Exposure of Fischer 344 rats to a weak power frequency magnetic field facilitates mammary tumorigenesis in the DMBA model of breast cancer.
The possibility that long-term exposure to relatively weak power frequency magnetic fields (MFs) emanating from the generation, transmission and use of electricity could increase the risk of breast cancer is a matter of ongoing debate. Laboratory studies using well-defined exposure conditions are useful to examine whether exposure to MF affects mammary tumorigenesis. Previous studies from different laboratories using the 7,12-dimethylbenz[a]anthracene (DMBA) model of breast cancer in female Sprague-Dawley (SD) rats have been inconclusive, which has been related to differences in MF sensitivity between SD substrains used in these studies. When we compared the effects of MF exposure on cell proliferation in the mammary gland of various outbred and inbred rat strains, Fischer 344 was the only inbred strain that exhibited a marked increase in cell proliferation. Based on these data, we suggested that MF exposure should significantly facilitate development and growth of mammary tumors in Fischer 344 rats, which was tested in the present study. Groups of 108 DMBA-treated rats were either MF exposed (100 muT, 50 Hz) or sham exposed for 26 weeks. MF exposure significantly facilitated mammary tumorigenesis. The incidence of rats with grossly recorded, histologically verified adenocarcinomas was increased by 45% (P = 0.0095). The most pronounced MF effect on tumor incidence was seen in the cranial inguinal complexes (L/R5). These data indicate that Fischer 344 rats are a suitable inbred strain to study the mechanisms underlying the effects of MF exposure on mammary tumorigenesis.


Double incontinence in urogynecologic practice: a new insight.
This study was undertaken to evaluate the prevalence of anal incontinence in an urogynecologic setting and to investigate the relationship between lower urinary tract dysfunction and anal incontinence. The study included 504 women referred to our urogynecologic outpatient clinic who were prospectively investigated and asked specific questions on anal incontinence. Clinical and instrumental data were compared between women with urinary incontinence and with double incontinence, with further analysis for subgroups in the anal incontinent group of women (passive/urge). For continuous variables, the Wilcoxon rank sum test was used, and the Fisher exact test was applied to dicotomic variables. Logistic regression was used for categorical data. A level of P<.005 was considered significant. Of the investigated women, 20.2% were also anally incontinent. Women with double incontinence showed higher scores for urinary urgency (P=.010), which reached the established level of significance only in the subgroup with urge anal incontinence (P=.003). In this group, a higher prevalence of detrusor overactivity was observed. Anal incontinence is highly prevalent among women with lower urinary tract disorders. The existence of subgroups of patients having different kinds of anal and urinary disorders should be taken into consideration both for research purposes and for new treatment perspectives.


Parasomnia with rhythmic movements manifesting as nocturnal tongue biting.
The case of a healthy 2-year-old girl with repeated nocturnal tongue biting as a result of rhythmic movements of the jaw associated with body rocking in non-REM sleep is described. Parasomnias manifesting with rhythmic, stereotyped movements of the head, trunk and extremities are well described in healthy children. The term rhythmic movement disorders (RMD) was introduced for these repetive movements in sleep which may appear as head banging (jactatio capitis), body rocking or leg rolling. Severe injuries including fractures, subdural effusions and eye injures are reported. Repeated tongue injuries have not been described as a consequence of RMD. The differential diagnosis from nocturnal seizures is crucial to avoid overtreatment of this benign albeit dramatically presenting condition.


Leaf Economics of Early- and Late-Successional Plants.
AbstractThe leaf economics spectrum ranges from cheap, short-lived leaves to expensive, long-lived leaves. Species with low leaf mass per area (LMA) and short leaf life span tend to be fast growing and shade intolerant (early successional), whereas species with high LMA and long leaf life span tend to be slow growing and shade tolerant (late successional). However, we have limited understanding of how different leaf mass components (e.g., metabolically active photosynthetic components vs. structural toughness components) contribute to variation in LMA and other leaf economics spectrum traits. Here, we develop a model of plant community dynamics in which species differ in just two traits, photosynthetic and structural LMA components, and we identify optimal values of these traits for early- and late-successional species. Most of the predicted increase in LMA from early- to late-successional species was due to structural LMA. Photosynthetic LMA did not differ consistently between early- and late-successional species, but the photosynthetic LMA to structural LMA ratio declined from early- to late-successional species. Early-successional species had high rates of instantaneous return on leaf mass investment, whereas late-successional species had high lifetime return. Our results provide theoretical support for the primary role of structural (rather than photosynthetic) LMA variation in driving relationships among leaf economics spectrum traits.


Malignant melanoma with metastasis to a colonic polyp.
Tumor-to-tumor metastases are rare occurrences. A 75-yr-old male presented with an enlarging axillary mass. Further investigation revealed an adenocarcinoma of the colon and a colonic polyp. Metastatic malignant melanoma was present within the colonic polyp and in axillary lymph nodes. In the polypectomy specimen, the distinctly dimorphic histologic appearance was the best clue to the metastatic nature of the malignant component of the polyp. The diagnosis was confirmed by histochemistry and immunocytochemistry. This is the third reported instance of a colonic polyp acting as the host in a case of tumor-to-tumor metastasis.


Integrated Approaches for the Management of Staple Line Leaks following Sleeve Gastrectomy.
Introduction. Aim of the study was trying to draw a final flow chart for the management of gastric leaks after laparoscopic sleeve gastrectomy, based on the review of our cases over 10 years' experience. Material and Methods. We retrospectively reviewed all patients who underwent LSG as a primary operation at the Bariatric Unit of Tor Vergata University Hospital in Rome from 2007 to 2015. Results. Patients included in the study were 418. There were 6 staple line leaks (1.44%). All patients with diagnosis of a leak were initially discharged home in good clinical conditions and then returned to A&E because of the complication. The mean interval between surgery and readmission for leak was 13,4 days (range 6-34 days, SD ± 11.85). We recorded one death (16.67%) due to sepsis. The remaining five cases were successfully treated with a mean healing time of the gastric leak of 55,5 days (range 26-83 days; SD ± 25.44). Conclusion. Choosing the proper treatment depends on clinical stability and on the presence or not of collected abscess. Our treatment protocol showed being associated with low complication rate and minor discomfort to the patients, reducing the need for more invasive procedures.


The nucleotide sequence of a regulatory gene present on a plasmid in an enterotoxigenic Escherichia coli strain of serotype O167:H5.
A DNA fragment that can functionally substitute for cfaD, the positive regulatory gene involved in expression of CFA/I fimbriae, has recently been cloned from an Escherichia coli strain of serotype O167:H5 that produces CS5 fimbriae. Nucleotide sequence determination showed that the fragment contained a gene, csvR (Coli Surface Virulence factor Regulator) homologous to the cfaD gene, which encoded for a protein of 301 amino acid residues. The csvR gene was found to be located between two different insertion sequences. Comparison of the amino acid sequence of the CsvR and CfaD proteins showed that CsvR is 34 amino acid residues longer at the C-terminus and, in the sequence, it also contains an insertion of two amino acid residues. The similarity between CfaD and Rns, the positive regulator of CS1 and CS2 expression, is much higher (97%) than between CsvR and CfaD (87%). This is reflected by the fact that the level of expression of CFA/I fimbriae induced by CsvR is not as high as when expression is induced by CfaD or Rns.


[Norovirus epidemic strain GII. 4 evolution--a review].
Noroviruses are regarded as the leading cause of epidemic gastroenteritis all over the world, with a wealth of genetic diversity. And GII. 4 is regarded as the predominant strain, which has constantly infected humans attributed to a fast rate of evolution in the past two decades. With the discovery of virus binding-receptor and understanding of immune specificity, the research of evolution mechanism of the virus has been continuously developed recently. It has been hypothesized that the receptor switching and antigenic drift maintains GII. 4 persistence in human populations. Also the RNA viruses, high mutation rate and the limited space of genomic variation have also affected the direction of norovirus evolution.


Interplay of Interfacial Viscosity, Specific-Ion, and Impurity Adsorption Determines Zeta Potentials of Phospholipid Membranes.
Ion-specific induced changes of the ζ-potential of phospholipid vesicles are commonly used to quantify the affinity of different ions to the lipid interface. The negative ζ-potential of zwitterionic net-neutral phospholipid vesicles in neat water, which changes sign and increases in solutions of NaCl or KCl, is a phenomenon consistently observed in experiments but not fully understood theoretically. Using atomistic molecular dynamics simulations in the presence of applied electric fields which drive electroosmotic flows, in combination with an electrostatic continuum model based on the modified Poisson-Boltzmann and Helmholtz-Smoluchowski equations, we study the electrokinetic and electrostatic properties as well as the specific ion affinities to the phospholipid-water interface, in order to resolve these puzzling observations. Our modified continuum equations account for the dielectric profile at the lipid-water interface, ion-specific interactions between ions and the lipid-water interface, and the interfacial viscosity profile, which are all extracted from our atomistic simulations and rather accurately predict ion-density and electrostatic-potential distributions as well as ζ-potentials in comparison with our atomistic simulations. Our continuum model can explain experimental ζ-potentials only when we assume minute amounts of surface-active anionic impurities in the aqueous solution. In fact, the amount of impurities needed to explain the experimental data increases linearly with the salt concentration, suggesting that surface-active species, which might be already present in the lab water or lipid samples, could further be introduced through the added salt.


Stereotactic body radiation therapy patient specific quality assurance using a two-dimensional array at extended source to surface distance.
Five patients with 38 fields have been analyzed in this study. The plans were optimized for the following clinical sites: one liver, one lung, one brain, one prostate and one spine. The detector array used for the measurements was the PTW Seven29 array. All the plans were optimized and calculated using Eclipse v8.9. The center of the array was setup at 215 cm from the source and all the fields were measured and analyzed one by one. All the 30 measurements were performed on a NovalisTX linear accelerator equipped with a high definition multileaf collimator. The evaluation was based mainly on gamma index passing rates using 2 mm distance to agreement (DTA) and 2% dose difference. The accuracy of the Eclipse Treatment Planning System (TPS) at extended Source to Surface Distances (SSDs) using an ionization chamber was measured to be within 1.0%. All the field measurements were performed and analyzed 35 individually. The percent of the points that had a gamma index of less than 1 using 3%/3 mm was >99% for all the measurements. In order to better evaluate our process and distinguish smaller differences a new set of results was obtained by applying gamma index tolerances of 2%/2mm. In this case, the gamma index passing rates ranged from 90.8 to 100% (95.5%±3%). The profile comparison showed that the detector array measurements followed closely the calculated 40 profiles, even for fields optimized with multiple peaks and valleys. The choice of the IMRT QA device has an important role in the results of the patient specific QA of the delivered dose to the patient in the case of small targets as in the treatment of spinal targets. In this study, we demonstrated that an extended SSD measurement can improve the sampling resolution of a two-dimensional (2D) detector array, in our case the PTW 45 Seven29 array. This method was shown to be accurate and efficient for measuring highly modulated small fields for pre-treatment patient specific QA.


