Key feature-cases as virtual patients in education of veterinary neurology.
To provide students of veterinary medicine with the necessary day 1 competences, e-learning offerings are increasingly used in addition to classical teaching formats such as lectures. For example, virtual patients offer the possibility of case-based, computer-assisted learning. A concept to teach and test clinical decision-making is the key feature (KF) approach. KF questions consist of three to five critical points that are crucial for the case resolution. In the current study usage, learning success, usability and acceptance of KF cases as neurological virtual patients should be determined in comparison to the long cases format. Elective courses were offered in winter term 2019/20 and summer term 2020 and a total of 38 virtual patients with neurological diseases were presented in the KF format. Eight cases were provided with a new clinical decision-making application (Clinical Reasoning Tool) and contrasted with eight other cases without the tool. In addition to the evaluation of the learning analytics (e.g., processing times, success rates), an evaluation took place after course completion. After 229 course participations (168 individual students and additional 61 with repeated participation), 199 evaluation sheets were completed. The average processing time of a long case was 53 min, while that of a KF case 17 min. 78% of the long cases and 73% of KF cases were successfully completed. The average processing time of cases with Clinical Reasoning Tool was 19 min. The success rate was 58.3 vs. 60.3% for cases without the tool. In the survey, the long cases received a ranking (1 = very good, 6 = poor) of 2.4, while KF cases received a grade of 1.6, 134 of the respondents confirmed that the casework made them feel better prepared to secure a diagnosis in a real patient. Flexibility in learning (n = 93) and practical relevance (n = 65) were the most frequently listed positive aspects. Since KF cases are short and highlight only the most important features of a patient, 30% (n = 70) of respondents expressed the desire for more specialist information. KF cases are suitable for presenting a wide range of diseases and for training students' clinical decision-making skills. The Clinical Reasoning Tool can be used for better structuring and visualizing the reasoning process.


Effect of single point mutations of the human tachykinin NK1 receptor on antagonist affinity.
Molecular modelling and site-directed mutagenesis were used to identify eleven amino acid residues which may be involved in antagonist binding of the human tachykinin NK1 receptor. Recombinant receptors were expressed in mammalian cells using the Semliki Forest virus system. Wild type and mutant receptors showed similar expression levels in BHK and CHO cells, verified by metabolic labelling. Binding affinities were determined for a variety of tachykinin NK1 receptor antagonists in SFV-infected CHO cells. The binding affinity for GR203040, CP 99,994 and CP 96,345 was significantly reduced by mutant Q165A. The mutant F268A significantly reduced the affinity for GR203040 and CP 99,994 and the mutant H197A had reduced affinity for CP 96,345. All antagonists seemed to bind in a similar region of the receptor, but do not all rely on the same binding site interactions. Functional coupling to G-proteins was assayed by intracellular Ca2+ release in SFV-infected CHO cells. The wild type receptor and all mutants except A162L and F268A responded to substance P stimulation.


Functional expression and pharmaceutical efficacy of cardiac-specific ion channels in human embryonic stem cell-derived cardiomyocytes.
Cardiomyocytes differentiated from human pluripotent stem cells provide promising tools for screening of cardiotoxic drugs. For evaluation of human pluripotent stem cell-derived cardiomyocytes for cardiotoxicity test, in the present study, human embryonic stem cells (hESCs) were differentiated to cardiomyocytes, followed by metabolic selection to enrich the differentiated cardiomyocytes. The highly purified hESC-derived cardiomyocytes (hESC-CMs) expressed several cardiomyocyte-specific markers including cTnT, MLC2a, and α-SA, but not pluripotency markers, such as OCT4 and NANOG. Patch clamp technique and RT-PCR revealed the expression of cardiomyocyte-specific Na+, Ca2+, and K+ channels and cardiac action potential in hESC-CMs. To explore the potential use of hESC-CMs as functional cardiomyocytes for drug discovery and cardiotoxicity screening, we examined the effects of bisindolylmaleimide (BIM) (I), which inhibits native cardiac Ca2+ channels, on the Ca2+ channel activity of hESC-CMs. We observed a similar response for the BIM (I)-induced modulation of Ca2+ channels between hESC-CMs and native cardiomyocytes through L-type Ca2+ channel current. These results suggest that hESC-CMs can be useful for evaluation of pharmaceutical efficacy and safety of novel drug candidate in cardiac research.


Sodium Influx and Potassium Efflux Currents in Sunflower Root Cells Under High Salinity.
Helianthus annuus L. is an important oilseed crop, which exhibits moderate salt tolerance and can be cultivated in areas affected by salinity. Using patch-clamp electrophysiology, we have characterized Na+ influx and K+ efflux conductances in protoplasts of salt-tolerant H. annuus L. hybrid KBSH-53 under high salinity. This work demonstrates that the plasma membrane of sunflower root cells has a classic set of ionic conductances dominated by K+ outwardly rectifying channels (KORs) and non-selective cation channels (NSCCs). KORs in sunflower show extreme Na+ sensitivity at high extracellular [Ca2+] that can potentially have a positive adaptive effect under salt stress (decreasing K+ loss). Na+ influx currents in sunflower roots demonstrate voltage-independent activation, lack time-dependent component, and are sensitive to Gd3+. Sunflower Na+-permeable NSCCs mediate a much weaker Na+ influx currents on the background of physiological levels of Ca2+ as compared to other species. This suggests that sunflower NSCCs have greater Ca2+ sensitivity. The responses of Na+ influx to Ca2+ correlates well with protection of sunflower growth by external Ca2+ in seedlings treated with NaCl. It can be, thus, hypothesized that NaCl tolerance in sunflower seedling roots is programmed at the ion channel level via their sensitivity to Ca2+ and Na+.


Measuring phonological awareness in deaf and hard-of-hearing children.
This study evaluated psychometric properties of 2 phonological awareness (PA) tests normed for hearing children when used with deaf and hard-of-hearing (DHH) children with functional hearing. It also provides an in-depth description of these children's PA. One hundred and eight DHH children (mean age = 63.3 months) with cochlear implants or hearing aids were assessed in the fall and spring of the school year. Sixty-three percent communicated only with spoken language; 37% communicated with both sign and speech. Examiners administered PA subtests from the Phonological Awareness Test-2 and the Test of Preschool Early Literacy, along with assessments of speech perception and early literacy. Item analyses indicated that both tests showed good psychometric properties (e.g., high item discriminations and internal consistencies). DHH children scored higher on subtests and items that measured words, rhymes, and syllables than those that assessed phonemes. Although subtest difficulty influenced the factor structure in the fall, spring PA was best characterized as a single factor. PA correlated concurrently and predictively with early literacy. This study suggests that these 2 standardized tests are valid for use with DHH children with functional hearing. Although delayed, these children's PA was structurally similar to that of hearing children.


Post-translational modification of human brain type I inositol-1,4,5-trisphosphate 5-phosphatase by farnesylation.
In brain, type I inositol-1,4,5-trisphosphate 5-phosphatase (InsP3 5-phosphatase) is the major isoenzyme hydrolyzing the calcium-mobilizing second messenger InsP3. Activity of this enzyme could be measured in both soluble and particulate fractions of tissue homogenates. The protein sequence showed a putative C-terminal isoprenylation site (CVVQ). In this study, two mutants have been generated. The first mutant (C409S) has a serine replacing a cysteine at position 409 of the wild-type enzyme. The second mutant (K407D1) is a deletion mutant that lacks the last five C-terminal amino acids. These constructs were individually expressed by transfection in COS-7 cells. Western blot analysis of wild-type transfected cells indicated that both soluble and particulate fractions had a 43-kDa immunoreactive band, with a higher proportion of the original homogenate associated with the particulate part. On the contrary, when the two mutated constructs were transfected in COS-7 cells, the phosphatase was predominantly soluble. Confocal immunofluorescence studies showed the wild-type enzyme to be present on the cell surface of transfected COS-7 cells and in subcellular compartments around the nucleus. This was not observed for the two mutants, where uniform immunofluorescence labeling was observed throughout the cytosol. Recombinant type I InsP3 5-phosphatase expressed in Escherichia coli was a substrate of purified farnesyltransferase. Altogether, the data therefore suggest a direct participation of Cys-409 in a C-terminally anchored InsP3 5-phosphatase by farnesylation.


Human annexins A1, A2, and A8 as potential molecular targets for Ni(II) ions.
Nickel is harmful for humans, but molecular mechanisms of its toxicity are far from being fully elucidated. One of such mechanisms may be associated with the Ni(II)-dependent peptide bond hydrolysis, which occurs before Ser/Thr in Ser/Thr-Xaa-His sequences. Human annexins A1, A2, and A8, proteins modulating the immune system, contain several such sequences. To test if these proteins are potential molecular targets for nickel toxicity we characterized the binding of Ni(II) ions and hydrolysis of peptides Ac-KALTGHLEE-am (A1-1), Ac-TKYSKHDMN-am (A1-2), and Ac-GVGTRHKAL-am (A1-3), from annexin A1, Ac-KMSTVHEIL-am (A2-1) and Ac-SALSGHLET-am (A2-2), from annexin A2, and Ac-VKSSSHFNP-am (A8-1), from annexin A8, using UV-vis and circular dichroism (CD) spectroscopies, potentiometry, isothermal titration calorimetry, high-performance liquid chromatography (HPLC), and electrospray ionization mass spectrometry (ESI-MS). We found that at physiological conditions (pH 7.4 and 37 °C) peptides A1-2, A1-3, A8-1, and to some extent A2-2 bind Ni(II) ions sufficiently strongly in 4N complexes and are hydrolyzed at sufficiently high rates to justify the notion that these annexins can undergo nickel hydrolysis in vivo. These results are discussed in the context of specific biochemical interactions of respective proteins. Our results also expand the knowledge about Ni(II) binding to histidine peptides by determination of thermodynamic parameters of this process and spectroscopic characterization of 3N complexes. Altogether, our results indicate that human annexins A1, A2, and A8 are potential molecular targets for nickel toxicity and help design appropriate cellular studies.


