Differences in output from corticosteroid inhalers used with a volumatic spacer.
Corticosteroid inhaler therapy using a spacer device is commonly used as an important part of asthma management. Increasingly, generic corticosteroid inhalers are being used with spacer devices. We have therefore tested whether these generic inhalers yield equivalence in dose when compared to the established inhalers. We measured the in vitro output, discharged into a Volumatic spacer from beclomethasone dipropionate inhalers (250 micrograms.puff-1) made by three manufacturers, Allen & Hanburys, 3M and Baker Norton. The output from 20 of each type of inhaler was sampled, in random order, by a computer driven pump system. Beclomethasone was absorbed onto a coded filter, which was analysed independently for drug content. The output per puff differed significantly between the inhalers of each manufacturer, with a 36% difference between the highest output from the Allen & Hanburys device and the lowest output device. We conclude that there are important differences in output from these inhalers when used with a spacer, and that substitution of one device with another will not necessarily give equivalent therapy to the patient.


Weather-Dependent Risk for Legionnaires' Disease, United States.
Using the Nationwide Inpatient Sample and US weather data, we estimated the probability of community-acquired pneumonia (CAP) being diagnosed as Legionnaires' disease (LD). LD risk increases when weather is warm and humid. With warm weather, we found a dose-response relationship between relative humidity and the odds for LD. When the mean temperature was 60°-80°F with high humidity (>80.0%), the odds for CAP being diagnosed with LD were 3.1 times higher than with lower levels of humidity (<50.0%). Thus, in some regions (e.g., the Southwest), LD is rarely the cause of hospitalizations. In other regions and seasons (e.g., the mid-Atlantic in summer), LD is much more common. Thus, suspicion for LD should increase when weather is warm and humid. However, when weather is cold, dry, or extremely hot, empirically treating all CAP patients for LD might contribute to excessive antimicrobial drug use at a population level.


USE OF FLUMETHRIN-IMPREGNATED COLLARS TO MANAGE AN EPIDEMIC OF SARCOPTIC MANGE IN AN URBAN POPULATION OF ENDANGERED SAN JOAQUIN KIT FOXES (VULPES MACROTIS MUTICA).
Sarcoptic mange epidemics can have long-lasting impacts on susceptible wildlife populations, potentially contributing to local population declines and extirpation. Since 2013, there have been 460 reported cases of sarcoptic mange in an urban population of endangered San Joaquin kit foxes (Vulpes macrotis mutica) in Bakersfield, CA, with many of them resulting in fatality. As part of a multifaceted response to mitigate mange-caused mortalities and reduce this conservation threat, a 2-yr randomized field trial was conducted to assess the efficacy of long-acting flumethrin collars against sarcoptic mange in kit foxes. Thirty-five kit foxes living in a high-density population on a college campus were captured, examined, administered selamectin, and each fox randomly assigned to either receive a flumethrin collar placed within a VHF radio collar or a VHF radio collar without flumethrin. The survival and mange-infestation status of study animals was monitored via radio telemetry, remote cameras, and periodic recapture examinations and compared among treated and control kit foxes using a Cox proportional hazards model. The average time to onset of mange for treated kit foxes (176 days) was similar to controls (171 days) and treatment with flumethrin did not significantly reduce mange risk for all kit foxes. Kit foxes that had a mild mange infestation at the beginning of the study were four times more likely to develop mange again, regardless of flumethrin treatment, compared with kit foxes that had no signs at initial recruitment. This study demonstrates an approach to evaluating population-level protection and contributes to the limited literature on efficacy, safety, and practicality of acaricides in free-ranging wildlife.


Charge-Noise Insensitive Chiral Photonic Interface for Waveguide Circuit QED.
A chiral photonic interface is a quantum system that has different probabilities for emitting photons to the left and right. An on-chip compatible chiral interface is attractive for both fundamental studies of light-matter interactions and applications to quantum information processing. We propose such a chiral interface based on superconducting circuits, which has wide bandwidth, rich tunability, and high tolerance to fabrication variations. The proposed interface consists of a core that uses Cooper-pair boxes (CPBs) to break time-reversal symmetry, and two superconducting transmons that connect the core to a waveguide in the manner reminiscent of a "giant atom." The transmons form a state decoupled from the core, akin to dark states of atomic physics, rendering the whole interface insensitive to the CPB charge noise. The proposed interface can be extended to realize a broadband fully passive on-chip circulator for microwave photons.


Evidence for state, community and systems-level prevention strategies to address the opioid crisis.
Practitioners and policy makers need evidence to facilitate the selection of effective prevention interventions that can address the ongoing opioid overdose epidemic in the United States. We conducted a systematic review of publications reporting on rigorous evaluations of systems-level interventions to address provider and patient/public behavior and prevent prescription and illicit opioid overdose. A total of 251 studies were reviewed. Interventions studied included 1) state legislation and regulation, 2) prescription drug monitoring programs (PDMPs), 3) insurance strategies, 4) clinical guideline implementation, 5) provider education, 6) health system interventions, 7) naloxone education and distribution, 8) safe storage and disposal, 9) public education, 10) community coalitions, and 11) interventions employing public safety and public health collaborations. The quality of evidence supporting selected interventions was low to moderate. Interventions with the strongest evidence include PDMP and pain clinic legislation, insurance strategies, motivational interviewing in clinical settings, feedback to providers on opioid prescribing behavior, intensive school and family-based programs, and patient education in the clinical setting. Although evidence is growing, further high-quality research is needed. Investigators should aim to identify strategies that can prevent overdose, as well as influence public, patient, and provider behavior. Identifying which strategies are most effective at addressing prescription compared to illicit opioid misuse and overdose could be fruitful, as well as investigating synergistic effects and unintended consequences.


Identification of dual receptor-binding specific strains of human H5N1 viruses in China.
Both the 2, 6 linkage and its topology on target cells are critical for the recognition by human influenza virus. The binding preference of avian flu virus H5N1 HA to the 2, 3-linked sialylated glycans is considered the major factor limiting its efficient infection and transmission in humans. To monitor potential adaptation of H5N1 virus in human population, the surveillance of receptor-binding specificity was undertaken in China. The binding specificity of 32 human H5N1 virus strains isolated from 2003 to 2009 was tested by 2, 3-specific sialidase-treated chicken red blood cell (CRBC) agglutination assay and a solid-phase direct binding assay with synthetic sialylglycopolymers. Dual binding preference to 2, 3 and 2, 6-glycans were found in two strains: A/Guangdong/1/06 (A/GD/1/06) and A/Guangxi/1/08 (A/GX/1/08). Though minor effect of short-2, 6-binding was detected in A/GX/1/08 at a low virus titer, both showed high affinity to the oligosaccharide at a high load. Notably both are of the long-2, 6-recognition, with the same topology as that of human H1N1 and H3N2 viruses. The findings suggest that human H5N1 virus in China likely acquired the potential human-adaptation ability. Further research and surveillance on receptor-binding specificity of H5N1 viruses are required.


