Treatment of type 2 diabetes mellitus in children and adolescents.
To study possible treatment modalities for type 2 diabetes mellitus (T2DM) in children and adolescents. We reviewed the medical records of the 25 children and adolescents most recently seen for T2DM in the U.T. Houston diabetes clinics, comparing treatment regimens and results over time. The most common treatment modalities were insulin in combination with oral insulin sensitizing agent (metformin), and metformin alone. End-points evaluated included HbA1c, body weight, and insulin dose. Patients ranged in age from 8 to 15 years at diagnosis. The female:male ratio was 1.3:1. Sixty percent of patients were Hispanic. All BMIs were above 85th percentile for age and sex. Acanthosis nigricans was present in 92% of the patients. Insulin was the only initial treatment in 18 patients (72%), with metformin added and insulin withdrawn as euglycemia developed. Only five of these 18 patients who were started on insulin were completely weaned to metformin monotherapy, and three of those patients later required reintroduction of insulin due to poor control. Metformin did permit reduction of insulin dose in the combination group. Metformin was used as monotherapy in seven patients (28%), but three of them later required another oral hypoglycemic agent. The mean change in HbA1c over the observed period was -2.9% in patients taking insulin only, -2.3% for patients treated with insulin + metformin, and -4.4% in patients who could be treated by metformin alone. HbA1c tended to rise after 2 years of therapy. Few patients sustained weight loss, regardless of treatment regimen. Metformin appears to be an effective medication for the treatment of T2DM in children, but did not seem to be a sufficient long-term monotherapy in our protocol, which required euglycemia for insulin withdrawal. Lifetime management strategies for children with T2DM will probably be as complex as those for adults.


Frontal cortical atrophy and negative symptoms in patients with chronic alcohol dependence.
It has been suggested that frontal lobe pathology is associated with negative symptoms in patients with chronic alcoholism. In his exploratory study, the authors examined 19 chronic alcoholic inpatients on an alcohol treatment unit and found a significant relationship between severity of frontal atrophy (as measured by CT) and negative symptoms (as measured by the Scale for the Assessment of Negative Symptoms).


Inhibition of mushroom tyrosinase by a newly synthesized ligand: inhibition kinetics and computational simulations.
Alterations in the synthesis of melanin contribute to a number of diseases; therefore, the design of new tyrosinase inhibitors is very important. Mushroom tyrosinase (MT) is a metalloenzyme, which plays an important role in melanin biosynthesis. In this study, the inhibitory effect of a novel designed compound, i.e. 2-((1Z)-(2-(2,4-dinitrophenyl)hydrazin-1-ylidene)methyl)phenol, as a specific ligand which can bind to the copper ion of MT, has been assessed. The ligand was found to competitively inhibit both the cresolase and catecholase activities of MT, with small inhibition constants of 2.8 and 2.6 μM, respectively. Intrinsic fluorescence studies were performed to gain more information on the binding constants. Docking results indicated that the ligand binds to copper ions in the active site of MT via the OH group of the ligand. The ligand makes four hydrogen bonds with aspartic acid and one hydrogen bond with the histidine residue in the active site. Molecular dynamics results show that ligand binds to the MT via both electrostatic and hydrophobic interactions with its different parts.


Long-term seizure outcomes in patients with autoimmune encephalitis: A prospective observational registry study update.
This study was undertaken to update and evaluate long-term seizure outcomes in patients with autoimmune encephalitis (AE) based on a large cohort study with long follow-up. In this prospective observational registry study, we analyzed data from patients with AE mediated by common types of neuronal surface antibodies (anti-N-methyl-d-aspartate receptor [NMDAR], anti-leucine-rich glioma-inactivated 1 [LGI1]/contactin-associated protein-like 2 [Caspr2], anti-γ-aminobutyric acid type B receptor [GABAB R]). All patients were recruited from the Department of Neurology at West China Hospital between October 2011 and June 2019, and data were collected prospectively on their demographic and clinical characteristics, treatment strategy, and seizure outcomes, with a median follow-up of 42 months (range = 6-93 months). Potential risk factors associated with seizure recurrence were also assessed. Of 320 AE patients, 75.9% had acute seizures, among whom >90% of patients had their last seizure within 12 months of disease onset. During our follow-up, 21 (9.3%) patients experienced seizure recurrence. Patients with anti-GABAB R encephalitis had a higher cumulative incidence of seizure recurrence than those with anti-NMDAR (log-rank p = .03) or anti-LGI1/Caspr2 encephalitis (log-rank p = .04). Among patients with anti-NMDAR encephalitis, women had a significantly higher cumulative incidence of seizure recurrence than men (log-rank p = .01). Interictal epileptiform discharges (IEDs) or seizures captured on continuous electroencephalogram (EEG) in the acute phase were identified as potential risk factors for seizure recurrence (p = .04, p = .007). Among 163 patients with ≥24 months of follow-up, five (3.1%) showed persistent seizures and required ongoing antiseizure medications despite aggressive immunotherapy. Seizure recurrence occurred in a small number of patients and chronic epilepsy occurred in 3.1% of patients during prolonged follow-up. Across all types of AE, risk factors for seizure recurrence were IEDs or seizures captured on EEG in the acute phase; for anti-NMDAR encephalitis, female sex was also a risk factor.


A highly efficient Ti-catalyst for the deoxygenative reduction of esters under ambient conditions: experimental and mechanistic insights from DFT studies.
In this paper, we report the synthesis of dianionic amidophosphineborane-supported titanium chloride [{Ph2P(BH3)N}2C6H4TiCl2] (1) and TiIV alkyl complex [{Ph2P(BH3)N}2C6H4Ti(CH2SiMe3)2] (2) using a salt metathesis reaction. TiIV complex 1 was obtained by the reaction of the bis-borane ligand [{Ph2P(BH3)NH}2C6H4] and TiCl4 in toluene followed by the addition of 2 equivalents of [LiN(SiMe3)2] at ambient temperature. TiIV bis-alkyl complex 2 was isolated from the reaction of complex 1 with 2.5 equivalents of LiCH2SiMe3 in toluene. The solid-state structure of complex 1 is established by single-crystal X-ray diffraction analysis. TiIV bis-alkyl complex 2 has proved to be a competent catalyst in the deoxygenative reduction of aliphatic and aromatic esters with pinacolborane (HBpin) to afford corresponding boryl ethers at room temperature under solvent-free conditions. Catalyst 2 exhibits chemoselectivity toward ester functionalities over halides, heteroatoms, olefins, and amino functional groups. DFT studies demonstrate that the active form of catalyst 2 is capable of easily transferring its hydrides to ester substrates at room temperature. The studies further reveal that the rate-limiting step (RLS) in an ester-to-boryl ether conversion is the cleavage of the C-O bond of an ester. In brief, the titanium-catalysed ester-to-boryl ether conversions are found to be downhill processes having small activation barriers along all mechanistic steps.


Reliable atrial septostomy by stenting of the atrial septum.
The aim of this report was to describe our experience with creating an interatrial communication by stenting the interatrial septum. In many forms of congenital heart disease, the presence of an appropriate interatrial shunt is critical. After the first several weeks of life, balloon atrial septostomy is not effective, and success with other methods is limited. Clinical records, echocardiograms, and catheterization data in patients who had an atrial septal stent placed between 2001 and 2004 at UCLA were reviewed. Changes in atrial pressures and systemic saturations were analyzed. Follow-up data and explant pathology were reviewed as available. Thirteen patients had stenting of the atrial septum (four restrictive, nine nonrestrictive). In patients with elevated right and left atrial pressures, there was a mean reduction of 2.4 and 7.4 mm Hg in right atrial and left atrial pressures, respectively. In patients with transposition physiology, there was a mean increase in oxygen saturation of 11.3%. Follow-up echocardiograms revealed patent stents with excellent position relative to the atrial septum. In six cases, the stents were removed during subsequent surgery and appeared endothelialized and patent. Stenting of the atrial septum is safe and effective in selected cases, allowing for a reliable, long-lasting, restrictive or nonrestrictive interatrial communication.


Multivesicular bodies mediate long-range retrograde NGF-TrkA signaling.
The development of neurons in the peripheral nervous system is dependent on target-derived, long-range retrograde neurotrophic factor signals. The prevailing view is that target-derived nerve growth factor (NGF), the prototypical neurotrophin, and its receptor TrkA are carried retrogradely by early endosomes, which serve as TrkA signaling platforms in cell bodies. Here, we report that the majority of retrograde TrkA signaling endosomes in mouse sympathetic neurons are ultrastructurally and molecularly defined multivesicular bodies (MVBs). In contrast to MVBs that carry non-TrkA cargoes from distal axons to cell bodies, retrogradely transported TrkA+ MVBs that arrive in cell bodies evade lysosomal fusion and instead evolve into TrkA+ single-membrane vesicles that are signaling competent. Moreover, TrkA kinase activity associated with retrogradely transported TrkA+ MVBs determines TrkA+ endosome evolution and fate. Thus, MVBs deliver long-range retrograde NGF signals and serve as signaling and sorting platforms in the cell soma, and MVB cargoes dictate their vesicular fate.


Folding intermediates of wild-type and mutants of barnase. I. Use of phi-value analysis and m-values to probe the cooperative nature of the folding pre-equilibrium.
It is difficult to determine whether transient folding intermediates have a cooperative (or first-order) folding transition without measuring their rates of formation directly. An intermediate I could be formed by a second-order transition from a denatured state D that is progressively changed into I as conditions are changed. We have not been able to monitor the rate of formation of the folding intermediate of barnase directly, but have analysed its reactivity and the equilibrium constant for its formation over a combination of wide ranges of temperature, concentration of denaturant and structural variation. Phase diagrams have been constructed for wild-type and 16 mutant proteins to map out the nature of the energy landscape of the denatured state. The free energy of unfolding of I, delta GD-I, changes with [urea] according to a highly cooperative transition. Further, mD-I (= delta delta GD-I/delta [urea]) for wild-type and several mutants is relatively insensitive to temperature, as would be expected for an intermediate that is formed cooperatively, rather than one that melts out according to a second-order transition. The phi-values for the formation of I change abruptly through the folding transitions rather than have the smooth changes expected for a second-order transition. There is a subset of mutants for which both mD-I and phi-value analysis indicate that a second intermediate becomes populated close to the melting temperatures of the native proteins. The folding intermediate of barnase is, thus, a relatively discrete and compact entity which is formed cooperatively.


