prior to his death, the Atlas of Human Anatomy was published, considered by many to be Dr. Netter's crowning achievement. The Atlas rapidly became the most widely used atlas of anatomy in American medical schools and currently is published in 16 languages. Netter's impressive career as an illustrator and his unique style and legacy to medical education are summarized briefly in this review.


Interaction of the sugars trehalose, maltose and glucose with a phospholipid bilayer: a comparative molecular dynamics study.
Molecular dynamics simulations are used to investigate the interaction of the sugars trehalose, maltose, and glucose with a phospholipid bilayer at atomic resolution. Simulations of the bilayer in the absence or in the presence of sugar (2 molal concentration for the disaccharides, 4 molal for the monosaccharide) are carried out at 325 and 475 K. At 325 K, the three sugars are found to interact directly with the lipid headgroups through hydrogen bonds, replacing water at about one-fifth to one-quarter of the hydrogen-bonding sites provided by the membrane. Because of its small size and of the reduced topological constraints imposed on the hydroxyl group locations and orientations, glucose interacts more tightly (at identical effective hydroxyl group concentration) with the lipid headgroups when compared to the disaccharides. At high temperature, the three sugars are able to prevent the thermal disruption of the bilayer. This protective effect is correlated with a significant increase in the number of sugar-headgroups hydrogen bonds. For the disaccharides, this change is predominantly due to an increase in the number of sugar molecules bridging three or more lipid molecules. For glucose, it is primarily due to an increase in the number of sugar molecules bound to one or bridging two lipid molecules.


Changes in the Composition and Synthesis of Proteins in Cellular Membranes of Echinochloa crus-galli (L.) Beauv. Seeds during the Transition from Dormancy to Germination.
The effect of alcohols which stimulate or have no effect on germination on the composition and synthetic pattern of proteins in the cellular membranes of Echinochloa crus-galli (L.) Beauv. seeds was studied. Imbibition of dry seeds was accompanied by an increase in the synthesis of proteins and by synthesis of new proteins in their intracellular membranes. The transition of the seeds from a dormant to a nondormant state was associated with synthesis of specific proteins and a decrease in content of others in the plasma membrane. The synthesis of a 23 kilodalton protein was strongly increased upon release from dormancy. The changes in the pattern of protein synthesis were not directly associated with the beginning of germination. The results suggest that the plasma membrane constitutes the first site in the seed cells, at which the stimulus from external factors affecting seed dormancy is detected.


The roles of motivation, anxiety and learning strategies in online Chinese learning among Thai learners of Chinese as a foreign language.
The impact of motivation, anxiety and learning strategies on the achievement of foreign language proficiency has been widely acknowledged in the context of traditional offline classroom settings. However, this issue has not been extensively documented in relation to online learning, which has become the predominant form of language learning during the period of the COVID-19 pandemic. The current study was conducted to investigate the relative prediction of motivation, anxiety and learning strategies for second language achievement among 90 Thai adult learners of Chinese as a foreign language (CFL) who took online Chinese courses. The participants completed a questionnaire dealing with motivation, anxiety, learning strategies, and their Chinese proficiency was measured by self-report and a Chinese vocabulary size test. A series of hierarchical regression analyses revealed two major findings. First, anxiety emerged as the most stable factor for the participants' CFL achievement, followed by learning strategies and motivation. Second, motivation, anxiety and learning strategies only significantly predicted the participants' self-rated Chinese language proficiency, but not their performance on the Chinese vocabulary size test. The overall results indicate the relative importance of motivation, anxiety and learning strategies to Chinese language learning in the online environment and suggest different measures of CFL achievement may lead to different research findings. The general findings were of theoretical and pedagogical significance for understanding and addressing individual differences factors in online language learning.


[Antibacterial effects of silver ions: effect on gram-negative bacteria growth and biofilm formation].
Minimal inhibiting AgNO3 concentration (MICs) in the gram-negative bacteria Escherichia coli K12, Serratia proteamaculans 94, and Serratia liquefaciens MG1 were found to be on the average within the range of 0.075-0.3 microg/ml, and for Pseudomonas aeruginosa PAO1 and P. chlororaphis 449, 0.15-0.3 microg/ml. Biofilm formation in Escherichia coli AB1157 and S. Proteamaculans 94 was completely inhibited at an AgNO3 concentration of 0.3 microg/ml, and in Pseudomonas aeruginosa PAO1, at 0.6 microg/mlAgNO3. Mutations in E. coli genes encoding for global regulators of gene expression, such as sigma S and sigma N subunits of RNA polymerase, catabolite repression protein CRP, and Lon protease, had no marked effect on the sensitivity of cells to silver. The wild-type E. coli strains and strains deficient in excision repair (uvrA, uvrB), SOS-repair or recombination (recA, lexA, recBC, recF mutants) did not differ in their silver sensitivity. This suggests that the sensitivity of bacteria to silver does not correlate with DNA lesions that could be repaired by these repair and recombination systems. E. coli mutant strains deficient in porins OmpF or OmpC, were 3-4-fold more resistant to silver ions as compared with the wild-type strain. Experiments with pME6863 plasmid harboring the gene of N-acyl-homoserine lactonase AiiA demonstrated that Quorum Sensing regulation (QS) did not participate in the control of S. proteamaculans 94 and P. chlororaphis 449 silver sensitivity. The same conclusion was drawn from the comparison of AgNO3 MICs for the S. liquefaciens wild-type strain and a mutant strain deficient in QS.


[Squamous cell carcinoma of the head and neck and pulmonary cancer. Report of 50 cases].
Association of a squamous cell carcinoma of the head and neck and a pulmonary cancer is frequent: prevalence is about 5 to 10 percent. The purpose of this study was to present the survival analysis of 50 patients, previously treated for a squamous cell carcinoma of the head and neck, and then treated for a pulmonary cancer between 1979 and 1996. Four patients were excluded from the analysis. Five pulmonary cancers were synchronous with the head and neck cancer, 41 were metachronous. Metachronous pulmonary cancer was asymptomatic in 87 percent and the mean interval between the two cancers was 53 months. Surgery was performed for every pulmonary cancer. Operative mortality was 11 percent. The overall 5-year survival rate was 25%. Survival rates were linked with the T and N stages of the pulmonary cancer: 46% for T1, 13% for T2 and 0% for T3 and T4, 67% for N0 ans 0% for N1-3. Indications for surgical treatment of synchronous and metachronous pulmonary cancers are discussed.


Angiotensin II and Na+/H+ exchange in human blood platelets.
Human blood platelets have a high potency for Na+/H+ exchange activity; they also bear receptors for angiotensin II (Ang II). To explore the effect of Ang II on the exchange, we have used a fluorimetric analysis capable of detecting cytoplasmic changes of 0.01 pH units in platelets, together with an Ang II preparation which has been proven to be effective as a vasoconstrictor. Thrombin and adenosine diphosphate (ADP) affected Na+/H+ exchange, but Ang II did not affect Na+/H+ exchange for a wide range of concentrations and experimental conditions. It is concluded that in contrast to its function in vascular smooth muscle cells, Ang II apparently does not play a role in the regulation of Na+/H+ exchange in human blood platelets.


