Investigating the Role of Ferritin in Determining Sexual Underdevelopment in Beta-Thalassemia Major Patients: A Cross-Sectional Analysis From Pakistan.
Background Beta-thalassemia major, a genetic disorder, delineates a vast spectrum of hematological and endocrinological complications. Elevated serum ferritin levels in beta-thalassemia patients represent various transfusion-related complications including infection, hemochromatosis, and severe iron overload that might lead to endocrinopathies such as hypogonadism leading to sexual underdevelopment. Our study, thus, aims to explore the role of ferritin in determining sexual underdevelopment in such patients. Methods This multicentric cross-sectional study included a total of 120 beta-thalassemia patients. The sexual development of the patients was assessed using the Tanner staging system. Serum ferritin levels and other demographical parameters of the patients were collected. Independent-samples t-test, chi-square test, and receiver operating characteristic (ROC) curve were used to analyze the data. Results Out of 120 patients, 70 patients were males with a mean age of 18.95 ± 4.21 years. According to the Tanner staging system, 48 patients were sexually underdeveloped while 72 patients achieved sexual maturity. ROC curve analysis showed that ferritin levels at a cutoff value of 4900 mg/dL were 73.7% sensitive and 71.1% specific to predict sexual underdevelopment in beta-thalassemia patients. Conclusions Elevated serum ferritin levels were moderately sensitive and specific in predicting sexual underdevelopment in beta-thalassemia patients. This can serve as a low-cost parameter in determining sexual underdevelopment in such patients. More prospective cohort studies are needed to establish the association between elevated serum ferritin levels and sexual underdevelopment.


Evidence-based esthetic dentistry.
Evidence-based clinical practice integrates the best available evidence with clinical expertise. This article presents a clinical case scenario and, using a four-step, evidence-based approach, demonstrates how to (1) ask an evidence-based question; (2) search MEDLINE for the best evidence; (3) critically appraise the evidence; and (4) apply the evidence to the patient. The procedure is demonstrated with the sample question, Does bleaching of bonded porcelain veneers increase marginal leakage? A MEDLINE search strategy was developed for synonyms of the key words that best identify the problem, the intervention, and the outcome. The synonyms were combined using the Boolean operator "or" to identify a "sensitive" (i.e., inclusive) universe of 140,000 journal articles. These categories were then combined using the Boolean operator "and" to identify the most "specific" (i.e., exclusive) four articles from among the 140,000. Finally, to find the best evidence, the articles were limited to "humans" and "randomized controlled trials." This identified one article. Critical appraisal of the limited data in this one article indicates that the methods are valid and statistically significant, but because of the methods employed, may not be clinically important. Evidence-based methods take one to the edge of the available information universe in about 15 minutes. The results can be both exhilarating and sobering. They can indicate the depth or limits of available information and suggest gaps in the knowledge-base that require further study. Most importantly, however, the results allow practitioners to communicate incisively and truthfully with patients and to make more informed clinical choices.


Lack of consensus between general practitioners and official guidelines on alcohol abstinence during pregnancy.
Many pregnant women in Denmark have been advised that some alcohol intake is acceptable. In the 1999-2007-period, the Danish National Board of Health advised pregnant women that some alcohol intake was acceptable. From 2007, alcohol abstinence has been recommended. We aimed to describe the attitudes towards and knowledge about alcohol in pregnancy among general practitioners (GPs) in Denmark in 2000 and in 2009. In 2000, we invited a representative sample of GPs in the catchment area of the Antenatal Care Centre in Aarhus to participate in the study. Participants were interviewed about their attitudes, beliefs, knowledge and information practice in relation to alcohol in pregnancy. Identical questions were sent to all GPs in the area in 2009. In 2000, most GPs (71%) considered that some alcohol intake in pregnancy was acceptable, mostly on a weekly level. There was considerable interperson variation in the participants' attitudes and recommendations to pregnant women. In 2009, significantly more GPs (51%) considered abstinence to be preferable, and significantly more GPs (53%) gave this advice to pregnant women than in 2000. Their knowledge about the official recommendations on alcohol was good. Older GPs were more likely to recommend abstinence. The attitudes towards and knowledge about drinking in pregnancy among GPs have changed along with the change in official policy. In 2000, data collection was funded by The Danish National Board of Health (J.no. 407-15-1999). not relevant.


New decoding algorithms for Hidden Markov Models using distance measures on labellings.
Existing hidden Markov model decoding algorithms do not focus on approximately identifying the sequence feature boundaries. We give a set of algorithms to compute the conditional probability of all labellings "near" a reference labelling lambda for a sequence y for a variety of definitions of "near". In addition, we give optimization algorithms to find the best labelling for a sequence in the robust sense of having all of its feature boundaries nearly correct. Natural problems in this domain are NP-hard to optimize. For membrane proteins, our algorithms find the approximate topology of such proteins with comparable success to existing programs, while being substantially more accurate in estimating the positions of transmembrane helix boundaries. More robust HMM decoding may allow for better analysis of sequence features, in reasonable runtimes.


Stereochemical course of glucan hydrolysis by barley (1-->3)- and (1-->3, 1-->4)-beta-glucanases.
The stereochemical course of hydrolysis of Laminaria digitata laminarin and barley (1-->3, 1-->4)-beta-glucan by barley (1-->3)-beta-glucanase (E.C. 184.108.40.206) isoenzyme GII and (1-->3, 1-->4)-beta-glucanase (EC 220.127.116.11) isoenzyme EII, respectively, has been determined by 1H-NMR. Both enzymes catalyse hydrolysis with retention of anomeric configuration (e-->e) and may therefore operate via a double displacement mechanism. We predict that all other members of Family 17 of beta-glycosyl hydrolases also follow this stereochemical course of hydrolysis.


Replacement of Trp28 in Escherichia coli thioredoxin by site-directed mutagenesis affects thermodynamic stability but not function.
Escherichia coli thioredoxin contains two tryptophan residues (Trp28 and Trp31) situated close to the active site disulfide/dithiol. In order to probe the structural and functional roles of tryptophan in the mechanism of E. coli thioredoxin (Trx), we have replaced Trp28 with alanine using site-directed mutagenesis and expressed the mutant protein W28A in E. coli. Changes in the behavior of the mutant protein compared with the wild-type protein have been monitored by a number of physical and spectroscopic techniques and enzyme assays. As expected, removal of a tryptophan residue causes profound changes in the fluorescence spectrum of thioredoxin, particularly for the reduced protein (Trx-(SH)2), and to a lesser extent for the oxidized protein (Trx-S2). These results show that the major contribution to the strongly quenched fluorescence of Trx-S2 in both wild-type and mutant proteins is from Trp31, whereas the higher fluorescence quantum yield of Trx-(SH)2 in the wild-type protein is dominated by the emission from Trp28. The fluorescence, CD, and 1H NMR spectra are all indicative that the mutant protein is fully folded at pH 7 and room temperature, and, despite the significance of the change, from a tryptophan in close proximity to the active site to an alanine, the functions of the protein appear to be largely intact. W28A Trx-S2 is a good substrate for thioredoxin reductase, and W28A Trx-(SH)2 is as efficient as wild-type protein in reduction of insulin disulfides. DNA polymerase activity exhibited by the complex of phage T7 gene 5 protein and Trx-(SH)2 is affected only marginally by the W28A substitution, consistent with the buried position of Trp28 in the protein. However, the thermodynamic stability of the molecule appears to have been greatly reduced by the mutation: guanidine hydrochloride unfolds the protein at a significantly lower concentration for the mutant than for wild type, and the thermal stability is reduced by about 10 degrees C in each case. The stability of each form of the protein appears to be reduced by the same amount, an indication that the effect of the mutation is identical in both forms of the protein. Thus, despite its close proximity to the active site, the Trp28 residue of thioredoxin is not apparently essential to the electron transfer mechanism, but rather contributes to the stability of the protein fold in the active site region.


Synthesis of Lectin-Like Protein in Developing Cotyledons of Normal and Phytohemagglutinin-Deficient Phaseolus vulgaris.
The genome of the common bean Phaseolus vulgaris contains a small gene family that encodes lectin and lectin-like proteins (phytohemagglutinin, arcelin, and others). One of these phytohemagglutinin-like genes was cloned by L. M. Hoffman et al. ([1982] Nucleic Acids Res 10: 7819-7828), but its product in bean cells has never been identified. We identified the product of this gene, referred to as lectin-like protein (LLP), as an abundant polypeptide synthesized on the endoplasmic reticulum (ER) of developing bean cotyledons. The gene product was first identified in extracts of Xenopus oocytes injected with either cotyledonary bean RNA or LLP-mRNA obtained by hybrid-selection with an LLP cDNA clone. A tryptic map of this protein was identical with a tryptic map of a polypeptide with the same SDS-PAGE mobility detectable in the ER of bean cotyledons pulse-labeled with either [(3)H]glucosamine or [(3)H]amino acids, both in a normal and in a phytohemagglutinin-deficient cultivar (cultivars Greensleeves and Pinto UI 111). Greensleeves LLP has M(r) 40,000 and most probably has four asparagine-linked glycans. Pinto UI 111 LLP has M(r) 38,500. Unlike phytohemagglutinin which is a tetramer, LLP appears to be a monomer by gel filtration analysis. Incorporation of [(3)H]amino acids indicates that synthesis of LLP accounts for about 3% of the proteins synthesized on the ER, a level similar to that of phytohemagglutinin.


Monitoring and assessment of ingestive chewing sounds for prediction of herbage intake rate in grazing cattle.
Accurate measurement of herbage intake rate is critical to advance knowledge of the ecology of grazing ruminants. This experiment tested the integration of behavioral and acoustic measurements of chewing and biting to estimate herbage dry matter intake (DMI) in dairy cows offered micro-swards of contrasting plant structure. Micro-swards constructed with plastic pots were offered to three lactating Holstein cows (608±24.9 kg of BW) in individual grazing sessions (n=48). Treatments were a factorial combination of two forage species (alfalfa and fescue) and two plant heights (tall=25±3.8 cm and short=12±1.9 cm) and were offered on a gradient of increasing herbage mass (10 to 30 pots) and number of bites (~10 to 40 bites). During each grazing session, sounds of biting and chewing were recorded with a wireless microphone placed on the cows' foreheads and a digital video camera to allow synchronized audio and video recordings. Dry matter intake rate was higher in tall alfalfa than in the other three treatments (32±1.6 v. 19±1.2 g/min). A high proportion of jaw movements in every grazing session (23 to 36%) were compound jaw movements (chew-bites) that appeared to be a key component of chewing and biting efficiency and of the ability of cows to regulate intake rate. Dry matter intake was accurately predicted based on easily observable behavioral and acoustic variables. Chewing sound energy measured as energy flux density (EFD) was linearly related to DMI, with 74% of EFD variation explained by DMI. Total chewing EFD, number of chew-bites and plant height (tall v. short) were the most important predictors of DMI. The best model explained 91% of the variation in DMI with a coefficient of variation of 17%. Ingestive sounds integrate valuable information to remotely monitor feeding behavior and predict DMI in grazing cows.