[Discussion on correlation between intrahepatic inflammatory pathogenesis and the TCM theory of liver collateral injury by toxins in patients of type 2 diabetes mellitus with insulin resistance].
Correlation between the intrahepatic inflammatory pathogenesis and the TCM theory of liver collateral injury by toxins in patients of type 2 diabetes mellitus (T2DM) with insulin resistance (IR) was investigated, to elucidate that removing toxins, dredging collateral and modulating Gan could be one of the effective approaches for inhibiting intrahepatic inflammation mechanism of T2DM with IR.


Resorbable dome device and guided bone regeneration: an alternative bony defect treatment around implants. A case series.
This case series presents the use of a resorbable "dome device" made of a slow, long-lasting resorbable suturing material to support the barrier creating and maintaining a secluded space to promote bone regeneration. Acellular dermal matrix or cross-linked resorbable collagen membrane, as barriers, combined with mineralized freeze-dried bone allograft, with simultaneous implant placement, were utilized in reconstructing non-space-making defects. Eight implants in six healthy patients were treated with a combination of these resorbable regenerative materials. Only one of seven was treated with a nonsubmerged approach. All sites remained completely covered and no implant exposure occurred during healing. At the 9- to 24-month reentry surgeries, the clinical bone density was equivalent to that of the native bone and the mean number of final exposed threads was 0.5. The mean buccal bone thickness achieved was 3.12 mm, with a mean total coverage of exposed threads in approximately 87.5% of the cases.


Clinical utility of bone turnover markers in the management of common metabolic bone diseases in adults.
Bone turnover marker (BTMs) concentrations in blood and urine reflect bone-remodelling activity, and may be useful adjuncts in the diagnosis and management of metabolic bone diseases. Newer biomarkers, mainly bone regulatory proteins, are currently being investigated to elucidate their role in bone metabolism and disease and may in future be useful in clinical diagnosis and management of metabolic bone disease. BTM concentrations increase around menopause in women, and at a population level the degree of increase in BTMs reflect bone loss. However, lack of adequate data precludes their use in individual patients for fracture risk assessment in clinical practice. The rapid and large changes in BTMs following anti-resorptive and anabolic therapies for osteoporosis treatment indicate they may be useful for monitoring therapy in clinical practice. The offset of drug effect on BTMs could be helpful for adjudicating the duration of bisphosphonate drug holidays. BTMs may offer useful additional data in skeletal diseases that are typically characterised by increased bone remodelling: chronic kidney disease (CKD), primary hyperparathyroidism (PHPT) and Paget's disease. In CKD, bone specific alkaline phosphatase (bAP) is currently endorsed for use for the assessment of mineral bone disease. The role of BTMsin predicting the bone mineral density response to successful parathyroidectomy in PHPT shows some utility but the data are not consistent and studies are limited in size and/or duration. In Paget's disease of bone, BTMs are used to confirm diagnosis, evaluate extent of disease or degree of activity and for monitoring the response to bisphosphonate treatment. Whilst BTMs are currently used in specific clinical practice instances when investigating or managing metabolic bone disease, further data are needed to consolidate their clinical use where evidence of utility is limited.


Curvature-driven coarsening in the two-dimensional Potts model.
We study the geometric properties of polymixtures after a sudden quench in temperature. We mimic these systems with the q -states Potts model on a square lattice with and without weak quenched disorder, and their evolution with Monte Carlo simulations with nonconserved order parameter. We analyze the distribution of hull-enclosed areas for different initial conditions and compare our results with recent exact and numerical findings for q=2 (Ising) case. Our results demonstrate the memory of the presence or absence of long-range correlations in the initial state during the coarsening regime and exhibit superuniversality properties.


Television in the hospital: programming patients' delusions.
Systematic collection of art products from 55 schizophrenic patients provided unexpected documentation of the impact of television on delusion-formation. Patients' drawings and descriptions demonstrate the ease with which they incorporate TV program material in their psychotic experience. It is suggested that clinicians consider television viewing a relevant variable in the design of treatment programs.


Asynchronous detection of optical code division multiple access signals using a bandwidth-efficient and wavelength-aware receiver.
We experimentally demonstrate what we believe to be a novel detection scheme for interfacing asynchronous optical code division multiple access (CDMA) signals with an electronic clock and data recovery system that operates only at the baseband bandwidth. This allows using a large optical bandwidth expansion factor in which the optical chip rate is much larger than the bandwidth of the optoelectronic receiver. The received optical CDMA signal is launched into a four-wave-mixing-based wavelength-aware all-optical front end that rejects multiaccess interference, followed by an amplitude-noise suppression stage comprised of a semiconductor optical amplifier. The clean signal is then converted into a non-return-to-zero-like signal by a baseband receiver. Using the proposed detection scheme, asynchronous transmission and detection of optical CDMA signals is implemented. With the novel detection scheme, the classic CDMA near-far problem is mitigated, and error-free detection is easily obtained.


In vitro exposure of human chondrocytes to pulsed electromagnetic fields.
The effect of pulsed electromagnetic fields (PEMFs) on the proliferation and survival of matrix-induced autologous chondrocyte implantation (MACI)-derived cells was studied to ascertain the healing potential of PEMFs. MACI-derived cells were taken from cartilage biopsies 6 months after surgery and cultured. No dedifferentiation towards the fibro- blastic phenotype occurred, indicating the success of the surgical implantation. The MACI-derived cultured chondrocytes were exposed to 12 h/day (short term) or 4 h/day (long term) PEMFs exposure (magnetic field intensity, 2 mT; frequency, 75 Hz) and proliferation rate determined by flow cytometric analysis. The PEMFs exposure elicited a significant increase of cell number in the SG2M cell cycle phase. Moreover, cells isolated from MACI scaffolds showed the presence of collagen type II, a typical marker of chondrocyte functionality. The results show that MACI membranes represent an optimal bioengineering device to support chondrocyte growth and proliferation in surgical implants. The surgical implant of MACI combined with physiotherapy is suggested as a promising approach for a faster and safer treatment of cartilage traumatic lesions.


Visualizing Epithelial Expression in Vertical and Horizontal Planes With Dual Axes Confocal Endomicroscope Using Compact Distal Scanner.
The epithelium is a thin layer of tissue that lines hollow organs, such as colon. Visualizing in vertical cross sections with sub-cellular resolution is essential to understanding early disease mechanisms that progress naturally in the plane perpendicular to the tissue surface. The dual axes confocal architecture collects optical sections in tissue by directing light at an angle incident to the surface using separate illumination and collection beams to reduce effects of scattering, enhance dynamic range, and increase imaging depth. This configuration allows for images to be collected in the vertical as well as horizontal planes. We designed a fast, compact monolithic scanner based on the principle of parametric resonance. The mirrors were fabricated using microelectromechanical systems (MEMS) technology and were coated with aluminum to maximize near-infrared reflectivity. We achieved large axial displacements [Formula: see text] and wide lateral deflections >20°. The MEMS chip has a 3.2×2.9 mm2 form factor that allows for efficient packaging in the distal end of an endomicroscope. Imaging can be performed in either the vertical or horizontal planes with [Formula: see text] depth or 1 ×1 mm2 area, respectively, at 5 frames/s. We systemically administered a Cy5.5-labeled peptide that is specific for EGFR, and collected near-infrared fluorescence images ex vivo from pre-malignant mouse colonic epithelium to reveal the spatial distribution of this molecular target. Here, we demonstrate a novel scanning mechanism in a dual axes confocal endomicroscope that collects optical sections of near-infrared fluorescence in either vertical or horizontal planes to visualize molecular expression in the epithelium.


Combined propranolol and digoxin therapy in angina pectoris.
The effects of oral propranolol and digoxin and digoxin alone and in combination on angina frequency, heart size, systolic time intervals and treadmill exercise tolerance, were assessed in 20 patients with coronary heart disease. Oral propranolol alone reduced the average frequency of angina pectoris from 16 to 7 attacks per week (P less than 0.02). However, the mean duration of exercise was not significantly improved because 8 patients with abnormal left ventricular function exhibited a decrease in exercise tolerance. Combined propranolol and digoxin improved exercise tolerance in these patients, and, consequently, mean exercise duration in all patients increased significantly from the control value of 390 +/- 42 to 458 +/- 46 s (P less than 0.01). Propranolol alone also resulted in a significant increase in left heart size from 46.5 +/- 1.3 to 47.7 +/- 1.5 mm/m2 (P less than 0.001), which was reversed by the addition of digoxin. Therefore, oral propranolol combined with digoxin is advantageous in patients with angina pectoris who have abnormal ventricular function or large hearts.


The connective tissue phenotype of glaucomatous cupping in the monkey eye - Clinical and research implications.
In a series of previous publications we have proposed a framework for conceptualizing the optic nerve head (ONH) as a biomechanical structure. That framework proposes important roles for intraocular pressure (IOP), IOP-related stress and strain, cerebrospinal fluid pressure (CSFp), systemic and ocular determinants of blood flow, inflammation, auto-immunity, genetics, and other non-IOP related risk factors in the physiology of ONH aging and the pathophysiology of glaucomatous damage to the ONH. The present report summarizes 20 years of technique development and study results pertinent to the characterization of ONH connective tissue deformation and remodeling in the unilateral monkey experimental glaucoma (EG) model. In it we propose that the defining pathophysiology of a glaucomatous optic neuropathy involves deformation, remodeling, and mechanical failure of the ONH connective tissues. We view this as an active process, driven by astrocyte, microglial, fibroblast and oligodendrocyte mechanobiology. These cells, and the connective tissue phenomena they propagate, have primary and secondary effects on retinal ganglion cell (RGC) axon, laminar beam and retrolaminar capillary homeostasis that may initially be "protective" but eventually lead to RGC axonal injury, repair and/or cell death. The primary goal of this report is to summarize our 3D histomorphometric and optical coherence tomography (OCT)-based evidence for the early onset and progression of ONH connective tissue deformation and remodeling in monkey EG. A second goal is to explain the importance of including ONH connective tissue processes in characterizing the phenotype of a glaucomatous optic neuropathy in all species. A third goal is to summarize our current efforts to move from ONH morphology to the cell biology of connective tissue remodeling and axonal insult early in the disease. A final goal is to facilitate the translation of our findings and ideas into neuroprotective interventions that target these ONH phenomena for therapeutic effect.