Fabrication of nanostructured transmissive optical devices on ITO-glass with UV1116 photoresist using high-energy electron beam lithography.
High-energy electron beam lithography for patterning nanostructures on insulating substrates can be challenging. For high resolution, conventional resists require large exposure doses and for reasonable throughput, using typical beam currents leads to charge dissipation problems. Here, we use UV1116 photoresist (Dow Chemical Company), designed for photolithographic technologies, with a relatively low area dose at a standard operating current (80 kV, 40-50 μC cm-2, 1 nAs-1) to pattern over large areas on commercially coated ITO-glass cover slips. The minimum linewidth fabricated was ∼33 nm with 80 nm spacing; for isolated structures, ∼45 nm structural width with 50 nm separation. Due to the low beam dose, and nA current, throughput is high. This work highlights the use of UV1116 photoresist as an alternative to conventional e-beam resists on insulating substrates. To evaluate suitability, we fabricate a range of transmissive optical devices, that could find application for customized wire-grid polarisers and spectral filters for imaging, which operate based on the excitation of surface plasmon polaritons in nanosized geometries, with arrays encompassing areas ∼0.25 cm2.


Evidence for BLM and Topoisomerase IIIalpha interaction in genomic stability.
The genomic instability of persons with Bloom's syndrome (BS) features particularly an increased number of sister-chromatid exchanges (SCEs). The primary cause of the genomic instability is mutation at BLM, which encodes a DNA helicase of the RecQ family. BLM interacts with Topoisomerase IIIalpha (Topo IIIalpha), and both BLM and Topo IIIalpha localize to the nuclear organelles referred to as the promyelocytic leukemia protein (PML) nuclear bodies. In this study we show, by analysis of cells that express various deletion constructs of green fluorescent protein (GFP)-tagged BLM, that the first 133 amino acids of BLM are necessary and sufficient for interaction between Topo IIIalpha and BLM. The Topo IIIalpha-interaction domain of BLM is not required for BLM's localization to the PML nuclear bodies; in contrast, Topo IIIalpha is recruited to the PML nuclear bodies via its interaction with BLM. Expression of a full-length BLM (amino acids 1-1417) in BS cells can correct their high SCEs to normal levels, whereas expression of a BLM fragment that lacks the Topo IIIalpha interaction domain (amino acids 133-1417) results in intermediate SCE levels. The deficiency of amino acids 133-1417 in the reduction of SCEs was not explained by a defect in DNA helicase activity, because immunoprecipitated 133-1417 protein had 4-fold higher activity than GFP-BLM. The data implicate the BLM-Topo IIIalpha complex in the regulation of recombination in somatic cells.


Achieving irreducibility of the Markov chain Monte Carlo method applied to pedigree data.
Markov chain Monte Carlo (MCMC) methods have been explored by various researchers as an alternative to exact probability computation in statistical genetics. The objective is to simulate a Markov chain with the desired equilibrium distribution. If the transition kernel is aperiodic and irreducible, then convergence to the equilibrium distribution is guaranteed; realizations of the Markov chain can thus be used to estimate desired probabilities. Aperiodicity is easily satisfied, but, although it has been shown that irreducibility is satisfied for a diallelic locus, reducibility is a potential problem for a multiallelic locus. This is a particularly serious problem in linkage analysis, because multiallelic markers are much more informative than diallelic markers and thus highly preferred. In this paper, the authors propose a new algorithm to achieve irreducibility of the Markov chain of interest by introducing an irreducible auxiliary chain. The irreducibility of the auxiliary chain is obtained by assigning positive probabilities to a small subset of the genotypic configurations inconsistent with the data, to bridge the gap between the irreducible sets.


[Multivariate analysis for the understanding of typical diabetic hemostasis criteria. 2. Prevalent thrombocytic markers].
Various thrombocyte functions and metabolic criteria were investigated in 309 test persons, among them 198 Patients affected with diabetes mellitus, 67 of type I and 131 of type II as well as 111 healthy control persons. From the variety of these factors an optimal amount was determined by means of the statistical method of multivariance analysis separating both types of diabetes and healthy control persons. In addition to haemoglobin A1 concentration, thrombocyte parameters have been found together with the degree of capillary fragility, adrenalin-induced aggregation, platelet aggregation test and clot retraction, which allow individuals to be assigned diagnostically to various groups of test persons. Thus, thrombocyte functions found in both types of diabetes and normal persons exhibit differences which may contribute to a diagnostic classification.


Early detection of bladder dysfunction following posterior urethral valves ablation.
Urinary incontinence following Posterior Urethral Valves (PUV) ablation has been attributed in the past to sphincter injury, but it is nowadays accepted that bladder dysfunction (BD) plays a determinant role. In order to assess BD evolution, we have evaluated, from 1982 to 1994, 48 boys with PUV by urodynamics (UD) studies. Age of the patients ranged from 10 months to 15 years. A total of 65 examinations were performed. We considered four groups: 0-3 years; 4-7 years; 8-12 years and > 12 years. Uninhibited detrusor contractions (instability), end filling pressure (EFP), bladder capacity and voiding detrusor pressure were evaluated in order to assess the presence of BD distinguishing it in: hypercontractility, hypocontractility and low-compliant bladder. The results collected confirm a high percentage of BD in PUV boys (71%) and the evolution of hypercontractility versus hypocontractility in 60% of patients considered.


A practical guide to nitrate use.
Nitrate preparations are useful in the treatment of acute and chronic angina, acute and chronic congestive heart failure, and acute myocardial infarction. Development of tolerance is best managed by providing a nitrate-free interval, thus avoiding continuous drug levels. This interval probably should be 10 to 12 hours with use of a transdermal patch. Nitrate treatment of the elderly may require lower doses to avoid hypotension.


Real-world treatment patterns and clinical outcomes in patients with AML unfit for first-line intensive chemotherapy.
Acute myeloid leukemia (AML) predominantly affects the elderly, and prognosis declines with age. Induction chemotherapy plus consolidation therapy is standard of care for fit patients; options for unfit patients include hypomethylating agents (HMA), low-dose cytarabine (LDAC), targeted therapies, and best supportive care (BSC). This retrospective chart review evaluated clinical outcomes in unfit patients with AML who initiated first-line treatment or BSC 01/01/2015-12/31/2018. Overall survival (OS), progression-free survival (PFS), time-to-treatment failure (TTF), and response rates were assessed. Of 1762 patients, 1310 received systemic therapies: 809 HMA, 199 LDAC, and 302 other therapies; 452 received BSC. Median OS was 9.9, 7.9, 5.4, and 2.5 months for HMA, LDAC, other, and BSC, respectively. Median PFS was 7.5, 5.3, 4.1, and 2.1 months for HMA, LDAC, other, and BSC, respectively; median TTF was 4.9, 2.1, 2.2, and 2.1 months, respectively. Our findings highlight the unmet need for novel therapies for unfit patients.


Predicting high risk of exacerbations in bronchiectasis: the E-FACED score.
Although the FACED score has demonstrated a great prognostic capacity in bronchiectasis, it does not include the number or severity of exacerbations as a separate variable, which is important in the natural history of these patients. Construction and external validation of a new index, the E-FACED, to evaluate the predictive capacity of exacerbations and mortality. The new score was constructed on the basis of the complete cohort for the construction of the original FACED score, while the external validation was undertaken with six cohorts from three countries (Brazil, Argentina, and Chile). The main outcome was the number of annual exacerbations/hospitalizations, with all-cause and respiratory-related deaths as the secondary outcomes. A statistical evaluation comprised the relative weight and ideal cut-off point for the number or severity of the exacerbations and was incorporated into the FACED score (E-FACED). The results obtained after the application of FACED and E-FACED were compared in both the cohorts. A total of 1,470 patients with bronchiectasis (819 from the construction cohorts and 651 from the external validation cohorts) were followed up for 5 years after diagnosis. The best cut-off point was at least two exacerbations in the previous year (two additional points), meaning that the E-FACED has nine points of growing severity. E-FACED presented an excellent prognostic capacity for exacerbations (areas under the receiver operating characteristic curve: 0.82 for at least two exacerbations in 1 year and 0.87 for at least one hospitalization in 1 year) that was statistically better than that of the FACED score (0.72 and 0.78, P<0.05, respectively). The predictive capacities for all-cause and respiratory mortality were 0.87 and 0.86, respectively, with both being similar to those of the FACED. E-FACED score significantly increases the FACED capacity to predict future yearly exacerbations while maintaining the score's simplicity and prognostic capacity for death.