PCR in meningoencephalitis diagnosis.
Polymerase chain reaction (PCR) detection of a stretch of nucleic acid sequence of microbial origin from a clinical sample is not always diagnostic of disease unless the identified agent is a strict pathogen or its growth is documented. We describe here a case of acute meningoencephalitis in a 21-y-old man, in whom no pathogen was isolated by traditional bacterial or viral culture. Standard DNA PCR performed on the cerebrospinal fluid (CSF) identified the presence of 3 infectious agents: HHV-6, HHV-7 and Mycoplasma pneumoniae. Additional PCRs performed on CSF fractions along with gene transcript analysis proved the bystander role of the 2 herpesviruses and indicated M. pneumoniae as the relevant replicating agent, most likely playing to be a pathogenic role. Until this useful analysis becomes routine, clinicians should deal carefully with DNA PCR results, especially when assessing the aetiological role of agents, such as herpesviruses, which are known to undergo latency.


Human epidermis reconstructed by culture: is it "normal"?
Human keratinocytes were grown on a dermal equivalent (or lattice) at the liquid-air interface in an attempt to reconstitute a functional epidermis in vitro. Although the multilayered epithelium thus obtained is well differentiated, as shown by the presence of keratohyaline granules and horny layer, several differences from its in vivo counterpart were also observed: In the reconstructed epidermis, basal keratinocytes do not have the cuboidal shape found in vivo; they synthesize bullous pemphigoid antigen and laminin, but the distribution of these antigens is not linear as in vivo; they contain the plasma-membrane antigens restricted to the basal layer in vivo (VM1, BC1), but these antigens are not polarized; lack of polarization is also evidenced by the distribution of actin. Differentiation markers appear but with a topography slightly different from that of epidermis in vivo; the 67-kD keratin does not appear in the first suprabasal layer as in vivo but above; involucrin, which appears in the granular layers in vivo appears as soon as the cells leave the basal layer. psi 3 antigen and fibronectin found in vivo only in hyperproliferative epidermis (wound healing, psoriasis) are detected. Hyperproliferation would also explain the unexpected straining of basal cells by KL1 monoclonal antibody. Because of the potential clinical or pharmacologic use of artificial epidermis, the question of whether the epidermis obtained in vitro can be considered as "normal" is discussed.


Application of ultrasound contrast agents for the characterization of female urethral vascularization in healthy pre- and postmenopausal volunteers: preliminary report.
Vascularization of the female urethra is an important factor contributing to the sealing effect responsible for the normal urethral closing system. The aim of this study was to assess whether contrast enhanced ultrasonography can be used to evaluate changes in urethral vascularization between pre- and postmenopausal women. We studied the vascularization of female urethra in 11 healthy premenopausal females during the midfollicular phase of the menstrual cycle and 10 healthy postmenopausal volunteers using ultrasound contrast agents with a 2-5 MHz curved-array transducer by a translabial approach. Reperfusion curves were analyzed by a blinded investigator. Ultrasound contrast agents were measured with specifically designed software, and results were evaluated using the Mann-Whitney U-test. The data suggest that the enhancement characteristics of the urethra were different in pre- and postmenopausal women and that the percent of blood volume and blood flow decreased with age. No changes were observed between pre- and postmenopausal women regarding the velocity of blood flow. The study of female urethra vascularization by ultrasound contrast agents is safe, feasible, and noninvasive.


The nontranscribed chicken calmodulin pseudogene cross-hybridizes with mRNA from the slow-muscle troponin C gene.
A chicken calmodulin pseudogene with no introns was previously shown to hybridize under stringent conditions with an mRNA species present in skeletal and cardiac muscles, yet it would not hybridize to calmodulin mRNA (J. P. Stein, R. P. Munjaal, L. Lagace', E. C. Lai, B. W. O'Malley, and A. R. Means, Proc. Natl. Acad. Sci. USA 80:6485-6489, 1983). Using the pseudogene as a probe, we isolated a full-length cDNA corresponding to this mRNA from a chicken breast muscle library and showed by sequence analysis that it encodes slow-muscle troponin C and not the pseudogene product. Hybridization between the calmodulin pseudogene and slow-muscle troponin C cDNA is due to a short region of high homology in those nucleotides that encode helices B and C of troponin C and calmodulin. Genomic Southern analysis showed the calmodulin pseudogene and the gene for slow-muscle troponin C to exist as distinct single copies.


In situ analysis of hepatitis B virus (HBV) antigen and DNA in HBV-induced hepatocellular carcinoma.
Hepatitis B Virus (HBV) infection is the major risk factor for hepatocellular carcinoma (HCC) in East Asia. Here we aimed to further investigate the abundance of viral antigen and DNA within HBV-related HCC and surrounding tissues at histological level. In addition to routine histopathology, in situ hybridization (ISH) of HBV DNA and immunohistochemistry (IHC) of HBsAg were performed in tissues from 131 HBsAg-positive HCC patients undergoing liver resection. Serum α-fetoprotein together with basic biochemical and immunological parameter was also measured. Overall, the ISH of HBV DNA and IHC of HBsAg showed 31.3% and 92.9% positive rate respectively (p < 0.0001). The level of correlation between these two markers was much more significant in tumor (p < 0.0001) than in tumor-surrounding tissue (p = 0.01). HBsAg exhibited a much higher positive rate in tumor-adjacent tissue than in tumor tissue (86.6% versus 29.9%, p < 0.0001) with significantly different staining pattern. By contrast, the positive rate of HBV DNA ISH was comparable in tumor and surrounding tissue (17.6% versus 22.9%, p = 0.36). Yet the HBV DNA signal in tumor tissue showed predominant nuclear localization (87.0%) whereas staining pattern in adjacent tissue was mixed (43.3% nuclear localization, p = 0.0015). Finally, no significant association between intra-tumor HBV DNA/HBsAg positivity and major histological markers (microvascular invasion, tumor differentiation, etc.) or recurrence after surgery was observed. These data confirmed the largely integrated state of HBV DNA, weaker expression and altered localization of surface antigen in tumor compared with surrounding tissue. The strikingly different prevalence and localization of HBsAg and HBV DNA reflected the complex and heterogeneous mechanisms leading to HBV-induced tumorigenesis.


[From chronobiology to chronotopobiology].
Based on the data available in the literature and his own findings, the author presents a concept of the spatial-temporary organization of biological systems. Experimental evidence is provided for this concept with emphasis on its theoretical and medical values. A role of spatial and temporary organization in the activity of the biological system is shown separately. It is emphasized that the spatial-temporary organization of biological system is not the sum of properties of components of its spatial and temporary organizations and has its own features. The author proposed to single out a section of theoretical biology dealing with the study of the spatial-temporary organization of biological systems and to call it chronotopobiology.


