Pre-steady-state kinetic characterization of thiolate anion formation in human leukotriene C₄ synthase.
Human leukotriene C₄ synthase (hLTC4S) is an integral membrane protein that catalyzes the committed step in the biosynthesis of cysteinyl-leukotrienes, i.e., formation of leukotriene C₄ (LTC₄). This molecule, together with its metabolites LTD₄ and LTE₄, induces inflammatory responses, particularly in asthma, and thus, the enzyme is an attractive drug target. During the catalytic cycle, glutathione (GSH) is activated by hLTC4S that forms a nucleophilic thiolate anion that will attack LTA₄, presumably according to an S(N)2 reaction to form LTC₄. We observed that GSH thiolate anion formation is rapid and occurs at all three monomers of the homotrimer and is concomitant with stoichiometric release of protons to the medium. The pK(a) (5.9) for enzyme-bound GSH thiol and the rate of thiolate formation were determined (k(obs) = 200 s⁻¹). Taking advantage of a strong competitive inhibitor, glutathionesulfonic acid, shown here by crystallography to bind in the same location as GSH, we determined the overall dissociation constant (K(d((GS) = 14.3 μM). The release of the thiolate was assessed using a GSH release experiment (1.3 s⁻¹). Taken together, these data establish that thiolate anion formation in hLTC4S is not the rate-limiting step for the overall reaction of LTC₄ production (k(cat) = 26 s⁻¹), and compared to the related microsomal glutathione transferase 1, which displays very slow GSH thiolate anion formation and one-third of the sites reactivity, hLTC4S has evolved a different catalytic mechanism.


Airway management and mechanical ventilation.
The care of the acutely head-injured patient involves rapid evaluation and correction of hypoxia with appropriate airway management and treatment of associated problems. The primary focus is correction of underlying pathophysiology and prevention of secondary brain injury. Anesthetics and muscle relaxants are used to control intracranial dynamics and maintain systemic and cerebral perfusion. Airway management requires prompt intervention and definitive control, while protecting the cervical spine. Preparation for the possibility of failed intubation is important.


Aging and comparative search for feature differences.
In a comparative visual search experiment, two halves of a display contained visual primitives of various shapes and colors. These halves were identical (50% of trials) or contained a non-matching pair (50% of trials). Response time (RT), accuracy, and eye movements were measured in both young and older adults. There were Age Group x Display Size interactions found for RT, with older adult RT affected more than younger adult RT by increases in display size. This interaction was consistent with predictions generated by sequential-sampling models for RT. There were age group main effects on fixation number and fixation duration, but no age group main effects on accuracy, saccade amplitude, or measures of scan-path efficiency; this indicated that search strategies were similar across age groups. Overall, the results showed no special age group deficits for comparative visual search.


Captopril gastrointestinal therapeutic system coated with cellulose acetate pseudolatex: evaluation of main effects of several formulation variables.
Maintenance of constant drug levels in the body for those drugs that are used in management of hypertension is extremely beneficial. This can be successfully achieved by delivering the antihypertensives as osmotically-controlled drug-delivery system that essentially eliminates the influence of pH on the drug release. The main objective of this study was to evaluate the main effects of the formulation variables on the release of captopril from osmotically-controlled drug-delivery system coated with a custom-made cellulose acetate (CA) pseudolatex reported earlier. A secondary objective was to identify a suitable antioxidant for incorporating in the formulation as the drug undergoes metal-catalyzed oxidative degradation. The drug showed good stability (> or = 90% intact captopril) in solution in the presence of ascorbic acid for a period of 48 h. A seven-factor, 12-run Plackett-Burman screening design was employed to study the main effects of amounts of Polyox(R) N10 and N80, Carbopol(R) 934P and 974P, sodium chloride, orifice size, and % coating weight gain. The response variable was cumulative percent of drug released in 12 h, Y(3), with constraints on lag time Y(1) and time for 50% drug released Y(2)amount of sodium chloride (1.97).


Synthesis and serotonergic activity of 3-[2-(pyrrolidin-1-yl)ethyl]indoles: potent agonists for the h5-HT1D receptor with high selectivity over the h5-HT1B receptor.
The design, synthesis, and biological evaluation of a novel series of 3-[2-(pyrrolidin-1-yl)ethyl]indoles with excellent selectivity for h5-HT1D (formerly 5-HT1Dalpha) receptors over h5-HT1B (formerly 5-HT1Dbeta) receptors are described. Clinically effective antimigraine drugs such as Sumatriptan show little selectivity between h5-HT1D and h5-HT1B receptors. The differential expression of h5-HT1D and h5-HT1B receptors in neural and vascular tissue prompted an investigation of whether a compound selective for the h5-HT1D subtype would have the same clinical efficacy but with reduced side effects. The pyrrolidine 3b was initially identified as having 9-fold selectivity for h5-HT1D over h5-HT1B receptors. Substitution of the pyrrolidine ring of 3b with methylbenzylamine groups gave compounds with nanomolar affinity for the h5-HT1D receptor and 100-fold selectivity with respect to h5-HT1B receptors. Modification of the indole 5-substituent led to the oxazolidinones 24a,b with up to 163-fold selectivity for the h5-HT1D subtype and improved selectivity over other serotonin receptors. The compounds were shown to be full agonists by measurement of agonist-induced [35S]GTPgammaS binding in CHO cells expressed with h5-HT receptors. This study suggests that the h5-HT1D and h5-HT1B receptors can be differentiated by appropriate substitution of the ligand in the region which binds to the aspartate residue and reveals a large binding pocket in the h5-HT1D receptor domain which is absent for the h5-HT1B receptor. The compounds described herein will be important tools to delineate the role of h5-HT1D receptors in migraine.


Definition of the tumor protein D52 (TPD52) gene family through cloning of D52 homologues in human (hD53) and mouse (mD52).
Cloning is reported of a cDNA homologue to the breast carcinoma-associated D52 cDNA, termed D53, and of a mouse D52 cDNA (HGMW-approved symbols TPD52L1 and TPD52). Human D53 and mouse D52 proteins are predicted to be 52 and 86% identical to human D52, respectively. Analysis of the three protein sequences identified a coiled-coil domain and N- and C-terminally located PEST domains in each. The conservation of homology between the D52 and the D53 sequences, combined with a lack of homology between these and known proteins, defines a new mammalian gene/protein family, the D52 family. The human D52 locus has been previously mapped to chromosome 8q21, and using in situ mapping in the present study, a human D53 locus was mapped to chromosome 6q22-q23. We observed coexpression of the human D52 and D53 genes in some breast tumors and derivative cell lines and found that maintenance of D52 and D53 transcript levels in estrogen receptor-positive MCF7 breast carcinoma cells depends upon estradiol. However, D52 and D53 genes were specifically expressed in HL-60 and K-562 leukemia cells, respectively, with 12-O-tetra-decanoylphorbol-13-acetate treatment decreasing D52 and D53 transcript levels in these cell lines. The presence of a coiled-coil domain, combined with observed co- or independent expression of the D52 and D53 genes, suggests that D52 and D53 proteins may be capable of hetero- and/or homodimer formation.


Accurate height and volume measurements on soft samples with the atomic force microscope.
The suitability of three common atomic force microscope (AFM) imaging modes for quantitative height and volume measurements on soft samples was investigated. The height and volume of rehydrated human metaphase chromosomes in liquid were measured using the contact mode, the tapping mode, and the force mapping mode. In both the contact and tapping modes, the measured height and volume strongly depended on the imaging setpoint that sets the imaging force. Measurement deviations up to 50% were observed. The force mapping mode, on the other hand, yielded reproducible height and volume measurements independent of the imaging force. It is therefore suggested that the force mapping mode should be used whenever the height or volume of soft samples need to be accurately determined.


When fasted is not empty: a retrospective cohort study of gastric content in fasted surgical patients†.
Perioperative aspiration leads to significant morbidity and mortality. Point-of-care gastric ultrasound is an emerging tool to assess gastric content at the bedside. We performed a retrospective cohort study of baseline gastric content on fasted elective surgical patients. The primary outcome was the incidence of full stomach (solid content or >1.5 ml kg−1 of clear fluid). Secondary outcomes included: gastric volume distribution (entire cohort, each antral grade); the association between gastric fullness, fasting intervals, and co-morbidities; anaesthetic management changes and incidence of aspiration. We identified 538 patients. Thirty-two patients (6.2%) presented with a full stomach. Nine of these (1.7%) had solid content and 23 (4.5%) had clear fluid >1.5 ml kg−1. An empty stomach was documented in 480 (89.8%) patients. The examination was inconclusive in the remaining 20 patients (5.0%). As expected, increasing antral grade was correlated with larger antral cross-sectional area and higher gastric volume (P<0.001). Of the 32 patients with a full stomach, only six had a documented risk factor for prolonged gastric emptying. The anaesthetic management was changed in all nine patients with solid content. No aspiration was reported. This retrospective cohort study suggests that a small proportion of elective surgical patients may present with a full stomach despite the recommended duration of fasting. Further research is needed to establish the clinical implications of these findings in the elective setting. At present, the clinical role of gastric ultrasound continues to be for the evaluation of gastric contents to guide management when the risk of aspiration is uncertain or unknown.


A novel Aspergillus oryzae esterase that hydrolyzes 4-hydroxybenzoic acid esters.
In this study we report the biochemical characterization of a hypothetical protein from Aspergillus oryzae exhibiting sequence identity with feruloyl esterase and tannase from the genus Aspergillus. The purified recombinant protein showed a hydrolytic activity toward the ethyl, propyl, or butyl esters of 4-hydroxybenzoic acid, but did not show feruloyl esterase or tannase activity. Finally, the enzyme decreased the antimicrobial activity of parabens against A. oryzae via hydrolysis of the ester bond present in butyl 4-hydroxybenzoic acid.


Genes, social transmission, but not maternal effects influence responses of wild Japanese macaques (Macaca fuscata) to novel-object and novel-food tests.
Using long-term maternal pedigree data, microsatellite analysis, and behavioral tests, we examined whether personality differences in wild Japanese macaques (Macaca fuscata) are associated with additive genetic effects, maternal influences, or belonging to a particular social group. Behaviors elicited by novel-object tests were defined by a component related to caution around novel-objects (Ob-PC1) and behaviors elicited by novel food-tests were defined by correlated components related to consummatory responses (Fo-PC1) and caution around novel foods (Fo-PC2). The repeatability of Ob-PC1 was modest and not significant; the repeatabilities of Fo-PC1 and Fo-PC2 were moderate and significant. Linear mixed effects models found that sex, age, sex × age, provisioning, trial number, date, time of day, season, and distance to the closest monkey were not related to personality. Linear mixed effects models of females older than 2 years found that high rank was associated with greater caution around novel objects. Linear models were used to determine whether sex, age, group membership, maternal kinship, or relatedness had independent effects on the personality similarity of dyads. These analyses found that pairs of macaques that lived in the same group were less similar in their caution around novel objects, more closely related pairs of macaques were more similar in their tendency to eat novel food, and that pairs of macaques in the same group were more similar in how cautious they were around novel foods. Together, these findings suggest that personality in this population of wild monkeys was driven by rank, genetic effects, and group effects, the latter possibly including the need to exploit different niches in the environment.