Modulation of E2F complexes during G0 to S phase transition in human primary B-lymphocytes.
The pocket protein-E2F complexes are convergence points for cell cycle signaling. In the present report, we identified and monitored the pocket protein-E2F complexes in human primary B-lymphocytes after activation by phorbol 12-myristate 13-acetate. Consistent with previous data from human and mouse fibroblasts and T-lymphocytes, E2F4 and DP1 form the predominant E2F heterodimers both in G0 and G1 phases of the human B-lymphocyte cell cycle, whereas E2F1 and -3 are first detected in late G1, and their expression levels increase towards S phase. Intriguingly, the major E2F complex that we detected in quiescent human B-lymphocytes is consisted of pRB, E2F4, and DP1. Though the levels of DP1 and -2 increase when cells progress from G0 to S, the proportion of DP1 to DP2 remains relatively constant during the cell cycle. We also observed an increase in electrophoretic mobility of the predominant E2F components, DP1 and E2F4, as B-lymphocytes progressed from G0 into early G1. This increase in mobility was attributable to dephosphorylation, as lambda phosphatase treatment could convert the slower migrating forms into the corresponding faster mobility forms. We further demonstrated that this change in phosphorylation status correlates with a decrease in DNA binding activity. This modulation of DNA binding activity mediated through the dephosphorylation of DP1 and E2F4 could help to explain the lack of in vivo DNA footprinting in late G1 and S phases of gene promoters negatively regulated through E2F sites and suggests a novel mechanism for controlling E2F transcriptional activity during the transition from quiescence to proliferation.


Documentation and appropriateness of prescribing for Veterans Administration ambulatory-care patients.
Information about active prescriptions in pharmacy medication profiles of outpatients at a Veterans Administration (VA) medical center was compared with corresponding information in the medical records to determine the completeness of prescription documentation. Appropriateness of prescribing was assessed by comparison with explicit criteria. Information about the active prescriptions included in 300 randomly selected patient medication profiles was collected from August to October 1984. The completeness of prescription information documentation was determined by comparing the data obtained from the patient's medication profile with the corresponding medical record entry. Medication profiles were screened for three types of potentially inappropriate prescribing: inappropriate daily dosage, inappropriate duplication of therapy, and interacting drug combinations. A total of 287 patient medication profiles and medical records were studied. Only 60 medical records (20.9%) had accurate documentation of all drug names, drug strengths, and directions for use when compared with the medication profiles. Evidence of potentially inappropriate prescribing was present in medication profiles of 43.4% of the patients. Medical record documentation was insufficient for a provider to detect 50.0% of the dosage deviations, 33.3% of the duplications of therapy, and 26.1% of the drug-drug interactions. The probability that evidence of potentially inappropriate prescribing would be present in a medication profile increased as the number of drugs per patient increased. However, there was no significant positive association between insufficient medical-record documentation and the presence of any of the three indicators of potentially inappropriate prescribing in the medication profile.(ABSTRACT TRUNCATED AT 250 WORDS)


Isotherm and kinetic modelling of Toluidine Blue (TB) removal from aqueous solution using Lemna minor.
The aim of this study was to investigate the ability of Lemna minor for Toluidine Blue (TB) removal. Influence of the initial concentration over the removal process was considered. Experimental data have been analyzed using Langmuir, Freundlich, Dubinin-Radushkevich (D-R), and Elovich isotherm models. In addition, several kinetic models, pseudo-first-, pseudo-second-order, intraparticle and film diffusion models were considered. Langmuir and Freundlich isotherm suggested a favorable adsorption of TB by Lemna minor plants. From the D-R the mean free energy was calculated to be 11.18 kJ/mol, which indicates that TB adsorption was characterized by a chemisorption process. Kinetic studies showed that liquid film diffusion plays an important role during the process. Adsorption capacities of up to 26.69 mg/g and a high capacity of adaptation indicated that phytoremediation using Lemna minor could be a valuable alternative for dyes removal from wastewaters.


Exotic behavior of the outer shell of bimetallic nanoalloys.
In order to build the phase diagram of Cu-Ag nanoalloys, segregation isotherms for the different sites of the outer shell of a 405-atom cluster have been obtained by means of Monte Carlo simulations using N-body interatomic potentials. A dynamical equilibrium in phase space is observed for the (001) facets as well as for the (111) facets of the truncated octahedron. For the (001) facets, the bistability originates from a structural transition, the facets oscillating collectively between a Cu-rich square shape of coordinence 4 and an Ag-rich diamond shape of coordinence 6. For the (111) facets, the bistability is purely chemical and affects each facet individually. We thus predict the possible coexistence of Cu-pure and Ag-pure (111) facets within the same nanoparticle.


Solution structure of the dimeric zinc binding domain of the chaperone ClpX.
ClpX (423 amino acids), a member of the Clp/Hsp100 family of molecular chaperones and the protease, ClpP, comprise a multimeric complex supporting targeted protein degradation in Escherichia coli. The ClpX sequence consists of an NH2-terminal zinc binding domain (ZBD) and a COOH-terminal ATPase domain. Earlier, we have demonstrated that the zinc binding domain forms a constitutive dimer that is essential for the degradation of some ClpX substrates such as gammaO and MuA but is not required for the degradation of other substrates such as green fluorescent protein-SsrA. In this report, we present the NMR solution structure of the zinc binding domain dimer. The monomer fold reveals that ZBD is a member of the treble clef zinc finger family, a motif known to facilitate protein-ligand, protein-DNA, and protein-protein interactions. However, the dimeric ZBD structure is not related to any protein structure in the Protein Data Bank. A trimer-of-dimers model of ZBD is presented, which might reflect the closed state of the ClpX hexamer.


Cholinoceptor blockers protect against ethanol-induced gastric mucosal damage in rats.
The role of the cholinergic nervous system in ethanol-induced gastric mucosal damage has been examined in rats. Oral administration of 50 or 80% ethanol produced haemorrhagic lesions which were reduced by atropine pretreatment (0.65, 2.5, 5 or 10 mg/kg injected i.p.); there was lesser protection against the higher dose of ethanol. Pirenzepine (a specific M1 receptor antagonist) pretreatment (0.1, 0.2, 1 or 2 mg/kg, injected s.c.) also protected against ethanol-induced gastric injury to a similar extent; it also increased the amount of adherent mucus on the glandular mucosa. This action may, therefore, account for the protective action of the ganglion blocker. It is concluded that ethanol may stimulate the stomach wall ganglionic nicotinic receptors to activate the postganglionic fibres and subsequently the muscarinic receptors which would then trigger off some of the ulcerogenic mechanisms in the stomach. However, ethanol could also produce gastric damage via the non-cholinergic mechanisms; this action becomes more prominent in gastric injury produced by high doses of ethanol.


Fluorimetric determination of rivastigmine in rat plasma by a reverse phase--high performance liquid chromatographic method. Application to a pharmacokinetic study.
A sensitive and selective high performance liquid chromatographic (HPLC) method was developed and validated for the rapid quantification of rivastigmine (CAS 123441-03-2) in micro quantity in rat plasma samples. The chromatographic separation was achieved with a reverse phase monomeric column C18 (4.6 x 250 mm, 5 microm) and the mobile phase consisted of acetonitrile and 20 mmol/L phosphate buffer pH 3.0 (25:75) with a flow rate of 1 mL/min. The effluents were measured by fluorimetric detection with excitation and emission wavelengths at 220 nm and 293 nm, respectively. The calibration curve was linear (r2 > 0.99) ranging from 25-3000 ng/mL and the lower limit of quantification was 25 ng/mL. The method was validated with excellent sensitivity, selectivity, accuracy, precision, recovery and stability. The method has been successfully applied in a pharmacokinetic study of rivastigmine in rats.


Synthesis of bimetallic nanoparticles and their application to growth of multiwalled carbon nanotube forest.
We synthesized bimetallic nanoparticles and used them to grow CNTs with an atmospheric-pressure plasma-enhanced chemical vapor deposition system. FePt and FeCo bimetallic nanoparticles were synthesized by the bottom-up high-temperature polyol process using a simple centrifugal method. The diameter of synthesized nanoparticles ranged from 2 to 5 nm with high uniformity, as measured with a transmission electron microscope. The CNTs synthesis was carried out on bimetallic nanoparticles as a catalyst using acetylene as a carbon source gas. The CNT forests grown exhibited a maximum height of 96 microm, which is relatively high compared with other growth technologies. A forest of highly pure multiwalled CNTs with diameters of 10-20 nm was successfully synthesized on a bimetallic nanoparticle catalyzed substrate. As the growth temperature increased, the quality of CNTs improved remarkably, indicating that the graphitization could be controlled by varying the growth temperature. Furthermore, the oxygen plasma pre-treatment of dispersed bimetallic nanoparticles before CNTs growth could contribute to the production of highly pure CNTs. By TEM measurements, we observed that pure multiwall CNTs without defects or amorphous carbon could be synthesized.


Effect of alpha 1- and alpha 2-adrenoceptor agonists and antagonists on ACTH secretion in intact and in hypothalamic deafferentated rats.
The effect of systemically injected alpha 1- and alpha 2-adrenoceptor agonists and antagonists on ACTH secretion was studied in rats. Epinephrine, norepinephrine, phenylephrine, clonidine, B-HT933, and B-HT920 caused a significant and dose-related increase of the ACTH concentration in the serum. The order of median effective dose (ED50) of these drugs on ACTH secretion was as follows: epinephrine not equal to norepinephrine less than B-HT920 less than clonidine less than phenylephrine much less than B-HT933. Isoproterenol, a beta-adrenoceptor agonist, had no effect on ACTH secretion. ACTH secretion induced by epinephrine or phenylephrine was significantly inhibited by alpha-adrenoceptor antagonists, phentolamine and phenoxybenzamine. However, propranolol, a beta-adrenoceptor antagonist, had no effect on ACTH secretion induced by epinephrine. Prazosin, an alpha 1-antagonist, and yohimbine, an alpha 2-antagonist, significantly blocked ACTH secretion induced by phenylephrine, an alpha 1-agonist, and B-HT933, an alpha 2-agonist, respectively. ACTH secretion induced by norepinephrine or a low dose of clonidine was inhibited by both prazosin and yohimbine. However, ACTH secretion induced by a high dose of clonidine was blocked only by prazosin. In rats with complete deafferentation of the medial basal hypothalamus (MBH), ACTH secretion induced by epinephrine, norepinephrine, and clonidine was significantly blocked, as compared with intact rats. These results suggest that both peripheral alpha 1- and alpha 2-adrenoceptors are involved in ACTH secretion induced by systemically injected adrenergic drugs in rats, and intact neural pathways entering the MBH are necessary for this ACTH releasing action.