Methamphetamine and inflammatory cytokines increase neuronal Na+/K+-ATPase isoform 3: relevance for HIV associated neurocognitive disorders.
Methamphetamine (METH) abuse in conjunction with human immunodeficiency virus (HIV) exacerbates neuropathogenesis and accelerates neurocognitive impairments in the central nervous system (CNS), collectively termed HIV Associated Neurocognitive Disorders (HAND). Since both HIV and METH have been implicated in altering the synaptic architecture, this study focused on investigating alterations in synaptic proteins. Employing a quantitative proteomics approach on synaptosomes isolated from the caudate nucleus from two groups of rhesus monkeys chronically infected with simian immunodeficiency virus (SIV) differing by one regimen, METH treatment, we identified the neuron specific Na(+)/K(+)-ATPase alpha 1 isoform 3 (ATP1A3) to be up regulated after METH treatment, and validated its up regulation by METH in vitro. Further studies on signaling mechanisms revealed that the activation of ATP1A3 involves the extracellular regulated kinase (ERK) pathway. Given its function in maintaining ionic gradients and emerging role as a signaling molecule, changes in ATP1A3 yields insights into the mechanisms associated with HAND and interactions with drugs of abuse.


Frequency effects on memory: A resource-limited theory.
We present a review of frequency effects in memory, accompanied by a theory of memory, according to which the storage of new information in long-term memory (LTM) depletes a limited pool of working memory (WM) resources as an inverse function of item strength. We support the theory by showing that items with stronger representations in LTM (e.g., high frequency items) are easier to store, bind to context, and bind to one another; that WM resources are involved in storage and retrieval from LTM; that WM performance is better for stronger, more familiar stimuli. We present a novel analysis of preceding item strength, in which we show from nine existing studies that memory for an item is higher if during study it was preceded by a stronger item (e.g., a high frequency word). This effect is cumulative (the more prior items are of high frequency, the better), continuous (memory proportional to word frequency of preceding item), interacts with current item strength (larger for weaker items), and interacts with lag (decreases as the lag between the current and prior study item increases). A computational model that implements the theory is presented, which accounts for these effects. We discuss related phenomena that the model/theory can explain. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Antidepressant-like effects and mechanism of action of SYG in depression model in rats.
The present study aimed to evaluate whether SYG, a Chinese herbal formula, could produce antidepressant-like effects in learned helplessness (LH) model and chronic mild stress (CMS) model in rats. The mechanism underlying the antidepressant-like action was investigated by exploring BDNF signaling way in the hippocampus. SYG was administrated for 5 consecutive days (100 and 200 mg/kg/day, intragastrically) in the learned helplessness model; SYG was administered daily by gastric gavages during both the 5-week stress session and behavior tests periods in the chronic mild stress model (100 and 200 mg/kg). The serum corticosterone level was measured in the learned helplessness model. Levels of BDNF and Tyrosine-related kinase B (TrkB), were evaluated in the hippocampus of chronic mild stress model. A deficit in avoidance learning and higher corticosterone level were observed in learned helplessness rats. SYG significantly reduced this deficit and reversed the corticosterone alteration. CMS induced significant reduction of sucrose intake in the sucrose preference test, an increased latency to feed in the novelty-suppressed feeding test and an increased immobility time in the forced swim test as compared to the control. It was also found that BDNF and TrkB levels were decreased in CMS model. Chronic treatment of SYG significantly suppressed the behavioral changes and up-regulated the BDNF signal pathway in the hippocampus. Our results suggest that SYG alleviates depression induced by LH and CMS model. The antidepressant-like activity of SYG is likely mediated by activation the BDNF signal pathway in the hippocampus.


The association between parity and birthweight in a longitudinal consecutive pregnancy cohort.
Nulliparity is associated with lower birthweight, but few studies have examined how within-mother changes in risk factors impact this association. We used longitudinal electronic medical record data from a hospital-based cohort of consecutive singleton live births from 2002-2010 in Utah. To reduce bias from unobserved pregnancies, primary analyses were limited to 9484 women who entered nulliparous from 2002-2004, with 23,380 pregnancies up to parity 3. Unrestricted secondary analyses used 101,225 pregnancies from 45,212 women with pregnancies up to parity 7. We calculated gestational age and sex-specific birthweight z-scores with nulliparas as the reference. Using linear mixed models, we estimated birthweight z-score by parity adjusting for pregnancy-specific sociodemographics, smoking, alcohol, prepregnancy body mass index, gestational weight gain, and medical conditions. Compared with nulliparas', infants of primiparas were larger by 0.20 unadjusted z-score units [95% confidence interval (CI) 0.18, 0.22]; the adjusted increase was similar at 0.18 z-score units [95% CI 0.15, 0.20]. Birthweight continued to increase up to parity 3, but with a smaller difference (parity 3 vs. 0 β = 0.27 [95% CI 0.20, 0.34]). In the unrestricted secondary sample, there was significant departure in linearity from parity 1 to 7 (P < 0.001); birthweight increased only up to parity 4 (parity 4 vs. 0 β = 0.34 [95% CI 0.31, 0.37]). The association between parity and birthweight was non-linear with the greatest increase observed between first- and second-born infants of the same mother. Adjustment for changes in weight or chronic diseases did not change the relationship between parity and birthweight.


Seascape Genetics and the Spatial Ecology of Juvenile Green Turtles.
Understanding how ocean currents impact the distribution and connectivity of marine species, provides vital information for the effective conservation management of migratory marine animals. Here, we used a combination of molecular genetics and ocean drift simulations to investigate the spatial ecology of juvenile green turtle (Chelonia mydas) developmental habitats, and assess the role of ocean currents in driving the dispersal of green turtle hatchlings. We analyzed mitochondrial (mt)DNA sequenced from 358 juvenile green turtles, and from eight developmental areas located throughout the Southwest Indian Ocean (SWIO). A mixed stock analysis (MSA) was applied to estimate the level of connectivity between developmental sites and published genetic data from 38 known genetic stocks. The MSA showed that the juvenile turtles at all sites originated almost exclusively from the three known SWIO stocks, with a clear shift in stock contributions between sites in the South and Central Areas. The results from the genetic analysis could largely be explained by regional current patterns, as shown by the results of passive numerical drift simulations linking breeding sites to developmental areas utilized by juvenile green turtles. Integrating genetic and oceanographic data helps researchers to better understand how marine species interact with ocean currents at different stages of their lifecycle, and provides the scientific basis for effective conservation management.