Cholesterol-sensing liver X receptors stimulate Th2-driven allergic eosinophilic asthma in mice.
Liver X receptors (LXRs) are nuclear receptors that function as cholesterol sensors and regulate cholesterol homeostasis. High cholesterol has been recognized as a risk factor in asthma; however, the mechanism of this linkage is not known. To explore the importance of cholesterol homeostasis for asthma, we investigated the contribution of LXR activity in an ovalbumin- and a house dust mite-driven eosinophilic asthma mouse model. In both models, airway inflammation, airway hyper-reactivity, and goblet cell hyperplasia were reduced in mice deficient for both LXRα and LXRβ isoforms (LXRα(-/-)β(-/-)) as compared to wild-type mice. Inversely, treatment with the LXR agonist GW3965 showed increased eosinophilic airway inflammation. LXR activity contributed to airway inflammation through promotion of type 2 cytokine production as LXRα(-/-)β(-/-) mice showed strongly reduced protein levels of IL-5 and IL-13 in the lungs as well as reduced expression of these cytokines by CD4(+) lung cells and lung-draining lymph node cells. In line herewith, LXR activation resulted in increased type 2 cytokine production by the lung-draining lymph node cells. In conclusion, our study demonstrates that the cholesterol regulator LXR acts as a positive regulator of eosinophilic asthma in mice, contributing to airway inflammation through regulation of type 2 cytokine production.


Polarized Raman Spectroscopy of Aligned Insulin Fibrils.
Amyloid fibrils are associated with many neurodegenerative diseases. The application of conventional techniques of structural biology, X-ray crystallography and solution NMR, for fibril characterization is limited because of the non-crystalline and insoluble nature of the fibrils. Here, polarized Raman spectroscopy was used to determine the orientation of selected chemical groups in aligned insulin fibrils, specifically of peptide carbonyls. The methodology is solely based on the measurement of the change in Raman scattered intensity as a function of the angle between the incident laser polarization and the aligned fibrils. The order parameters 〈 P2 〉 and 〈 P4 〉 of the orientation distribution function were obtained, and the most probable distribution of C=O group orientation was calculated. The results indicate that the peptides' carbonyl groups are oriented at an angle of 13±5° from the fibril axis, which is in consistent with previously reported qualitative descriptions of an almost parallel orientation of the C=O groups relative to the main fibril axis.


[Effect of vascular endothelial growth factor C and collagen triple helix repeat containing 1 expression on prognosis of rectal carcinoma patients].
To explore the relationship of vascular endothelial growth factor C (VEGF-C) and collagen triple helix repeat containing 1 (CTHRC1) expression with the carcinogenesis and prognosis of rectal cancer. Cancer tissue samples from 120 rectal cancer patients confirmed by pathology in the People's Hospital of Yichun City from September 2005 to September 2010 were included in the study. Expressions of CTHRC1 and VEGF-C were examined by immunohistochemistry and their correlations with clinicopathological features and prognosis were analyzed. The expression of VEGF-C was positively correlated with tumor size (r=0.943), TNM stages (r=0.784) and tumor differentiation (r=0.773) (all P<0.05). Similarly, the expression of CTRHC1 was also positively correlated with tumor size (r=0.829), TNM stages (r=0.632) and tumor differentiation (r=0.532) (all P<0.05). Rectal cancer patients with low expression of VEGF-C and CTHRC1 had significantly longer survival than those with high expression of VEGF-C and CTHRC1 [(40.0±1.3) vs. (35.4±0.5) months, P<0.01, (39.0±0.5) vs. (35.0±0.5) months, P=0.014]. VEGF-C and CTHRC1 may synergistically promote the invasion and metastasis of human rectal cancer, and provide evidence in predicting the prognosis of patients.


The nurse executive in Operation Desert Shield/Desert Storm.
The Army Medical Department's Chief Nurse describes a corporate nurse executive's role in the Persian Gulf campaign to free Kuwait in early 1991. Although language and cultural barriers presented problems, U.S. Army and Host Nation nurses were able to integrate their resources to assure smooth operations during wartime.


Ameliorated pancreatic β cell dysfunction in type 2 diabetic patients treated with a sodium-glucose cotransporter 2 inhibitor ipragliflozin.
It remains to be seen whether pancreatic β cell dysfunction in type 2 diabetic patients can be ameliorated just by correcting hyperglycemia. The current pilot study investigated β cell function after a four-week treatment with a sodium-glucose cotransporter 2 (SGLT2) inhibitor ipragliflozin in Japanese patients with type 2 diabetes mellitus. Ten participants (age, 51±13 years; hemoglobin A1c levels, 9.4±1.0%) took 50 mg of ipragliflozin L-proline for four weeks and thereafter discontinued the agent for one week. A 75-g oral glucose tolerance test (OGTT) was performed at 0 (baseline), 4 (end of medication), and 5 weeks (end of washout). The β cell function was evaluated using the disposition index, which was calculated as the product of the ΔIns₀₋₁₂₀/ΔGlu₀₋₁₂₀ and the Matsuda index, where ΔIns₀₋₁₂₀/ΔGlu₀₋₁₂₀ represents the ratio of the incremental concentrations of insulin to those of glucose during the 0- to 120-min time period of the OGTT. The fasting glucose level was 182±34 mg/dL at 0 week, 137±20 mg/dL at 4 weeks (p<0.001), and 154±31 mg/dL at 5 weeks (p=0.001). Compared to baseline, the disposition index was significantly elevated not only at 4 weeks (p<0.001) but also at 5 weeks (p=0.008). In conclusion, the current pilot study showed that the β cell function assessed by the OGTT-derived disposition index was significantly improved after a four-week treatment with ipragliflozin in Japanese patients with type 2 diabetes mellitus.


Evaluation of a Molecular Test for Detection of Mycobacterium tuberculosis Isolates Resistant to Rifampicin and Isoniazid.
Multidrug-resistant tuberculosis (MDR-TB) is increasing worldwide and is a major cause of death in many countries. It has become a major challenge for national tuberculosis control programs. Therefore, rapid identification of MDR strains of Mycobacterium tuberculosis and monitoring of their transmission could contribute significantly to the fight against tuberculosis. The GenoType MTBDRplus assay has been recommended by the World Health Organization to identify rifampicin (RIF)- and isoniazid (INH)-resistant M. Tuberculosis isolates. The objectives of this study were to evaluate the performance of the GenoType MTBDRplus test in the detection of rifampicin and isoniazid resistance of M. tuberculosis isolates in a Moroccan hospital and then to determine the frequency of mutations associated with resistance to these two major anti-tuberculosis drugs. This is a retrospective study conducted at the bacteriology department of the Mohammed V military hospital over a period of one year from 01/01/2018 to 12/31/2019. A total of 92 isolates of M. tuberculosis from pulmonary and extra-pulmonary specimens were evaluated for drug susceptibility by MGIT™ 960 AST system and compared to the GenoType MTBDRplus assay. The MGIT™ 960 AST system was used as the gold standard for the evaluation of the GenoType MTBDRplus assay. Sensitivity and specificity of the GenoType MTBDRplus assay for the detection of RIF-resistant M. tuberculosis isolates were 83.33% and 100%, respectively. Its sensitivity and specificity for the detection of INH-resistant M. tuberculosis were 88.23% and 100% respectively. The concordances of the GenoType MTBDRplus assay and the MGIT™ 960 AST system for the detection of sensitivity to RIF and INH were 99% (1/92) and 98% (2/92), respectively. Among the five RIF-resistant isolates, the MUT3 mutation in the rpoB gene (codon S531L mutation) was present in 80% of isolates, whereas mutations in the rpoB MUT1 gene were present in only one (20%) RIF-resistant isolate. INH resistance was detected in 15 isolates, of which nine isolates (60%) had specific mutations of the katG gene (codon S315T1) and conferred a high level of resistance to INH. The results of this study have shown that the GenoType MTBDRplus test has a high sensitivity and specificity for the detection of resistance to RIF and INH.


[Treatment modalities in infected knee alloarthroplasties].
The purpose of this study was to present and to evaluate different treatment options in the infected knee alloarthroplasty. We followed 47 infected knee alloarthroplasties with a mean follow-up of 62 months which were surgically treated by different techniques. There were 20 cases with early infection (< or = 12 months) and 27 cases with late infections (> 12 months). In 10 patients a two stage exchange of the implant were undertaken. In 6 of those 10 cases the infection could be successfully treated. 30 patients underwent an arthrodesis, two of those after an unsuccessful exchange procedure. In this group only in two patients the infection was not managed successfully. 28 of the patients with an arthrodesis showed a good result of the fusion side. One case was only debrided and in 8 cases bony and soft tissue damage lead to amputation. The HSS-score showed an excellent results in 5.3%, a good result in 21%, a fair result in 26.3% and a poor results in 47.4% of the cases. Comparable distribution was documented with the Hungerford-score. Patients with a stable and painless fusion showed a comparable functional outcome to those patients with a new replacement. Revision of an infected knee implant is best managed by a two stage procedure and can lead to a good functional result. Fusion is indicated in cases with bad bony and soft tissue situation. A solid arthrodesis gives a painfree and stable extremity.


Side-Chain Engineering of Conjugated Polymers for High-Performance Organic Field-Effect Transistors.
Past decades have witnessed the rapid development of conjugated polymers because of their promising semiconducting properties and applications in organic field-effect transistors (OFETs). Recent studies have shown that side-chain engineering of conjugated polymers is an efficient strategy to increase semiconducting performance. This Perspective focuses on the side-chain modulation of conjugated polymers and evaluating their effects on the performance of OFETs. The challenges and potential applications of functional high-performance OFETs through side-chain engineering are also discussed.


