Encapsulation of bilayer vesicles by self-assembly.
Vesicles of lipid bilayers have been investigated as drug-delivery vehicles for almost 20 years. The vesicles' interior space is separated from the surrounding solution because small molecules have only limited permeability through the bilayer. Single-walled (unilamellar) vesicles are made by a variety of non-equilibrium techniques, including mechanical disruption of lamellar phases by sonication or extrusion through filters, or chemical disruption by detergent dialysis or solvent removal. These techniques do not, however, allow the encapsulation of a specific volume, nor can they be used to encapsulate other vesicles. Here we show that molecular-recognition processes mediated by lipophilic receptors and substrates (here the biotin-streptavidin complex) can be used to produce a multicompartmental aggregate of tethered vesicles encapsulated within a large bilayer vesicle. We call these encapsulated aggregates vesosomes. Encapsulation is achieved by unrolling bilayers from cochleate cylinderss which are tethered to the aggregate by biotin-streptavidin coupling. These compartmentalized vesosomes could provide vehicles for multicomponent or multifunctional drug delivery; in particular, the encapsulating membrane could significantly modify permeation properties, or could be used to enhance the biocompatibility of the system.


[Ultrasonography as a method to determine the correct implantation of intratubaric devices].
Essure procedure consists in the placement of two coils in the intramural segment of Fallopian tubes by hysteroscopic causing a fibrosis reaction that unleashes a physiological obstruction. Hysterosalpingography, until today, is the gold standard checking the success of this method of sterilization. Determining if a scan at three months postimplantation is sufficient to confirm the correct positioning of the device. Descriptive study with 61 patients undergoing definitive hysteroscopic sterilization to validate transvaginal ultrasound as a technique to determine the effectiveness of the method. There were placed 120 devices, of which 117 (97'5%) were visible by ultrasound. Comparing ultrasound findings with gold standard, we obtain that in cases of proper bilateral implantation by hysterosalpingography, with ultrasound we diagnosed the 81 '13%; in cases of correct unilateral implantation we detected 75% with ultrasound, except one patient who was considered proper placement of the coil by ultrasound but hysterosalpingography reported that it was misplaced and the Fallopian tube was permeable. Transvaginal ultrasound is an appropriate method to confirm the correct position of intratubaric Essure devices, its safety, low cost and reproducibility. However, our study cannot replace the hysterosalpingography as gold standard.


Surgical management of craniosynostosis.
With an incidence of approximately 1 in 2,000 per head of population, most neurosurgeons are presented at times with the problem of craniosynostosis. This paper summarises the different clinical effects of different skull deformities, and describes the present state of the art with regard to surgical management.


Role of AMP-activated protein kinase during postovulatory aging of mouse oocytes†.
Studies suggested that postovulatory oocyte aging might be prevented by maintaining a high maturation-promoting factor (MPF) activity. Whether AMP-activated protein kinase (AMPK) plays any role in postovulatory oocyte aging is unknown. Furthermore, while activation of AMPK stimulates meiotic resumption in mouse oocytes, it inhibits meiotic resumption in pig and bovine oocytes. Thus, the species difference in AMPK regulation of oocyte MPF activities is worth in-depth studies. This study showed that AMPK activation with metformin or 5-aminoimidazole- 4-carboxamide- 1-beta-d- ribofuranoside and inactivation with compound C significantly increased and decreased, respectively, the activation susceptibility (AS) and other aging parameters in aging mouse oocytes. While AMPK activity increased, MPF activity and cyclic adenosine monophosphate (cAMP) decreased significantly with time post ovulation. In vitro activation and inactivation of AMPK significantly decreased and increased the MPF activity, respectively. MPF upregulation with MG132 or downregulation with roscovitine completely abolished the effects of AMPK activation or inactivation on AS of aging oocytes, respectively. AMPK facilitated oocyte aging with increased reactive oxygen species (ROS) and cytoplasmic calcium. Furthermore, treatment with Ca2+/calmodulin-dependent protein kinase (CaMK) inhibitors significantly decreased AS and AMPK activation. Taken together, the results suggested that AMPK facilitated oocyte aging through inhibiting MPF activities, and postovulatory oocyte aging activated AMPK with decreased cAMP by activating CaMKs via increasing ROS and cytoplasmic calcium.


Topographic Sonoanatomy of Infraclavicular Brachial Plexus: Variability and Correlation with Anthropometry.
The aim of the study was to assess the effectiveness of ultrasound in analyzing topographic relationship of nerve cords with axillary artery at lateral infraclavicular level, their variations, and the distance from the skin and to correlate findings with anthropometric parameters. Two hundred patients aged 18-75 years were enrolled for the study after informed written consent. A 7-12 MHz linear ultrasonic transducer was used for scanning of the brachial plexus at lateral infraclavicular fossa. The results of the cord positions were expressed on a 12-section pie chart, and the number of arteries and veins was reported. Measurements included the vertical distance from the upper part of the artery to the skin, diagonal distance to the apical corner of the ultrasound image, and distances from center of cords to the center of artery. Age, sex, weight, height, body mass index, and biceps girth were recorded. Data were expressed as mean with standard deviation or frequency and percentage for categorical variables, and statistical analysis was done using correlation analysis and two-sample t-test. The most frequent positions of the cords were observed in 2-4 sections (92%) for the medial cord, 6-7 sections (92%) for the posterior cord, 10-11 sections (89%) for the lateral cord, and 4-5 sections (95%) for the axillary vein. More than one axillary vein was seen in 12.5% and two axillary arteries were seen in 1.5% of cases. Cord visibility and distance between artery and apical corner of the ultrasound image correlated with anthropometric parameters. A topographical study of brachial plexus at lateral infraclavicular fossa showed anatomical variations and abnormal vascular formations. This sonoanatomic knowledge can be helpful in improving safety and success of nerve blocks.


Clinical Parameters Are More Likely to Be Associated with Thyroid Hormone Levels than with Thyrotropin Levels: A Systematic Review and Meta-Analysis.
Background: Though the functional states of other endocrine systems are not defined on the basis of levels of controlling hormones, the assessment of thyroid function is based on levels of the controlling hormone thyrotropin (TSH). We, therefore, addressed the question as to whether levels of thyroid hormones [free thyroxine (fT4), total triiodothyronine (TT3)/free triiodothyronine (fT3)], or TSH levels, within and beyond the reference ranges, provide the better guide to the range of clinical parameters associated with thyroid status. Methods: A PubMed/MEDLINE search of studies up to October 2019, examining associations of levels of thyroid hormones and TSH, taken simultaneously in the same individuals, with clinical parameters was performed. We analyzed atrial fibrillation, other cardiac parameters, osteoporosis and fracture, cancer, dementia, frailty, mortality, features of the metabolic syndrome, and pregnancy outcomes. Studies were assessed for quality by using a modified Newcastle-Ottawa score. Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed. A meta-analysis of the associations was performed to determine the relative likelihood of fT4, TT3/fT3, and TSH levels that are associated with the clinical parameters. Results: We identified 58 suitable articles and a total of 1880 associations. In general, clinical parameters were associated with thyroid hormone levels significantly more often than with TSH levels-the converse was not true for any of the clinical parameters. In the 1880 considered associations, fT4 levels were significantly associated with clinical parameters in 50% of analyses. The respective frequencies for TT3/fT3 and TSH levels were 53% and 23% (p < 0.0001 for both fT4 and TT3/fT3 vs. TSH). The fT4 and TT3/fT3 levels were comparably associated with clinical parameters (p = 0.71). More sophisticated statistical analyses, however, indicated that the associations with TT3/fT3 were not as robust as the associations with fT4. Conclusions: Thyroid hormones levels, and in particular fT4 levels, seem to have stronger associations with clinical parameters than do TSH levels. Associations of clinical parameters with TSH levels can be explained by the strong negative population correlation between thyroid hormones and TSH. Clinical and research components of thyroidology currently based on the measurement of the thyroid state by reference to TSH levels warrant reconsideration.


Asphyxia in Motor Vehicle Crashes: Analysis of Crash-Related Variables Using National Automotive Sampling System Crashworthiness Data System and Forensic Case Studies.
Rates of death because of asphyxia in motor vehicle crashes have been previously estimated using county and statewide data sets, but national estimates have not been reported. The literature regarding asphyxia in motor vehicle crashes primarily involves discussions about clinical findings, and crash-related variables have been sparsely reported. The current study calculated a nationwide fatality rate for asphyxia in motor vehicle crashes of 1.4%. Seventeen case studies of asphyxia were also reported providing crash-, vehicle-, and occupant-related variables. These included type of accident, crash severity, seat belt use, containment status, extent of occupant compartment intrusion, height, weight, and injury pattern. The data presented can be used to better understand the injury mechanism, identify risk factors, develop possible protective countermeasures, and create situational awareness for emergency responders and investigators.


Supercoiling in prokaryotic and eukaryotic DNA: changes in response to topological perturbation of plasmids in E. coli and SV40 in vitro, in nuclei and in CV-1 cells.
Changes in DNA linking number have been observed in plasmid DNA purified from E. coli cells after the cells were treated with chloroquine. Chloroquine, a DNA intercalating drug, unwinds the DNA, decreasing the levels of negative supercoiling. Following this in vivo topological perturbation, within minutes DNA gyrase decreases DNA linking number producing more negatively supercoiled DNA topoisomers. Following the removal of the drug from cells, within minutes topoisomerase 1 or DNA gyrase increases the linking number restoring the original level of supercoiling. Analogous changes in DNA linking number after addition of chloroquine are observed in purified plasmid DNA, and in purified SV40 minichromosomes in the presence of exogenous topoisomerase. Changes in linking number are also observed in SV40 chromosomes in isolated nuclei and in SV40 DNA purified from CV-1 cells following topological perturbation with chloroquine. These results suggest that eukaryotic cells may have mechanisms to maintain a defined level of DNA supercoiling.