The influence of sex, stroke and distance on the lactate characteristics in high performance swimming.
In order to achieve world-class performances, regular performance diagnostics is required as an essential prerequisite for guiding high performance sport. In high performance swimming, the lactate performance diagnostic is an important instrument in testing the sport specific endurance capacity. Although the role of lactate as a signaling molecule, fuel and a gluconeogenic substrate is accepted, lactate parameters are discussed concerning stability, explanatory power and interpretability. We calculated the individual anaerobic threshold (IAT) of Bunc using the swimming-specific lactate threshold test by Pansold. The cross-sectional analysis (ANOVA) of n = 398 high performance swimmers showed significant effects for sex, stroke and distance on the IAT, the percentage of personal best time on the IAT (% of PB on IAT) and maximal lactate values (max. bLA). For the freestyle events the IAT decreased, % of PB on IAT and max. bLA increased from 100 to 400 m significantly in men and women. Women showed significantly higher % of PB on IAT with descriptive lower IAT in 7 of 8 analyzed events. Men showed significantly higher max. bLA in 5 of 8 events. In the second step, the analysis of 1902 data sets of these 398 athletes with a multi-level analysis (MLA) showed also significant effects for sex, swimming distance and stroke. For initial status and development over time, the effect sizes for the variables distance and sex were medium to large, whereas for stroke there were no or small effect sizes. These significant results suggest that lactate tests in swimming specifically have to consider the lactate affecting factors sex and distance under consideration of the time period between measurements. Anthropometrical factors and the physiology of women are possible explanations for the relative better performance for lower lactate concentrations compared to men.


Early use of brachial-basilic arteriovenous fistula.
The aim of this study was to evaluate the long-term patency rate and complications associated with the use of the BBAVF in the early period. The records of all patients undergoing BBAVFs for hemodialysis access between June 2001 and June 2011 were retrospectively evaluated. We allowed the use of the BBAVF beginning two weeks after the fistula creation. The primary and secondary patencies were estimated using the Kaplan-Meier method. A total of 44 BBAVFs were created for 41 patients. Most (73.2%) of the patients had previously been on hemodialysis. A previous history of AVG creation was noted in 36.6% and previous insertion of a catheter was reported for 72.7% of the patients, respectively. The mean time to the first cannulation of the BBAVF was 18.8 days (13-42 days). In two cases, the BBAVFs were not used. Postoperative complications were noted in 2 cases, and included prolonged arm edema and thrombosis. There was no infection of the wound or steal syndrome. The primary and secondary patency rates were 68.1% and 84.2% at 1 year, 55.0% and 80.7% at 2 years, and 38.1% and 70.1% at 5 years, respectively. In this study, the patency rates following the early use of the BBAVFs were not inferior to the previously reported patency rates in the literature. In cases where the patients already have an inserted central catheter, the early use of the BBAVFs decreases the complications associated with catheters.


Graft and Patient Survival in Kidney Transplant Recipients Over the Age of Sıxty-Five.
Elderly patients have increased morbidity and mortality compared to younger patients due to existing comorbid diseases and chronic immunosuppression. Therefore, the option of kidney transplantation for renal replacement therapy in elderly patients is still being controversial. Our aim in this study was to evaluate graft function, graft and patient survival, and associated factors in kidney transplant recipients over 65 years of age, at 11 years of follow-up. The study included 53 patients aged 65-76 years, out of a total of 1319 patients who underwent live kidney transplantation in the Organ Transplant Center of Acibadem International Hospital between October 2010 and July 2021. Demographic characteristics and creatinine values were recorded. Graft survival rates and patient survival rates at one, three, and five years were analyzed. Fifty-three patients, 14 female, 39 male, aged 65-76 years were included in the study. The follow-up period of the patients was 7-125 months. During the follow-up, 20 patients died. Graft loss occurred in two of 20 patients who died, and 18 patients died with working grafts. Graft loss developed in two of the 33 surviving patients. In the whole group, one-, three-, and five-year patient survival rates were 94%, 81%, and 76%, respectively. These results emphasize that kidney transplantation is a viable treatment option in elderly patients who have been well evaluated before kidney transplantation.


[Palliative treatment in neoplastic jaundice. Personal experience].
The palliative treatment of biliary duct neoplastic obstruction represents a problem of great importance and frequently can't leave out of consideration patients clinical conditions and phase of neoplastic disease. Authors, in this article refers their experience on palliative treatment of neoplastic jaundice and indications for surgical or endoscopic treatment. Their experience shows that surgical palliation must be performed in patients with preoperative instrumental investigations without "surgical risk", this vouches for a better quality of life than endoscopic procedure performed with diffuse neoplastic disease and in patients with surgical risk.


Four new species of isopods (Crustacea, Isopoda) from South Korea.
Four new isopods, Amakusanthura intermedia sp. nov., Apanthura laevipedata sp. nov., Idarcturus trispinosus sp. nov., and Neastacilla paralongipectus sp. nov., are reported from the sublittoral zones in Korean waters. Amakusanthura intermedia sp. nov. differs from its congeners by the following features: the uropodal exopod is sinuous distally and with pointed apex; the maxillipedal endite is present and reaching to the distal end of fused palp articles I and II; and the propodal palm of pereopod I is stepped. Apanthura laevipedata sp. nov. can be distinguishable from its related species by the following characteristics: the eye is lacking; the propodal palm of pereopod I is not stepped; and the uropodal exopod is not sinuous. Idarcturus trispinosus sp. nov. is diagnosed by the following features: the cephalon has three dorsal spines and a pair of lateral spines; pereonite IV has two pairs of small dorsolateral spines, four pairs of dorsal spines, and one posterior spine; and the pleotelson has three pairs of wings laterally. Neastacilla paralongipectus sp. nov. can be distinguished by the following characteristics: the body is smooth and lacking dorsal spines or tubercles; pereonite IV is approximately 5.4× longer than pereonites II and III together; and the pleotelson has two pairs of lateral wings. In this paper, detailed descriptions and illustrations of the four species are presented. A key to the genera of the family Arcturidae and keys to the species of the four genera are also provided.


Bimodal shape of individual variation in behavior of Wistar rats: the overall outcome of a fundamentally different make-up and reactivity of the brain, the endocrinological and the immunological system.
An overview of the most important features of the two distinct types of individuals which normally co-occur in an unselected population of Wistar rats is given. It reveals that the overall make-up and reactivity of the brain, as well as the endocrinological and immunological systems differ completely between the two types of individuals. Each of these types of individuals has its own individual-specific hardware and software to cope with challenges from the internal or external environment, requires its own optimal niche, and is vulnerable for its own set of stressors.


[Shape conservatism and shaping variability. The comparative analysis of Hydrozoa and Scyphozoa early development].
The morphogenetic pathways based on the self-organization take an important part in the early development of White Sea Cnidarians--Dynamena pumila (Hydrozoa) and Aurelia aurita (Scyphozoa). Comparative analysis of their early development revealed two patterns of embryonic spatial structure reproduced in the morphogenesis of both species in spite of the differences of morphogenetic paths. These are toroidal and bilaterally symmetrical shapes. It is possible that these shapes correspond to the equilibrium states of developing system and their stable reproduction is a result of epigenetic rather than genetic program.


Respiratory syncytial virus infection in children with neuromuscular impairment.
Clinically obvious reasons why children with neurological impairment (NMI) may be more severely affected in case of a viral respiratory tract infection include reduced vital capacity due to muscular weakness or spastic scoliosis, disturbed clearance of respiratory excretions (weak coughing and dysphagia), inability to comply actively with physiotherapeutic interventions, recurrent micro-aspirations (gastroesophageal reflux disease, vomiting related to coughing), a history of frequent exposure to antibiotics and health care institutions, colonization with resistant pathogens, impaired immunologic defence mechanisms due to severe malnutrition and cachexia, and early clinical deterioration in case of high fever with metabolic acidosis and hypercapnia, and maybe associated seizures or febrile convulsions.Data from the literature suggests that in all children with NMI, who have to be hospitalized with severe clinical deterioration due to an airway infection, at least one specimen of nasopharyngeal secretions should be sent as soon as possible to a virologic laboratory to detect viral pathogens. Children with severe NMI and those mechanically ventilated for other reasons being hospitalized during the RSV season must be strictly protected against nosocomial RSV infection by means of standard and droplet precautions. Finally, children with severe NMI and age below 24 months of life should receive passive immunization with palivizumab following international recommendations.


Clinical efficacy of sertraline alone and augmented with gabapentin in recently abstinent cocaine-dependent patients with depressive symptoms.
Cocaine dependence is a major public health problem with no available robustly effective pharmacotherapy. This study's aim was to determine if treatment with sertraline (SERT) or SERT plus gabapentin (GBP) improved treatment retention, depressive symptoms, and/or cocaine use. Depressed cocaine-dependent patients (N = 99) were enrolled in a 12-week, double-blind, randomized, placebo (PLA)-controlled, clinical trial and placed in research beds at a residential treatment facility (Recovery Centers of Arkansas). They were randomized by depressive symptom severity and inducted onto 1 of the following while residing at the Recovery Centers of Arkansas: SERT (200 mg/d), SERT (200 mg/d) plus GBP (1200 mg/d), or PLA. Participants transferred to outpatient treatment at the start of their third week, continued receiving study medications or PLA (weeks 3-12), and participated in weekly individual cognitive behavioral therapy. Compliance was facilitated through the use of contingency management procedures. Supervised urine samples were obtained thrice weekly and self-reported mood weekly. At the end of 12 weeks, participants were tapered off the study medication over 5 days and referred to a local treatment program. Sertraline, but not SERT plus GBP, showed a significantly lower overall percentage of cocaine-positive urine samples compared with that of PLA. A significantly greater percentage of participants experienced relapse in the PLA group (88.9%) compared with that of the SERT group (65.2%). Hamilton depression ratings decreased significantly over time regardless of the treatment group. Retention in treatment did not differ significantly between the treatment groups. Sertraline plus GBP may not be superior to SERT alone in delaying relapse among abstinent cocaine-dependent individuals undergoing cognitive behavioral therapy.


[Clinical observation of the pathological changes of axial length, corneal curvature and posterior segment wall of eyeball in eyes with high myopia].
To study the correlation between the characteristics of the morphologic changes in the wall of eyeball with high myopia and the visual function. The axial length, corneal curvature, etc., of 280 eyes in 140 cases (the diopter was from -6.25D to approximately -30.00D) were examined and the data were settled statistically. (1) The corrected visual acuity in the patents with high myopia decreased apparently with the increase of diopter. The difference was significant (P < 0.001). (2) The axial length of anteroposterior diameter in 96.1% eyes increased, with which the diopter also increased. (3) 27.1% exophthalmos were forward. (4) There was no significant difference when compared the anterior surface corneal curvature with emmetropic eyes. (5) Posterior scleral staphyloma occurred in 80.7% eyes. (6) Optic nerve atrophy and optic disk atrophic arc spot occurred in 82.3% eyes. (7) The intraocular pressure increases in 5.3% eyes. The severe damage to the visual function because of the pathological changes on the wall of eyeball is the main cause that vision can not be corrected in clinics.