[Psoriasis is associated with type 2 diabetes].
Psoriasis is a chronic inflammatory skin disease with a global prevalence of 2-3%. In recent years it has been established that patients with psoriasis carry an increased risk of type 2 diabetes, but the underlying pathophysiological mechanisms remain unclear. The association is most likely due to a combination of shared genes, immunoinflammatory mechanisms and a number of diabetes risk factors in patients with psoriasis. The current review summarises the evidence in the field and calls for attention on diabetes risk assessment, preventive measures and treatment in patients with psoriasis.


Sequence characterization of river buffalo Toll-like receptor genes 1-10 reveals distinct relationship with cattle and sheep.
The present study was undertaken to characterize the full-length transcripts of Toll-like receptor (TLR) genes 1-10 of river buffalo. The conceptualized amino acid identity of bubaline TLRs ranged between 86% to 100% with ruminants, while it ranged between 45% to 91% with other vertebrate species. Simple modular architecture tool (SMART) analysis revealed the presence of TIR domains and varying numbers of leucine-rich repeat motifs in all the buffalo TLRs. With respect to TIR domains, TLRs 1, 2 and 3 of river buffalo were found to have 99.3% identity with cattle and 100% identity of TLRs 4, 6 and 10 with sheep. Phylogenetic analysis of TLRs of buffalo and different vertebrate species revealed the clustering of major TLR gene subfamilies with high bootstrap values. The evolutionary relationship between buffalo and other ruminant species was found to vary among different TLRs. In order to understand the relationship between TLRs of different ruminant species, multidimensional scaling (MDS) analysis of pairwise amino acid differences between different species within each TLR was performed. Buffalo and cattle were found to be closely related only with respect to TLRs 1, 2 and 7, while buffalo and sheep were found to be clustering together with respect to TLRs 3, 6, 8 and 10. The distinct relationship of bubaline TLRs with cattle and sheep revealed the possible differences in the pathogen recognition receptor systems in these animals and consequently the differences in their susceptibility/resistance to various invading organisms.


Perspectives for using genetically encoded fluorescent biosensors in plants.
Genetically encoded fluorescent biosensors have long proven to be excellent tools for quantitative live imaging, but sensor applications in plants have been lacking behind those in mammalian systems with respect to the variety of sensors and tissue types used. How can this be improved, and what can be expected for the use of genetically encoded fluorescent biosensors in plants in the future? In this review, we present a table of successful physiological experiments in plant tissue using fluorescent biosensors, and draw some conclusions about the specific challenges plant cell biologists are faced with and some of the ways they have been overcome so far.


Airway Memory CD4(+) T Cells Mediate Protective Immunity against Emerging Respiratory Coronaviruses.
Two zoonotic coronaviruses (CoVs)-SARS-CoV and MERS-CoV-have crossed species to cause severe human respiratory disease. Here, we showed that induction of airway memory CD4(+) T cells specific for a conserved epitope shared by SARS-CoV and MERS-CoV is a potential strategy for developing pan-coronavirus vaccines. Airway memory CD4(+) T cells differed phenotypically and functionally from lung-derived cells and were crucial for protection against both CoVs in mice. Protection was dependent on interferon-γ and required early induction of robust innate and virus-specific CD8(+) T cell responses. The conserved epitope was also recognized in SARS-CoV- and MERS-CoV-infected human leukocyte antigen DR2 and DR3 transgenic mice, indicating potential relevance in human populations. Additionally, this epitope was cross-protective between human and bat CoVs, the progenitors for many human CoVs. Vaccine strategies that induce airway memory CD4(+) T cells targeting conserved epitopes might have broad applicability in the context of new CoVs and other respiratory virus outbreaks.


Differences in Sociocognitive Beliefs between Involved and Noninvolved Employees during the Implementation of an Electronic Health Record System.
Electronic health records (EHRs) can improve quality and efficiency in patient care. However, the intention to work with such a new system is often relatively low among employees because the work processes of the healthcare organization may change. Involving employees in an EHR implementation may increase their beliefs and perceived capabilities concerning the new system. The current study aimed to assess the role of involvement and its effects on sociocognitive beliefs regarding the implementation of a new EHR system. The study was performed in June 2015 among all eligible employees of a hospital in the Netherlands. Both involved and noninvolved employees were invited to complete a paper-based questionnaire concerning their sociocognitive beliefs (i.e., attitude, social influence, self-efficacy, and intention) related to the EHR implementation. Independent sample t-tests were used to assess potential differences in sociocognitive beliefs between employees who were involved in the implementation process and those who were not. Effect sizes (Cohen's d) were calculated to indicate the standardized difference between the means. A total of 359 participants completed the paper-based questionnaire and were included in the analyses. Involved employees (n = 94) reported significantly higher levels of attitude (p < .001, d = .62), perceived self-efficacy (p = .01, d = .31), social support (p < .001, d = .68), and a higher intention to work with the new EHR system (p < .001, d = .60), compared with the group of employees who were not involved in the implementation process (n = 265). Involving employees during an EHR implementation appears to enhance employees' sociocognitive beliefs and increases their intention to work with the new system.


The major outer sheath protein (Msp) of Treponema denticola has a bipartite domain architecture and exists as periplasmic and outer membrane-spanning conformers.
The major outer sheath protein (Msp) is a primary virulence determinant in Treponema denticola, as well as the parental ortholog for the Treponema pallidum repeat (Tpr) family in the syphilis spirochete. The Conserved Domain Database (CDD) server revealed that Msp contains two conserved domains, major outer sheath protein(N) (MOSP(N)) and MOSP(C), spanning residues 77 to 286 and 332 to 543, respectively, within the N- and C-terminal regions of the protein. Circular dichroism (CD) spectroscopy, Triton X-114 (TX-114) phase partitioning, and liposome incorporation demonstrated that full-length, recombinant Msp (Msp(Fl)) and a recombinant protein containing MOSP(C), but not MOSP(N), form amphiphilic, β-sheet-rich structures with channel-forming activity. Immunofluorescence analysis of intact T. denticola revealed that only MOSP(C) contains surface-exposed epitopes. Data obtained using proteinase K accessibility, TX-114 phase partitioning, and cell fractionation revealed that Msp exists as distinct OM-integrated and periplasmic trimers. Msp(Fl) folded in Tris buffer contained slightly less β-sheet structure than detergent-folded Msp(Fl); both forms, however, partitioned into the TX-114 detergent-enriched phase. CDD analysis of the nine Tpr paralogs predicted to be outer membrane proteins (OMPs) revealed that seven have an Msp-like bipartite structure; phylogenetic analysis revealed that the MOSP(N) and MOSP(C) domains of Msp are most closely related to those of TprK. Based upon our collective results, we propose a model whereby a newly exported, partially folded intermediate can be either processed for OM insertion by the β-barrel assembly machinery (BAM) or remain periplasmic, ultimately forming a stable, water-soluble trimer. Extrapolated to T. pallidum, our model enables us to explain how individual Tprs can localize to either the periplasmic (e.g., TprK) or OM (e.g., TprC) compartments.


Enantioselective strecker reaction of phosphinoyl ketoimines catalyzed by in situ prepared chiral N,N'-dioxides.
The enantioselective Strecker reaction of N-diphenylphosphinoyl ketoimines has been achieved by use of in situ prepared chiral N,N'-dioxide catalyst from l-piperidinamide 3f and m-chloroperoxybenzoic acid (m-CPBA). Excellent yields (up to 99%) and high enantioselectivities (up to 92% ee) were obtained. In particular, in situ prepared catalyst with readily available chiral material made the procedure more convenient. Moreover, the l-piperidinamide 3f-derived N,N'-dioxide 9 could be recycled and reused at least five times without any loss of either catalytic activity or enantioselectivity.


[Implementation of performance indicators in the Czech Breast Cancer Screening Programme - results of the regular monitoring].
The Czech organised breast cancer screening programme was initiated in 2002. Collection of data on screening mammography examinations, subsequent diagnostic procedures, and final dia-gnosis is an indispensable part of the programme. Data collection is obligatory for all accredited centres, in accordance with regulations issued by the Czech Ministry of Health. This contribution aims to demonstrate the recent results of quality monitoring of the accredited centres. Quality indicators, whose definition complies with international standards, involve the women's participation, the volume of performed examinations, the accuracy of screening mammography, the use of preoperative diagnostics, and the proportion of early detected tumours. Our evaluation documents a continuous improvement in quality of the Czech mammography screening programme, which is thereby in full agreement with international recommendations on quality assurance.


Post-traumatic inclusion cysts of the iris: a longterm prospective case series.
Post-traumatic cysts of the iris pose a diagnostic and therapeutic challenge for ophthalmic surgeons. This prospective case series highlights the clinical spectrum and longterm outcomes of different modes of treatment in these cases. Eleven cases of post-traumatic iris inclusion cysts, treated with Nd:YAG laser and/or surgical excision were evaluated prospectively over periods ranging from 6 months to 3 years. Ultrasound biomicroscopy features and postoperative outcomes in each were evaluated. Laser iridotomy of the cyst offers a non-invasive method of therapy in these cases but has a high rate of recurrence. The outcomes in most cases were poor, with worse results and more complications encountered in younger age groups. Iris inclusion cysts have overall poor surgical outcomes as the result of the extensive proliferation of epithelial cells, which may explain why the condition takes a rapid course in younger patients and why severe complications are encountered postoperatively in this age group.