The cycle of schizoaffective disorder, cognitive ability, alcoholism, and suicidality.
In this study we investigated the putative role of cognitive dysfunction, diagnosis (schizoaffective versus schizophrenia disorder), and alcoholism as risk factors for suicidal behavior among individuals with DSM-TV schizophrenia or schizoaffective disorders. Subjects received cognitive tests and medical records were reviewed for evidence of a history of suicide attempts or suicidal ideation. Discriminant analysis was used to identify cognitive test performance measures that distinguished those with versus those without suicidal behavior. None of the cognitive measures discriminated between the two groups. The rates of suicidal behavior (suicidal ideation and suicide attempts) did not differ between participants with versus those without comorbid alcohol use. An association was found between suicidal behavior and the diagnosis of schizoaffective disorder. It was concluded that the history of prominent mood syndromes characteristic of schizoaffective disorder contributes to increased risk of suicidal behaviors. Cognitive dysfunction and/or alcoholism did not contribute additionally to risk in this study.


Using Exercise as a Stress Management Technique During the COVID-19 Pandemic: The Differences Between Men and Women in College.
Psychological stress is a major concern in college students and can lead to negative mental and physical health outcomes. The COVID-19 pandemic has increased psychological stress. Using exercise as a stress management technique has been shown to have a large effect in preventing and treating psychological stress. This study attempts to understand the gender differences between how using exercise as a stress management technique predicts perceived stress levels during the COVID-19 pandemic. Students completed an online survey to self-report their stress management techniques, perceived stress (PSS-10), grade point average (GPA) and demographics (age, race/ethnicity, sexual orientation, gender identity). Independent samples t-tests compared each PSS-10 item for those who did/not use exercise as a stress management technique for each gender. Separate linear regression models compared perceived stress levels in those who did/not use exercise as a stress management tool for each gender. GPA, sexual orientation, and race/ethnicity were included as covariates. Data from 384 students were analyzed. Four PSS-10 items showed significant differences in women who did/not use exercise as a stress management technique. Women who used exercise as a stress management technique reported significantly lower levels of perceived stress compared to those women who did not (p < 0.05); while men showed no significant differences whether or not they used exercise as a stress management technique. University officials should recognize gender differences in stress among their students when creating programs/interventions to prevent and treat student psychological stress.


The role of induction (neoadjuvant) chemotherapy in stage IIIA NSCLC.
Induction (neoadjuvant) chemotherapy has become an accepted treatment for stage IIIA (T1-3N2M0) non-small cell lung cancer. In two recent randomized trials, neoadjuvant chemotherapy plus surgery gave an increase in median survival at least fivefold greater than surgery alone. The Spanish Lung Cancer Group trial of preoperative chemotherapy, in which the cisplatin dose was randomized to either 50 mg/m2 or 100 mg/m2 plus 3 g/m2 ifosfamide and 6 mg/m2 mitomycin, examines the effect of K-ras gene mutations on tumor response and survival. Patients whose tumors contain K-ras gene mutations are more likely to develop distant metastases and have lower median survival than patients without such mutations. Microsatellite instability seems to be a frequent mechanism of genetic aberrations. Knowledge about these genetic alterations could have prognostic importance and may identify the patients who should receive the most aggressive additional treatment.


The Fusarium Graminearum virulence factor FGL targets an FKBP12 immunophilin of wheat.
Wheat scab, caused by the fungal pathogen Fusarium graminearum is a devastating disease worldwide. Despite an extensive and coordinated effort to investigate this pathosystem, little progress has been made to understand the molecular basis of host-pathogen interactions, for example how the pathogen causes disease in plant. Recently, a secreted lipase (FGL1) has been identified from the fungus and shown to be an important virulence factor; however, the intrinsic function of FGL1 in plant is unknown. Here, we report the identification of the molecular components that may possibly be involved in the FGL virulence pathway using yeast two hybrid system. FGL gene was amplified from a local virulent strain (F15) and shown to be 99.5% identical to the original published FGL at the amino acid level. We showed that transient expression of this FGL gene by Agroinfiltration in tobacco leaves causes cell death further implicating the role of FGL in virulence. To identify FGL initial physical target in plant, we screened two wheat cDNA libraries using the FGL protein as the bait. From both libraries, a small FKBP-type immunophilin protein, designated wFKBP12, was found to physically interact with FGL. The direct interaction of FGL with wFKBP12 was confirmed in living onion epidermal cells by biomolecular fluorescence complementation (BiFC) assay. To investigate further, we then used wFKBP12 protein as bait and identified an elicitor-responsive protein that contains a potential Ca(2+) binding domain. Semi-quantitative PCR showed that this elicitor-responsive gene is down-regulated during the F. graminearum infection suggesting that this protein may be an important component in FGL virulence pathway. This work serves as an initial step to reveal how fungal lipases act as a general virulence factor.


Morphology of the dorsal lingual papillae in the Japanese macaque and Savanna monkey.
The dorsal lingual surfaces of infant Japanese macaque (Macaca fuscata) and adult savanna monkey (Cercopithecus aethiopus) were examined by scanning electron microscopy. Filiform, fungiform, foliate and vallate papillae were found. The filiform papillae were distributed over the entire dorsal surface of the tongue. The fungiform papillae were round in shape, and more densely distributed on the lingual apex. The foliate papillae were seen on the dorsolateral aspect of the tongue. The three vallate papillae were arranged like a triangle with the apex of the triangle directing caudally. Each papilla was surrounded by a groove. The rudiments of the fungiform, foliate and vallate papillae were visible earlier than those of the filiform papillae.


Differences in glutamate uptake between cortical regions impact neuronal NMDA receptor activation.
Removal of synaptically-released glutamate by astrocytes is necessary to spatially and temporally limit neuronal activation. Recent evidence suggests that astrocytes may have specialized functions in specific circuits, but the extent and significance of such specialization are unclear. By performing direct patch-clamp recordings and two-photon glutamate imaging, we report that in the somatosensory cortex, glutamate uptake by astrocytes is slower during sustained synaptic stimulation when compared to lower stimulation frequencies. Conversely, glutamate uptake capacity is increased in the frontal cortex during higher frequency synaptic stimulation, thereby limiting extracellular buildup of glutamate and NMDA receptor activation in layer 5 pyramidal neurons. This efficient glutamate clearance relies on Na+/K+-ATPase function and both GLT-1 and non-GLT-1 transporters. Thus, by enhancing their glutamate uptake capacity, astrocytes in the frontal cortex may prevent excessive neuronal excitation during intense synaptic activity. These results may explain why diseases associated with network hyperexcitability differentially affect individual brain areas.


Thyroid vascular conductance: differential effects of elevated plasma thyrotropin (TSH) induced by treatment with thioamides or TSH-releasing hormone.
We have reported previously that thyroid gland blood flow, expressed as vascular conductance (C) per mass, is decreased at very low and increased at very high chronic plasma TSH concentrations, but is apparently unchanged over a broad range of plasma TSH concentrations encompassing normal levels. The aim of the present study was to examine the apparently very steep dose-response relationship between elevated plasma TSH and thyroid vascular C/mass. In the first series of experiments, endogenous plasma TSH concentrations were manipulated by treating male Sprague-Dawley rats (250-280 g) for 6 days as follows: 1) controls (0.5 ml saline/day, ip), 2) propylthiouracil injections (2.0 mg PTU/day, ip), 3) PTU plus partial thyroid hormone replacement (2.0 mg PTU/day and 0.3-0.9 microgram T4 plus 0.075-0.225 microgram T3/100 g.day via continuous sc infusion), or 4) TRH (9-1200 micrograms TRH/100 g.day via continuous iv infusion). The vascular C values of the thyroid gland, salivary gland, kidney, and pancreas were determined using the reference sample version of the radioactive microsphere technique. PTU treatment led to the expected hypothyroidism, increased plasma TSH concentrations (959 +/- 66 vs. 154 +/- 22 ng/dl), increased thyroid weight (9.19 +/- 0.36 vs. 4.60 +/- 0.15 mg/100 g), and increased thyroid vascular C/mass (495 +/- 51 vs. 127 +/- 20 microliters/mm Hg.g/min). PTU-treated rats receiving partial thyroid hormone replacement demonstrated a dose-related suppression of plasma TSH, thyroid weight, and thyroid vascular C. Although, TRH treatments resulted in increased plasma TSH concentrations (e.g. 1200 micrograms TRH, 706 +/- 46 ng/dl) and thyroid weight (e.g. 1200 micrograms TRH, 7.45 +/- 0.41 mg/100 g), thyroid vascular C per tissue mass was not significantly increased after any TRH treatment (e.g. 1200 micrograms TRH, 166 +/- 19 microliters/mm Hg.g/min). Thus, at similarly elevated plasma TSH concentrations, the thyroid vascular C/mass of PTU- and TRH-treated rats constituted separate populations. Both PTU- and TRH-induced thyroid growth were accompanied by similar alterations in thyroid gland morphology (i.e. increased cellular mass with little change in the total amount of colloid). To investigate the mechanisms involved, groups of rats were treated for 6 days as follows: 1) control, 2) PTU or methimazole (25 mg MMI/day, ip), 3) PTU or MMI plus thyroid hormone replacement (1.2 micrograms T4 plus 0.3 microgram T3/d.100 g), 4) TRH (12 micrograms/100 g.day), and 5) PTU or MMI, thyroid hormones, and TRH.(ABSTRACT TRUNCATED AT 400 WORDS)


How to proteins move along DNA? Lessons from type-I and type-III restriction endonucleases.
Protein-mediated communications on DNA are universally important. The translocation of DNA driven by a high-energy phosphoryl potential allows long stretches of DNA to be traversed without dissociation. Type-I and type-III enzymes both use a common DNA-tracking mechanism to move along DNA, dependent on the hydrolysis of ATP. Type-I enzymes cleave DNA at distant DNA sites (and in some cases close to the site), due to a stall in enzyme motion. This can be due to collision with another translocating type-I enzyme or, on circular DNA, due to an increased topological load. ATP hydrolysis is considerable, and continues after DNA cleavage. Type-III enzymes only cleave DNA proximal to their sites due to collision between two endonucleases tracking with defined polarity. ATP hydrolysis is less than with the type-I enzymes. Homology to DNA helicases has been found within the HsdR and Res subunits. Mutagenesis of the DEAD-box motifs affects both ATP hydrolysis and DNA cleavage. This demonstrates a tight link between ATPase and endonuclease activities. A strand-separation mechanism akin to the DNA helicases is a possibility. The DNA-based motor proteins are mechanistically ill-defined. Further study using some of the techniques pioneered with classical motor proteins will be needed to reveal more detail.