Sudden unexplained death in a psychiatric patient--a case report: the role of phenothiazines and physical restraint.
Psychotropic drug use has long been associated with sudden unexplained and unexpected death in psychiatric patients despite controversies surrounding the issue. Physical restraint following violent episodes in psychiatric in-patients is also associated with neurally mediated sudden cardiac death. A case where these two mechanisms have jointly resulted in sudden death is reported. The literature on the subject is reviewed and the measures which may be useful in reducing the incidence of such deaths are discussed. The need for accurate and detailed reporting of such cases is emphasized.


Psychotherapy Alone and Combined With Medication as Treatments for Bipolar II Depression: A Randomized Controlled Trial.
Bipolar II disorder (BP-II) is associated with marked morbidity and mortality. Quetiapine, the treatment with greatest evidence for efficacy in BP-II depression, is associated with metabolic burden. Psychotherapy, a treatment with few side effects, has not been systematically evaluated in BP-II. This study compared psychotherapy plus placebo to psychotherapy plus pharmacotherapy as treatments for BP-II depression. From 2010 to 2015, unmedicated adults (n = 92) with DSM-IV-TR BP-II depression were randomly assigned to weekly sessions of Interpersonal and Social Rhythm Therapy (IPSRT) plus placebo or IPSRT plus quetiapine and followed for 20 weeks. For primary outcomes, IPSRT + quetiapine yielded significantly faster improvement on 17-item Hamilton Depression Rating Scale (F₁,₁₁₅.₄ = 3.924, P = .048) and greater improvement on Young Mania Rating Scale (F₅₈.₅ = 4.242, P = .044) scores. Both groups, however, improved significantly over time with comparable response rates (≥ 50% reduction in depression scores): 67.4% (62/92) in the entire sample, with no between-group differences. Those randomly assigned to their preferred treatment were 4.5 times more likely to respond (OR = 4.48, 95% CI = 1.20-16.77, P = .026). IPSRT + quetiapine assignment was associated with significantly higher body mass index over time (F₆₇.₉₆ = 6.671, P = .012) and rates of dry mouth (79% v. 58%; χ² = 4.0, P = .046) and a trend toward more complaints of oversedation (100% vs 92%; χ² = 3.4, P = .063). IPSRT plus quetiapine resulted in greater symptomatic improvement but also more side effects than IPSRT alone. A subset of participants improved with IPSRT alone, although absence of an inactive comparator limits interpretation of this finding. Receipt of preferred treatment was associated with better outcomes. Harms, benefits, and preferences should be considered when recommending treatments for BP-II depression. ClinicalTrials.gov identifier: NCT01133821.


Are Antimalarial Hybrid Molecules a Close Reality or a Distant Dream?
Emergence of drug-resistant Plasmodium falciparum strains has led to a situation of haste in the scientific and pharmaceutical communities. Hence, all their efforts are redirected toward finding alternative chemotherapeutic agents that are capable of combating multidrug-resistant parasite strains. In light of this situation, scientists have come up with the concept of hybridization of two or more active pharmacophores into a single chemical entity, resulting in "antimalarial hybrids." The approach has been applied widely for generation of lead compounds against deadly diseases such as cancer and AIDS, with a proven potential for use as novel drugs, but is comparatively new in the sphere of antimalarial drug discovery. A sudden surge has been evidenced in the number of studies on the design and synthesis of hybrids for treating malaria and may be regarded as proof of their potential advantages over artemisinin-based combination therapy (ACT). However, it is evident from recent studies that most of the potential advantages of antimalarial hybrids, such as lower toxicity, better pharmacokinetics, and easier formulation, have yet to be realized. A number of questions left unaddressed at present need to be answered before this approach can progress to the late stages of clinical development and prove their worth in the clinic. To the best of our knowledge, this compilation is the first attempt to shed light on the shortcomings that are surfacing as more and more studies on molecular hybridization of the active pharmacophores of known antimalarials are being published.


[Results of treatment of children with chronic myelogenous leukaemia (CML) obtained by the Polish Paediatric Leukaemia/Lymphoma Study Group].
Retrospective analysis of 102 children with CML from 9 paediatric centres in Poland has been performed. A total number of 102 children: 58 boys and 44 girls aged 1-17 years (median 9.4 years old) with CML, treated in the period 1975-1999 were included in the study. Forty eight of 102 (47.1 %) children were treated with cytostatic drugs without IFN alpha: busulfan, hydroxyurea, 6-mercaptopurine or etoposide (VP-16). Fifty four of 102 (52.9%) patients were treated with interferon alpha (IFN alpha) after cytoreductive pretreatment. Thirty out of 102 (29.4%) patients underwent stem cell transplantation (SCT): 24 - matched related donor allo-BMT, 2 - matched unrelated donor allo-BMT, 1 - partially matched related donor T-cell depleted allo-PBPCT, 1 - syngeneic allo-BMT and 2 - autologous PBPCT. Overall survival analysis revealed that 46 of the 102 (45.1%) children remained alive: 5/35 (14.3%) children treated with cytostatics alone, 22/37 (59.5%) children treated with IFN alpha and 19/30 (63.3%) children treated with SCT. Among SCT survivors there are 10/17 (58.8%) children treated with IFN alpha prior to SCT and 9/13 (69.2%) children treated with cytostatics alone prior to SCT. The probability of 5-year survival is 0.51 in the group treated with SCT (median follow-up 58 months); 0.43 in the group treated with IFN alpha (median follow-up 53 months) and 0.23 in the group treated with cytostatics (median follow-up 31 months). Our data show, that BMT is the treatment of choice in CML in children. IFN alpha could be successfully applied as an alternative treatment for those, who do not have a suitable donor for allogeneic SCT. Better outcome in post BMT children, who were not treated with IFN alpha prior to SCT requires confirmation by studies on larger groups of patients. However, it seems to be justified to stop IFN alpha therapy at least 3 months before SCT. The main reason for unsuccessful treatment outcome in patients with CML in Poland remains the still insufficient access to MUD-BMT.


Effect of Feeding History and Time Elapsed From Field Collection on the Movement Behavior and Response to Stimulation in Cimex lectularius (Hemiptera: Cimicidae).
The common bed bug (Cimex lectularius L.) (Hemiptera: Cimicidae) is an obligate blood-sucking insect that has been resurging in many countries. Researching this pest's behavior will help design more effective control methods. In this study, we evaluated the effect of feeding history and time elapsed from field collection on bed bug movement behavior and response to chemical lure or carbon dioxide stimulation in the laboratory. After CO2 was released, bed bugs unfed for 3 d began to return to harborages; in contrast, the ones unfed for 2 and 4 wk spent significantly more time outside their harborages during the first 1 h after than the 1 h before CO2 release. After CO2 release, there was an increase in activity (time spent moving outside harborage) in all bed bugs with different feeding history or time elapsed from field collection. During the 8-h observation period when CO2 was present, bed bug males unfed for 4 wk spent significantly more time exploring outside harborages than the ones unfed for 3 d, 1 wk, and 2 wk. Nymphs collected 1-2 wk and 1 yr ago spent significantly more time exploring outside harborages than the ones collected 43 yr ago. Bed bug's exploratory activity (the total percentage of bed bugs trapped in both baited and unbaited interceptors) was significantly affected by their time elapsed from field collection and their exploratory activity level was 1-2 wk > 6 mo > 5 and 43 yr. Both feeding history and time elapsed from field collection significantly affected bed bug movement, whereas bed bug's response to chemical lure or CO2 (the percentage of bed bugs trapped in the baited interceptor, summarized as the number of bed bugs trapped in the baited interceptor divided by the total number of trapped bed bugs in both baited and unbaited interceptors) was unaffected by the time elapsed from field collection.


Human recombinant interleukin-1 receptor antagonist blocks bone resorption induced by interleukin-1 beta but not interleukin-1 alpha.
Both interleukin-1 alpha (IL-1 alpha) and interleukin-1 beta (IL-1 beta) are powerful stimulators of bone resorption in vivo and in vitro. Interleukin-1 receptor antagonist (IL-1ra) binds to many interleukin-1 receptors. It does not activate the receptor and effectively blocks the action of IL-1 alpha and IL-1 beta. In this study, human recombinant IL-1ra, at 100-fold excess, was found to block bone resorption in cultured mouse calvaria due to IL-1 beta but not IL-1 alpha. These observations may be explained by differential affinities of receptors for IL-1 alpha, IL-1 beta and rhIL-1ra on target bone cells.


Effective concentration and detection of cryptosporidium, giardia, and the microsporidia from environmental matrices.
Cryptosporidium spp., Giardia spp., and members of Microsporidia are enteropathogenic parasites of humans and animals, producing asymptomatic to severe intestinal infections. To circumvent various impediments associated with current detection methods, we tested a method providing multistage purification and separation in a single, confined step. Standard real-time PCR was used as a detection method. Samples spiked with C. parvum and G. intestinalis were split for comparison to standard Method 1623. Results were equivalent to immunomagnetic procedures for Cryptosporidium, and Giardia. Overall percent recovery for Cryptosporidium with Method 1623 averaged 26.89% (std 21.44%; min = 0%; max = 73%) and was similar but less variable for qPCR method at an estimated average of 27.67 (std 17.65%; min = 5%; max = 63%). For Giardia, Method 1623 had an overall average recovery of 27.11% (std 17.98%; min = 1%; max = 58%), while multistage purification and qPCR had an estimated lower overall recovery at 18.58% (std 13.95%; min = 0%; max = 35%). Microsporidia were also readily detected with an estimated recovery of 46.81% overall (std 17.66%; min = 18%; max = 70%) for E. intestinalis and 38.90% (std 14.36%; min = 13%; max = 62%) for E. bieneusi.


[INCIDENCE, PREDISPOSING RISK FACTORS FOR THE DEVELOPMENT AND SPREADING OF ACUTE INTESTINAL INFECTIONS IN THE NORTH-EASTERN REGION OF UKRAINE].
Using data of the branch statistical reporting of the State Sanitary and Epidemiological Service in Sumy region and Sumy Regional State Laboratory of Veterinary Medicine, the incidence rate, modern risk factors for the development and spreading of acute infectious diarrheas were determined in the North-Eastern region of Ukraine. Under the current conditions incidence rate indices of acute intestinal infections and food toxicoinfections are within the range of 159.8-193.6 per 100 thousands. pop. Seasonal and epidemical rises are associated with a species of the agent. In the etiological structure of acute diarrheal infections there are dominated viruses, of food toxicoinfections--Klebsiellae pneumoniae, Staphylococcus aureus and Enterobacter cloacae (p < 0.05). Predictors of the complication of epidemiological situation of Shigella infections are the gain in the detection of bacterially contaminated samples of milk and dairy products (r = 0.75), for food toxicoinfections caused by Klebsiellae pneumoniae and Enterobacter cloacae--pastry with cream and cooking meat products (r = 0.64; r = 0.75). Epizootic situation in the region affects on the salmonellosis incidence rate of the population (r = 0.89). There were revealed correlations between the selection of E. coli bacteria from swabs taken from the enterprises of catering, in child care centers and the levels of incidence rates of salmonellosis, acute intestinal infections of unknown etiology (r = 0.59; r = 0.60). Timely detection and sanitation of Shigella carriers are a powerful instrument to reduce the incidence rate of shigellosis (r = 0.83).