George Mandler (1924-2016).
Presents an obituary for George Mandler, who died in London on May 6, 2016 at the age of 91. Mandler was one of the pioneers of the cognitive revolution in psychology. He was instrumental in moving the study of human learning from notions based largely on associations to a view of memory as an organized, nested hierarchical structure. Mandler was also a major proponent of the dual-process theory of recognition memory, in which general feelings of familiarity are distinguished from the context-rich experience of recollection. He brought the study of emotion into prominence, suggesting how emotion and cognition are related. Finally, he repatriated the concept of consciousness from its intellectual exile under behaviorism, stating boldly in 1975 that the construct was respectable, useful, and probably necessary. Mandler edited the Psychological Review from 1970 to 1976, chaired the Governing Board of the Psychonomic Society, and was president of APA Divisions 1 (General Psychology) and 3 (Experimental Psychology and Cognitive Science). (PsycINFO Database Record


Identification and characterization of a novel peptide ligand of epidermal growth factor receptor for targeted delivery of therapeutics.
Epidermal growth factor receptor (ErbB1, EGFR) is overexpressed in a variety of human cancer cells. It has been considered as a rational target for drug delivery. To identify novel ligands with specific binding capabilities to EGFR, we screened a phage display peptide library and found an enriched phage clone encoding the amino acid sequence YHWYGYTPQNVI (designated as GE11). Competitive binding assay and Scatchard analysis revealed that GE11 peptide bound specifically and efficiently to EGFR with a dissociation constant of approximately 22 nM, but with much lower mitogenic activity than with EGF. We showed that the peptides were internalized preferentially into EGFR highly expressing cells, and they accumulated in EGFR overexpressing tumor xenografts after i.v. delivery in vivo. In gene delivery studies, GE11-conjugated polyethylenimine (PEI) vectors were less mitogenic, but still quite efficient at transfecting genes into EGFR highly expressing cells and tumor xenografts. Taken together, GE11 is a potentially safe and efficient targeting moiety for selective drug delivery systems mediated through EGFR.


Strategies for repeat ablation for atrial fibrillation: A multicentre comparison of nonpulmonary vein versus pulmonary vein target ablation.
Approximately 18% of patients with atrial fibrillation (AF) undergo a repeat ablation within 12 months after their index ablation. Despite the high prevalence, comparative studies on nonpulmonary vein (PV) target strategies in repeat AF ablation are scarce. Here, we describe 12 months efficacy of non-PV and PV target ablations as a repeat ablation strategy. A multicentre retrospective, descriptive study was conducted with data of 280 patients who underwent repeat AF ablation. The ablation strategy for repeat ablation was at the operators' discretion. Non-PV target ablation (n = 140) included PV reisolation, posterior wall isolation, mitral line, roofline, and/or complex fractionated atrial electrogram ablation. PV target ablation (n = 140), included reisolation and/or wide atrium circumferential ablation. Patients' demographics and rhythm outcomes during 12 months follow-up were analyzed. At 12 months, more atrial tachyarrhythmias were observed in the non-PV target group (48.6%) compared to the PV target group (29.3%, p = .001). Similarly, a significantly higher AF and atrial tachycardia (AT) recurrence rate was observed after non-PV target ablation compared to PV target ablation (36.4% vs. 22.1% and 22.9% vs. 10.7%). After adjustment, a significantly higher risk of AT recurrence remained in the non-PV target group. Both groups significantly de-escalated antiarrhythmic drug use; de-escalation was more profound after PV target ablation. Patients with isolated PVs during non-PV target ablation had a significantly higher risk for AF recurrence than those with reconnected PVs. Compared to PV target ablation, non-PV target repeat ablation did not improve outcomes after 12 months and was independently associated with an increased risk for AT recurrences.


Clinical antibiotic-resistance plasmids have small effects on biofilm formation and population growth in Escherichia coli in vitro.
Antimicrobial resistance (AR) mechanisms encoded on plasmids can affect other phenotypic traits in bacteria, including biofilm formation. These effects may be important contributors to the spread of AR and the evolutionary success of plasmids, but it is not yet clear how common such effects are for clinical plasmids/bacteria, and how they vary among different plasmids and host strains. Here, we used a combinatorial approach to test the effects of clinical AR plasmids on biofilm formation and population growth in clinical and laboratory Escherichia coli strains. In most of the 25 plasmid-bacterium combinations tested, we observed no significant change in biofilm formation upon plasmid introduction, contrary to the notion that plasmids frequently alter biofilm formation. In a few cases we detected altered biofilm formation, and these effects were specific to particular plasmid-bacterium combinations. By contrast, we found a relatively strong effect of a chromosomal streptomycin-resistance mutation (in rpsL) on biofilm formation. Further supporting weak and host-strain-dependent effects of clinical plasmids on bacterial phenotypes in the combinations we tested, we found growth costs associated with plasmid carriage (measured in the absence of antibiotics) were moderate and varied among bacterial strains. These findings suggest some key clinical resistance plasmids cause only mild phenotypic disruption to their host bacteria, which may contribute to the persistence of plasmids in the absence of antibiotics.


Higher Aminopeptidase Activity Determined by Electroosmotic Push-Pull Perfusion Contributes to Selective Vulnerability of the Hippocampal CA1 Region to Oxygen Glucose Deprivation.
It has been known for over a century that the hippocampus, the center for learning and memory in the brain, is selectively vulnerable to ischemic damage, with the CA1 being more vulnerable than the CA3. It is also known that leucine enkephalin, or YGGFL, is neuroprotective. We hypothesized that the extracellular hydrolysis of YGGFL may be greater in the CA1 than the CA3, which would lead to the observed difference in susceptibility to ischemia. In rat organotypic hippocampal slice cultures, we estimated the Michaelis constant and the maximum velocity for membrane-bound aminopeptidase activity in the CA1 and CA3 regions. Using electroosmotic push-pull perfusion and offline capillary liquid chromatography, we inferred enzyme activity based on the production rate of GGFL, a natural and inactive product of the enzymatic hydrolysis of YGGFL. We found nearly 3-fold higher aminopeptidase activity in the CA1 than the CA3. The aminopeptidase inhibitor bestatin significantly reduced hydrolysis of YGGFL in both regions by increasing apparent Km. Based on propidium iodide cell death measurements 24 h after oxygen-glucose deprivation, we demonstrate that inhibition of aminopeptidase activity using bestatin selectively protected CA1 against delayed cell death due to oxygen-glucose deprivation and that this neuroprotection occurs through enkephalin-dependent pathways.