Environmental performance of construction waste: Comparing three scenarios from a case study in Catalonia, Spain.
The main objective of this paper is to evaluate environmental impacts of construction wastes in terms of the LIFE 98 ENV/E/351 project. Construction wastes are classified in accordance with the Life Program Environment Directive of the European Commission. Three different scenarios to current waste management from a case study in Catalonia (Spain) have been compared: landfilling, recycling and incineration, and these scenarios were evaluated by means of Life Cycle Assessment. The recommendations of the Catalan Waste Catalogue and the European Waste Catalogue have been taken into account. Also, the influence of transport has been evaluated. Results show that in terms of the Global Warming Potential, the most environmentally friendly treatment was recycling, followed by incineration and lastly landfilling. According to the influence of treatment plants location on the GWP indicator, we observe that incineration and recycling of construction wastes are better than landfilling, even for long distances from the building site to the plants. This is true for most wastes except for the stony types, than should be recycled close to the building site. In summary, data from construction waste of a Catalan case study was evaluated using the well established method of LCA to determine the environmental impacts.


Diesel engine exhaust and lung cancer: an unproven association.
The risk of lung cancer associated with diesel exhaust has been calculated from 14 case-control or cohort studies. We evaluated the findings from these studies to determine whether there is sufficient evidence to implicate diesel exhaust as a human lung carcinogen. Four studies found increased risks associated with long-term exposure, although two of the four studies were based on the same cohort of railroad workers. Six studies were inconclusive due to missing information on smoking habits, internal inconsistencies, or inadequate characterization of diesel exposure. Four studies found no statistically significant associations. It can be concluded that short-term exposure to diesel engine exhaust (< 20 years) does not have a causative role in human lung cancer. There is statistical but not causal evidence that long-term exposure to diesel exhaust (> 20 years) increases the risk of lung cancer for locomotive engineers, brakemen, and diesel engine mechanics. There is inconsistent evidence on the effects of long-term exposure to diesel exhaust in the trucking industry. There is no evidence for a joint effect of diesel exhaust and cigarette smoking on lung cancer risk. Using common criteria for determining causal associations, the epidemiologic evidence is insufficient to establish diesel engine exhaust as a human lung carcinogen.


Analyses of the relationship between a 'number of reflux episodes' exceeding 70 and the pH index in neurologically impaired children by evaluating esophageal combined pH-multichannel intraluminal impedance measurements.
The present study aimed to evaluate the characteristics associated with a number of reflux episodes (NoRE) of 70 by comparing the clinical and multichannel intraluminal impedance pH measurements (pH/MII) and pH index (pHI) in neurologically impaired (NI) children. NI children (1-16 years of age) in whom pH/MII had been measured for GERD study were enrolled in this study. All children were divided into NoRE >70 or ≤70 and pHI >4.0 or ≤4.0, >5.0 or ≤5.0 or >7.0 or ≤7.0. In addition, the NI children with pHI >4.0, >5.0 and >7.0 were subdivided into NoRE >70 and ≤70 groups. The clinical and pH/MII measurements were compared between each of the two groups. The cutoff values of pHI and baseline impedance (BI) (Z6) were calculated to discriminate NoRE >70 and ≤70. A total of 61 NI children were enrolled in this study. There was a significant difference in the acid-related parameters, the NoRE (nonacid) and BI between NoRE >70 and ≤70, acid-related parameters and BI between pHI >4.0 and ≤4.0, >5.0 and ≤5.0 and >7.0 and ≤7.0 groups. Furthermore, a significant difference was still observed in the BI between NoRE >70 and ≤70 groups among patients with pHI >4.0, >5.0 or >7.0. The cutoff values of pHI and BI (Z6) for discriminating NoRE >70 and ≤70 were 9.2 and 1049Ω, respectively. The present study indicates that NoRE 70 corresponds to GERD in which patients suffer severe acid exposure with pH of around 9% and esophageal mucosal damage with low BI value in NI children.


A prospective cohort study to assess the acceptability of Sayana Press among 18-49-year-old women in Nepal.
We compared acceptability and continuation of Sayana Press, a subcutaneous formulation of depot-medroxyprogesteone acetate (DMPA) in a Uniject injection system, to intramuscular (IM) DMPA, among both current users of DMPA-IM and new users in Nepal. We recruited women seeking injectable contraception at 14 public health facilities in Nepal selected for geographic diversity. We enrolled women who self-selected either Sayana Press or DMPA-IM and used structured interviews to obtain baseline demographics and assess satisfaction and continuation rates at 1, 3, and 6 months. Seven hundred ninety-four women (71%) selected and received Sayana Press, while 318 women (28.6%) selected and received DMPA-IM. One hundred and seventy-eight (48%) women continuing Sayana Press injection reported that they experienced "no possible side effects" compared to 29 (22%) among DMPA-IM selectors during the previous 6 months. The continuation rate of Sayana Press at 6 months was higher than DMPA-IM (Sayana Press 46.5% vs DMPA-IM 34.4%; p < 0.001). Selection of Sayana Press method (ORadj. 1.74; 95% confidence interval 1.32-2.3) and approval from husband (ORadj. 1.59; 95% confidence interval 1.21-2.09) were associated with injection continuation. Sayana Press is acceptable to women in Nepal with the preference for Sayana Press over DMPA-IM (higher proportion chose the method when counseled and given the option, better continuation). The potential for self-injection with Sayana Press® may have implications for continuation and opportunity for future research and strategies to roll out this innovative technology must be explored.


SlMYB102 expression enhances low-temperature stress resistance in tomato plants.
Herein, we identified the tomato SlMYB102 gene as a MYB family transcription factor of the R2R3-MYB subfamily. We additionally determined that the SlMYB102 promoter region contains photoresponsive, abiotic stress-responsive, and hormone-responsive regulatory elements, and we detected higher SlMYB102 expression in the reproductive organs of tomato than that in vegetative organs, with the expression being highest in ripe fruits and in roots. SlMYB102 expression was also shown to be cold-inducible. The protein encoded by SlMYB102 localized to the nucleus wherein it was found to mediate the transcriptional activation of target genes through its C-terminal domain. Overexpression of SlMYB102 in tomato plants conferred enhanced tolerance to cold stress. Under such cold stress conditions, we found that proline levels in the leaves of SlMYB102 overexpressing transgenic plants were higher than those in WT plants. In addition, S1MYB102 overexpression was associated with the enhanced expression of cold response genes including SlCBF1, SlCBF3, SlDREB1, SlDEB2, and SlICE1. We also found that the overexpression of SlMYB102 further enhanced the cold-induced upregulation of SlP5CS and SlAPX2. Taken together, these results suggest that SlMYB102 may be involved in the C-repeat binding transcription factor (CBF) and proline synthesis pathways, thereby improving tomato plant cold resistance.


A new method to measure oxygenator oxygen transfer performance during cardiopulmonary bypass: clinical testing using the Medtronic Fusion oxygenator.
There is no acceptable method of testing oxygen transfer performance in membrane oxygenators quickly and easily during cardiopulmonary bypass. Pre-clinical testing of oxygenators is performed under controlled situations in the laboratory, correlating oxygen transfer to blood flow using 100% oxygen. This laboratory method cannot be used clinically as oxygen transfer values vary significantly at each blood flow and the FiO2 is not kept at 1. Therefore, a formula was developed which corrects the existing FiO2 to attain a PaO2 of 150 mmHg: the corrected FiO2 at 150 mmHg. In graph form, this corrected FiO2 (x-axis) is correlated to the patient's oxygen consumption levels (y-axis), which determines the membrane oxygenator oxygen transfer performance. Blood gas and hemodynamic parameters taken during cardiopulmonary bypass using the Medtronic Fusion were used to calculate the oxygen consumption (inlet conditions to the oxygenator) and the corrected FiO2 for a PaO2 of 150 mmHg. Validation of the formula "FiO2-PaO2/(Pb-pH2O)+0.21" was carried out by plotting the calculated values on a graph using PaO2 values between 145 to 155 mmHg and then, using the corrected FiO2 for PaO2s outside of this range. All trend-lines correlated significantly to confirm that the Medtronic Fusion had an extrapolated oxygen transfer of 419 milliliters O2/min at an FiO2 of 1 to achieve a PaO2 of 150 mmHg. Use of the corrected FiO2 correlated to the oxygen transfer conditions of the membrane oxygenator can easily be used on a routine basis, providing valuable information clinically. When used by the manufacturer under laboratory conditions, further clinically relevant data is provided in terms of FiO2 and resultant PaO2s instead of the present limitations using blood flow. In this way, a clinically justifiable method has been developed to finally establish a standard in testing membrane oxygenator performance.


Acculturation and Cardiovascular Risk Screening among African Immigrants: The African Immigrant Health Study.
Acculturation and immigration-related factors may impact preventive, routine cardiovascular risk (CV) screening among African immigrants. We examined the associations between length of stay, percent of life spent in the U.S. (proxy for acculturation), and CV screening. Outcomes were recent screening for hypertension, diabetes, and dyslipidemia. Multivariable logistic regression analyses were used to examine these relationships. Among 437 African immigrants, 60% were males, mean age was 47 years, 61% had lived in the U.S. for ≥10 years, mean length of stay was 15 years, and 81% were employed. Only 67% were insured. In the 12 months prior, 85% had screened for hypertension, 45% for diabetes, and 63% for dyslipidemia. African immigrants with a ≥10-year length of U.S. stay had 2.20 (95%Confidence Intervals: 1.31−3.67), and those with >25% years of life spent in the U.S. had 3.62 (95%CI: 1.96−6.68) higher odds of dyslipidemia screening compared to those with a <10-year length of stay and ≤25% years of life spent in the U.S., respectively. Overall, screening for CV risk higher in African immigrants who have lived longer (≥10 years) in the U.S. Recent African immigrants may experience challenges in accessing healthcare. Health policies targeting recent and uninsured African immigrants may improve access to CV screening services.