Diagnostic potential of plasmatic MicroRNA signatures in stable and unstable angina.
We examined circulating miRNA expression profiles in plasma of patients with coronary artery disease (CAD) vs. matched controls, with the aim of identifying novel discriminating biomarkers of Stable (SA) and Unstable (UA) angina. An exploratory analysis of plasmatic expression profile of 367 miRNAs was conducted in a group of SA and UA patients and control donors, using TaqMan microRNA Arrays. Screening confirmation and expression analysis were performed by qRT-PCR: all miRNAs found dysregulated were examined in the plasma of troponin-negative UA (n=19) and SA (n=34) patients and control subjects (n=20), matched for sex, age, and cardiovascular risk factors. In addition, the expression of 14 known CAD-associated miRNAs was also investigated. Out of 178 miRNAs consistently detected in plasma samples, 3 showed positive modulation by CAD when compared to controls: miR-337-5p, miR-433, and miR-485-3p. Further, miR-1, -122, -126, -133a, -133b, and miR-199a were positively modulated in both UA and SA patients, while miR-337-5p and miR-145 showed a positive modulation only in SA or UA patients, respectively. ROC curve analyses showed a good diagnostic potential (AUC ≥ 0.85) for miR-1, -126, and -483-5p in SA and for miR-1, -126, and -133a in UA patients vs. controls, respectively. No discriminating AUC values were observed comparing SA vs. UA patients. Hierarchical cluster analysis showed that the combination of miR-1, -133a, and -126 in UA and of miR-1, -126, and -485-3p in SA correctly classified patients vs. controls with an efficiency ≥ 87%. No combination of miRNAs was able to reliably discriminate patients with UA from patients with SA. This work showed that specific plasmatic miRNA signatures have the potential to accurately discriminate patients with angiographically documented CAD from matched controls. We failed to identify a plasmatic miRNA expression pattern capable to differentiate SA from UA patients.


[Effect glutargin in blinding function of serum albumin and other indicators of functional state of liver in acute toxic alcoholic hepatitis].
Acute toxic alcoholic hepatitis continue to be relevant problem of modern medicine as a result of a significant spread of alcoholism in Ukraine and world. Aim - to explore the effect glutargin in blinding function of serum albumin and other indicators of functional state of liver in acute alcoholic toxic hepatitis in experiments on white rats. All animals were divided into four groups. The first (control group) consisted of 20 healthy intact animals, second - 17 rats with acute toxic alcoholic hepatitis, which was taken out of the experiment on the second day of its commencement, the third - 16 animals with similarly modeled pathology, which was taken out on the seventh day from the beginning of the experiment, fourth - 20 animals with acute toxic alcoholic hepatitis, which underwent correction of 4.0% solution glutargin during seven days. Shown, that blinding function of serum albumin, reduced in conditions studied pathology, take place pronounced biochemical signs of liver parenchyma. Under the influence of glutargin studied parameters significantly improved. In acute toxic alcoholic hepatitis significantly disturbing protein-synthetic liver function, occur phenomena cytolysis, suppressed blinding function of serum albumin with maximum expression on the second day of the experiment and with signs of recovery on the seventh day. Under the influence of glutargin upgraded indicators of blinding function of serum albumin: total protein, aminotransferase, alkaline phosphatase, total bilirubin. The activity of serum aspartate aminotransferase normalized and reached the level of control.


The female brindled mouse as a model of Menkes' disease: the relationship of fur pattern to behavioral and neurochemical abnormalities.
The brindled mottled mutant mouse, a model of Menkes' disease, has alterations in copper homeostasis which cause, among other sequelae, neuronal degeneration in selected areas of brain. This work examined the neurochemical changes at postnatal days (PND) 15, 30 and 60 in females heterozygous for the sex-linked brindled mutation. These data were compared to behavioral alterations and to fur coat color at these same time points. The brindled heterozygotic females had lower concentrations of norepinephrine (NE) in the cingulate cortex, and higher levels of dopamine or dopamine metabolites in the cingulate cortex, thalamus and hypothalamus across all ages, although the difference was greatest at PND 15. The brindled females were much less active than their normal littermates at PND 15, but the differences were no longer evident at PND 30 and 60. Mottling of the fur is believed to result from low tyrosinase activity caused by abnormalities in copper metabolism. The fur pattern and behavior of the brindled mice were highly correlated with NE levels in the cingulate cortex and thalamus. These data show that female brindled mice have neurochemical abnormalities similar to (if less severe than) the male hemizygotes, that these abnormalities are regionally specific, are most apparent prior to 30 days of age, and are linked to behavioral deficits. These data also show that the extent of such deficits can be predicted by a quantitative analysis of the fur pattern of these females.


[The enzymatic isolation of hepatocytes from the mouse liver].
A modified version of the two-step enzymatic method for isolation of hepatocytes from the liver of adult mice is described. The method yields 6.10(7)-7.10(7) cells with viability of 70-80%. It is simple and economical, requiring no great amounts of collagenase.


State of the art of carbon nanotube fibers: opportunities and challenges.
The superb mechanical and physical properties of individual carbon nanotubes (CNTs) have provided the impetus for researchers in developing high-performance continuous fibers based upon CNTs. The reported high specific strength, specific stiffness and electrical conductivity of CNT fibers demonstrate the potential of their wide application in many fields. In this review paper, we assess the state of the art advances in CNT-based continuous fibers in terms of their fabrication methods, characterization and modeling of mechanical and physical properties, and applications. The opportunities and challenges in CNT fiber research are also discussed.


Integration of Magnetic-Field-Directed Self-Assembly-Based Cell Culture and Biosensing Platform for Improving hPSCs-Derived Neurons and Quantitative Detection of Neurotransmitter.
Despite the fact that human neural cell models have played significant roles in both research and cell replacement therapies for neurological diseases, the existing techniques for obtaining neurons from human pluripotent stem cells (hPSCs) are arduous and intricate. Additionally, the evaluation of neuron quality in the natural environment remains deficient. Consequently, we have developed a comprehensive platform utilizing magnetic-field-directed self-assembly (MDSA) of MXenes@Fe3O4 (M/F) nanocomposites. This platform facilitates the cultivation and in situ analysis of differentiated dopaminergic (DA) neurons. Our results showed that the introduction of M/F enhances neurite outgrowth and leads to the development of more intricate ramifications. Moreover, with the increase of magnetic field intensity, neurite outgrowth is further enhanced, and the proportion of differentiated mature neurons from hPSCs increases. This suggests that our platform promotes the maturation of neurons, emphasizing the crucial role of biophysical cues in expediting the differentiation process. The homogenization platform formed by MDSA of M/F nanocomposites exhibits high conductivity, leading to its exceptional performance in the real-time monitoring of the release of dopamine neurotransmitter from hPSC-derived DA neurons. Hence, this platform demonstrates significant potential for monitoring cell quality. In conclusion, our integrated platform, based on MDSA of M/F nanocomposites, offers a reliable and efficient means for the in vitro generation of human neurons with a controllable quality. The as-prepared platform holds potential for enhancing neuronal maturation and ensuring consistent cell quality, showing significant implications for in vitro biological research, disease modeling, and cell replacement therapy.


