Formation of Benzimidazoisoquinolinium and Benzimidazoisoindolinum Cyclic Systems by the Reaction of 2-(2-Alkynylphenyl)benzimidazoles with Iodine and Iodine-Iodine Interaction Including Halogen Bonding in Their Crystal Structures.
The reaction of 2-(2-alkynylphenyl)benz[d]imidazoles with molecular iodine constructed 5- and 6-membered rings as novel organic salts in high yield. The constituted number of ring systems was influenced by the substituent at the triple bond: 6-membered rings were formed from compounds bearing aryl substituents, whereas 5-membered ones were obtained from compounds with hydrogen or alkyl substituents. The products were obtained with triiodide as a counteranion; however, compounds with iodide were also obtainable under certain conditions. We also revealed that they had an iodine-iodine interaction included in halogen bonding between an iodo moiety of the cation and a triiodide or iodide of the counteranion. The iodine-iodine interaction was formed with greater preference than the electrostatic interaction between the cationic atom and triiodide or iodide.


Chemical processing of materials on silicon: more functionality, smaller features, and larger wafers.
The invention of the transistor followed by more than 60 years of aggressive device scaling and process integration has enabled the global information web and subsequently transformed how people communicate and interact. The principles and practices built upon chemical processing of materials on silicon have been widely adapted and applied to other equally important areas, such as microfluidic systems for chemical and biological analysis and microscale energy storage solutions. The challenge of continuing these technological advances hinges on further improving the performance of individual devices and their interconnectivity while making the manufacturing processes economical, which is dictated by the materials' innate functionality and how they are chemically processed. In this review, we highlight challenges in scaling up the silicon wafers and scaling down the individual devices as well as focus on needs and challenges in the synthesis and integration of multifunctional materials.


Electron attachment to hydrated oligonucleotide dimers: guanylyl-3',5'-cytidine and cytidylyl-3',5'-guanosine.
The dinucleoside phosphate deoxycytidylyl-3',5'-deoxyguanosine (dCpdG) and deoxyguanylyl-3',5'-deoxycytidine (dGpdC) systems are among the largest to be studied by reliable theoretical methods. Exploring electron attachment to these subunits of DNA single strands provides significant progress toward definitive predictions of the electron affinities of DNA single strands. The adiabatic electron affinities of the oligonucleotides are found to be sequence dependent. Deoxycytidine (dC) on the 5' end, dCpdG, has larger adiabatic electron affinity (AEA, 0.90 eV) than dC on the 3' end of the oligomer (dGpdC, 0.66 eV). The geometric features, molecular orbital analyses, and charge distribution studies for the radical anions of the cytidine-containing oligonucleotides demonstrate that the excess electron in these anionic systems is dominantly located on the cytosine nucleobase moiety. The pi-stacking interaction between nucleobases G and C seems unlikely to improve the electron-capturing ability of the oligonucleotide dimers. The influence of the neighboring base on the electron-capturing ability of cytosine should be attributed to the intensified proton accepting-donating interaction between the bases. The present investigation demonstrates that the vertical detachment energies (VDEs) of the radical anions of the oligonucleotides dGpdC and dCpdG are significantly larger than those of the corresponding nucleotides. Consequently, reactions with low activation barriers, such as those for O-C sigma bond and N-glycosidic bond breakage, might be expected for the radical anions of the guanosine-cytosine mixed oligonucleotides.


Campylobacter coli meningitis in a 57-year-old patient.
Campylobacter coli is a major pathogen rarely responsible for extra-intestinal infections. We report a case of Campylobacter coli bacteremia and meningitis in a 57-year-old immunocompetent Belgian man. The strain, isolated from cerebrospinal fluid, belonged to the unusual sequence type 8418 (ST8418). The patient fully recovered after meropenem treatment.


COVID-19: lessons for junior doctors redeployed to critical care.
Approximately 4% of patients with coronavirus disease 2019 (COVID-19) will require admission to an intensive care unit (ICU). Governments have cancelled elective procedures, ordered new ventilators and built new hospitals to meet this unprecedented challenge. However, intensive care ultimately relies on human resources. To enhance surge capacity, many junior doctors have been redeployed to ICU despite a relative lack of training and experience. The COVID-19 pandemic poses additional challenges to new ICU recruits, from the practicalities of using personal protective equipment to higher risks of burnout and moral injury. In this article, we describe lessons for junior doctors responsible for managing patients who are critically ill with COVID-19 based on our experiences at an urban teaching hospital.


Threshold dynamics of a stochastic SIHR epidemic model of COVID-19 with general population-size dependent contact rate.
In this paper, we propose a stochastic SIHR epidemic model of COVID-19. A basic reproduction number $ R_{0}^{s} $ is defined to determine the extinction or persistence of the disease. If $ R_{0}^{s} < 1 $, the disease will be extinct. If $ R_{0}^{s} > 1 $, the disease will be strongly stochastically permanent. Based on realistic parameters of COVID-19, we numerically analyze the effect of key parameters such as transmission rate, confirmation rate and noise intensity on the dynamics of disease transmission and obtain sensitivity indices of some parameters on $ R_{0}^{s} $ by sensitivity analysis. It is found that: 1) The threshold level of deterministic model is overestimated in case of neglecting the effect of environmental noise; 2) The decrease of transmission rate and the increase of confirmed rate are beneficial to control the spread of COVID-19. Moreover, our sensitivity analysis indicates that the parameters $ \beta $, $ \sigma $ and $ \delta $ have significantly effects on $ R_0^s $.


Thermal modulation voltammetry with laser heating at an aqueous|nitrobenzene solution microinterface: determination of the standard entropy changes of transfer for tetraalkylammonium ions.
Thermal modulation voltammetry (TMV) with laser heating was successfully performed at an aqueous|nitrobenzene (NB) solution microinterface, by taking advantage of the fact that laser light with a wavelength of 325.0 nm is optically transparent to the aqueous solution but opaque to the NB solution. When the laser beam impinges upon the interface from the aqueous solution side, a temperature is raised around the interface through the thermal diffusion subsequent to the light-to-heat conversion following the optical absorption by the NB solution near the interface. Based on such a principle, we achieved a fluctuating temperature perturbation around the interface for TMV by periodically irradiating the interface with the laser beam. On the other hand, the fluctuating temperature perturbation has influence on currents for transfer of an ion across the interface to produce fluctuating currents synchronized with the perturbation through temperature coefficients of several variables concerning the transfer, such as the standard transfer potential and the diffusion coefficient of the ion. Consequently, TMV has the possibility of providing information about the standard entropy change of transfer corresponding to a temperature coefficient of the standard transfer potential and a temperature coefficient of the diffusion coefficient. In this work, the aqueous|NB solution interface of 30 microm in diameter was irradiated with the laser beam at 10 Hz, and the currents synchronized with the periodical irradiation were recorded as a function of the potential difference across the interface in order to construct a TM voltammogram. TM voltammograms were measured for transfer of tetramethylammonium, tetraethylammonium, tetrapropylammonium, and tetra-n-butylammonium ions from the aqueous solution to the NB solution, and the standard entropy change of transfer was determined for each ion, according to an analytical procedure based on a mathematical expression of the TM voltammogram. Comparison of the values obtained in this work with the literature values has proved that TMV with laser heating is available for the determination of the standard entropy change of transfer for an ion.


Youth Advocates' Perceptions of Tobacco Industry Marketing Influences on Adolescent Smoking: Can They See the Signs?
Point-of-sale (POS) advertising at retail stores is one of the key marketing avenues used by the tobacco industry. The United States Surgeon General urges actions to eliminate POS tobacco advertisements because of their influence on youth smoking. Many youth empowerment programs are implemented to address tobacco industry marketing influences, including POS tobacco advertisements. While youth are asked to take on such collective action, little is known regarding their perceptions and understanding of tobacco industry marketing influences and related advocacy activities. This mixed methods study examined Oklahoma's tobacco control youth empowerment program members' perceptions of tobacco industry marketing influences. Four focus groups were held with active program members from rural and urban areas. Overall, the focus group participants viewed the program as purposeful, as an avenue to help others, and as a way to make a difference. Specifically, the older participants (median age = 18 years) identified tobacco industry marketing influences such as POS, movies, and magazine advertisements and reported participating in activities that counter POS tobacco advertisements at retail stores. Likewise younger participants (median age = 16 years), identified similar tobacco industry marketing influences, but also included tobacco use by friends and family as tobacco industry marketing influences. Moreover, the younger participants did not report engaging in activities that addressed POS tobacco advertisements. The study results suggest that the empowerment program should tailor its programming, training, materials, and activities with input from youth of various ages. Thoughtfully developed messages and specific activities can truly empower youth and maximize their contribution as change agents who address POS or other initiatives at the retail environments to prevent chronic diseases.


Adult onset hydrocephalus and situs inversus: new autosomal dominant syndrome?
Familial adult onset hydrocephalus is unusual and its genetic basis is unknown. We report a two-generation family with three members having hydrocephalus, two of them with complete situs inversus. Laterality syndromes were considered in the differential diagnosis and are unlikely. We suggest that this family represents a previously unrecognised form of autosomal dominant late onset hydrocephalus with situs inversus.


[Subsolid pulmonary nodules].
Subsolid nodules represent almost 20% of all pulmonary nodules found incidentally at chest computed tomography (CT). Their detection is steadily rising, in parallel with the increasing number of CT scans performed. Subsolid nodules differ from solid lung nodules in several ways: morphology, course of progression, risk of malignancy and prognosis. Although they remain a diagnostic challenge, a good correlation has been established between radiological appearance and histopathology. Whilst 75% of persistent subsolid nodules represent a form of adenocarcinoma, their prognosis is generally excellent when resected. Non-resected subsolid nodules require a long follow-up of 3 to 5 years due to their slow-growing nature and high prevalence of malignancy. Specific guidelines have been published in 2013 and in 2015.


Clinical and polygraphic evolution of sleep-related breathing disorders in adolescents.
It has been suggested that sleep-related breathing disorders (SRBD) involve a continuum that develops over the course of life. If modifiable factors could be identified, the progression of SRBD could perhaps be addressed early in life. Although some studies have looked at the evolution of SRBD in pre-pubertal children, very few studies obtained data in adolescents. Anthropometric, clinical and polygraphic variables were collected during a 4-yr follow-up study among 148 normal adolescents after initial cross-sectional analysis. From a total of 267 adolescents studied at baseline (mean+/-sd age 14.3+/-2.1 yrs), 148 (55.4%) were followed up for 4 yrs. During follow-up, there were no significant changes in snoring and polygraphic parameters. However, a tendency toward weight gain with centrally distributed fat was observed. Habitual snorers had a significantly higher body mass index and more centrally distributed fat than nonsnorers. Males had a higher snoring prevalence and a higher number of respiratory events than females. Snoring at baseline, male sex and poor academic performance were significant predictors of snoring at follow-up. Snoring tends to persist during adolescence and male sex acts as a risk factor. A relationship between snoring and academic performance was observed. These findings may have implications for long-term management of sleep-related breathing disorders.