The role of RAGE in host pathology and crosstalk between RAGE and TLR4 in innate immune signal transduction pathways.
Although the innate immune receptor protein, Receptor for Advanced Glycation End products (RAGE), has been extensively studied, there has been renewed interest in RAGE for its potential role in sepsis, along with a host of other inflammatory diseases of chronic, noninfectious origin. In contrast to other innate immune receptors, for example, Toll-like receptors (TLRs), that recognize ligands derived from pathogenic organisms that are collectively known as "pathogen-associated molecular patterns" (PAMPs) or host-derived "damage-associated molecular patterns" (DAMPs), RAGE has been shown to recognize a broad collection of DAMPs exclusively. Historically, these DAMPs have been shown to be pro-inflammatory in nature. Early studies indicated that the adaptor molecule, MyD88, might be important for this change. More recent studies have explored further the mechanisms underlying this inflammatory change. Overall, the newer results have shown that there is extensive crosstalk between RAGE and TLRs. The three canonical RAGE ligands, Advanced Glycation End products (AGEs), HMGB1, and S100 proteins, have all been shown to activate both TLRs and RAGE to varying degrees in order to induce inflammation in in vitro models. As with any field that delves deeply into innate signaling, obstacles of reagent purity may be a cause of some of the discrepancies in the literature, and we have found that commercial antibodies that have been widely used exhibit a high degree of nonspecificity. Nonetheless, the weight of published evidence has led us to speculate that RAGE may be physically interacting with TLRs on the cell surface to elicit inflammation via MyD88-dependent signaling.


Automatic magnetic resonance prostate segmentation by deep learning with holistically nested networks.
Accurate automatic segmentation of the prostate in magnetic resonance images (MRI) is a challenging task due to the high variability of prostate anatomic structure. Artifacts such as noise and similar signal intensity of tissues around the prostate boundary inhibit traditional segmentation methods from achieving high accuracy. We investigate both patch-based and holistic (image-to-image) deep-learning methods for segmentation of the prostate. First, we introduce a patch-based convolutional network that aims to refine the prostate contour which provides an initialization. Second, we propose a method for end-to-end prostate segmentation by integrating holistically nested edge detection with fully convolutional networks. Holistically nested networks (HNN) automatically learn a hierarchical representation that can improve prostate boundary detection. Quantitative evaluation is performed on the MRI scans of 250 patients in fivefold cross-validation. The proposed enhanced HNN model achieves a mean ± standard deviation. A Dice similarity coefficient (DSC) of [Formula: see text] and a mean Jaccard similarity coefficient (IoU) of [Formula: see text] are used to calculate without trimming any end slices. The proposed holistic model significantly ([Formula: see text]) outperforms a patch-based AlexNet model by 9% in DSC and 13% in IoU. Overall, the method achieves state-of-the-art performance as compared with other MRI prostate segmentation methods in the literature.


The concentration of criminal victimization and patterns of routine activities.
Although many repeat victimization studies have focused on describing the prevalence of the phenomenon, this study attempted to explain variations in the concentration of victimization by applying routine activities as a theoretical model. A multivariate analysis of repeat victimization based on the 2005 Taiwan criminal victimization data supported the general applicability of the routine activity model developed in Western culture for predicting repeat victimization. Findings that diverged from Western patterns included family income to assault, gender to robbery, and marital status, family income, and major activity to larceny incidents. These disparities illustrated the importance of considering the broader sociocultural context in the association between risk predictors and the concentration of criminal victimization. The contradictory results and nonsignificant variance also reflected untapped information on respondents' biological features and psychological tendencies. Future victimization research would do well to integrate measurements that are sensitive to salient sociocultural elements of the society being studied and individuals' biological and psychological traits.


What non-prescription treatments do UK women with breast cancer use?
Understanding the self-prescribing behaviours of patients as well as their attitudes towards prescribed medication regimens is essential if healthcare professionals are to support treatment adherence and avoid unwanted pharmacological interactions and compromises in treatment efficacy. Evidence shows that women with breast cancer are particularly likely to use complementary and alternative therapies. This paper describes the reported treatment profile of a sample of 208 women with breast cancer in the UK. The information was gathered as part of a study exploring the preferences for injection or tablets in the administration of breast cancer treatment. Almost two-thirds of the sample were currently taking prescribed breast cancer treatment, mostly a single hormone therapy. Prescribed medications for co-morbid diseases were also common, and 53% of the women were self-medicating mainly with supplements, principally vitamins, various oils and minerals. In line with other studies, higher levels of education, socio-economic status and internal locus of control were associated with non-prescription use as well as a body mass index <30.


The estimation of protein equivalents of total nitrogen in Chinese CAPD patients: an explanatory study.
The protein equivalent of total nitrogen appearance (PNA) formula, based on the urea nitrogen appearance (UNA), is popularly used by stable continuous ambulatory peritoneal dialysis (CAPD) patients to estimate dietary daily protein intake (DPI). However, we found that the estimated DPI was higher than that directly evaluated from the dietary records of most of our CAPD patients. Therefore, in the present study, we tried to determine possible bias in PNA estimation by UNA with a nitrogen balance study of our CAPD patients. Thirty-one CAPD patients with stable clinical conditions were included. Their 3-day dietary records were reviewed by a dedicated dietitian to calculate their energy, protein, and nitrogen intake (NI). The nitrogen removal (NR) from urine and dialysate was measured by the Kjeldahl technique. Then, we calculated the proportion of urea nitrogen appearance (UNA) in total nitrogen appearance (TNA) and analyzed the possible factors that could affect this proportion. Among these patients, 17 males and 14 females, the mean age was 64.19 ± 12.42, and the dialysate drainage volume was 6700 (2540) ml/day. The percentage of UNA in TNA was 63.22 ± 6.66%. Compared with the other classic nitrogen balance studies in the CAPD population, the protein nitrogen and other nonurea nitrogen losses in this study were all lower. Based on these 31 nitrogen balance studies, we proposed a pair of new equations to estimate PNA by UNA. (1) PNA = 9.3 + 7.73 UNA; (2) PNA = PNPNA + TPL = 6.7 + 7.28 UNA + TPL. Our study suggested that the PNA formula generated from previous European studies overestimated DPI in our CAPD patients.


Linear epidermal nevus and nevus sebaceus syndromes: a clinicopathologic study of 3 patients.
Linear epidermal nevus syndrome and linear sebaceus nevus syndrome are rare neurocutaneous syndromes characterized by epidermal nevi, epilepsy, and mental retardation. Pathologic descriptions of the central nervous system findings in such patients are rare. We examined the clinicopathologic features of 2 patients with linear epidermal nevus syndrome and 1 with nevus sebaceus syndrome who underwent surgical resections for chronic epilepsy in a tertiary referral center with a high volume of epilepsy surgery. Patients included 3 females, aged 11 months (patient 1), 8 years (patient 2), and 2 1/2 years (patient 3) at the time of surgery. The duration of seizures prior to surgery was 11 months, 6 years, and 28 months, respectively. Two patients had epidermal nevi involving the head region (patients 1 and 3), and 1 had a nevus sebaceus of Jadassohn (patient 2); patient 2 had a choristoma, and patient 3 had a dermoid cyst in the eye region. Patient 1 demonstrated hemimegalencephaly radiographically. Histologic examination of resected cortical tissue in patients 1 and 2 demonstrated severe diffuse cortical dysplasia characterized by a disorganized cortical architectural pattern, a haphazard orientation of cortical neurons, and increased molecular layer neurons. Gyral fusion was seen in patient 1. Pial glioneuronal hamartomas were observed in patient 1. Prominent cortical astrocytosis was seen in patients 1 and 2, and foci of microcalcification were evident in patient 1. Cortical dysplasia was milder in patient 3 and consisted of an increased number of molecular layer neurons. Neuronal heterotopia was observed in all 3 patients. The spectrum of neuronal migration abnormalities in the setting of these syndromes may be variable in terms of its histologic phenotypic manifestations.


Recurrent contrast-induced encephalopathy following coronary angiography.
Contrast-induced encephalopathy (CIE) is an acute and reversible neurological disturbance associated with the intra-arterial administration of iodinated contrast medium during cardiac catheterisation. It may manifest with encephalopathy, motor and sensory disturbances; vision disturbances, including cortical blindness, ophthalmoplegia, aphasia; and seizures. Disruption of the blood-brain barrier and direct neuronal toxicity are believed to be implicated in the pathophysiology of the syndrome. Symptoms appear soon after contrast administration and resolve completely within 24-48 h. Risk factors may include hypertension, diabetes mellitus, renal impairment, the administration of large volumes of iodinated contrast, percutaneous coronary intervention or selective angiography of internal mammary grafts and previous adverse reaction to iodinated contrast. On cerebral imaging, CIE may mimic subarachnoid haemorrhage or cerebral ischaemia, but imaging may be normal. Prognosis is excellent with supportive management alone. CIE may recur, but re-challenge with iodinated contrast without adverse effects has been documented. CIE is a diagnosis of exclusion and is an important clinical entity to consider in the differential diagnosis of stroke following cardiac catheterisation. Physicians should be aware of it and consider it prior to initiating thrombolysis.


Expression levels of the agr locus and prfA gene during biofilm formation by Listeria monocytogenes on stainless steel and polystyrene during 8 to 48 h of incubation 10 to 37 °C.
The objective of this study was to compare the gene expression levels of the agr locus and prfA gene during adhesion and biofilm formation by four L. monocytogenes isolates (2 biofilm-forming and 2 non-forming) on stainless steel and polystyrene surfaces at different temperatures (10 °C, 20 °C and 37 °C), and times (8 h, 12 h, 24 h and 48 h). The agrA and prfA genes were expressed at higher levels than the agrBCD genes. The levels of agr locus expression were higher in the biofilm-forming strains, and the greatest difference between biofilm-forming and non-forming isolates was observed for the agrB, agrC and agrD genes. However, no difference in the expression of the prfA gene was seen among the isolates, independent of the biofilm-forming ability. Maximum expression of the agr locus and prfA gene was observed at 37 °C, whereas expression was lowest at 10 °C. The agr locus, and particularly the agrB, agrC and agrD genes, is important in the initial adhesion phase of biofilm production by L. monocytogenes, with this expression independent of prfA. In addition, the agr locus and prfA gene expression levels were strongly influenced by time and temperature.