Ab initio investigation of the complexes between bromobenzene and several electron donors: some insights into the magnitude and nature of halogen bonding interactions.
Halogen bonding, a specific intermolecular noncovalent interaction, plays crucial roles in fields as diverse as molecular recognition, crystal engineering, and biological systems. This paper presents an ab initio investigation of a series of dimeric complexes formed between bromobenzene and several electron donors. Such small model systems are selected to mimic halogen bonding interactions found within crystal structures as well as within biological molecules. In all cases, the intermolecular distances are shown to be equal to or below sums of van der Waals radii of the atoms involved. Halogen bonding energies, calculated at the MP2/aug-cc-pVDZ level, span over a wide range, from -1.52 to -15.53 kcal/mol. The interactions become comparable to, or even prevail over, classical hydrogen bonding. For charge-assisted halogen bonds, calculations have shown that the strength decreases in the order OH- > F- > HCO2- > Cl- > Br-, while for neutral systems, their relative strengths attenuate in the order H2CS > H2CO > NH3 > H2S > H2O. These results agree with those of the quantum theory of atoms in molecules (QTAIM) since bond critical points (BCPs) are identified for these halogen bonds. The QTAIM analysis also suggests that strong halogen bonds are more covalent in nature, while weak ones are mostly electrostatic interactions. The electron densities at the BCPs are recommended as a good measure of the halogen bond strength. Finally, natural bond orbital (NBO) analysis has been applied to gain more insights into the origin of halogen bonding interactions.


Choroidal Changes at the Leakage Site in Acute Central Serous Chorioretinopathy.
Purpose: To analyze the choroidal vasculature at leak site and at the center of macula in acute central serous chorioretinopathy (CSCR) and to evaluate their co-relation with eccentricity of leak site. Methods: This retrospective study involved optical coherence tomography analysis of 27 eyes with acute CSCR. Relationship between macular thickness; large choroidal vessels diameter; baseline subfoveal and leakage point choroidal thickness, and eccentricity of leak point was evaluated. Results: A larger choroidal vessel caliber/choroidal thickness ratio was found at the leak site than fovea in both active (p = 0.0001) and resolved (p = 0.003) CSCR. Ratio at leakage point decreased after resolution of SRF (p = 0.004). Choroidal thickness at subfovea (p = 0.004), leakage point (p = 0.02); and difference between central and leakage point choroidal thickness (r = 0.6, p = 0.009) were significantly associated with the eccentricity of leakage point. Conclusion: Subfoveal and leak site choroidal profile could predict the eccentricity of leakage in CSCR.


Development of ecotoxicity assay based on inhibition of respiring activity in microbial community using XTT reduction.
The aim of this study is to develop ecotoxicity assay for evaluating the influence of chemicals on a microbial ecosystem based on XTT reduction inhibition (XTT assay). XTT reduction method is used for quantification of the microbial respiratory activity. Since the XTT assay indicates the inhibition of microbial respiratory activity, it could evaluate the toxicity of chemicals. Suitable conditions for the XTT assay were determined to be 200 mg/L of particulate organic carbon as test microbe concentration and 15 min of assay time using activated sludge. Toxicities of several chemicals evaluated by activated sludge as test microbes were examined under these conditions. Sensitivity for the toxicity evaluated by the XTT assay using activated sludge microbes was almost the same value was that for the OECD activated sludge respiration inhibition test (ASRI test). XTT assay was also applied for evaluating the influence of chemicals on the soil microbial community and the XTT assay was used to evaluate a median effective concentration (EC(50)) value of 3,5-dichlorophenol (3,5-DCP). The EC(50) value of 3,5-DCP was almost the same as the value using activated sludge as test microbes. These results suggest that the XTT assay using both mixed cultures of non-contaminated environments and chemical extracts from various contaminated environments could evaluate the influence on microbial ecosystems affected by toxic chemicals.


Metals in boat paint fragments from slipways, repair facilities and abandoned vessels: an evaluation using field portable XRF.
Paint flaking off abandoned vessels or generated during boat repair is hazardous to human health and wildlife. In this study, a means of screening paint fragments using a field portable-X-ray fluorescence (FP-XRF) spectrometer is described. The technique is capable of delivering rapid, surficial measurements of Ba, Cu, Pb and Zn down to concentrations less than 150 μg g(-1), and Sn and Cr to concentrations of a few hundred μg g(-1). Application of the technique to fragments collected from slipways, yards, hardstandings, abandoned boats and ships undergoing maintenance throughout the EU reveal highly variable concentrations of metals among samples from the same environment or from the same region of a given boat; in many cases, variability is also evident in different areas or on different surfaces of the same fragment. Of particular concern are elevated concentrations of substances that have been restricted or banned (e.g. Sn, an indicator of organotin, and up to concentrations of 40,000 μg g(-1), and Pb up to concentrations of 200,000 μg g(-1)). Although FP-XRF can rapidly screen samples whose composition and origin are unknown and can assist in instantaneous decision making, a full risk assessment will rely on additional analyses of the precise species (including organo-forms) of the metals present.


Activation of group I mGluRs elicits different responses in murine CA1 and CA3 pyramidal cells.
The group I metabotropic glutamate receptor agonist DHPG has been shown to produce two major effects on CA3 pyramidal cells at rest: a reduction in the background conductance and an activation of a voltage-gated inward current (I(mGluR(V))). Both effects contribute to depolarising CA3 pyramidal cells and the latter has been implicated in eliciting prolonged epileptiform population bursts. We observed that DHPG-induced depolarisation was smaller in CA1 pyramidal cells than in CA3 cells. Voltage clamp studies revealed that while DHPG elicited I(mGluR(V)) in CA3 pyramidal cells, such a response was absent in CA1 pyramidal cells. Both mGluR1 and mGluR5 have been localised in CA3 pyramidal cells, whereas only mGluR5 has been detected in CA1 pyramidal cells. Using mGluR1 knockout mice, we evaluated whether the absence of an I(mGluR(V)) response can be correlated with the absence of mGluR1. In these experiments, DHPG failed to elicit I(mGluR(V)) in CA3 pyramidal cells. This suggests that the smaller depolarising effects of DHPG on wild-type CA1 pyramidal cells is caused, at least in part, by the absence of I(mGluR(V)) in these cells and that the difference in the responses of CA1 and CA3 cells may be attributable to the lack of mGluR1 in CA1 pyramidal cells.


Geometric-phase-based axicon lens for computational achromatic imaging.
Conventional optical imaging systems usually utilize several lenses within a precise assembly to eliminate chromatic aberration, which increases the difficulty of system integration. In recent years, with the rapid development of metasurfaces and liquid crystals (LCs), planar optical elements provide feasible solutions to realize flexible light manipulation and lightweight systems. However, there also exists chromatic aberration, which can be corrected but at the cost of a complex device design. Here, a geometric-phase-based axicon lens is utilized to correct chromatic aberration across a broadband wavelength with the assistance of a post-process algorithm. The axicon lens is fabricated through arranging orientations of liquid-crystal molecules with a standard photoalignment technique, and it produces an approximately invariant point spread function (PSF) at several discrete wavelengths, which is used as the prior information to extract the object in the blurred image. In the experiment, the reconstruction quality is significantly improved after the post-process algorithm. We expect our work to provide further development to reduce the dispersion with both the device design and the computational image technique.


Renal imino acid and glycine transport system ontogeny and involvement in developmental iminoglycinuria.
Renal maturation occurs post-natally in many species and reabsorption capacity at birth can vary substantially from the mature kidney. However, little is known regarding the maturation of amino acid transport mechanisms, despite the well-known physiological state of developmental iminoglycinuria. Commonly seen during early infancy, developmental iminoglycinuria is a transient version of the persistent inherited form of the disorder, referred to as iminoglycinuria, and manifests as a urinary hyperexcretion of proline, hydroxyproline and glycine. The transporters involved in developmental iminoglycinuria and their involvement in the improvement of renal reabsorption capacity remain unknown. qPCR (quantitative real-time PCR) and Western blot analysis in developing mouse kidney revealed that the expression of Slc6a18, Slc6a19, Slc6a20a and Slc36a2 was lower at birth (approx. 3.4-, 5.0-, 2.4- and 3.0-fold less than adult kidney by qPCR respectively) and increased during development. Furthermore, immunofluorescence confocal microscopy demonstrated the absence of apical expression of Slc6a18, Slc6a19, Slc6a20a and the auxiliary protein collectrin in kidneys of mice at birth. This correlated with the detection of iminoglycinuria during the first week of life. Iminoglycinuria subsided (proline reduction preceded glycine) in the second week of life, which correlated with an increase in the expression of Slc6a19 and Slc6a20a. Mice achieved an adult imino acid and glycine excretion profile by the fourth week, at which time the expression level of all transporters was comparable with adult mice. In conclusion, these results demonstrate the delayed expression and maturation of Slc6a18, Slc6a19, Slc6a20a and Slc36a2 in neonatal mice and thus the molecular mechanism of developmental iminoglycinuria.


[Length of service as a nurse: continuing to burnout?].
Medical professionals are particularly exposed to stress. It is therefore important for them to learn how to cope with work stress and prevent burnout. This study was undertaken in a group of nurses from the province of Kuyavia and Pomerania to determine the extent to which strategies and attitudes required for work effectiveness change with length of service. Four groups were formed according to seniority: up to 15 years, 16-20 years, 21-25 years, and more than 25 years at work. The survey instrument was the AVEM questionnaire consisting of scales which cover the following personality domains: commitment to service, resistance to stress, problem-solving strategies, emotional well-being at work. The results were analyzed basing on percentile norms for hospital staff. It was found that career ambitions and offensive problem-solving strategies correlate with length of service. Nurses with the shortest length of service were least active in coping with problems. Competence increased with seniority. The distribution of results regarding career ambitions was greatest in group 3 (15-25 years at work). It seems plausible that on the one hand this finding can be attributed to seniority, on the other to different social roles undertaken concurrently. Qualitative assessment of the present results demonstrated that commitment to service is important for nurses regardless of work experience. This study did not take into account the total personality structure as a modifying variable which determines the direction of personal development, including professional development, and integrates human activities.


[Turnover Experience of Male Nurses].
The aim of this study was to identify turnover experiences of men in nursing and to derive a substantive theory on the turnover experience of men who are nurses. Data were collected through in-depth interviews with 13 men who had worked as a nurse for 1 year or more, and had a turnover experience during that period. Collected data were analyzed on the basis of Strauss and Corbin's grounded theory. The core category in the turnover experiences of the respondents was 'seeking a stable place for me'. In the analysis of the core category, types of 'contentment', 'seeking', 'survival' and 'confusion' were identified. The sequential stages of these nurses' turnover experience were 'confrontation', 'incertitude', 'retrying' and 'realization'. However, when a problem arose in the process, they returned to the stage of confusion. Thus, these stages could occur in a circular fashion. These findings provide a deep understanding of the turnover experience of men in nursing and offers new information about how they adapt to nursing practice. The findings should be useful as foundational data for men who hope to become nurses and also for managers responsible for nurses who are men.