Endoscopic full-thickness resection for gastric submucosal tumors arising from the muscularis propria layer.
To evaluate the efficacy, safety and feasibility of endoscopic full-thickness resection (EFR) for the treatment of gastric submucosal tumors (SMTs) arising from the muscularis propria. A total of 35 gastric SMTs arising from the muscularis propria layer were resected by EFR between January 2010 and September 2013. EFR consists of five major steps: injecting normal saline into the submucosa; pre-cutting the mucosal and submucosal layers around the lesion; making a circumferential incision as deep as the muscularis propria around the lesion using endoscopic submucosal dissection and an incision into the serosal layer around the lesion with a Hook knife; a full-thickness resection of the tumor, including the serosal layer with a Hook or IT knife; and closing the gastric wall with metallic clips. Of the 35 gastric SMTs, 14 were located at the fundus, and 21 at the corpus. EFR removed all of the SMTs successfully, and the complete resection rate was 100%. The mean operation time was 90 min (60-155 min), the mean hospitalization time was 6.0 d (4-10 d), and the mean tumor size was 2.8 cm (2.0-4.5 cm). Pathological examination confirmed the presence of gastric stromal tumors in 25 patients, leiomyomas in 7 and gastric autonomous nerve tumors in 2. No gastric bleeding, peritonitis or abdominal abscess occurred after EFR. Postoperative contrast roentgenography on the third day detected no contrast extravasation into the abdominal cavity. The mean follow-up period was 6 mo, with no lesion residue or recurrence noted. EFR is efficacious, safe and minimally invasive for patients with gastric SMTs arising from the muscularis propria layer. This technique is able to resect deep gastric lesions while providing precise pathological information about the lesion. With the development of EFR, the indications of endoscopic resection might be extended.


The impact of omalizumab on paid and unpaid work productivity among severe Japanese cedar pollinosis (JCP) patients.
Japanese cedar pollinosis (JCP) is a form of seasonal allergic rhinitis that affects 38.8% of the Japanese population. Particularly severe and most severe symptoms among JCP patients can lead to impairments of paid work productivity and unpaid work activities. Indeed, the current standard of care (SoC) is not always able to relieve these symptoms. Omalizumab, a novel JCP treatment recently approved in Japan, provides an effective add-on therapy to the SoC. This study estimates the effect of omalizumab on paid and unpaid work activities (i.e. its social impact) in patients with severe and most severe JCP symptoms in Japan. The impact of omalizumab was estimated through a one-year static cohort model using the Work Productivity and Activity Impairment Allergy Specific (WPAI-AS) questionnaire derived from a clinical trial on omalizumab enrolling patients with severe and most severe JCP symptoms, which had been conducted in Japan. This effect was quantified using Japanese official statistics on employment and time use. The human capital approach and the proxy good approach were employed to monetize paid and unpaid work activities, respectively. A sensitivity analysis was implemented to account for modeling structural uncertainties. Our results show that the use of omalizumab might reduce the paid and unpaid work productivity losses due to severe and most severe JCP by nearly one-third. In the severe symptom period of three weeks, 36.6 million hours of lost paid and unpaid work hours could be avoided, which sums up to a monetized productivity loss of 728.3 million USD. Omalizumab could provide substantial benefits in terms of paid and unpaid work activities in patients with severe and most severe JCP. Our results also highlight the importance of considering unpaid work in estimating productivity costs due to poor health.


A geographical analysis of multiethnic households in the United States.
"Using the household-level data provided by the 5% PUMS [Public Use Microdata Sample] data from the 1990 Census, this paper reports the pattern of ethnic mixing at the household level in the U.S. and also describes the geographical patterns of different types of multiethnic households at both the state level and the PUMA [Public Use Microdata Area] level. Several of the largest metropolitan areas are also examined in greater detail. The strong dominance of whites in the process of ethnic mixing is clear, as is the expected dominance of blacks in southeastern U.S. and the dominance of Hispanics in the southwest at the state level. The PUMA-level analysis reveals local clusters of ethnic mixing that are not apparent at the state-level analysis."


Effect of age on the pattern of short-term albumin uptake by the rabbit aortic wall near intercostal branch ostia.
Lipid deposition occurs more frequently downstream than upstream of branches in immature human aorta but the opposite pattern is seen in mature vessels. These distributions may reflect variation in the uptake of plasma macromolecules by the aortic wall. We have recently shown that the quasi-steady state uptake of albumin is greater downstream than upstream of branches in immature rabbit aortas and that the opposite pattern occurs in mature animals. Additionally, there is a sharp drop in the mean uptake shortly after weaning. In the present study, the mechanisms underlying these phenomena were investigated by examining the short-term uptake of albumin and its distribution across the wall. Albumin was labeled with a fluorescent dye and introduced into the circulation of conscious New Zealand White rabbits. Thoracic aortas were fixed in situ 10 minutes later and were sectioned through the center of intercostal ostia. Fluorescence from sections was measured by using digital imaging fluorescence microscopy and was converted to tracer concentrations after appropriate autofluorescence levels had been subtracted. In animals aged 45 days, more tracer was detected in the wall downstream than upstream of branches; the difference between regions was > 100% of the mean value. This percentage halved and the mean uptake decreased almost threefold by 75 days. In mature animals, the mean value remained at the 75-day level but the converse distribution was seen; 22% more tracer was detected upstream than downstream. These trends were insensitive to the depth of the intimal-medial layer examined. In each region, the maximum tracer concentration occurred close to the luminal surface but not always within the first 2.9-microns-thick layer of the wall. Maxima were similar in magnitude to those observed at quasi-steady state, but the fall with increasing distance into the wall was much sharper. In many cases concentrations remained constant over most of the media, and rises toward the adventitial boundary were rarely seen. Uptake after 10 minutes predominantly reflects the rate at which tracer enters the wall. The concentration profiles were consistent with most of the tracer having entered from the luminal surface and with the involvement of convective transport. The trends observed with age closely paralleled those occurring at quasi-steady state. Consequently, the latter are also likely to be determined by changes in the resistance of the wall to macromolecule influx.


Persistent organic pollutants (POPs) in surface sediments of Donghu Lake, Wuhan, Hubei, China.
Surface sediment samples from five different sites were collected in Donghu Lake, Wuhan City, Hubei Province, China during November 2000. Over 180 organic chemicals were detected using GC-MS controlled by a Hewlett Packard Chemstation after soxhlet extraction. Derivatives of benzene, phthalate esters, PAHs, phenols, isophorone as priority pollutants or endocrine disruptors, respectively, were detected. The concentration of organic pollutants were found to be highest at the sampling site located at Southwest Donghu Lake (Shuiguo), caused most probably by the untreated wastewater discharge, average at the southern and lowest at the northern part of the lake.


Increased posterior tibial slope results in increased incidence of posterior lateral meniscal root tears in ACL reconstruction patients.
While the association with acute anterior cruciate ligament (ACL) tears has been established, other risk factors and associated pathologies which occur with a concomitant lateral meniscal posterior root tear (LMPRT) are not well defined. The purpose of this study was to compare the risk factors and concomitant pathologies between patients with LMPRT and patients without LMPRTs in the setting of a primary ACL tear. Patients with a LMPRT identified at the time of primary ACL reconstruction by a single surgeon were identified. These patients were matched by age and sex to patients undergoing primary ACL reconstruction who were not found to have lateral meniscus root tears (control group) in a 1:1 ratio. Lateral posterior tibial slope (PTS), medial PTS, lateral femoral condyle height and depth, lateral tibial plateau depth, and lateral tibial plateau subluxation were measured on MRI. Anteroposterior full-limb alignment radiographs were used to measure the medial proximal tibia angle (MPTA), the mechanical lateral distal femoral angle (mLDFA), and the mechanical weightbearing axis for the injured extremity. One-hundred three patients were included in both the LMPRT group and the matched control group. Patients with a LMPRT had a significantly steeper lateral PTS (9.1° vs. 7.0°, p = 0.001), a steeper medial PTS (7.0° vs. 6.0°, p = 0.03), and a greater lateral-to-medial slope asymmetry (2.0° vs. 1.0°, p = 0.001). There were no differences in lateral femoral condyle depth or height, lateral tibial plateau depth, lateral tibial plateau subluxation, MPTA, mLDFA, or mechanical weightbearing axis between groups. There was a significantly increased incidence of medial meniscus ramp lesions in patients with lateral meniscus posterior root tears compared with controls (34.0% vs. 15.5%, odds ratio: 2.8, p = 0.002). There were no associations with concomitant ligament injuries, medial meniscus root tears, or non-ramp tears based on case/control grouping. In conclusion, LMPRTs in the setting of primary ACL injuries were associated with significantly increased lateral and medial PTSs, and increased asymmetry between lateral and medial PTSs. In addition, clinicians should be aware of the increased incidence of concurrent medial meniscal ramp lesions in patients with LMPRTs. Knowledge of these associations helps guide clinical decision-making and counselling of patients in the setting of ACL tears with concomitant LMPRTs. IV.


High HBV-DNA serum levels are associated with type 2 diabetes in adults with positive HBsAg: An observational study.
The prevalence of diabetes is higher in hepatitis B virus (HBV)-infected population. We aimed to examine the relationship between different serum HBV-DNA levels and type 2 diabetes in adults with positive HBV surface antigen (HBsAg). We conducted cross-sectional analyses of data obtaining from the Clinical Database System of Wuhan Union Hospital. Diabetes was defined by self-report of type 2 diabetes, fasting plasma glucose (FPG) ≥7mmol/L, or glycated hemoglobin (HbA1c) ≥6.5%. Binary logistic regression analyses were performed to investigate the factors associated with diabetes. Among 12,527 HBsAg-positive adults, 2,144 (17.1%) were diabetic. Patients with serum HBV-DNA <100, 100-2000, 2000-20000 and ≥20000 IU/mL accounted for 42.2% (N=5,285), 22.6% (N=2,826), 13.3% (N=1,665) and 22.0% (N=2,751), respectively. The risk of type 2 diabetes, FPG ≥7mmol/L and HbA1c ≥6.5% in individuals with highly elevated serum HBV-DNA level (≥20000 IU/mL) were 1.38 (95% confidence interval [CI]: 1.16 to 1.65), 1.40 (95% CI: 1.16 to 1.68) and 1.78 (95% CI: 1.31 to 2.42) times relative to those with negative or lowly elevated serum HBV-DNA (<100 IU/mL). However, the analyses showed no association of moderately (2000-20000 IU/mL) to slightly (100-2000 IU/mL) raised serum HBV-DNA levels with type 2 diabetes (OR=0.88, P=0.221; OR=1.08, P=0.323), FPG ≥7mmol/L (OR=1.00, P=0.993; OR=1.11, P=0.250) and HbA1c ≥6.5% (OR=1.24, P=0.239; OR=1.17, P=0.300). In HBsAg-positive adults, highly elevated level rather than moderately to slightly raised levels of serum HBV-DNA is independently associated with an increased risk of type 2 diabetes.