Right atrial myxoma associated with acute cor pulmonale. Case report.
Atrial myxomas are the most common type of primary intracardiac tumors. Although they are benign, it is recommended its immediate removal as soon as the diagnosis is confirmed, since they are associated with tumor embolization and their harmful consequences. The objective of this report was to present the case of an intracardiac tumor of rare location (right atrium) that developed intraoperative embolization and to alert anesthesiologists for the possibility of this complication, besides discussing the anesthetic conduct. A male patient, 42 years old, presented with a large mass in the right atrium, being scheduled for removal of the tumor. Anesthetic induction consisted of ethomidate, fentanyl and rocuronium bromide and it was maintained with isoflurane and fentanyl. Intraoperatively, the patient developed acute cor pulmonale secondary to tumor embolization, with the immediate institution of support measures and cardiopulmonary bypass. The remaining of the surgery was uneventful and the patient was discharged on the 7th postoperative day in good conditions. Although intracardiac myxoma is a benign tumor, it can be associated with severe and even fatal complications. Knowledge of the disease is important for the proper management of those patients by the anesthesiologist, as well as to diagnose and treat possible intraoperative complications.


Addition of Radiotherapy to Immunotherapy: Effects on Outcome of Different Subgroups Using a Propensity Score Matching.
Immune checkpoint inhibition (ICI) has been established as successful modality in cancer treatment. Combination concepts are used to optimize treatment outcome, but may also induce higher toxicity rates than monotherapy. Several rationales support the combination of radiotherapy (RT) with ICI as radioimmunotherapy (RIT), but it is still unknown in which clinical situation RIT would be most beneficial. Therefore, we have conducted a retrospective matched-pair analysis of 201 patients with advanced-stage cancers and formed two groups treated with programmed cell death protein 1 (PD-1) inhibitors only (PD1i) or in combination with local RT (RIT) at our center between 2013 and 2017. We collected baseline characteristics, programmed death ligand 1 (PD-L1) status, mutational status, PD-1 inhibitor and RT treatment details, and side effects according to the Common Terminology Criteria for Adverse Events (CTCAE) v.5.0. Patients received pembrolizumab (n = 93) or nivolumab (n = 108), 153 with additional RT. For overall survival (OS) and progression-free survival (PFS), there was no significant difference between both groups. After propensity score matching (PSM), we analyzed 96 patients, 67 with additional and 29 without RT. We matched for different covariates that could have a possible influence on the treatment outcome. The RIT group displayed a trend towards a longer OS until the PD1i group reached a survival plateau. PD-L1-positive patients, smokers, patients with a BMI ≤ 25, and patients without malignant melanoma showed a longer OS when treated with RIT. Our data show that some subgroups may benefit more from RIT than others. Suitable biomarkers as well as the optimal timing and dosage must be established in order to achieve the best effect on cancer treatment outcome.


A novel scaffold with longitudinally oriented microchannels promotes peripheral nerve regeneration.
Longitudinally oriented microstructures are essential for a nerve scaffold to promote significant regeneration of injured peripheral axons across nerve gaps. Extensive attention has been devoted to develop scaffolds with inner structures mimicking the nerve-guiding basal lamina microchannels in autografts. However, to date, little information has been obtained about scaffolds with similar inner microstructures, and the efficacy of such scaffolds in bridging peripheral nerve gaps in vivo has never been examined. In the present study, we describe a novel nerve-guiding collagen-chitosan (CCH) scaffold with inner dimensions resembling the basal lamina microchannels of normal nerves. The scaffold has a number of structural advantages, including longitudinally orientated microchannels and extensive interconnected pores between the parallel microchannels. We evaluated the efficacy of the CCH scaffold to bridge a 15-mm-long sciatic nerve defect in rats using a combination of morphological and functional techniques. The in vivo animal study showed that the CCH scaffold achieved nerve regeneration and functional recovery equivalent to that of an autograft, without the exogenous delivery of regenerative agents or cell transplantation. These findings demonstrate that CCH scaffolds may be used as alternatives to nerve autografts for peripheral nerve regeneration.


Coexistence of neurovascular compression syndrome and unruptured cerebral aneurysm.
Unruptured cerebral aneurysms (UCAs) are usually asymptomatic and detected incidentally by intracranial examinations. The coexistence of neurovascular compression syndrome (NVCS) and UCAs has not been well described. The aim of this study was to clarify the characteristics of UCAs with the NVCS. A total of 103 cases that underwent microvascular decompression (MVD) for trigeminal neuralgia (TN) or hemifacial spasm (HFS) were assigned to the NVCS group. The prevalence of UCAs in the NVCS group was compared retrospectively to that in 110 control cases (a control group) by neuro-imaging. Overall treatment courses for NVCS and UCAs were investigated in the NVCS group. Sixteen (15.3%; TN 11 cases, HFS 5 cases) of 103 MVD cases had 19 UCAs, a significantly higher prevalence than the 3.6% in the control group. Binomial logistic regression showed that NVCS is a significant factor for predicting the presence of UCAs, with an odds ratio of 4.80. In the NVCS group, 18 UCAs (94.7%) were supratentorial aneurysms, and 17 UCAs (89.5%) were less than 5 mm in size. Nine UCAs were surgically treated with clipping or coiling. Of the surgical cases, 2 UCAs were treated before MVD for NVCS, whereas the other 7 UCAs were treated after MVD. No aneurysms ruptured during the treatment course. The NVCS occurred with UCAs at a significantly higher rate than in the control group. Most UCAs with the NVCS were supratentorial, small aneurysms that did not affect the surgical treatment of NVCS.


Interprofessional education for delirium care: a systematic review.
Recent delirium prevention and treatment guidelines recommend the use of an interprofessional team trained and competent in delirium care. We conducted a systematic review to identify the evidence for the value of interprofessional delirium education programs on learning outcomes. We searched several databases and the grey literature. Studies describing an education intervention, involving two or more healthcare professions and reporting on at least one learning outcome as classified by Kirkpatrick's evaluation framework were included in this review. Ten out of 633 abstracts reviewed met the study inclusion criteria. Several studies reported on more than one learning outcome. Two studies focused on learner reactions to interprofessional delirium education; three studies focused on learning outcomes (e.g. delirium knowledge); six studies focused on learner behavior in practice; and six studies reported on learning results (e.g. patient outcomes), mainly changes in delirium rates post-intervention. Studies reporting changes in patient outcomes following the delirium education intervention used an interprofessional practice (IPP) intervention in combination with interprofessional education (IPE). Our review of the limited evidence suggests that IPE programs may influence team and patient outcomes in delirium care. More systematic studies of the effectiveness of interprofessional delirium education interventions are needed.


Revision of the genus Ctenophilothis Kryzhanovskij, 1987 (Coleoptera: Histeridae: Saprininae).
The Saharan genus Ctenophilothis Kryzhanovskij, 1987 is revised. Its two species, C. chobauti (Th6ry, 1900) and C. altus (Lewis, 1885), differ mainly by the shape of their mandibles, protibia, and elytral striae. Ctenophilothis is likely a monophyletic genus known so far only from the Algerian, Moroccan, and Egyptian Sahara. The neotype of C. chobauti and lectotype of C. altus are designated. The extremely rare C. altus is redescribed and both species are illustrated by SEM micrographs. The male genitalia of C. chobauti are also illustrated.


Are prejudices against disabled persons determined by personality characteristics? Reviewing a theoretical approach on the basis of empirical research findings.
Taking as point of departure the results obtained from research on prejudice, many authors believe that the quality of attitudes toward disabled persons is influenced by the personality structure of the nondisabled. In order to verify this assumption, a secondary analysis of 67 empirical studies was undertaken. These studies referred to different personality variables such as authoritarianism, ethnocentrism, dogmatism, rigidity, intolerance of ambiguity, cognitive simplicity, anxiety, ego-weakness, self-concept, body-concept, aggressiveness, empathy, intelligence, etc. The results can be summarized as follows: Statistical criteria show that single personality traits have relatively little influence on the attitudes towards disabled persons. An adequate evaluation of the research findings is complicated by, at times, considerable methodological problems which arise when applying the proper test instruments to non-clinical populations. Marked correlations are to be found in particular in the case of authoritarianism, ethnocentrism, intolerance of ambiguity, anxiety, and ego-weakness. The intercorrelations, however, between most of the personality variables are rather high, which by cumulation of "extreme" factors may, in fact, sometimes result in particularly unfavorable attitudes toward the disabled. Thus, personality-related research findings to provide certain valuable explanations. Special attention should be devoted to the multiple connections between personality structure and social structure.


Prediction of response to anti-PD-1 therapy in patients with non-small-cell lung cancer by electronic nose analysis of exhaled breath.
Immune checkpoint inhibitors have improved survival outcome of advanced non-small-cell lung cancer (NSCLC). However, most patients do not benefit. Therefore, biomarkers are needed that accurately predict response. We hypothesized that molecular profiling of exhaled air may capture the inflammatory milieu related to the individual responsiveness to anti-programmed death ligand 1 (PD-1) therapy. This study aimed to determine the accuracy of exhaled breath analysis at baseline for assessing nonresponders versus responders to anti-PD-1 therapy in NSCLC patients. This was a prospective observational study in patients receiving checkpoint inhibitor therapy using both a training and validation set of NSCLC patients. At baseline, breath profiles were collected in duplicate by a metal oxide semiconductor electronic nose (eNose) positioned at the rear end of a pneumotachograph. Patients received nivolumab or pembrolizumab of which the efficacy was assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 at 3-month follow-up. Data analysis involved advanced signal-processing and statistics based on independent t-tests followed by linear discriminant and receiver operating characteristic (ROC) analysis. Exhaled breath data of 143 NSCLC patients (training: 92, validation: 51) were available at baseline. ENose sensors contributed significantly (P < 0.05) at baseline in differentiating between patients with different responses at 3 months of anti-PD-1 treatment. The eNose sensors were combined into a single biomarker with an ROC-area under the curve (AUC) of 0.89 [confidence interval (CI) 0.82-0.96]. This AUC was confirmed in the validation set: 0.85 (CI 0.75-0.96). ENose assessment was effective in the noninvasive prediction of individual patient responses to immunotherapy. The predictive accuracy and efficacy of the eNose for discrimination of immunotherapy responder types were replicated in an independent validation set op patients. This finding can potentially avoid application of ineffective treatment in identified probable nonresponders.