The origins of primitive blood in Xenopus: implications for axial patterning.
The marginal zone in Xenopus laevis is proposed to be patterned with dorsal mesoderm situated near the upper blastoporal lip and ventral mesoderm near the lower blastoporal lip. We determined the origins of the ventralmost mesoderm, primitive blood, and show it arises from all vegetal blastomeres at the 32-cell stage, including blastomere C1, a progenitor of Spemann's organizer. This demonstrates that cells located at the upper blastoporal lip become ventral mesoderm, not solely dorsal mesoderm as previously believed. Reassessment of extant fate maps shows dorsal mesoderm and dorsal endoderm descend from the animal region of the marginal zone, whereas ventral mesoderm descends from the vegetal region of the marginal zone, and ventral endoderm descends from cells located vegetal of the bottle cells. Thus, the orientation of the dorsal-ventral axis of the mesoderm and endoderm is rotated 90( degrees) from its current portrayal in fate maps. This reassessment leads us to propose revisions in the nomenclature of the marginal zone and the orientation of the axes in pre-gastrula Xenopus embryos.


Winter Bird Assemblages in Rural and Urban Environments: A National Survey.
Urban development has a marked effect on the ecological and behavioural traits of many living organisms, including birds. In this paper, we analysed differences in the numbers of wintering birds between rural and urban areas in Poland. We also analysed species richness and abundance in relation to longitude, latitude, human population size, and landscape structure. All these parameters were analysed using modern statistical techniques incorporating species detectability. We counted birds in 156 squares (0.25 km2 each) in December 2012 and again in January 2013 in locations in and around 26 urban areas across Poland (in each urban area we surveyed 3 squares and 3 squares in nearby rural areas). The influence of twelve potential environmental variables on species abundance and richness was assessed with Generalized Linear Mixed Models, Principal Components and Detrended Correspondence Analyses. Totals of 72 bird species and 89,710 individual birds were recorded in this study. On average (± SE) 13.3 ± 0.3 species and 288 ± 14 individuals were recorded in each square in each survey. A formal comparison of rural and urban areas revealed that 27 species had a significant preference; 17 to rural areas and 10 to urban areas. Moreover, overall abundance in urban areas was more than double that of rural areas. There was almost a complete separation of rural and urban bird communities. Significantly more birds and more bird species were recorded in January compared to December. We conclude that differences between rural and urban areas in terms of winter conditions and the availability of resources are reflected in different bird communities in the two environments.


Lid lag and lagophthalmos: a clarification of terminology.
Lid lag, lagophthalmos and von Grafe's sign are useful terms which refer to important clinical signs. Despite the fact that they have discrete meanings, they are often used interchangeably and incorrectly by many ophthalmologists and, therefore, their value has been degraded. We provide definitions for these commonly used (but often confused) ophthalmic terms: Lagophthalmos is the inability to completely close the eyes; Lid lag is the static situation in which the eyelid is higher than normal with the globe in downgaze; and von Grafe's sign is a dynamic sign describing the retarded descent of the eyelid during movement of the globe from primary position to downgaze. It is our hope that these terms will be adopted by the ophthalmic community so that precision in definition will lead to clarity of thought and communication.


Older People in the Context of COVID-19: A European Perspective.
The Coronavirus pandemic and associated measures for the protection of the public have impacted differently on different parts of the population and across different nations. In many areas, COVID-19 has also either exacerbated already existing or created new inequalities in relation to specific parts of the population. Older individuals are one group in society that has been widely impacted, while social isolation/shielding measures have placed them in higher risk of loneliness, isolation, financial deprivation and mental health challenges, to name a few. This commentary reflects on such inequalities across four European nations (the United Kingdom (UK), Republic of Ireland, Finland, Spain) and draws attention to the critical role of Gerontological Social Work (GSW), while emphasizing the ways in which social work can intervene. First, we identify common concerns for the rights of older people that span across all four nations, and second, we identify significant roles for GSW practitioners at the individual, community and policy levels and conclude with a call for GSW in these four nations to be reimagined in a time of global crisis.


BCMA CAR T cells: the winding path to success.
Chimeric antigen receptor (CAR) T cells have been shown to successfully treat some hematopoietic malignancies. Recognition of a relevant target on malignant cells and the proper costimulatory molecule are essential for CAR T cell efficacy. In this issue of the JCI, Cohen et al. conducted an early phase trial to evaluate B cell maturation antigen-targeting (BCMA-targeting) CAR T cells in patients with refractory multiple myeloma. Patients who received the highest dose of BCMA-targeting CAR T cells in combination with lymphodepletion had the greatest response. The results of the study provide further support for the use of BCMA-targeting CAR T cells for myeloma, and reiterate the importance of space and cell dose for CAR T cell success.


Cytopathologic findings in breast masses in men with HIV infection.
To report the cytologic findings on 15 men with HIV infection who presented with breast masses and underwent fine needle aspiration (FNA). The cytopathology files of The Johns Hopkins Hospital (JHH) and the University of Texas Southwestern Medical Center (UTSW) were searched for cases of men with breast masses evaluated by FNA. The HIV status of these men was then ascertained. A total of 15 cases (9 at JHH, 6 at UTSW) of 259 (5.79%) were identified in which the patient was HIV seropositive. The pathologic diagnoses were reviewed, and the clinical history, along with the medication list at the time of FNA, was determined. The men ranged in age from 12 to 51 years (mean, 38). Breast masses were present on either the right (n = 6) or left (n = 7) side or were bilateral (n = 2). In all 15 cases, the masses were retroareolar, firm and tender. FNA showed a ductal and stromal proliferative process, often with focal cytologic atypia and numerous background naked myoepithelial nuclei, features consistent with a diagnosis of gynecomastia. Thirteen of these men were on drug regimens, which included indinivir, stavudine and saquinivir. Two of the men were on azidothymidine only. Gynecomastia, although rare in young men, was the sole cause of breast masses in HIV-seropositive men in this study. It has been described as an extremely rare side effect of certain antiretroviral medications, including indinivir, stavudine and saquinivir. FNA is an important tool in determining the benign nature of these lesions and excluding other causes of breast masses in this patient population, such as infections, malignant lymphoma and breast carcinoma.