Case report: a 10-year-old girl with primary hypoparathyroidism and systemic lupus erythematosus.
Objectives Hypoparathyroidism is a rare disease in children that occurs as a result of autoimmune destruction of the parathyroid glands, a defect in parathyroid gland development or secondary to physical parathyroid gland disturbance. Typical symptoms of hypoparathyroidism present as hypocalcaemia and hyperphosphatemia due to decreased parathyroid hormone secretion and may lead to nerve and muscles disturbances resulting in clinical manifestation of tetany, arrhythmias and epilepsy. Currently, there is no conventional hormone replacement treatment for hypoparathyroidism and therapeutic approaches include normalising mineral levels using an oral calcium supplement and active forms of vitamin D. Case presentation We present the case of a 10-year-old girl with primary hypoparathyroidism who had no prior history of autoimmune disorders, but who subsequently developed systemic lupus erythematosus.


Dysphagia management in Parkinson's disease: Comparison of the effect of thickening agents on taste, aroma, and texture.
Dysphagia is a frequent symptom in Parkinson's disease (PD). Thickening liquids facilitates safe swallowing, however, low treatment compliance is a major issue, due to patients' dislike of thickened liquids. Some studies suggest a negative impact of gum-based thickeners, currently most used in clinical practice, on sensory properties compared to starch-based thickeners. This has not yet been investigated in PD. This study's aim was to compare taste, texture, and aroma of gum-based and starch-based thickened soups in participants with PD. Gum-based resource thicken up clear (RTUC) and starch-based kitchen products potato starch (PS) and quinoa flour (QF) were evaluated in broccoli soup. Texture, aroma, and taste were characterized by rheology, volatile, and sensory profiling. Thickened soups were evaluated in participants with PD and controls through a paired comparison test. Reduced release of 61.4%, 46.2%, and 38.5% of volatiles was observed after thickening with RTUC, PS, and QF, respectively. Overall taste intensity was reduced in RTUC- and PS-thickened soup, respectively. Taste and aroma of PS-thickened soup were considered more intense by 70.3% and 63.8% of all participants, respectively (n = 36 PD, n = 41 controls), 56.3% preferred the PS-thickened soup's texture . Taste and aroma of QF-thickened soup were considered more intense by 68.1% and 65.6% of all participants, respectively (n = 47 PD, n = 31 controls), 58.0% preferred the QF-thickened soup's texture. Starch-based thickeners demonstrated higher taste and aroma intensity. However, volatile and sensory profiling demonstrated reduced taste and aroma in all thickeners. Combining kitchen products with flavor enhancers may increase palatability of thickened beverages.


Cues to deception in context: response latency/gaps in denials and blame shifting.
Over 40 years of work on lying in psychology and communication has investigated numerous 'cues to deception'- the subtle signals people show when they are lying. One of these cues to deception is 'response latency' or the gap that occurs between questions and the lying response. The current investigation uses the methodology of conversation analysis to re-consider the question of response latency in the context of lying. Drawing on data from two naturalistic sources, the television shows COPS and the Jeremy Kyle Show, this investigation analyses response latencies in order to show the regular organization of gaps between turns in both lies and non-lies. The current investigation demonstrates that in blame shifting turns which are lies, any gaps between turns result from a display of upcoming 'trouble', rather than being related to lying per se. The investigation highlights the need to analyse lies in the contexts in which they are told, taking prior and subsequent talk into account.


Congenital and evolving vascular disorders associated with cutaneous hemangiomas: case report.
Conventional arteriography in an 11-month-old boy with cardiopathy, aortic arch coarctation and haemangiomas showed the absence of the right internal carotid and vertebral arteries, hypertrophy of the right external carotid artery, with enlargement of the internal maxillary and ophthalmic arteries that supplied the right cerebral hemisphere. An MRI study showed an infarcted area in the posterior zone of the left cerebral hemisphere vascularised by the middle cerebral artery that was caused by a thrombosis during a severe bout of gastroenteritis. MRA studies performed at 16 and 23 years of age revealed progressive narrowing of the left carotid and vertebral arteries, persistence of the proatlantal and trigeminal arteries, and poor cerebral vascularisation that, at adult age, was entirely supplied through collateral arteries, branches of both external carotids, the presence of unilateral duplication of the vertebral arteries and ascending pharyngeal artery.


[TRPV1: an important molecule involved in the peripheral sensitization during chronic pain and central pain modulation].
As chronic pain is a severe problem in clinics, study of the mechanisms of chronic pain and development of novel analgesic agents is of significance. In the past decade, our lab completed a series of studies on the regulatory mechanisms of functional sensitization and membrane trafficking of transient receptor potential vanilloid type 1 (TRPV1), a key molecule involved in the development of peripheral sensitization. Our studies elucidated the important regulatory roles of several protein kinases, including PKD1 (protein kinase D1), Cdk5 (cyclin-dependent kinase 5) and LIMK (LIM-motif containing kinase), in inflammatory thermal hyperalgesia. Moreover, based on these findings, we constructed a series of transmembrane Tat-fusion peptides for pain relief. The potential role of central TRPV1 was discussed as well. Prelimbic subregion of prefrontal cortex was revealed to be a critical brain region involved in the interaction between pain sensation and pain emotions by our recent studies. In addition, our work attempted to improve the analgesic effects of the agents targeting TRPV1 and concurrently reduce their side effects. Herein we summarized the work of our lab in pain and pain modulation during the past decade.


Structure of the membrane domain of human erythrocyte anion exchanger 1 revealed by electron crystallography.
The membrane domain of human erythrocyte anion exchanger 1 (AE1) works as a Cl(-)/HCO(3)(-) antiporter. This exchange is a key step for CO(2)/O(2) circulation in the blood. In spite of their importance, structural information about AE1 and the AE (anion exchanger) family are still very limited. We used electron microscopy to solve the three-dimensional structure of the AE1 membrane domain, fixed in an outward-open conformation by cross-linking, at 7.5-A resolution. A dimer of AE1 membrane domains packed in two-dimensional array showed a projection map similar to that of the prokaryotic homolog of the ClC chloride channel, a Cl(-)/H(+) antiporter. In a three-dimensional map, there are V-shaped densities near the center of the dimer and slightly narrower V-shaped clusters at a greater distance from the center of the dimer. These appear to be inserted into the membrane from opposite sides. The structural motifs, two homologous pairs of helices in internal repeats of the ClC transporter (helices B+C and J+K), are well fitted to those AE1 densities after simple domain movement.


Recurrent ventricular tachycardia managed with balloon aortic valvuloplasty: an unusual presentation of severe aortic stenosis.
A 68-year-old woman was transferred from a regional hospital with recurrent polymorphic ventricular tachycardia associated with haemodynamic instability. A diagnosis of severe aortic stenosis (AS) with normal left ventricular systolic function had recently been established on echocardiography. Correction of hypokalaemia and intravenous amiodarone infusion were ineffective. On transfer, ongoing ventricular arrhythmias requiring repeat defibrillation occurred. Urgent coronary angiography was unremarkable. Following consultation with the cardiosurgical team, emergency bridging balloon aortic valvuloplasty (BAV) was performed. Two weeks later the patient proceeded to an uneventful inpatient surgical aortic valve replacement (AVR). This case highlights an unusual presentation of severe AS, and describes the use of emergency BAV to correct arrhythmia-induced haemodynamic instability prior to surgical AVR.