Myokines and Heart Failure: Challenging Role in Adverse Cardiac Remodeling, Myopathy, and Clinical Outcomes.
Heart failure (HF) is a global medical problem that characterizes poor prognosis and high economic burden for the health system and family of the HF patients. Although modern treatment approaches have significantly decreased a risk of the occurrence of HF among patients having predominant coronary artery disease, hypertension, and myocarditis, the mortality of known HF continues to be unacceptably high. One of the most important symptoms of HF that negatively influences tolerance to physical exercise, well-being, social adaptation, and quality of life is deep fatigue due to HF-related myopathy. Myopathy in HF is associated with weakness of the skeletal muscles, loss of myofibers, and the development of fibrosis due to microvascular inflammation, metabolic disorders, and mitochondrial dysfunction. The pivotal role in the regulation of myocardial and skeletal muscle rejuvenation, attenuation of muscle metabolic homeostasis, and protection against ischemia injury and apoptosis belongs to myokines. Myokines are defined as a wide spectrum of active molecules that are directly synthesized and released by both cardiac and skeletal muscle myocytes and regulate energy homeostasis in autocrine/paracrine manner. In addition, myokines have a large spectrum of pleiotropic capabilities that are involved in the pathogenesis of HF including cardiac remodeling, muscle atrophy, and cardiac cachexia. The aim of the narrative review is to summarize the knowledge with respect to the role of myokines in adverse cardiac remodeling, myopathy, and clinical outcomes among HF patients. Some myokines, such as myostatin, irisin, brain-derived neurotrophic factor, interleukin-15, fibroblast growth factor-21, and growth differential factor-11, being engaged in the regulation of the pathogenesis of HF-related myopathy, can be detected in peripheral blood, and the evaluation of their circulating levels can provide new insights to the course of HF and stratify patients at higher risk of poor outcomes prior to sarcopenic stage.


Secondary primary tumor mimicking osteoradionecrosis.
Nasopharyngeal carcinoma (NPC) is a malignant tumor rarely found in the head and neck, representing about 1% of all malignancies. The main treatment for NPC is radiation therapy, which is often given in combination with chemotherapy. However, such treatment may lead to long-term complications, including second primary tumors (SPTs) and osteoradionecrosis (ORN). Both complications have similar radiological characteristics, which can lead to erroneous diagnoses. This paper describes a case of a second primary tumor in a patient after 20 years of radiotherapy in the area where a previous extraction was performed, mimicking an osteoradionecrosis process.


IL-2 contributes to the IL-5 response in granulomas from mice infected with Schistosoma mansoni.
Th cells within the granulomas of murine schistosomiasis mansoni produce IL-5, which is essential for granuloma eosinophil growth and development. The mechanisms regulating granuloma IL-5 production are unknown. The granulomas also make IL-2 in small quantities. rIL-2 therapy stimulates eosinophilia and IL-5 synthesis. Therefore, we studied the effect of IL-2 on IL-5 production within the liver granulomas of murine Schistosoma mansoni. Dispersed granuloma cells and intact granulomas cultured in vitro released IL-5. Adding anti-IL-2 or anti-IL-2R to the cultures, to block IL-2 activity, significantly inhibited IL-5 production. However, supplementing the cultures with small quantities of rIL-2 markedly stimulated IL-5 release in a dose-dependent fashion. Blocking anti-IL-4 mAb had no effect. Also, granuloma T cells were isolated by FACS. These highly purified T cells produced IL-5 both in the presence and absence of plate-bound anti-CD3. Once again, the IL-5 production was dependent on IL-2. The requirement of IL-2 for normal IL-5 production was not dependent on an IL-2-induced expansion of the IL-5-producing, T lymphocyte population. Thus, IL-2 mediates T cell interactions within the granuloma that regulate granuloma IL-5 secretion.


Leukocytapheresis in patients with inflammatory bowel diseases.
Leukocytapheresis, a blood purification therapy, exerts anti-inflammatory effects by removing activated leukocytes from the peripheral blood through extracorporeal circulation. It is a potential option of treatment for patients with inflammatory bowel diseases (IBD), especially those with ulcerative colitis (UC), who do not respond to conventional therapy. Given that it has a favourable safety profile and seems to have steroid sparing effects, its position in the treatment of UC is likely to expand. However, there is inadequate evidence to draw any conclusions about the efficacy of leukocytapheresis in patients with Crohn's disease, and it should only be used in accordance with special arrangements for consent. Considering the current level of knowledge, it is essential to conduct large, well-designed, randomized clinical trials to evaluate the effects of leukocytapheresis in the management of IBD patients.


Double-Layer Agar (DLA) Modifications for the First Step of the Phage-Antibiotic Synergy (PAS) Identification.
The research carried out so far for phage-antibiotic synergy (PAS) differs as regards the technique of modifying the double-layer agar (DLA) method to show the PAS effect on Petri plates, which may contribute to non-uniform research results. Therefore, there is a need to unify the method to effectively detect the PAS effect, at its most basic in vitro test. In this study, bacteriophage T45 and 43 antibiotics belonging to different antibiotic classes were used. Seven different DLA method modifications were tested, in terms of antibiotic addition placement and presence or absence of the base agar. The overall number of phage plaques per plate mainly depended on the antibiotic used. Differences in plaque quantity depended on the type of the DLA method modification. The largest total number of plaques was obtained by the addition of an antibiotic to a bottom agar with the presence of a top agar. This indicates that even though an antibiotic could manifest the PAS effect by a standard disk method, it would be worth examining if the effect is equally satisfactory when applying antibiotics directly into the agar, with regards to using the same bacteriophage and bacterial host.


Effects of abstinence on the ability of clinical laboratory tests to identify male alcoholics.
Quadratic discriminant analysis of 25 commonly ordered clinical laboratory tests resulted in correct classification of 100% of nonalcoholic inpatients (n = 41), 100% of medical ward alcoholics as alcoholic (n = 63), and 95% of alcoholism treatment program participants as alcoholic (n = 274). Admission laboratory values for a random sample of 138 additional alcoholism treatment program participants were used to correctly classify 96% of them as alcoholics. Repeat analysis of these same laboratory tests after some 27 days of hospitalization resulted in 94% of the 138 patients still being classified as alcoholic, even though significant improvements in individual hepatic and hematologic laboratory values were noted. Classification was not changed with reanalysis after long-term abstinence (7 or 24 months), suggesting widespread and persistent alcohol-related alterations in organ system functioning with chronic alcohol abuse. Quadratic discriminant analysis of laboratory tests is an effective means of identifying people with present or past alcohol abuse but is not yet of value in detecting compliance with a treatment goal of abstinence.


Expression, purification, and physical properties of recombinant flavocytochrome fusion proteins containing rat cytochrome b(5) linked to NADPH-cytochrome P450 reductase by different membrane-binding segments.
Reconstitution of the enzymatic activities using purified microsomal cytochrome P450s (P450) requires the presence of a membrane-binding segment in the mammalian flavoprotein, NADPH--cytochrome P450 reductase (CPR), and the hemeprotein, cytochrome b(5) (b(5)). The mechanism(s) by which the membrane-binding segments of these proteins exert such a critical role in influencing the reconstitution of the NADPH-supported activity of a P450 remains undefined. In the present work we describe the construction, expression, and purification of four different types of recombinant flavocytochromes containing rat b(5) and rat CPR linked by various membrane-binding segments. The physical properties of these artificial fusion proteins have been studied to determine their ability to serve as electron transfer agents. These studies are a prelude to the subsequent study (accompanying paper) evaluating the functional roles of the hydrophobic (membrane-binding) sequences of b(5) and CPR in the reconstitution of P450 activities. The present study shows that the purified recombinant fusion proteins can serve as active electron transport carriers from NADPH to cytochrome c as well as b(5) by intramolecular as well as intermolecular reactions. It is shown here that the electron transport properties of these purified fusion proteins are influenced by high concentrations of KCl, suggesting a role for charged amino acids in protein-protein interactions. The present study illustrates the application of artificial recombinant flavocytochromes as useful proteins for the study of intramolecular electron transport reactions for comparison with intermolecular interactions.


Geometrical Nonlinearity for a Timoshenko Beam with Flexoelectricity.
The Timoshenko beam model is applied to the analysis of the flexoelectric effect for a cantilever beam under large deformations. The geometric nonlinearity with von Kármán strains is considered. The nonlinear system of ordinary differential equations (ODE) for beam deflection and rotation are derived. Moreover, this nonlinear system is linearized for each load increment, where it is solved iteratively. For the vanishing flexoelectric coefficient, the governing equations lead to the classical Timoshenko beam model. Furthermore, the influence of the flexoelectricity coefficient and the microstructural length-scale parameter on the beam deflection and the induced electric intensity is investigated.


Reflex control of fetal arterial pressure and hormonal responses to slow hemorrhage.
Late-gestation fetal sheep respond to slow hemorrhage with increases in plasma concentrations of adrenocorticotropic hormone (ACTH), hydrocortisone, arginine vasopressin (AVP), and plasma renin activity (PRA) that correlate to the acidemia and hypercapnia also produced by hemorrhage. This study was designed to investigate the role of peripheral chemoreceptors in the mediation of these responses. Chronically catheterized fetal sheep were left intact or were subjected to bilateral section of cervical vagosympathetic trunks and carotid sinus nerves. At least 5 days after surgical preparation (between 121 and 138 days of gestation) fetuses were bled at a rate of 11 ml/10 min for 2 h. Denervated fetuses were studied with or without simultaneous infusion of phenylephrine. Denervation exaggerated the decrease in mean arterial pressure and arterial pH and the increase in arterial PCO2 during hemorrhage. Infusion of phenylephrine in the denervated fetuses prevented the decrease in blood pressure and reduced the magnitudes of changes in blood gases. Fetal plasma ACTH, hydrocortisone, and PRA responses to the hemorrhage were exaggerated in the denervated fetuses (not infused with phenylephrine) compared with the intact fetuses. Phenylephrine infusion attenuated the ACTH response and inhibited the AVP response but did not alter the PRA response. We conclude that the sectioned fibers are important for the maintenance of blood pressure and blood gases during hemorrhage and that the PRA, AVP, and ACTH responses to slow hemorrhage are not mediated by peripheral chemoreceptors.