Density gradient localization of plasma membrane and tonoplast from storage tissue of growing and dormant red beet : characterization of proton-transport and ATPase in tonoplast vesicles.
Membranes from homogenates of growing and of dormant storage roots of red beet (Beta vulgaris L.) were centrifuged on linear sucrose gradients. Vanadate-sensitive ATPase activity, a marker for plasma membrane, peaked at 38% to 40% sucrose (1.165-1.175 grams per cubic centimeter) in the case of growing material but moved to as low as 30% sucrose (1.127 grams per cubic centimeter) during dormancy.A band of nitrate-sensitive ATPase was found at sucrose concentrations of 25% to 28% or less (around 1.10 grams per cubic centimeter) for both growing and dormant material. This band showed proton transport into membrane vesicles, as measured by the quenching of fluorescence of acridine orange in the presence of ATP and Mg(2+). The vesicles were collected on a 10/23% sucrose step gradient. The phosphate hydrolyzing activity was Mg dependent, relatively substrate specific for ATP (ATP > GTP > UTP > CTP = 0) and increased up to 4-fold by ionophores. The ATPase activity showed a high but variable pH optimum, was stimulated by Cl(-), but was unaffected by monovalent cations. It was inhibited about 50% by 10 nanomolar mersalyl, 20 micromolar N,N'-dicyclohexylcarbodiimide, 80 micromolar diethylstilbestrol, or 20 millimolar NO(3) (-); but was insensitive to molybdate, vanadate, oligomycin, and azide. Proton transport into vesicles from the 10/23% sucrose interface was stimulated by Cl(-), inhibited by NO(3) (-), and showed a high pH optimum and a substrate specificity similar to the ATPase, including some proton transport driven by GTP and UTP.The low density of the vesicles (1.10 grams per cubic centimeter) plus the properties of H(+) transport and ATPase activity are similar to the reported properties of intact vacuoles of red beet and other materials. We conclude that the low density, H(+)-pumping ATPase of red beets originated from the tonoplast. Tonoplast H(+)-ATPases with similar properties appear to be widely distributed in higher plants and fungi.


Behavioural Indicators of Intra- and Inter-Specific Competition: Sheep Co-Grazing with Guanaco in the Patagonian Steppe.
In extensive livestock production, high densities may inhibit regulation processes, maintaining high levels of intraspecific competition over time. During competition, individuals typically modify their behaviours, particularly feeding and bite rates, which can therefore be used as indicators of competition. Over eight consecutive seasons, we investigated if variation in herd density, food availability, and the presence of a potential competitor, the guanaco (Lama guanicoe), was related with behavioural changes in domestic sheep in Chilean Patagonia. Focal sampling, instantaneous scan sampling, measures of bite and movement rates were used to quantify behavioural changes in domestic sheep. We found that food availability increased time spent feeding, while herd density was associated with an increase in vigilant behaviour and a decrease in bite rate, but only when food availability was low. Guanaco presence appeared to have no impact on sheep behaviour. Our results suggest that the observed behavioural changes in domestic sheep are more likely due to intraspecific competition rather than interspecific competition. Consideration of intraspecific competition where guanaco and sheep co-graze on pastures could allow management strategies to focus on herd density, according to rangeland carrying capacity.


Application of chemicals in organic solvents to dry seeds.
Various chemicals were applied to dry seeds by means of organic solvents. The gibberellic acid-treated (1 mm) lettuce seeds (Lactuca sativa L.) germinated nearly 100% in the dark even after prolonged storage, and those treated with abscisic acid (1 mm or 0.5 mm) failed to germinate in the light. The seedlings emerging from morphactin-treated (1 mm) cucumber seeds (Cucumis sativus L.) exhibited profound changes in morphology. Different combinations of hormones applied to lettuce seeds caused a promotion or an inhibition of germination. Germination promotion or inhibition studies showed that the applied chemicals could be removed by washing with an organic solvent or water. Progressively larger amounts of chemicals were removed with increasing periods of washing. Thus the chemical appeared to penetrate the seed to some degree. The potential of the organic solvent method is discussed.


Bioethanol Production by Enzymatic Hydrolysis from Different Lignocellulosic Sources.
As the need for non-renewable sources such as fossil fuels has increased during the last few decades, the search for sustainable and renewable alternative sources has gained growing interest. Enzymatic hydrolysis in bioethanol production presents an important step, where sugars that are fermented are obtained in the final fermentation process. In the process of enzymatic hydrolysis, more and more new effective enzymes are being researched to ensure a more cost-effective process. There are many different enzyme strategies implemented in hydrolysis protocols, where different lignocellulosic biomass, such as wood feedstocks, different agricultural wastes, and marine algae are being used as substrates for an efficient bioethanol production. This review investigates the very recent enzymatic hydrolysis pathways in bioethanol production from lignocellulosic biomass.


Co-location of mental health professionals in primary care settings: three North Carolina models.
The pressing need for identification and treatment of behavioral health disorders in primary care has renewed interest in the concept of co-located models of care. The purpose of this article is to describe three North Carolina practice models in which mental health professionals are co-located with pediatric primary care providers. Each of the models was sustainable, partly due to systemic changes brought about by advocacy efforts. In addition to providing practical guidance for possible replication in primary care, this article reflects on how advocacy efforts can impact the success of co-location models.


Complex genomic alterations and intellectual disability: an interpretative challenge.
Complex chromosomal rearrangements (CCRs) are structural rearrangements involving more than three chromosomes or having more than two breaks; approximately 70% are not associated with any clinical phenotype. Here, we describe a CCR segregating in a two-generation family. A 4-year-old male was evaluated for developmental delay, mild intellectual disability and epicanthus. Karyotype, fluorescence in situ hybridisation (FISH) analysis and array comparative genomic hybridisation (aCGH) analysis were performed on the patient and of all family members. Array CGH analysis of the proband detected two non-contiguous genomic gains of chromosome 2 at bands q32.3q33.2 and bands q36.1q36.3. Both karyotype and FISH analysis revealed a recombinant chromosome 2 with a direct insertion of regions q32.3q33.2 and q36.1q36.3 into region q12. Both of these regions were also present in their original location. Karyotype and FISH analysis of the father revealed a de novo direct insertion of regions q32.3q33.2 and q36.1q36.3 into region q12. Moreover, a de novo balanced translocation involving the q arm of the same chromosome 2 and the p arm of chromosome 10 was observed in the father of the proband. The single nucleotide polymorphism (SNP) array analysis and haplotype reconstruction confirmed the paternal origin of the duplications. Karyotype, FISH analysis and array CGH analysis of other family members were all normal. This report underlines the importance of using different methods to correctly evaluate the origin and the structure of CCRs in order to provide an appropriate management of the patients and a good estimation of the reproductive risk of the family.


[Nursing performance on specialty units, hospital departments and for patient groups--a comparison based on minimal nursing care data].
Nursing in Germany hides behind structural data like quantity and costs of nursing staff. This must be changed in aspect of the transparency of services in hospitals. The aim of this pilot study is to describe nursing services, find main focuses of nursing and point out significant differences between field units, wards and patient groups. On the basis of Belgian Nursing-Data-Sets, which was modified, all in all 2347 inpatient-days of 550 patients were collected. Analogous to the Belgian action, a Ridit Analysis was conducted, which allowed the construction of nursing profiles for every desired aggregation level. The knowledge of experience available regarding the different nursing services in departments and on the stations can at least be made valid, possibly even revised with the existing data equipment for the participating clinic. The easy to handle minimal Nursing Data Set allows the creation of a data basis, that can support decisions regarding the allocation of financial and personnel resources.


Comprehensive analysis of prognostic value and immune infiltration of calpains in pancreatic cancer.
Calpains (CAPNs) are intracellular calcium-activated neutral cysteine proteinases involved in cancer initiation, progression, and metastasis. However, its role in pancreatic cancer (PC) is still unclear. This study aims to identify the prognostic value and immune infiltration of CAPNs for PC patients using comprehensive bioinformatics analyzes. We analyzed the transcription levels of CAPNs in different cancers from Oncomine, differential gene expression in tumor/normal tissues and pathological stage through GEPIA database, the prognostic value of the mRNA expression of CAPNs by Kaplan-Meier plotter, the protein expression comparison of different CAPNs in human tumor/normal tissues from The Human Protein Atla, the CAPNs gene alterations through cBioPortal, the prediction of protein-protein interactions by STRING and GeneMANIA, the functional enrichment of discrepant CAPNs by GO and KEGG, and the immune infiltration of CAPNs by ssGSEA. Our results showed that CAPN1, 2, 4, 5, 6, 8, 9, 10, and 12 were highly expressed in PC. CAPN1, 5, 8, and 12 expression levels were positively correlated with individual cancer stages. Furthermore, CAPN1, 2, 5, and 8 expression levels were negatively correlated with overall survival (OS) and recurrence-free survival (RFS), while CAPN10 was positively correlated with OS and RFS. We found that CAPN1, 2, 5, and 8 were correlated with tumor-infiltrating T follicular helper cells and CAPN10 with tumor-infiltrating T helper 2 cells. Functional enrichment analysis showed that differentially expressed CAPNs (CAPN1, 2, 5, 8, and 10) are involved in axonogenesis, cell-substrate adhesion, immune response-activating cell surface receptor signaling pathway, and cell junction organization in PC. These results suggested that CAPN1, 2, 5, 8, and 10 could be used as prognostic biomarkers in PC and improve individualized treatment strategies.


The development of choroidal neovascularization in pregnancy.
To evaluate the possible association between the development of choroidal neovascularization (CNV) and pregnancy. A retrospective review was performed of the clinical records of three patients who were pregnant at the time a choroidal neovascular membrane (CNVM) was diagnosed. The clinical presentations and treatment of the CNVM occurring in association with the pregnancies are described. Each patient had a decrease in visual acuity during her pregnancy: one in the first trimester, one in the second trimester, and one in the third trimester. Two patients were diagnosed with CNV related to presumed ocular histoplasmosis syndrome (POHS) and one with an idiopathic CNVM. The two-patients with POHS showed progression of CNV after childbirth. All patients received laser photocoagulation directly to the site of the CNV. The two patients with ocular histoplasmosis experienced recurrence after treatment; one received further photocoagulation treatment, and the other underwent vitrectomy with removal of the CNVM. Pregnancy and the immediate postpartum period may be associated with development or recurrence of CNV in POHS or idiopathic cases. This may be related to hormonal changes during pregnancy, or the cases described may reflect only a coincidental association. This report discusses possible causal factors and mechanisms.