Blood pressure variability is more important than blood pressure level in determination of end-organ damage in rats.
This study was designed to determine how important a novel risk factor of elevated blood pressure variability (BPV) is in the determination of end-organ damage by comparison with the classic risk factor of a high blood pressure (BP) level. The effects of haemodynamics on cardiovascular morphology were evaluated by univariate and multivariate regression analysis in two different rat models with an enlarged distribution of haemodynamics. In male sham-operated and sinoaortic-denervated Wistar-Kyoto rats and spontaneously hypertensive rats (n = 34), BPV was more important than BP in cardiac and renal damage and aortic hypertrophy. BPV and BP had independent effects, explaining 59.4% of the variation in damage to these organs. In male (n = 44) and female (n = 46) F1 hybrids of Sprague-Dawley rats and spontaneously hypertensive rats, the greater importance of BPV than BP was further demonstrated in left ventricular hypertrophy, glomerular damage and aortic hypertrophy. The phenomenon was more evident in females than males for cardiovascular hypertrophy. BPV and BP or BPV alone had independent effects, explaining 46.9% (male) or 37.5% (female) of the variation in damage to these organs. BPV is a more critical determinant than BP level for cardiac damage, renal lesions and aortic hypertrophy in rats, strongly suggesting the significance of BPV control for the protection of these organs.


Cutting Edge: CRISPR-Based Transcriptional Regulators Reveal Transcription-Dependent Establishment of Epigenetic Memory of Foxp3 in Regulatory T Cells.
Transcription factor Foxp3 specifies and maintains regulatory T cell (Treg) identity. During Treg differentiation, a CpG-rich Foxp3 intronic enhancer, conserved noncoding sequence 2 (CNS2), is activated via DNA demethylation to establish epigenetic memory of Foxp3 expression to protect Treg identity. However, it is unclear how this epigenetic memory of Foxp3 expression is established, as CNS2 is thought to be demethylated independently of Foxp3 expression. In this article, we uncover an unexpected causal relationship between Foxp3-transcriptional activation and CNS2 demethylation in mice. CRISPR/dCas9-mediated Foxp3-transcriptional activation elicits CNS2 demethylation. Sustaining Foxp3-transcriptional activation in induced Tregs also promotes CNS2 demethylation, enhancing Treg lineage stability and suppressive function. Importantly, CRISPR-mediated silencing of Foxp3 transcription, but not protein expression, abolishes CNS2 demethylation. The novel finding that Foxp3-transcriptional activation promotes CNS2 demethylation may facilitate the development of Treg-based therapies and represent a general mechanism for the establishment of epigenetic memory of immune gene expression.


The implications of a growing evidence base for drug use in elderly patients. Part 1. Statins for primary and secondary cardiovascular prevention.
Although elderly patients represent a rapidly growing population often requiring multiple drug treatment, the evidence of effectiveness is limited for many interventions and therapies in this age group. Only during the last 30 years has a requirement to incorporate evidence into the treatment of older subjects become part of the pre- and postmarketing regulatory process in Europe and the United States. Recently, elderly patients have been shown to benefit comparably from several treatments. These studies have supported the validity of an increasingly interventional approach to disorders common in late life. However, an important issue is the applicability of the growing body of clinical trials to 'real life' patients. This is particularly true in very old (i.e. >80 years) patients and those with significant comorbidities. We review the current evidence and controversies related to the effectiveness and safety of several therapeutic strategies in cardiovascular disease (i.e. statins, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, beta-adrenoceptor blockers, and thrombolytic agents) and bone health (i.e. vitamin D and bisphosphonates).


The informed consent process and the use of the exception to informed consent in the clinical trial of diaspirin cross-linked hemoglobin (DCLHb) in severe traumatic hemorrhagic shock. DCLHb Traumatic Hemorrhagic Shock study group.
In the clinical trial of diaspirin cross-linked hemoglobin (DCLHb), optimal therapy required the immediate enrollment of patients with severe, uncompensated, traumatic hemorrhagic shock. When it was not feasible to obtain prospective consent, an exception to informed consent was used according to FDA regulation 21 CFR 50.24. To examine the informed consent process and the use of the consent exception and consent to continue (CTC), and to describe the patients for whom this process was used. This was a multicenter, randomized, controlled, single-blinded efficacy trial of DCLHb as an adjunct to standard therapy in the treatment of severe, traumatic hemorrhagic shock. Patients with unstable vital signs or a critical base deficit were treated, with a primary study endpoint of 28-day mortality. During the 11-month study period, 112 patients were randomized in 18 U.S. trauma centers, and data from 98 of the infused patients were analyzed. Prospective consent was obtained from two patients, three family members, and one legally authorized representative (LAR) (6%). Consent to continue was requested for 89 patients (89%), and full participation was granted for 87 of these patients (98%). Consent to continue was provided by 54 (98%) of the 55 patients approached. The mean number of days for family/LAR CTC was 1.1 +/-3.8 days, and 50% of the time it was obtained on the day of study enrollment. Patient CTC was obtained in an average of 13 +/- 23 days, with a median of four days. Patients treated in this protocol were more likely to have sustained penetrating trauma than the overall trauma patient population treated in these trauma centers (44% vs 21%, p = 0.002). Informed consent in this study of an emergent therapy most often involved the use of the consent exception and consent to continue, the latter of which occurred in a timely manner. Nearly all of those who were approached for CTC approved full participation in the study, suggesting acceptance of the process outlined in the new regulations. Patients treated in a hemorrhagic shock clinical trial may differ from the general trauma patient population.


[Low-dose combination oral contraceptives use in women with uterine leiomyomas].
To evaluate the effects of the last generation of oral contraceptives (OC) on uterine leiomyomas. non-randomized perspective study on the effects of the last generation of oral contraceptives on uterine myomas during 24 months follow-up. III Unit of Obstetrics and Gynecology, University of Bari. between 1999 and 2000 a total of 121 asymptomatic women with only one subserous and/or intramural uterine myoma, having diameter pound 25 mm have been recruited. These patients were divided into two groups: the treatment group was composed of 53 women and was treated with last generation pill containing 20 microgram of ethynilestradiol and 150 microgram of desogestrel or 20 microgram of ethynilestradiol and 75 microgram of gestodene, while the control group was composed of 68 women having no hormonal therapy. In both groups the uterine myoma size (evaluated by transvaginal ultrasonography), the duration of menstrual flow and the hematocrit at the time of recruitment, after 12 months and after 24 months were examined. Forty-eight (90.6%) women belonging to the study group completed 2 years of OC use; only sixty women (88.2%) belonging to the control group completed the study. The use of the last generation oral contraceptives for 2 years didn't increase significantly uterine myomas size; besides after 24 months there was a significant reduction of more than two days of menstrual flow, and a significant increase of two and a half points of hematocrit. On the contrary, in the control group, we found a significant increase of uterine myoma volume, a not significant increase of menses duration and a not significant reduction of hematocrit. The prolonged use of the last generation of oral contraceptives does not affect the uterine myomas volume increase and furthermore it produces a significant reduction in the duration of menstrual flow with a significant increase in hematocrit.