Exocrine pancreatic dysfunction is common in hepatocyte nuclear factor 1β-associated renal disease and can be symptomatic.
Heterozygous mutations in the HNF1B gene are the most common monogenic cause of developmental kidney disease. Extrarenal phenotypes frequently occur, including diabetes mellitus and pancreatic hypoplasia; the latter is associated with subclinical exocrine dysfunction. We measured faecal elastase-1 in patients with HNF1B-associated disease regardless of diabetes status and assessed the degree of symptoms associated with pancreatic exocrine deficiency. Faecal elastase-1 was measured in 29 patients with a known HNF1B mutation. We defined a low faecal elastase-1 concentration based on the 2.5 percentile of 99 healthy control individuals (410 μg/g stool). Symptoms related to pancreatic exocrine dysfunction were assessed and a subset of the HNF1B cohort (n = 6) underwent pancreatic imaging. Faecal elastase-1 was below the 2.5 percentile of the control cohort in 18/29 (62%) patients with HNF1B-associated renal disease. A total of 8/29 (28%) had a measurement suggestive of exocrine pancreatic insufficiency at <200 μg/g stool; of these, 3 suffered with abdominal pain, loose stools and/or unintentional weight loss. All three experienced symptomatic improvement and weight gain after commencing pancreatic enzyme replacement therapy. Faecal elastase-1 was low in 7/15 (47%) HNF1B patients without diabetes compared with 11/14 (79%) of those with diabetes (P = 0.1). Faecal elastase-1 deficiency is a common feature of HNF1B-associated renal disease even when diabetes is not present and pancreatic exocrine deficiency may be more symptomatic than previously suggested. Faecal elastase-1 should be measured in all patients with known HNF1B-associated disease complaining of chronic abdominal pain, loose stools or unintentional weight loss. The discovery of a low faecal elastase-1 concentration in individuals with developmental kidney disease of uncertain cause should prompt referral for HNF1B genetic testing.


Radiolabeled HER2-directed exosomes exhibit improved cell targeting and specificity.
Aim: Here, we established a reliable strategy for generation and characterization of targeted radiolabeled exosomes for the detection of HER2-positive cells quantitatively. Materials & methods: Targeted exosomes (T-exos) were radiolabeled by two different radiotracers, [99mTc]Tc-HMPAO or [111In]In-oxine. The labeling efficiency and stability were assessed using exosome exclusive spin columns. HER2-positive and -negative cells were treated with [111In]In-oxine-exosomes after 3 and 24 h. Results: [111In]In-oxine labeling did not change the binding ability and general features of the exosomes. With [111In]In-oxine, 70% labeling efficiency and 78% radiochemical stability over 24 h were achieved. [111In]In-oxine-T-exos showed greater uptake by HER2-positive cells compared with untargeted exosomes. Conclusion: [111In]In-oxine-T-exos could potentially be used as an effective imaging tool for HER2 expression.


Comparison of acceleration subjects to other populations: spinal anomaly distribution.
Two Armstrong Laboratory (AL) human volunteer subject panels (sustained and impact acceleration) at Wright Patterson AFB, OH, were compared to each other and to other samples of different populations in terms of spinal anomalies. These sample populations were obtained from the scientific literature: French, Norwegian, Netherlands, and U.S. pilots; U.S. Air Force (AF) and Navy subjects, and from representative "normal" civilian populations, and then compared using the proportion parameters for various spinal anomalies. There were only a few common parameters between the two panels and between each panel compared with the foreign military, human subjects, and "normal" population. However, there were two to six times as many similar spinal anomaly incidence rates between the AL panels and the U.S. pilot sample. It was reassuring that the AL subject panels used in AF acceleration research have more in common with AF pilots than other populations in regards to spinal anomalies, even though the pilot sample may not be representative of the true pilot population. Recommendations are to establish a common reference point in nomenclature and description of spinal anomalies (modeled after the French) and to start collecting spinal radiographs on all U.S. pilots. These radiographs would not be for screening but for establishing a database following the occupational pathology of flying. This data would also facilitate comparisons with research acceleration panels, as well as with foreign air forces. Informed decisions can then be made regarding screening criteria for the future as aircraft and ejection seat performance envelopes continue to expand.


Development of a clinical prediction model to calculate patient life expectancy: the measure of actuarial life expectancy (MALE).
To develop a clinical prediction model enabling the calculation of an individual patient's life expectancy (LE) and survival probability based on age, sex, and comorbidity for use in the joint decision-making process regarding medical treatment. A computer software program was developed with a team of 3 clinicians, 2 professional actuaries, and 2 professional computer programmers. This incorporated statistical spreadsheet and database access design methods. Data sources included life insurance industry actuarial rating factor tables (public and private domain), Government Actuary Department UK life tables, professional actuarial sources, and evidence-based medical literature. The main outcome measures were numerical and graphical display of comorbidity-adjusted LE; 5-, 10-, and 15-year survival probability; in addition to generic UK population LE. Nineteen medical conditions, which impacted significantly on LE in actuarial terms and were commonly encountered in clinical practice, were incorporated in the final model. Numerical and graphical representations of statistical predictions of LE and survival probability were successfully generated for patients with either no comorbidity or a combination of the 19 medical conditions included. Validation and testing, including actuarial peer review, confirmed consistency with the data sources utilized. The evidence-based actuarial data utilized in this computer program design represent a valuable resource for use in the clinical decision-making process, where an accurate objective assessment of patient LE can so often make the difference between patients being offered or denied medical and surgical treatment. Ongoing development to incorporate additional comorbidities and enable Web-based access will enhance its use further.


Human cytomegalovirus does not induce human leukocyte antigen class II expression on arterial endothelial cells.
Human cytomegalovirus (CMV) has been associated with allograft rejection and, in particular, with transplant-associated arteriosclerosis. However, the role CMV plays in the development of transplant-associated arteriosclerosis remains unclear. CMV can infect the endothelium, the interface between allograft tissue and the host immune cells, but the direct induction of endothelial human leukocyte antigen (HLA) class II by CMV remains controversial. Our previous studies with venous endothelial cells (EC) have shown that CMV does not directly induce this antigen on infected EC and, furthermore, renders these cells refractory to interferon (IFN)-gamma induction. However, questions have arisen regarding the relevance of these findings to arterial endothelia. Thus, we have extended these studies to determine whether similar interactions occur in arterial EC. EC derived from human coronary artery, aorta, and umbilical artery were assayed by immunofluorescence flow cytometry and dual immunohistochemical staining following IFN-gamma treatment and/or inoculation with CMV. Data generated by these experiments demonstrate that regardless of vascular origin: (1) CMV does not directly induce endothelial surface or cytoplasmic HLA class II, and (2) although uninfected arterial EC are HLA class II inducible by IFN-gamma, infected cells are completely refractory to this effect. These results suggest that CMV-mediated inhibition of HLA class II expression is a phenomenon shared by human arterial and venous endothelia of both fetal and adult origin.


Sorption equilibrium of a wide spectrum of organic vapors in Leonardite humic acid: experimental setup and experimental data.
The environmental fate of volatile and semivolatile organic compounds is determined by their partitioning between air and soil constituents, in particular soil organic matter (SOM). While there are many studies on the partitioning of nonpolar compounds between water and SOM, data on sorption of polar compounds and data for sorption from the gas phase are rather limited. In this study, Leonardite humic acid/air partition coefficients for 188 polar and nonpolar organic compounds at temperatures between 5 and 75 degrees C and relative humidities between < 0.01% and 98% have been determined using a dynamic flow-through technique. To the best of our knowledge, this is by far the largest and most diverse and consistent data set for sorption into humic material published so far. The major results are as follows: the relative humidity affected the experimental partition coefficients by up to a factor of 3; polar compounds generally sorbed more strongly than nonpolar compounds due to H-bonding (electron donor/ acceptor interactions) with the humic acid; no glass transitions in the range of 5-75 degrees C that would be relevant with respect to the sorption behavior of hydrated Leonardite humic acid were observed; our experimental data agree well with experimental partition coefficients from various literature sources.


Synthetic Physical Interactions Map Kinetochore-Checkpoint Activation Regions.
The spindle assembly checkpoint (SAC) is a key mechanism to regulate the timing of mitosis and ensure that chromosomes are correctly segregated to daughter cells. The recruitment of the Mad1 and Mad2 proteins to the kinetochore is normally necessary for SAC activation. This recruitment is coordinated by the SAC kinase Mps1, which phosphorylates residues at the kinetochore to facilitate binding of Bub1, Bub3, Mad1, and Mad2. There is evidence that the essential function of Mps1 is to direct recruitment of Mad1/2. To test this model, we have systematically recruited Mad1, Mad2, and Mps1 to most proteins in the yeast kinetochore, and find that, while Mps1 is sufficient for checkpoint activation, recruitment of either Mad1 or Mad2 is not. These data indicate an important role for Mps1 phosphorylation in SAC activation, beyond the direct recruitment of Mad1 and Mad2.


Rod phosphorylation favors folding in a catch muscle myosin.
Myosin from a molluscan catch muscle is unusual in being phosphorylated in the rod by an endogenous heavy chain kinase. The overall structure of the molecule resembles that of other muscle myosins, although the tail is somewhat longer (approximately equal to 1700 A). At low ionic strength the unphosphorylated molecules associate in filaments that display a striking axial repeat of 145 A. Phosphorylation of the rod enhances myosin solubility in the range of NaCl between 0.05 and 0.15 M. Depending on the ionic strength and the counterions present, the soluble species corresponds to an antiparallel folded dimer (15 S) or to a folded monomer (10 S). Unphosphorylated myosin can also be partially solubilized into folded monomers by addition of ATP in 0.15 M NaCl. A similar molecular folding has also been observed in smooth muscle and nonmuscle myosins that depends, however, on the state of phosphorylation of the light chains in the myosin head. We discuss these results in relation to possible mechanisms for control of catch contraction.


Effectiveness of hypertonic saline-dextran 70 for initial fluid resuscitation of major burns.
Small-volume resuscitation (4 ml/kg) with hypertonic saline-dextran (HSD) has been shown effective in hemorrhagic shock. In the present study the effectiveness of an initial 4 ml/kg bolus infusion of HSD on cardiovascular function and fluid resuscitation requirements after a major burn injury was evaluated in anesthetized sheep following a 40% BSA scald burn. One hour after injury resuscitation was initiated by a rapid intravenous bolus infusion (4 ml/kg) of either hypertonic saline-dextran (7.5% NaCl in 6% dextran 70) (HSD) or the same volume of normal (isotonic) saline (NS). Lactated Ringer's was later infused as needed to maintain cardiac output at 90% of baseline. HSD rapidly and effectively restored cardiac output and mean arterial pressure significantly better than the same volume of NS. Hemodynamic improvement by HSD was short lived, and need for further fluid therapy was only marginally delayed (HSD 38 +/- 8 min, NS 20 +/- 3 min; p = 0.06) (mean +/- SEM). The total requirements for fluid therapy during the first 6 hr postburn were not reduced by the initial HSD bolus (HSD 3,145 +/- 605 ml, NS 2,905 +/- 495 ml; n.s.), nor was skin edema formation reduced. We conclude that in anesthetized sheep HSD resuscitation was only transiently effective in treating burn shock. This may be attributed to the sustained increase in vascular permeability and continued plasma leak following thermal injury.