Design, construction, and performance of a device for directional recrystallization of metallic alloys.
A device was designed to apply the directional recrystallization method to Fe-based alloys in order to obtain bamboo-like microstructures. This microstructure is suitable for improving creep properties and resistance to fatigue in some alloys and for enhancing pseudoelastic properties in shape memory alloys. The design and construction of a flat coil are described in detail. In addition, we developed an electromechanical system to control the movement of a wire within the flat coil. The construction details and system performance are presented. Furthermore, metallographic studies taken from the directionally recrystallized low-carbon steel samples are shown. Nearly monocrystalline and bamboo-like microstructures were achieved in the steel wires.


Differential modulation by exogenous carbon monoxide of TNF-alpha stimulated mitogen-activated protein kinases in rat pulmonary artery endothelial cells.
Heme oxygenase-1 (HO-1) is an enzyme that is highly inducible by various cellular stressors, especially oxidant injury. Our laboratory and others have demonstrated that induction of HO-1 exerts an antiinflammatory effect both in vitro and in vivo. We hypothesized that carbon monoxide (CO), a major catalytic byproduct of heme catalysis by HO-1, may mediate this antiinflammatory effect by modulating signal transduction pathways, in particular the mitogen-activated protein (MAP) kinase pathway. Confluent primary cultures of rat pulmonary artery endothelial cells (RPAEC) were treated with tumor necrosis factor-alpha (TNF-alpha; 50 ng/ml), and whole-cell extracts were assayed for phosphorylated ERK1/2, JNK1/2, and p38 MAP kinases. These three major MAP kinase pathways were activated by TNF-alpha in a time-dependent manner. RPAEC treated with TNF-alpha in the presence of a low concentration of CO (1%) exhibited marked attenuation of the phosphorylation of ERK1/2 MAP kinase when compared with cells treated with TNF-alpha alone. A similar effect was seen on the upstream MEK 1/2 kinase. Interestingly, CO (1%) accentuated TNF-alpha-induced phosphorylated p38 MAP kinase. These effects of exogenous CO on the ERK1/2 and p38 systems could be replicated by overexpression of HO-1 in RPAEC, using an adenoviral vector. As these MAP kinases are implicated in the regulation of various inflammatory molecules and adhesion molecules, our data provide a potential mechanism by which HO-1, acting via CO, may modulate the inflammatory response by differential activation of the MAP kinase pathway.


Primary small bowel malignant tumors. Unrecognized until emergent laparotomy.
Forty-five consecutive cases of primary small bowel malignant tumors treated at our institution from 1969-1983 were reviewed. Sixty-four per cent of the patients had surgical emergencies. Fourteen patients had intestinal obstruction, 11 had gastrointestinal (GI) hemorrhage, and 4 had perforation of the small bowel. The remaining 16 patients were explored for persistent symptoms, an abnormality on GI series, or a mass lesion on CT scan. Thirty-eight patients underwent resection of the tumor and seven had palliative bypass procedures. This study suggests that a high index of suspicion and early diagnostic evaluation including a small bowel series is necessary to prevent the large number of small bowel tumors presenting as surgical emergencies. In particular, small bowel tumors should be suspected in patients with abdominal pain of unknown etiology, unexplained weight loss, or occult GI bleeding.


Molecular system bioenergetics: regulation of substrate supply in response to heart energy demands.
This review re-evaluates regulatory aspects of substrate supply in heart. In aerobic heart, the preferred substrates are always free fatty acids, and workload-induced increase in their oxidation is observed at unchanged global levels of ATP, phosphocreatine and AMP. Here, we evaluate the mechanisms of regulation of substrate supply for mitochondrial respiration in muscle cells, and show that a system approach is useful also for revealing mechanisms of feedback signalling within the network of substrate oxidation and particularly for explaining the role of malonyl-CoA in regulation of fatty acid oxidation in cardiac muscle. This approach shows that a key regulator of fatty acid oxidation is the energy demand. Alterations in malonyl-CoA would not be the reason for, but rather the consequence of, the increased fatty acid oxidation at elevated workloads, when the level of acetyl-CoA decreases due to shifts in the kinetics of the Krebs cycle. This would make malonyl-CoA a feedback regulator that allows acyl-CoA entry into mitochondrial matrix space only when it is needed. Regulation of malonyl-CoA levels by AMPK does not seem to work as a master on-off switch, but rather as a modulator of fatty acid import.


Factors Influencing Rural Physician Retention Following Completion of a Rural Training Track Family Medicine Residency Program.
Rural training track residency programs were created to aid in addressing the shortage of rural physicians. While these programs have been shown to increase rural recruitment and retention, the reasons for improved retention are unclear. We analyzed survey results of 16 graduates of the UW-Baraboo Rural Training Track Family Medicine Residency Program on which factors influenced rural retention. Participants cited the wishes of significant others, meaningful work, and integration into the local community as the most important factors in rural retention. Loan repayment and teaching opportunities were least important. The factors identified in this study as important to rural retention were supported by previous literature and have remained consistent over time for rural physicians, including rural training track graduates. Rural Training Track alumni physicians in our study found similar factors important to rural retention when compared to other rural physicians in the United States reported in the literature, regardless of residency background. These factors continue to be important to shape retention strategies employed by rural health care systems; future studies should evaluate rural retention strategies that utilize these factors.


Creation of macroporous calcium phosphate cements as bone substitutes by using genipin-crosslinked gelatin microspheres.
Macroporous calcium phosphate cements (CPCs) were developed using genipin-crosslinked gelatin microspheres (GMs) with two weight ratios (2.5 wt% and 5 wt%). The initial setting time of the composite was prolonged by GMs. After GMs/CPCs were soaked in phosphate-buffered saline (PBS) for several weeks, macropores appeared as a result of the degradation of GMs. The presence of GMs accelerated the setting reaction and improved the structure of the composite. The compressive strength increased up to 12 MPa (2.5 wt% GMs/CPCs) and 14 MPa (5 wt% GMs/CPCs) after one week of PBS soaking, then gradually decreased to 9 MPa (2.5 wt% GMs/CPCs) and 7 MPa (5 wt% GMs/CPCs) after three weeks of soaking, and further to 6 MPa (2.5 wt% GMs/CPCs) and 2 MPa (5 wt% GMs/CPCs) after five weeks of soaking. CPCs with 2.5 wt% GMs were the most favorable composite in the tested samples. Cell experiments showed that rat osteoblasts displayed normal morphologies when exposed to the 2.5 wt% GMs/CPCs, and proliferation of the cells was also enhanced. An in vivo study showed that new bone tissue was able to grow into the pores that resulted from GM degradation. This study suggests that the new composite could be a promising candidate for use as a bone substitute under non-compression-loaded circumstances.


[Study on chemical constituents in rhizome of Securidaca inappendiculata].
To study the chemical constituents of Securidaca inappendiculata. Column chromatographic techniques were applied to isolate constituents. A combination of MS and NMR spectroscopy was used to identify structures of constituents. Seven compounds were isolated from the CHCl3 fraction and their structures were elucidated as 3, 4-dihydroxybezoic acid (1), 3-hydroxy-4-methoxylbenzoic acid (2), coniferaldehyde (3), 7-hydroxy-1, 2, 3, 8-tetrame thoxyxanthone (4), 1, 3, 8-trihydroxy-4-methoxyxanthone (5), 1, 3, 8-trihydroxy-2-methoxyxanth-one (6), 1, 3, 6-trihydroxy-2,7-dimethoxyxanthone (7). Compounds 1-6 were isolated for the first time from the genus. The antioxidant activities of compounds 3-6 were assayed by the method of DPPH and compound 3 showed the IC50 value of 4.14 microg x mL(-1).


Running from Disease: Molecular Mechanisms Associating Dopamine and Leptin Signaling in the Brain with Physical Inactivity, Obesity, and Type 2 Diabetes.
Physical inactivity is a primary contributor to diseases such as obesity, cardiovascular disease, and type 2 diabetes. Accelerometry data suggest that a majority of US adults fail to perform substantial levels of physical activity needed to improve health. Thus, understanding the molecular factors that stimulate physical activity, and physical inactivity, is imperative for the development of strategies to reduce sedentary behavior and in turn prevent chronic disease. Despite many of the well-known health benefits of physical activity being described, little is known about genetic and biological factors that may influence this complex behavior. The mesolimbic dopamine system regulates motivating and rewarding behavior as well as motor movement. Here, we present data supporting the hypothesis that obesity may mechanistically lower voluntary physical activity levels via dopamine dysregulation. In doing so, we review data that suggest mesolimbic dopamine activity is a strong contributor to voluntary physical activity behavior. We also summarize findings suggesting that obesity leads to central dopaminergic dysfunction, which in turn contributes to reductions in physical activity that often accompany obesity. Additionally, we highlight examples in which central leptin activity influences physical activity levels in a dopamine-dependent manner. Future elucidation of these mechanisms will help support strategies to increase physical activity levels in obese patients and prevent diseases caused by physical inactivity.


Single-Cell Transcriptional Profiling Reveals Low-Level Tragus Stimulation Improves Sepsis-Induced Myocardial Dysfunction by Promoting M2 Macrophage Polarization.
Sepsis can lead to multiple organ damage, of which the heart is one of the most vulnerable organs. Vagal nerve stimulation can reduce myocardial injury in sepsis and improve survival rates. However, the potential impact of low-level tragus stimulation and disparate cell populations on sepsis-induced myocardial dysfunction remains undetermined. A cardiac single-cell transcriptomic approach was used for characterizing cardiac cell populations that form the heart. Single-cell mRNA sequencing data were used for selecting all cardiac macrophages from CD45+ cells. Then, echocardiography, western blot, flow cytometry, immunofluorescence, and immunohistochemistry were performed to verify the single-cell mRNA sequencing results. Using single-cell mRNA sequencing data, we uncovered the multiple cell populations contributing to myocardial injury in sepsis under low-level tragus stimulation, thereby illustrating a comprehensive map of the cardiac cellular landscape. Pseudotiming analysis in single-cell sequencing showed that low-level vagal nerve stimulation played an anti-inflammatory role by promoting cardiac monocytes into M2 macrophages, which significantly increased α7nAChR expression in heart tissues. Echocardiography assessment indicated that low-level vagal nerve stimulation could also improve cardiac functions in mice with sepsis-induced myocardial dysfunction. In addition, the heart tissues of mice from the sepsis group with low-level tragus stimulation had significantly lower interleukin-1β expression levels than those from the sepsis group. Flow cytometry analysis showed that different acetylcholine concentrations promoted cardiac monocytes into M2 macrophages in in vitro experiments. Low-level tragus stimulation could improve sepsis-induced myocardial dysfunction by promoting cardiac monocytes to M2 macrophages.