Interventions for raising breast cancer awareness in women.
Breast cancer continues to be the most commonly diagnosed cancer in women globally. Early detection, diagnosis and treatment of breast cancer are key to better outcomes. Since many women will discover a breast cancer symptom themselves, it is important that they are breast cancer aware i.e. have the knowledge, skills and confidence to detect breast changes and present promptly to a healthcare professional. To assess the effectiveness of interventions for raising breast cancer awareness in women. We searched the Cochrane Breast Cancer Group's Specialised Register (searched 25 January 2016), Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 12) in the Cochrane Library (searched 27 January 2016), MEDLINE OvidSP (2008 to 27 January 2016), Embase (Embase.com, 2008 to 27 January 2016), the World Health Organization's International Clinical Trials Registry Platform (ICTRP) search portal and ClinicalTrials.gov (searched 27 Feburary 2016). We also searched the reference lists of identified articles and reviews and the grey literature for conference proceedings and published abstracts. No language restriction was applied. Randomised controlled trials (RCTs) focusing on interventions for raising women's breast cancer awareness i.e. knowledge of potential breast cancer symptoms/changes and the confidence to look at and feel their breasts, using any means of delivery, i.e. one-to-one/group/mass media campaign(s). Two authors selected studies, independently extracted data and assessed risk of bias. We reported the odds ratio (OR) and 95% confidence intervals (CIs) for dichotomous outcomes and mean difference (MD) and standard deviation (SD) for continuous outcomes. Since it was not possible to combine data from included studies due to their heterogeneity, we present a narrative synthesis. We assessed the quality of evidence using GRADE methods. We included two RCTs involving 997 women: one RCT (867 women) randomised women to receive either a written booklet and usual care (intervention group 1), a written booklet and usual care plus a verbal interaction with a radiographer or research psychologist (intervention group 2) or usual care (control group); and the second RCT (130 women) randomised women to either an educational programme (three sessions of 60 to 90 minutes) or no intervention (control group). Knowledge of breast cancer symptomsIn the first study, knowledge of non-lump symptoms increased in intervention group 1 compared to the control group at two years postintervention, but not significantly (OR 1.1, 95% CI 0.7 to 1.6; P = 0.66; 449 women; moderate-quality evidence). Similarly, at two years postintervention, knowledge of symptoms increased in the intervention group 2 compared to the control group but not significantly (OR 1.4, 95% CI 0.9 to 2.1; P = 0.11; 434 women; moderate-quality evidence). In the second study, women's awareness of breast cancer symptoms had increased one month post intervention in the educational group (MD 3.45, SD 5.11; 65 women; low-quality evidence) compared to the control group (MD -0.68, SD 5.93; 65 women; P < 0.001), where there was a decrease in awareness. Knowledge of age-related riskIn the first study, women's knowledge of age-related risk of breast cancer increased, but not significantly, in intervention group 1 compared to control at two years postintervention (OR 1.8; 95% CI 0.9 to 3.5; P < 0.08; 447 women; moderate-quality evidence). Women's knowledge of risk increased significantly in intervention group 2 compared to control at two years postintervention (OR 4.8, 95% CI 2.6 to 9.0; P < 0.001; 431 women; moderate-quality evidence). In the second study, women's perceived susceptibility (how at risk they considered themselves) to breast cancer had increased significantly one month post intervention in the educational group (MD 1.31, SD 3.57; 65 women; low-quality evidence) compared to the control group (MD -0.55, SD 3.31; 65 women; P = 0.005), where a decrease in perceived susceptibility was noted. Frequency of Breast CheckingIn the first study, no significant change was noted for intervention group 1 compared to control at two years postintervention (OR 1.1, 95% CI 0.8 to 1.6; P = 0.54; 457 women; moderate-quality evidence). Monthly breast checking increased, but not significantly, in intervention group 2 compared to control at two years postintervention (OR 1.3, 95% CI 0.9 to 1.9; P = 0.14; 445 women; moderate-quality evidence). In the second study, women's breast cancer preventive behaviours increased significantly one month post intervention in the educational group (MD 1.21, SD 2.54; 65 women; low-quality evidence) compared to the control group (MD 0.15, SD 2.94; 65 women; P < 0.045). Breast Cancer AwarenessWomen's overall breast cancer awareness did not change in intervention group 1 compared to control at two years postintervention (OR 1.8, 95% CI 0.6 to 5.30; P = 0.32; 435 women; moderate-quality evidence) while overall awareness increased in the intervention group 2 compared to control at two years postintervention (OR 8.1, 95% CI 2.7 to 25.0; P < 0.001; 420 women; moderate-quality evidence). In the second study, there was a significant increase in scores on the Health Belief Model (that included the constructs of awareness and perceived susceptibility) at one month postintervention in the educational group (mean 1.21, SD 2.54; 65 women) compared to the control group (mean 0.15, SD 2.94; 65 women; P = 0.045).Neither study reported outcomes relating to motivation to check their breasts, confidence to seek help, time from breast symptom discovery to presentation to a healthcare professional, intentions to seek help, quality of life, adverse effects of the interventions, stages of breast cancer, survival estimates or breast cancer mortality rates. Based on the results of two RCTs, a brief intervention has the potential to increase women's breast cancer awareness. However, findings of this review should be interpreted with caution, as GRADE assessment identified moderate-quality evidence in only one of the two studies reviewed. In addition, the included trials were heterogeneous in terms of the interventions, population studied and outcomes measured. Therefore, current evidence cannot be generalised to the wider context. Further studies including larger samples, validated outcome measures and longitudinal approaches are warranted.


Predicting the outcome in patients with unexplained syncope and suspected cardiac cause: role of electrophysiologic studies.
Unexplained syncope is a challenge facing electrophysiologists. The prognosis varies widely depending on underlying causes, specially, cardiac ones. We sought to determine the abnormal electrophysiolgic (EP) study results as predictors of prognosis in syncope patients with suspected cardiac cause and risk factors associated with mortality. A total of 227 consecutive patients with unexplained syncope were prospectively enrolled in this study. EP study was performed in 177 patients in base of inclusion criteria. These patients, in whom a cardiac cause of syncope was suspected, underwent EP study and if negative, head-up tilts test (HUTT). Complete follow-up was obtained for 132 patients for 20.0±10.8 months. A cardiac cause of syncope was established in 35%, a neurally mediated syncope in 35.6%, and in the rest 29.4% the cause of syncope remained unexplained despite a throughout neurologic and cardiologic evaluation. Logistic analysis revealed that the significant predictors of a cardiac cause of syncope were the absence of prodromal symptoms, left bundle branch block (LBBB), sever left ventricle (LV) dysfunction and male gender. At logistic analysis, the presence of LBBB (OR=6.63; 95% CI: 1.09-40) was significantly associated with outcome of death. The present study provides evidence that presence of LBBB, abnormal EP study result and structural heart disease (SHD) have prognostic value in patients with suspected cardiac cause of syncope. The patients with SHD and unexplained syncope who had a negative EP study have a good long-term prognosis even in the presence of LV dysfunction.


Post insult enriched housing improves the 8-arm radial maze performance but not the Morris water maze task in ventral subicular lesioned rats.
The present study attempted to evaluate the efficacy of enriched housing conditions in promoting behavioral recovery following subicular lesion. Rats with bilateral ibotenic acid lesions of ventral subiculum were exposed to either enriched housing conditions or standard housing for 6 h daily for 10 days. The performance of the lesioned rats reared in standard housing conditions was severely impaired in both 8-arm radial maze and water maze tasks. Lesioned rats exposed to enriched housing showed behavioral recovery in the 8-arm radial maze but not in the water maze. Our study suggests the possibility that recovery may be based on the functional demand of spatial tasks and may require more appropriate environmental stimulation.


Human infectivity trait in Trypanosoma brucei: stability, heritability and relationship to sra expression.
Some Trypanosoma brucei lines infect humans whereas others do not because the parasites are lysed by human serum. We have developed a robust, quantitative in vitro assay based on differential uptake of fluorescent dyes by live and dead trypanosomes to quantify the extent and kinetics of killing by human serum. This method has been used to discriminate between 3 classes of human serum resistance; sensitive, resistant and intermediate. TREU 927/4, the parasite used for the T. brucei genome project, is intermediate. The phenotype is expressed in both bloodstream and metacyclic forms, is stably expressed during chronic infections and on cyclical transmission through tsetse flies. Trypanosomes of intermediate phenotype are distinguished from sensitive populations of cells by the slower rate of lysis and by the potential to become fully resistant to killing by human serum as a result of selection or long-term serial passaging in mice, and to pass on full resistance phenotype to its progeny in a genetic cross. The sra gene has been shown previously to determine human serum resistance in T. brucei but screening for the presence and expression of this gene indicated that it is not responsible for the human serum resistance phenotype in the trypanosome lines that we have examined, indicating that an alternative mechanism for HSR exists in these stocks. Examination of the inheritance of the phenotype in F1 hybrids for both bloodstream and metacyclic stages from 2 genetic crosses demonstrated that the phenotype is co-inherited in both life-cycle stages in a manner consistent with being a Mendelian trait, determined by only one or a few genes.


Intersystem crossing processes in the 2CzPN emitter: a DFT/MRCI study including vibrational spin-orbit interactions.
Multireference quantum chemical calculations were performed in order to investigate the (reverse) intersystem crossing ((R)ISC) mechanisms of 4,5-di(9H-carbazol-9-yl)-phthalonitrile (2CzPN). A combination of density funcional theory (DFT) and multireference configuration interaction methods (MRCI) was used. The excellent agreement of the computed absorption spectrum with available experimental absorption spectra lends confidence to the chosen computational protocol. Vertically, two triplet excited states (T1 and T2) are found below the S1 state. At the excited state minima, the calculated adiabatic energies locate only the T1 state below the S1 state. The enhanced charge transfer (CT) character of the geometrically relaxed excited states causes their mutual (direct) spin-orbit coupling (SOC) interaction to be low. Contributions of vibronic SOC to the (R)ISC probability, evaluated by a Herzberg-Teller-like procedure for a temperature of 300 K, are small but not negligible. For ISC, the S1→ T1 channel is the fastest (8 × 106 s-1), while the S1→ T2 channel is found to be thermally activated (9 × 104 s-1) and less efficient when proceeding from the adiabatic S1 state. Our calculations also reveal, however, a barrierless S1→ T2 ISC pathway near the Franck-Condon region. RISC is found to essentially proceed via the T1→ S1 channel, with a rate constant of (3 × 104 s-1) if our adiabatic singlet-triplet energy gap in vacuum (ΔEST = 0.12 eV) is employed. Shifting the potentials to match two experimentally reported singlet-triplet energy gaps in toluene (ΔEST = 0.21 and 0.31 eV, respectively) leads to a drastic reduction of the computed rate constant by up to 4 orders of magnitude. The T2 state is not expected to play a major role in mediating triplet-singlet transitions in 2CzPN unless it is directly populated by hot excitons. No indication for a strong vibronic coupling of the T2 and T1 potentials is found, which could help overcome the negative exponential dependence of the RISC rate constant on the magnitude of the energy gap.