Evaluation of the effectiveness of BG-Sentinel and CDC light traps in assessing the abundance, richness, and community composition of mosquitoes in rural and natural areas.
Vector-borne diseases are a major burden to public health. Controlling mosquitoes is considered the most effective way to prevent vector-borne disease transmission. Mosquito surveillance is a core component of integrated vector management, as surveillance programs are often the cornerstone for the development of mosquito control operations. Two traps are the most commonly used for the surveillance of adult mosquitoes: Centers for Disease Control and Prevention miniature light trap (CDC light trap) and BG-Sentinel trap (BioGents, Regensburg, Germany). However, despite the importance of the BG-Sentinel trap in surveillance programs in the United States, especially in the Southern states, its effectiveness in consistently and reliably collecting mosquitoes in rural and natural areas is still unknown. We hypothesized that BG-Sentinel and CDC light traps would be more attractive to specific mosquito species present in rural and natural areas. Therefore, our objective was to compare the relative abundance, species richness, and community composition of mosquitoes collected in natural and rural areas by BG-Sentinel and CDC light traps. Mosquitoes were collected from October 2020 to March 2021 using BG-Sentinel and CDC light traps baited with dry ice, totaling 105 trap-nights. The BG-Sentinel traps collected 195,115 mosquitoes comprising 23 species from eight genera, and the CDC light traps collected 188,594 mosquitoes comprising 23 species from eight genera. The results from the permutational multivariate analysis of variance (PERMANOVA) and generalized estimating equation model for repeated measures indicate the BG-Sentinel and CDC light traps had similar sampling power. Even though BG-Sentinel traps had a slightly better performance, the difference was not statistically significant indicating that both traps are suitable to be used in mosquito surveillance in rural and natural areas.


Treatment with dexamethasone or liposome-encapsuled vitamin E provides beneficial effects after chemical-induced lung injury.
The pathogenesis of lung injury by exposure to highly toxic sulfur and nitrogen mustards involves alkylating damage of the respiratory epithelium followed by an acute inflammatory response and lung edema. The acute phase is followed by long-term respiratory complications characterized by bronchitis, lung fibrosis, and airway hyperreactivity. In this study, we utilized a mouse model for airway inflammation induced by inhalation exposure to the alkylating nitrogen mustard melphalan, in order to investigate possible beneficial treatment effects by the corticosteroid dexamethasone. In addition, we investigated therapeutic efficacy of liposome-encapsuled vitamin E, an antioxidant formulation previously shown to be efficient in counteracting inflammatory conditions. Influx of inflammatory cells to airways, edema formation, and expression of different cytokines were analyzed 6 and 18 hours after exposure to melphalan. In order to evaluate long-term lung effects, we also investigated collagen deposition and accumulation of lymphocytes at 2 and 4 weeks after exposure. A single intraperitoneal injection of dexamethasone (10 mg/kg body weight) 1 hour after melphalan exposure significantly reduced interleukin (IL)-1 and IL-6 in bronchoalveolar lavage fluid (BALF) and diminished the acute airway inflammation. Our results also indicate that early single-dose treatment with dexamethasone protects against long-term effects observed 2-4 weeks after melphalan exposure, as indicated by reduced lymphocytic response in airways and decreased collagen deposition. Furthermore, our results indicate that also vitamin E (50 mg/kg) reduces acute inflammatory cell influx, and suppresses collagen formation in lung tissue, indicating that this drug could be used in combination with corticosteroids for protection against chemical-induced lung injury.


Electrofluorescence study of polycyclic hydrocarbon diol-epoxide binding to DNA.
By the use of a novel electrofluorescence method, estimates have been made of the geometry of binding to DNA of racemic mixtures of the anti-diol-epoxide derivatives of three polycyclic hydrocarbon carcinogens. These anti-configurations bind in a manner consistent with the planar diol-epoxide ring's being inclined at approximately 50 degrees to the DNA axis. This is true for the derivatives of benzo(a)pyrene, benz(a)anthracene and 3-methylcholanthrene. This binding is thus different from the regular intercalative interaction associated with the native hydrocarbons. As the (+ anti)-diol-epoxides are thought to be the initiatory compounds for carcinogenesis, the common binding characteristics for the three hydrocarbons may be significant in understanding the molecular interactions precursive to cancer.


Cardiac resynchronization therapy in heart failure patients: tough road but clear future.
Cardiac resynchronization therapy (CRT) based on biventricular pacing (BVP) is an invaluable intervention currently used in heart failure (HF) patients. The therapy involves electromechanical dyssynchrony, which can not only improve heart function and quality of life but also reduce hospitalization and mortality rates. However, approximately 30% to 40% of patients remain unresponsive to conventional BVP in clinical practice. In the recent years, extensive research has been employed to find a more physiological approach to cardiac resynchronization. The His-Purkinje system pacing (HPSP) including His bundle pacing (HBP) and left bundle branch area pacing (LBBaP) may potentially be the future of CRT. These technologies present various advantages including offering an almost real physiological pacing, less complicated procedures, and economic feasibility. Additionally, other methods, such as isolated left-ventricular pacing and multipoint pacing, may in the future be important but non-mainstream alternatives to CRT because currently, there is no strong evidence to support their effectiveness. This article reviews the current situation and latest progress in CRT, explores the existing technology, and highlights future prospects in the development of CRT.


Association of levels of HIV-1-infected breast milk cells and risk of mother-to-child transmission.
Understanding how the level of human immunodeficiency virus type 1 (HIV-1)-infected breast milk cells (BMCs) affects HIV transmission via breast-feeding can shed light on the mechanism of infection and aid in establishing effective interventions. The proportion of infected cells to total cells was measured in serial breast milk samples collected from 291 HIV-1-infected women in Nairobi, Kenya, by use of real-time DNA polymerase chain reaction amplification of BMCs. The number of infected BMCs per million cells was associated with levels of cell-free viral RNA in breast milk (R=.144; P=.032), levels of cell-free virus in blood plasma (R=.365; P<.001), and the detection of proviral DNA in cervical and vaginal secretions (P<.001 and P = .030, respectively). The number of infected BMCs per million cells was lower in colostrum or early milk than in mature milk (P<.001). Previous studies demonstrated that the concentration of BMCs varies throughout lactation, and we used these data to transform infected BMCs per million cells to infected BMCs per milliliter. The estimated concentration of infected BMCs per milliliter was higher in colostrum or early milk than in mature milk (P<.001). Each log10 increase in infected BMCs per milliliter was associated with a 3.19-fold-increased risk of transmission (P=.002), after adjustment for cell-free virus in plasma (hazard ratio [HR], 2.09; P=.03) and breast milk (HR, 1.01; P=1.00). This suggests that infected BMCs may play a more important role in transmission of HIV via breast-feeding than does cell-free virus.


Endoscopic ligation of the sphenopalatine artery and the maxillary artery for the treatment of intractable posterior epistaxis.
Intractable posterior epistaxis sometimes requires intensive treatment, such as surgery or embolization. Maxillary artery ligation has been widely used for the treatment of intractable posterior epistaxis. It is highly effective, but significant complications may occur, including an oroantral fistula and damage to the infraorbital nerve. Embolization is less invasive and can be performed in poor surgical candidates. However, it has more serious complications, such as facial nerve paralysis and hemiplegia. This investigation evaluates the effectiveness and complications of endoscopic ligation of the sphenopalatine or maxillary artery for the treatment of intractable posterior epistaxis. Between April 2003 and March 2007, 46 patients were hospitalized for the treatment of severe posterior epistaxis in our University Hospital. Thirty patients were successfully treated by anterior and/or posterior nasal packing, and five patients were treated by electrocoagulation. Endoscopic ligation was performed under general anesthesia in 11 patients (6 men and 5 women; age range, 50-80 years). Eight patients underwent endoscopic ligation of the sphenopalatine artery, and three patients underwent endoscopic ligation of the maxillary artery through the middle meatus and posterior antral wall opening. There were no complications, and the patients' postoperative courses were uneventful. Recurrent epistaxis occurred in one patient on oral anticoagulants 15 months after ligation of the sphenopalatine artery, and it was successfully treated by anterior nasal packing. Endoscopic ligation of the sphenopalatine or maxillary artery is safer than arterial embolization and is less invasive than transantral ligation of the maxillary artery. This technique appears to be a simple and highly effective surgical treatment for patients with intractable posterior epistaxis.