Fragment-Based, Structure-Enabled Discovery of Novel Pyridones and Pyridone Macrocycles as Potent Bromodomain and Extra-Terminal Domain (BET) Family Bromodomain Inhibitors.
Members of the BET family of bromodomain containing proteins have been identified as potential targets for blocking proliferation in a variety of cancer cell lines. A two-dimensional NMR fragment screen for binders to the bromodomains of BRD4 identified a phenylpyridazinone fragment with a weak binding affinity (1, Ki = 160 μM). SAR investigation of fragment 1, aided by X-ray structure-based design, enabled the synthesis of potent pyridone and macrocyclic pyridone inhibitors exhibiting single digit nanomolar potency in both biochemical and cell based assays. Advanced analogs in these series exhibited high oral exposures in rodent PK studies and demonstrated significant tumor growth inhibition efficacy in mouse flank xenograft models.


Aggregation Temperature of Escherichia coli Depends on Steepness of the Thermal Gradient.
Bacterial chemotaxis, the directed migration of bacteria in a gradient of chemoattractant, is one of the most well-studied and well-understood processes in cell biology. On the other hand, bacterial thermotaxis, the directed migration of bacteria in a gradient of temperature, is understood relatively poorly, with somewhat conflicting reports by different groups. One of the reasons for that is the relative technical difficulty of the generation of well-defined gradients of temperature that are sufficiently steep to elicit readily detectable thermotaxis. Here, we used a specially designed microfluidic device to study thermotaxis of Escherichia coli in a broad range of thermal gradients with a high rate of data collection. We found that in shallow temperature gradients with narrow temperature ranges, E. coli tended to aggregate near a sidewall of the gradient channel at either the lowest or the highest temperature. On the other hand, in sufficiently steep gradients with wide temperature ranges, E. coli aggregated at intermediate temperatures, with maximal cell concentrations found away from the sidewalls. We observed this intermediate temperature aggregation in a motility buffer that did not contain any major chemoattractants of E. coli, in contradiction to some previous reports, which suggested that this type of aggregation required the presence of at least one major chemoattractant in the medium. Even more surprisingly, the aggregation temperature strongly depended on the gradient steepness, decreasing by ∼10° as the steepness was increased from 27 to 53°C/mm. Our experiments also highlight the fact that assessments of thermal gradients by changes in fluorescence of temperature-sensitive fluorescent dyes need to account for thermophoresis of the dyes.


Comparing the Concept of Caring in Islamic Perspective with Watson and Parse's Nursing Theories.
In the nursing profession, it is apparent that the definition of caring differs between various perspectives. This article compares the difference of caring in Islamic with the Parse and Watson theories. In this study, we use concept analyses of Walker-Avants and compare research methods. Material used is all Islamic documents. According to Islamic documents, there are four major types of caring, namely, (1) God taking care of humans, (2) Humans taking care of themselves, (3) Other humans taking care of humans, and (4) The universe taking care of humans and vice versa. God caring for humans affects the three other types of caring. All three definitions of caring have humanistic and holistic view. According to Watson's and Parse's definition, the development of the caring theory is based on the person's experiences that result from human interactions with, and experiences of, their environment. In Islamic definition, although the caring process is affected by environmental experiences and interactions, human not developed only base the effect of environment; rather, it is developed on the basis of human nature and divine commands. God taking care of humans is specific to Islamic perspective and is not found in other definitions. Islamic perspective maintains that God is the creator of humanity and is in charge of guiding humans. A superior form of human can always be discovered. Thus, nursing implementation in Muslims must be done based on Islamic commands, and Islamic commands are superior to human experiences. However, Islamic commands interpreted with human wisdom and thought can be striving toward excellence.


[Campylobacter jejuni gastroenteritis].
Acute gastroenteritis is a major cause of hospital admission with attendant morbidity and occasional mortality. Campylobacter jejuni recently has been recognized as a common cause of acute bacterial gastroenteritis in children and adults. Its frequency of isolation is comparable to and in many studies exceeds that of Salmonella isolations from diarrheal stools of hospitalized patients. Medical workers in many parts of the world confirmed that Campylobacter jejuni was found more commonly in feces in diarrheic than in non-diarrheic people. The feces is loose to watery and commonly contains blood and leukocytes. Although, Campylobacter jejuni has been isolated from feces and gallbladder of healthy and diarrheic animals, until now, to our knowledge, there is no report on the isolation of the microorganism from healthy or diarrheic subjects in Turkey. This paper reports three human infections found to have Campylobacter jejuni in their stools as part of our ongoing investigation of the incidence of diarrheal disease due to this organism.


A recombinant rabies virus expressing Echinococcus granulosus EG95 induces protective immunity in mice.
Cystic echinococcosis (CE), caused by Echinococcus granulosus (E, is a zoonosis with a worldwide distribution, resulting in heavy impact to public health and social economics. In this study, we generated a recombinant rabies virus (RABV) expressing EG95 protein of E. granulosus (LBNSE-EG95) as a bivalent candidate vaccine for use in sheep and cattle against CE and rabies, which is another severe health threat in CE-endemic areas. It was found that EG95 was successfully expressed without altering the pathogenicity of parent LBNSE vector. Further study showed that LBNSE-EG95 immunization in mice elicited activation of dendric cells (DCs) and B cells and induced Th1-/Th2-mediated cellular immune responses, leading to robust production of RABV neutralizing antibodies and high level of EG95-sepecific antibodies with more than 90% protection against CE. In addition, single dose of LBNSE-EG95 conferred full protection against lethal RABV challenge in mice. Collectively, these results suggest that the recombinant LBNSE-EG95 has the potential to be developed as an efficient bivalent vaccine for sheep and cattle use in endemic areas of CE and rabies.


Histological examination of the effect of concentrated growth factor (CGF) on healing outcomes after maxillary sinus floor augmentation surgery.
A double-blind clinical trial was conducted to examine the effect of concentrated growth factor (CGF), a new generation of platelet derivatives, on the healing outcome of maxillary sinus floor augmentation during maxillary sinus lift surgery. The study included 9 patients referred to the Tabriz University, Faculty of Dentistry, aged 30-80 years, with bilateral posterior partial edentulous or edentulous maxilla who underwent the procedure using a split-mouth technique. After lifting the Schneiderian membrane, bovine xenograft was randomly applied on one side (for example, left maxillary sinus) and CGF on the other side (for example, right maxillary sinus). Results from alizarin red and hematoxylin-eosin staining methods showed that the percentage of bone formed in the CGF group (112.41±26.34% and 96.16±24.49%, respectively) was significantly higher than in the control group (64.99±24.96% and 60.16±16.39%, respectively) (P<0.05). In addition, after 6 months, the amount of residual graft material in the control group (xenograft) was significantly higher than in the CGF group (P<0.05). These findings demonstrate that the use of CGF during open sinus lift surgery is reliable for the placement of dental implants.


Interactions of HSP22 (HSPB8) with HSP20, alphaB-crystallin, and HSPB3.
Seven of the 10 mammalian small heat shock proteins (sHSP) are expressed in muscle where they constitute 3% or more of total protein. sHSPs interact with one another, and these interactions are believed to be important for their functions. In cell types expressing multiple sHSPs, it is of interest to know which sHSPs interact with one another. We have previously shown that HSP22 interacts with itself as well as with HSP27, MKBP, and cvHSP. Using yeast two-hybrid assays and Förster resonance energy transfer microscopy, we now show that HSP22 also can interact with two additional members of the sHSP family, alphaB-crystallin and HSP20. We also show that HSP22 is found in HPLC fractions of primate cardiac muscle containing high molecular weight complexes that include alphaB-crystallin and HSP20. Our results suggest that a variety of oligomers composed of different proportions of different sHSPs may form in cell types expressing multiple sHSPs.


Vitamins, minerals and race performance in ultra-endurance runners--Deutschlandlauf 2006.
We investigated the effect of pre-race intake of vitamins and minerals, in the form of supplementation, before a multi-stage ultra-endurance run and their effect on race performance. At the Deutschlandlauf 2006 in Germany, where athletes had to run across Germany from the north (Kap Arkona-Rügen) to the south (Lörrach) over 1,200 km within 17 consecutive stages, twenty male ultra runners (46.2+/-9.6 years, 71.8+/-5.2 kg, 179+/-6 cm, BMI 22.5+/-1.9 kg/m2) completed a questionnaire about their intake of vitamin and mineral supplements in the four weeks before the race. Race performance of athletes with- and athletes without regular intake of these supplements were compared. In the four weeks before the run, nine runners (45%) ingested vitamin- and twelve athletes (60%) mineral supplements. Athletes with an intake of vitamins (152.8+/-14.1 h versus 160.6+/-14.6 h, p>0.05) and minerals (151.6+/-14.5 h versus 165.3+/-10.8 h, p>0.05) finished the race no faster than athletes without an intake of vitamins and minerals. We concluded that in the Deutschlandlauf 2006 of over 1,200 km within 17 consecutive stages, athletes with a regular intake of vitamin and mineral supplements in the four weeks before the race finished the competition no faster than athletes without an intake of vitamins and minerals.


Engaging women at risk for poor perinatal mental health outcomes: a mixed-methods study.
Risk factors for poor perinatal mental health are well known. Psychosocial assessment and depression screening during the perinatal period aim to identify women at risk for poor perinatal outcomes. Early intervention programmes are known to improve the mental health outcomes of women and infants. Key to any intervention is initial and ongoing engagement in the therapeutic process. This mixed-methods study reports the proportion of women who engage/do not engage with services and their characteristics, as well as the strategies clinicians use to engage women. Data were collected by reviewing medical records, interviewing perinatal and infant mental health (PIMH) clinicians, their managers, key stakeholders, and women service users. Analyses identified that most (71.3%) women referred engaged with the PIMH service. Themes related to non-engagement are 'time to rethink' and 'stigma'. Themes reflecting the engagement strategies used by PIMH clinicians are initial engagement: 'back to basics' and 'building trust', therapeutic engagement: 'making myself useful', engagement at discharge: 'woman or clinician led', and models that facilitate engagement.


Synthesis and properties of a solution-processable truxene derivative for OLED devices.
A soluble truxene derivative (TR1) attached with triphenylamine at the peripheral position was designed and synthesized. The structure and purity of TR1 were carefully characterized by 1H NMR, UV/vis and photoluminescent spectroscopy, mass spectroscopy, and thermal analyses. It exhibited good solubility in common organic solvents and good film forming properties. The maximum absorption and emission peaks in THF solution were shown at 358 nm and 415 nm, respectively. Bright blue emission was observed in both solution and solid states under UV excitation. The fluorescent quantum efficiency was 0.46. The best luminous efficiency was found to be 3.65 cd/A with CIE coordinates of (0.163, 0.260) in electroluminescence devices.