Diagnostic accuracy of peripheral blood Kisspeptin mRNA and plasma CA125 protein for detection of epithelial ovarian cancer in patients who have ever been pregnant.
To evaluate the diagnostic accuracy of peripheral blood kisspeptin (KISS1) mRNA and plasma cancer antigen 125 (CA125) protein of epithelial ovarian cancer (EOC) in previously pregnant patients, we prospectively enrolled 40 EOC patients as cases and 20 uterine fibroids patients with normal ovary as controls. Levels of peripheral blood KISS1 mRNA and plasma CA125 protein was respectively measured by RT-PCR and electrochemiluminescent method, respectively. Receiver operating characteristic curves with area under curve (AUC) were used to evaluate the diagnostic accuracy. Logistic regression analysis was used to obtain a prediction model for combined diagnosis of KISS1 mRNA and CA125 protein. Both KISS1 mRNA and CA125 protein and had good diagnostic accuracy for EOC, early EOC and advanced EOC (AUC > 0.5, P < 0.05). The CA125 protein had higher diagnostic accuracy than KISS1 mRNA for advanced EOC (P = 0.0009). Moreover, the combination of KISS1 mRNA and CA125 protein had higher diagnostic accuracy for EOC than them alone (P 0.05). Peripheral blood KISS1 mRNA was a novel biomarker for detecting EOC in previously pregnant patients. Combination application of KISS1 mRNA and CA125 protein was recommended for the diagnosis of EOC, but not for advanced and early EOC.


The utility of a novel antibody in the pathological diagnosis of pancreatic acinar cell carcinoma.
Acinar cell carcinomas (ACCs) are rare tumours of the exocrine pancreas accounting for about 1-2% of all pancreatic neoplasms in adults. It is therefore difficult to come across a large number of ACC cases in a single medical institution, and only a few serial studies have been published. Since ACCs present a wide variety of morphological patterns, immunohistochemical analysis is useful. In this study, the authors established a novel monoclonal antibody 2P-1-2-1 by means of a subtractive immunisation method. Immunohistochemical staining was performed using 50 primary pancreatic tumors, including 7 ACCs, 7 neuroendocrine tumours (NETs), 5 solid-pseudopapillary neoplasms (SPNs), and 31 ductal carcinomas and organs other than the pancreas. Non-neoplastic acinar cells were stained diffusely, but epithelial cells of the pancreatic duct and the islets of Langerhans were not stained. In pancreatic tumours, all the seven ACCs were diffusely positive for the 2P-1-2-1 antibody. However, no positive staining was found in other pancreatic tumours including NETs, SPNs and ductal adenocarcinomas. The sensitivity and specificity of the 2P-1-2-1 antibody for ACCs were both 100%. In other organs studied, positive staining was observed only in the ectopic pancreas. It was shown that the 2P-1-2-1 antibody specifically stained the pancreatic acinar cells and tumours of acinar cell origin, such as ACCs. Although it remains unclear at this time to which proteins the monoclonal antibody 2P-1-2-1 is directed, it is suggested to be useful for the pathological diagnosis of ACCs and for the exclusion of other pancreatic tumours.


Protein kinase C-dependent and -independent inhibition of Ca(2+) influx by phorbol ester in rat pancreatic beta-cells.
Phorbol esters were used to investigate the action of protein kinase C (PKC) on insulin secretion from pancreatic beta-cells. Application of 80 nM phorbol 12-myristate 13-acetate (PMA), a PKC-activating phorbol ester, had little effect on glucose (15 mM)-induced insulin secretion from intact rat islets. In islets treated with bisindolylmaleimide (BIM), a PKC inhibitor, PMA significantly reduced the glucose-induced insulin secretion. PMA decreased the level of intracellular Ca(2+) concentration ([Ca(2+)](i)) elevated by the glucose stimulation when tested in isolated rat beta-cells. This inhibitory effect of PMA was not prevented by BIM. PMA inhibited glucose-induced action potentials, and this effect was not prevented by BIM. Further, 4alpha-phorbol 12,13-didecanoate (4alpha-PDD), a non-PKC-activating phorbol ester, produced an effect similar to PMA. In the presence of nifedipine, the glucose stimulation produced only depolarization, and PMA applied on top of glucose repolarized the cell. When applied at the resting state, PMA hyperpolarized beta-cells with an increase in the membrane conductance. Recorded under the voltage-clamp condition, PMA reduced the magnitude of Ca(2+) currents through L-type Ca(2+) channels. BIM prevented the PMA inhibition of the Ca(2+) currents. These results suggest that activation of PKC maintains glucose-stimulated insulin secretion in pancreatic beta-cells, defeating its own inhibition of the Ca(2+) influx through L-type Ca(2+) channels. PKC-independent inhibition of electrical excitability by phorbol esters was also demonstrated.


COVID-19 in Kidney Transplantation: Epidemiology, Management Considerations, and the Impact on Kidney Transplant Practice.
The novel severe acute respiratory syndrome coronavirus 2 was identified in the late 2019 as the cause of coronavirus disease 2019 (COVID-19), an acute respiratory viral illness. Patients with chronic underlying conditions may have an increased risk of morbidity and mortality from COVID-19. Kidney transplant recipients may be at a uniquely increased risk of serious complications from COVID-19 as compared to the general population because of a chronically immunosuppressed state and a high prevalence of comorbidities like diabetes, heart disease, and lung disease. Early data suggest that the mortality of patients on dialysis may be comparable to those with kidney transplants, although more research is needed. This concise review aims to describe the epidemiology of COVID-19 in kidney transplant recipients, manifestations, appropriate management, and clinical outcomes based on the available literature. Current evidence on many of the specific antiviral measures against COVID-19 has not shown a clear-cut benefit in smaller studies and the results of several ongoing larger clinical trials are awaited. In addition, we also highlight the impact of COVID-19 on kidney transplant center practice and volumes; potential living or deceased donors, recipients; and induction immunosuppression and surgical strategies.


Suspected outbreak of riboflavin deficiency among populations reliant on food assistance: a case study of drought-stricken Karamoja, Uganda, 2009-2010.
In 2009, a humanitarian response was launched to address a food security and livelihoods crisis in Karamoja, Uganda. During a polio immunization campaign in mid-August 2009, health workers in Nakapiripit District reported a concern about an increase in mouth sores, or angular stomatitis (AS) and gum ulcerations, among children in one village, and an investigation was launched. This article describes the investigation, lessons learned, and provides guidance for monitoring micronutrient deficiencies among populations receiving food assistance. An investigation into a suspected outbreak of riboflavin (vitamin B2) deficiency was initiated, including a rapid assessment, mass screening, a convenience sample collection of blood specimens (n = 58 symptomatic cases and n = 18 asymptomatic individuals), and analysis of the general food ration (70% ration). Findings showed signs of AS in only 399 (0.2%) of 179,172 screened individuals, including adults and children. Biochemical analysis confirmed riboflavin deficiency in 84.5% of specimens from symptomatic individuals and 94.4% of specimens from asymptomatic individuals. Ration distribution data showed that 55% of distributions provided less than half the riboflavin RDA. Evidence was insufficient to confirm an actual outbreak of riboflavin deficiency, though the present investigation adds further documentation that micronutrient deficiencies continue to persist among populations in emergency settings. This article describes challenges, lessons learned, and guidance for monitoring micronutrient deficiencies among food assistance recipients, including: ongoing nutrition monitoring and surveillance; training and sensitization about micronutrient deficiencies, sensitization of the population about locally-available food, and identifying ways to improve micronutrient interventions.


Individual Susceptibility to Erosive Tooth Wear: Wine Tasters.
Erosive tooth wear is the classic gene-environmental model. It requires the exposure to acids, typically from the diet or from the gastric content of the host, and shows variation among individuals and populations, which suggests it to be determined by more than one gene, each with small individual effects. This genetic component is not easily studied since a precise assessment of acidic exposure is complicated. In humans, this is commonly done by self-reported data. In this chapter, evidence is discussed that supports the assumption that a genetic component exists, inspecting data from wine tasters, and ex vivo experiments combining different dental enamel specimens and saliva compositions. These data can be found "hidden" in reports that do not directly deal with individual susceptibility to erosive tooth wear.


The adenovirus E1A protein targets the SAGA but not the ADA transcriptional regulatory complex through multiple independent domains.
Expression of the adenovirus E1A protein in the simple eukaryote Saccharomyces cerevisiae inhibits growth. We tested four regions of E1A that alter growth and transcription in mammalian cells for their effects in yeast when expressed as fusions to the Gal4p DNA binding domain. Expression of the N-terminal/conserved region (CR) 1 or CR3, but not of the CR2 or the C-terminal portion of E1A, inhibited yeast growth. Growth inhibition was relieved by deletion of the genes encoding the yGcn5p, Ngg1p, or Spt7p components of the SAGA transcriptional regulatory complex, but not the Ahc1p component of the related ADA complex, indicating that the N-terminal/CR1 and CR3 regions of E1A target the SAGA complex independently. Expression of the pCAF acetyltransferase, a mammalian homologue of yGcn5p, also suppressed growth inhibition by either portion of E1A. Furthermore, the N-terminal 29 residues and the CR3 portion of E1A interacted independently with yGcn5p and pCAF in vitro. Thus, two separate regions of E1A target the yGcn5p component of the SAGA transcriptional activation complex. A subregion of the N-terminal/CR1 fragment spanning residues 30-69 within CR1 also inhibited yeast growth in a SAGA-dependent fashion. However, this region did not interact with yGcn5p or pCAF, suggesting that it makes a third contact with another SAGA component. Our results provide a new model system to elucidate mechanisms by which E1A and the SAGA complex regulate transcription and growth.


Therapist immediacy: The association with working alliance, real relationship, session quality, and time in psychotherapy.
This longitudinal analysis examined the relationship between amount of therapist immediacy in sessions and client post-session ratings of working alliance (WAI), real relationship (RRI), and session quality (SES). Using hierarchal linear modeling (HLM), we disaggregated the variables into within-client (differences between sessions in immediacy) and between-clients (differences between clients in immediacy) components, in order to test associations over time in treatment. Three hundred and sixty four sessions were nested within 16 clients and 9 therapists. When therapists used more immediacy in a session, clients gave higher SES ratings for that session, compared to their sessions with less immediacy (within-client effect). For WAI, it appeared to matter when immediacy was used in treatment. The interaction effect between time in treatment and within-client immediacy revealed that early in treatment, more immediacy in a session was related to lower WAI for that session, whereas later in treatment, more immediacy in a session was related to higher WAI for that session. Another interaction effect was found between time in treatment and between-clients immediacy. Clients with less immediacy in treatment, gave higher SES scores for early sessions, than clients with more immediacy in treatment. Immediacy has an overall positive effect on session quality, but the time in which it is used in treatment and client characteristics should be taken into account both in practice and research.