Biomechanics of Scar Tissue and Uninjured Skin.
Skin exhibits direction-dependent biomechanical behavior, influenced by the structural orientation of its collagen-rich fibrous network and its viscous ground-substance matrix. Injury can affect the skin's structure and composition, thereby greatly influencing the biomechanics and directionality of the resulting scar tissue. A combination of stress-relaxation and tensile failure testing identifies both the tissue's physiologically relevant viscoelastic behavior and resistance to rupture. When studied in mutually orthogonal directions in the plane of the tissue, these measures give insight into the directional properties of healthy tissue, and how they change with injury. By controlling the biomechanics of the wound environment, a new force-modulating dressing has demonstrated the ability to improve healing and reduce scar formation. Skin and scar biomechanics are typically characterized by using tensile failure, which identifies the tissue's resistance to rupture but offers limited insight into its normal daily function. Characterizing physiologically relevant biomechanics of skin, and how they change with injury, is critical to understand the tissue's ability to resist elongation, bear load, and dissipate energy via viscous means. Compared with uninjured skin, scar tissue demonstrates similar high-load stiffness, greatly reduced resistance to failure, reduced low-load compliance, and altered material directionality. These findings, identified through combined stress relaxation and failure testing, suggest morphological changes with injury that are consistent with the viscoelastic and directional changes observed biomechanically. A more complete understanding of the directional, physiologically relevant skin biomechanics can guide the design and critical functional assessment of wound treatments, scaffolds, and tissue-engineered skin replacements.


Treatment outcome by risk group after radical prostatectomy in Japanese men.
North American investigators have suggested the usefulness of risk-group stratification based on prostate-specific antigen (PSA), clinical stage and biopsy Gleason score for predicting the biochemical outcome of prostate cancer after radical prostatectomy. There have been no reports of the application of this stratification to early biochemical outcome after radical surgery in Japanese men. The study population consisted of 178 men treated with radical retropubic prostatectomy and bilateral pelvic lymph node dissection at Kitasato University Hospital (n = 110) and Kurashiki Central Hospital (n = 68) between October 1992 and May 1999. Pathologic and biochemical outcomes after radical prostatectomy were analyzed based on risk-group stratification. Risk groups were further analyzed according to detailed pathologic findings at biopsy. The median follow-up period for the 178 patients after radical surgery was 41.5 months (range, 2.0--82.0 months; mean, 40.9 months). Fifty-eight patients experienced PSA failure at a median of 8.0 months following surgery (range, 0.0--58.0). Risk-group stratification distinctly defined groups of pathologic findings in the radical prostatectomy specimens. The proportion of patients with PSA failure for low, intermediate and high-risk groups were 9.5%, 23.9% and 56.9%, respectively (P < 0.0001). Use of the number of cores with cancer and maximum cancer length in biopsy cores failed to improve risk stratification for PSA outcome in all risk groups. Risk-group stratification based on preoperative variables may significantly improve a physician's ability to counsel patients about PSA outcome after radical prostatectomy. Further improvement in risk stratification may call for use of variables other than the pathologic information in biopsy cores.


[From the transformation of age groups to the evolution of social relationships].
"In Western societies, change in family behaviour patterns, increased life expectancy, transformations in the socioeconomic environment and in culture have effected important modifications in the 'age pyramid', the significance of which has fed the debate between experts who have recorded them and who have anticipated their foreseeable consequences. These consequences are examined here in the light of some of their effects on social ties, inside the family and on the community level: the recomposition of the deviations between generations, the appearance of a pre-adult stage, the growth of concomitant responsibilities in relation to ascendants and descendants within family networks, potential concurrent intergenerational conflicts, and the aging of the social fabric [at] the community level. These phenomena in full evolution are a particular incentive to reinforcing the dialogue between demography and sociology." (SUMMARY IN ENG AND SPA)


Delta-opioid receptor immunoreactivity on astrocytes is upregulated during mitosis.
Endogenous opioid peptides and opioid receptors are expressed by brain cells early during normal development, and exogenous opiate exposure in this period is known to affect brain cell proliferation and maturation. Despite the abundant evidence that opioids affect brain development, little is known about the mechanisms involved. In this study cortical astrocytes in primary culture were examined immunohistochemically by using antibodies against the opioid receptors. The immunoreactivity for delta-opioid receptors was strongly upregulated during mitosis with an increase in immunostaining that started in early prophase and lasted through the M-phase to cytokinesis. Similar effects could not be observed when antibodies against the mu- or kappa-opioid receptor subtypes were used. Cultured neurons and microglia presented a strong and homogenous immunostaining for the delta-opioid receptor and no further upregulation of immunoreactivity could be detected in these cells. The presence of functional delta-opioid receptors on the mitotic astrocytes was verified by using microspectrofluorometry for detection of delta-opioid agonist induced changes in intracellular free calcium concentrations ([Ca2+]i). In these experiments fluo-3/AM incubated cells showed a rapidly induced delta-opioid agonist (DPDPE, 10(-6) M) evoked increase in [Ca2+]i. These results suggest an upregulation of the delta-opioid receptors that could represent a mechanism involved in the response to opioids in the developing brain.


Juxtacrine interactions of endothelial cells with leukocytes: tethering and signaling molecules.
The interaction of blood leukocytes with the endothelium of post-capillary venules and other vessels involves regulated expression of molecules on both the endothelial cell (EC) and the leukocyte. This is true for each of the major classes of leukocytes, including lymphocytes, monocytes, and granulocytes. Interaction of polymorphonuclear leukocytes (PMNs), a particular subset of granulocytes, with cultured human endothelium illustrates this concept and also illustrates the diversity of structure, mechanisms of expression, and mechanisms of action of the molecules involved. One group of molecules binds, or "tethers", the PMN to the EC without requiring PMN activation; P-selectin and E-selectin, which are glycoproteins that are expressed by translocation from subcellular granules or synthesis under transcriptional regulation, respectively, are examples. A second group of molecules activates the PMN by binding to signal-transducing receptors. Platelet-activating Factor (PAF), a biologically-active phospholipid, is an example of this class. Its production is controlled by regulation of synthetic enzymes and is induced rapidly (minutes) when EC are appropriately stimulated. PAF is translocated to the EC surface, where it mediates juxtacrine activation of PMNs by binding to a "7 membrane-spanning" receptor. One consequence of juxtacrine activation of PMNs by PAF is functional upregulation of CD11/CD18 integrins on the PMN. These integrins bind to counterreceptors on the EC, enhancing the avidity of adhesion over that provided by P-selectin alone. Thus, combinations of tethering and signaling molecules regulate PMN adhesive interactions with EC. Combinations of such molecules also regulate other functional responses of the PMNs that are important in inflammation. The time-dependent expression of different patterns of tethering and signaling molecules by EC provides a general mechanism for differential adhesion and activation of different classes leukocytes in acute and subacute inflammation.