Pediatric and adult hepatic embryonal sarcoma: a comparative ultrastructural study with morphologic correlations.
Hepatic embryonal (undifferentiated) sarcoma (ES) is a rare pediatric tumor occurring predominantly in the first decade of life, but a few examples of adult ES have also been described. Isolated ultrastructural reports describe contradictory lines of differentiation in these tumors. Four pediatric and 3 adult ES cases were studied ultrastructurally and features were correlated with morphology. Morphologically, tumors were composed of mixture of plump spindle cells and bizarre giant cells, showing abundant cytoplasmic eosinophilic globules. Ultrastructurally, the hallmark features in all cases included dilated RERs and secondary lysosomes with dense precipitates. Dilated mitochondria and mitochondrial-RER complexes were often seen. Other features included intracytoplasmic fat droplets, scant actin microfilaments, and focal glycogen pools. In summary, pediatric and adult ES show similar morphologic and ultrastructural features. Ultrastructurally, hepatic ES have distinctive findings, including dilated RER and electron-dense lysosomal precipitates, which correlate with the eosinophilic hyaline bodies seen microscopically. These findings suggest that ES are composed of fibroblastic, fibrohistiocytic, and undifferentiated cells. Other lines of differentiation were not identified.


Effect of liver transplantation on intestinal permeability and correlation with infection episodes.
Liver cirrhosis has been known to be associated with increased intestinal permeability (IP); however, little is known about the modification of IP after liver transplantation (LT). The present study was aimed to assess IP after LT and evaluated its association with laboratory tests and clinical parameters, as well as with the development of infections. LT recipients were consecutively enrolled and compared with an equal number of patients with liver cirrhosis and healthy subjects. IP was assessed by urinary excretion of chromium-51 ethylenediaminetetraacetic acid (51Cr-EDTA). The median 51Cr-EDTA excretion was found to be higher in 35 LT recipients as compared with that in the healthy controls [4.77% (2.79-6.03) vs. 2.07% (1.57-2.42), p<0.0001], and comparable to that in the cirrhotic patients [3.69% (2.34-6.57), p = 0.445]. 51Cr-EDTA excretion was not associated with clinical variables, the type of immunosuppressive therapy, donor-related factors, comorbidities and incidence of infections [infection/no infection: 4.97% (3.14-7.03) vs 4.62% (2.79-5.82), p = 0.938]. LT recipients show an increased IP, similar to that in patients with liver cirrhosis. However, it is not associated with a high risk of infections. Further investigations into the pathogenesis of this persistent impairment of the intestinal barrier are warranted.


Cardiovascular risk reduction in sedentary postmenopausal women during organised physical activity.
Cardiovascular (CV) diseases are a major cause of death in elderly women. Aerobic training improves component CV risk factors. Long-term, higher-intensity, group-based and home-based exercise training has been shown to improve exer-cise performance. However, it is not clear if short-term, group-based or home-based training with an educational programme permanently improves cardiometabolic parameters in elderly women. The aim of the study was to evaluate the effectiveness of organised physical activity programmes dedicated to elderly, sedentary women. Thirty-five sedentary women, aged > 55 years (mean 65.4 ± 7.3 years) were enrolled in a two-week group-based physical training programme of moderate intensity (2.5-5.0 METs) followed by three months of organised, home-based physical activity targeting all major muscle groups with special emphasis on postural muscles, combined with an educational programme about physical activity and CV risk. Eighteen months of self-guided physical activity was the final stage of training. Medical examination and blood samples were collected at baseline and after each step of exercises. Each step of training resulted in a reduction of systolic and diastolic blood pressure (p < 0.05), body mass index (p < 0.05), waist to hip ratio (p < 0.02), and low-density lipoprotein (p < 0.05) as compared to baseline. The time of exercise (p < 0.01), maximal tolerated load, and maximal oxygen consumption (p < 0.001) were significantly improved after two-weeks of training, as well as the high-density lipoprotein (p < 0.001). These changes remained significant after three months. Finally, the 10-year risk of fatal CV disease reduced significantly (p < 0.05). After 18 months 2/3 of subjects continued physical activity at a sufficient level to achieve additional health benefits according to the World Health Organisation. Organised, group-based exercise followed by home-based training and self-guided physical activities constantly improves cardiometabolic parameters and reduces CV risk.


Phosphorus pentasulfide mediated conversion of organic thiocyanates to thiols.
In this paper we report an efficient and mild procedure for the conversion of organic thiocyanates to thiols in the presence of phosphorus pentasulfide (P2S5) in refluxing toluene. The method avoids the use of expensive and hazardous transition metals and harsh reducing agents, as required by reported methods, and provides an attractive alternative to the existing methods for the conversion of organic thiocyanates to thiols.


Difficulties in assessing depressive-like reactions to chronic severe external stress as exemplified by spouse caregivers of Alzheimer patients.
Problems in making differential diagnoses and severity ratings of depressive-like reactions in chronically, heavily stressed persons are described. These assessment concerns are especially pertinent to older persons. The assessment concern discussed relates to difficulties in determining the extent to which stress reactions are inevitable consequences of stressor demands versus excessive pathological reactions versus natural manifestations of aging. The newly revised criteria of the Diagnostic and Statistical Manual of Mental Disorders, 3rd edition (DSM-III-R) and its associated structured interviews do not lessen the difficulties described. However, they reflect progress in specifying the amount of cross-sectional and longitudinal consistency required before maladaptive behaviours meet diagnostic and/or severity criteria as pathological indicators. Stressor level is important among the criteria for the less severe DSM-III-R depression-related disorders, but the specific response demands of the stressors are ignored. By contrast, biomedical factors are consistently given significant weight. To clarify these matters, the five DSM-III-R diagnostic axes, depressive diagnostic criteria, and associated structured interviews for eliciting relevant data are reviewed.


Risky sexual behaviors associated with recreational drug use among men who have sex with men in an international resort area: challenges and opportunities.
South Florida is home to a highly transient population of approximately 145,000 men who have sex with men (MSM) and annually hosts over 1.8 million gay and bisexual visitors. To develop more effective interventions for HIV/sexually transmitted infections (STI) prevention in this setting, we conducted a cross-sectional study of recreational drug use and risky sexual behaviors among MSM. A standardized, self-administered questionnaire, reviewed and approved by a university Institutional Review Board, was offered to men 18 years of age and older who reported ever having sex with a man. Men were approached on weekends in five diverse locations in Miami-Dade County and five in Broward County in winter 2004. An honorarium of $10 was offered to those who completed and returned a questionnaire. Of 407 participants, 115 men (28%) lived in Miami-Dade, 147 (36%) lived in Broward, 46 (11%) lived in another county in south Florida, and 99 (24%) lived elsewhere. Overall, 32% reported using one or more "club drugs" in the past year. Club drug use was highly associated with unprotected anal intercourse (UAI) (P < .001). MSM residing outside of south Florida were more likely than local residents to report using cocaine and ketamine and engaging in unprotected receptive anal intercourse (URAI) in the past month (P = .03). Tourists may be even more likely than residents to engage in risky sexual behaviors and use certain recreational drugs. Interventions must be developed, implemented, and evaluated that take into account the unique characteristics of international resort areas.


Target cells in internal dosimetry.
Data related to radium induced bone sarcomas in humans are used as a method of defining target cells on bone surfaces and in the bone marrow. The differential distribution of radiation induced bone sarcoma types, with a high ratio of non-bone producing, mainly fibroblastic tumours, challenges the ICRP concept that the bone lining cells are target cells. Multipotential mesenchymal stem cells are located within the range of alpha particles and are the most likely target cells for the fibroblastic type of bone sarcoma. The histogenesis of bone sarcomas after irradiation with alpha emitters shows that their final histopathology is not dependent on a single target cell. Each target cell has a microenvironment, which has to be regarded as a synergistic morpho-functional tissue unit. For this the concept of 'histion', a term used in general pathology, is proposed. Interactions between target cells that have been hit by alpha particles, leading to lethal, mutational or transformation events with all components of a 'histion', will prove critical to understanding the pathogenesis of both deterministic and stochastic late effects.


Environmental factors, sleep duration, and sleep bruxism in Brazilian schoolchildren: a case-control study.
The purpose of our study was to evaluate the association between environmental factors, sleep duration, and sleep bruxism (SB) in schoolchildren. A case-control study was performed. Individuals participating in the study were randomly chosen from public and private schools in Belo Horizonte, Brazil. A total of 120 children with bruxism and 240 without bruxism (mean age, 8 years) participated in our study. A questionnaire for parents was used to collect data based on criteria taken from the American Academy of Sleep Medicine. Conditional binary logistic regression statistical tests and χ2 tests were used for analysis. The final logistical model found that children with a median sleep time < or = 8 h per night (odds ratio [OR], 2.561 [95% confidence interval {CI}, 1.480-4.433]), who did not enjoy a good night's sleep (OR, 3.253 [95% CI, 1.600-6.615]), who slept with noise in the room (OR, 2.699 [95% CI, 1.645-4.429]), and who had the light on (OR, 2.370 [95% CI, 1.446-3.884]), were more likely to have SB. Children who sleep for less than 8h a night are more likely to have SB. Light and noise in the room were two predisposing factors for the occurrence of SB.


Detection of Parietaria judaica airborne allergenic activity: comparison between immunochemical and morphological methods including clinical evaluation.
Airborne pollen grains and small plant particles of respirable size are the main causes of rhinitis and asthma in pollinosis patients. Consequently, it could be useful to quantify atmospheric variations in these biological aerosols and their allergenic activity as a basis for establishing correlations with the clinical symptoms in these allergic subjects. Our study was conducted in Naples from May to August 1992 and from May to August 1993 and concentrated on Parietaria judaica (Par j) the most important hay fever-provoking plant in southern Italy. The aim of this study was to evaluate the day-to-day variation in counts of Par j. pollen, the day-to-day variation in allergenic activity specific for this plant, and to relate these two variables to symptom scores in patients with respiratory allergy to Par j. The airborne pollen grains were collected by a Hirst-like volumetric trap and examined through an optical microscope, while the allergenic activity of particles trapped on glass fibre filters in a high volume air-sampler was determined by immunochemical assay. The two devices were placed on the flat roof of the 'A. Cardarelli' Hospital. The results of this preliminary study suggest that both methods could have useful clinical relevance, since these two biological parameters were significantly correlated with the symptom scores of allergic patients. However, pollen count with morphological quantification of grains/m3 of air is a more simple technique.