Nivolumab-Induced Myocarditis Concomitant with Myasthenia Gravis.
We report a 69-year-old female patient with advanced lung cancer who developed myocarditis concomitant with myasthenia gravis (MG), also known as "Herzmyasthenie," after 3 cycles of nivolumab administration. Her initial symptoms were general malaise and double vision. However, her myocarditis deteriorated rapidly the following day, necessitating a temporary pacemaker and noninvasive positive pressure ventilation in the intensive care unit. Immunohistochemical examination of a myocardial biopsy suggested an immune response on the basis of HLA associations. The patient also developed impaired adduction of her left eye and elevated serum levels of acetylcholine receptor antibody, suggesting the onset of MG. Her condition gradually improved after immediate methylprednisolone pulse therapy. This case of nivolumab-induced "Herzmyasthenie" highlights the need to be aware that fulminant myocarditis might occur at the same time as MG during treatment with anti-programmed cell death-1 monoclonal antibodies.


A special conditions register.
A special conditions register (SCR) linked to the child health system's register of all children has been in use in West Sussex since 1977. This paper describes the aims, organisation, and use of the SCR and gives examples of the aggregated data that may be obtained. Of the 155,000 children aged 0-17 resident in West Sussex in 1990, 4.3% were included on the SCR. Altogether 45.7% of children on the SCR had physical conditions with mild or no disability and 17.2% had moderate educational problems. The prevalence of severe hearing loss as defined was 1.7 per 1000 aged 5-17. The prevalence of diabetes mellitus was 1.2 per 1000 children aged 0-17. Validation of the SCR for diabetes mellitus found 35/36 of the eligible children were correctly registered and no child was incorrectly included. The conflicting priorities for maintaining a register for the care of individual children, for service planning, and for epidemiological research are discussed.


Mapping the public first-aid training landscape: a scoping review.
While the public can play a vital role in saving lives during emergencies, intervention is only effective if people have the skills, confidence, and willingness to help. This review employs a five-stage framework to systematically analyse first aid and emergency helping literature from 22 countries (predominately in Asia, Australia, Europe, and the United States). The review covers 54 articles that investigate public first-aid knowledge and uptake of first-aid training (40); public confidence in first-aid skills and willingness to help during an emergency (21); and barriers to or enablers of learning first aid and delivering first aid in an emergency (25). The findings identify high levels of perceived knowledge, confidence, and willingness to help, supporting the contention that the public can play a vital role during an emergency. However, the findings also point to low uptake levels, low tested skill-specific knowledge, and barriers to learning first aid and helping, indicating that the first-aid training landscape is in need of improvement.


Effect of surface charge distribution on the adsorption orientation of proteins to lipid monolayers.
The adsorption orientation of the proteins lysozyme and ribonuclease A (RNase A) to a neutral 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and a negatively charged stearic acid lipid film was investigated by means of X-ray reflectivity. Both proteins adsorbed to the negatively charged lipid monolayer, whereas at the neutral monolayer, no adsorption was observed. For acquiring comprehensive information on the proteins' adsorption, X-ray reflectivity data were combined with electron densities obtained from crystallographic data. With this method, it is possible to determine the orientation of adsorbed proteins in solution underneath lipid monolayers. While RNase A specifically coupled with its positively charged active site to the negatively charged lipid monolayer, lysozyme prefers an orientation with its long axis parallel to the Langmuir film. In comparison to the electrostatic maps of the proteins, our results can be explained by the discriminative surface charge distribution of lysozyme and RNase A.


TSS-EMOTE, a refined protocol for a more complete and less biased global mapping of transcription start sites in bacterial pathogens.
Bacteria rely on efficient gene regulatory mechanisms to switch between genetic programs when they are facing new environments. Although this regulation can occur at many different levels, one of the key steps is the initiation of transcription. Identification of the first nucleotide transcribed by the RNA polymerase is therefore essential to understand the underlying regulatory processes, since this provides insight on promoter strength and binding sites for transcriptional regulators, and additionally reveals the exact 5' untranslated region of the transcripts, which often contains elements that regulate translation. Here we present data from a novel TSS-EMOTE assay (Transcription Start Specific Exact Mapping Of Transcriptome Ends) to precisely map the transcription initiation sites of four entire transcriptomes. TSS-EMOTE is a variation of the dRNA-seq method, which has been combined with the EMOTE protocol, in order to increase detection of longer transcripts and limit biases introduced by PCR amplification of the Illumina sequencing library. Using TSS-EMOTE, 2018 promoters were detected in the opportunistic pathogen Staphylococcus aureus, and detailed consensus sequences could be obtained for the RNA polymerase recognition elements (e.g. sigma factor binding sites). The data also revealed a 94 nt median length of the 5' untranslated region in S. aureus, giving important insights for future work on translational regulation. Additionally, the transcriptomes of three other opportunistic pathogens, Staphylococcus epidermidis, Acinetobacter baumannii and Enterobacter aerogenes, were examined, and the identified promoter locations were then used to generate a map of the operon structure for each of the four organisms. Mapping transcription start sites, and subsequent correlation with the genomic sequence, provides a multitude of important information about the regulation of gene expression, both at the transcriptional and translational level, by defining 5' untranslated regions and sigma-factor binding sites. We have here mapped transcription start sites in four important pathogens using TSS-EMOTE, a method that works with both long and 3'-phosphorylated RNA molecules, and which incorporates Unique Molecular Identifiers (UMIs) to allow unbiased quantification.


Intrahepatic cholangiocarcinoma and hepatolithiasis: an unusual association in Western countries.
Hepatolithiasis is uncommon in Western countries and the relationship with cholangiocarcinoma is unusual. We report the association of hepatolithiasis and a cholangiocarcinoma in a Caucasian patient with a 17-year history of recurrent pancreatitis associated with hepatolithiasis. We discuss work-up and surgical treatment, and stress the need to keep in mind the possible association between hepatolithiasis and cholangiocarcinoma even in Western countries.


NMR and molecular dynamics studies of the interaction of melatonin with calmodulin.
Pineal hormone melatonin (N-acetyl-5-methoxytryptamine) is thought to modulate the calcium/calmodulin signaling pathway either by changing intracellular Ca(2+) concentration via activation of its G-protein-coupled membrane receptors, or through a direct interaction with calmodulin (CaM). The present work studies the direct interaction of melatonin with intact calcium-saturated CaM both experimentally, by fluorescence and nuclear magnetic resonance spectroscopies, and theoretically, by molecular dynamics simulations. The analysis of the experimental data shows that the interaction is calcium-dependent. The affinity, as obtained from monitoring (15)N and (1)H chemical shift changes for a melatonin titration, is weak (in the millimolar range) and comparable for the N- and C-terminal domains. Partial replacement of diamagnetic Ca(2+) by paramagnetic Tb(3+) allowed the measurement of interdomain NMR pseudocontact shifts and residual dipolar couplings, indicating that each domain movement in the complex is not correlated with the other one. Molecular dynamics simulations allow us to follow the dynamics of melatonin in the binding pocket of CaM. Overall, this study provides an example of how a combination of experimental and theoretical approaches can shed light on a weakly interacting system of biological and pharmacological significance.


Imaging of mucocoele of the appendix with emphasis on the CT findings: a report of 10 cases.
Mucocoele of the appendix denotes an obstructive dilatation of the appendiceal lumen due to abnormal accumulation of mucus. It is sometimes associated with pseudomyxoma peritonei, which predicts a malignant origin. We present the CT findings and additional imaging studies of 10 patients with neoplastic appendiceal mucocoele and discuss the clinical implications. Abdominal CT findings from 10 patients with appendiceal mucocoele were reviewed. Barium enema, US and MRI were additionally performed in three patients. There were five men and five women aged 45-80 years. Special attention was directed to the shape and nature of the mass, its relation to the caecum and the presence of ascites or peritoneal implants, as well as possible additional ovarian tumours in female patients. The mucocoele was an incidental finding in five patients. They were either spherical or elongated cystic lesions, attached to the wall of the caecum, six of them with mural calcification. Ascites were present in six patients and hypodense large peritoneal implants representing pseudomyxoma peritonei in four. Pathologically the series included five cases of cystadenoma (in one, a malignant pseudomyxoma peritonei subsequently developed), four cases of cystadenocarcinoma and one villous adenoma (this patient later developed pseudomyxoma peritonei). Pseudomyxoma peritonei was found in five cases. Three women had associated ovarian cystic tumour. The appearance of an appendiceal mucocoele is quite characteristic and can be diagnosed on CT. CT can also depict additional findings suggesting pseudomyxoma peritonei. In women with an appendiceal mucocoele the ovaries should be examined closely for cystic tumour and vice versa.


From water and ions to crowded biomacromolecules: in vivo structuring of a prokaryotic cell.
The interactions and processes which structure prokaryotic cytoplasm (water, ions, metabolites, and biomacromolecules) and ensure the fidelity of the cell cycle are reviewed from a physicochemical perspective. Recent spectroscopic and biological evidence shows that water has no active structuring role in the cytoplasm, an unnecessary notion still entertained in the literature; water acts only as a normal solvent and biochemical reactant. Subcellular structuring arises from localizations and interactions of biomacromolecules and from the growth and modifications of their surfaces by catalytic reactions. Biomacromolecular crowding is a fundamental physicochemical characteristic of cells in vivo. Though some biochemical and physiological effects of crowding (excluded volume effect) have been documented, crowding assays with polyglycols, dextrans, etc., do not properly mimic the compositional variety of biomacromolecules in vivo. In vitro crowding assays are now being designed with proteins, which better reflect biomacromolecular environments in vivo, allowing for hydrophobic bonding and screened electrostatic interactions. I elaborate further the concept of complex vectorial biochemistry, where crowded biomacromolecules structure the cytosol into electrolyte pathways and nanopools that electrochemically "wire" the cell. Noncovalent attractions between biomacromolecules transiently supercrowd biomacromolecules into vectorial, semiconducting multiplexes with a high (35 to 95%)-volume fraction of biomacromolecules; consequently, reservoirs of less crowded cytosol appear in order to maintain the experimental average crowding of ∼25% volume fraction. This nonuniform crowding model allows for fast diffusion of biomacromolecules in the uncrowded cytosolic reservoirs, while the supercrowded vectorial multiplexes conserve the remarkable repeatability of the cell cycle by preventing confusing cross talk of concurrent biochemical reactions.