Correlation between Random Urinary Protein-to-creatinine Ratio and 24-h Urinary Protein Excretion in Preeclampsia.
This study aimed to determine the correlation between random urinary protein-to-creatinine ratio in single-voided urine samples and 24-h urinary protein excretion in pregnant women with preeclampsia. A cross-sectional study was conducted at the Department of Gynecology and Obstetrics, Abbasi Shaheed Hospital, Karachi, Pakistan, from July 2019 to June 2020. Fifty women with singleton pregnancy after 20 weeks of gestation with hypertension and 2+ proteinuria or more, according to a dipstick test, were included. Those with chronic hypertension; preexisting renal disease; gestational diabetes; eclampsia; hemolysis, elevated liver enzymes, a low platelet count syndrome; and coexisting urinary tract infections were excluded. Two random urine samples taken at 9:00 a.m. and 2:00 p.m. and 24-h urine samples were collected to evaluate the random urinary protein-to-creatinine and the 24-h protein excretion, respectively. The correlation coefficient (r) between them was calculated using Pearson's correlation test. The patients' mean age was 28.58 ± 5.09 years and their mean gestational age was 32.74 ± 4.44 weeks. Twenty-eight (56%) women were primigravidas, and 22 (44%) were multiparous. The average serum creatinine was 0.80 ± 0.16 mg/dL. The mean random urinary protein-to-creatinine ratio was 0.93 ± 0.7 mg/mg, and the mean 24-h urine was 481.08 ± 20.10 mL. A strong positive correlation was found between the protein-to-creatinine ratio and 24-h urinary protein excretion (r = 0.655; P = 0.01). We concluded that the protein-to-creatinine ratio in spot urine samples could be used as an alternative to in 24-h collection of urine to determine protein excretion in preeclamptic pregnant women.


Extent of BOLD Vascular Dysregulation Is Greater in Diffuse Gliomas without Isocitrate Dehydrogenase 1 R132H Mutation.
Purpose To determine the effect that R132H mutation status of diffuse glioma has on extent of vascular dysregulation and extent of residual blood oxygen level-dependent (BOLD) abnormality after surgical resection. Materials and Methods This study was an institutional review board-approved retrospective analysis of an institutional database of patients, and informed consent was waived. From 2010 to 2017, 39 treatment-naïve patients with diffuse glioma underwent preoperative echo-planar imaging and BOLD functional magnetic resonance imaging. BOLD vascular dysregulation maps were made by identifying voxels with time series similar to tumor and dissimilar to healthy brain. The spatial overlap between tumor and vascular dysregulation was characterized by using the Dice coefficient, and areas of BOLD abnormality outside the tumor margins were quantified as BOLD-only fraction (BOF). Linear regression was used to assess effects of R132H status on the Dice coefficient, BOF, and residual BOLD abnormality after surgical resection. Results When compared with R132H wild-type (R132H-) gliomas, R132H-mutated (R132H+) gliomas showed greater spatial overlap between BOLD abnormality and tumor (mean Dice coefficient, 0.659 ± 0.02 [standard error] for R132H+ and 0.327 ± 0.04 for R132H-; P < .001), less BOLD abnormality beyond the tumor margin (mean BOF, 0.255 ± 0.03 for R132H+ and 0.728 ± 0.04 for R132H-; P < .001), and less postoperative BOLD abnormality (residual fraction, 0.046 ± 0.0047 for R132H+ and 0.397 ± 0.045 for R132H-; P < .001). Receiver operating characteristic curve analysis showed high sensitivity and specificity in the discrimination of R132H+ tumors from R132H- tumors with calculation of both Dice coefficient and BOF (area under the receiver operating characteristic curve, 0.967 and 0.977, respectively). Conclusion R132H mutation status is an important variable affecting the extent of tumor-associated vascular dysregulation and the residual vascular dysregulation after surgical resection. © RSNA, 2018 Online supplemental material is available for this article.


Memory for position and dynamic representations.
Memory for the position of an object is biased. When asked to judge whether an object has changed its position with respect to a position shown a few milliseconds before, observers tend to detect the displacement more often when the displacement is not in the expected direction (downward for a falling object). The hypothesis proposed by Freyd (1983, 1987) states that the internal representation of an object is intrinsically dynamic. Therefore, the forces perceived as acting on the object affect the representation. Quantitative predictions of this model were tested in three experiments by measuring memory distortion for the position of an object on an inclined plane. Angle of inclination and retention interval were varied. The results for different inclinations support the physical model. The time course of the memory distortion suggests a new view about the relation between this phenomenon and very short-term memory.


C-reactive protein, antiinflammatory drugs, and quality of life in diabetes.
C-reactive protein (CRP) is an important biological marker of inflammation that has been linked to cardiovascular disease. The extent to which the inflammatory processes associated with elevated CRP concentrations impair physical functioning and quality of life, and whether this is modulated by hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) and aspirin, which have been shown to lower CRP concentrations, is unclear. To determine whether an association exists between CRP concentrations and health-related quality of life among patients with diabetes, and to determine whether the association is affected by use of statins and nonsteroidal antiinflammatory drugs (NSAIDs). A trained interviewer collected self-reported information regarding demographics, health-related quality of life (SF-12), and medication use, and a nurse collected a blood sample from 86 adult subjects with type 2 diabetes mellitus who were part of a larger population-based survey. The serum was analyzed for CRP using a highly sensitive assay. In simple bivariate analysis, there was a significant inverse relationship between CRP and the physical health component score of health-related quality of life (Spearman correlation coefficient [r] = -0.26; p = 0.025). For subjects on statins (r = -0.44; p = 0.02; n = 27), this relationship persisted, while for patients on NSAIDs or aspirin (r = -0.21; p = 0.17; n = 44), no relationship was observed. Similar findings were observed with self-rated health alone as an outcome variable. However, stepwise linear regression revealed no consistent relationship between CRP and health-related quality of life (i.e., standardized SF-12 physical component score) when demographic variables, disease duration, glucose control, serum creatinine, smoking, and medication use were controlled for. In multivariate regression modeling, the initial inverse relationship between CRP and health-related quality of life was lost, suggesting that other covariates are responsible for this association. While statins and NSAIDs may impact CRP or health-related quality of life independently, they do not appear to modulate a relationship between these factors.


Inhibition of the Aggregation and Toxicity of the Minimal Amyloidogenic Fragment of Tau by Its Pro-Substituted Analogues.
Inhibiting the toxic aggregation of amyloid-β and the tau protein, the key pathological agents involved in Alzheimer's, is a leading approach in modulating disease progression. Using an aggregative tau-derived model peptide, Ac-PHF6-NH2 , the substitution of its amino acids with proline, a known efficient β-breaker, is shown to reduce self-assembly. This effect is attributed to the steric hindrance created by the proline substitution, which results in disruption of the β-sheet formation process. Moreover, several of the proline-substituted peptides inhibit the aggregation of Ac-PHF6-NH2 amyloidogenic peptide. Two of these modified inhibitors also disassemble pre-formed Ac-PHF6-NH2 fibrils and one inhibits induced cytotoxicity of the fibrils. Taken together, these lead β-breaker peptides may be developed into novel Alzheimer's disease therapeutics.


Alternatives to conventional enterocystoplasty in children: a critical review of urodynamic outcomes.
Alternatives to conventional enterocystoplasty have been developed in order to avoid the most common complications derived from contact of the urine with intestinal mucosa. In this article critically we review the literature on the topics: ureterocystoplasty, detrusorectomy, detrusorotomy, seromuscular gastroenterocystoplasty, use of off the shelf biomaterials, and bladder augmentation by bioengineering. Recognizing the difficulty of deciding when a child with a history of posterior urethral valves requires and augmentation and that the development of a large megaureter in cases of neurogenic dysfunction represents a failure of initial treatment, we conclude that ureterocystoplasty can be useful in selected cases when a large dilated ureter is available. Seromuscular colocystoplasty lined with urothelium (SCLU) has been urodynamically effective in several series when the outlet resistance is high and no additional intravesical procedures are necessary. Seromuscular gastrocystoplasty lined with urothelium seems to offer no distinct advantages and involves a much more involved operation. The use of seromuscular segments without urothelial preservation, with or without the use of an intravesical balloon has been reported as successful in two centers but strict urodynamic evidence of its effectiveness is lacking. The published evidence argues strongly against the use of detrusorectomy or detrusorotomy alone because of the lack of significant urodynamic benefits. Two recent reports discourage the use of small intestinal submucosa patches because of a high failure rate. Finally, research into the development of a bioengineered bladder constructed with cell harvested from the same patient continues but is fraught with technical and conceptual problems. In conclusion of the methods reviewed, only ureterocystoplasty and SCLU have been proven urodynamically effective and reproducible.


Brain Metastasis from Colorectal Cancer: Predictors and Treatment Outcomes.
Difficulties are associated with the management of brain metastasis (BM), which portends a poor prognosis in the treatment of colorectal cancer (CRC). The aim of the present study was to identify risk factors for BM in CRC and evaluate the outcomes of various treatment modalities. We retrospectively reviewed data on a total of 2,238 patients with primary CRC who underwent surgical resection at our hospital between 1999 and 2014. Predictive factors for BM and prognostic factors after the diagnosis of BM were examined by univariate and multivariate analyses using Cox proportional hazards models. Three patients (0.1%) had BM at the initial diagnosis, and 23 patients (1.2%) developed metachronous BM during the median follow-up period of 44.6 months. Lung and bone metastases were identified as independent predictive factors for BM. Median survival after the diagnosis of BM was 7.4 months. Stereotactic radiosurgery, administered to 41% of the patients with BM, was associated with a better postdiagnostic survival. CRC patients with metastasis to the lung or bone were at a higher risk of BM. Because the survival is still limited, it is crucial to determine the treatment strategy in consideration of the characteristics of each therapy and quality of life in CRC patients with BM.