A randomized comparison of an emollient containing skin-related lipids with a petrolatum-based emollient as adjunct in the treatment of chronic hand dermatitis.
Hand dermatitis is a multifactorial skin disorder in which skin barrier impairment is involved in the pathogenesis. The development of topical agents that improve skin barrier function is therefore a promising approach for the management of hand dermatitis. Topically applied lipids may interfere with skin barrier function, and emollients containing skin-related lipids have been suggested to facilitate repair of the skin barrier. However, evidence for the superiority of emollients containing skin-related lipids over the more traditional emollients is still lacking. The aim of this study was to compare an emollient containing skin-related lipids (Locobase Repair) with a traditional petrolatum-based emollient for the management of hand dermatitis. Adult males and females (n = 30) with mild to moderate chronic hand dermatitis were treated twice daily for 2 months either with an emollient containing skin-related lipids or with a pet.-based emollient. In the case of exacerbation, the patients of both treatment groups were allowed to use a mild corticosteroid according to instructions. Both treatment regimes significantly improved clinical signs of hand dermatitis as assessed by the investigator global assessment, hand eczema area and severity score. We did not observe significant differences in the improvement of clinical signs, itching, patients' assessment of efficacy, cosmetic acceptability or usage of topical corticosteroids between both treatment groups. In conclusion, this study confirms that the frequent use of emollients may be useful in the therapy of hand dermatitis. However, we could not demonstrate the superiority of this particular emollient containing skin-related lipids in patients with chronic hand dermatitis.


[Changes in food consumption pattern among Chilean school children after the implementation of a healthy kiosk].
In Chilean school there is a kiosk that sells a large number of high-calorie products. The aim of this study was to determine the barriers that children have for buying healthy food and evaluate changes in the pattern of food purchases during a school year at a school where a "Healthy Space" was created. We designed implemented and assessed changes in food purchases by developing a "Healthy Space" which included a kiosk that incorporated a range of healthy food at affordable prices. The staff in charge of the kiosk was trained and we generate communication and marketing strategies to promote the consumption of healthy food. A validated survey to determine food purchases was applied to 9-12 year-old children from both schools at baseline and follow up 8 months later. The total number of schoolchildren was 477 (291 from the intervention and 115 from the control school). There weren't significant differences in the amount of money available to buy food between children of both schools. There was a significant increase in the purchase of fruit, milk, yoghurt, soft drinks and light juices, dried seeds, healthy sandwiches and non-fat ice cream (p < 0.05) of school children from the intervention school. At the control school, no change in consumption was observed. The increase in the supply of affordable healthy food, including communication and marketing strategies, significantly increases the consumption of these products among school children.


A xanthine oxidase inhibitor 1'-acetoxychavicol acetate inhibits azoxymethane-induced colonic aberrant crypt foci in rats.
The modifying effect of dietary administration of a xanthine oxidase inhibitor 1'-acetoxychavicol acetate (ACA) present in an edible plant Languas galanga in Thailand on the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) was investigated in rats. Male F344 rats were given s.c. injections of AOM (15 mg/kg body wt) once a week for 3 weeks to induce colonic ACF. They were fed the diets containing 100 or 200 ppm ACA for 5 weeks, starting 1 week before the first dosing of AOM. At the termination of the study (week 5), AOM induced 118 +/- 28 ACF/colon. Dietary administration of ACA caused significant reduction in the frequency of ACF (41% inhibition by 100 ppm ACA feeding and 37% inhibition by 200 ppm ACA feeding, P<0.01). Such inhibition might be associated with suppression of the proliferation biomarkers' expression such as ornithine decarboxylase activity in the colonic mucosa, number of silver-stained nucleolar organizer regions' protein in the colonic mucosal cell nuclei and blood polyamine content. These results indicate that ACA could inhibit the development of AOM-induced ACF through its suppression of cell proliferation in the colonic mucosa and ACA might be a possible chemopreventive agent against colon tumourigenesis.


The role of the serotonergic and noradrenergic neurotransmitter systems in the treatment of psychological and physical symptoms of depression.
Major depressive disorder is a medical condition that includes abnormalities of affect and mood, cognition, and physical functioning. In particular, as many as 76% of patients suffering from depression are found to report somatic symptoms, including various types of pain such as headaches, stomach pain, back pain, and vague, poorly localized pain. Although the pathophysiology of depression is still unknown, there is significant evidence for abnormalities of the norepinephrine (NE) and serotonin (5-HT) neurotransmitter systems in depressive disorders. Interestingly, both 5-HT and NE also appear to exert analgesic effects via descending pain pathways and therefore play a modulating role in pain. There are many effective antidepressant treatments available. However, residual symptoms are relatively common, among both partial responders and responders without remission. A recent study from our group has shown that responders who have not achieved remission have significantly more somatic symptoms than remitters following 8 weeks of treatment with fluoxetine. These data may suggest that antidepressants that are particularly effective in the treatment of pain and painful physical symptoms may yield higher remission rates in major depressive disorder.


Overexpression of growth and differentiation factor-5 inhibits inflammatory factors released by intervertebral disc cells.
Low back pain (LBP) is one of the most common musculoskeletal diseases in the world. The incidence is ~70% in adults and many of them suffer from disability. Recently, intervertebral disc degeneration (IDD) has been deemed as a main cause of LBP. The present study aimed to investigate the potentials of growth and differentiation factor-5 (GDF-5) in IDD. The protein levels of prostaglandin-E2 (PGE2), tumor necrosis factor (TNF)-α and interleukin (IL)-1β in culture medium were evaluated by ELISA. mRNA and protein expression levels in nucleus pulposus (NP) cells were evaluated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting, respectively. Griess reaction was applied to test the nitric oxide (NO) concentration in the culture supernatant. The expression levels of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in NP cells were measured by RT-qPCR. Collagen-II, aggrecan, IκBα and phosphorylated (p)-p65 expression levels were detected by western blotting. Compared with the control group, protein expression levels of TNF-α, IL-1β and PGE2, and NO concentration in culture medium were upregulated by LPS, which were significantly repressed by GDF-5 overexpression (P<0.05). Additionally, GDF-5 overexpression reduced lipopolysaccharide-induced upregulation of TNF-α, IL-1β, iNOS, COX-2, collagen-II, aggrecan, IκBα and p-p65 expression levels in NP cells.


Laboratory Administration of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS): Technique, Targeting, and Considerations.
Non-invasive vagus nerve stimulation (VNS) may be administered via a novel, emerging neuromodulatory technique known as transcutaneous auricular vagus nerve stimulation (taVNS). Unlike cervically-implanted VNS, taVNS is an inexpensive and non-surgical method used to modulate the vagus system. taVNS is appealing as it allows for rapid translation of basic VNS research and serves as a safe, inexpensive, and portable neurostimulation system for the future treatment of central and peripheral disease. The background and rationale for taVNS is described, along with electrical and parametric considerations, proper ear targeting and attachment of stimulation electrodes, individual dosing via determination of perception threshold (PT), and safe administration of taVNS.


Effects of digital tourniquet ischemia: a single center study.
There is little information regarding the detrimental effects of tourniquet ischemia, although it is a widely used technique in extremity surgery. We endeavored to study some of the physiologic changes involved in the finger during the ischemic phase and throughout the recovery phase after tourniquet release. This was a single-center, prospective observational study involving healthy adults designed to assess the appropriate application time of a digital T-ring tourniquet without a pH or acidosis <7.0 to avoid any potential risk to local tissues. There was no pH difference before tourniquet application between men and women, but after tourniquet application, the women's fingers became more acidotic at 10 and 20 minutes than the mens', but after 30 minutes the acidosis of the two groups was similar. Participants who weighed less had a more acidotic pH level than heavier participants. This study was performed in a laboratory setting on healthy people rather than on those with existing medical conditions, so clinical recommendations cannot be explicitly made. Tourniquet application time is precious. While operating under tourniquet control, the extremity becomes increasingly acidotic. Tourniquet ischemia longer than 20 minutes causes local acidosis and muscle fatigue. Women and persons who weighed less could reach acidotic pH values faster than men or heavier patients. If applications longer than 20 minute are expected, the tourniquet should be released at 20 minutes, allowing the finger to reperfuse for 3-5 minutes to clear the acidosis before reapplication of tourniquet.


Speakers' overestimation of their effectiveness.
Successful communication depends in part on an ability to anticipate miscommunication. We investigated speakers' ability to gauge their addressees' understanding. Participants in our experiments were asked to say ambiguous sentences while attempting to convey a specific intention to their addressee. When they estimated the addressee's understanding of the intended meaning, they showed a consistent tendency to overestimate their effectiveness. They expected the addressee to understand more often than the addressee actually did. In contrast, overhearers who were informed about the speakers intention did not systematically overestimate the speakers' effectiveness. Our findings suggest that when speakers monitor their own utterances, they do not act as unbiased observers. Instead, they underestimate the ambiguity of their own utterances and overestimate the extent to which their disambiguating cues make their intention transparent. Such overestimation could be a systematic source of miscommunication in natural conversation, and should be accounted for by any theory of language production.


AORTA Gene: Polygenic prediction improves detection of thoracic aortic aneurysm.
Thoracic aortic disease is an important cause of morbidity and mortality in the US, and aortic diameter is a heritable contributor to risk. Could a polygenic prediction of ascending aortic diameter improve detection of aortic aneurysm? Deep learning was used to measure ascending thoracic aortic diameter in 49,939 UK Biobank participants. A genome-wide association study (GWAS) was conducted in 39,524 participants and leveraged to build a 1.1 million-variant polygenic score with PRScs-auto. Aortic diameter prediction models were built with the polygenic score ("AORTA Gene") and without it. The models were tested in a held-out set of 4,962 UK Biobank participants and externally validated in 5,469 participants from Mass General Brigham Biobank (MGB), 1,298 from the Framingham Heart Study (FHS), and 610 participants from All of Us. In each test set, the AORTA Gene model explained more of the variance in thoracic aortic diameter compared to clinical factors alone: 39.9% (95% CI 37.8-42.0%) vs 29.2% (95% CI 27.1-31.4%) in UK Biobank, 36.5% (95% CI 34.4-38.5%) vs 32.5% (95% CI 30.4-34.5%) in MGB, 41.8% (95% CI 37.7-45.9%) vs 33.0% (95% CI 28.9-37.2%) in FHS, and 34.9% (95% CI 28.8-41.0%) vs 28.9% (95% CI 22.9-35.0%) in All of Us. AORTA Gene had a greater AUROC for identifying diameter ≥4cm in each test set: 0.834 vs 0.765 (P=7.3E-10) in UK Biobank, 0.808 vs 0.767 in MGB (P=4.5E-12), 0.856 vs 0.818 in FHS (P=8.5E-05), and 0.827 vs 0.791 (P=7.8E-03) in All of Us. Genetic information improved estimation of thoracic aortic diameter when added to clinical risk factors. Larger and more diverse cohorts will be needed to develop more powerful and equitable scores.