Comparative proteomic analysis of regenerative acellular matrices: The effects of tissue source and processing method.
Acellular tissue matrices are used in regenerative medicine from weak tissue re-enforcement to cosmetic augmentation. However, proteomic signatures leading to different clinical outcomes among matrices are not well understood. In an attempt to investigate the effects of tissue source and processing method, we examined by liquid chromatography tandem mass spectrometry (LC-MS/MS) the proteomic profiles of 12 regulatory agency-approved acellular matrices (AlloMax, AlloDerm, CollaMend, Heal-All, JayyaLife, ReGen, Renov, Strattice, SurgiMend, Surgisis, UniTrump and Vidasis). The compositions of acellular matrices varied greatly with the number of identified proteins ranging from 7 to 106. The content of individual proteins was between 0.0001% and 95.8% according to their abundances measured by the M/Z signal intensities. Most acellular matrices still contained numerous cellular proteins. AlloMax, AlloDerm, ReGen, Strattice, SurgiMend and Surgisis retained necessary structural and functional proteins to form the extracellular protein-protein interaction networks for cell adhesion, proliferation and tissue regeneration, whereas CollaMend, Heal-All, JayyaLife, Renov, UniTrump and Vidasis had only retained certain structural collagens. Principal component analysis showed that proteomic variations among acellular matrices were largely attributed to tissue source and processing method. Differences in proteomic profiles among acellular matrices offers insights into molecular interpretation for different clinical outcomes, and can serve as useful references for rational design of regenerative bio-scaffolds.


[Blood flow pattern in pulmonary atelectasis with color Doppler flow imaging].
Blood flow pattern in the lesion was evaluated in 4 patients with pulmonary atelectasis by color Doppler flow imaging synchronized electrocardiography. The pulsatile signal and triphasic signal were detected, whereas the continuous signal was not. It seemed that in pulmonary atelectasis the pulsatile signal was the blood flow signal in the pulmonary artery and the triphasic signal was the blood flow signal in the pulmonary vein.


Loss of variability in Graves' disease: stimulatory TSH-receptor antibodies bind to the TSH-receptor in a continued, non-pulsatile and non-chaotic fashion.
Thyroid-stimulating hormone (TSH) regulates thyroid growth and differentiated function by binding to the TSH-receptor (TSH-R). In Graves' disease, hyperthyroidism and goiter growth are thought to be mediated by prolonged, continued activation of the TSH-R by TSH receptor-stimulating antibodies (TSAb). However, continuous experimental stimulation of the TSH-R with TSH or TSAb leads to a desensitization of the thyrocyte with a decrease of thyroid function in vitro and in vivo. In order to clarify this discrepancy we determined serum levels of TSH-binding-inhibiting immunoglobulins (TBII) in 10 patients with GD every 10 minutes over 6h (patients 1 to 5, group A) and over 24h (patients 6 to 10, group B) using a commercially available radio ligand receptor assay (TRAK, Henning Berlin, FRG). Visual and computer analysis revealed some variation of TBII serum levels but no obvious pattern indicative of circadian variation nor major secretory peaks could be distinguished. Variation of TBII serum levels were within or only slightly above intraassay CV. Data were tested in order to decide whether the observed fluctuations are of chaotic (deterministic) or of stochastic (random) origin. In none of these tests did we find evidence for chaos in the data suggesting that the observed fluctuations reflect other sources of noise such as sampling errors or intraassay variation. We conclude that in Graves' disease, patients are rendered hyperthyroid by continued, non-pulsatile and non-chaotic binding of stimulatory antibodies to the TSH binding site of the TSH-R.


Permeability characteristics of calu-3 human bronchial epithelial cells: in vitro-in vivo correlation to predict lung absorption in rats.
The goal of this study was to evaluate the permeability characteristics of Calu-3, human bronchial epithelial cells to passive and actively transported drugs and to correlate the data with other in vitro models and rat lung absorption in vivo. Air-interface cultured Calu-3 cells grown on collagen-coated permeable filter supports formed "tight" polarized and well differentiated cell monolayers with apical microvilli and tight-junctional complexes. Within 8-10 days, cell monolayers developed trans-epithelial electrical resistance (TEER) > 1000 ohm cm2 and potential difference about 11-16 mV. Solute permeability was dependent on lipophilicity, and inversely related to molecular size. Calu-3 cells actively transported amino acids, nucleosides and dipeptide analogs, but not organic anions, organic cations or efflux pump substrates. The permeability characteristics of Calu-3 cells correlated well with primary cultured rabbit tracheal epithelial cells in vitro (r2 = 0.91), and the rate of drug absorption from the rat lung in vivo (r2 = 0.94). The absorption predicted from the regression equation correlated well with observed values. In conclusion, in vitro-in vivo correlation studies indicate that the Calu-3 cell culture model is a potentially useful model to predict absorption of inhalation delivery drug candidates.


Ailanthone inhibits cell growth and migration of cisplatin resistant bladder cancer cells through down-regulation of Nrf2, YAP, and c-Myc expression.
Ailanthone (Aila) is a natural active compound isolated from the Ailanthus altissima, which has been shown to possess an "in vitro" growth-inhibitory effect against several cancer cell lines. Advanced bladder cancer is a common disease characterized by a frequent onset of resistance to cisplatin-based therapy. The cisplatin (CDDP) resistance is accompanied by an increase in Nrf2 protein expression which contributes to conferring resistance. Recently, we demonstrated a cross-talk between Nrf2 and YAP. YAP has also been demonstrated to play an important role in chemoresistance of bladder cancer. We analyzed the antitumor effect of Aila in sensitive and CDDP-resistant bladder cancer cells and the molecular mechanisms involved in Aila activity. Sensitive and CDDP-resistant 253J B-V and 253J bladder cancer cells, intrinsically CDDP-resistant T24 bladder cancer cells and HK-2 human renal cortex cells were used. Cells were treated with diverse concentrations of Aila and proliferation, cell cycle, apoptosis and gene expressions were determined. Aila toxicity and proliferation were determined by MTT and colony forming methods, respectively. Cell cycle was determined by cytofluorimetric analysis through PI staining method. Apoptosis was detected using Annexin V and PI double staining followed by quantitative flow cytometry. Expressions of Nrf2, Yap, c-Myc, and house-keeping genes were determined by western blot with specific antibodies. Cell migration was detected by wound healing and Boyden chamber analysis. Aila inhibited the growth of sensitive and CDDP-resistant bladder cancer cells with the same effectiveness. On the contrary, the growth of HK-2 cells was only slightly reduced by Aila. Cell cycle analysis revealed an accumulation of Aila-treated bladder cancer cells in the G0/G1 phase. Interestingly, Aila strongly reduced Nrf2 expression in these cell lines. Moreover, Aila significantly reduced YAP, and c-Myc protein expression. The random and the oriented migration of bladder cancer cells were strongly inhibited by Aila treatment, in particular in CDDP-resistant cells. Aila inhibited proliferation and invasiveness of bladder cancer cells. Its high effectiveness in CDDP resistant cells could be related to the inhibition of Nrf2, YAP, and c-Myc expressions. Aila could represent a new tool to treating CDDP-resistant bladder cancers.


Determination of nanoparticle surface coatings and nanoparticle purity using microscale thermogravimetric analysis.
The use of nanoparticles in some applications (i.e., nanomedical, nanofiltration, or nanoelectronic) requires small samples with well-known purities and composition. In addition, when nanoparticles are introduced into complex environments (e.g., biological fluids), the particles may become coated with matter, such as proteins or lipid layers. Many of today's analytical techniques are not able to address small-scale samples of nanoparticles to determine purity and the presence of surface coatings. Through the use of an elevated-temperature quartz crystal microbalance (QCM) method we call microscale thermogravimetric analysis, or μ-TGA, the nanoparticle purity, as well as the presence of any surface coatings of nanomaterials, can be measured. Microscale thermogravimetric analysis is used to determine the presence and amount of surface-bound ligand coverage on gold nanoparticles and confirm the presence of a poly(ethylene glycol) coating on SiO2 nanoparticles. Results are compared to traditional analytical techniques to demonstrate reproducibility and validity of μ-TGA for determining the presence of nanoparticle surface coatings. Carbon nanotube samples are also analyzed and compared to conventional TGA. The results demonstrate μ-TGA is a valid method for quantitative determination of the coatings on nanoparticles, and in some cases, can provide purity and compositional data of the nanoparticles themselves.


[The clinical peculiarities of psychogenically-induced exacerbations of paranoid schizophrenia].
One hundred and twenty-eight patients diagnosed with paranoid schizophrenia were studied. A main group comprised 84 patients with psychogenically-induced paranoid psychoses. A control group consisted of 44 patients with spontaneous exacerbations of the disease. Psychogenically-induced exacerbations of paranoid schizophrenia differed by the clinical polymorphism, heterogeneity and atypism. Three types of psychogenically-induced relapses of paranoid schizophrenia were singled out: endoreactive, delusional with affective symptoms and delusional. Higher frequencies of suicidal tendencies (32.1%), absolute therapy resistance (25.0%), hospitalism (21.4%), non-compliance (46.4%) were observed in the main group of patients. These features predicted the poor outcome comparing to paranoid psychoses developed spontaneously. In conclusion, treatment of patients with paranoid schizophrenia with psychogenically-induced exacerbations demands the obligatory administration of psychotherapy. A combination of traditional neuroleptics with symptomatic pharmacotherapy of psychopathological presentations is the most efficient.