Multiresidue Determination of Growth Promoters in Bovine Serum using QuEChERS and UHPLC-Q-ORBITRAP: Validation and In Vivo Study.
A reliable method using a QuEChERS approach and liquid chromatography coupled to Q-Orbitrap mass spectrometry was optimized and validated for the quantification of 20 growth promoters in bovine serum. The recoveries ranged from 91.4-114.1%, relative standard deviations varied between 0.3-4.0%, and CCα values were between 0.023-0.350 μg L-1. The developed method was applied in an in vivo study using steers, which were intramuscularly treated with commercial injections containing stanozolol. A rapid metabolization was observed, with a detection window ranging from 3 to 10 days. The stability of incurred stanozolol was confirmed after 240 days at -20 °C and also after 5 freeze-thaw cycles. To the best of our knowledge, this is the first work in which an in vivo study was performed to support the monitoring of stanozolol in bovine serum. In addition, the use of Q-Orbitrap high-resolution mass spectrometry allows for retrospective analysis from a surveillance perspective.


Unusual mechanism of hypotensive activity exerted by erytrho-1-(1-[2-(1,4-benzodioxan-2-yl)-2-OH-ET-a1-4-piperidyl)-2-benzimidazolinone (R 28935).
In the dog, erythro-1-[2-(1,4benzodioxan-2-yl)-2-OH-ET]-4-piperidyl)-2-benzimidazolinone (R 28935) lowers the blood pressure for several hours at dosages of 80 mug/kg when injected intravenously, of 10 mug/kg when injected into the vertebral artery and of 1.25 mug/kg when injected suboccipitally. No alpha- or beta-receptor blocking activity can be elicited at these doses. The carotid occlusion reflex is markedly reduced by low doses of R 28935 (40 to 80 mug/kg i.v.), whereas the pressor response elicited by electrical stimulation of the hypothalamus remains unimpaired. The hypotensive effect of R 28935 is not antagonized by piperoxan, desmethylimipramine or nalorphine. This lowering of the blood pressure is associated with a decrease of the peripheral vascular resistance and with a slight tendency towards bradycardia. It is concluded that R 28935 is a potent blood pressure lowering drug, acting on the brain stem, presumably in the pontomedullary region--although the drug has no alpha-sympathomimetic activity.


Global gene profiling of VCP-associated inclusion body myopathy.
Inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia (IBMPFD) is an autosomal dominant disorder caused by mutations in the Valosin-containing protein (VCP) gene on chromosome 9p12-13. Patients demonstrate limb girdle muscle weakness, which eventually progresses to involve respiratory muscles, and death from respiratory and cardiac failure. This is the first investigation to analyze key molecular mediators and signaling cascades in skeletal muscle causing myopathy by global gene microarray in hopes of understanding the dysregulated genes and molecular mechanisms underlying IBMPFD and the hope of finding novel therapeutic targets. We determined expression profiles using Human Genome Array microarray technology in Vastus lateralis muscles from patients and their first-degree relatives. We analyzed gene annotations by Database for Annotation, Visualization and Integration Discovery and identified differentially dysregulated genes with roles in several novel biological pathways, including regulation of actin cytoskeleton, ErbB signaling, cancer, in addition to regulation of autophagy, and lysosomal signaling, known disrupted pathways in VCP disease. In this report, we present data from the first global microarray analyzing IBMPFD patient muscles and elucidating dysregulated pathways to further understand the pathogenesis of the disease and discover potential therapeutics.


In vitro and cellular activities of the selected fruits residues for skin aging treatment.
Peel extracts of litchi and rambutan, and that of tamarind seed coat were investigated in relation to their utility in skin-aging treatments. Standardized extracts of tamarind were significantly (p < 0.05) more efficient at O2 •- scavenging (IC50 = 27.44 ± 0.09) than those of litchi and rambutan (IC50 = 29.57 ± 0.30 and 39.49 ± 0.52 μg/ml, respectively) and the quercetin standard (IC50 = 31.88 ± 0.15 μg/ml). Litchi extract proved significantly (p < 0.05) more effective for elastase and collagenase inhibition (88.29 ± 0.25% and 79.46 ± 0.92%, respectively) than tamarind (35.43 ± 0.68% and 57.69 ± 5.97%) or rambutan (31.08 ± 0.38% and 53.99 ± 6.18%). All extracts were safe to human skin fibroblasts and inhibit MMP-2, with litchi extract showing significantly (p < 0.01) enhanced inhibition over the standard, vitamin C (23.75 ± 2.74% and 10.42 ± 5.91% at 0.05 mg/ml, respectively). Extracts suppress melanin production in B16F10 melanoma cells through inhibition of tyrosinase and TRP-2, with litchi extract being the most potent, even more so than kojic acid (standard). These results highlight the potential for adding value to agro-industrial waste, as the basis for the sustainable production of innovative, safe, anti-aging cosmetic products.


Minimally Invasive Endoscopic Approach to the Cervicothoracic Junction for Vertebral Osteomyelitis.
The selection of an anterior, lateral, or posterior approach to the cervicothoracic junction for surgical treatment of vertebral osteomyelitis is still a matter of debate. These ordinary approaches generally require an extensile exposure. This article describes a less invasive approach case of a vertebral osteomyelitis of T2/3 using a video-assisted operating technique of thoracic surgery (VATS). A 78-year-old female underwent anterior debridement and interbody fusion with bone graft at T2/3 using a lateral surgical approach through a right thoracotomy with VATS. The VATS through two small skin incisions in the axillary region provides a good view without requiring elevation of the scapula with extensile muscle dissection and rib resection. There was no complication without partial lobectomy due to pleural adhesion during the perioperative period. Currently, at 1 year after operation, the patient has no back pain with neurologically normal findings and no inflammation findings (CRP was 0.01 mg/dl). Although the operating field of the upper thoracic level in the lateral approach is generally deep and narrow, the VATS provides a good view and allows us to perform adequate debridement and bone fusion at the T2/3 level with a less invasive approach than those previously described anterior or laterally or posterior approach.


Autosomal dominant carpal tunnel syndrome in a Karaite family.
A clinical examination and a history of 64 members belonging to four generations of a Karaite kindred revealed 11 patients with carpal tunnel syndrome (CTS). Bilateral involvement and early age of onset are salient features. The mutation may be traced in four generations. Hereditary primary CTS may be more prevalent than hitherto suspected.


Palladium-catalyzed alkylation of sp2 and sp3 C-H bonds with methylboroxine and alkylboronic acids: two distinct C-H activation pathways.
Palladium-catalyzed alkylations of sp2 and sp3 C-H bonds with either methylboroxine or alkylboronic acids were developed. Ag2O or AgCO3 is used as a crucial oxidant and promoter for the transmetalation step. Ether, ester, alcohol, and alkene functional groups are tolerated. A new C-H activation pathway differing from the cyclometalation process is elucidated using methylboroxine as the coupling partner.


Revascularization after surgical repositioning of one-tooth dento-osseous segments.
Vascularization, revascularization, and bone healing were studied after two different surgical techniques for surgical repositioning of single-tooth dento-osseous segments in adult mongrel dogs. Microangiographic and histologic studies of both one-stage and two-stage techniques for immediate surgical repositioning of single-tooth dento-osseous segments showed early but transient vascular ischemia, minimal osteonecrosis, and osseous union between most of the osteotomized segments. The attached soft tissue provided an adequate vascular pedicle for immediate repositioning of small dento-osseous segments by interdental and subapical osteotomies. The results of these clinically analogues studies support the clinical use of techniques that maximize the attachment of the gingiva to the mobilized dento-osseous segment.


Sample sizes for estimation of the odds ratio in unmatched case-control studies.
A method is presented to obtain sample sizes for cases and controls that are required to provide approximate confidence intervals on the log odds ratio of predetermined width 2d and probability of coverage as a function of assumed exposure rates in the control group, assumed odds ratio psi, required d, and ratio C:1 of controls to cases.


Asymmetric synthesis of isoquinolinonaphthyridines catalyzed by a chiral Brønsted acid.
A catalytic asymmetric method for the synthesis of chiral isoquinolinonaphthyridines has been developed. A chiral disulfonimide catalyzes a redox cyclization reaction between 2-methyl-3-aldehydeazaarenes and 1,2,3,4-tetrahydroisoquinolines to deliver a range of isoquinolinonaphthyridines with good to high yields (up to 91%) and up to 92 : 8 er.


An Engineered Pathway for Production of Terminally Sialylated N-glycoproteins in the Periplasm of Escherichia coli.
Terminally sialylated N-glycoproteins are of great interest in therapeutic applications. Due to the inability of prokaryotes to carry out this post-translational modification, they are currently predominantly produced in eukaryotic host cells. In this study, we report a synthetic pathway to produce a terminally sialylated N-glycoprotein in the periplasm of Escherichia coli, mimicking the sialylated moiety (Neu5Ac-α-2,6-Gal-β-1,4-GlcNAc-) of human glycans. A sialylated pentasaccharide, Neu5Ac-α-2,6-Gal-β-1,4-GlcNAc-β-1,3-Gal-β-1,3-GlcNAc-, was synthesized through the activity of co-expressed glycosyltransferases LsgCDEF from Haemophilus influenzae, Campylobacter jejuni NeuBCA enzymes, and Photobacterium leiognathi α-2,6-sialyltransferase in an engineered E. coli strain which produces CMP-Neu5Ac. C. jejuni oligosaccharyltransferase PglB was used to transfer the terminally sialylated glycan onto a glyco-recognition sequence in the tenth type III cell adhesion module of human fibronectin. Sialylation of the target protein was confirmed by lectin blotting and mass spectrometry. This proof-of-concept study demonstrates the successful production of terminally sialylated, homogeneous N-glycoproteins with α-2,6-linkages in the periplasm of E. coli and will facilitate the construction of E. coli strains capable of producing terminally sialylated N-glycoproteins in high yield.


Posttraumatic growth is related to subjective well-being of aid workers exposed to cumulative trauma in Palestine.
The present study examined how stress reactions after traumatic events influence subjective well-being (SWB) via the indirect effect of posttraumatic growth (PTG) in two samples of Palestinian professional helpers from the Gaza Strip and West Bank ( n = 201). Using the General Health Questionnaire (GHQ-12) as a dependent measure of well-being, and PTGI-10, PANAS-20, WHO-5 BREF, and IES-13 questionnaires as independent variables, structural equation modelling (SEM) was used to examine whether: (a) cumulative trauma was negatively and directly related to subjective well-being; (b) levels of trauma were positively and directly related to posttraumatic growth; and (c) PTG was positively and directly related to subjective well-being. The findings suggest that posttraumatic growth contributes to mitigating and buffering (on the order of approximately 10%) the effect of trauma on subjective well-being. PTG seems to be a resource that can help aid workers deal with the consequences of stressful life events. Clinical implications and directions for supervision and training are discussed.