Adaptive MR-Guided Stereotactic Radiotherapy is Beneficial for Ablative Treatment of Lung Tumors in High-Risk Locations.
To explore the benefit of adaptive magnetic resonance-guided stereotactic body radiotherapy (MRgSBRT) for treatment of lung tumors in different locations with a focus on ultracentral lung tumors (ULT). A prospective cohort of 21 patients with 23 primary and secondary lung tumors was analyzed. Tumors were located peripherally (N = 10), centrally (N = 2) and ultracentrally (N = 11, planning target volume (PTV) overlap with proximal bronchi, esophagus and/or pulmonary artery). All patients received MRgSBRT with gated dose delivery and risk-adapted fractionation. Before each fraction, the baseline plan was recalculated on the anatomy of the day (predicted plan). Plan adaptation was performed in 154/165 fractions (93.3%). Comparison of dose characteristics between predicted and adapted plans employed descriptive statistics and Bayesian linear multilevel models. The posterior distributions resulting from the Bayesian models are presented by the mean together with the corresponding 95% compatibility interval (CI). Plan adaptation decreased the proportion of fractions with violated planning objectives from 94% (predicted plans) to 17% (adapted plans). In most cases, inadequate PTV coverage was remedied (predicted: 86%, adapted: 13%), corresponding to a moderate increase of PTV coverage (mean +6.3%, 95% CI: [5.3-7.4%]) and biologically effective PTV doses (BED10) (BEDmin: +9.0 Gy [6.7-11.3 Gy], BEDmean: +1.4 Gy [0.8-2.1 Gy]). This benefit was smaller in larger tumors (-0.1%/10 cm³ PTV [-0.2 to -0.02%/10 cm³ PTV]) and ULT (-2.0% [-3.1 to -0.9%]). Occurrence of exceeded maximum doses inside the PTV (predicted: 21%, adapted: 4%) and violations of OAR constraints (predicted: 12%, adapted: 1%, OR: 0.14 [0.04-0.44]) was effectively reduced. OAR constraint violations almost exclusively occurred if the PTV had touched the corresponding OAR in the baseline plan (18/19, 95%). Adaptive MRgSBRT is highly recommendable for ablative treatment of lung tumors whose PTV initially contacts a sensitive OAR, such as ULT. Here, plan adaptation protects the OAR while maintaining best-possible PTV coverage.


[Value of serum carcinoembryonic antigen in prediction of chemotherapy efficacy and prognosis in patients with advanced non-small cell lung cancer treated with EGFR-tyrosine kinase inhibitor].
The aim of this study was to detect the pre- and post-treatment serum carcinoembryonic antigen (CEA) levels after 4 weeks of EGFR-TKIs treatment in advanced non-small cell lung cancer (NSCLC) patients to evaluate the clinical value of CEA in the prediction of chemotherapy response and prognosis in those patients. Pre- and post-treatment serum CEA levels of the patients were measured with immunoradiometric kits after 4 weeks of EGFR-TKIs treatment to evaluate the relationship between chemotherapy response and prognosis. After 4 weeks of EGFR-TKIs treatment, one patient in the total of 75 patients (1.3%) achieved complete response (CR), 17 patients (22.7%) achieved partial response (PR), 31 patients (41.3%) achieved disease stable (SD) and 26 patients had progressive disease (PD). The radiological objective response rate(ORR) and disease control rate (DCR) were 24.0% and 65.3%, respectively. The median survival time (MST) of all patients was 8.1 months. The MST of SD patients was similar to that in the OR patients (P = 0.06), but both longer than that in the PD patients (P < 0.001). The MST of DC patients was similar to that in OR patients (P = 0.358), but longer than that in PD patients (P < 0.001). Serum CEA levels decreased ≥ 32% and ≥ 61% were closely related with the objective response and disease control. The median survival time (MST) of patients with serum CEA decreased ≥ 32% was longer than those with CEA decreased < 32% (9.5 months vs 6.7 months, P < 0.0001). The MST of patients with serum CEA decreased ≥ 32% was similar to those with CEA decreased ≥ 61% (9.5 months vs 10.5 months, P = 0.370), but both longer than those with CEA decreased < 32% (6.7 months, P < 0.001). Cox multivariate survival analysis confirmed that serum CEA level decreased ≥ 32%, CEA level decreased ≥ 61%, PS score, and DC are independent prognostic factor, but not OR. To advanced NSCLC patients, the disease control rate (DCR) may be more suitable than objective response rate (ORR) as an indicator in predicting the efficacy and prognosis in advanced NSCLC patients. Serum CEA levels decreased ≥ 32% may be a reliable indicator to determine the therapeutic efficacy of EGFR-TKIs.


Global analysis of transcript and protein levels across the Plasmodium falciparum life cycle.
To investigate the role of post-transcriptional controls in the regulation of protein expression for the malaria parasite, Plasmodium falciparum, we have compared mRNA transcript and protein abundance levels for seven different stages of the parasite life cycle. A moderately high positive relationship between mRNA and protein abundance was observed for these stages; the most common discrepancy was a delay between mRNA and protein accumulation. Potentially post-transcriptionally regulated genes are identified, and families of functionally related genes were observed to share similar patterns of mRNA and protein accumulation.


Immunosuppressive Activity of Abatacept on Circulating T Helper Lymphocytes from Juvenile Idiopathic Arthritis Patients.
Abatacept is used in the treatment of juvenile idiopathic arthritis (JIA) patients, but the activity of the drug on T helper cell function is not yet fully known. The ability of abatacept to affect cytokine production in vitro and the proliferative response to both recall antigens and polyclonal stimulation was firstly assessed in healthy donors. Then, 10 JIA patients who were due to start abatacept treatment were recruited and longitudinally evaluated during the first 90 days of therapy. Both their clinical response to the treatment and in vitro analysis aimed to assess the proliferative response to recall antigens and the proportions of circulating T helper subsets. Abatacept reduced the proliferative response to recall antigens and the production of proinflammatory cytokines such as IFN-γ and TNF-α in healthy donors in vitro. It was also efficient in improving symptoms and reducing parameters of inflammation in JIA patients. Abatacept reduced the proliferative response to recall antigens, and this effect was significant soon after drug infusion (2 days). Regarding the proportions of circulating CD4+ T lymphocytes, only a reduction in the frequencies of circulating Treg cells was observed. Abatacept in vitro inhibits proliferation and cytokine production in healthy donors, and reduces parameters of inflammation in vivo in JIA patients. The reduction of the proliferative response to recall antigens induced by abatacept was evident only soon after drug administration, suggesting that its immunosuppressive activity is maintained only for a short time.


Transvaginal ultrasonography with bowel preparation is able to predict the number of lesions and rectosigmoid layers affected in cases of deep endometriosis, defining surgical strategy.
Successful surgical treatment of deep bowel endometriosis depends on obtaining detailed information about the lesions, prior to the procedure. The objective of this study was to determine the capability of transvaginal ultrasonography with bowel preparation (TVUS-BP) to predict the presence of one or more rectosigmoid nodules and the deepest bowel layer affected by the disease. A prospective study of 194 patients with clinical and TVUS-BP suspected deep endometriosis submitted to videolaparoscopy. Image data were compared with surgical and histological results. With respect to bowel nodule detection and presence of at least two rectosigmoid lesions, TVUS-BP had a sensitivity of 97 and 81%, specificity 100 and 99%, positive predictive value (PPV) 100 and 93% and negative predictive value (NPV) 98 and 96%, respectively. Regarding diagnosis of infiltration of the submucosal/mucosal layer, TVUS-BP had a sensitivity of 83%, specificity 94%, PPV 77%, NPV 96%. These findings show that TVUS-BP is an adequate exam for evaluating the presence of one or more rectosigmoid nodules and the deepest layer affected in deep infiltrating bowel endometriosis, confirming the importance of this technique for defining the most appropriate surgical strategy to be implemented.