Metabolic and nutritional factors in the pathogenesis of idiopathic osteonecrosis of the head of the femur (preliminary results of a long-term follow-up investigation).
A double statistical study of a group of 56 patients affected by idiopathic osteonecrosis of the head of the femur is presented. A comparative investigation was undertaken into this group, taking into consideration the principal biochemical parameters, clinical findings, dietary and living habits. The statistical data that were analysed confirmed the role of some of the aetiological factors concerned. A long-term study was also undertaken, with a preliminary follow-up at 22 months, on the progress of the patients with monolateral idiopathic osteonecrosis of the femoral head who were subjected to a therapeutic programme of dietary correction and the administration of medicaments.


Fever and fever syndrome--current problems.
Research into the complex humoral and neurophysiological events of pyrogen-induced fever has proceeded rapidly to establish the thermal and non-thermal components of the fever syndrome. The major breakthroughs derive from the elucidation of the identity of the endogenous pyrogen interleukin 1 with the humoral factors responsible for the acute phase reaction and for the activation of lymphocytic, cellular, and immunological defence as host responses to infections. As a consequence, fever research is no longer concerned primarily with the changes in temperature regulation responsible for the febrile alteration of temperature regulation, but aims at the elucidation of the contributions that are made by both the thermal and non-thermal components of the fever syndrome to the defence of the host against the microbial intruder responsible for this syndrome. In order to account for this development in these introductory remarks to the current issues of fever research, this review has tried to pay particular attention to the following points: 1) The role of humoral factors in the generation of febrile hyperthermia, including endogenous pyrogens as well as mediators acting on the thermoregulatory center. 2) The "fever syndrome" with special consideration of its regulation and of the significance of its components from the viewpoint of fever as a host-defence reaction. 3) The assessment of the role of PG's in the generation of the fever syndrome, both as putative central mediators and as systemically released agents, with special consideration of the inhibitory action of the established antipyretic drugs on PG synthesis.


Chronic experimental hyperuricemic nephropathy.
Sustained, moderately severe hyperuricemia and severe uricosuria were produced in male Wistar rats by feeding dietary supplements of oxonic acid (0.4 gm. per day) and uric acid (0.6 gm per day). After 1 month, the kidneys showed the previously described histologic features of urate-blockade nephropathy characterized by intratubular deposits, tubular injury, and an exudative response consisting of neutrophilic granulocytes with early tophus formation. After 36 and 52 weeks of hyperuricemia, and with no gross evidence of renal failure, the kidneys showed a predominantly interstitial mononuclear cell infiltrate around regenerated tubules, an increase in interstitial fibrous tissue, infrequent renal tophi, and renal stones. The glomeruli and blood vessels appeared completely normal. There was no evidence of arthritis and no other target organ damage was detected. The chronic renal changes present in this animal model of induced hyperuricemia resemble those seen in human gouty nephropathy. The evolution of the experimental urate nephropathy observed during 1 year suggests that a primary acute inflammatory tubular injury is followed by a diffuse chronic interstitial nephritis and that the glomeruli and blood vessels are not primarily involved in the renal disease. This animal model may provide the opportunity to study factors influencing the renal sequelae of sustained hyperuricemia.


Facilitated transfer of IncP beta R751 derivatives from the chromosome of Bacteroides uniformis to Escherichia coli recipients by a conjugative Bacteroides tetracycline resistance element.
The broad-host-range IncP beta plasmid R751 can mobilize itself from Escherichia coli to Bacteroides spp, but it is not maintained in Bacteroides spp. If R751 carries the Bacteroides transposon Tn4351, it can be integrated into the Bacteroides chromosome. Previously we showed that R751, integrated in the chromosome of Bacteroides uniformis, cannot mobilize itself out of B. uniformis into E. coli or isogenic B. uniformis strains. In this report, we showed that if the Bacteroides conjugative tetracycline resistance element Tcr ERL was coresident with the R751 insertion in B. uniformis, derivatives of R751 were transferred to E. coli, where they were recovered as plasmids. The most common derivatives were R751::Tn4351 and R751::IS4351, but some strains transferred R751 derivatives, containing additional DNA segments ranging in size from 10 to 23 kilobases. These DNA inserts cross-hybridized with chromosomal DNA from B. uniformis which did not carry the Tcr ERL element. Therefore, the inserts appeared to be segments of the wild-type B. uniformis chromosome and were not associated with the Tcr ERL element. The transfer of integrated R751 from B. uniformis was independent of the RecA phenotype of the E. coli recipients and did not appear to be due to transfer of B. uniformis chromosomal DNA, followed by RecA-dependent recombination between homologous IS4351 sequences to form the resultant R751 plasmid derivatives. Consistent with this, no transfer of Tn4351 (associated with the cointegrated R751) from B. uniformis donors to isogenic B. uniformis recipients was detected (< 10(-8)). Our data support the hypothesis that R751 excises from the B. uniformis chromosome by recombination involving flanking Tn4351 or IS4351 sequences and forms nonreplicating circles. The mobilization of these circular forms out of B. uniformis to E.coli is then facilitated by the Tcr ERL element.


Conscious sedation: for a TEE, is it always required?
Conscious sedation is an anesthesia technique frequently used to facilitate transesophageal echocardiography, but it is not really necessary for performing routine adult cases. Children and complicated circumstances generally do warrant sedation. Using such anesthesia does increase complication rates and financial costs, therefore, omitting it should be considered when appropriate. Conscious sedation does diminish pain and anxiety, but results in patients being temporarily not decisional; without sedation they remain at full decisional capacity and can resume routine activities immediately after the procedure.


Complement C1q activates canonical Wnt signaling and promotes aging-related phenotypes.
Wnt signaling plays critical roles in development of various organs and pathogenesis of many diseases, and augmented Wnt signaling has recently been implicated in mammalian aging and aging-related phenotypes. We here report that complement C1q activates canonical Wnt signaling and promotes aging-associated decline in tissue regeneration. Serum C1q concentration is increased with aging, and Wnt signaling activity is augmented during aging in the serum and in multiple tissues of wild-type mice, but not in those of C1qa-deficient mice. C1q activates canonical Wnt signaling by binding to Frizzled receptors and subsequently inducing C1s-dependent cleavage of the ectodomain of Wnt coreceptor low-density lipoprotein receptor-related protein 6. Skeletal muscle regeneration in young mice is inhibited by exogenous C1q treatment, whereas aging-associated impairment of muscle regeneration is restored by C1s inhibition or C1qa gene disruption. Our findings therefore suggest the unexpected role of complement C1q in Wnt signal transduction and modulation of mammalian aging.


The joining of the 30-S initiation complex with the 50-S subunit, the main target for thiostrepton.
The study undertaken in this paper on the mode of action of thiostrepton provides data which permit a more precise localization of the main target of thiostrepton. There is severe impairment of the joining of the 50-S subunit, probably carrying thiostrepton, with either the 30-S subunit or the 30-S initiation complex. The degree of impairment of this coupling is temperature dependent, being almost completely inhibited at 0 degrees C, whereas at 37 degrees C the effect is much less marked, provided that natural messenger RNA is present. The inhibition of initiation by thiostrepton is more severe in the presence of IF-1, a factor, which similar to thiostrepton, is able to shift the dynamic equilibrium of 70-S in equilibrium 50-S + 30-S more towards dissociation. By means of 14C-labeled IF-2 it is demonstrated that the binding of IF-2 into the 70-S initiation complex is prevented by thiostrepton, which seems to be the main cause for non-coupling.


Breast Primary Angiosarcoma: A Clinicopathologic and Imaging Study of a Series Cases.
The aim of our study is to provide clinicopathologic and imaging features of breast primary angiosarcoma. We retrospectively analyzed cases of primary angiosarcoma diagnosed at the Pathological Laboratory of Lomé over a period of 20 years (2000-2019). Eight cases of primary angiosarcoma of the breast were collected, including 6 from women and 2 from men. The median age was 41.63 years (range from 17 to 66 years). Depending on the location, there were 4 of 8 cases in the left breast. Ultrasound classifications were BI-RADS 4 and 5. Histology revealed a malignant vascular proliferation composed of small lumens lined by atypical endothelial cells, evident mitoses, and foci of necrosis. On immunohistochemistry, the lesional cells expressed CD31, CD34, and Factor VIII. Based on Federation Nationale des Centers de Lutte Contre Le Cancer (FNCLCC) grading, the cases were grade II and III. Overall survival at 6 months was estimated to be 25% in a woman.


Assessing computer projection technology needs.
Computer projection technology is a widely accepted tool for delivering presentations. Many educators are responsible for purchasing the equipment for their departments to use, however, deciding which product to buy can be overwhelming. The authors present an overview of essential factors to consider when examining computer projectors. Also included is a 4-step process to assist educators when making these purchasing decisions.