Presumed acute posterior multifocal placoid pigmentary epitheliopathy associated with Bartonella infection.
To report a unique case of acute posterior multifocal placoid pigment epitheliopathy (APMPPE) in a patient with positive serology for Bartonella, presenting with ocular signs and symptoms not attributable to other diseases. A 27-year-old woman presented with decreased visual acuity in both eyes. Multimodal fundus image analysis was performed. A color fundus photograph of both eyes revealed peripapillary and macular yellow-white placoid lesions. The fundus autofluorescence of both eyes demonstrated hypo- and hyperautofluorescence of the macular lesions. Fluorescein angiography showed early-stage hypofluorescence and late staining of placoid lesions in both eyes. Spectral domain optical coherence tomography (SD-OCT) of both eyes revealed irregular elevations in the retinal pigment epithelium with the disruption of the ellipsoid zone on the topography of macular lesions. At 3 months after the treatment initiation for Bartonella infection, the placoid lesions became atrophic and hyperpigmented, and SD-OCT revealed loss of both the outer retinal layers and retinal pigment epithelium on the topography of macular lesions in both eyes.


A Segment-Based Trajectory Similarity Measure in the Urban Transportation Systems.
With the rapid spread of built-in GPS handheld smart devices, the trajectory data from GPS sensors has grown explosively. Trajectory data has spatio-temporal characteristics and rich information. Using trajectory data processing techniques can mine the patterns of human activities and the moving patterns of vehicles in the intelligent transportation systems. A trajectory similarity measure is one of the most important issues in trajectory data mining (clustering, classification, frequent pattern mining, etc.). Unfortunately, the main similarity measure algorithms with the trajectory data have been found to be inaccurate, highly sensitive of sampling methods, and have low robustness for the noise data. To solve the above problems, three distances and their corresponding computation methods are proposed in this paper. The point-segment distance can decrease the sensitivity of the point sampling methods. The prediction distance optimizes the temporal distance with the features of trajectory data. The segment-segment distance introduces the trajectory shape factor into the similarity measurement to improve the accuracy. The three kinds of distance are integrated with the traditional dynamic time warping algorithm (DTW) algorithm to propose a new segment-based dynamic time warping algorithm (SDTW). The experimental results show that the SDTW algorithm can exhibit about 57%, 86%, and 31% better accuracy than the longest common subsequence algorithm (LCSS), and edit distance on real sequence algorithm (EDR) , and DTW, respectively, and that the sensitivity to the noise data is lower than that those algorithms.


Portuguese women's knowledge and health beliefs about cervical cancer and its screening.
Currently little is known about Portuguese women's knowledge and beliefs about cervical cancer screening, so this information is crucial to the success of cervical cancer screening programs. The intention of this study was to describe the knowledge and beliefs of women in Portugal. In-depth, face-to-face, individual interviews were conducted. Twenty-five females were recruited, the age range was 30 to 60. The results showed a lack of knowledge on cervical cancer and the Pap smear test. From a public policy point of view, it may be important to further explore the extent to which perceived barriers to screening will affect screening uptake when a national screening program is implemented.


Poorer aging trajectories are associated with elevated serotonin synthesis capacity.
The dorsal raphe nucleus (DRN) is one of the earliest targets of Alzheimer's disease-related tau pathology and is a major source of brain serotonin. We used [18F]Fluoro-m-tyrosine ([18F]FMT) PET imaging to measure serotonin synthesis capacity in the DRN in 111 healthy adults (18-85 years-old). Similar to reports in catecholamine systems, we found elevated serotonin synthesis capacity in older adults relative to young. To establish the structural and functional context within which serotonin synthesis capacity is elevated in aging, we examined relationships among DRN [18F]FMT net tracer influx (Ki) and longitudinal changes in cortical thickness using magnetic resonance imaging, longitudinal changes in self-reported depression symptoms, and AD-related tau and β-amyloid (Aβ) pathology using cross-sectional [18F]Flortaucipir and [11C]Pittsburgh compound-B PET respectively. Together, our findings point to elevated DRN [18F]FMT Ki as a marker of poorer aging trajectories. Older adults with highest serotonin synthesis capacity showed greatest temporal lobe cortical atrophy. Cortical atrophy was associated with increasing depression symptoms over time, and these effects appeared to be strongest in individuals with highest serotonin synthesis capacity. We did not find direct relationships between serotonin synthesis capacity and AD-related pathology. Exploratory analyses revealed nuanced effects of sex within the older adult group. Older adult females showed the highest DRN synthesis capacity and exhibited the strongest relationships between entorhinal cortex tau pathology and increasing depression symptoms. Together these findings reveal PET measurement of the serotonin system to be a promising marker of aging trajectories relevant to both AD and affective changes in older age.


[Brain embolism associated with atrial septal aneurysm].
We studied the clinical significance of atrial septal aneurysm on brain embolism. Of two-hundred twenty-eight consecutive ischemic stroke patients, 128 cases were performed transesophageal echocardiography to find cardiac lesions that could be embolic sources. Three cases were diagnosed as having atrial septal aneurysm with right-to-left shunt demonstrated by contrast echocardiography under Valsalva maneuver. These cases were all diagnosed as brain embolism from clinical courses and findings from brain CT scan, and cerebral angiography. Neurosonologic study, 24 hours Holter ECG, and transthoracic echocardiography did not reveal any other embolic sources. Paradoxical embolic mechanism is supposed to have occurred in these cases. Atrial septal aneurysm often coexists with right-to-left shunt and is clinically significant as a finding suggesting paradoxical embolism.


[Investigations on the combined effect of zinc and lead (author's transl)].
The effect of zinc and the combined effect of zinc and lead on the Ala-D of the erythrocytes were experimentally followed in vivo and vitro. It was demonstrated that the zinc effect on the Ala-D is a function of the zinc-concentrate in blood. It was hence traced that ZnCl2 dosis up to 500 mug/ml blood raises the activity of Ala-D. Higher levels of ZnCl2 on other side leads to supression of the Ala-D activity. The experiments demonstrated further zinc exerts a dosis dependent antagonistic effect on the lead suppression of the Ala-D. Possible explanations of the effect of zinc on the Ala-D, and the antagonistic zinc effect after lead applications are still in discussion.


The association between a family history of type 2 diabetes and coronary artery disease in a type 1 diabetes population.
To examine whether a potential marker for type 2 diabetes (family history) is related to CAD in type 1 diabetic subjects. The two major types of primary diabetes, type 1 and type 2, are both associated with an increased risk of developing coronary artery disease (CAD). However, the etiology and associated risk factors may differ by type of diabetes. In type 2 diabetes, CAD is likely to be linked with the insulin resistance associated with the type 2 "process," while CAD in type 1 diabetes has, so far, been more closely linked to renal disease. Because the etiologies of type 1 and type 2 diabetes are different, it is possible that some CAD in type 1 diabetes may be related to the coexistence of type 2 diabetes susceptibility (i.e., insulin resistance). We evaluated the interrelationships between family history of type 2 diabetes (age at onset > 30 years, no insulin for 1st year) and presence of CAD in a cohort of childhood-onset type 1 diabetic subjects using the Pittsburgh Epidemiology of Diabetes Complications study (n = 658). A first-degree family history of type 2 diabetes was reported in 112 subjects, and CAD was present in 119 subjects. Those subjects reporting a family history of type 2 diabetes were significantly older, had a longer duration of type 1 diabetes, had higher triglyceride and LDL cholesterol levels, and had a borderline significantly increased Beck depression inventory. Sex differences in CAD risk factors were also noted. Using logistic regression analysis, the odds ratio (95% CI) for the presence of CAD in association with a family history of NIDDM was 1.89 (1.27-2.84). The odds ratio (95% CI) after adjusting for disease duration, triglycerides, hypertension, Beck depression, and nephropathy status was 1.45 (0.87-2.28). We conclude that a family history of type 2 diabetes is a risk factor for CAD in type 1 diabetic subjects. This supports the concept that insulin resistance may contribute to development of CAD in type 1 diabetes.


Distribution of Trop 3 and 4 antigens in human endometrial glandular epithelium.
The reactivities of three monoclonal antibodies (MAbs), Trop 3, Trop 4, and W6/32, were studied on human uterine tissue by using an indirect immunoperoxidase method. Nonpregnant endometrial glandular epithelium was stained by all three MAbs. During pregnancy, Trop 3 expression was not detectable, but Trop 4 and W6/32 showed variable staining on the endometrial glandular epithelium, especially during late pregnancy. These findings support previous work suggesting a local regulation of antigenic expression by endometrial glandular epithelial cells.


Enhanced Expression of Fibroblast Growth Factor Receptor 3 IIIc Promotes Human Esophageal Carcinoma Cell Proliferation.
Deregulated expression of fibroblast growth factor receptors (FGFRs) and their ligands plays critical roles in tumorigenesis. The gene expression of an alternatively spliced isoforms of FGFR3, FGFR3IIIc, was analyzed by RT-PCR in samples from patients with esophageal carcinoma (EC), including esophageal squamous cell carcinoma (ESCC) and adenocarcinoma (EAC). The incidence of FGFR3IIIc was higher in EC [12/16 (75%); p=0.073] than in non-cancerous mucosa (NCM) [6/16 (38%)]. Indeed, an immunohistochemical analysis of early-stage ESCC showed that carcinoma cells expressing FGFR3IIIc stained positively with SCC-112, a tumor marker, and Ki67, a cell proliferation marker, suggesting that the expression of FGFR3IIIc promotes cell proliferation. We used EC-GI-10 cells endogenously expressing FGFR3IIIc as a model of ESCC to provide mechanistic insight into the role of FGFR3IIIc in ESCC. The knockdown of endogenous FGFR3 using siRNA treatment significantly abrogated cell proliferation and the overexpression of FGFR3IIIc in cells with enhanced cell proliferation. EC-GI-10 cells and ESCC from patients with EC showed endogenous expression of FGF2, a specific ligand for FGFR3IIIc, suggesting that the upregulated expression of FGFR3IIIc may create autocrine FGF signaling in ESCC. Taken together, FGFR3IIIc may have the potential to be an early-stage tumor marker and a molecular target for ESCC therapy.


Effect of dietary acidification on kidney damage induced in immature chickens by excess calcium and infectious bronchitis virus.
Experiments were designed to evaluate the effect of dietary acidification on the development of kidney lesions induced by excess dietary calcium (Ca) and Gray strain infectious bronchitis virus (IBV). Specific pathogen-free (SPF) chicks and SPF chicks inoculated with Gray strain IBV were fed one of three diets: a commercial pullet grower ration (1% Ca); a commercial layer ration (3.25% Ca); or layer ration plus .5% ammonium chloride (acidified layer ration). Gray strain IBV significantly reduced total kidney weights in males, reduced total kidney weight as a percentage of body weight in males, increased the number of gross kidney lesions, and decreased the number of filtering nephrons when compared with uninoculated birds when both groups were fed the grower ration. The layer ration induced a 60% incidence of kidney lesions, caused a significant increase in kidney weight asymmetry ratios, and caused a 25% reduction in the number of filtering nephrons. Acidifying the layer ration significantly reduced the incidence of gross kidney lesions and reduced kidney weight asymmetry ratios, but did not prevent Ca-induced reductions in filtering nephrons.