Development of Various Leishmania (Sauroleishmania) tarentolae Strains in Three Phlebotomus Species.
Leishmania (Sauroleishmania) tarentolae is transmitted by reptile-biting sand flies of the genus Sergentomyia, but the role of Phlebotomus sand flies in circulation of this parasite is unknown. Here, we compared the development of L. (S.) tarentolae strains in three Phlebotomus species: P. papatasi, P. sergenti, and P. perniciosus. Laboratory-bred sand flies were membrane-fed on blood with parasite suspension and dissected on days 1 and 7 post blood meal. Parasites were measured on Giemsa-stained gut smears and five morphological forms were distinguished. In all parasite-vector combinations, promastigotes were found in Malpighian tubules, often in high numbers, which suggests that this tissue is a typical location for L. (S.) tarentolae development in sand flies. All three studied strains colonized the hindgut, but also migrated anteriorly to both parts of the midgut and colonized the stomodeal valve. Significant differences were demonstrated between sand fly species: highest infection rates, high parasite loads, and the most frequent anterior migration with colonization of the stomodeal valve were found in P. perniciosus, while all these parameters were lowest in P. sergenti. In conclusion, the peripylarian type of development was demonstrated for three L. (S.) tarentolae strains in three Phlebotomus sand flies. We suggest paying more attention to Phlebotomus species, particularly P. perniciosus and P. papatasi, as potential secondary vectors of Sauroleishmania.


Acute Abducens Nerve Palsy Following the Second Dose of the AstraZeneca COVID-19 Vaccine.
The authors report the case of an otherwise healthy 65-year-old man who presented with an acute right abducens nerve palsy 3 days after receiving the second dose of the AstraZeneca coronavirus disease 2019 (COVID-19) vaccine. Abducens nerve palsies typically results from microvascular disease or compressive tumors, although they are known to arise following routine vaccinations. Given the lack of preexisting risk factors, normal computed tomography scan results, and the timing of the symptoms, the abducens nerve palsy was believed to be related to the vaccination. This report highlights the potential neurologic adverse effects associated with COVID-19 vaccines. [J Pediatr Ophthalmol Strabismus. 2021;58(6):e49-e50.].


Frailty syndrome: A target for functional nutrients?
Frailty is a late life phenotype characterized by a decline in physiological reserve across several organ systems, resulting in the increased susceptibility to endogenous and/or exogenous stressors. Although the etiology of frailty remains poorly understood, an interconnected network of putative mechanisms linked to the ageing process has been proposed. However, frailty is a dynamic process that may be prevented, delayed, or even reversed. The syndromic nature of frailty requires a multidomain approach, such as proper nutrition, as part of modifiable environmental factors, and represents one of the most promising and least costly ways to prevent and reduce frailty among older adults. Nutrient deficiencies have been consistently associated with frailty; however, mounting evidence also supports the hypothesis that beyond the traditional nutritional value, specific dietary components may exert function-enhancing effects and mitigate the extent of frailty. Thus, further mechanistic studies, along with large clinical trials, are imperative to establish the exact role of functional nutrients in the clinical management of frailty. Here, we provide a contemporary discussion of how emerging functional nutrients may contribute to modify the trajectory of the frailty syndrome.


[Development of acute type, CD 8 positive adult T-cell leukemia in a carrier of hepatitis B virus--possible therapeutic effect of lamivudine combined with chemotherapy].
Cases of adult T-cell leukemia (ATL) with aberrant phenotypes have a very poor prognosis. We report the development of acute type, CD 8 positive ATL in a carrier of hepatitis B virus (HBV). The patient was treated with a combination of lamivudine and chemotherapy and consequently had longer-term survival than those reported previously. A 64-year-old(corrected 65-year-old) man was referred to our hospital in January 2002 because of ascites and abdominal tumor. He was positive for anti-HTLV-1 antibody and HBV surface antigen. Generalized computed tomography demonstrated bilateral pleural effusion, abdominal mass, and massive ascites. Cytological examination of ascitis revealed numerous atypical lymphoid cells,which were positive for CD 2, CD 5, CD 8, and CD 25. Monoclonal integration of HTLV-1 provirus was detected by Southern blot analysis on DNA extracted from lymphoid cells. A diagnosis of acute type, CD 8 positive ATL was made. Lamivudine was administered for prevention of chemotherapy induced HBV reactivation. Subsequently, he was treated with 6 cycles of CHOP and went into remission. He maintained clinical remission during a follow-up of 13 months and then relapsed. Further salvage therapies were provided with a transient effect. He died of sepsis in February 2004. The overall survival time of this patient was 25 months. It is possible that lamivudine combined with chemotherapy may have had a therapeutic effect on ATL in this case.


[The problem of immigration in Russia].
"The article examines the threefold immigration problem currently facing Russia: the influx of refugees from the developing world who hope eventually to reach the West, and the large numbers of non-Russians and ethnic Russians entering the country from the other former Soviet republics. The institutions established recently to tackle immigration are insufficiently funded and often find themselves in conflict with other agencies, both Russian and international. Legislation on the status of immigrants is also confused. The most pressing issue, however, is that of Russian immigration into Russia. This has implications for domestic policies: the immigrants are regarded as a potential solution to the problem of rural depopulation and are prevented from entering densely populated regions. The exodus of ethnic Russians from the other former Soviet republic may also affect Russia's relations with these countries, which it has accused of discriminating against their Russian populations." (SUMMARY IN ENG)


Successful treatment of a critically burned patient (case report).
The objective of this study was to document that treatment of a critically burned patient could be, although with some problems, ultimately very successful. The commonplace of such successful therapy is certainly not only current, up-to-date and most intensive care, but also good teamwork and professionalism of the whole team in the specialized workplace--Burn and Reconstructive Surgery Departments of the Faculty Hospital in Brno.


Prenatal cocaine exposure increases synaptic localization of a neuronal RasGEF, GRASP-1 via hyperphosphorylation of AMPAR anchoring protein, GRIP.
Prenatal cocaine exposure causes sustained phosphorylation of the synaptic anchoring protein, glutamate receptor interacting protein (GRIP1/2), preventing synaptic targeting of the GluR2/3-containing alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptors (AMPARs; J. Neurosci. 29: 6308-6319, 2009). Because overexpression of GRIP-associated neuronal rasGEF protein (GRASP-1) specifically reduces the synaptic targeting of AMPARs, we hypothesized that prenatal cocaine exposure enhances GRASP-1 synaptic membrane localization leading to hyper-activation of ras family proteins and heightened actin polymerization. Our results show a markedly increased GRIP1-associated GRASP-1 content with approximately 40% reduction in its rasGEF activity in frontal cortices (FCX) of 21-day-old (P21) prenatal cocaine-exposed rats. This cocaine effect is the result of a persistent protein kinase C (PKC)- and downstream Src tyrosine kinase-mediated GRIP phosphorylation. The hyperactivated PKC also increased membrane-associated GRASP-1 and activated small G-proteins RhoA, cdc42/Rac1 and Rap1 as well as filamentous actin (F-actin) levels without an effect on the phosphorylation state of actin. Since increased F-actin facilitates protein transport, our results suggest that increased GRASP-1 synaptic localization in prenatal cocaine-exposed brains is an adaptive response to restoring the synaptic expression of AMPA-GluR2/3. Our earlier data demonstrated that persistent PKC-mediated GRIP phosphorylation reduces GluR2/3 synaptic targeting in prenatal cocaine-exposed brains, we now show that the increased GRIP-associated GRASP-1 may contribute to the reduction in GluR2/3 synaptic expression and AMPAR signaling defects.


Neocucurbitaria keratinophila: An emerging opportunistic fungus causing superficial mycosis in Spain.
Although there have been few reports of opportunistic infections (superficial and systemic) caused by coelomycetous fungi, they are becoming more frequent. Neocucurbitaria keratinophila (formerly Pyrenochaeta keratinophila), characterized by producing pycnidial conidiomata and small hyaline conidia, seems to be an emergent opportunistic pathogen in Spain. Since this fungus was first reported from human keratitis, eight strains have been isolates from clinical cases in Spain. This is a retrospective study of these fungal strains, including phenotypic and molecular characterizations, and in vitro antifungal susceptibility assays. These clinical strains were identified by sequencing four phylogenetic markers such as the internal transcribed spacer region (ITS1-5.8S-ITS2) and fragments of the 28S nrRNA (LSU), beta-tubulin (tub2), and RNA polymerase II subunit 2 (rpb2) genes, and by morphological characterization. All the strains tested were susceptible to the majority of antifungals, being isavuconazole the only drug that showed a poor antifungal activity.


The evolution of gene expression studies in drug safety assessment.
Since the identification in the 1950s of deoxyribonucleic acid as the building block of life, the impact of molecular biology has been far-reaching. Understanding the processes of how DNA is replicated, transcribed into RNA and then translated into protein products has not only provided a fundamental knowledge of life but has also spawned a plethora of applications. Molecular biology has been high profile and widespread in research into the biology of disease and in drug discovery. It has additionally found application in understanding the adverse effects, or toxicity, of candidate drugs and how they interfere with biochemical and biological processes. In recent times the biggest impact of molecular biology in toxicology has been through the study of differential gene expression, largely as a result of the advent of genomics. This review seeks to describe how toxicogenomics strategies have been implemented and integrated into nonclinical studies of drug safety.


Regulation of enzymatic activity: one possible role of dietary boron in higher animals and humans.
It is well established that vascular plants, diatoms, and some species of marine algal flagellates have acquired an absolute requirement for boron (B), although the primary role remains unknown. Discovery of naturally occurring organoboron compounds, all ionophoric macrodiolide antibiotics with a single B atom critical for activity, established at least one biochemical role of B. The unusual nature of B chemistry suggests the possibility of a variety of biological roles for B. At physiological concentrations and pH, B may react with one N group or one to four hydroxyl groups on specific biological ligands with suitable configuration and charge to form dissociable organoboron compounds or complexes. Suitable ligands include pyridine (e.g., NAD+ or NADP) or flavin (e.g., FAD) nucleotides and serine proteases (SP). B reacts with the cis adjacent hydroxyls on the ribosyl moiety of the nucleotides or, in the serine proteases, the N on the imidazole group of histidine or the hydroxyl group on the serine moiety. Reversible inhibition by B of activity of SP or oxidoreductases that require pyridine or flavin nucleotides is well known. Therefore, a proposed essential role for B is as a regulator of relevant pathways, including respiratory burst, that utilize these enzymes.