The two-headed antigen. B-cell co-receptors.
Lymphocytes often recognize antigens using not only their antigen receptors but also 'co-receptors' that bind other molecules associated with the antigen; the co-receptors then modulate the response to antigen. This concept has been used to make chimeric antigens that are extremely potent inducers of antibody responses.


Development of associations and kinetic models for microbiological data to be used in comprehensive food safety prediction software.
The objective of this study was to use an existing database of food products and their associated processes, link it with a list of the foodborne pathogenic microorganisms associated with those products and finally identify growth and inactivation kinetic parameters associated with those pathogens. The database was to be used as a part of the development of comprehensive software which could predict food safety and quality for any food product. The main issues in building such a predictive system included selection of predictive models, associations of different food types with pathogens (as determined from outbreak histories), and variability in data from different experiments. More than 1000 data sets from published literature were analyzed and grouped according to microorganisms and food types. Final grouping of data consisted of the 8 most prevalent pathogens for 14 different food groups, covering all of the foods (>7000) listed in the USDA Natl. Nutrient Database. Data for each group were analyzed in terms of 1st-order inactivation, 1st-order growth, and sigmoidal growth models, and their kinetic response for growth and inactivation as a function of temperature were reported. Means and 95% confidence intervals were calculated for prediction equations. The primary advantage in obtaining group-specific kinetic data is the ability to extend microbiological growth and death simulation to a large array of product and process possibilities, while still being reasonably accurate. Such simulation capability could provide vital ''what if'' scenarios for industry, Extension, and academia in food safety.


Electrical artifact during intraoperative electromyographic neuromonitoring.
Acoustic electromyography is a commonly employed neuromonitoring modality for protecting cranial and peripheral nerves for a variety of neck, cranial, and spinal surgeries. An artifact resembling an electromyographic (EMG) response caused by contact between two metal instruments within the surgical field may contaminate the interpretation of mechanically-elicited activity that occurs from neural irritation during surgery. This artifact has been casually referred to as the "crossed swords" effect and has not been adequately described. A series of manipulations were devised to determine if this artifact: 1) required an electrolytic medium for its occurrence, 2) could be produced between a metal and nonmetal object, 3) could be detected in a control channel outside the surgical site, 4) could be detected in background waveforms using parameters for averaging a somatosensory evoked potential (SSEP), and lastly 5) could be quantified electrically. The metal-to-metal artifact could be produced when instruments made contact in a fluid medium. In contrast, metal-to-nonmetal contact did not produce the artifact in or outside a fluid medium. This artifact was not detected on a control channel from surface electrodes over the deltoid muscle. When tapped or rubbed, the artifact sounded like an EMG response, but the morphology was unique. Only when the two metals were rubbed together were the morphologies and acoustic "signatures" similar to an EMG response. Metal-to-metal contact in a fluid medium did not produce an artifact that could be detected in the background activity recorded using parameters for SSEPs. The electrical potential discharge was approximately 100 mV after the instruments stayed in solution and made contact after 150 seconds. This artifact is likely attributable to current discharge when two metals contact each other, a phenomenon referred to as a galvanic couple.


Falls in older ambulatory care patients with cancer in Iran: Implications for clinical practice.
Falls can have severe consequences particularly for older patients with cancer undergoing ambulatory care. The aim of the study is to identify the predictors of falls in older patients receiving cancer ambulatory care and evaluate the accuracy of the final multivariable model in detecting older patients with falls. A retrospective study was conducted on 300 older patients aged 60 years and above that were referred for ambulatory care in three oncology clinics based at hospitals in Tehran, Iran. Participants completed a questionnaire comprising demographic, history of falls, and cancer-related factors. Logistic regression was used to determine risk factors associated with falls. A total of 35.3% of the older patients with cancer had experienced a fall in the 6 months following the start of their ambulatory care. The most important predictors of falls include the fourth stage of cancer (odds ratio [OR]: 6.47, 95% confidence interval [CI]: 3.20-13.08, p < 0.001), fear of falling (OR: 5.64, 95% CI: 2.58-12.33, p < 0.001), use of hearing (OR: 2.38, 95% CI: 1.07-5.29, p = 0.033) and visual aids (OR: 2.36, 95% CI: 1.12-5.01, p = 0.025), and the number of visits to the doctor (OR: 1.10, 95% CI: 1.01-1.21, p = 0.035). The results indicate that a reduction in falls is possible by introducing strategies to improve care for older patients in the advanced stage of cancer, eliminating the causes of fear of falling, examining and improving vision and hearing, and identifying and addressing the underlying causes of visits to the doctor.


Asymmetric random walk in a reaction intermediate of homologous recombination.
At an intermediate step of the homologous recombination between two double-stranded DNA molecules, a point (often called Holliday structure) connecting two strands coming from two recombining partners migrates along the homologous region. Assuming random walk of a connecting point, we previously explained the dependence of recombination frequency on the homology length observed in vivo. In this model, the random walk was assumed to be symmetric in that the forward transition rate equals the backward one. According to observations in vitro, however, catalysed migration appears unidirectional. Taking into account possible asymmetry, we thus reformulate our random walk model to reexamine the observations in vivo. We also derive some theoretical results to analyse dynamic processes observed in vitro.


[Diagnostic accuracy of cell-block or tissue-fragment histology and cytology by fine needle lung aspiration].
Study on the diagnostic accuracy and value of cell block and tissue fragment preparations collected from lung fine needle aspiration (FNA). A total of 187 FNA (22G) samples from the lungs with matched histological diagnosis were studied. Among them, the diagnosis made by depending on 124 cell block and fragment preparations were analyzed in comparing retrospectively with the diagnosis of 187 cases by smear preparations. (1) Of the 124 cell blocks cases, 89 cases were true positives, 22 cases were true negatives, 13 cases were false negatives and no false positives. Of the 187 smears cases, the figure were 136, 30, 19 and 2 cases respectively. The diagnostic accuracy of cell blocks was 87.3% in sensitivity, 100% in specificity, 89.5% in overall accuracy. The figures for smears were 87.7%, 93.8% and 88.8% respectively. (2) For malignant tumours, the histological typing accuracy of cell blocks was 93.3% (83/89), and to be 67.9% (91/134) by diagnosis depending on the smears (P < 0.01). For the benign lesions, the figures were 86.4% (19/22) and 60% (18/30) respectively (P < 0.05). (3) It was possible to obtain many minisections for further studies from cell blocks. Immunoperoxidase staining on minisections was reliable and agreed with those on the surgical specimens. The diagnostic accuracy of cell block is high, particularly in histological typing which approaches to that of the diagnosis made depending on the postoperative specimens. A combined use of smears and cell block is recommended which may raise further the diagnostic accuracy.


Transferrin increases adherence of iron-deprived Neisseria gonorrhoeae to human endometrial cells.
Our purpose was to study the effects of iron deprivation with and without human transferrin supplementation on the adherence and invasion of Neisseria gonorrhoeae to human endometrial cells. N. gonorrhoeae grown with our without iron was placed in media alone or media containing 2.5 mg/ml saturated human transferrin or unsaturated transferrin. N. gonorrhoeae was inoculated onto polarized human endometrial carcinoma cell (HEC 1-B) monolayers, and at various intervals monolayers were washed and incubated with media containing gentamicin or media alone. Colony-forming units per milliliter of N. gonorrhoeae associated with HEC 1-B cells were then determined. N. gonorrhoeae strains tested included both a transferrin receptor-positive (wild-type) and a transferrin receptor-negative mutant. Differences in percent of original inoculum remaining at varying time points were analyzed by the Mann-Whitney U test. Transmission electron microscopy using a primary endometrial cell line was used to verify findings. Iron-negative N. gonorrhoeae exhibited less adherence than did iron-positive N. gonorrhoeae. No difference in HEC 1-B adherence was seen when either saturated transferrin or unsaturated transferrin was added to the iron-positive N. gonorrhoeae. With iron-negative N. gonorrhoeae addition of either saturated transferrin or unsaturated transferrin significantly increased N. gonorrhoeae adherence although unsaturated transferrin did not permit growth of iron-negative N. gonorrhoeae in tissue culture media alone. Transmission electron microscopy confirmed increased adherence of iron-negative N. gonorrhoeae supplemented with unsaturated transferrin. An iron-negative N. gonorrhoeae mutant lacking the transferrin receptor exhibited no adherence regardless of addition of saturated transferrin or unsaturated transferrin. Invasion could not be quantitated reliably because of persistence of gentamicin effect. Iron and transferrin increased attachment of N. gonorrhoeae to human endometrial cells.


Hyperintentionality during automatic perception of naturalistic cooperative behavior in patients with schizophrenia.
Social cognition and the corresponding functionality of involved brain networks are essential for effortless social interaction. Patients with schizophrenia exhibit impaired social functioning. In this study, we focused on the neural networks involved in the automatic perception of cooperative behavior and their alterations in schizophrenia. We performed a functional magnetic resonance imaging study of 19 schizophrenia patients and 19 healthy matched controls. Participants watched a set of short videos with two actors manipulating objects, either with (C+) or without cooperation (C-). Additionally, we assessed delusional symptoms in patients using the Scales for the Assessment of Positive Symptoms and psychosis proneness in healthy controls using the brief schizotypal personality questionnaire. The observed group-by-condition interaction revealed a contrasting activation pattern for patients versus healthy controls in the medial and lateral prefrontal cortex, the middle cingulate cortex, and the left angular gyrus. Furthermore, increased activation of the middle prefrontal areas, left angular gyrus, and the posterior sulcus temporalis superior in response to the noncooperative condition (C-) was positively correlated with delusional symptoms in patients. Our findings suggest an overactivated "theory of mind" network in patients for the processing of noncooperative behavior. Thus, "overmentalizing" might be based on delusions and altered processing of cooperative behavior in patients with schizophrenia.


Diminished sense of self-existence and self-reported aggression among Japanese students.
This study examined the relationship between a diminished sense of self-existence and self-reported aggression among Japanese undergraduate students. Based on the previous scales, 81 items were developed to measure the diminished sense of self-existence and were assumed to represent three dimensions: self, others, and time. 286 undergraduate students rated themselves on the Diminished Sense of Self-existence Scale and the 1992 Buss-Perry Aggression Questionnaire. Analysis indicated that men and women had low scores on Verbal Aggression and high scores on Hostility with the diminished sense of self-existence. The diminished sense of self-existence was not generally related to Anger or Physical Aggression in men, whereas in women, Anger and Physical Aggression were found particularly when the sense of self-existence in relations with others was diminished.