Strong binding active constituents of phytochemical to BMPR1A promote bone regeneration: In vitro, in silico docking, and in vivo studies.
Two of the most problematic orthopedic and neurosurgeon visits are associated with spine and craniofacial fractures. Therefore, more attention needs to be paid to finding a medicine to repair these fractures. Amongst the most mysterious herbs, Aloe vera stands out. In the present study, the ameliorating function of A. vera on osteogenesis was studied in vitro and in vivo. Osteoblast-like cells were exposed to A. vera, followed by analysis of cell viability, lactate dehydrogenase release, and intracellular reactive oxygen species (ROS) production. The results showed an enhanced cell biocompatibility in a dose-dependent manner due to attenuated intracellular ROS production. Furthermore, a docking study indicated that the strong affinity of A. vera constituents to type I bone morphogenic protein receptor (BMPR1A) without the involvement of the BMPR1A chain B. The induction of osteogenesis prompts extracellular calcium deposition by osteoblasts, which affirms successful in vitro bone regeneration. However, injection of A. vera in rats with critical size calvarial defects induced Runx2, alkaline phosphatase (ALP), OCN, and BMP2 genes overexpression, which led to the formation of victorious bone with enhanced bone density and ALP activity. It is worthy to note that Aloin has the highest affinity to BMPR1A, whereas there are no reports regarding the impact of Aloenin, Aloesin, and γ-sitosterol on osteogenesis. Furthermore, some of them have antitumor potency, and it might be proposed that they are considered as a bone substitute in the osteotomy site of osteosarcoma with the aim of bone recovery and suppression of osteosarcoma. The whole consequences of this investigation manifests the plausibility of using A. vera as an antioxidant and osteoconductive substitute.


Protective effects of betulin and betulinic acid against ethanol-induced cytotoxicity in HepG2 cells.
Plant triterpenes, such as oleanolic acid and betulin were described as hepatoprotectants active against cytotoxicity of acetaminophen or cadmium. The aim of this paper is to compare the cytoprotective activity of betulin, betulinic acid and oleanolic acid against ethanol-induced cytotoxicity in HepG2 cells. The influence of three triterpenes on ethanol-induced production of superoxide anion and hydrogen peroxide was also examined. Among the examined triterpenes, betulin was the most active protectant of HepG2 cells against ethanol-induced cytotoxicity. Betulin and betulinic acid significantly decreased ethanol-induced production of superoxide anion. Oleanolic acid inhibited only ethanol- and phorbol ester-induced production of hydrogen peroxide. The results indicate that cytoprotective or antioxidative activity of triterpenes depends on their chemical structure.


Localization of nascent RNA and CREB binding protein with the PML-containing nuclear body.
The cellular role of the PML-containing nuclear bodies also known as ND10 or PODs remains elusive despite links to oncogenesis and viral replication. Although a potential role in transcription has been considered, direct evidence has been lacking. By developing a novel in vivo nucleic acid labeling approach, we demonstrate the existence of nascent RNA polymerase II transcripts within this nuclear body. In addition, PML and the transactivation cofactor, CREB binding protein (CBP), colocalize within the nucleus. Furthermore, we show that CBP in contrast to PML is distributed throughout the internal core of the structure. Collectively, these findings support a role for this nuclear body in transcriptional regulation.


Hepatic stellate cells--from the viewpoint of retinoid handling and function of the extracellular matrix.
Hepatic stellate cells (vitamin A-storing cells, lipocytes, fat-storing cells, Ito cells) exist in the perisinusoidal space of the hepatic lobule, and store 80% of retinoids in the whole body as retinyl palmitate in lipid droplets in the cytoplasm. In physiological conditions, these cells play pivotal roles in the regulation of retinoid homeostasis; they express specific receptors for retinol-binding protein (RBP), a binding protein specific for retinol, on their cell surface, and take up the complex of retinol and RBP by receptor-mediated endocytosis. By contrast, in pathological conditions such as liver fibrosis, these cells lose retinoids, and synthesize a large amount of extracellular matrix (ECM) components including collagen, proteoglycan and adhesive glycoproteins. The morphology of these cells also changes from the star-shaped stellate cells to that of fibroblasts or myofibroblasts. It is concluded that three-dimensional structure of the ECM components reversibly regulates the morphology, proliferation, and functions of the hepatic stellate cells.


The CAM movement and the integration of quality health care: the case of chiropractic.
High and increasing consumer demand for complementary and alternative medicine (CAM) services necessitates a concerted focus to determine the effectiveness of such practices and to ensure that future possible integration of CAM with conventional medicine is founded on sound evidence-based principles of quality health care delivery. The example of chiropractic provides useful insights to guide further research and integration of evidence-based CAM into mainstream health care in the United States. A critical point of departure for this area of inquiry is identifying and addressing barriers to conducting scientifically sound and meaningful cross-disciplinary, practice-based research.


Comparison of Effect of C-Factor on Bond Strength to Human Dentin Using Different Composite Resin Materials.
The study was planned to assess the use of low shrinkage composites for restoring cavities with high configuration factor (C-factor) which are subjected to high stresses. The aim of the study was to evaluate the effect of C- factor on tensile bond strength to human dentin using methacrylate based nanohybrid and low shrinkage silorane composite. In this study 40 non carious human molar teeth were selected and assigned into two main groups - cavity (Class I cavity with high C-factor) and flat group (flat surface with low C-factor). Two different composite materials- methacrylate based and silorane low shrinkage composite were used to restore the teeth. Dentin surface was treated, adhesive application was done and composite was applied as per manufacturer's instructions. Samples were stored in distilled water then subjected to tensile bond strength measurement using universal testing machine. Statistical analysis was done using Independent sample t-test. The mean bond strength in methacrylate based and silorane composite was significantly higher in flat preparation (Low C-factor) than cavity preparation. The mean bond strength in both cavity (High C-factor) and flat preparation(Low C-factor) was significantly higher in silorane than in conventional methacrylate based composite. The bond strength of composites to dentin is strongly influenced by C-factor and type of composite resin material used.


The actin cytoskeleton regulates exocytosis of all neutrophil granule subsets.
A comprehensive analysis of the role of the actin cytoskeleton in exocytosis of the four different neutrophil granule subsets had not been performed previously. Immunoblot analysis showed that, compared with plasma membrane, there was less actin associated with secretory vesicles (SV, 75%), gelatinase granules (GG, 40%), specific granules (SG, 10%), and azurophil granules (AG, 5%). Exocytosis of SV, SG, and AG was measured as increased plasma membrane expression of CD35, CD66b, and CD63, respectively, with flow cytometry, and GG exocytosis was measured as gelatinase release with an ELISA. N-formylmethionyl-leucyl-phenylalanine (FMLP) stimulated exocytosis of SV, GG, and SG with an ED(50) of 15, 31, and 28 nM, respectively, with maximal response at 10(-7) M FMLP by 5 min, while no exocytosis of AG was detected. Disruption of the actin cytoskeleton by latrunculin A and cytochalasin D induced a decrease in FMLP-stimulated CD35 expression after an initial increase. Both drugs enhanced the rate and extent of FMLP-stimulated GG, SG, and AG exocytosis, while the EC(50) for FMLP was not altered. We conclude that the actin cytoskeleton controls access of neutrophil granules to the plasma membrane, thereby limiting the rate and extent of exocytosis of all granule subsets. Differential association of actin with the four granule subsets was not associated with graded exocytosis.


Heterologous expression of a fatty acid hydroxylase gene in developing seeds of Arabidopsis thaliana.
Expression of a cDNA encoding the castor bean ( Ricinus communis L.) oleate Delta12-hydroxylase in the developing seeds of Arabidopsis thaliana (L.) Heynh. results in the synthesis of four novel hydroxy fatty acids. These have been previously identified as ricinoleic acid (12-hydroxy-octadec- cis-9-enoic acid: 18:1-OH), densipolic acid (12-hydroxy-octadec- cis-9,15-enoic acid: 18:2-OH), lesquerolic acid (14-hydroxy-eicos- cis-11-enoic acid: 20:1-OH) and auricolic acid (14-hydroxy-eicos- cis-11,17-enoic acid: 20:2-OH). Using mutant lines of Arabidopsis that lack the activity of the FAE1 condensing enzyme or FAD3 ER Delta-15-desaturase, we have shown that these enzymes are required for the synthesis of C20 hydroxy fatty acids and polyunsaturated hydroxy fatty acids, respectively. Analysis of the seed fatty acid composition of transformed plants demonstrated a dramatic increase in oleic acid (18:1) levels and a decrease in linoleic acid (18:2) content correlating to the levels of hydroxy fatty acid present in the seed. Plants in which FAD2 (ER Delta12-desaturase) activity was absent showed a decrease in 18:1 content and a slight increase in 18:2 levels corresponding to hydroxy fatty acid content. Expression of the castor hydroxylase protein in yeast indicates that this enzyme has a low level of fatty acid Delta12-desaturase activity. Lipase catalysed 1,3-specific lipolysis of triacylglycerol from transformed plants demonstrated that ricinoleic acid is not excluded from the sn-2 position of triacylglycerol, but is the only hydroxy fatty acid present at this position.


Target weight achievement and ultrafiltration rate thresholds: potential patient implications.
Higher ultrafiltration (UF) rates and extracellular hypo- and hypervolemia are associated with adverse outcomes among maintenance hemodialysis patients. The Centers for Medicare and Medicaid Services recently considered UF rate and target weight achievement measures for ESRD Quality Incentive Program inclusion. The dual measures were intended to promote balance between too aggressive and too conservative fluid removal. The National Quality Forum endorsed the UF rate measure but not the target weight measure. We examined the proposed target weight measure and quantified weight gains if UF rate thresholds were applied without treatment time (TT) extension or interdialytic weight gain (IDWG) reduction. Data were taken from the 2012 database of a large dialysis organization. Analyses considered 152,196 United States hemodialysis patients. We described monthly patient and dialysis facility target weight achievement patterns and examined differences in patient characteristics across target weight achievement status and differences in facilities across target weight measure scores. We computed the cumulative, theoretical 1-month fluid-related weight gain that would occur if UF rates were capped at 13 mL/h/kg without concurrent TT extension or IDWG reduction. Target weight achievement patterns were stable over the year. Patients who did not achieve target weight (post-dialysis weight ≥ 1 kg above or below target weight) tended to be younger, black and dialyze via catheter, and had shorter dialysis vintage, greater body weight, higher UF rate and more missed treatments compared with patients who achieved target weight. Facilities had, on average, 27.1 ± 9.7% of patients with average post-dialysis weight ≥ 1 kg above or below the prescribed target weight. In adjusted analyses, facilities located in the midwest and south and facilities with higher proportions of black and Hispanic patients and higher proportions of patients with shorter TTs were more likely to have unfavorable facility target weight measure scores. Without TT extension or IDWG reduction, UF rate threshold (13 mL/h/kg) implementation led to an average theoretical 1-month, fluid-related weight gain of 1.4 ± 3.0 kg. Target weight achievement patterns vary across clinical subgroups. Implementation of a maximum UF rate threshold without adequate attention to extracellular volume status may lead to fluid-related weight gain.