Anticonvulsant and Neuroprotective Effects of Paeonol in Epileptic Rats.
Paeonol is the main active compound in the root bark extract of the peony tree, and it has antioxidative and anti-inflammatory effects. Recent studies have reported the neuroprotective effects of paeonol including its capacity in improving impaired memory. However, the effect of paeonol on epilepsy is yet to be demystified. We aimed to investigate the therapeutic effect of paeonol in epilepsy and its relationship with oxidative stress damage and neuronal loss in the rat brain to reveal the underlying mechanisms of epileptic seizures. A rat model for chronic epilepsy was established, and the seizure scores of the rats in different groups were recorded. The seizure duration and the seizure onset latency were used to evaluate the anticonvulsant effects of paeonol. Terminal deoxynucleotidyl transferase dUTP nick end-labeling staining, Nissl staining and H/E staining were used to evaluate the effects of paeonol on neuronal loss and apoptosis in epileptic rats. The colorimetric assessment of malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, catalase activity and total antioxidant capacity of paeonol were used in assessing paeonol's effect on oxidative stress in epileptic rats. Evaluation of Caspase-3 mRNA and protein expression levels were determined using western blot and quantitative real-time (RT-q)PCR. In this study, we found that paeonol reduced the seizure scores of epileptic rats and attenuated the duration and onset latency of seizures. Paeonol can also increase the activities of total antioxidant capacity, SOD and catalase activity and reduce MDA content as well. This suggests that paeonol can improve the level of oxidative stress in rats. More significantly, paeonol can improve neuronal loss and apoptosis in epileptic rats. These results indicate that paeonol has anticonvulsant and neuroprotective effects in epileptic rats. This effect may be caused by reducing oxidative stress.


Role of plasma levels of CA-125 in predicting outcome of primary PCI after acute myocardial infarction in male patients.
Introduction: Cancer antigen 125 (CA-125) is a tumor marker of ovarian cancer, which has shown to be increased in different cardiovascular diseases. Although the prognostic role of CA-125 in heart failure and coronary heart disease is well-established, there is little known about its role in acute myocardial infarction (AMI). In this study we aimed to evaluate the serum levels of CA-125 in patients with AMI and its prognostic role in evaluating the in-hospital outcome of AMI. Methods: We evaluated 120 male patients with AMI and 120 male normal subjects. CA-125 levels were measured upon the patient's admission to hospital. The in-hospital major adverse cardiac events (MACE) and its predictors were also recorded for AMI patients. Results: CA-125 levels were significantly higher in AMI patients compared to normal subjects (7.99±6.83 vs. 5.70±4.62, P = 0.003). We found significant positive correlations between CA-125 levels with creatine kinase-MB (CKMB) (r=0.621, P < 0.001) and CTnI (r=0.491, P < 0.001). The in-hospital MACE was observed in 19 cases (15.8%). Patients with MACE had significantly higher value of CA-125, CKMB and CTnI and lower LVEF compared to patients without MACE. CKMB (OR=0.967, 95% CI [0.943-0.991], P = 0.007) and CA-125 levels (OR=0.821, 95% CI [0.688-0.979], P = 0.02) were independent predictors of MACE. Conclusion: Serum CA-125 levels are significantly higher in male patients with AMI compared to normal subjects and have a significant role in predicting in-hospital MACE after AMI. In patients with higher CA-125 more aggressive treatment and close observation should be performed in order to reduce the possible adverse outcomes.


Chromosomal instability by inefficient Mps1 auto-activation due to a weakened mitotic checkpoint and lagging chromosomes.
Chromosomal instability (CIN), a feature widely shared by cells from solid tumors, is caused by occasional chromosome missegregations during cell division. Two of the causes of CIN are weakened mitotic checkpoint signaling and persistent merotelic attachments that result in lagging chromosomes during anaphase. Here we identify an autophosphorylation event on Mps1 that is required to prevent these two causes of CIN. Mps1 is phosphorylated in mitotic cells on at least 7 residues, 4 of which by autophosphorylation. One of these, T676, resides in the activation loop of the kinase domain and a mutant that cannot be phosphorylated on T676 is less active than wild-type Mps1 but is not kinase-dead. Strikingly, cells in which endogenous Mps1 was replaced with this mutant are viable but missegregate chromosomes frequently. Anaphase is initiated in the presence of misaligned and lagging chromosomes, indicative of a weakened checkpoint and persistent merotelic attachments, respectively. We propose that full activity of Mps1 is essential for maintaining chromosomal stability by allowing resolution of merotelic attachments and to ensure that single kinetochores achieve the strength of checkpoint signaling sufficient to prevent premature anaphase onset and chromosomal instability. To our knowledge, phosphorylation of T676 on Mps1 is the first post-translational modification in human cells of which the absence causes checkpoint weakening and CIN without affecting cell viability.


Effectiveness of percutaneous balloon compression (PBC) in improving physical function and quality of life in trigeminal neuralgia: a retrospective study.
To evaluate the effectiveness of percutaneous balloon compression (PBC) in treating trigeminal neuralgia (TN) and determine improvements in quality of life (QoL) and daily functional status. Data from primary TN (pTN) patients treated with PBC from December 2018 to April 2021 were retrospectively analyzed. Short-Form 36 (SF-36) Health Survey and Functional Independence Measure (FIM) assessments were used to evaluate patients' QoL and physical function every 6 months after surgery, and facial pain was evaluated every 3 to 6 months post-surgery. A total of 80 pTN patients were enrolled for analysis. The Barrow Neurological Institute (BNI) scores of I-II were achieved in 67 (83.8%) patients immediately after the surgery. The estimated rates of BNI I-II pain relief at one, two, and three years were 94.2%, 87.6%, and 83.2%, respectively. All aspects of the SF-36 questionnaire were significantly improved after the PBC, especially in terms of role physical (RP), bodily pain (BP), and social functioning (SF). Patients' functional outcomes measured by FIM at the 6-month follow-up examination were 108.6 ± 9.9, which was significantly improved compared with the pretreatment scores (90.8 ± 12.7). There was no difference between the severity of facial numbness in FIM and any item of the SF-36 except RP (P = 0.004) at 6 months after surgery. There was also no difference in SF-36 and FIM between patients with or without facial hyperalgesia. PBC can produce long-term and stable pain relief and significantly improve the patient's QoL and physical function. However, further well-designed, high-level, evidence-based studies are needed to precisely assess the efficacy of PBC for pTN patients.


Voyager 1 observes low-energy galactic cosmic rays in a region depleted of heliospheric ions.
On 25 August 2012, Voyager 1 was at 122 astronomical units when the steady intensity of low-energy ions it had observed for the previous 6 years suddenly dropped for a third time and soon completely disappeared as the ions streamed away into interstellar space. Although the magnetic field observations indicate that Voyager 1 remained inside the heliosphere, the intensity of cosmic ray nuclei from outside the heliosphere abruptly increased. We report the spectra of galactic cosmic rays down to ~3 × 10(6) electron volts per nucleon, revealing H and He energy spectra with broad peaks from 10 × 10(6) to 40 × 10(6) electron volts per nucleon and an increasing galactic cosmic-ray electron intensity down to ~10 × 10(6) electron volts.