Case Report: Preimplantation Genetic Testing and Pregnancy Outcomes in Women With Alport Syndrome.
Alport syndrome, a monogenic kidney disease, is characterized by progressive hemorrhagic nephritis, sensorineural hearing loss, and ocular abnormalities. Mutations in COL4A5 at Xq22 accounts for 80-85% of X-linked Alport syndrome patients. Three couples were referred to our reproductive genetics clinic for prenatal or preconception counseling. Prenatal diagnoses were performed by amplifying targeted regions of COL4A5. Targeted next-generation sequencing (NGS)-based haplotype analysis or karyomapping was performed in two patients. Pregnancy outcomes in the three patients were collected and analyzed. Published Alport syndrome cases were searched in Pubmed and Embase. Prenatal diagnoses in two cases showed one fetus harbored the same pathogenic mutation as the proband and the other was healthy. The couple with an affected fetus and the patient with a family history of Alport syndrome chose to take the preimplantation genetic testing (PGT) procedure. One unaffected embryo was transferred to the uterus, and a singleton pregnancy was achieved, respectively. Two patients presented non-nephrotic range proteinuria (<3 g/24 h) during pregnancy and the three cases all delivered at full-term. However, published Alport cases with chronic kidney disease or proteinuria during pregnancy were came with a high rate (75%) of adverse maternal and fetal outcomes. The PGT procedure performed in this study was proven to be practicable and might be expanded to be applied in other monogenic diseases. Moderate or severe renal impairments in Alport syndrome were strongly associated with adverse maternal and fetal outcomes, and baseline proteinuria was a potential predictor for pregnancy outcomes of Alport syndrome as other kidney diseases.


Immunostaining with HAM56 in the diagnosis of adenocarcinomas.
Data has been presented suggesting that the monoclonal antibody HAM56 reacts with many adenocarcinomas but not with colonic adenocarcinomas. Previous studies have suggested that immunostaining with HAM56 may be useful in the differential diagnosis of adenocarcinoma of unknown origin. To test the specificity of HAM56 immunostaining in the diagnosis of adenocarcinomas, we studied formalin-fixed, paraffin-embedded tissue from 213 adenocarcinomas from a variety of sites using an avidin-biotin immunohistochemical technique. Positive reactivity was seen in some tumors of all types including 39% of colonic adenocarcinomas. We conclude that immunostaining with HAM56 is not specific in the differential diagnosis of adenocarcinoma of unknown origin.


Comparison of Short-Term Efficacy Between Endoscopic Submucosal Tunnel Dissection and Endoscopic Submucosal Dissection in Treatment of Wide Esophageal Squamous Cell Carcinoma of Early Stage.
The goal of this study was to compare the efficacy and safety of endoscopic submucosal tunnel dissection (ESTD) with endoscopic submucosal dissection (ESD) for the removal of early-stage esophageal squamous cancer wider than or equal to one half the circumference of the esophagus. Although ESD has been successfully applied for resection of early-stage esophageal cancer, there are still technical challenges and postoperative stenosis when it is applied to treat large lesions. A total of 40 patients with early-stage esophageal cancer wider than or equal to one half its circumference were enrolled in this study and randomly assigned to an ESTD or ESD group for treatment of esophageal superficial squamous cell carcinoma. All of the patients received oral steroids after endoscopic dissection. We then compared the 2 groups in terms of average operating time, dissection speed, en bloc resection rate, R0 resection rate, and complications during a 1-year follow-up period. The dissection speed in the ESTD group was significantly faster than that in the ESD group (P=0.047). There were no significant differences in operating time, en bloc resection rates, or R0 resection rates between the ESTD and ESD group (P=0.319, 1.000, 1.000, respectively). There were also no significant differences in perforation, bleeding, or stenosis rates between the ESTD and ESD group (P=1.000, 0.748, 1.000, respectively). Both ESTD and ESD are safe and effective therapies for early-stage esophageal cancer wider than or equal to one half the esophageal circumference. The dissection speed of ESTD is faster than that of ESD.


An explorative study into learning on international traineeships: experiential learning processes dominate.
To explore the learning processes of undergraduate medical students undertaking international traineeships. Semi-structured, in-depth interviews were conducted with 24 undergraduate medical students from Maastricht University Medical School, the Netherlands. The 24 subjects were selected by purposeful sampling. Research methods resembled the grounded theory method. Although the data were initially gathered for an earlier study, the richness of the data enabled renewed scrutiny. The data yielded the following categories concerning the description of the learning processes: motivation, preparation, internal supervisor, external supervisor, assessment, and positive and negative incidents. The majority of supervisors' influences on the learning process were facilitative or negligible. Socio-cultural differences between students and supervisors sometimes appeared to blur productive learning. The greater proportion of the students seemed to learn by 'experiential learning', a smaller proportion learned by 'active learning', and the learning of a very small minority of the students appeared to be 'guided'. Although experiential learning seemed to be the dominant learning process, it is not clear whether this is also the most fruitful approach to learning. It could be argued that structuring learning outcomes by a more active learning process might be more effective. To guide the learning process and learning outcomes, it might be advisable to develop guidelines for writing international traineeship reports. Supervision of these reports should be more co-ordinated to prevent arbitrariness and to scaffold active learning.


Accidental ligature strangulation due to a roller-type massage device.
A case is reported in which a woman was accidentally strangled when her blouse became entangled in a roller-type electric massage device that she was using to massage the back of her neck. Accidental strangulation in adults, outside of the workplace, is uncommon, and to our knowledge this is the first reported case of a strangulation due to this type of device. The findings of this interesting and unusual case are presented.


High-resolution mapping of probes near the X-linked lymphoproliferative disease (XLP) locus.
Fluorescence in situ hybridization (FISH) was employed in high-resolution mapping of probes near the X-linked lymphoproliferative disease (XLP) locus. The map includes the DXS42, DXS12, DXS6, DXS982, DXS739, DXS75, DXS100, DXS10, and DXS177 loci. Metaphase analysis showed that DXS12 and DXS42 mapped to proximal Xq25, while DXS10 and DXS177 mapped to proximal Xq26.1. DXS6, DXS982, DXS739, DXS75, and DXS100 were in Xq25. The order of probes deduced from interphase FISH was: Xq24-(DXS12, DXS42)-DXS6-DXS982-DXS739-DXS75-DXS100+ ++-DXS10-DXS177-Xq26.2. We estimate that the entire region between DXS12 and DXS177 is about 7 Mb. Our previous study indicated that all three XLP deletions (63-3, 66-1, and 43-4) lacked DXS739. We now report that DXS75 and DXS982 are also missing in these deletions. Using interphase FISH measurements, we estimate that 2 Mb are absent in 63-3, and 4 Mb are absent in 66-1 and 43-4. This FISH map confines the XLP candidate gene region to a 2-Mb interval between DXS6 and DXS100 and places DXS100 distal to the XLP locus. This study also demonstrates that small probes (0.6 to 3.6 kb) can be utilized in FISH.


Expanded clinical uses of a novel tissue-retraction material.
Impression making for all fixed prostheses requires access to the prosthetic margin while minimally traumatizing the tissue, so that clinicians can provide as much clinical information as possible to the laboratory technician. This information allows the technician to design the prosthesis to meet the criteria of the periodontium and allow the gingival tissues to recover to their original state. Until now, there have been three traditional options in the armamentarium for retraction procedures: packing cord, electrosurgery, and laser surgery. These procedures all have degrees of trauma that vary based on the experience of the clinician. The gingival tissue may be very delicate and susceptible to recession if too much trauma occurs. This article describes an expanded use of Expa-syl, a newly introduced tissue retraction material, as it relates to minimally invasive tissue management, while still providing an ideal gingival tissue environment for long-term health.


Theoretical investigation of the rubicordifolin cascade.
The results of a theoretical investigation on the complex cascade reaction leading to the natural product rubicordifolin are reported. These computations analyze the discrete transformations that are required during the conversion of the vinyl naphthoquinone starting material into the natural product, including two pseudopericyclic cyclizations as well as a diastereoselective, hetero-Diels-Alder reaction.


The implications of model formulation when transitioning from spatial to landscape ecology.
In this article we compare and contrast the predictions of some spatially explicit and implicit models in the context of a thought problem at the interface of spatial and landscape ecology. The situation we envision is a one-dimensional spatial universe of infinite extent in which there are two disjoint focal patches of a habitat type that is favorable to some specified species. We assume that neither patch is large enough by itself to sustain the species in question indefinitely, but that a single patch of size equal to the combined sizes of the two focal patches provides enough contiguous favorable habitat to sustain the given species indefinitely. When the two patches are separated by a patch of unfavorable matrix habitat, the natural expectation is that the species should persist indefinitely if the two patches are close enough to each other but should go extinct over time when the patches are far enough apart. Our focus here is to examine how different mathematical regimes may be employed to model this situation, with an eye toward exploring the trade-off between the mathematical tractability of the model on one hand and the suitability of its predictions on the other. In particular, we are interested in seeing how precisely the predictions of mathematically rich spatially explicit regimes (reaction-diffusion models, integro-difference models) can be matched by those of ostensibly mathematically simpler spatially implicit patch approximations (discrete-diffusion models, average dispersal success matrix models).


Tetrahydrobiopterin and maternal PKU.
A 29-year-old woman with PKU is presented, who was successfully treated with phenylalanine restriction as well as oral BH4 during this pregnancy, with a normal outcome. Her PAH mutation was R408W/F39L. Remarkably, the blood phenylalanine control was easily accomplished during this pregnancy. The lack of nausea and vomiting during the first trimester suggests that the occurrence of CHD in babies born to women with PKU may be reduced with BH4.


Electrical impedance spectroscopy and diagnosis of tendinitis.
There have been a number of studies that investigate the usefulness of bioelectric signals in diagnoses and treatment in the medical field. Tendinitis is a musculoskeletal disorder with a very high rate of occurrence. This study attempts to examine whether electrical impedance spectroscopy (EIS) can detect pathological changes in a tendon and find the exact location of the lesion. Experimental tendinitis was induced by injecting collagenase into one side of the patellar tendons in rabbits, while the other side was used as the control. After measuring the impedance in the tendinitis and intact tendon tissue, the dissipation factor was computed. The real component of impedance and the dissipation factor turned out to be lower in tendinitis than in intact tissues. Moreover, the tendinitis dissipation factor spectrum showed a clear difference from that of the intact tendon, indicating its usefulness as a tool for detecting the location of the lesion. Pathologic findings from the tissues that were obtained after measuring the impedance confirmed the presence of characteristics of tendinitis. In conclusion, EIS is a useful method for diagnosing tendinitis and detecting the lesion location in invasive treatment.