Instrument Adaptation, Modification, and Validation for Cultural Beliefs About Colorectal Cancer Screening Among Korean Americans.
Studies on colorectal cancer (CRC) screening among Korean Americans (KAs) lack culturally sensitive, reliable, and validated belief scales. The purpose of this study was to adapt, modify, and validate instruments measuring cultural beliefs (physical space, health temporal orientation, personal control, colon cancer fatalism, and health fatalism) about CRC screening in KAs. In phase I, instrument adaptation and modification (translation from English into Korean, individual interviews using cognitive interviewing, and expert reviews) were used to make existing cultural beliefs instruments culturally appropriate for KAs. In phase II, instrument validation (pilot test and cross-sectional survey) was used to examine the psychometric properties of the instrument among 202 KAs. Construct validity and reliability of the final Korean version of the instruments were examined using exploratory and confirmatory factor analyses and internal consistency reliability. Exploratory factor analysis using all of the cultural beliefs items resulted in 5 factors accounting for 46.55% of the variance. Factor loadings were greater than 0.40 for most items to be added to the scales reflecting Korean cultural perspectives. Cronbach's αs for all the cultural beliefs subscales were greater than .70. Findings from this study show that KAs have unique cultural beliefs that should be reflected in the instruments used for CRC screening research with this population. The revised instrument could be useful in accurately measuring cultural beliefs among KAs and in developing culturally sensitive interventions to increase CRC screening behaviors among KAs.


Environmental and ecological risk assessment of municipal sewage sludge management using a sustainable solar drying system.
Providing a cost-effective and suitable way for sewage sludge refinement with the purpose of reducing environmental impacts or reutilization of sewage sludge can be an important issue for researchers. This study is inclined at bringing an economical and sustainable solution to sludge management in a municipal wastewater treatment plant. Three types of sludges were collected for the experiments: raw sludge was collected during winter (R.S.), digested sludge was collected during winter (D.S.1), and digested sludge was collected during summer time (D.S.2). This study proposes replacing mechanical drying by a solar drying system. Experimental analysis was carried out to determine the total solids (TS), volatile solids (VS), heavy metals concentration, and pollution index (index of geo accumulation, contamination factor, ecological risk factor). The solar drying system was demonstrated to be very efficient with the three samples achieving a dry solid content of 96.96% for R.S., 96.75% for D.S.1, and 93.60% for D.S.2. after solar drying. While pollution index calculations showed that all three sludges present a low potential ecological risk.


Simultaneous removal of As, Cd, Cr, Cu, Ni and Zn from stormwater: experimental comparison of 11 different sorbents.
The potential of using alumina, activated bauxsol-coated sand (ABCS), bark, bauxsol-coated sand (BCS), fly ash (FA), granulated activated carbon (GAC), granulated ferric hydroxide (GFH), iron oxide-coated sand (IOCS), natural zeolite (NZ), sand, and spinel (MgAl(2)O(4)) as sorbents for removing heavy metals from stormwater are investigated in the present study. The ability of the sorbents to remove a mixture of As, Cd, Cr, Cu, Ni and Zn from synthetic stormwater samples were evaluated in batch tests at a starting pH of 6.5. The metal speciation and saturation data is obtained using the PHREEQ-C geochemical model and used to elucidate the sorption data. It is found that BCS, FA, and spinel have significantly higher affinity towards heavy metals mainly present as cationic or non-charged species (i.e. Cd, Cu, Ni and Zn) compared to those present as anionic species (i.e. As and Cr). However, IOCS, NZ and sand have higher affinity towards As and Cr, while alumina has equally high affinity to all tested heavy metals. The Freundlich isotherm model is found to fit the data in many cases, but ill fitted results are also observed, especially for FA, BCS and GAC, possibly due to leaching of some metals from the sorbents (i.e. for FA) and oversaturated conditions making precipitation the dominant removal mechanism over sorption in batches with high heavy metal concentrations and pH. Calculated sorption constants (i.e. K(d)) are used to compare the overall heavy metal removal efficiency of the sorbents, which in a decreasing order are found to be: alumina, BCS, GFH, FA, GAC, spinel, ABCS, IOCS, NZ, bark, and sand. These findings are significant for future development of secondary filters for removal of dissolved heavy metals from stormwater runoff under realistic competitive conditions in terms of initial heavy metal concentrations, pH and ionic strength.


Endobronchial lipoma.
We have described three cases of endobronchial lipoma, which is among the least common neoplasms found in the tracheobronchial tree. If these tumors, which occur most commonly in men, are not recognized early and removed, they may produce progressive bronchial obstruction and cause recurrent bouts of obstructive pneumonitis, irreversible bronchiectasis, and pulmonary damage. Endobronchial lipomas are usually accessible to endoscopic excision, preventing permanent lung damage.


Identification of multiple associative and dissociative proliferative and uveitogenic T-cell sites in human interstitial retinoid-binding protein.
Human interstitial retinoid-binding protein (HIRBP) is a 136 kDa retinal protein capable of inducing experimental autoimmune uveoretinitis (EAU) and experimental autoimmune pinealitis (EAP) in Lewis (LEW) rats. In order to identify the T-cell recognition sites of HIRBP responsible for uveitogenic and proliferative responses, 125 overlapping peptides corresponding to its entire 1262 amino acid sequence were synthesized. Individual peptides were tested for their ability to induce EAU in LEW rats and to stimulate lymphocyte proliferation in rats immunized with the native molecule. Our previous results showed the presence of nine uveitogenic peptides in HIRBP with a minimum requirement of eight amino acids needed to induce EAU in LEW rats. Our present studies show nine proliferative peptides, four of which are also responsible for uveitogenicity. Another four peptides known to actively induce EAU were unable to elicit proliferative responses. However, these peptides overlapped or were adjacent to peptides that elicited good proliferative responses. A single, highly proliferative peptide was located on the amino terminus of HIRBP. In addition, EAU was adoptively transferred with lymph node cells (LNC) of LEW rats previously immunized with two synthetic peptides known to be uveitogenic. Our study indicates that human IRBP is a complex molecule containing multiple and spatially distinct T-cell epitopes responsible for its uveitogenicity, adoptive transfer of EAU and proliferative responses.


The Measurement Approaches to Partnership Success (MAPS) Questionnaire and Facilitation Guide: A Validated Measure of CBPR Partnership Success.
Partnerships that effectively engage in certain key structural and process functions are more likely to meet their research goals and contribute to longer-term health equity outcomes. Ongoing evaluation of partnerships' level of achievement of these key functions, along with their fidelity to the guiding principles of community-based participatory research (CBPR), is therefore essential to understand how they can achieve desired partnership outcomes. This article describes the validated Measurement Approaches to Partnership Success (MAPS) Questionnaire and the use of an accompanying Facilitation Guide in helping members of CBPR partnerships evaluate their partnership's state of development and interpret findings to improve its structure, processes, and outcomes. We describe the conceptual framework guiding the development of the MAPS Questionnaire and its 81-item across seven key outcome dimensions, along with 28 items measuring precursor characteristics of CBPR partnership outcomes. The Facilitation Guide provides general guidelines for sharing, interpreting, and applying results within partnerships using a participatory process, definitions and items for each dimension, an example of presenting summary means, and dimension-specific reflective questions for discussion. We offer recommendations for practical uses of the MAPS Questionnaire and Facilitation Guide. Whether used as a comprehensive tool or by dimension, the MAPS Questionnaire is conceptually sound and empirically validated for evaluating how CBPR partnerships can achieve long-standing success. CBPR partnerships at any stage of development will find the MAPS Questionnaire and Facilitation Guide useful in measuring and interpreting indicators of partnership success, sharing results, and improving their ability to contribute to achieving health equity goals.


Apparent zinc absorption and zinc status of weanling rats fed moderately zinc-deficient diets enriched with beef tallow or sunflower oil.
The aim of the study was to compare apparent Zn absorption and Zn status of weanling rats fed diets that differed in Zn level, fat level and fat source. Semi-synthetic diets, which were about isoenergetic and contained 3% soyabean oil, were supplemented with 7 or 100 mg Zn/kg to create a mild Zn deficiency (LZ) or a high Zn supply (HZ) and with 0 (LF), 22% beef tallow (BT) or 22% sunflower oil (SF) according to a 2 × 3 factorial design of treatments. They were fed ad libitum to 6 × 8 rats for 28 days. Energy intake and growth rates were comparable among the HZ groups. Weight gains in the LZ-LF, LZ-BT and LZ-SF groups averaged 5.54, 4.95 and 4.15 g/day, and apparent Zn absorption averaged 79.4, 60.3 and 48.0 μg Zn/day, respectively, whereas faecal Zn excretion was comparable among these groups. Apparent Zn absorption, and plasma and femur Zn concentrations were lower in the high-fat groups than in the LF group, possibly due to the high cellulose content of the BT and SF diets. Plasma Zn concentrations were higher in the animals fed the BT-based than in the SF-based diets, whereas femur and soft tissue Zn concentrations were comparable among these groups. The differences between the LZ-BT and LZ-SF groups in growth rate, Zn absorption rate and Zn status were confirmed in a second experiment. The results indicate that moderately Zn-deficient diets enriched with SF in relation to BT affect Zn metabolism of weanling rats by a yet unknown mechanism.