Deciphering the Pharmacological Mechanisms of Taohe-Chengqi Decoction Extract Against Renal Fibrosis Through Integrating Network Pharmacology and Experimental Validation In Vitro and In Vivo.
Taohe-Chengqi decoction (THCQ), a classical traditional Chinese medicinal (TCM) formula, has been extensively used for treating chronic kidney disease (CKD). However, the biological activity and mechanisms of action of its constituents against renal fibrosis have not yet been investigated thoroughly. This study was aimed at devising an integrated strategy for investigating the bioactivity constituents and possible pharmacological mechanisms of the n-butanol extract of THCQ (NE-THCQ) against renal fibrosis. The n-butanol extract of THCQ was prepared by the solvent extraction method. The components of NE-THCQ were analyzed using UPLC-Q/TOF-MS/MS techniques and applied for screening the active components of NE-THCQ according to their oral bioavailability and drug-likeness index. Then, we speculated the potential molecular mechanisms of NE-THCQ against renal fibrosis through pharmacological network analysis. Based on data mining techniques and topological parameters, gene ontology, and pathway enrichment, we established compound-target (C-T), protein-protein interaction (PPI) and compound-target-pathway (C-T-P) networks by Cytoscape to identify the hub targets and pathways. Finally, the potential molecular mechanisms of NE-THCQ against renal fibrosis, as predicted by the network pharmacology analyses, were validated experimentally in renal tubular epithelial cells (HK-2) in vitro and against unilateral ureteral obstruction models in the rat in vivo. We identified 26 components in NE-THCQ and screened seven bioactive ingredients. A total of 118 consensus potential targets associated with renal fibrosis were identified by the network pharmacology approach. The experimental validation results demonstrated that NE-THCQ might inhibit the inflammatory processes, reduce ECM deposition and reverse EMT via PI3K/AKT/mTOR and HIF-1α/VEGF signaling pathways to exert its effect against renal fibrosis. This study identified the potential ingredients of the NE-THCQ by UPLC-Q/TOF-MS/MS and explained the possible mechanisms of NE-THCQ against renal fibrosis by integrating network pharmacology and experimental validation.


Turning chaotic sample group clusterization into organized ones by feature selection: Application on photodiagnosis of Brucella abortus serological test.
Bovine brucellosis diagnosis is a major problem to be solved; the disease has a tremendous economic impact with significant losses in meat and dairy products, besides the fact that it can be transmitted to humans. The sanitary measures instituted in Brazil are based on disease control through diagnosis, animal sacrifice, and vaccination. Although the currently available diagnostic tests show suitable quality parameters, they are time-consuming, and the incidence of false-positive and/or false-negative results is still observed, hindering effective disease control. The development of a low-cost, fast, and accurate brucellosis diagnosis test remains a need for proper sanitary measures at a large-scale analysis. In this context, spectroscopy techniques associated with machine learning tools have shown great potential for use in diagnostic tests. In this study, bovine blood serum was investigated by UV-vis spectroscopy and machine learning algorithms to build a prediction model for Brucella abortus diagnosis. Here we first pre-treated the UV raw data by using Standard Normal Deviate method to remove baseline deviation, then apply principal component analysis - a clustering method - to observe the group formation tendency; the first results showed no clustering tendency with a messy sample score distribution, then we properly select the main principal components to improve clusterization. Finally, by using machine learning algorithms (SVM and KNN), the predicting models achieved a 92.5% overall accuracy. The present methodology provides a test result in an average time of 5 min, while the standard diagnosis, with the screening and confirmatory tests, can take up to 48 h. The present result demonstrates the method's viability for diagnosing bovine brucellosis, which can significantly contribute to disease control programs in Brazil and other countries.


Privileged knowledge and mothers' "perceptions": the case of breast-feeding and insufficient milk in Bangladesh.
This article uses the example of breast-feeding and insufficient-milk syndrome in Bangladesh to illustrate the privileged status of professional discourse. While health professionals' discourse is given the status of scientific knowledge, the views and opinions expressed by breast-feeding women are referred to as "perceptions" and thus regarded as less objective. We use data gathered in two anthropological studies undertaken between 1987 and 1992 to examine some of the ambiguous qualities that breast-feeding mothers, their relatives, and health practitioners attribute to breast milk in Bangladesh. We discuss how old beliefs are incorporated into new systems and how bottles, which are associated with allopathy and science, provide a way of circumventing anxieties about female physiology and breast milk. Medical, religious, and popular ideas on breast-feeding and insufficient milk represent different intersecting discourses on the same theme-that female physiology and sexuality are problematic.


Regional patterns of brain activity in adults with a history of childhood-onset depression: gender differences and clinical variability.
The study investigated the hypothesis that EEG asymmetry scores (indicating higher right and lower left frontal brain activity) are associated with vulnerability to negative mood states and depressive disorders. Gender and clinical history variables were examined as factors that may influence the relation between EEG and depression. EEG measures of asymmetrical alpha frequency (7.5-12.5 Hz) suppression were analyzed in 55 young adults with a documented clinical history of childhood-onset depression and 55 comparison subjects with no history of major psychopathology. EEG patterns were examined in relation to operational diagnoses of mental disorders during childhood and adulthood. Differences in EEG asymmetry between childhood depression probands and comparison subjects varied with gender, diagnostic history, and current symptoms. Women with childhood depression had higher right midfrontal alpha suppression, and men with childhood depression had higher left midfrontal alpha suppression, relative to comparison subjects. At all scalp sites, women showed greater alpha power than men. Probands with a bipolar spectrum course had the most extreme midfrontal asymmetry. Frontal asymmetry was more extreme in probands with current depressive symptoms than in those without current symptoms. Regional brain activity is influenced by gender and variability in clinical course. The findings have implications for investigating brain correlates of mood disorder and may help to develop more refined phenotypes.


Nasal cavity metastasis of breast cancer: a case report and review of the literature.
The nasal cavity is an uncommon site for metastasis to develop and thus metastases arising from breast cancer are rarely observed. We report a case of a 61-year-old female with two-year history of breast cancer who presented with a nasal cavity that was diagnosed as metastatic breast carcinoma by histopathological analysis of the nasal cavity specimen. We reviewed the clinical records of the patient and the appropriate world literature. The patient had been diagnosed with breast cancer two years before. Her present complain was oculus dexter visual acuity decreased. CT and MRI scan revealed a palpable mass on the right nasal cavity. PET/CT demonstrated no additional uptake at the level of other organ. ER and PR demonstrated a similar expression pattern in primary breast carcinoma and nasal cavity lesions. As further treatment she received systemic palliative chemotherapy in addition to intravenous treatment with bisphosphonates, and a total dose of 36 Gy of X-ray (3 Gy per day, 12 fractions) was given to the local site of the right nasal cavity. In patient with a previous history of breast cancer who complains even of ophthalmologic symptoms such as visual acuity decreased, it is important to consider nasal cavity metastatic disease. 18FDG-PET/CT is useful to rule out the presence of other organ metastasis. Histopathological analysis may aid the diagnosis. The establishment of treatment strategies based on a comprehensive understanding of both etiology and pathophysiology is needed for rare cases such as this.


Genes and athletes.
Genetics plays an important role in determining characteristics desired for success in a given sport. Advances in biotechnology pose interesting and perplexing dilemmas for athletes, parents, health care providers, and society at large. Gene therapy holds great prospects for disease prevention and treatment. The same techniques also can be misused for genetic manipulation to enhance athletic prowess. This chapter reviews selective aspects of genotype influence on sport performance, uses and misuses of genetic technology, and ethical as well as legal dilemmas.


Toward a 3D cellular model for studying in vitro the outcome of photodynamic treatments: accounting for the effects of tissue complexity.
Clinical therapies have traditionally been developed using two-dimensional (2D) cell culture systems, which fail to accurately capture tissue complexity. Therefore, three-dimensional (3D) cell cultures are more attractive platforms to integrate multiple cues that arise from the extracellular matrix and cells, closer to an in vivo scenario. Here we report the development of a 3D cellular model for the in vitro assessment of the outcome of oxygen- and drug-dependent therapies, exemplified by photodynamic therapy (PDT). Using a synthetic self-assembling peptide as a cellular scaffold (RAD16-I), we were able to recreate the in vivo limitation of oxygen and drug diffusion and its biological effect, which is the development of cellular resistance to therapy. For the first time, the production and decay of the cytotoxic species singlet oxygen could be observed in a 3D cell culture. Results revealed that the intrinsic mechanism of action is maintained in both systems and, hence, the dynamic mass transfer effects accounted for the major differences in efficacy between the 2D and 3D models. We propose that this methodological approach will help to improve the efficacy of future oxygen- and drug-dependent therapies such as PDT.


Minor groove binder distamycin remodels chromatin but inhibits transcription.
The condensed structure of chromatin limits access of cellular machinery towards template DNA. This in turn represses essential processes like transcription, replication, repair and recombination. The repression is alleviated by a variety of energy dependent processes, collectively known as "chromatin remodeling". In a eukaryotic cell, a fine balance between condensed and de-condensed states of chromatin helps to maintain an optimum level of gene expression. DNA binding small molecules have the potential to perturb such equilibrium. We present herein the study of an oligopeptide antibiotic distamycin, which binds to the minor groove of B-DNA. Chromatin mobility assays and circular dichroism spectroscopy have been employed to study the effect of distamycin on chromatosomes, isolated from the liver of Sprague-Dawley rats. Our results show that distamycin is capable of remodeling both chromatosomes and reconstituted nucleosomes, and the remodeling takes place in an ATP-independent manner. Binding of distamycin to the linker and nucleosomal DNA culminates in eviction of the linker histone and the formation of a population of off-centered nucleosomes. This hints at a possible corkscrew type motion of the DNA with respect to the histone octamer. Our results indicate that distamycin in spite of remodeling chromatin, inhibits transcription from both DNA and chromatin templates. Therefore, the DNA that is made accessible due to remodeling is either structurally incompetent for transcription, or bound distamycin poses a roadblock for the transcription machinery to advance.


Coordination chemistry of phosphinocarbynes: phosphorus vs. carbyne site selectivity.
The phosphinocarbyne complex [W([triple bond, length as m-dash]CPPh2)(CO)2(Tp*)] (1: Tp* = hydrotris(dimethylpyrazolyl)borate) coordinates transition metal fragments via the phosphine to form bimetallic species [W{[triple bond, length as m-dash]CPPh2RhCl2(Cp*)}(CO)2(Tp*)] (2) and [W([triple bond, length as m-dash]CPPh2AuCl)(CO)2(Tp*)] (3). Appropriately tailored sterics allow for complexation of a second equivalent of AuCl to afford the trimetallic complex [W{η2-C(AuCl)PPh2AuCl}(CO)2(Tp*)] (4), containing an Au-W-C dimetallacyclopropene connectivity. Similarly, AuCl binds to the carbyne linkage in [W{[triple bond, length as m-dash]CP([double bond, length as m-dash]S)Ph2}(CO)2(Tp*)], yielding [W{η2-C(AuCl)P([double bond, length as m-dash]S)Ph2}(CO)2(Tp*)] (5). In the case of auration of the ditungsten species [W2(μ-C2PPh)(CO)4(Tp*)2] (6), variation in the stoichiometry leads to trimetallic [W2(μ-C2PPhAuCl)(CO)4(Tp*)2] (7) and pentametallic [W2{μ-(η2-CAuCl)2PPhAuCl}(CO)4(Tp*)2] (8) complexes, via a proposed tetrametallic intermediate [W2{μ-(η2-CAuCl)2PPh}(CO)4(Tp*)2], the site selectivity being dictated by aurophilic interactions.