Molecular basis for PHF7-mediated ubiquitination of histone H3.
The RING-type E3 ligase has been known for over two decades, yet its diverse modes of action are still the subject of active research. Plant homeodomain (PHD) finger protein 7 (PHF7) is a RING-type E3 ubiquitin ligase responsible for histone ubiquitination. PHF7 comprises three zinc finger domains: an extended PHD (ePHD), a RING domain, and a PHD. While the function of the RING domain is largely understood, the roles of the other two domains in E3 ligase activity remain elusive. Here, we present the crystal structure of PHF7 in complex with the E2 ubiquitin-conjugating enzyme (E2). Our structure shows that E2 is effectively captured between the RING domain and the C-terminal PHD, facilitating E2 recruitment through direct contact. In addition, through in vitro binding and functional assays, we demonstrate that the N-terminal ePHD recognizes the nucleosome via DNA binding, whereas the C-terminal PHD is involved in histone H3 recognition. Our results provide a molecular basis for the E3 ligase activity of PHF7 and uncover the specific yet collaborative contributions of each domain to the PHF7 ubiquitination activity.


Volume-dependent taurine release from cultured astrocytes requires permissive [Ca(2+)](i) and calmodulin.
Cell swelling results in regulatory activation of multiple conductive anion pathways permeable toward a broad spectrum of intracellular organic osmolytes. Here, we explore the involvement of extracellular and intracellular Ca(2+) in volume-dependent [(3)H]taurine efflux from primary cultured astrocytes and compare the Ca(2+) sensitivity of this efflux in slow (high K(+) medium induced) and fast (hyposmotic medium induced) cell swelling. Neither Ca(2+)-free medium nor Ca(2+)-channel blockers prevented the volume-dependent [(3)H]taurine release. In contrast, loading cells with the membrane-permeable Ca(2+) chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA)-AM suppressed [(3)H]taurine efflux by 65-70% and 25-30% under high-K(+) and hyposmotic conditions, respectively. Fura 2 measurements confirmed that BAPTA-AM, but not Ca(2+)-free media, significantly reduced resting intracellular Ca(2+) concentration ([Ca(2+)](i)). The calmodulin antagonists trifluoperazine and fluphenazine reversibly and irreversibly, respectively, inhibited the high-K(+)-induced [(3)H]taurine release, consistent with their known actions on calmodulin. In hyposmotic conditions, the effects were less pronounced. These data suggest that volume-dependent taurine release requires minimal basal [Ca(2+)](i) and involves calmodulin-dependent step(s). Quantitative differences in Ca(2+)/calmodulin sensitivity of high-K(+)-induced and hyposmotic medium-induced taurine efflux are due to both the effects of the inhibitors on high-K(+)-induced cell swelling and their effects on transport systems and/or signaling mechanisms determining taurine efflux.


Complete genome sequence of the mosquitocidal bacterium Bacillus sphaericus C3-41 and comparison with those of closely related Bacillus species.
Bacillus sphaericus strain C3-41 is an aerobic, mesophilic, spore-forming bacterium that has been used with great success in mosquito control programs worldwide. Genome sequencing revealed that the complete genome of this entomopathogenic bacterium is composed of a chromosomal replicon of 4,639,821 bp and a plasmid replicon of 177,642 bp, containing 4,786 and 186 potential protein-coding sequences, respectively. Comparison of the genome with other published sequences indicated that the B. sphaericus C3-41 chromosome is most similar to that of Bacillus sp. strain NRRL B-14905, a marine species that, like B. sphaericus, is unable to metabolize polysaccharides. The lack of key enzymes and sugar transport systems in the two bacteria appears to be the main reason for this inability, and the abundance of proteolytic enzymes and transport systems may endow these bacteria with exclusive metabolic pathways for a wide variety of organic compounds and amino acids. The genes shared between B. sphaericus C3-41 and Bacillus sp. strain NRRL B-14905, including mobile genetic elements, membrane-associated proteins, and transport systems, demonstrated that these two species are a biologically and phylogenetically divergent group. Knowledge of the genome sequence of B. sphaericus C3-41 thus increases our understanding of the bacilli and may also offer prospects for future genetic improvement of this important biological control agent.


Fishing pluripotency mechanisms in vivo.
To understand the molecular mechanisms that regulate the biology of embryonic stem cells (ESCs) it is necessary to study how they behave in vivo in their natural environment. It is particularly important to study the roles and interactions of the different proteins involved in pluripotency and to use this knowledge for therapeutic purposes. The recent description of key pluripotency factors like Oct4 and Nanog in non-mammalian species has introduced other animal models, such as chicken, Xenopus, zebrafish and medaka, to the study of pluripotency in vivo. These animal models complement the mouse model and have provided new insights into the evolution of Oct4 and Nanog and their different functions during embryonic development. Furthermore, other pluripotency factors previously identified in teleost fish such as Klf4, STAT3, Sox2, telomerase and Tcf3 can now be studied in the context of a functional pluripotency network. The many experimental advantages of fish will fuel rapid analysis of the roles of pluripotency factors in fish embryonic development and the identification of new molecules and mechanisms governing pluripotency.


Nanostructure Introduces Artifacts in Quantitative Immunofluorescence by Influencing Fluorophore Intensity.
Quantitative analysis of fluorescence signals from cells reacted with fluorescently labeled probes is a widely-used method for assessing cell biology. This method has become especially powerful for screening novel nanostructured materials for their influence on cell behavior. However, the effect of nanostructured surface on fluorescence intensity has largely been ignored, which likely leads to erroneous conclusions about cell behavior. This paper investigates this possibility by using fibroblasts cultured on nanoporous gold (np-Au) as a model nanostructured material system. We found that fibroblasts stained for f-actin using phalloidin conjugated with common fluorophores display different levels of fluorescence on np-Au, planar gold, and glass, suggesting different levels of f-actin composition. However, direct quantification via western blots indicates that the actin expression is the same across all conditions. We further investigated whether the fluorescence intensity depended on np-Au feature size, complementing the findings with reflection dark field measurements from different np-Au surfaces. Overall, our experimental measurements in agreement with our electrodynamic simulations suggest that nanostructured surfaces alter the fluorescence intensity of fluorophores by modulating both the excitation and light emission processes. We conclude that comparison of fluorescence on materials with different nanostructures should be done with a quantification method decoupled from the nanostructure's influence.