Serum relaxin in patients with invasive mole, choriocarcinoma and persistent trophoblastic disease.
Human chorionic gonadotropin (hCG) is considered to be one of the factors which regulate relaxin secretion in humans. Serum immunoreactive relaxin levels are increased and are detectable by radioimmunoassay both in normal and molar pregnancy. Circulating hCG levels are increased in trophoblastic disease. In the present study, relaxin and hCG levels were sequentially measured in patients with invasive mole, choriocarcinoma and persistent trophoblastic disease. Serum relaxin levels were detectable by radioimmunoassay in these patients before treatment, though they were significantly lower than in normal pregnancy. The corpus luteum of pregnancy is the main source of circulating relaxin in normal pregnancy. The existence of a corpus luteum was confirmed in the 2 patients who underwent laparotomy. Consequently, the corpus luteum may also be the main source of circulating relaxin in trophoblastic disease. Parallel changes in hCG and relaxin levels were observed during the courses of trophoblastic disease. The finding suggests that relaxin secretion is dependent on hCG stimulation in trophoblastic disease in the presence of corpus luteum.


Identification of α-Glucosidase Inhibitors in Machilus litseifolia by Combined Use of High-Resolution α-Glucosidase Inhibition Profiling and HPLC-PDA-HRMS-SPE-NMR.
Type 2 diabetes is a chronic multifactorial disease affecting more than 425 million people worldwide, and new selective α-glucosidase inhibitors with fewer side effects are urgently needed. In this study, a crude ethyl acetate extract of Machilus litseifolia was fractionated by solid-phase extraction using C18 cartridges to give a fraction enriched in α-glucosidase inhibitors. Subsequent microfractionation and bioassaying of the eluate by high-performance liquid chromatography (HPLC) using a complementary pentafluorophenyl column allowed construction of a high-resolution α-glucosidase inhibition profile (biochromatogram). This was used to target high-performance liquid chromatography-photodiode array detection-high-resolution mass spectrometry-solid-phase extraction-nuclear magnetic resonance spectroscopy (HPLC-PDA-HRMS-SPE-NMR) analysis toward α-glucosidase inhibitors. This led to the identification of 13 dicoumaroylated flavonol rhamnosides, of which seven (8, 10, 12a, 12b, 16, 17, and 18) are reported for the first time, and two lignans, of which one (5) is reported for the first time. IC50 values of isolated compounds toward α-glucosidase range from 5.9 to 35.3 μM, which is 8 to 91 times lower than the IC50 value of 266 μM measured for the reference compound acarbose.


[Intravenous hydrocortisone in large doses in the treatment of delayed ischemic neurological deficits following subarachnoid hemorrhage--results of a multi-center controlled double-blind clinical study].
Glucocorticoid in high dose has known to reduce vascular sensitivity to various vasoconstrictive stimuli. It inhibits phospholipase to reduce production of prostaglandins. It stabilizes the cell membrane and prevents cerebral edema. All these pharmacological effects indicate possible usefulness of this drug for the treatment of cerebral ischemia due to vasospasm. Based on these theoretical backgrounds a multi-center controlled double blind clinical study was carried out. The patient who showed manifestations of delayed cerebral ischemia due to vasospasm were selected for this study. As soon as the clinical manifestation appeared, the patient was given either 3 grams of hydrocortisone intravenously in a 60 ml solution or the placebo. The administration was repeated 6 times with interval of 12 hours. The patients were allowed to be treated according to the independent protocol of each institute except for the maximum daily use of glucocorticoid. The effect of the therapy was evaluated at 4th, 7th day and 1 month after the initiation. The study involved 52 institutes and a total of 140 patients, seventy-one patients who received hydrocortisone (group A) and 69 patients who received placebo (group P) was analysed. There were no significant differences in background data between both groups. In patients with grade I, II or III on admission, the favorable effects of hydrocortisone were demonstrated on changes in neurological findings. In group A, there were significantly more cases of improvement at 4th day for orientation about place and person. At 1 month or on discharge group A showed significant improvement almost in every aspect of neurological findings including mental, speech and motor functions.(ABSTRACT TRUNCATED AT 250 WORDS)


Uniform, Strain-Free, Large-Scale Graphene and h-BN Monolayers Enabled by Hydrogel Substrates.
Translation of the unique properties of 2D monolayers from non-scalable micron-sized samples to macroscopic scale is a longstanding challenge obstructed by the substrate-induced strains, interface nonuniformities, and sample-to-sample variations inherent to the scalable fabrication methods. So far, the most successful strategies to reduce strain in graphene are the reduction of the interface roughness and lattice mismatch by using hexagonal boron nitride (h-BN), with the drawback of limited uniformity and applicability to other 2D monolayers, and liquid water, which is not compatible with electronic devices. This work demonstrates a new class of substrates based on hydrogels that overcome these limitations and excel h-BN and water substrates at strain relaxation enabling superiorly uniform and reproducible centimeter-sized sheets of unstrained monolayers. The ultimate strain relaxation and uniformity are rationalized by the extreme structural adaptability of the hydrogel surface owing to its high liquid content and low Young's modulus, and are universal to all 2D materials irrespective of their crystalline structure. Such platforms can be integrated into field effect transistors and demonstrate enhanced charge carrier mobilities in graphene. These results present a universal strategy for attaining uniform and strain-free sheets of 2D materials and underline the opportunities enabled by interfacing them with soft matter.


Quantum magnetic impurities in magnetically ordered systems.
We discuss the problem of a spin 1/2 impurity immersed in a spin S magnetically ordered background. We show that the problem maps onto a generalization of the dissipative two level system with two independent heat baths, associated with the Goldstone modes of the magnet, that couple to different components of the impurity spin operator. Using analytical perturbative renormalization group methods and accurate numerical renormalization group we show that contrary to other dissipative models there is quantum frustration of decoherence and quasiscaling even in the strong coupling regime. We make predictions for the behavior of the impurity magnetic susceptibility. Our results may also have relevance to quantum computation.


KRIT1 Loss-Of-Function Associated with Cerebral Cavernous Malformation Disease Leads to Enhanced S-Glutathionylation of Distinct Structural and Regulatory Proteins.
Loss-of-function mutations in the KRIT1 gene are associated with the pathogenesis of cerebral cavernous malformations (CCMs), a major cerebrovascular disease still awaiting therapies. Accumulating evidence demonstrates that KRIT1 plays an important role in major redox-sensitive mechanisms, including transcriptional pathways and autophagy, which play major roles in cellular homeostasis and defense against oxidative stress, raising the possibility that KRIT1 loss has pleiotropic effects on multiple redox-sensitive systems. Using previously established cellular models, we found that KRIT1 loss-of-function affects the glutathione (GSH) redox system, causing a significant decrease in total GSH levels and increase in oxidized glutathione disulfide (GSSG), with a consequent deficit in the GSH/GSSG redox ratio and GSH-mediated antioxidant capacity. Redox proteomic analyses showed that these effects are associated with increased S-glutathionylation of distinct proteins involved in adaptive responses to oxidative stress, including redox-sensitive chaperonins, metabolic enzymes, and cytoskeletal proteins, suggesting a novel molecular signature of KRIT1 loss-of-function. Besides providing further insights into the emerging pleiotropic functions of KRIT1, these findings point definitively to KRIT1 as a major player in redox biology, shedding new light on the mechanistic relationship between KRIT1 loss-of-function and enhanced cell sensitivity to oxidative stress, which may eventually lead to cellular dysfunctions and CCM disease pathogenesis.


The effect of spatial attention on contrast response functions in human visual cortex.
Previous electrophysiology data suggests that the modulation of neuronal firing by spatial attention depends on stimulus contrast, which has been described using either a multiplicative gain or a contrast-gain model. Here we measured the effect of spatial attention on contrast responses in humans using functional MRI. To our surprise, we found that the modulation of blood oxygenation level-dependent (BOLD) responses by spatial attention does not greatly depend on stimulus contrast in visual cortical areas tested [V1, V2, V3, and MT+ (middle temporal area)]. An additive model, rather than a multiplicative or contrast-gain model best describes the attentional modulations in V1. This inconsistency with previous single-unit electrophysiological data has implications for the population-based neuronal source of the BOLD signal.


A descriptive study of women's perceptions of their asthma during pregnancy.
To determine the impact of asthma during pregnancy from the perspective of the pregnant woman. A descriptive survey using the Internet for subject recruitment and data collection was conducted using an adaptation of the Cancer Survivors Survey Questionnaire. Women with asthma who were pregnant or who had recently given birth (n = 166) were the sample. Women responded from the United States, Canada, Europe, and Asia. Physical symptoms, emotional responses, and coping strategies to deal with the asthma were queried. Women reported a variety of respiratory difficulties including wheezing, coughing, and shortness of breath. They were concerned about avoiding triggers leading to acute asthma, the effect of the asthma medications on the fetus, and losing their jobs due to absenteeism. They wanted to know more about how to prevent an asthma attack and what effect their disease could have on their unborn infants. Women need education and support to help them deal with asthma during pregnancy. Nursing can have an important role in teaching these women and helping them monitor their asthma status during pregnancy.


Hyperfine-field-mediated spin beating in electrostatically bound charge carrier pairs.
Organic semiconductors offer a unique environment to probe the hyperfine coupling of electronic spins to a nuclear spin bath. We explore the interaction of spins in electron-hole pairs in the presence of inhomogeneous hyperfine fields by monitoring the modulation of the current through an organic light emitting diode under coherent spin-resonant excitation. At weak driving fields, only one of the two spins in the pair precesses. As the driving field exceeds the difference in local hyperfine field experienced by electron and hole, both spins precess, leading to pronounced spin beating in the transient Rabi flopping of the current. We use this effect to measure the magnitude and spatial variation in hyperfine field on the scale of single carrier pairs, as required for evaluating models of organic magnetoresistance, improving organic spintronics devices, and illuminating spin decoherence mechanisms.


On informative detection bias in screening studies.
The problem of estimating the effect of hormone replacement therapy (HRT) on breast cancer has attracted much attention in the causal inference literature. It is known that the HRT effect on diagnosis (observed) is potentially larger than the effect on true cancer status (of interest), and that the standard approach (stratification) to deal with this detection bias is not valid when screening pattern and cancer status share common causes. We propose a sensitivity analysis to deal with detection bias, and demonstrate that the earlier proposed approach of data restriction is not valid.