The effects of aging on the secretion of the common alpha-subunit of the glycoprotein hormones in men.
To investigate the effects of aging on the secretion of the common alpha-subunit of the glycoprotein hormones, we measured basal levels of luteinizing hormone (LH), testosterone (T) and alpha-subunit in 176 normal men aged 19 to 89 years. In addition, in two groups of young (less than 65 years; n = 25) and old (greater than 65 years; n = 15) subjects, the effects of luteinizing hormone-releasing hormone (LHRH) on LH and alpha-subunit secretion were determined. Age-related increases in serum alpha-subunit and LH were noted only in the oldest men while T levels decreased progressively with advancing age. LHRH stimulation resulted in significantly greater secretion of alpha-subunit in the old subjects while no difference in LH release between young and old men was observed. Moreover, there was a delay to peak LH and alpha-subunit levels after LHRH in the old subjects. These data suggest that the aging process in males involves deficits in both testicular and gonadotroph functions as demonstrated by (1) the relative hypogonadotropic hypogonadism seen until the ninth decade; (2) the hypergonadotropic hypogonadism apparent in men greater than 80 years; (3) the delay in the timing of peak responses of LH and alpha-subunit after LHRH administration; and (4) the disproportionate increase in the secretion of alpha subunit relative to intact LH.


Maternally inherited hypercholesterolemia does not modify the cardiovascular phenotype in familial hypercholesterolemia.
Familial hypercholesterolemia (FH) is a codominant autosomal disease characterized by a high risk of cardiovascular disease when not in lipid-lowering treatment. However, there is a large variability in the clinical presentation in heterozygous subjects (HeFH). Maternal hypercholesterolemia has been proposed as a cardiometabolic risk factor later in life. Whether this phenotype variability depends on the mother or father origin of hypercholesterolemia is unknown. The objective of this study was to analyze potential differences in anthropometry, superficial lipid deposits, comorbidities, and lipid concentrations depending on the parental origin of hypercholesterolemia within a large group of HeFH. This is a cross-sectional observational, multicenter, nation-wide study in Spain. We recruited adults with HeFH to study clinical differences according to the parental origin. Data on HeFH patients were obtained from the Dyslipidemia Registry of the Spanish Atherosclerosis Society. HeFH patients were grouped in 1231 HeFH-mother-offspring aged 45.7 (16.3) years and 1174 HeFH-father-offspring aged 44.8 (16.7) years. We did not find any difference in lipid parameters (total cholesterol, triglycerides, LDLc, HDLc, and Lp(a)), nor in the comorbidities studied (cardiovascular disease prevalence, age of onset of cardiovascular disease, obesity, diabetes, and hypertension) between groups. Lipid-lowering treatment did not differ between groups. The prevalence of comorbidities did not show differences when they were studied by age groups. Our research with a large group of subjects with HeFH shows that a potential maternal effect is not relevant in FH. However, due to the size of our sample, potential differences between genders cannot be completely ruled out. This implies that severe maternal hypercholesterolemia during pregnancy is not associated with additional risk in the FH affected offspring.


N-acetylcysteine attenuates cyclosporin-induced nephrotoxicity in rats.
Cyclosporin (CsA) has played an important role in the improvement of solid-organ transplant patients and graft survival. However, nephrotoxicity due to CsA remains an important clinical challenge. The renal toxicity of CsA is attributed to reduced renal blood flow which leads to hypoxia reoxygenation injury accompanied by excessive generation of oxygen-derived free radicals (ODFR). N-acetyl-L-cysteine (NAC) is a highly potent antioxidant that has been shown to reduce ODFR injury. In this study an attempt was made to assess the effect of NAC on CsA-induced lipid peroxidation and nephrotoxicity. Adult Sprague-Dawley rats were treated orally with CsA (25 and 50 mg/kg) alone and in combination with different doses of NAC (10, 20 and 40 mg/kg) for a period of 3 weeks. Twenty-four hours after the last treatment, animals were sacrificed and blood was analysed for blood urea nitrogen (BUN) and serum creatinine (SCr), and kidney samples were analysed for lipid hydroperoxides, conjugated dienes and glutathione, and histopathological changes. Treatment of rats with CsA produced a significant increase in BUN and SCr level and histological abnormalities. CsA-induced impairment of renal toxicity was accompanied by significant increase in renal oxidative stress. NAC treatment significantly protected animals against CsA-induced structural and functional impairment of kidney. CsA-induced nephrotoxicity was significantly attenuated by NAC. This study clearly suggests the role of oxidative stress in the pathogenesis of CsA-induced nephrotoxicity. Concomitant use of antioxidants such as NAC to minimize CsA-induced nephrotoxicity in humans warrant further studies.


Improved Arabic Alphabet Characters Classification Using Convolutional Neural Networks (CNN).
Handwritten characters recognition is a challenging research topic. A lot of works have been present to recognize letters of different languages. The availability of Arabic handwritten characters databases is limited. Motivated by this topic of research, we propose a convolution neural network for the classification of Arabic handwritten letters. Also, seven optimization algorithms are performed, and the best algorithm is reported. Faced with few available Arabic handwritten datasets, various data augmentation techniques are implemented to improve the robustness needed for the convolution neural network model. The proposed model is improved by using the dropout regularization method to avoid data overfitting problems. Moreover, suitable change is presented in the choice of optimization algorithms and data augmentation approaches to achieve a good performance. The model has been trained on two Arabic handwritten characters datasets AHCD and Hijja. The proposed algorithm achieved high recognition accuracy of 98.48% and 91.24% on AHCD and Hijja, respectively, outperforming other state-of-the-art models.


Pekin ducks are motivated to access their nest site and exhibit a stress-induced hyperthermia when unable to do so.
The origins of floor-laying in ducks could be low motivation for a nest, or stress related to difficulties with accessing a nest (e.g. competition). Using a behavioural demand test, we investigated if increasing the work required to access their nest impacted ducks' behaviour and two indicators of stress: egg corticosterone concentration and elevation of core body temperature (stress-induced hyperthermia (SIH)). Twelve laying Pekin ducks previously trained in an operant push-door task were required to use a push-door to access their nest. The door was loaded with increasing weight (0-160% of individual BW, four nights per workload) and eventually blocked to prevent nest access. Before testing, temperature data loggers were implanted in the abdomen. Eggs were collected daily to measure corticosterone concentrations. Behaviour towards the push-door was quantified. Three birds were excluded from the experiment at an early stage. Five of the nine remaining birds pushed all workloads up to 160% BW and attempted to pass the blocked door, with another two birds pushing up to 80 and 140% BW. For those that pushed at all workloads (n = 5) the area under the curve (AUC) of hyperthermia was larger at workloads of 80% (P < 0.001), 120% (P < 0.01), 140% (P < 0.001), 160% (P < 0.001), and when the door was blocked (P < 0.001), compared with 0%. On the first night when the door was blocked, all five birds pushed more at the door, but no attempts were made to push on the following 3 nights, yet the AUC of hyperthermia did not differ between nights 2-4 of the blocked door, compared with the first night that the door was blocked. Increasing workload and inability to access the nest had no effect on corticosterone in egg albumen. It was concluded that laying Pekin ducks were motivated to access a nest. Although it was not possible to differentiate metabolic from psychogenic stress on the first night that nest access was denied, we suggest that the occurrence of hyperthermia on the subsequent nights was due to SIH resulting from frustration at their inability to use their preferred nest. Floor-laying therefore is unlikely due solely to low nest-seeking motivation. Egg corticosterone was not a relevant indicator of acute stress. Strategies to improve nest availability (e.g. decreasing competition) could improve the welfare of commercial ducks.


Hypothalamic injury patterns after resection of craniopharyngiomas and correlation to tumor origin: A study based on endoscopic observation.
The precise understanding of hypothalamic injury (HI) patterns and their relationship with different craniopharyngioma (CP) classifications remains poorly addressed. Here, four HI patterns after CP resection based on endoscopic observation were introduced. A total of 131 CP cases treated with endoscopic endonasal approach (EEA) were reviewed retrospectively and divided into four HI patterns: no-HI, mild-HI, unilateral-HI and bilateral-HI, according to intraoperative findings. The outcomes were evaluated and compared between groups in terms of weight gain, endocrine status, electrolyte disturbance and neuropsychological function before and after surgery. A systematic correlation was found between CP origin and subsequent HI patterns. The majority of intrasellar and suprasellar stalk origins lead to a no-HI pattern, the central-type CP mainly develops a mild or bilateral HI pattern, and the majority of tumors with hypothalamic stalk origins result in unilateral HI and sometimes bilateral HI patterns. The proportion of tumors with a maximum diameter >3 cm in the no-HI group was higher than that in the mild-HI group, BMI and quality of life in the no-HI group showed better results than those in the other groups. The incidence of new-onset diabetes insipidus in the bilateral-HI group was significantly higher than that in the other groups. Memory difficulty was observed mainly in the unilateral-HI and bilateral-HI groups. However, the outcomes of electrolyte disturbance, sleep, and cognitive disorder in the unilateral-HI group were significantly better than those in the bilateral-HI group. This study suggests the possibility of using pre- and intraoperative observation of CP origin to predict four HI patterns and even subsequent outcomes after tumor removal.