JUN-Mediated Downregulation of EGFR Signaling Is Associated with Resistance to Gefitinib in EGFR-mutant NSCLC Cell Lines.
Mutations or deletions in exons 18-21 in the EGFR) are present in approximately 15% of tumors in patients with non-small cell lung cancer (NSCLC). They lead to activation of the EGFR kinase domain and sensitivity to molecularly targeted therapeutics aimed at this domain (gefitinib or erlotinib). These drugs have demonstrated objective clinical response in many of these patients; however, invariably, all patients acquire resistance. To examine the molecular origins of resistance, we derived a set of gefitinib-resistant cells by exposing lung adenocarcinoma cell line, HCC827, with an activating mutation in the EGFR tyrosine kinase domain, to increasing gefitinib concentrations. Gefitinib-resistant cells acquired an increased expression and activation of JUN, a known oncogene involved in cancer progression. Ectopic overexpression of JUN in HCC827 cells increased gefitinib IC50 from 49 nmol/L to 8 μmol/L (P < 0.001). Downregulation of JUN expression through shRNA resensitized HCC827 cells to gefitinib (IC50 from 49 nmol/L to 2 nmol/L; P < 0.01). Inhibitors targeting JUN were 3-fold more effective in the gefitinib-resistant cells than in the parental cell line (P < 0.01). Analysis of gene expression in patient tumors with EGFR-activating mutations and poor response to erlotinib revealed a similar pattern as the top 260 differentially expressed genes in the gefitinib-resistant cells (Spearman correlation coefficient of 0.78, P < 0.01). These findings suggest that increased JUN expression and activity may contribute to gefitinib resistance in NSCLC and that JUN pathway therapeutics merit investigation as an alternate treatment strategy. Mol Cancer Ther; 16(8); 1645-57. ©2017 AACR.


Increased peak systolic velocity in the renal artery of paediatric kidneys transplanted to adult recipients.
Paediatric kidneys transplanted to adult recipients increase in size after transplantation. It is unknown if the renal artery diameter increases concomitantly with the kidney. This study was performed to assess if peak systolic velocity (PSV) in the renal arteries of paediatric kidneys transplanted to adult recipients is comparable to PSV in the renal arteries of adult kidneys transplanted to adult recipients. Subjects and methods. Fifteen adult patients with paediatric renal transplants were examined with ultrasound Doppler and compared with a control group of adult recipients with adult transplants. MR angiography (MRA) or intra-arterial angiography (IA) was performed in patients with elevated PSV. MRA renal diameters of the paediatric transplants were compared with adult transplants. The mean maximum PSV of the paediatric kidneys was 2.0 m/s (0.9-3.8), almost twice compared with the adult grafts transplanted to adult recipients, 1.1 m/s (0.7-1.6), P < 0.001. Seven paediatric transplants had a PSV >1.8 m/s, but only two had significant stenosis on MRA/IA. All patients had excellent blood pressure and renal function. The mean diameter of the paediatric renal arteries was 4.1 mm (3.4-6.0), whereas the mean for the adult renal arteries was 5.6 mm (4.8-6.9), P = 0.02. Adult recipients of paediatric kidneys have significantly higher maximum PSV in the renal artery compared to adult recipients of adult grafts. The significantly smaller renal artery diameter might explain the high PSV. A PSV >1.8 m/s by itself does not necessarily indicate transplant renal artery stenosis in paediatric kidneys transplanted to adult recipients, but should be related to clinical findings.


Epidemiologic and clinical studies of Chlamydia trachomatis infection in northeastern Poland.
We tested a total of 735 men and women, who either had clinical symptoms of lower urogenital tract infection or were considered for epidemiological reasons to be at high risk for sexually transmitted diseases, for Chlamydia trachomatis infection. Microbiologic examinations were performed by tissue culture with cycloheximide-treated McCoy cells. C. trachomatis infection was diagnosed in approximately 50% of men with nongonococcal urethritis, 23.5% of men with gonococcal urethritis, 69% of men with postgonococcal urethritis, and in 45% of male partners of C. trachomatis-positive women. Among men under 35 years of age with epididymitis, C. trachomatis was isolated from 42%, whereas Neisseria gonorrhoeae was found in only 21 men. C. trachomatis was isolated from 59% of women with nongonococcal cervicitis, 46% of those with gonococcal cervicitis, and 74% of those with postgonococcal cervicitis. Among female partners of men with nongonococcal urethritis, 68% were C. trachomatis-positive, as were 73.5% of the female contacts of C. trachomatis-positive men. In the groups of men and women without clinical or epidemiologic evidence of sexually transmitted infection, C. trachomatis-positive cultures were obtained from 3.8% and 3.6%, respectively. These studies revealed that the prevalence of C. trachomatis infection in northeastern Poland is high and is similar to that reported in Western countries.


Multiplicative Lévy processes: Itô versus Stratonovich interpretation.
Langevin equation with a multiplicative stochastic force is considered. That force is uncorrelated, it has the Lévy distribution and the power-law intensity. The Fokker-Planck equations, which correspond both to the Itô and Stratonovich interpretation, are presented. They are solved for the case without drift and for the harmonic oscillator potential. The variance is evaluated; it is always infinite for the Itô case whereas for the Stratonovich one it can be finite and rise with time slower that linearly, which indicates subdiffusion. Analytical results are compared with numerical simulations.


[Hypostamine (tritoqualine), a synthetic reference antihistaminic].
The role of histamine in hypersensitivity reactions justifies the use of antagonistic medication. The symptomatic action of the antihistamines has led many workers to forget the role of the drug in reducing histamine (hypohistaminic), in which interest should remain as a curative and mainly preventive medication. The main indications for the action of this drug at the level of physiopathological mechanism involved are: disorders that implicate the production of endogenous histamine, prevention of histamine release, reduction of over-production of histamine by regulation of receptor saturation, symptomatic action without side effects.


Time-resolved crystallography using the Hadamard transform.
We describe a method for performing time-resolved X-ray crystallographic experiments based on the Hadamard transform, in which time resolution is defined by the underlying periodicity of the probe pulse sequence, and signal/noise is greatly improved over that for the fastest pump-probe experiments depending on a single pulse. This approach should be applicable on standard synchrotron beamlines and will enable high-resolution measurements of protein and small-molecule structural dynamics. It is also applicable to other time-resolved measurements where a probe can be encoded, such as pump-probe spectroscopy.


Immobilization of DNA on 11-mercaptoundecanoic acid-modified gold (111) surface for atomic force microscopy imaging.
Immobilized DNA on preformed 11-mercaptoundecanoic acids (MUDA) self-assembled monolayers (SAMs) on a gold (111) surface was bound by a divalent cation bridges was imaged by atomic force microscopy (AFM). The DNA immobilization was attributed to the formation of ionic bridges between the carboxylate groups of MUDA and the phosphate groups of DNA. AFM images revealed that DNA molecules could be immobilized strongly enough to permit stable and reproducible imaging. The effect of different bridge cations, such as Mg(2+), Zn(2+) and Cu(2+), and the pH of DNA assembled solution on immobilization and conformation of DNA was studied. Plasmid DNA pBR 322/Pst I molecules were straightened by using a molecular combing technique on the MUDA surface.


miR-330 regulates Drp-1 mediated mitophagy by targeting PGAM5 in a rat model of permanent focal cerebral ischemia.
Growing evidence have suggested that mitophagy could exert a neuroprotective role in brain ischemia by removing the damaged mitochondria. However the upstream mechanisms of mitophagy are remain unclear. We previously observed a decrease of miR-330 in a miRNA profile of plasma from patients within 3 h after a stroke. Our study further focused on the role and mechanism of miR-330 in mitophagy induced by hypoxia-ischemia (H/I) in rats. Cerebral ischemia model in rats was made with permanent middle cerebral artery occlusion (pMCAO). In vitro, ischemic model in primary neurons was established with oxygen-glucose deprivation. Various methods, including TTC staining, immunofluorescence staining, Western blot, ELISA, flow cytometry, and transmission electron microscopy were used to clarify the role of miR-330 after H/I, and whether miR-330/phosphoglycerate mutase family member 5 (PGAM5) axis could regulate dynamin-related protein 1 (Drp-1) mediated mitophagy. MiR-330 levels decreased both in rat plasma and in ipsilateral brain tissues after H/I. Pretreating animals with miR-330 antagomir could decrease cerebral infarction, edema, mortality, and apoptosis after 6-h pMCAO. PGAM5 was validated as a target of miR-330. MiR-330 agomir and antagomir transfection respectively decreased and increased the PGAM5 protein expression. MiR-330 could down-regulate mitophagy by inhibiting PGAM5-induced Drp1 dephosphorylation, thus reducing the recruitment of Drp1 to mitochondrial outer membrane and Drp1-mediated mitophagy after H/I. Our results suggest a role of miR-330 in regulating mitophagy. Our study suggested a novel miR-based intervention strategy for stroke.


Major determinants and long-term outcomes of successful balloon dilatation for the pediatric patients with isolated native valvular pulmonary stenosis: a 10-year institutional experience.
We report herein major determinants and long-term outcomes of balloon dilatation (BD) for 27 pediatric patients with isolated native valvular pulmonary stenosis (VPS). From May 1997 to May 2003, 27 pediatric patients with VPS (pressure gradients >or= 40 mmHg) were enrolled in this retrospective study. Single-balloon maneuver was applied in 26 patients, and double-balloon maneuver in 1. After BD, the pressure gradients were documented simultaneously by pullback maneuver by cardiac catheterization and echocardiography within 24 hours, at 1-month, 3-month, 1-year, and 4-to-10-year follow-ups. Before BD, the echocardiographic gradients ranged from 40 to 101 mmHg (61+/-19, 55), and from 40 to 144 mmHg (69+/-32, 60) by pressure recordings. After BD, the gradients ranged from 12 to 70 mmHg (29+/-13, 27) by pressure recording (p<0.001), and from 11 to 64 mmHg (27+/-12, 26) by echocardiography within 24 hrs (p<0.001). The ratios of the systolic pressure of the right ventricle to those of the left ventricle were 55 to 157% (89+/-28, 79%) before BD, and 30 to 79% (47 +/- 13, 42%) after BD (p<0.001). Follow-up (7.7+/-5.7, 4.5 years) echocardiographic gradients ranged from 11 to 61 mmHg (25+/-11, 24). Two patients did not have immediate success owing to infundibular spasm. Improved right ventricular compliance could be accounted for the ultimate success in these 2 patients. The ultimate successful rate was 100%. BD can achieve excellent long-term outcomes in the pediatric patients with isolated native VPS.