COVID-19: booster(s) vs. hospitalization and Intensive Care Unit admission.
As the pandemic continues, different vaccine protocols have been implemented to maintain the protection of vaccines and to provide protection against new variants. The aim of this study was to assess hospitalized patients' vaccination status and document the efficacy of boosters. The patients that were hospitalized due to COVID-19 were enrolled from 28 hospitals in Turkey for five months from September 2021. 5,331 confirmed COVID-19 patients from collaborating centers were randomly enrolled to understand/estimate the distribution of vaccination status in hospitalized patients and to compare the efficacy of vaccination/booster protocols. 2,779 men and 2,552 women of which 2,408 (45.2%) were admitted to Intensive Care Units participated in this study. It was found that the highest risk reduction for all age groups was found in groups that received 4 doses. Four doses of vaccination for every 3.7 people under 50 years of age, for every 5.7 people in the 50-64 age group, and for every 4.3 people over 65 years of age will prevent 1 patient from being admitted to intensive care. Regardless of the type of vaccine, it was found that the risk of ICU hospitalization decreased in those who were vaccinated compared to those who were not vaccinated. Regardless of the type of vaccine, the ICU risk was found to decrease 1.25-fold in those who received 1 or 2 doses of vaccine, 1.18-fold in those who received 3 doses, and 3.26-fold in those who received 4 doses. The results suggested that the addition of a fourth dose is more effective in preventing intensive unit care even in disadvantaged groups.


Increased affective empathy in bipolar patients during a manic episode.
To assess both cognitive and affective empathy in patients with bipolar disorder (BD) during an acute manic or depressive episode. The study included 25 patients with BD (aged 35±14 years) during an acute manic episode, 25 bipolar patients (aged 41±14 years) during a depressive episode, and 25 healthy control subjects (aged 36±11 years). Cognitive and affective empathy were assessed using the Multifaceted Empathy Test. In both manic and depressive patients, a significant deficit in cognitive empathy was demonstrated. However, indices of affective empathy were significantly higher in the manic group than in depressed and control subjects. In the depressed patients, indices did not differ from those of healthy controls. For affective empathy, a significant positive correlation was found with intensity of manic symptoms and a negative correlation was found with intensity of depressive symptoms. No such correlations were observed with cognitive empathy. We found evidence of increased affective empathy (overempathizing) during a manic episode in bipolar patients. This phenomenon may be connected with disturbances in emotion inhibition related to anastrophic thinking and associated with increased activity of mirror neurons, all of which occur during a manic episode.


An effective and efficient approach for manually improving geocoded data.
The process of geocoding produces output coordinates of varying degrees of quality. Previous studies have revealed that simply excluding records with low-quality geocodes from analysis can introduce significant bias, but depending on the number and severity of the inaccuracies, their inclusion may also lead to bias. Little quantitative research has been presented on the cost and/or effectiveness of correcting geocodes through manual interactive processes, so the most cost effective methods for improving geocoded data are unclear. The present work investigates the time and effort required to correct geocodes contained in five health-related datasets that represent examples of data commonly used in Health GIS. Geocode correction was attempted on five health-related datasets containing a total of 22,317 records. The complete processing of these data took 11.4 weeks (427 hours), averaging 69 seconds of processing time per record. Overall, the geocodes associated with 12,280 (55%) of records were successfully improved, taking 95 seconds of processing time per corrected record on average across all five datasets. Geocode correction improved the overall match rate (the number of successful matches out of the total attempted) from 79.3 to 95%. The spatial shift between the location of original successfully matched geocodes and their corrected improved counterparts averaged 9.9 km per corrected record. After geocode correction the number of city and USPS ZIP code accuracy geocodes were reduced from 10,959 and 1,031 to 6,284 and 200, respectively, while the number of building centroid accuracy geocodes increased from 0 to 2,261. The results indicate that manual geocode correction using a web-based interactive approach is a feasible and cost effective method for improving the quality of geocoded data. The level of effort required varies depending on the type of data geocoded. These results can be used to choose between data improvement options (e.g., manual intervention, pseudocoding/geo-imputation, field GPS readings).


Kinetics of Inhibition of Monoamine Oxidase Using Curcumin and Ellagic Acid.
Curcumin and ellagic are the natural polyphenols having a wide range of pharmacological actions. They have been reported to have their use in various neurological disorders. This study was aimed to evaluate the effect of curcumin and ellagic acid on the activity of monoamine oxidase (MAO), the enzyme responsible for metabolism of monoamine neurotransmitters which are pivotal for neuronal development and function. The in vitro effects of these selected polyphenols on MAO activities in mitochondria isolated from rat brains were examined. Brain mitochondria were assayed for MAO type-B (MAO-B) using benzylamine as substrates. Rat brain mitochondrial MAO preparation was used to study the kinetics of enzyme inhibition using double reciprocal Lineweaver-Burk plot. MAO activity was inhibited by curcumin and ellagic acid; however, higher half maximal inhibitory concentrations of curcumin (500.46 nM) and ellagic acid (412.24 nM) were required compared to the known MAO-B inhibitor selegiline. It is observed that the curcumin and ellagic acid inhibit the MAO activity with both the competitive and noncompetitive type of inhibitions. Curcumin and ellagic acid can be considered a possible source of MAO inhibitor used in the treatment of Parkinson's and other neurological disorders. Monoamine oxidase (MAO) is involved in a variety of neurological disorders including Parkinson's disease (PD)Curcumin and ellagic acid inhibit the monoamine oxidase activityEllagic acid revealed more potent MAO type-B (MAO-B) inhibitory activity than curcuminKinetic studies of MAO inhibition using different concentrations of curcumin and ellagic acid were plotted as double reciprocal Lineweaver-Burk plotThe mode of inhibition of both compounds toward MAO-B is mixed (competitive and uncompetitive) type of inhibition with both the competitive and noncompetitive type of inhibitions. Abbreviations used: MAO: Monoamine oxidase, IC50: Higher half maximal inhibitory concentrations, PD: Parkinson's disease, LB: Lewy bodies, SNpc: Substantia nigra pars compacta, ROS: Reactive oxygen species, SG: Selegiline, DMC: demethoxycurcumin, BDMC: Bisdemethoxycurcumin.


Humoral immune response in healthcare workers after two doses of a BNT162b2 mRNA vaccine in Yucatan, Mexico.
The antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as well as the host immune response after vaccination and viral infection have shown to be highly heterogeneous. This is a case series study analysing humoral immune response and vaccination side effects after two doses of a BNT162b2 mRNA among healthcare workers (HCWs) in Mexico. All participants were scheduled for their two doses of mRNA BNT162b2 vaccine and provided information through a questionnaire: demographic characteristics, antibody serum titres and vaccination-related side effects. Blood samples were obtained for serology testing after the first and second doses of vaccine. No serious adverse effects due to vaccination were reported; nonetheless, non-medical HCWs reported more side effects after the second dose. The previous infection with SARS-CoV-2 boosted immune response after receiving the first vaccination (roughly 30 times higher than those without previous infection); nonetheless, after the second dose, the immune response did not show a higher titre as might be expected.


Carbohydrate ingestion and brain serotonin synthesis: relevance to a putative control loop for regulating carbohydrate ingestion, and effects of aspartame consumption.
The ingestion of a meal of carbohydrates by fasting rats rapidly increases brain tryptophan level and serotonin (5-HT) synthesis. The rise in brain tryptophan level follows from an increase in tryptophan transport into brain, the consequence of an insulin-induced reduction in the blood levels of several amino acids that compete with tryptophan for brain uptake. In contrast, ingesting protein with carbohydrate does not stimulate brain tryptophan uptake or 5-HT synthesis, because the blood levels of tryptophan's transport competitors are increased, not reduced. These observations form the biochemical basis of a current proposal for a regulatory loop governing meal-to-meal appetite for carbohydrates. This review briefly analyzes the experimental basis for the carbohydrate appetite regulatory loop, and finds it wanting. It also considers the proposal that the ingestion of the artificial sweetener aspartame might disrupt the putative regulatory loop for carbohydrate intake regulation, and thus promote rather than help to limit carbohydrate appetite, and finds this hypothesis unrealistic as well. In general, the conclusion is that while single meals do readily influence brain tryptophan uptake and 5-HT synthesis, it is presently unclear what role such neurochemical effects of food ingestion have in the control of specific appetites.


[Changes in hemodynamics with a combination of epidural anesthesia and propofol sedation in children].
Hemodynamic profiles and myocardial contractility were investigated in children aged 3-14 years during epidural anesthesia with propofol. Anesthesia was induced by intravenous bolus propofol (3.5 mg/kg). Ketamine (2.4 mg/kg) was used to potentiate analgesia during intubation. Xilocaine (5 mg/kg) was used for epidural analgesia. Anesthesia was maintained by continuous i.v. propofol infused in a dose of 191-312 micrograms/kg x min (mean dose 243 +/- 30.3 micrograms/kg x min) until the peak of epidural analgesic activity was reached, after which propofol dose was gradually reduced to 53-143 micrograms/kg x min (mean 108.8 +/- 14.6 micrograms/kg x min). This variant of epidural anesthesia with i.v. propofol ensured a hemodynamically stable anesthesia and good analgesia in operations of any complexity. It was however paralleled by a moderate decrease of myocardial contractility.


Change detection in multi-voice music: the role of musical structure, musical training, and task demands.
This study evaluated the relationship between primitive and scheme-driven grouping (A. S. Bregman, 1990) by comparing the ability of different listeners to detect single note changes in 3-voice musical compositions. Primitive grouping was manipulated by the use of 2 distinctly different compositional styles (homophony and polyphony). The effects of scheme-driven processes were tested by comparing performance of 2 groups of listeners (musicians and nonmusicians) and by varying task demands (integrative and selective listening). Following previous studies, which had tested only musically trained participants, several variables were manipulated within each compositional style. The results indicated that, although musicians demonstrated a higher sensitivity to changes than did nonmusicians, the 2 groups exhibited similar patterns of sensitivity under a variety of conditions.


Representation theory for strange attractors.
Embeddings are diffeomorphisms between some unseen physical attractor and a reconstructed image. Different embeddings may or may not be equivalent under isotopy. We regard embeddings as representations of the attractor, review the labels required to distinguish inequivalent representations for an important class of dynamical systems, and discuss the systematic ways inequivalent embeddings become equivalent as the embedding dimension increases until there is finally only one "universal" embedding in a suitable dimension.