Stellera chamaejasme L. extracts in the treatment of glioblastoma cell lines: Biological verification based on a network pharmacology approach.
Stellera chamaejasme L (RXLD) has been demonstrated with good clinical effects and medicinal value in the treatment of cancer in vivo and in vitro. Specifically, RXLD can eliminate aggregation accumulation, which is depicted as a vital characteristic feature of intracranial tumors. The potential pharmacological mechanisms of anti-glioblastoma (GBM) have not been adequately identified. The 3D structures of the chemical ingredients in RXLD were imported into the PharmMapper database to construct the pharmacophore models. The gene targets of GBM were obtained from databases. The pharmacophore-targets network and the protein-protein interactions (PPI) were constructed using the String database and were visualized by using Cytoscape. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were conducted using Bioconductor software. Cytoscape visualized the relationship of pathways and candidate genes to screen for key target genes. Software packages PyMOL, AutoDock, and Vina acquired the molecular docking results. In vitro experiments were undertaken to characterize RXLD extracts' effects on A172 cell line proliferation, viability, apoptosis, cell cycle, cell wound healing, cell migration, reactive oxygen species generation, and mitochondrial membrane potential. The expression of core genes in the related pathways was detected by Western blotting. We identified 216 potential targets associated with GBM. The core components in RXLD were neochamaejasmin A, wikstrol A, isochamaejasmin, chamaejasmine, and subtoxin A. The undertaken GO enrichment analysis revealed that oxidative stress, cell proliferation, cell cycle, cell invasion, and cell migration were involved in the biological processes. The KEGG enrichment analysis revealed that the crucial pathway was MAPK pathway, while HRAS, PRKCB, MAPK9, CCND1, and TP53 were distributed in core locations. A total of seven RXLD pharmacophores demonstrated strong spontaneous docking activities with MAPK9. In vitro assays indicated that RXLD can induce apoptosis, block the cell cycle in the G2/M and S phases, inhibit cell migration via the Wnt/β-catenin pathway, and inhibited p62/Nrf2 pathway. We speculate that the RAS/MAPK pathway might be an upstream pathway through which the RXLD exerts its anti-GBM effects and might be able to regulate further the Wnt/β-catenin, the oxidative stress, and the ferroptosis pathways.


Trehalose An Additive Solution for Platelet Concentrate to Protect Platelets from Apoptosis and Clearance during Their Storage at 4°C.
Although cold storage of platelets (PLTs) could decrease the risk of bacterial growth, it could affect on the PLTs viability and hemostatic function. At cold temperatures, trehalose can be used to substitute water, inhibit the solid-liquid transition phase of the PLT membrane, and stop Glycoprotein Ibα (GPIbα) polymerization. In this study, we evaluated the potential of trehalose for reducing the negative effects of cold storage on the apoptosis and the clearance rates of PLTs after long-term storage at cold. In this experimental study, PLT concentrates (PCs) were maintained for five days in the different circumstances. PLTs were subsequently counted by using an automated hematology analyzer. Also water-soluble tetrazolium salt (WST-1) assay was performed to estimate the viability of PLTs. The activity of lactate dehydrogenase enzyme (LDH) was determined by a biochemical analyzer. And human active caspase-3 levels were measured by using enzyme-linked immunosorbent assay (ELISA) method. Also, we applied flow cytometry technique. PLTs count and viability were higher, while LDH amount was lower in trehalose-treated PLTs when compared with two other groups (P=0.03). The highest increase in the amount of caspase-3 levels in the PLTs was observed at 4°C. However, trehalose-treated and 4°C PLTs had a lower amount of active caspase-3 in comparison with 4°C PLTs. The level of PS expression on PLTs was lower in the trehalose-treated PLTs in compared with the two other groups (P=0.03). PLTs ingestion by HepG2 cells was enhanced in the 4°C-stored PLTs. However, the ingestion rate was significantly reduced in the trehalose-treated PLTs on day 5 of storage (P=0.03). Trehalose can moderate the effects of cold temperature on the apoptosis, viability, and the survival rate of PLTs. It also decreases the ingestion rate of refrigerated PLTs in vitro.


Differential virial theorem in relation to a sum rule for the exchange-correlation force in density-functional theory.
Holas and March [Phys. Rev. A. 51, 2040 (1995)] gave a formally exact theory for the exchange-correlation (xc) force F(xc)(r)= -inverted Deltaupsilon(xc)(r) associated with the xc potential upsilon(xc)(r) of the density-functional theory in terms of low-order density matrices. This is shown in the present study to lead, rather directly, to the determination of a sum rule nF(xc)=0 relating the xc force with the ground-state density n(r). Some connection is also made with an earlier result relating to the external potential by Levy and Perdew [Phys. Rev. A. 32, 2010 (1985)] and with the quite recent study of Joubert [J. Chem. Phys. 119, 1916 (2003)] relating to the separation of the exchange and correlation contributions.


Intraparenchymal drug delivery via positive-pressure infusion: experimental and modeling studies of poroelasticity in brain phantom gels.
We have used agarose gel to develop a robust model of the intraparenchymal brain tissues for the purpose of simulating positive-pressure infusion of therapeutic agents directly into the brain. In parallel with that effort, we have synthesized a mathematical description of the infusion process on the basis of a poroelastic theory for the swelling of the tissues under the influence of the infusate's penetration into the interstitial space. Infusion line pressure measurements and video microscopy determinations of infusate volume of distribution within the gel demonstrate a good match between theory and experiment over a wide range of flow rates (0.5-10.0 microliters/min) and have clinical relevance for the convection-enhanced delivery of drugs into the brain without hindrance by the blood-brain barrier. We have put the brain phantom gel and the infusion measurement system into routine use in determining performance characteristics of novel types of neurosurgical catheters. This approach simplifies the catheter design process and helps to avoid some of the costs of in vivo testing. It also will allow validation of the elementary aspects of treatment planning systems that predict infusion distribution volumes on the basis of theoretical descriptions such as those derived from the poroelastic model.


Hoarding cases involving older adults: the transition from a private matter to the public sector.
Hoarding interventions with older adults require significant resources from multiple public agencies, yet recidivism occurs frequently. To improve services through better coordination, some communities have formed multiagency hoarding teams (MAHT), which include aging services. MAHTs requested this mixed methods study to understand the progression of cases through the public sector. Quantitative data collected on 52 cases involving adults ages 60+ identified steps in this process. Qualitative data collected from MAHT members were the basis for case studies illustrating the progression of cases through the public sector. Findings have implications for social workers involved in local service coordination, training, and policy.


Prediction Model for Gastric Cancer With DNA Mismatch Repair Deficiency.
DNA mismatch repair (MMR) deficiency has received increasing attention as a biomarker of anti-PD-1 treatments of solid tumors including gastric cancer (GC). However, efficient screening has not been established. A total of 513 patients were tested for the expression of MMR proteins by immunohistochemistry to identify MMR deficient GC. Development of a prediction model was attempted using the common clinicopathological features. In total, 11% (57/513) of the patients showed loss of expression of either one or more MMR proteins (MMR protein deficiency; MMR-D). Multivariate analysis demonstrated that age (≥70 years), sex (female), tumor location (lower 1/3), depth invasion (low, T1/T2/T3), and absence of distant metastasis were significantly independent predictive factors of MMR-D GCs. The MMR-D GC probability estimated by the prediction model ranged from 0.4% to 62.2%, and the area under the curve of the receiver operating characteristics curve was 0.82 (95% confidence interval=0.75-0.87). Our prediction model can sufficiently and efficiently identify MMR-D GCs using clinical features.


Coming Out and the Potential for Growth in Sexual Minorities: The Role of Social Reactions and Internalized Homonegativity.
Coming out is a significant and sometimes difficult process in the lives of sexual minorities, but disclosure can also affect wellbeing in positive ways, including reduced distress and greater relationship satisfaction. This study investigates the possibility of stress-related growth and depreciation following coming out. To obtain a diverse sample with varying coming-out experiences, data were collected from undergraduate students as well as from online sources, including lesbian, gay, and bisexual support groups and Pride groups. Regression analyses indicated that negative social reactions to coming out predicted both growth and depreciation, although they more strongly predicted depreciation. Positive social reactions were positively related to stress-related growth, while internalized homonegativity was inversely associated with growth. Although the two sample sources (online and campus) differed in some ways, sample source was not a significant predictor in the regressions, nor was it indicated as a moderator in exploratory ANOVA analyses.


Determination of Equilibrium Adsorbed Morphologies of Surfactants at Metal-Water Interfaces Using a Modified Umbrella Sampling-Based Methodology.
Surfactants adsorb to metal-water interfaces in various morphologies, including self-assembled monolayers (SAMs), cylindrical and spherical micelles, or hemimicelles. Current molecular simulation methods are unable to efficiently sample the formation of these morphologies because of the large diffusive/energetic barriers. We introduce a modified umbrella sampling-based methodology that allows sampling of these morphologies from any initial configuration and provides free energy differences between them. Using this methodology, we have studied adsorption behavior of cationic [quaternary ammonium (quat) of 4 and 12 carbon long alkyl tails], uncharged [decanethiol], and anionic [phosphate monoester] surfactants and their mixtures at a gold-water interface. We find that while Coulombic repulsion between the charged head groups of quat-4 limits their adsorption to a sparse layer, stronger hydrophobic interactions between the alkyl tails of quat-12 promote adsorption resulting in a morphology with adsorbed hemispherical micelles sitting atop a monolayer. Decanethiol molecules adsorb in a densely packed bilayer with the molecules standing-up on the surface in the first layer and lying parallel to the surface in the second layer. Cationic and anionic surfactant mixtures display a synergistic adsorption behavior. These results elucidate the role of molecular characteristics in dictating the nature of adsorbed morphologies of surfactants at metal-water interfaces.


Splanchnic Vein Thrombosis - an Uncommon Complication after Laparoscopic Sleeve Gastrectomy.
Laparoscopic sleeve gastrectomy (LSG) is an innovative and relatively safe surgical approach for weight reduction in morbidly obese people. Splanchnic vein thrombosis (SVT) is an extremely rare complication of LSG and, if not recognized, carries a high mortality rate. This paper highlights a potentially lethal condition of SVT after LSG. A 37-year-old morbidly obese woman was referred to our institution for LSG. Three weeks after the intervention, she was readmitted with abdominal pain, vomiting, nausea, diarrhea, and fever with positive family anamnesis to viral disease. Abdominal X-ray as well as utrasonography were both normal, and no X-ray contrast medium leakage was observed. One week later, she was readmitted with septic condition. An abdominal computed tomography scan diagnosed lienal vein thrombosis along its whole length and partial thrombosis of the superior mesenteric vein. SVT presents very heterogeneously, which makes it extremely challenging to diagnose and to make an appropriate treatment decision. With regard to the high prevalence of obesity and the increasing frequency of LSG, prompt diagnosis and management are crucial.