Pulmonary tuberculosis in HIV-infected patients presenting with normal chest radiograph and negative sputum smear.
HIV-infected patients with pulmonary tuberculosis exhibit atypical radiological presentation and negative sputum smear more frequently than their HIV-negative counterparts. We performed a retrospective study based on a chart review of 146 HIV-infected patients with pulmonary symptoms and culture-proven pulmonary tuberculosis. We compared clinical characteristics and the outcome in 71 patients (49%) with positive sputum smear (SS+), 62 patients (42%) with negative sputum smear/abnormal chest X-ray (SS-/CXR+) and 13 patients (9%) with negative sputum smear/normal chest X-ray (SS-/CXR-). Patients were enrolled from January 1987 to December 1998, and were followed up until December 1999. On hospital admission the three groups of patients examined did not differ significantly in demographic characteristics, degree of immunosuppression or Mycobacterium tuberculosis drug-susceptibility pattern. SS-/CXR- patients were significantly Less LikeLy to present with prolonged fever and dyspnea. Median survival was shorter for SS-/CXR- patients (6.4 months vs 20.2 and 18.8 months in the other two groups). In multivariate analysis, SS-/CXR-patients had a significantly increased risk of death (hazard ratio 3.0, 95% confidence interval, 1.4 to 6.4, p = 0.004) compared to SS+ patients. This increase in risk was no longer statistically significant when initiation of antituberculous therapy within 8 weeks from the collection date of the first specimen yielding M. tuberculosis was included in the multivariate model. Decreased survival was observed in HIV-infected patients with pulmonary tuberculosis and with both negative sputum smear and normaL chest X-ray presentation. This may primarily be a resuLt of delayed tuberculosis diagnosis and initiation of antituberculous therapy. The latter delay may also lead to a faster progression of HIV infection in SS-/CXR patients, in whom diagnostic oversight may be common.


Structure and dynamics in liquid bismuth and Bi(n) clusters: a density functional study.
Density functional/molecular dynamics simulations with more than 500 atoms have been performed on liquid bismuth at 573, 773, 923, and 1023 K and on neutral Bi clusters with up to 14 atoms. There are similar structural patterns (coordination numbers, bond angles, and ring patterns) in the liquid and the clusters, with significant differences from the rhombohedral crystalline form. We study the details of the structure (structure factor, pair, and cavity distribution functions) and dynamical properties (vibration frequencies, diffusion constants, power spectra), and compare with experimental results where available. While the three short covalent bonds typical to pnictogens are characteristic in both liquid and clusters, the number of large voids and the total cavity volume is much larger in the liquid at 1023 K, with larger local concentration variations. The inclusion of spin-orbit coupling results in a lowering of the cohesive energies in Bin clusters of 0.3-0.5 eV/atom.


Cognitive variability.
Children's thinking is highly variable at every level of analysis, from neural and associative levels to the level of strategies, theories, and other aspects of high-level cognition. This variability exists within people as well as between them; individual children often rely on different strategies or representations on closely related problems presented close in time. Recognizing such variability can help us both describe development more accurately and better explain how cognitive change occurs.


Double-blind controlled crossover high-dose study of Azaribine in psoriasis.
Azaribine used in high doses of 200 mg/kg a day is an effective agent in inducing temporary remissions in patients with severe psoriasis but potentially serious neurotoxicity may occur. Therapy should be initiated at lower doses of 125 mg/kg a day and advanced carefully only if clinical response does not ensue at the lower level.


Therapeutic Effects of Plant Extracts of Anoectochilus roxburghii on Side Effects of Chemotherapy in BALB/c Breast Cancer Mice.
Breast cancer is the most common cancer in women, and chemotherapy is an effective treatment. However, chemotherapy often causes adverse side effects such as cardiotoxicity, myelosuppression, immunodeficiency, and osteoporosis. Our study focused on the alleviating effects of Anoectochilus roxburghii extracts (AREs) on the adverse side effects of chemotherapy in mice with breast cancer. We individually evaluated the antioxidant capacity and cytotoxicity of the AREs using DPPH and MTT assays. We also examined the effects of the AREs on intracellular F-actin, reactive oxygen species (ROS), and the mitochondrial membrane potential (MMP) of 4T1 cancer cells before and after doxorubicin (DOX) treatment. Our results showed that ARE treatment enhanced the effects of DOX chemotherapy by promoting cell morphology damage, oxidative stress, and ROS generation, as well as by reducing MMP in the 4T1 breast cancer cells. By using BALB/c mice with breast cancer with DOX treatment, our results showed that the DOX treatment reduced body weight, blood pressure, and heart rate and induced myelosuppression, immunodeficiency, cardiotoxicity, and osteoporosis. After oral ARE treatment of BALB/c mice with breast cancer, the chemotherapeutic effects of DOX were enhanced, and the adverse side effects of DOX chemotherapy were alleviated. Based on the above results, we suggest that AREs can be used as an adjuvant reliever to DOX chemotherapy in BALB/c mice with breast cancer.


Efficient and convenient heterogeneous palladium-catalyzed regioselective deuteration at the benzylic position.
The Pd/C-catalyzed efficient and regioselective hydrogen-deuterium (H-D) exchange reaction on the benzylic site proceeded in D2O in the presence of a small amount of H2 gas. The use of the Pd/C-ethylenediamine complex [Pd/C(en)] as a catalyst instead of Pd/C led to the efficient deuterium incorporation into the benzylic site of O-benzyl protective groups without hydrogenolysis. These H-D exchange reactions provide a post synthetic and D(2)-gas-free deuterium-labeling method on a wide variety of benzylic sites using D2O as the deuterium source and heterogeneous Pd/C or Pd/C(en) as a reusable heterogeneous palladium catalyst under mild and neutral conditions.


A retrospective review of 226 hospitalized patients with fever.
To describe characteristics and outcomes for patients hospitalized with fever, not only patients with fever of unknown origin (FUO). Medical records were reviewed for 226 consecutive patients hospitalized in a Japanese referral hospital with fever as one of the clinical problems. Although the majority of illnesses involved some sort of infection (54%), noninfectious inflammatory diseases, particularly adult Still's disease (n=6) and primary vasculitis syndromes (n=5) including 3 cases of Behçet's disease, represented the leading cause in patients who met the definition of FUO [16/51(31%)]. Tuberculosis (n=6) and psychological disorders (n=6) were associated with late diagnosis. However, there was only one patient meeting the definition of FUO among those with a psychological disorder. Among the patients with prolonged fever who did not strictly meet the definition of FUO, there was a considerable number of patients with critical illnesses, such as intra-abdominal abscess, polymyalgia rheumatica, sarcoidosis, ulcerative colitis, Castleman's disease, hematological and solid malignancies, and panhypopituitarism. Drug-induced fever, systemic viral infection and unspecified vasculitis were difficult to definitively diagnose, although these pathologies were suspected as causes of fever. Follow-up of patients without definitive diagnosis at discharge confirmed that the fever subsided spontaneously or the cause of fever was properly treated after diagnosis in every patient and that none died of the underlying febrile illness. The present findings, from all patients displaying fever at hospitalization, are in agreement with findings from prior FUO series. Strict use of the definition of FUO is thus unwarranted when managing patients with prolonged fever.


Plain language summary and patient perspective of the European Society for Medical Oncology expert consensus statements on treating EGFR-positive non-small-cell lung cancer.
This article provides a plain language summary and patient perspective of a new set of recommendations made by the European Society for Medical Oncology (ESMO for short). These recommendations are also called expert consensus statements. They cover the management of people with a type of lung cancer called epidermal growth factor receptor-positive non-small-cell lung cancer (EGFR-positive NSCLC for short). The ESMO Clinical Practice Guidelines are used by healthcare professionals when treating people with cancer, but they don't necessarily have all the information healthcare professionals need to make decisions for with people with EGFR-positive NSCLC. So, in 2021, 32 healthcare professionals who are experts in treating people with EGFR-positive NSCLC worked together to produce recommendations to fill these gaps about EGFR-positive NSCLC. This was called a consensus-building process and it also included patient advocates. The experts discussed four main topics including how people with different stages of EGFR-positive NSCLC are diagnosed and treated, and how clinical studies are done. They reviewed the scientific information that exists on these subjects. They reached an agreement and developed the recommendations that are summarized here.


Analysis of RNA synthesis of type 1 poliovirus by using an in vitro molecular genetic approach.
Membranous crude replication complexes (CRC) were isolated from poliovirus-infected HeLa cells as recently described (N. Takeda, R.J. Kuhn, C.-F. Yang, T. Takegami, and E. Wimmer, J. Virol. 60:43-53, 1986). Viruses used to produce the CRC were poliovirus type 1 (Mahoney), [PV-1(M)], poliovirus type 1 (Sabin) [PV-1(S)], and four in vitro recombinants that were constructed from infectious cDNA clones. RNA synthesis in CRC was studied. No end-linked, full-length double-stranded poliovirus RNA was detected in CRC regardless of whether nonionic detergent (Nonidet P-40) was added prior to incubation. Synthesis of VPg-pU and VPg-pUpU, two nucleotidyl proteins presumed to be involved in the initiation of RNA synthesis, was slower at 30 degrees C in CRC induced by PV-1(S) than by PV-1(M). This observation was used to design a pulse-chase experiment whose result suggested that synthesis of VPg-pUpU occurred by uridylylation of VPg-pU. Synthesis of VPg-pU(pU) was thermosensitive in CRC induced by PV-1(S). With CRC of recombinant viruses, the thermosensitive block covaried to nucleotide substitutions in PV-1(S) that mapped to the virus-induced RNA polymerase 3Dpol. We conclude that plus-stranded RNA synthesis in CRC does not proceed via hairpin structures. The results of VPg-pU----VPg-pUpU synthesis are consistent with a model in which VPg-pU is the primer of RNA synthesis mediated by 3Dpol. The data suggest that uridylylation of VPg or a precursor thereof may be catalyzed by 3Dpol itself, a mechanism resembling events occurring in adenovirus DNA replication.


Arginine and nitrogen mobilization in cyanobacteria.
Cyanobacteria have evolved mechanisms to adapt to environmental stress and nutrient availability, including accumulation of storage compounds in inclusions and granules. As arginine is a key building block of cyanophycin, a dynamic nitrogen reservoir in many cyanobacteria, arginine metabolism plays a key role in cyanobacterial nitrogen storage and remobilization. Recently, an arginine dihydrolase AgrE/ArgZ was identified as a major arginine-degrading enzyme in nondiazotrophic Synechocystis, which catalyzes the conversion of arginine into ornithine and ammonia. The N-terminal domain of AgrE/ArgZ is responsible for arginine dihydrolase activity. Burnat et al. (2019) identified the arginine catabolic pathway in diazotrophic Anabaena, which starts with the reaction catalyzed by AgrE/ArgZ. Moreover, this study identified the C-terminal domain of AgrE/ArgZ as an ornithine cyclodeaminase that catalyze the conversion of ornithine to proline. The results demonstrated that arginine is catabolized to generate glutamate by the concerted action of AgrE/ArgZ and bifunctional proline oxidase PutA in the vegetative cells of Anabaena. These findings expand our knowledge on nitrogen mobilization and redistribution in Anabaena under nitrogen-fixation conditions. AgrE/ArgZ is widely present in many diazotrophic cyanobacteria and may be important for their contribution to marine nitrogen fixation. AgrE/ArgZ may have potential applications in metabolic engineering and biotechnology.