Sequential Social Exclusion in a Novel Cyberball Paradigm Leads to Reduced Behavioral Repair and Plasma Oxytocin in Borderline Personality Disorder.
Patients with borderline personality disorder (BPD) show interpersonal deficits, and altered emotional and oxytocin (OT) responses to social exclusion (Cyberball). In order to extend previous findings, this study applies a novel Cyberball variant. Nineteen BPD patients and 56 healthy controls (HC) played Cyberball for 2 minutes of inclusion, 5 minutes of partial exclusion by one of two co-players, and 2 minutes total exclusion by both. Plasma OT levels at baseline and after 7, 9, 15, and 40 minutes were measured with radioimmunoassay. BPD patients showed a greater aversive reaction and a trend for greater OT reduction after social exclusion than HC. BPD patients also tended to play less frequently with the excluder. Though limited by our sample size, we partially replicate previous findings. Our preliminary behavioral data support the notion of an altered OT regulation and reduced capacity for social cooperation in BPD.


Adjustable higher SNR and long-range 3D-imaging cluster lidar based on a coded full-waveform technique.
Three-dimensional (3D) lidar imaging technology is developing rapidly in civil, commercial, and military fields. Especially in the military field, lidar with a high signal-to-noise ratio (SNR) and long range is essential. However, high SNR is contradictory to long-range detection, which is a difficult problem to be resolved. In this paper, we propose an adjustable higher SNR and long-range 3D-imaging cluster lidar (C-Lidar) based on a coded full-waveform technique. C-Lidar makes full use of linear mode avalanche photodiode (Lm-APD) multiplexing and space-time domain laser codec technology. The system uses only an 8×8 Lm-APD array to acquire 64×64×64 pixels in a single imaging process within 6.4×10-3 s. Based on the C-Lidar system, we establish a mathematical model to analyze the increased SNR by 18 dB. It is noteworthy that the SNR can be increased much higher when the product of the number of Lm-APDs and the length of the encoding sequence increase. The SNR is adjusted with the product, and C-Lidar changes the SNR by controlling the product. To verify the feasibility of the above theory, we conduct a principle prototype imaging experiment, and the result shows that C-Lidar achieves a clear image at 2 km.


Wolf in sheep's clothes: An uncommon case of pneumonic-type adenocarcinoma.
We report a case of a patient who presented with clinical and radiological features of a non-resolving pneumonia. Special investigations and a poor response to antibiotic therapy excluded an infective aetiology. A diagnosis of invasive mucinous adenocarcinoma, previously termed bronchioloalveolar carcinoma, was made from lung biopsy. This case illustrates the challenges of establishing a timely diagnosis of an uncommon pneumonic-type of adenocarcinoma.


Nonequilibrium thermodynamics of stochastic systems with odd and even variables.
The total entropy production of stochastic systems can be divided into three quantities. The first corresponds to the excess heat, while the second two comprise the housekeeping heat. We denote these two components the transient and generalized housekeeping heat and we obtain an integral fluctuation theorem for the latter, valid for all Markovian stochastic dynamics. A previously reported formalism is obtained when the stationary probability distribution is symmetric for all variables that are odd under time reversal, which restricts consideration of directional variables such as velocity.


Hydrolytic rate at low drug concentration as a limiting factor in resistance to newer cephalosporins.
Hydrolysis kinetics of two cephalosporinases from Citrobacter freundii and Proteus vulgaris having different affinities for cefotaxime and ceftazidime was assessed in studies with cefotaxime, ceftazidime, BMY-28142, and imipenem. The two cephalosporinase genes were cloned into strains of Escherichia coli. The production of these cephalosporinases in strains of E. coli, as well as in the derepressed mutants of C. freundii and P. vulgaris, caused a decrease in susceptibility to the newer cephalosporins. The difference in the rate of hydrolysis at a 0.1 microM concentration of substrate adequately explains the difference in antibacterial activity between cefotaxime and BMY-28142 against E. coli strains with the two cephalosporinases. The results indicate that hydrolysis rate at low substrate concentration, rather than binding with beta-lactams, would be a limiting factor in resistance. The low affinity of cephalosporinases for BMY-28142 means high stability of the agent to the enzymes at low concentration. Furthermore, outer membrane permeability affects the susceptibility of E. coli to cephalosporins synergistically with hydrolysis by cephalosporinases.


A p53-p66Shc signalling pathway controls intracellular redox status, levels of oxidation-damaged DNA and oxidative stress-induced apoptosis.
Correlative evidence links stress, accumulation of oxidative cellular damage and ageing in lower organisms and in mammals. We investigated their mechanistic connections in p66Shc knockout mice, which are characterized by increased resistance to oxidative stress and extended life span. We report that p66Shc acts as a downstream target of the tumour suppressor p53 and is indispensable for the ability of stress-activated p53 to induce elevation of intracellular oxidants, cytochrome c release and apoptosis. Other functions of p53 are not influenced by p66Shc expression. In basal conditions, p66Shc-/- and p53-/- cells have reduced amounts of intracellular oxidants and oxidation-damaged DNA. We propose that steady-state levels of intracellular oxidants and oxidative damage are genetically determined and regulated by a stress-induced signal transduction pathway involving p53 and p66Shc.


Interactions of annexins with the mu subunits of the clathrin assembly proteins.
A number of biochemical and genetic studies have suggested that certain annexins play important roles in the endocytic pathway, possibly involving the generation, localization, or fusion of endocytic compartments. In a yeast two-hybrid screen for proteins that interact with the N-terminal domain of annexin A2 we identified the mu2 subunit of the clathrin assembly protein complex AP-2. The interaction depended upon two copies of a Yxx phi amino acid sequence motif (Y = tyrosine, x = variable residue, phi = bulky, hydrophobic residue) in the annexin that is also characteristic of the binding site for mu2 on the cytoplasmic domains of transmembrane receptors. The interaction between mu2 and full-length annexin A2 was demonstrated in vitro to be direct, to require calcium, and to be functional in the sense that annexin A2 was able to recruit the mu2 to immobilized lipids. Examination of other annexins and mu subunits demonstrated that annexin A2 also binds the mu1 subunit of the AP-1 complex, that annexin A6 binds mu1 and mu2, and that annexin A1 binds only mu1. We propose that annexins can "masquerade" as transmembrane receptors when they are attached to membranes in the presence of calcium and that they might therefore function to initiate calcium-regulated coated pit formation at the cell surface or on intracellular organelles.


MicroRNA-18a attenuates DNA damage repair through suppressing the expression of ataxia telangiectasia mutated in colorectal cancer.
miR-18a is one of the most up-regulated miRNAs in colorectal cancers (CRC) based on miRNA profiling. In this study, we examined the functional significance of miR-18a in CRC. Expression of miR-18a was investigated in 45 CRC patients. Potential target genes of miR-18a were predicted by in silico search and confirmed by luciferase activity assay and Western blot. DNA damage was measured by comet assay. Gene function was measured by cell viability, colony formation and apoptosis assays. The up-regulation of miR-18a was validated and confirmed in 45 primary CRC tumors compared with adjacent normal tissues (p<0.0001). Through in silico search, the 3'UTR of Ataxia telangiectasia mutated (ATM) contains a conserved miR-18a binding site. Expression of ATM was down-regulated in CRC tumors (p<0.0001) and inversely correlated with miR-18a expression (r = -0.4562, p<0.01). Over-expression of miR-18a in colon cancer cells significantly reduced the luciferase activity of the construct with wild-type ATM 3'UTR but not that with mutant ATM 3'UTR, inferring a direct interaction of miR-18a with ATM 3'UTR. This was further confirmed by the down-regulation of ATM protein by miR-18a. As ATM is a key enzyme in DNA damage repair, we evaluated the effect of miR-18a on DNA double-strand breaks. Ectopic expression of miR-18a significantly inhibited the repair of DNA damage induced by etoposide (p<0.001), leading to accumulation of DNA damage, increase in cell apoptosis and poor clonogenic survival. miR-18a attenuates cellular repair of DNA double-strand breaks by directly suppressing ATM, a key enzyme in DNA damage repair.


Stochastic rotation dynamics. I. Formalism, Galilean invariance, and Green-Kubo relations.
A detailed analytical and numerical analysis of a recently introduced stochastic model for fluid dynamics with continuous velocities and efficient multi-particle collisions is presented. It is shown how full Galilean invariance can be achieved for arbitrary Mach numbers and how other low temperature anomalies can be removed. The relaxation towards thermal equilibrium is investigated numerically, and the relaxation time is measured. Equations of motions for the correlation functions of coarse-grained hydrodynamic variables are derived using a discrete-time projection operator technique, and the Green-Kubo relations for all relevant transport coefficients are given. In the following paper (Part 2), analytic expressions for the transport coefficients are derived and compared with simulation results. Long-time tails in the velocity and stress autocorrelation functions are measured and shown to be in good agreement with previous mode-coupling theories for continuous systems.


[Anxiety disorders as a risk factor for sleep disorders and headaches].
Anxiety and related sleep disorders are a problem in modern society. Sleep disorders cover more than 45% of the world's population and have become a global health problem in recent decades. Numerous studies have shown an association of sleep disorders with pain, depression, and anxiety, as well as a causal relationship between chronic pain and sleep deficits. Patients with headaches are at a higher risk of mood and anxiety disorders than people in the general population; these results are particularly noticeable for patients with chronic daily headache as well as medication overuse headache. This interaction between mood/anxiety problems and medication overuse may be an important factor in chronification of episodic headache. Detection and treatment of comorbid diseases will not only provide better results, but also improve the quality of life of patients. In the treatment of this category of patients, it is possible to use noofen, which improves sleep, cognitive functions, and reduces headache.


Nuclear proteins in mouse brain cells bind specifically to the myelin basic protein regulatory region.
Expression of myelin basic protein (MBP) in mice is regulated in a cell- and stage-specific manner during brain development. The MBP control region contains multiple cis-acting elements, shown by in vivo and in vitro assays, which are responsible for its unique pattern of transcription. Using synthetic DNA fragments spanning the MBP control region, we have analyzed nuclear proteins obtained from newborn (2-3 d), young adult (18-30 d), and adult (60 d) animals; these nuclear proteins form DNA-protein complexes with the MBP regulatory region. Brain extracts from young adult and adult mice showed enhanced binding activities with the sequences supporting transcriptional activation in glial cells. Deletion analysis of the proximal activating sequence located at position -14 to -50 with respect to the RNA initiation site resulted in identification of a small region, located between nucleotides -14 to -37, which is required for formation of the complexes. Southwestern assay revealed a major 39-kD protein from young adult brain extract that recognizes the sequences between nucleotides -14 to -37. An additional minor 37-kD protein, derived from young adult brain extract, was also found to be associated with this proximal activating region. Of particular interest is the observation that the minor 37-kD protein became more abundant in the extract derived from adult brain, whereas the major 39-kD protein became less abundant. The possible role of these proteins in cell/stage-specific transcription of MBP is discussed.