High homocysteine induces betaine depletion.
Betaine is the substrate of the liver- and kidney-specific betaine-homocysteine (Hcy) methyltransferase (BHMT), an alternate pathway for Hcy remethylation. We hypothesized that BHMT is a major pathway for homocysteine removal in cases of hyperhomocysteinaemia (HHcy). Therefore, we measured betaine in plasma and tissues from patients and animal models of HHcy of genetic and acquired cause. Plasma was collected from patients presenting HHcy without any Hcy interfering treatment. Plasma and tissues were collected from rat models of HHcy induced by diet and from a mouse model of cystathionine β-synthase (CBS) deficiency. S-adenosyl-methionine (AdoMet), S-adenosyl-homocysteine (AdoHcy), methionine, betaine and dimethylglycine (DMG) were quantified by ESI-LC-MS/MS. mRNA expression was quantified using quantitative real-time (QRT)-PCR. For all patients with diverse causes of HHcy, plasma betaine concentrations were below the normal values of our laboratory. In the diet-induced HHcy rat model, betaine was decreased in all tissues analysed (liver, brain, heart). In the mouse CBS deficiency model, betaine was decreased in plasma, liver, heart and brain, but was conserved in kidney. Surprisingly, BHMT expression and activity was decreased in liver. However, in kidney, BHMT and SLC6A12 expression was increased in CBS-deficient mice. Chronic HHcy, irrespective of its cause, induces betaine depletion in plasma and tissues (liver, brain and heart), indicating a global decrease in the body betaine pool. In kidney, betaine concentrations were not affected, possibly due to overexpression of the betaine transporter SLC6A12 where betaine may be conserved because of its crucial role as an osmolyte.


Discordant results of visual and quantitative estimates of stenosis severity before and after coronary angioplasty.
The ability to accurately estimate the severity of epicardial coronary stenoses is critical in the assessment of the immediate and long-term results of percutaneous transluminal coronary angioplasty (PTCA). We prospectively compared visual estimates, performed by experienced interventional cardiologists, with computerized quantitative angiographic measurements of stenosis severity in a group of patients (n = 305) before, immediately after and 6 months after PTCA. Before PTCA the visual estimate of the mean (+/- SD) percentage stenosis severity, 80.6 (+/- 9.7)%, was significantly (P < 0.001) higher than the equivalent value, 73.4 (+/- 11.1)%, obtained with use of quantitative angiography. Immediately after PTCA the visual estimate of the mean residual stenosis, 18.8 (+/- 12.3)%, was significantly (P < 0.0001) lower than the equivalent quantitative estimate, 37.4 (+/- 14)%. Additionally, the residual stenosis was more frequently (18% vs. 3%) classified as significant (> 50%) by quantitative angiography. At follow-up, quantitative measurements of stenosis severity showed a Gaussian distribution with a mean of 54.8 (+/- 21)%, whereas visual estimates had a bimodal distribution with populations greater than 70% and less than 50%. Visual estimates provide an inaccurate assessment of the immediate and medium term results of PTCA. Quantitative measurements suggest that the immediate results of PTCA are frequently misclassified as successful by the operator. Conversely, restenosis rates are underestimated by the operators suggesting that a more objective method must be used in trials to assess the impact of new therapies on the rate of restenosis.


Aberrant expression of chromogranin A, miR-146a, and miR-146b-5p in prostate structures with focally disrupted basal cell layers: an early sign of invasion and hormone-refractory cancer?
Our recent studies have suggested that prostate tumor invasion is triggered by autoimmunoreactions induced focal basal cell layer disruptions (FBCLD) that selectively favor monoclonal proliferation of the overlying progenitors or of a biologically more aggressive cell clone. As circulating chromogranin-A (CgA) levels are found to correlate with tumor progression and the status of hormone refractoriness, our current study attempted to assess whether CgA-positive cells would be preferentially distributed in epithelial structures with FBCLD. Paraffin-embedded specimens from 50 patients with organ-confined prostate cancer were subjected to double immunohistochemical analysis with monoclonal antibodies to basal cells and CgA. From each case, 3-5 randomly selected fields were digitally photographed and the photos were magnified 400% and the numbers of CgA-positive cells in epithelial structures with non-disrupted, focally disrupted, and lost basal cell layer were separately counted. The averaged number of cell for each category was statistically compared with the Pearson's Chi-square test. In addition, morphologically similar structures with and without CgA-positive cell clusters were microdissected from four selected cases and subjected to a comparison of differential micro-RNA expression levels. Our study revealed that, although isolated CgA-positive cells were seen in both the basal cell layer and the luminal cell population in all cases, only 8 cases (16%) harbored large clusters of CgA-positive cells that were concentrated in a given area, in which all or nearly all cells appeared to share a similar morphological and immunohistochemical profile. Microdissected epithelial structures with CgA-positive cell clusters exhibited a more than 5- and 7-fold lower expression of miR-146a and miR-146b-5p than their CgA-negative counterparts. As focal basal cell layer disruptions and the reduction or loss of miR-146a and miR-146b-5p has been documented to correlate with prostate tumor invasion and hormone refractoriness, our findings suggest that aberrant CgA expression in epithelial structures with FBCLD may represent an early sign of these events.


Videotaped cue for urge to drink alcohol.
The urge to drink alcohol can be robustly and reliably induced via actual exposure to a person's preferred alcoholic beverage. Unfortunately, these exposure paradigms are unwieldy for functional magnetic resonance imaging studies. The goal of this study was to examine whether viewing a personalized videotaped cue could induce alcohol craving. The following hypotheses were tested: (1) individualized cue videotapes can reliably elicit the urge to drink alcohol in alcohol-dependent participants and (2) alcohol drinking histories can predict reactivity to cue. DSM-IV criteria were used to identify an alcohol-dependent group (ADG). Controls included a light-drinking group and a moderate-drinking group. Urge to drink alcohol was assessed at baseline and after each of five in vivo exposure conditions: water (W), alcohol 1 (A1), mood induction (M), alcohol 2 (A2), and relaxation (R). The entire exposure session was videotaped. Each participant's video footage was digitally edited to produce a 17.5-min cue that was presented to the participant 24 to 72 hr later. Ratings of urge to drink alcohol across the five exposure conditions were compared for both the in vivo and the video exposure sessions. Fourteen participants (five in the light-drinking group, four in the moderate-drinking group, and five in the ADG) completed both sessions. Participants in each group showed differences between neutral cue exposure (W and R) and alcohol-related cue exposure (A1, M, and A2) in both the in vivo cue session (p < 0.002) and the videotape session (p < 0.02). Post hoc comparisons among the groups to alcohol-related cues established that, in both sessions (p(in vivo) = 0.04; p(videotape) = 0.04), the ADG demonstrated the greatest urge to drink. Alcohol cue reactivity can be reliably induced and assessed in alcohol-dependent participants via personalized videotapes. History of alcohol consumption is positively correlated with the degree of cue reactivity. This study advances our ability to assess alcohol cue reactivity in the absence of alcohol.


Metastatic Adenocarcinoma of the Prostate to the Brain Initially Suspected as Meningioma by Magnetic Resonance Imaging.
Brain metastasis from prostate cancer is rare, occurring in less than 1% of metastatic prostate cancer patients. Brain metastasis can cause edema, neurologic symptoms, and may be misdiagnosed as primary brain tumors on imaging. A 68-year-old male presented to the emergency department complaining of headaches, right-sided weakness, multiple falls, and a 45 pounds of unintentional weight loss. Computerized tomography (CT) scan without contrast of the head showed a 3.2 cm right frontal mass with edema suspicious for meningioma. Associated nonspecific bony lesions were found on CT of the abdomen and pelvis. Magnetic resonance imaging (MRI) of the brain showed a 2.8 cm right frontal mass with an enhanced dural tail. Preoperative labs were noteworthy for a hemoglobin of 9.7 and prostate-specific antigen (PSA) of 66.7 ng/ml. Craniotomy with resection of tumor was performed with a frozen sample diagnosed as meningioma. Permanent pathology with stains were positive for PSA and prostatic-specific acid phosphatase (PSAP), making the diagnosis of metastatic prostate adenocarcinoma. Postoperatively, nuclear bone scan showed uptake in the axial skeleton consistent with metastasis. After the diagnosis of metastatic prostate cancer was made, bicalutamide was administered followed by degarelix with plans to transition to leuprorelin one month later. This is to be followed up by whole brain radiation therapy (WBRT). PSA was 118.53 ng/ml three weeks after craniotomy, but prior to androgen deprivation therapy. Metastatic prostate cancer can present with neurological symptoms most commonly following spread to the axial skeleton and impingement of the spinal cord. Metastasis to the brain is rare and is usually associated with vague symptomatology depending on extent and location of the lesion. While brain metastasis can occur in known prostate cancer patients, this case shows that metastasis can occur prior to any formal prostate cancer diagnosis and can be mistaken for meningioma on imaging and frozen sectioning. Practitioners must be vigilant, and precautions should be taken to rule in metastatic prostate cancer as a possible cause for a brain lesion in patients of the appropriate demographics.


Effects of Iron and Oxygen on Chlorophyll Biosynthesis : II. OBSERVATIONS ON THE BIOSYNTHETIC PATHWAY IN ISOLATED ETIOCHLOROPLASTS.
The conversion of l-glutamate to delta-aminolevulinate, in preparations of cucumber etiochloroplasts incubated in vitro, was inhibited by protoheme IX and Mg-protoporphyrin IX. Mg-protoporphyrin IX was destroyed in the presence of air and plastids; this breakdown was accelerated by S-adenosyl methionine. Mg-protoporphyrin IX was also converted to protochlorophyllide in vitro. This conversion exhibited an absolute requirement for atmospheric oxygen and was strongly stimulated by S-adenosyl methionine and by darkness.Based on these results, and on the results of the preceding paper (Spiller, Castelfranco, Castelfranco 1981 Plant Physiol 68: 107-111), a comprehensive hypothesis for the role of O(2) and Fe in chlorophyll biosynthesis is formulated.