An investigation of white matter integrity and attention deficits following traumatic brain injury.
This study aimed to investigate the association between white matter tracts and multiple aspects of attention and working memory deficits in a relatively acute traumatic brain injury (TBI) sample. Neuropsychological measures of attention and working memory were administered to 20 participants with complicated mild-to-very severe TBI and 20 control participants. Tract-based spatial statistics was used to assess fractional anisotropy (FA) and mean diffusivity (MD) of white matter tracts for 15 TBI participants and 20 controls. When compared to controls, participants with TBI were found to have lower FA (p < 0.001) and higher MD (p < 0.001) values in the majority of white matter tracts. TBI participants were also slower to complete tasks including Trail Making Test, Hayling, computerized Selective Attention Task, n-back and Symbol Digit Modalities Test (p < 0.001), when compared to controls. When controlling for age and estimated premorbid intelligence, slowed information processing speed following TBI was found to be associated with FA values in the corpus callosum, superior longitudinal fasciculus, cingulum, inferior fronto-occipital fasciculi, corona radiata and cerebral white matter. The results highlight the widespread damage associated with TBI, as well as the impact of these alterations on information processing speed.


Polarographic measurement of oxygen uptake using lipoxygenase in reverse micelles.
Lipoxygenase-catalyzed linoleic acid peroxidation was chosen as a model system to study the applicability of oxygraphy to monitor the oxygen uptake in organic solvents containing reverse micelles. Care was taken to control the oxygen back transfer from the atmosphere to the sample micellar solution, resulting in a significant improvement of electrode response. Under these conditions, lipoxygenase activity was linear up to 100 mug of enzyme. Given the quality of the calibration curve and the good correlation between lipoxygenase and ascorbate oxidase, the described technique is proposed as an alternative method for determining lipoxygenase activity in reverse micelles. The reliability of this technique was confirmed by the good agreement between polarography and classic spectrophotometry in kinetic studies. Preliminary experiments carried out on soybean cells solubilized in a Tween 85-isopropylpalmitate system demonstrated that a light-dependent oxygen uptake can be measured. The authors propose that the Clark-type electrode be employed to study both the activity of oxidasic enzymes in reverse micelles and cell viability and physiology in organic solvents.


Nucleoid Associated Proteins: The Small Organizers That Help to Cope With Stress.
The bacterial chromosome must be efficiently compacted to fit inside the small and crowded cell while remaining accessible for the protein complexes involved in replication, transcription, and DNA repair. The dynamic organization of the nucleoid is a consequence of both intracellular factors (i.e., simultaneously occurring cell processes) and extracellular factors (e.g., environmental conditions, stress agents). Recent studies have revealed that the bacterial chromosome undergoes profound topological changes under stress. Among the many DNA-binding proteins that shape the bacterial chromosome structure in response to various signals, NAPs (nucleoid associated proteins) are the most abundant. These small, basic proteins bind DNA with low specificity and can influence chromosome organization under changing environmental conditions (i.e., by coating the chromosome in response to stress) or regulate the transcription of specific genes (e.g., those involved in virulence).


Sex-specific differences and predictors of echocardiographic measures of diastolic dysfunction in rhesus macaques (Macaca mulatta).
Diastolic dysfunction in humans is an age-related process with an overrepresentation in women. In rhesus macaques (Macaca mulatta), the incidence and predictors of diastolic dysfunction have yet to be reported. Data from routine echocardiographic evaluations on clinically healthy rhesus macaques was obtained and used for univariate, bivariate, hypothesis testing, and linear regression statistical analyses interrogating differences and predictors of diastolic function. Rhesus macaques fully recapitulate previously reported human hemodynamic studies. Female monkeys display impaired diastology and are at an increased risk for developing diastolic dysfunction. Age, sex, and proxies of exercise activity are confirmed predictors for measures of diastolic dysfunction, regardless of specific pathogen-free status. Rhesus macaques share common sex- and age-related echocardiographic findings as humans, therefore, serve as a valuable translational nonhuman primate model for future studies of diastolic dysfunction. These findings confirm the importance of sex- and age-matching within future rhesus macaque cardiovascular research.


[Attitude of general practitioners faced to schizophrenia].
The chronic character of schizophrenia, the suffering that it generates, its triple social and human economic cost, make of it a major stake of public health. The general practitioners are the first actors in the tracking of onset schizophrenia and the follow-up of this chronic pathology. To study knowledge, the attitudes and the practices of the general practitioners faced to schizophrenia. A descriptive cross-sectional study, using an auto questionnaire, including 300 general practitioners registered in the table of the order of the Doctors of the area of Large Tunis, exerting in private and public sectors. The rate of answer was 22.6% (68) of general practitioners. The middle age of the participants was 48.1 years (± 8.3). The sex ratio was 1.6; including 58.8% exerting in the private sector. Meadows the fifth (19.1%) of them knew the exact prevalence of schizophrenia in the general population, whereas 77.9% did not have any idea of the rate of suicide among patients. 76.5% of the doctors estimated that prodromal signs preceded the emergence of schizophrenia. The odd behaviors, hallucinations/delirum and social withdrawal constituted the most evocative symptoms in respectively 80.8%; 79.4% and 64.7%. In case of onset- schizophrenia; 20.5% of the experts thought that it was not necessary to prescribe any treatment and 48.5% were unable to mention the exact drug to be prescribed in case of first episode psychotic. Our results highlight gaps in knowledge and the practical conduits of the general practitioners faced to schizophrenia. Measurements aiming the improvements in education and the sensitizing of the general practitioners are necessary.


Burn Injuries: Prevention, Advocacy, and Legislation.
Each year in the United States and Canada, thousands of individuals seek medical care for a burn injury. Some individuals are burned significantly enough they require treatment at specialized burn care facilities. Most of these injuries are preventable. This article presents an historical perspective related to burn prevention and elements of successful burn prevention programs and explores ways in which the plastic surgeon can promote burn prevention through education, advocacy, and the legislative process. Prevention efforts undertaken by the surgeon can increase awareness, ensure a safe environment, and reduce burn injuries.


A new 3D-printed polylactic acid-bioglass composite for bone tissue engineering induces angiogenesis in vitro and in ovo.
Large bone defects such as those that occur after trauma or resections due to cancer still are a challenge for surgeons. Main challenge in this area is to find a suitable alternative to the gold-standard therapy, which is highly risky, and a promising option is to use biomaterials manufactured by 3D printing. In former studies, we demonstrated that the combination of polylactic acid (PLA) and bioglass (BG) resulted in a stable 3D-printable material, and porous and finely structured scaffolds were printed. These scaffolds exhibited osteogenic and anti-inflammatory properties. This 3D-printed material fulfills most of the requirements described in the diamond concept of bone healing. However, the question remains as to whether it also meets the requirements concerning angiogenesis. Therefore, the aim of this study was to analyze the effects of the 3D-printed PLA-BG composite material on angiogenesis. In vitro analyses with human umbilical vein endothelial cells (HUVECs) showed a positive effect of increasing BG content on viability and gene expression of endothelial markers. This positive effect was confirmed by an enhanced vascular formation analyzed by Matrigel assay and chicken chorioallantoic membrane (CAM) assay. In this work, we demonstrated the angiogenic efficiency of a 3D-printed PLA-BG composite material. Recalling the osteogenic potential of this material demonstrated in former work, we manufactured a mechanically stable, 3D-printable, osteogenic and angiogenic material, which could be used for bone tissue engineering.


[The first selective coronarographies in the former Czecho-Slovakia].
The study observes the history and the beginning of selective coronarographies performed in the territory of the Slovak Republic. The first aortocoronary bypass in Slovakia was performed in Bratislava. It was realized by the team of the Surgical Clinic of Academician Dérer in november 1969, namely on the basis of coronarographic examinations which were performed by Smrecanský, Cagán and Krajcovic. Coronographies have been performed in the Central X-ray Department of the Hospital and Clinic of Academician Dérer since the end of the year 1968. During the period of december 1968 to june 1970 selective coronographies were realized in 70 patients and they represented the first performances of this method in former Czechoslovakia. (Ref. 8.)


Isolation and structure of the mouse 14-3-3 eta chain gene and the distribution of 14-3-3 eta mRNA in the mouse brain.
14-3-3 protein is a brain-specific protein discovered by Moore and Perez, but at present is thought to be a multifunctional protein. To clarify the brain-specific function of the protein, we intend constructing a 14-3-3 eta gene knock-out mouse. As the first step of this process, we isolated the mouse 14-3-3 eta chain gene and determined its structure. The mouse gene is about 10 kb long and composed of two exons separated by a long intron. The transcription start site was identified and the polyadenylation signals (AATAAA) were found in exon 2 of the mouse gene. In the 5'-upstream sequence, we found several cis elements including a CRE sequence, a TATA box-like sequence, and a C/EBP element. Furthermore, the distribution of 14-3-3 eta mRNA in the mouse brain was examined by in situ hybridization histochemistry. The highest signals were found in the Purkinje cells of the cerebellum, the pyramidal cells of the hippocampus and the olfactory bulb neurons of the adult mouse. Neuronal expression of 14-3-3 eta in these regions mRNA may generally increase during postnatal brain development. The distribution of protein kinase C gamma in the mouse brain was also examined by immunohistochemistry. From the distribution of 14-3-3 eta mRNA and protein kinase C gamma in the mouse brain, the involvement of these compounds in the induction and maintenance of LTP was discussed.


Comparison of xeromammography and film mammography in the diagnosis of breast lesions.
A comparative study of xeromammography and film mammography was terminated after 104 patients had undergone treatment, as it was readily appreciated that the xerograms provided increased information and detail. Apart from skin thickening and skin retraction, image quality for all other anatomical structures in the breast is greatly superior on xerograms and microcalcification is particularly well shown. Xerograms are more easily interpreted provided the radiologist has been given the necessary training, and the over-all accuracy is greater than that achieved by film mammography.