Physiological and developmental implications of motor unit anatomy.
There is increasing evidence that the architectural design and arrangement of the fibers within a motor unit have important physiological and developmental ramifications. Limited data, however, are available to directly address this issue. In the present study the physiological properties of one motor unit in each of seven cat tibialis anterior (TA) muscles were determined. Each of these units then was repetitively stimulated to deplete the glycogen in all muscle fibers within the unit. Subsequently, the length, type of ending, and spatial distribution of fibers sampled from these physiologically and histochemically typed motor units were determined. Four fast fatigable (FF), one fast, fatigue resistant (FR), and two slow (S) motor units (MU) were studied. The samples consisted of all those glycogen-depleted fibers (9-27) contained within a single fascicle or a circumscribed area of each of the motor unit territories. The mean fiber lengths for the two slow motor units were 35.9 and 45.5 mm. The mean fiber lengths for the fast motor unit samples ranged from 8.8 to 48.5 mm. Some fibers of both the fast and slow units reached lengths of 58 mm. Most of the fibers in the slow units extended the entire distance between the proximal and distal musculotendinous planes, had relatively constant cross-sectional areas, and terminated at the tendon as blunt endings. In contrast, the majority of the fibers in the fast units terminated intrafascicularly at one end, and the cross-sectional area decreased progressively along their lengths, that is, showed a tapering pattern for a significant proportion of their lengths. Therefore, the force generated by units that end midfascicularly would appear to be transmitted to connective tissue elements and/or adjacent fibers. All fibers of a fast unit within a fascicle were located at approximately the same proximo-distal location. Thus, developmentally the selection of muscle fibers by a motoneuron would seem to be influenced by their spatial distribution. The architectural complexities of motor units also have clear implications for the mechanical interactions of active and inactive motor units. For example, the tension capabilities of a motor unit may be influenced not only by the spatial arrangement of its own fibers, but also by the level of activation of neighboring motor units.


Encouraging change in anesthesiology practice through electronic feedback to physicians: results from prototype system.
Implementation of best care practices is difficult because the status quo is often perpetuated; many providers treat patients based on anecdotal experience rather than evidence-based medicine. Our goal was to develop and evaluate an electronic feedback system that feeds back practice and outcome data combined with educational material to anesthesiologists. Best care practices for postoperative nausea/vomiting (PONV) control were selected to evaluate this system because PONV is a common outcome and guidelines have been published.


Effects of phospholipase A2 inhibitors on Ca2+ oscillations in pancreatic acinar cells.
High-affinity cholecystokinin (CCK) receptors were reported to be coupled with phospholipase A2 (PLA2)-arachidonic acid (AA) pathways to mediate Ca2+ oscillations and amylase secretion in rat pancreatic acinar cells. To investigate which types of PLA2 were involved in PLA2-AA pathways, the effects of specific inhibitors for type II and type IV PLA2 on Ca2+ oscillations and amylase secretion were studied in isolated rat pancreatic acini. An inhibitor of type IV (cytosolic) PLA2, AACOCF3 inhibited Ca2+ oscillations elicited by CCK-8 (30 pM) and JMV-180 (100 nM). AACOCF3 inhibited amylase secretion stimulated by JMV-180 and low concentrations of CCK-8 (< or =30 pM). On the other hand, an inhibitor of type II (secretory, nonpancreatic) PLA2 had no effects on Ca2+ oscillations and amylase secretion stimulated by CCK-8 and JMV-180. These results suggest that high-affinity CCK receptors are coupled to cytosolic PLA2 to mediate Ca2+ oscillations and amylase secretion in rat pancreatic acinar cells.


Effect of Water Content in Extraction Mixture on the Pressurized Liquid Extraction Efficiency-Stability of Quercetin 4'-Glucoside During Extraction from Onions.
Pressurized liquid extraction (PLE) is considered as an effective and quick sample preparation method, especially in plant analysis. This quick extraction process favors the isolation of compounds for which long exposure time in high temperatures is undesirable. However, despite this advantage, the application of PLE for plant compounds extraction involves certain problems, such as instability of the compounds. The obtained data proved that even in short-lasting PLE, quercetin 4'-glucoside undergoing the hydrolytical degradation process produces the corresponding aglycon quercetin when water is a component of the applied extractant. The increase of water content in methanol-water extractant mixture heightens the transformation degree of quercetin 4'-glucoside into quercetin and increases its concentration in the PLE extracts. The degradation is accelerated by increased extraction temperature and time. In plant samples, the degradation of quercetin 4'-glucoside is much higher because of the plant matrix effects. The presented results explain why extraction of quercetin from plants by pure methanol is less efficient than by water containing alcohol solutions. More importantly, they prove that the application of water-alcohol extractant during sample preparation leads to the hydrolytical degradation of glycosides to aglycones, and, as a consequence, to false conclusions in plant analysis.


Pharmacokinetics of a transdermal testosterone system in men with end stage renal disease receiving maintenance hemodialysis and healthy hypogonadal men.
Androgen deficiency is common in men with end stage renal disease (ESRD) on maintenance hemodialysis. Pharmacokinetics of transdermal testosterone in men receiving maintenance hemodialysis have not been studied. Our objective was to compare the pharmacokinetics of a transdermal testosterone system in healthy hypogonadal men and in men with ESRD on maintenance hemodialysis. We recruited 10 healthy hypogonadal men and 8 medically stable men on maintenance hemodialysis, 18--70 yr old, who had serum testosterone less than 300 ng/dL. After baseline sampling during a 24-h control period, two testosterone patches were applied daily for 28 days, to achieve a nominal delivery of 10-mg testosterone daily. In addition to single, pooled samples on days 7, 14, and 21, blood was drawn at 0, 2, 4, 6, 8, and 24 h on day 28 in healthy hypogonadal men and on an interdialytic day (day 21 or 28) as well as a dialysis day (day 21 or 28) in men on hemodialysis. On the dialysis day (day 21 or 28), serum free and total testosterone levels were measured hourly for 4 h before hemodialysis and for 4 h during hemodialysis. The dialysate was sampled for testosterone measurement. Baseline mean + SD total (92 +/- 82 vs. 222 +/- 50 ng/dL) and free (11 +/- 9 vs. 27 +/- 6 pg/mL) testosterone concentrations were lower in healthy hypogonadal men than in men with ESRD. After application of two testosterone patches, serum total and free testosterone concentrations rose into the midnormal range in both groups of men. Time-average, steady state (total testosterone, 506 +/- 88 vs. 516 +/- 86 ng/dL; free testosterone, 55 +/- 9 vs. 67 +/- 11 pg/mL), minimum, and maximum total and free testosterone concentrations were not significantly different between the two groups of men during treatment. Increments in total and free testosterone concentrations above baseline, baseline-subtracted areas under the total and free testosterone curves, and half-life of testosterone elimination (t(1/2), 2.1 +/- 0.1 vs. 2.1 +/- 0.2 h, P = not significant) were not significantly different between the two groups. In men receiving hemodialysis, time-average, steady state, and maximal total and free testosterone concentrations and baseline-subtracted areas under the total and free testosterone curves were higher on dialysis day than on an interdialytic day. On the day of hemodialysis, time-average total and free testosterone concentrations were not significantly different during the 4 h before or during hemodialysis. The amount of testosterone removed in the dialysate (8.4 +/- 1.6 microg during 4 h of hemodialysis) was small compared with the daily testosterone production rates in healthy young men. Serum dihydrotestosterone and estradiol concentrations increased into the normal male range and were not significantly different between the two groups. Percent suppression of LH was greater in men with ESRD than in healthy hypogonadal men. A regimen of two Testoderm TTS testosterone patches (Alza Corp., Mountain View, CA) daily can maintain serum concentrations of total and free testosterone and its metabolites dihydrotestosterone and estradiol in the midnormal range in healthy hypogonadal men and men on hemodialysis. The amount of testosterone cleared by hemodialysis is small, and hemodialysis does not significantly affect serum total and free testosterone concentrations in men treated with the testosterone patch.


Control of breathing at high altitude.
Ventilatory acclimatization to high altitude has been discussed in a chronologic fashion, i.e. the acute, prolonged, and chronic or lifelong phases, and the integration of exercise ventilation as it relates to each of these phases has been outlined. Unanswered questions in each of these areas have been posed as fertile grounds for future investigation.


Water Interaction with Fe2NiP Schreibersite (110) Surface: a Quantum Mechanical Atomistic Perspective.
Phosphorus is an element of primary importance for all living creatures, being present in many biological activities in the form of phosphate (PO4 3-). However, there are still open questions about the origin of this specific element and on the transformation that allowed it to be incorporated in biological systems. The most probable source of prebiotic phosphorus is the intense meteoritic bombardment during the Archean era, a few million years after the solar system formation, which brought tons of iron-phosphide materials (schreibersite) on the early Earth crust. It was recently demonstrated that by simple wetting/corrosion processes from this material, various oxygenated phosphorus compounds are produced. In the present work, the wetting process of schreibersite (Fe2NiP) was studied by computer simulations using density functional theory, with the PBE functional supplemented with dispersive interactions through a posteriori empirical correction. To start disentangling the complexity of the system, only the most stable (110) surface of Fe2NiP was used simulating different water coverages, from which structures, water binding energies, and vibrational spectra have been predicted. The computed (ana-)harmonic infrared spectra have been compared with the experimental ones, thus, confirming the validity of the adopted methodology and models.


[Natural electrical activity of human sympathetic nerve fibers recorded from the body surface].
The electrical potentials recorded from human forearm were stored and averaged as synchronous with the cardiac rhythm. The R-wave of the ECG was used to synchronize the averaging system. The record obtained with this technique from human forearm during transient stop of blood flow to avoid mechanical artifacts was a sinusoid-like curve with peaks between the R-waves of the ECG. The nature of this electronegative wave was investigated by means of comparing electrograms and rheograms recorded from forearm of normal subjects and subjects after denervation or desympathization of their upper extremities. The data obtained suggest that the electronegative wave recorded with this technique is the averaged sum of tonic pulse-synchronous electrical activity of sympathetic nerve's fibers innervating vasoconstrictors of the skeletal muscle.


Biological activities and structural properties of the atypical bacteriocins mesenterocin 52b and leucocin b-ta33a.
The antibacterial spectra and modes of action of synthetic peptides corresponding to mesenterocin 52B and leucocin B-TA33a greatly differ despite their high sequence homology. Circular dichroism experiments establish the capacity of each of these two peptides to partly fold into an amphiphilic helix that might be crucial for their adsorption at lipophilic-hydrophilic interfaces.