Differential expression of cell adhesion molecules within inflamed ileal pouch mucosa: relationship to recruited cell subtypes.
Endothelial-bound cell adhesion molecules are important in recruiting inflammatory cells to the mucosa in inflammatory bowel disease (IBD). Little is known of the expression of these molecules in relation to the recruitment of particular cell subtypes in the early course of mucosal inflammation. We therefore studied the expression of several adhesion molecules to examine their potential correlation with the cellular infiltrate in the inflamed ileal pouch, a possible disease model for ulcerative colitis. Eleven patients (group 1) with familial adenomatous polyposis (FAP) with no evidence of ileal pouch inflammation and 14 patients (group 2) with ileal pouch inflammation (all with a prior diagnosis of ulcerative colitis) underwent pouch endoscopy with biopsy. Cryostat sections of biopsies were immunostained using a three-stage immunoperoxidase method for the adhesion molecules intercellular adhesion molecule (ICAM-1), vascular cellular adhesion molecule (VCAM-1), E-selectin and mucosal addressin cell adhesion molecule 1 (MAdCAM-1). These results were correlated with immunostaining for the cell markers CD3, CD4, CD8, CD45RO, CD14 and CD15, which were quantified by computer image analysis. MAdCAM-1, ICAM-1 and VCAM-1 were expressed to similar degrees on the endothelia of groups 1 and 2. In contrast, E-selectin was significantly increased in group 2 (P = 0.003) and correlated with immunostaining for CD15 (r = 0.72), CD4 (r = 0.55) and CD14 (r = 0.53). MAdCAM-1 expression did not correlate with any cell subset. CD15 was the only cell marker to be altered significantly, being increased in group 2 (P = 0.002). The inflammatory process seen in ileal pouch inflammation is characterized by up-regulation of E-selectin and recruitment of CD15-positive cells, emphasizing the role of neutrophil recruitment and migration to the epithelium in the pathogenesis of this condition.


Scanning iron response regulator binding sites using Dap-seq in the Brucella genome.
Iron is an essential element required for all organisms. Iron response regulator (Irr) is a crucial transcriptional regulator and can affect the growth and iron uptake of Brucella. The growth rate of Brucella melitensis M5-90 irr mutant was significantly lower than that of B. melitensis M5-90 under normal or iron-sufficient conditions, however, the growth rate of the B. melitensis M5-90 irr mutant was significantly higher than that of B. melitensis M5-90 under iron-limited conditions. In addition, irr mutation significantly reduced iron uptake under iron-limited conditions. Previous studies suggested that the Irr protein has multiple target genes in the Brucella genome that are involved in iron metabolism. Therefore, in the present study, a Dap-seq approach was used to investigate the other iron metabolism genes that are also regulated by the Irr protein in Brucella. A total of seven genes were identified as target genes for Irr in this study and the expression levels of these seven genes was identified using qRT-PCR. The electrophoretic mobility shift assay confirmed that six out of the seven genes, namely rirA (BME_RS13665), membrane protein (BME_RS01725), hypothetical protein (BME_RS09560), ftrA (BME_RS14525), cation-transporting P-type ATPase (zntA) (BME_RS10660), and 2Fe-2S binding protein (BME_RS13655), interact with the Irr protein. Furthermore, the iron utilization and growth assay experiments confirmed that rirA was involve in iron metabolism and growth of Brucella. In summary, our results identified six genes regulated by the Irr protein that may participate in iron metabolism, and the rirA was identified as a regulon of Irr and it also plays a role in iron metabolism of Brucella. Collectively, these results provide valuable insights for the exploration of Brucella iron metabolism.


Functional overexpression of genes involved in erythritol synthesis in the yeast Yarrowia lipolytica.
Erythritol, a four-carbon polyol synthesized by microorganisms as an osmoprotectant, is a natural sweetener produced on an industrial scale for decades. Despite the fact that the yeast Yarrowia lipolytica has been reported since the 1970s as an erythritol producer, the metabolic pathway of this polyol has never been characterized. It was shown that erythritol synthesis in yeast occurs via the pentose phosphate pathway (PPP). The oleaginous yeast Y. lipolytica is a good host for converting inexpensive glycerol into a value-added product such as erythritol. Glycerol is a renewable feedstock which is produced on a large scale as a waste product by many branches of industry. In this study, we functionally overexpressed four genes involved in the pentose phosphate pathway (PPP): gene YALI0E06479g encoding transketolase (TKL1), gene YALI0F15587g encoding transaldolase (TAL1), gene YALI0E22649g encoding glucose-6-phosphate dehydrogenase (ZWF1), and gene YALI0B15598g encoding 6-phosphogluconate dehydrogenase (GND1). Here, we show that the crucial gene for erythritol synthesis in Y. lipolytica is transketolase. Overexpression of this gene results in a twofold improvement in erythritol synthesis during a shake-flask experiment (58 g/L). Moreover, overexpression of TKL1 allows for efficient production of erythritol independently from the supplied dissolved oxygen. Fermentation conducted in a 5-L bioreactor at low agitation results in almost 70% higher titer of erythritol over the control strain. This work presents the importance of the PPP in erythritol synthesis and the feasibility for economic production of erythritol from glycerol by the yeast Y. lipolytica.


[Biliary atresia - signs and symptoms, diagnosis, clinical management].
Biliary atresia is a chronic cholangiopathy leading to progressive fibrosis of both intra- and extrahepatic bile ducts. The cause of the condition is unknown. Fundamental management of biliary atresia is surgical intervention and the outcomes of the treatment depend on the child's age with best results when performed within the first 2 months of life. Thus, the main role of pediatric healthcare is an urgent differential diagnosis and prompt qualification for the surgery, optimal postoperative management and early qualification for the liver transplantation in patients with persistent cholestasis. The authors discuss the clinical presentation, diagnosis and management of biliary atresia.


Relationship Between Types of Social Support, Coping Strategies, and Psychological Distress in Individuals Living With Congenital Heart Disease.
Many people with congenital heart disease (CHD) experience psychological distress related to medical complications and psychosocial issues related to the disease. Although studies show that social support and coping strategies are closely associated with psychological distress in people struggling with different chronic health challenges, very little is known about whether the same factors hold true for the psychological distress of people living with CHD. The purpose of this study was to examine the relationships between types of social support, coping strategies, and psychological distress for individuals living with CHD. A cross-sectional survey design with self-report questionnaires was used. A convenience sample of 272 participants was obtained from the Adult Congenital Heart Disease program at a tertiary care hospital in Western Canada. Structural equation modeling was conducted to examine hypothesized relationships among study variables. Perceived social support was directly related to both anxiety and depression. Received social support influenced anxiety and depression, but its effect was through perceived social support. Wishful-thinking coping strategies mediated the relationships between perceived social support and both anxiety and depression. Individuals with CHD who have low perceived and received social support are vulnerable to experiences of psychological distress. Assessments of social support and facilitation of positive coping strategies are integral to nursing care for adults with CHD.


Expression of chitinase-like proteins in the skin of chronic proliferative dermatitis (cpdm/cpdm) mice.
Mammalian chitinase-like proteins belong to a family of proteins structurally related to chitinases but devoid of enzymatic activity. They have a postulated role in remodeling of extracellular matrix and defense mechanisms against chitin-containing pathogens. The expression of these proteins is increased in parasitic infections and allergic airway disease, but their expression in dermatitis has not been examined. The mRNA expression of two chitinase 3-like (Chi3L) proteins, Chi3L3 (Ym1) and Chi3L4 (Ym2), was determined in the skin of normal mice, chronic proliferative dermatitis (cpdm/cpdm) mutant mice and mice with experimentally induced contact hypersensitivity reaction. The localization of Chi3L3 and Chi3L4 proteins in cells was determined by fluorescence microscopy of double-labeled frozen sections of skin, and confirmed in vitro by stimulation of macrophages and mast cells with cytokines. Quantitative RT-PCR demonstrated a 976-fold increase of Chi3l4 mRNA expression and a 24-fold increase of Chi3l3 mRNA expression in the skin of cpdm/cpdm mice. Their expression was also increased in the ears of mice with 2,4-dinitrofluorobenzene-induced contact hypersensitivity, but the increase was greater for Chi3l3 mRNA (51-fold) than Chi3l4 mRNA (32-fold). Western blot analysis with an antibody against Chi3L3 and Chi3L4 confirmed the increased amount of these proteins in the skin of cpdm/cpdm mice. Two-color immunofluorescence identified macrophages, dendritic cells and mast cells as cellular sources of Chi3L3 and Chi3L4 proteins. Eosinophils and neutrophils did not contain detectable concentrations of these proteins. Treatment of macrophages and mast cells in vitro with interleukin-4 induced expression of Chi3l3 and Chi3l4 mRNA.


The fetal prognosis in pemphigoid gestationis (herpes gestationis).
We have studied the infants in fifty pregnancies affected by pemphigoid gestationis (herpes gestationis). There was a significant increase in the frequency of infants that were 'small for dates'. As such infants have a raised mortality and morbidity it follows that in pemphigoid gestationis the fetal prognosis is impaired. In view of this it is essential that patients with pemphigoid gestationis are delivered in maternity units which have facilities for intensive care of the newborn.


The equine endometrial mast cell during the puerperal period: evaluation of mast cell numbers and types in comparison to other inflammatory changes.
Endometrial biopsies of 44 broodmares were histologically examined on days 3, 6, and 9 postpartum. The mares were subdivided into three groups according to the course of the puerperal period. In 29 mares, parturition and expulsion of the placenta was normal, six mares showed dystocia, and in nine mares, the placenta was retained for > 2 hours. Tissue samples were evaluated histologically, and the average numbers of granulocytes, lymphocytes, macrophages, siderophages, and mast cells was determined. Protease content of mast cells was examined with a double-enzyme immunohistochemical staining technique, using a histochemical reaction for chloroacetate esterase and fast blue to detect chymase activity and an immunohistochemical staining method with a polyclonal antibody and fast red for the detection of tryptase. Analyzing the cell numbers using the statistical software Statistica, a marked inflammatory reaction was observed in the endometrium postpartum. Although the number of granulocytes decreased during the first 9 days postpartum, the number of lymphocytes, macrophages, and siderophages increased. No significant difference in the number of any of these cell types could be demonstrated in the three different courses of the puerperal period, although the numbers of these cells seemed to be lower in mares with dystocia. In contrast with other cells, no change in the number of endometrial mast cells was observed during the puerperal period, but a significantly lower number were found in the endometrium of mares with retained placenta. The enzyme immunohistochemical double-labeling technique could demonstrate only tryptase-positive mast cells; no chymase activity was detectable in any endometrial mast cells. The number of mast cells detected with the metachromatic staining technique was significantly higher than that detected with double labeling. These results support the hypothesis that a sufficient number of mast cells may be necessary for a normal postnatal period and suggest a mast cell subtype in the equine endometrium that is tryptase and chymase negative.