One-year outcome of argon laser photocoagulation of pinguecula.
To determine the efficacy and safety of argon laser photocoagulation of pinguecula by evaluating 1-year outcomes. Twenty-one eyes of 15 patients treated with argon laser photocoagulation (photocoagulation group) and 23 eyes of 16 patients treated with surgical excision (excision group) were retrospectively reviewed. Cosmetic outcome was evaluated by patient's self-report on a 5-grade scale (excellent, good, acceptable, poor, and very poor), and evaluation of treatment outcome was based on objective findings of anterior segment photography and anterior segment optical coherence tomography. Overall cosmetic results were excellent or good in 90.5% of laser-treated cases and 78.6% of surgically treated cases. There was no significant difference in cosmetic outcome (P = 0.15). Nineteen (90.5%) and 17 (63.9%) cases demonstrated complete removal of pingueculae after laser photocoagulation and surgical excision, respectively. The anatomic outcome was not significantly different between the 2 groups (P = 0.25). Subconjunctival hemorrhage and conjunctival scarring with an irregular surface occurred less frequently in the photocoagulation group than in the excision group [34.8% vs. 0% (P = 0.003) and 30.4% vs. 4.8% (P = 0.048), respectively]. Argon laser photocoagulation is an effective and safe method for removing a pinguecula for cosmetic purposes. The method facilitates control of the extent and depth of removal and thus minimizes conjunctival defects and other complications.


Factors affecting adherence to asthma treatment in an international cohort of young and middle-aged adults.
A major reason of the poor control of asthma is that patients fail to adhere to their treatment. The aim of the study was to identify factors affecting changes in asthma treatment adherence in an international cohort. A follow-up study was carried out by means of a structured clinical interview in 971 subjects with asthma from 12 countries who participated in both the European Community Respiratory Health Survey: ECRHS-I (1990-94) and ECRHS-II (1998-2002). Subjects were considered adherent if they reported they normally took all the prescribed drugs. A logistic model was used to study the adjusted effect of the determinants. The net change in adherence to anti-asthmatic treatment per 10 years of follow-up was -2% (95% CI: -9.5, 5.5), 7.5% (-2.6, 17.6), 15.0% (6.6, 23.5) and 19.8% (4.1, 35.5), respectively, in Nordic, Mediterranean, Continental and extra-European areas. Among the 428 non-adherent subjects in ECRHS-I, having regular consultations with health care professionals was the strongest predictor of increased adherence (OR 3.32; 95% CI: 1.08-10.17). Among the 543 adherent subjects in ECRHS-I, using inhaled corticosteroids significantly predicted a persistence of adherence (OR 2.04; 95% CI: 1.11-3.75). No effect of gender, age, duration of the disease, smoking habit and educational level was observed. Our findings highlight the key role of doctors and nurses in educating and regularly reviewing the patients and support the efforts for an improvement of clinical communication.


Quantification of morphologic, cytologic, and kinetic parameters of unirradiated swine skin: a histologic model.
The gross changes of erythema and desquamation produced by irradiation indicate population and functional variations occurring in the epidermis, microvasculature, and dermis. However, the parameters do not distinguish the individual population kinetics. This study determines multiple histologic and cell kinetic parameters of unirradiated swine skin. The prickle cell layer exists as a shell three to six cells thick. The proliferative basal layer exists as a confluent monolayer with 2031 +/- 48 cells/cm; it has a growth fraction of 1, an average cell generation time of 12.3 +/- 2.4 days, a TS of 9.4 +/- 2.9 hr, and a TS + T1/2M of 17 to 19 hr. The labeling index is 3.9 +/- 0.1% with a diurnal variation having a 5% peak at 1800 hr and a 2.5% nadir at 0900-1100 hr. The mitotic index varies from 1.7 to 3.2% and has no clear-cut diurnal variation. These values are similar to those available for man. These data and those published previously are utilized to define a histologic model of the irradiated epidermal cell renewal system. These measured values are compared with those derived from analysis of available time-dose isoeffect data using a single-hit multitarget and a linear-quadratic model. The derived dose-survival curve is steeper with a D0 between 97 and 255 rad compared to the measured value of 337 rad.


The odorant receptor co-receptor from the bed bug, Cimex lectularius L.
Recently, the bed bug, Cimex lectularius L. has re-emerged as a serious and growing problem in many parts of the world. Presence of resistant bed bugs and the difficulty to eliminate them has renewed interest in alternative control tactics. Similar to other haematophagous arthropods, bed bugs rely on their olfactory system to detect semiochemicals in the environment. Previous studies have morphologically characterized olfactory organs of bed bugs' antenna and have physiologically evaluated the responses of olfactory receptor neurons (ORNs) to host-derived chemicals. To date, odorant binding proteins (OBPs) and odorant receptors (ORs) associated with these olfaction processes have not been studied in bed bugs. Chemoreception in insects requires formation of heteromeric complexes of ORs and a universal OR coreceptor (Orco). Orco is the constant chain of every odorant receptor in insects and is critical for insect olfaction but does not directly bind to odorants. Orco agonists and antagonists have been suggested as high-value targets for the development of novel insect repellents. In this study, we have performed RNAseq of bed bug sensory organs and identified several odorant receptors as well as Orco. We characterized Orco expression and investigated the effect of chemicals targeting Orco on bed bug behavior and reproduction. We have identified partial cDNAs of six C. lectularius OBPs and 16 ORs. Full length bed bug Orco was cloned and sequenced. Orco is widely expressed in different parts of the bed bug including OR neurons and spermatozoa. Treatment of bed bugs with the agonist VUAA1 changed bed bug pheromone-induced aggregation behavior and inactivated spermatozoa. We have described and characterized for the first time OBPs, ORs and Orco in bed bugs. Given the importance of these molecules in chemoreception of this insect they are interesting targets for the development of novel insect behavior modifiers.


Metallothionein Gene Deficiency Facilitates the Differentiation of C2C12 Myoblasts into Slow-Twitch Myotubes.
Metallothionein (MT) 1 and 2 are ubiquitously expressed cysteine-rich, low molecular weight proteins. MT expression is upregulated in skeletal muscle during aging. MTs also play role in multiple types of skeletal muscle atrophy. Meanwhile, it has been reported that MT1 and MT2 gene deficiency increases myogenesis in MT knockout (MTKO) mice. However, little is known about the effect of MTs on muscle formation and atrophy. In this study, we investigated the effect of MT1 and MT2 gene knock-out using the clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (CRISPR-Cas9) system in an in vitro skeletal muscle differentiation model (C2C12 cell line). MT deficiency promoted myogenic differentiation and myotube formation in C2C12 cells. Muscle-specific transcription factors MyoD and myogenin were found to be upregulated at the late stage of myotube differentiation in MTKO cells. Furthermore, the fast-twitch myosin heavy chain (MyHC) protein expression was similar in MTKO and mock-transfected myotubes, but slow-MyHC expression was higher in MTKO cells than in mock cells. The MT gene deletion did not affect the number of fast MyHC-positive myotubes but increased the number of slow MyHC-positive myotubes. Treatment with the antioxidant N-acetylcysteine (NAC) inhibited the increase in the number of slow MyHC-positive myotubes as well as slow-MyHC expression in MTKO cells. In contrast, NAC treatment did not alter the number of fast MyHC-positive myotubes or the expression of fast-MyHC in MTKO cells. These results suggest that the antioxidant effects of MTs may be involved in slow-twitch myofiber formation in skeletal muscle.


Implementation of Telemedicine Consultation to Assess Unplanned Transfers in Rural Long-Term Care Facilities, 2012-2015: A Pilot Study.
Public and private entities in the United States spend billions of dollars each year on potentially avoidable hospitalizations. This is a common occurrence in long-term care (LTC) facilities, especially in rural jurisdictions. This article details the creation of a telemedicine approach to assess residents from rural LTC facilities for potential transfer to hospitals. An electronic LTC (eLTC) pilot was conducted in 20 pilot LTC facilities from 2012-2015. Each site underwent technologic assessment and upgrading to ensure that 2-way video communication was possible. A new central "hub" was staffed with advanced practice providers and registered nurses. Long-term care pilot sites were trained and rolled out over 3 years. This article reports development and implementation of the pilot, as well as descriptive statistics associated with provider assessments and averted transfers. Over 3 years, 736 eLTC consultations occurred in pilot sites. One-quarter of consultations occurred between 10 pm and 9 am. Overall, approximately 31% of cases were transferred. This decreased from 54% of cases in 2013 to 17% in 2015. Rural pilot facilities had an average of 23 eLTC consults per site per year. Averted transfers represent a dramatic benefit to the residents, as potentially avoidable hospitalizations cause undue stress and allow for nosocomial infections, among other risks. In addition, averting these unnecessary transfers likely saved the taxpayers of the United States over $5 million in admission-related charges to Centers for Medicare and Medicaid Services (511 avoided transfers × $11,000 per average hospitalization from a LTC facility). Overall, the eLTC pilot showed promise as a proof-of-concept. The pilot's implementation resulted in increasing utilization and promising reductions in unnecessary transfers to emergency departments and hospitalizations.


Tumor infiltrating lymphocytes in squamous cell carcinoma of the head and neck: mechanisms of enhancement using prostaglandin synthetase inhibitors.
Indomethacin has been shown clinically to inhibit growth of SCCHN (Panje, 1981). This inhibition appears to be due to augmentation of cellular immunity. The inhibitory effect of indomethacin may act by limiting tumor associated prostaglandin E2 production, thereby allowing return of costimulatory cytokines by antigen presenting cells. This would have the net result of relief from host unresponsiveness and promotion of B-cell and CTL differentiation, allowing the individual to mount an effective response. The enhancement of tumor infiltrating lymphocytes in SCCHN seen with indomethacin administration could presumably be further augmented when given in combination with cytokine therapy. Future investigation may allow the biochemical staging of an individuals' tumor to determine the optimal combination of cytokine therapy and prostaglandin inhibition through selective use of NSAID's. The effect of NSAID manipulation of prostaglandin and leukotriene metabolism on prevention of metastatic disease in SCCHN has yet to be studied. Given that a preselected, potentially responsive subset of immunocytes exists within the tumor tissue and lymph nodes, the development of the LAK phenomenon in TIL's and tumor draining lymph nodes from surgical specimens is a viable and exceedingly interesting area for future investigations in autologous LAK immunotherapy. The potential exists to harvest a preselected population of tumor infiltrating (Boscia, 1988) or tumor draining immunocytes (McKinnon, 1990). These can then potentially be returned to a state of antigen responsiveness with a combination of cytokine exposure (e.g. rIL-2) and systemic cytokine therapy. With subsequent inhibition of tumor associated prostaglandin synthesis by the systemic administration of prostaglandin synthesis inhibitors, it may be possible to successfully alter the host response to tumor.