The role of neurotrophins in neurotransmitter release.
The neurotrophins (NTs) have recently been shown to elicit pronounced effects on quantal neurotransmitter release at both central and peripheral nervous system synapses. Due to their activity-dependent release, as well as the subcellular localization of both protein and receptor, NTs are ideally suited to modify the strength of neuronal connections by "fine-tuning" synaptic activity through direct actions at presynaptic terminals. Here, using BDNF as a prototypical example, the authors provide an update of recent evidence demonstrating that NTs enhance quantal neurotransmitter release at synapses through presynaptic mechanisms. The authors further propose that a potential target for NT actions at presynaptic terminals is the mechanism by which terminals retrieve synaptic vesicles after exocytosis. Depending on the temporal demands placed on synapses during high-frequency synaptic transmission, synapses may use two alternative modes of synaptic vesicle retrieval, the conventional slow endosomal recycling or a faster rapid retrieval at the active zone, referred to as "kiss-and-run." By modulating Ca2+ microdomains associated with voltage-gated Ca2+ channels at active zones, NTs may elicit a switch from the slow to the fast mode of endocytosis of vesicles at presynaptic terminals during high-frequency synaptic transmission, allowing more reliable information transfer and neuronal signaling in the central nervous system.


Transcriptome, methylome and genomic variations analysis of ectopic thyroid glands.
Congenital hypothyroidism from thyroid dysgenesis (CHTD) is predominantly a sporadic disease characterized by defects in the differentiation, migration or growth of thyroid tissue. Of these defects, incomplete migration resulting in ectopic thyroid tissue is the most common (up to 80%). Germinal mutations in the thyroid-related transcription factors NKX2.1, FOXE1, PAX-8, and NKX2.5 have been identified in only 3% of patients with sporadic CHTD. Moreover, a survey of monozygotic twins yielded a discordance rate of 92%, suggesting that somatic events, genetic or epigenetic, probably play an important role in the etiology of CHTD. To assess the role of somatic genetic or epigenetic processes in CHTD, we analyzed gene expression, genome-wide methylation, and structural genome variations in normal versus ectopic thyroid tissue. In total, 1011 genes were more than two-fold induced or repressed. Expression array was validated by quantitative real-time RT-PCR for 100 genes. After correction for differences in thyroid activation state, 19 genes were exclusively associated with thyroid ectopy, among which genes involved in embryonic development (e.g. TXNIP) and in the Wnt pathway (e.g. SFRP2 and FRZB) were observed. None of the thyroid related transcription factors (FOXE1, HHEX, NKX2.1, NKX2.5) showed decreased expression, whereas PAX8 expression was associated with thyroid activation state. Finally, the expression profile was independent of promoter and CpG island methylation and of structural genome variations. This is the first integrative molecular analysis of ectopic thyroid tissue. Ectopic thyroids show a differential gene expression compared to that of normal thyroids, although molecular basis could not be defined. Replication of this pilot study on a larger cohort could lead to unraveling the elusive cause of defective thyroid migration during embryogenesis.


Postmastectomy/Axillary Node Dissection Chyloma: The Additional Value of SPECT/CT Lymphoscintigraphy.
After mastectomy and axillary node dissection, chylous leakage is rare. However, considerable anatomical variation in the termination of the thoracic duct has been reported. Hence, during breast surgery, injury to the lateral terminating branch is not unlikely and might lead to retrograde chyle leak. Herein, we describe a patient who had a chylous leakage at her wound site after a left simple mastectomy and axillary node dissection and for whom lymphoscintigraphy with Tc-99m albumin nanocolloid was performed. In this case, additional hybrid single-photon emission computed tomography/computed tomography study was done, and has helped with the accurate identification of the chyle leakage site, thus aiding in surgical management.


Vaccines and their impact on the control of disease.
Disease control exerts evolutionary pressures that can lead to the evolution of resistance. This has been seen in a spectacular fashion in the evolution of resistance to antibiotics, anti-virals and anti-parasitics. Despite intense (and often successful) attempts to control infectious diseases through vaccination, there is still rather little evidence of the emergence of strains of pathogen resistant to vaccines. This chapter asks why this should be so and what are the exceptions indicating that the evolution of vaccine resistance, though currently rare, is a possibility that should be planned for.


Activation of heterotrimeric G proteins by a high energy phosphate transfer via nucleoside diphosphate kinase (NDPK) B and Gbeta subunits. Complex formation of NDPK B with Gbeta gamma dimers and phosphorylation of His-266 IN Gbeta.
G protein betagamma dimers can be phosphorylated in membranes from various tissues by GTP at a histidine residue in the beta subunit. The phosphate is high energetic and can be transferred onto GDP leading to formation of GTP. Purified Gbetagamma dimers do not display autophosphorylation, indicating the involvement of a separate protein kinase. We therefore enriched the Gbeta-phosphorylating activity present in preparations of the retinal G protein transducin and in partially purified G(i/o) proteins from bovine brain. Immunoblots, autophosphorylation, and enzymatic activity measurements demonstrated enriched nucleoside diphosphate kinase (NDPK) B in both preparations, together with residual Gbetagamma dimers. In the retinal NDPK B-enriched fractions, a Gbeta-specific antiserum co-precipitated phosphorylated NDPK B, and an antiserum against the human NDPK co-precipitated phosphorylated Gbetagamma. In addition, the NDPK-containing fractions from bovine brain reconstituted the phosphorylation of purified Gbetagamma. For identification of the phosphorylated histidine residue, bovine brain Gbetagamma and G(t)betagamma were thiophosphorylated with guanosine 5'-O-(3-[(35)S]thio)triphosphate, followed by digestion with endoproteinase Glu-C and trypsin, separation of the resulting peptides by gel electrophoresis and high pressure liquid chromatography, respectively, and sequencing of the radioactive peptides. The sequence information produced by both methods identified specific labeled fragments of bovine Gbeta(1) that overlapped in the heptapeptide, Leu-Met-Thr-Tyr-Ser-His-Asp (amino acids 261-267). We conclude that NDPK B forms complexes with Gbetagamma dimers and contributes to G protein activation by increasing the high energetic phosphate transfer onto GDP via intermediately phosphorylated His-266 in Gbeta(1) subunits.


Circumcision: how do urologists do it?
To determine the range of surgical techniques, analgesic practice, post-operative care and follow-up procedures used in the circumcision of children by urologists in the United Kingdom, and to suggest changes which would improve patient care and medical training in the relatively simple procedure of circumcision. In 1994, all consultant urologists in the United Kingdom were sent detailed questionnaires asking about their practices in the circumcision of children. Of 308 urologists, 61% replied; of these, 55% use the sleeve-resection technique and 39% the free-hand method, and 57% use diathermy, half of which is bipolar. There is wide variation in the type of post-operative analgesia; 95% use an initial dressing but few recommend any subsequent dressing, 70% perform all circumcisions as day cases and 48% review patients in the clinic. There is significant concern that circumcision is not taught adequately to junior surgeons. The sleeve technique of resection should be more widely used. Analgesic practice could be improved with greater use of regional anaesthetics. Most urologists promote no specific care after discharge. There is probably a place for increasing the use of alternative procedures to circumcision.


Comparison of dentoalveolar protrusion values in Moroccans and other populations.
The aim of this retrospective study was to evaluate bimaxillary protrusion among Moroccans and to compare the Moroccan population with other Arabic, Caucasian, and Mediterranean populations. Cephalometric radiographs of 102 Moroccan adult university students (73 females and 29 males, mean age: 21 years 6 months +/- 1 year 6 months) with a normal occlusion were traced. Fifteen measurements concerning the upper and lower incisors, upper and lower lips, and the Frankfort to mandibular plane angle were assessed. Statistical analysis of the data was undertaken using independent t-tests. Eight angular and six linear measurements were statistically significantly different compared with Caucasian cephalometric norms (P < 0.001). Significant differences were observed compared with other adult Arabic populations (Palestinians and Saudis) and with Turkish Anatolian adults. Relative to Caucasian cephalometric norms, Moroccans showed bimaxillary protrusion and, therefore, these norms cannot be applied to Moroccan faces. In general, there was a great similarity in incisor position between the Moroccan and Saudi populations.


Signout: a collaborative document with implications for the future of clinical information systems.
Signout is an unofficial clinical document used traditionally to facilitate patient handoff. Qualitative studies have suggested its importance in clinical care. We used a novel technique to quantify the use of signout by analyzing clinical information system logfiles. Viewing and editing events were collected for 1,677 unique patients admitted to our internal medicine service. We found the average patient's signout on a given day is viewed frequently (>6x) and edited frequently (>2x) with multiple unique viewers (>3) and editors (>1). We also found that signouts are used throughout a 24-hour period, not just at the time of handoff. Finally, we showed that they are viewed months and even years after their creation. Signout is therefore a highly utilized, collaborative, clinical document used for more than patient handoff. Our findings also suggest that clinical information systems may benefit from the introduction of collaborative tools such as subscription, versioning, and author-attribution utilities.


[Minilaparotomy cholecystectomy with clinical analysis of 50 cases].
Fifty cases of gallbladder disease operated with minilaparotomy cholecystectomy (MC) and fifty cases operated with conventional cholecystectomy (CC) were reviewed and compared in terms of their need of postoperative analgesic and hospitalization days. The results showed that the MC was better than the CC. The merits and demerits of MC. CC and LC were discussed. The operative indexes of MC were presented by author.


[The choice of the mode of operation of the XeCl-laser for angioplasty].
The authors relate the results of studies carried out on an outfit model for laser angioplasty designed on the basis of exiplex laser. Optimal conditions for laser introduction into a quartz guide have been found. It is shown that the efficacy of interaction between XeCl-laser and tissue rises as the intensity of radiation increases. The energy of radiation at the guide outlet being 9 mJ, the resources of fiber work remained at a high level (greater than 10(4) impulses) whereas high velocity of tissue evaporation allowed elimination of an area 3 mm3 in volume during 1 minute, with the rate of impulse repetition amounting to 10 Hz.


The impact of the 1997 Balanced Budget Amendment's prospective payment system on patient case mix and rehabilitation utilization in skilled nursing.
This study examines the impact of the post-acute prospective payment system (PPS) on Medicare-funded rehabilitation services in skilled nursing facilities (SNFs) and whether such impact varies under different payment mechanisms. We interviewed 214 Medicare beneficiaries admitted to three SNFs in southern California for rehabilitation. We compared patients' admission characteristics and therapy utilization among those receiving post-acute rehabilitation before and after the implementation of PPS. Patients admitted after PPS implementation were more likely to have orthopedic problems or stroke and poorer self-reported physical health. They had significantly shorter lengths of stay in rehabilitation and received significantly less therapy, although those in managed care had less reduction in treatment after SNF-PPS implementation than those in fee-for-service. After SNF-PPS implementation, rehabilitation treatment levels in the study sites were reduced. Whereas changes in Medicare managed care were comparatively modest, we observed significant changes in intensity and duration of physical and occupational therapies in Medicare fee-for-service.