Hypermethylation of E-cadherin gene is frequent and independent of p16INK4A methylation in non-small cell lung cancer: potential prognostic implication.
E-cadherin gene is often termed a 'metastasis suppressor' gene and inactivation of this gene through promoter methylation occurs in various epithelial cancer. This study assessed the methylation status of p16INK4a and E-cadherin genes, correlated with clinical characteristics in lung cancer patients. Forty-five patients with non-small cell lung cancer (NSCLC) were evaluated for methylation status of p16INK4a and E-cadherin genes by using the methylation-specific PCR. E-cadherin expression in tumor samples was examined by immunohistochemistry. Overall duration of survival in different subsets of NSCLC with or without p16INK4a or E-cad methylation at diagnosis was compared by using the Kaplan-Meier method and log-rank test. We found the hypermethylation of p16INK4a gene in 38% (17/45) of our subjects. While the E-cadherin gene was hypermethylated in 62% (28/45) related with reduced E-cadherin expression, and methylation status of both p16INK4a and E-cadherin genes seemed to be independent. Seventy-six percent (34/45) of NSCLC patients had an abnormal methylation pattern in at least one gene. Although there was no difference in overall survival of patients between methylated p16INK4a and unmethylated p16INK4a, NSCLS patients with hypermethylation of both genes (concordant pattern) had a significantly good prognosis. In contrast, NSCLC patients with hypermethylated p16INK4a but un-methylated E-cadherin gene (discordant pattern) had a significantly poor prognosis. E-cadherin and p16INK4a are commonly methylated in NSCLC and the methylation pattern of p16INK4a and E-cadherin genes may have prognostic value for the outcome of NSCLC patients.


The innervation of the adrenal gland. IV. The source of pre- and postganglionic nerve fibres to the guinea-pig adrenal gland.
The pre- and postganglionic sympathetic innervation of the guinea-pig adrenal medulla was investigated using the retrograde neuronal tracers Fast Blue and WGA-HRP. Labelled preganglionic cell bodies were located in the intermediolateral horn of spinal segments T3-L2, the majority (73.9%) were found between T6-T12 representing 70.2% of the total number of labelled cells; the segment T10 contained the largest number of labelled neurons. Labelled postganglionic cell bodies were found in the paravertebral ganglia between vertebral levels T3-T12 (representing 22.6% of the total labelled neurons), the maximum number was found at T10. In addition, labelled neurons were found in the suprarenal ganglion (representing 7.2%). No labelled cells were found in the coeliac ganglia. The labelled neurons were found ipsilateral to the site of injection into the left adrenal gland. It is concluded that the guinea-pig adrenal gland receives both a pre- and a significant postganglionic sympathetic innervation. The destination of these nerve fibres within the adrenal gland has yet to be determined.


Epidemiology of infective endophthalmitis in France. The French Collaborative Study Group on Endophthalmitis.
Data from retrospective studies of endophthalmitis vary widely with respect to incidence and to the pathogens implicated. To see whether we could provide more accurate data, we have done a prospective multicentre national survey of endophthalmitis over one year in France. Records of 36,241 operations and 1148 cases of ocular trauma from 64 centres specialising in eye surgery were analysed. There were 167 cases of endophthalmitis; incidence of postoperative endophthalmitis was 0.31 per 100 operations, and the risk after penetrating ocular trauma was 2.8%. In contrast with most previous studies, Staphylococcus epidermidis was the most frequently isolated organism, with gram-negative organisms accounting for only a small proportion of cases. Patients infected with streptococci had the least favourable outcome. The survey confirms data from retrospective studies showing that the incidence of postoperative or post-injury endophthalmitis is low. The low frequency means that large numbers of patients would be required for a trial of antibiotic efficacy, but such a trial is worthwhile because there are now antibiotics with good ocular bioavailability that are effective against most of the bacteria that cause endophthalmitis.


Bone fragility: failure of periosteal apposition to compensate for increased endocortical resorption in postmenopausal women.
The increase in bone fragility after menopause results from reduced periosteal bone formation and increased endocortical resorption. Women with highest remodeling had greatest loss of bone mass and estimated bone strength, whereas those with low remodeling lost less bone and maintained estimated bone strength. Bone loss from the inner (endocortical) surface contributes to bone fragility, whereas deposition of bone on the outer (periosteal) surface is believed to be an adaptive response to maintain resistance to bending. To test this hypothesis, changes in bone mass and estimated indices of bone geometry and strength of the one-third distal radius, bone turnover markers, and fracture incidence were measured annually in 821 women 30-89 years of age for 7.1 +/- 2.5 years. The analyses were made in 151 premenopausal women, 33 perimenopausal women, 279 postmenopausal women, and 72 postmenopausal women receiving hormone replacement therapy (HRT). In premenopausal women, periosteal apposition increased the radius width, partly offsetting endocortical resorption; therefore, the estimated cortical thickness decreased. Outward displacement of the thinner cortex maintained bone mass and cortical area and increased estimated bending strength. Estimated endocortical resorption accelerated during perimenopause, whereas periosteal apposition decreased. Further cortical thinning occurred, but estimated bending strength was maintained by modest outward cortical displacement. Endocortical resorption accelerated further during the postmenopausal years, whereas periosteal apposition declined further; cortices thinned, but because outward displacement was minimal, estimated cortical area and bending strength now decreased. Women with highest remodeling had the greatest loss of bone mass and strength. Women with low remodeling lost less bone and maintained estimated bone strength. In HRT-treated women, loss of bone strength was partly prevented. These structural indices predicted incident fractures; a 1 SD lower section modulus doubled fracture risk. Periosteal apposition does not increase after menopause to compensate for bone loss; it decreases. Bone fragility of osteoporosis is a consequence of reduced periosteal bone formation and increased endocortical resorption. Understanding the mechanisms of the age-related decline in periosteal apposition will identify new therapeutic targets. On the basis of our results, it may be speculated that the stimulation of periosteal apposition will increase bone width and improve skeletal strength.


A new species of Petalobrissus Lambert 1916 (Echinoidea: Faujasiidae) from the Jandaíra Formation, Potiguar Basin (Brazil).
A new Late Cretaceous species of Petalobrissus, Petalobrissus lehugueurae sp. nov., is described from the Jandaíra Formation, Potiguar Basin, state of Rio Grande do Norte. To date, this genus comprises a total of 20 species, only two of which, Petalobrissus setifensis and Petalobrissus cubensis have so far been recorded from the Jandaíra Formation. Petalobrissus lehugeurae sp. nov. is distinguished from its congeners in that gonopores occupy only a small portion of the genital plates, in having a slit-like periproct and a unique abrupt depression of the test that forms a pronounced keel below the periproct. In addition, an identification key to species of Petalobrissus is presented.


Risks and outcomes in community acquired pneumonia.
Risks and probable outcomes in patients with community acquired pneumonia have always been assessed intuitively by clinicians, but are now being intensively and formally studied. Several risk scoring systems have been developed to assign patients to different risk categories, with respect to important outcomes such as mortality or intensive care unit admission. Predictive factors include demographic characteristics such as age and sex, comorbidities such as neoplastic disease or congestive heart failure, abnormalities on physical examination and abnormal laboratory findings. Prospective use of one such prediction rule found a mortality rate of 0.5% in the lowest risk category, rising to 27.1% in the highest risk group. Formal assessment of risk can assist the clinician in deciding whether to treat a patient at home or in hospital, and can be an important step in developing clinical practice guidelines.


[Anaerobic gas-producing clostridial endogenic infection in patient with salmonellosis].
Anaerobic gas-producing clostridial infection is one of most severe complications of mainly gunshot wound of war period, in peace time occurs very seldom. The rare clinical case of anaerobic gas-producing clostridial endogenic infection with fulminant course in patient with salmonellosis produced by group B salmonella typhimurium. The disease was finished with fatal outcome in 8.5 hours after appearance of pain syndrome in right thigh with consequent fulminant development of gas gangrene with arterial hypotension on 4th day after onset of gastroenteric form of medium severity salmonellosis. Clinical, microbiological and postmortem data are represented.


Nonsurgical Periodontal Therapy decreases the Severity of Rheumatoid Arthritis: A Case-control Study.
Rheumatoid arthritis (RA) and periodontitis are common chronic inflammatory conditions. Several studies suggested a relationship between RA and periodontitis. Recent studies have shown a beneficial effect of periodontal treatment on the severity of active RA. So the aim of this study was to examine the effect of nonsurgical periodontal therapy on the clinical parameters of RA. A total of 60 subjects with moderate-to-severe chronic generalized periodontitis and active RA in the age range 18 to 65 were selected for the study. They were divided into two groups. Group A (control group) consisted of 30 subjects with chronic generalized periodontitis and RA, and group B of 30 subjects with chronic generalized peri-odontitis and RA and they received nonsurgical periodontal therapy (scaling, root planning, and oral hygiene instructions). Evaluation of clinical observations of Simplified Oral Hygiene Index (OHI-S), gingival index (GI), bleeding on probing (BOP), probing pocket depth (PPD), clinical attachment level (CAL), number of swollen joints (SJ), number of tender joints (TJ), values of erythrocyte sedimentation rate (ESR), visual analogue scale (VAS) for patient's global assessment, 3 months disease activity score (DAS) index, and C-reactive protein (CRP) was done at baseline and 3 months. Statistical evaluation of clinical observations was carried out. Group B subjects who received nonsurgical periodon-tal therapy showed statistically significant improvement in all periodontal and RA parameters at 3 months, compared with group A who did not receive periodontal therapy. It can be concluded from the result that nonsurgical periodontal therapy may contribute to reduction in severity and symptoms of RA. Rheumatoid arthritis patients should be evaluated for periodontitis and treated for the same in order to reduce its severity level.