The Spliced Leader RNA Silencing (SLS) Pathway in Trypanosoma brucei Is Induced by Perturbations of Endoplasmic Reticulum, Golgi Complex, or Mitochondrial Protein Factors: Functional Analysis of SLS-Inducing Kinase PK3.
In the parasite Trypanosoma brucei, the causative agent of human African sleeping sickness, all mRNAs are trans-spliced to generate a common 5' exon derived from the spliced leader (SL) RNA. Perturbations of protein translocation across the endoplasmic reticulum (ER) induce the spliced leader RNA silencing (SLS) pathway. SLS activation is mediated by a serine-threonine kinase, PK3, which translocates from the cytosolic face of the ER to the nucleus, where it phosphorylates the TATA-binding protein TRF4, leading to the shutoff of SL RNA transcription, followed by induction of programmed cell death. Here, we demonstrate that SLS is also induced by depletion of the essential ER-resident chaperones BiP and calreticulin, ER oxidoreductin 1 (ERO1), and the Golgi complex-localized quiescin sulfhydryl oxidase (QSOX). Most strikingly, silencing of Rhomboid-like 1 (TIMRHOM1), involved in mitochondrial protein import, also induces SLS. The PK3 kinase, which integrates SLS signals, is modified by phosphorylation on multiple sites. To determine which of the phosphorylation events activate PK3, several individual mutations or their combination were generated. These mutations failed to completely eliminate the phosphorylation or translocation of the kinase to the nucleus. The structures of PK3 kinase and its ATP binding domain were therefore modeled. A conserved phenylalanine at position 771 was proposed to interact with ATP, and the PK3F771L mutation completely eliminated phosphorylation under SLS, suggesting that the activation involves most if not all of the phosphorylation sites. The study suggests that the SLS occurs broadly in response to failures in protein sorting, folding, or modification across multiple compartments. IMPORTANCE In this study, we found that SLS is induced by depletion of the essential ER-resident chaperones BiP and calreticulin, ER oxidoreductin 1 (ERO1), and the Golgi complex-localized quiescin sulfhydryl oxidase (QSOX). Most strikingly, silencing of Rhomboid-like 1 (TIMRHOM1), involved in mitochondrial protein import, also induces SLS. We also report on the autophosphorylation of PK3 during SLS induction. This study has implications for our understanding of how trypanosomes keep the homeostasis between the ER and the mitochondria and suggests that PK3 may participate in the connection between these two organelles. The pathway, when induced, leads to the suicide of these parasites, and its induction offers a potential novel drug target against these parasites.


Ceramide kinase and the ceramide-1-phosphate/cPLA2alpha interaction as a therapeutic target.
Ceramide kinase (CERK) was discovered more than a decade ago. Since then, numerous reports have been published demonstrating a role for CERK in various signal transduction pathways involved in inflammation, immunity or cancer. In this review, the biosynthesis of ceramide-1-phosphate (C1P) and the various roles of CERK and C1P in biological mechanisms will be overviewed. We will focus on the role of C1P in eicosanoid synthesis, more specifically, in the activation and translocation of cPLA(2)alpha. Furthermore, the possible therapeutic relevance of inhibitors of these mechanisms is discussed.


Effects of crystal shape on the energy levels of zero-dimensional PbS quantum dots.
Nanometer-size PbS quantum dots have been made by electrodeposition on a Au(111) substrate. The deposited nanocrystals have a flattened cubic shape. We probed the single-electron energy-level spectrum of individual quantum dots by scanning tunneling spectroscopy and found that it deviates strongly from that of spherical PbS quantum dots. The measured energy-level spectrum is successfully explained by considering strong confinement in a flattened cubic box.


Transrectal ultrasonically-guided core biopsies in the assessment of local cure of prostatic cancer after radical external beam radiotherapy.
Fifty-five patients were included in an extended follow-up after radical radiation therapy (RRT) for localized prostatic cancer (T1-3, Nx, M0). Local cure was assessed by a combination of digital rectal examination (DRE), transrectal ultrasound (TRUS) and systematic 'mapping' with TRUS-guided core biopsies (TGCB). After a mean follow-up of 6.8 years, 33% (18/55) of the patients were locally free of tumour, while in 67% (37/55) of cases residual cancer was demonstrated in the biopsies. Endocrine treatment did not influence the local cure rate, nor did the T stage of tumour grade at diagnosis or the cumulative radiation effect (CRE) values within the range of the present study. The sensitivity of DRE and TRUS was low; 37% and 20% respectively, while the specificity of the DRE and TRUS methods was 83% and 94% respectively. The conclusion of the study is that residual tumour was found in the high proportion of biopsied patients nearly 7 years after RRT and that multiple, TRUS-guided core biopsies are mandatory in the assessment of local cure in patients irradiated for prostatic cancer; both DRE and TRUS on their own are less reliable.


[Insulin resistance and pathogenesis of non-insulin-dependent diabetes mellitus (I)].
The authors present a review of current knowledge of insulin mechanism on cellular level and of the defects leading to diminished cellular insulin sensitivity and to development of insulin resistance (IR). Attention is focused primarily on IR in subjects with non-insulin dependent diabetes mellitus (NIDDM) with main stress on the postreceptor level of insulin effect which includes glucose transport, storage (glycogen-synthesis) and glycolysis. The defects of these mechanisms (namely the decrease in glycogen-synthase activity) are considered the main causes of IR in patients with NIDDM. Beside the above mentioned factors the authors discuss some of the less well-known mechanisms that can be found in the background of IR in patients with NIDDM (tissue blood flow, capillary density, transport of insulin across the endothelial barrier, glucose toxicity, role of intracellular calcium and others.


A New Amphotericin B-loaded Trimethyl Chitosan Nanoparticles as a Drug Delivery System and Antifungal Activity on Candida albicans Biofilm.
Amphotericin B (AmB) is an effective antifungal agent; however, the application of AmB is associated with a number of drawbacks. Application of nanoparticles (NPs) is known to improve the efficiency of drug delivery to the target tissues, compared to the traditional methods. In this study, a novel method of NPs preparation was developed. The trimethyl chitosan (TMC) was synthesized using low molecular weight chitosan and was used for the preparation of TMC-NPs through ionic gelation method. Afterward, AmB-loaded TMC-NPs (TMC-NPs/AmB) were prepared and their drug delivery potential was testes. The TMC-NPs and TMC-NPs/AmB were characterized for their structure, particle size, Zeta potential, polydispersity index, morphology, loading efficiency, loading capacity, in vitro release profile, release kinetic, and entrapped AmB potency. The cytotoxicity and antifungal activity of TMC-NPs/AmB against Candida albicans biofilm were evaluated. The quaternization of TMC was estimated to be 36.4%. The mean particle size of TMC-NPs and TMC NPs/AmB were 210±15 and 365±10 nm, respectively, with a PDI of 0.30 and 0.4, ZP of +34±0.5 and +28±0.5 mV, respectively. Electron microscopy analysis indicated uniform spherical shapes with smooth surfaces. The TMC-NPs/AmB indicated LE of 76% and LC of 74.04 % with a potency of 110%. The release profile of TMC-NPs/AmB was best explained by the Higuchi model. The initial release after 10 h was obtained at 38%, and the rates of release after 36 and 84 h were determined at 67% and 76% respectively, which was significantly different (P<0.05) from previous time points. The minimum inhibitory concentration (MIC) (50%) of NPs/AmB and AmB were 0.65 and 1.75 μg/mL, and the MIC 80% were determined at 1.95 and 7.75 μg/mL, respectively, demonstrating a significant improvement in antifungal activity. The half-maximal inhibitory concentration for TMC-NPs/AmB and AmB were estimated at 86 and 105 μg/mL, respectively, indicating a significant reduction in cytotoxicity and the adverse effect. This study could successfully introduce a practical method to synthesize TMC-NPs. The encapsulation process was efficient and significantly improved the antifungal activity of AmB. The developed method can be applied to improve the feasibility of oral delivery while reducing the adverse effects associated with traditional methods.


Respiratory syncytial virus infection in infants is associated with predominant Th-2-like response.
Viral infections have been associated with cellular immune responses and production of Th-1 cytokines. Respiratory syncytial virus (RSV), however, induces virus-specific IgE, which might be a consequence of a Th-2-like activation. To test this hypothesis we quantified interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) in the supernatant of peripheral blood mononuclear cells cultured for 24 and 48 h in the presence or absence of phytohemaglutinin and pokeweed mitogen and the lymphocyte phenotypes to analyze subsets and their activation markers, from 15 hospitalized infants during an acute lower respiratory infection caused by RSV and 17 healthy control infants from 1 to 15 mo of age. Compared with the control infants, those infected with RSV had an increase in the number of B-cells (p < 0.02) and decreases in both CD8+ T-cells (p < 0.01) and activated CD8+/CD25+ suppressor/ cytotoxic T-cells (p < 0.007). In RSV-infected infants, IFN-gamma production was subtotally suppressed, whereas IL-4 production was decreased to a lesser degree, giving significantly (p < 0.001) increased IL-4/IFN-gamma ratio compared with that in the control infants. These findings suggest a predominant Th-z-like response in RSV-infected infants, which could explain some aspects of the immunopathogenesis of RSV infection and the RSV-specific and nonspecific IgE antibody responses observed.


Combination of static and temporal data analysis to predict mortality and readmission in the intensive care.
There are approximately 4 million intensive care unit (ICU) admissions each year in the United States with costs accounting for 4.1% of national health expenditures. Unforeseen adverse events contribute disproportionately to these costs. Thus, there has been substantial research in developing clinical decision support systems to predict and improve ICU outcomes such as ICU mortality, prolonged length of stay, and ICU readmission. However, the data in the ICU is collected at diverse time intervals and includes both static and temporal data. Common methods for static data mining such as Cox and logistic regression and methods for temporal data analysis such as temporal association rule mining do not model the combination of both static and temporal data. This work aims to overcome this challenge to combine static models such as logistic regression and feedforward neural networks with temporal models such as conditional random fields(CRF). We demonstrate the results using adult patient records from a publicly available database called Multi-parameter Intelligent Monitoring in Intensive Care - II (MIMIC-II). We show that the combination models outperformed individual models of logistic regression, feed-forward neural networks and conditional random fields in predicting ICU mortality. The combination models also outperform the static models of logistic regression and feed-forward neural networks for the prediction of 30 day ICU readmissions when tested using Matthews correlation coefficient and accuracy as the metrics.


Replacement of nuclear protein by histone in pig sperm nuclei during in vitro fertilization.
Sperm-specific nuclear protamines are dissociated before decondensation of sperm nuclei during fertilization in pigs. In the present study, replacement of nuclear protein by histone in boar spermatozoa during in vitro fertilization was evaluated by immunohistochemistry using anti-histone antibody. First, the specificity of the antibody used in this study was examined. Immunohistochemistry of the testes and epididymides indicated that somatic nuclei, but not elongated spermatids or maturing spermatozoa, were immunoreactive. Furthermore, immunoreaction was diminished after the antibody had been preincubated with unfractionated histone, indicating that the antibody was specific for the somatic nuclear histone. Immunohistochemistry of serial sections of oocytes, which were matured and co-cultured with boar spermatozoa for 2 to 6 h indicated that, at 2 to 3 h after insemination, penetrating sperm nuclei in the condensed state were not immunoreactive. At 4 to 5 h after insemination, some of the condensed sperm nuclei were immunoreactive in part or over the whole area of the nucleus, and all of the decondensing nuclei and male pronuclei were immunoreactive. At 6 h after insemination, the decondensing sperm nuclei and well-developed male pronuclei were immunoreactive. These results imply that, in pigs, remodelling of sperm nuclear protein from protamine to histone is initiated at the time of sperm penetration, before onset of decondensation and male pronuclear formation.