Inpatient care or outplacement: which is better for the psychiatric medically infirm patient?
Eighty-four geriatirc ward patients were randomly assigned to groups targeted for outplacement planning or inpatient care. During the following year, half of the former were placed in community settings while nearly all of the latter remained in the hospital. Neither the physical health, level of self-care, or psychiatric condition ratings of the two groups changed differentially over that time. However, the mean Morale Inventory score of the outplacement sample improved while that of the in-patient group remained static. Additional analyses were run between three groups - outplacement planning subjects who were released, those who were not released, and inpatient planning men who were not released. These results confirmed those of the first analyses; the only significant difference appeared on the Morale Inventory, the patients who left showing more improvement than the other two groups. The results argue for an increased emphasis on outplacement programs among geriatric patients.


Detection of HPV 52, 58 and 87 in cervicovaginal intraepithelial lesions of HIV infected women.
HIV positive or otherwise immunosuppressed patients are susceptible to cervicovaginal infections with a wide spectrum of HPV types. The aim of our study was to investigate the distribution of HPV in squamous intraepithelial lesions (SIL) with regard to HIV infection. We evaluated the HPV status in 20 HIV positive women with cytologically assessed SIL (11 high grade, 9 low grade) in relation to clinical and histological/cytological findings. Twenty HIV negative patients (15 high grade, 5 low grade SIL) served as a control. HPV typing was performed by polymerase chain reaction followed by PCR-ELISA (HPV 6/11, 16/18, 31/33, 40, 45, 52, 58) or sequence analysis of the amplicon (HPV 73, 87). HPV 52 was the most common type in the HIV positive group (8 HIV positive cases vs. 1 HIV negative case). HPV 16/18 was found in 6 HIV positive and 11 HIV negative patients. Further types detected in HIV positive patients were HPV 40, 58, 73 and 87 (one case each). No correlation was found between the HPV status and the CD4+ count or the grading of SIL. Persisting HPV infection with recurrence of SIL was documented in 5 cases after initial therapy of HPV positive lesions (HPV 87, 73, 58, 31/33, 16/18). HIV infected patients reveal a wider spectrum of HPV types in cervicovaginal SIL than HIV negative women. Especially HPV 87 and its relation with HIV infection and development and persistence of SIL needs further investigation. Our results indicate the inclusion of otherwise rare HPV types in screening programs for HIV positive and immunosuppressed patients.


Immediate early induction of mRNAs for ethylene-responsive transcription factors in tobacco leaf strips after cutting.
To investigate the functional relationship between the expression of genes for ethylene-responsive transcription factors (ERFs) and the expression of ethylene-responsive genes, we examined the expression of genes for ERFs and the expression of a reporter gene in transgenic tobacco that carried a gene for β-glucuronidase (GUS) under the control of the ethylene-responsive element, which includes four copies of the 11-bp consensus sequence (designated the GCC-box, TAAGAGCCGCC). In strips of leaves of transgenic tobacco, the GCC-box-mediated expression of the reporter gene was induced in response to treatment with ethylene. We also observed the ethylene-independent immediate early induction of the synthesis of mRNAs for ERFs in wounded leaves and the enhancement of this induction by cycloheximide (CHX). Since CHX suppressed the induction of mRNAs for chitinase and GUS by ethylene, protein synthesis de novo was required for induction of the ethylene-dependent GCC-box-mediated transcription of genes. In contrast, the enhancement by CHX of the wound-induced expression of ERFs suggested that no synthesis of new proteins was required for the wounding signal transduction leading to rapid expression of ERFs. Methyl jasmonate did not stimulate the wounding-responsive accumulation of ERF mRNAs, but it reduced such accumulation of mRNAs for ERF1, ERF2, ERF4 and the ethylene-dependent GCC-box-mediated transcription of the reporter gene. Thus, the immediate early induction of the expression of genes for ERFs in strips of tobacco leaves appears to be a novel type of wound-responsive activation of transcription. These results suggested that the expression of ERFs was not sufficient for activation of the GCC-box-mediated transcription but the expression of ERF1, ERF2 and ERF4, and that conversion of these ERFs by ethylene to their active form might be crucial for the GCC-box-mediated activation of the transcription of defense genes.


Severe hypoglycemia attributable to surreptitious injection of insulin in a mare.
A mare with signs of hypoglycemia had high serum insulin concentrations before it was euthanatized. High pressure liquid chromatography revealed that the insulin in the mare's blood was of commercial origin. Surreptitious insulin injection has been suspected as the cause of several suspicious deaths of insured horses. The use of high-pressure liquid chromatography should help put an end to this practice.


A Multipronged Intervention to Reduce Readmissions and Readmission Intensity After Radical Cystectomy.
To develop a multipronged, evidence-based protocol to reduce readmission risk and readmission intensity, as represented by the duration of the index readmission, after radical cystectomy. A per-protocol study was performed. The protocol included preoperative nutritional supplementation, early stent removal, and a follow-up phone call within 4-5days of discharge. The preprotocol period was from February 1, 2020 to July 31, 2021 and the postprotocol period was from December 1, 2020 to November 31, 2021. Using multivariate regression models, we compared outcomes among patients treated with radical cystectomy before and after protocol initiation. We identified 70 preprotocol patients and 126 postprotocol patients. After adjusting for age, sex, BMI, and frailty score, there was a significant reduction in 90-day readmission intensity (7 vs 5days; P = .048) among postprotocol patients. After implementation of an evidence-based protocol for patients undergoing radical 90-day readmission intensity decreased significantly. This protocol may move the needle forward on reducing readmissions, but a larger randomized trial is needed.


Carotid body tumors.
A review of carotid body tumors is presented together with a personal series of 16 patients managed in 4 years. Angiography was diagnostic in all instances. Five patients showed evidence of local invasion, while no patient had distant spread. Early recognition and surgical management were effective in the treatment of all operable tumors. Local removal of group 1 tumors without shunting is safe, with no morbidity or mortality in this series. The use of an indwelling shunt in group 2 tumors is recommended because of the risk of vessel wall damage during dissection and because reduction in blood supply to these large tumors facilitates their removal. We also recommend the use of an indwelling shunt in group 3 tumors when an en bloc resection of the vessels and tumor is performed in order to maintain cerebral perfusion.


Prognostic value of different biomarkers for cardiovascular death in unselected older patients in the emergency department.
Risk stratification of elderly patients presenting with heart failure (HF) to an emergency department (ED) is an unmet challenge. We prospectively investigated the prognostic performance of different biomarkers in unselected older patients in the ED. We consecutively enrolled 302 non-surgical patients ⩾70 years presenting to the ED with a wide range of cardiovascular and non-cardiovascular comorbid conditions. N-terminal pro-B-type natriuretic peptide (NT-proBNP), mid-regional pro-adrenomedullin (MR-proADM), mid-regional pro-atrial natriuretic peptide (MR-proANP), C-terminal pro-endothelin-1 (CT-proET-1), ultrasensitive C-terminal pro-arginine-vasopressin (Copeptin-us) and high-sensitivity cardiac troponin T (hs-cTnT) were measured at admission. Two cardiologists independently adjudicated the final diagnosis of HF after reviewing all available baseline data using circulating NT-proBNP levels. A final diagnosis of HF was found in 120 (40%) of the 302 patients. All patients were followed up for cardiovascular death within the following 12 months. In order to test the prognostic performance of the investigated biomarkers we used boosting models with age and sex as mandatory covariates. Boosting is a statistical learning technique with built-in variable selection developed to obtain sparse and interpretable prediction models. Follow-up was 100% complete. During a median follow-up time of 225 days (interquartile range (IQR) 156-319 days), 30 (9.9%) of 302 patients (aged 81±6 years) had cardiovascular deaths. Of these 30 patients, 21 had HF and nine had no HF diagnosed prior to admission. The boosting model selected MR-proADM and hs-cTNT as predictors of cardiovascular deaths. The median values of MR-proADM and hs-cTnT at presentation were significantly higher in patients with cardiovascular deaths compared to surviving patients during follow-up (2.56 nmol/L (IQR 1.62-4.48) vs. 1.11 nmol/L (IQR 0.83-1.80), P<0.001 and 81 ng/L (IQR 38-340) vs. 17 ng/L (IQR 0.9-38), P=0.004). One unit increase in the log-transformed MR-proADM levels was associated with a 1.99-fold risk of death (95% confidence interval (CI) 1.61-2.45, P<0.001). The second marker, hs-cTnT, showed an increased predicted risk but was not significantly correlated to event-free survival (hazard ratio 3.22, 95% CI 0.97-10.68, P=0.056). Within different biomarkers, MR-proADM was the only predictor of cardiovascular deaths in unselected older patients presenting to the ED.


Contemporary Drug-Eluting Stent Platforms: Design, Safety, and Clinical Efficacy.
First-generation drug-eluting stents significantly improved treatment of coronary disease, decreasing rates of revascularization. This was offset by high rates of late adverse events, driven primarily by stent thrombosis. Research and design improvements of individual DES platform components led to next-generation devices with superior clinical safety and efficacy profiles compared with bare-metal stents and first-generation drug-eluting stents. These design improvements and features are explored, and their resulting clinical safety and efficacy reviewed, focusing on platforms approved by the Food and Drug Administration currently widely used in the United States.


Moving Forward by Looking Back: Understanding Why Some Spanish-Speaking English Learners Fall Behind.
This study investigated early indicators of Spanish-speaking English learners (ELs) at risk for reading difficulties at the end of Grade 2 by examining their early bilingual oral language development, taking into account language of academic instruction. Standardized measures of reading and narrative samples were collected in English and Spanish from kindergarten to Grade 2 from 1,243 ELs primarily instructed in English or Spanish. Conditional growth curve models yielded four primary findings of reading and oral language development. First, ELs with low reading achievement at the end of Grade 2 demonstrated early reading difficulties during kindergarten. Second, although ELs demonstrated overall higher reading achievement in their instructed language, this difference decreased over time. Third, ELs with low reading achievement at the end of Grade 2 demonstrated lower oral language skills in each language over time. Fourth, ELs demonstrated overall higher oral language skills in their instructed language, yet these differences varied over time. The study provided a detailed description of the longitudinal relations among the bilingual reading and oral language skills of Spanish-speaking ELs during the early school years. These findings help to inform the processes of early identification and intervention for Spanish-speaking ELs who are likely to demonstrate reading achievement difficulties.