Biosynthesis of the labdane diterpene marrubiin in Marrubium vulgare via a non-mevalonate pathway.
The biosynthesis of the furanic labdane diterpene marrubiin has been studied in plantlets and shoot cultures of Marrubium vulgare (Lamiaceae). The use of [2-14C]acetate, [2-14C]pyruvate, [2-14C]mevalonic acid and [U-14C]glucose incorporation experiments showed that the labelling of sterols in etiolated shoot cultures of M. vulgare was in accordance with their biosynthesis via the acetate-mevalonate pathway. In contrast, the incorporation rates of these precursors into the diterpene marrubiin could not be explained by biosynthesis of this compound via the acetate-mevalonate pathway. Cultivation of etiolated shoot cultures of M. vulgare on medium containing [1-13C]glucose and subsequent 13C-NMR spectroscopy of marrubiin led to the conclusion that the biosynthesis of marrubiin follows a non-mevalonate pathway. All isoprenic units of 13C-labelled marrubiin were enriched in those carbons that correspond to positions 1 and 5 of a putative precursor isopentenyl diphosphate. This labelling pattern from [1-13C]glucose is consistent with an alternative pathway via trioses, which has already been shown to occur in Eubacteria and Gymnospermae. The labdane skeleton is a precursor of many other skeletal types of diterpenes. Therefore it becomes obvious that in connection with the few known examples of a non-mevalonate pathway to isoprenoids the formation of some isoprenoids in plants via a non-mevalonate pathway might be quite common.


Identification of siderophore biosynthesis genes essential for growth of Aeromonas salmonicida under iron limitation conditions.
Aeromonas salmonicida subsp. salmonicida, the etiological agent of furunculosis in fish, produces a catechol-type siderophore under iron-limiting conditions. In this study, the Fur titration assay (FURTA) was used to identify a cluster of six genes, asbG, asbF, asbD, asbC, asbB, and asbI, encoding proteins similar to components of the siderophore biosynthetic machinery in other bacteria. Reverse transcriptase PCR analyses showed that this cluster consists of four iron-regulated transcriptional units. Mutants with deletions in either asbD (encoding a multidomain nonribosomal peptide synthetase), asbG (encoding a histidine decarboxylase), or asbC (encoding a predicted histamine monooxygenase) did not grow under iron-limiting conditions and did not produce siderophores. Growth of the DeltaasbG strain under iron starvation conditions was restored by addition of histamine, suggesting that the siderophore in this species could contain a histamine-derived moiety. None of the mutants could grow in the presence of transferrin, indicating that A. salmonicida uses the catechol-type siderophore for removal of iron from transferrin rather than relying on a receptor for this iron-binding protein. All 18 A. salmonicida strains analyzed by DNA probe hybridization were positive in tests for the presence of the asbD gene, and all of them promoted the growth of asbD, asbG, and asbC mutants, suggesting that this siderophore-mediated iron uptake system is conserved among A. salmonicida isolates. This study provides the first description of siderophore biosynthesis genes in this fish pathogen, and the results demonstrate that the asbD, asbG, and asbC genes are necessary for the production of a catecholate siderophore that is essential for the growth of A. salmonicida under iron limitation conditions.


Role of Helicobacter pylori infection in the incidence and clinical course of monoclonal gammopathy of undetermined significance.
We aimed to evaluate the hypothesis that chronic antigenic stimulation is an etiological factor of monoclonal gammopathy of undetermined significance (MGUS) with special relevance to Helicobacter pylori infection. We performed a retrospective, observational study. The diagnosis of MGUS was based on serum protein electrophoresis, serum IgM levels (<3 gr/dl), urinary M protein, a normal bone marrow biopsy, normal renal function, and a negative skeletal survey. H. pylori infection was ascertained by rapid urease testing and endoscopy with gastric biopsy for histology. Eradication of H. pylori was assessed by urea breath test and stool antigen assay 4 wk after completion of an appropriate treatment regimen. Sixty-nine patients with MGUS were included in the study. Of these, 57 had undergone evaluation for H. pylori infection for various GI symptoms. Thirty-nine of 57 patients (68.42%) with MGUS also had evidence of H. pylori infection. In 11 of these 39 patients (28.21%), eradication of H. pylori infection with an appropriate regimen led to normalization of the serum protein electrophoresis and resolution of the gammopathy. The results of our study give increased credibility to the theory that in a proportion of patients the pathogenesis of MGUS involves chronic antigenic stimulation and H. pylori is implicated. The search for H. pylori infection and an attempt to eradicate the bacterium in positive cases seem to be appropriate in patients diagnosed with MGUS.


Particle separation using ultrasound can be used with human shed mediastinal blood.
Shed mediastinal blood collected by cardiotomy suction has been shown to be a large contributor to lipid microemboli ending up in different organs. The aim of this study was to test the separation efficiency on human shed blood of a new separation method developed to meet this demand. Shed mediastinal blood collected from the pericardial cavity of 13 patients undergoing cardiac surgery with cardiopulmonary bypass was collected. The blood was processed in an eight-channel parallel PARSUS separator, and separation efficiency was determined. Erythrocyte recovery, in terms of a separation ratio, varied between 68% and 91%. Minor electrolyte changes took place, where levels of sodium increased and levels of potassium and calcium decreased. This study demonstrates that PARSUS technology can be used on human shed mediastinal blood with good separation efficiency. The technology is, thereby, suggested to have future clinical relevance.


Fathers' experiences after having a child: sexuality becomes tailored according to circumstances.
to identify and describe men's experiences of sexuality after having a child. a qualitative study using an interpretative phenomenological approach for analysing in-depth interviews. purposeful sampling was used. 12 men were interviewed six to 13 months after having a child. Informants were men who became fathers for the first time or had already fathered a child. a mid-sized town located in the centre of Sweden. four themes became apparent; a new way of closeness due to non-existing sexuality immediately after birth, an expression of sexuality influenced by the consequences of caring for a child, the expression of love and consideration taking priority over sexual activities, and the father's expression of sexuality being limited by the lack of reciprocation from the partner. after having a child, the expression of sexuality became subjective to the change in circumstances. Sexuality itself was not experienced any differently, but the expression of sexuality for the fathers was modified depending on how the circumstances presented themselves. Sexuality was extended to different avenues of expression where a sense of belonging evolved and a display of love and affection preceded sexual activities. it is important that health care professionals are aware that as sexuality can have various avenues of expression after having a child it is important to not only focus on providing information regarding sexual activities. Fathers should be involved in discussions about possible circumstances affecting sexuality to be able to prepare accordingly.


Kidney transplantation and wait-listing rates from the international Dialysis Outcomes and Practice Patterns Study (DOPPS).
The international Dialysis Outcomes and Practice Patterns Study (DOPPS I and II) allows description of variations in kidney transplantation and wait-listing from nationally representative samples of 18- to 65-year-old hemodialysis patients. The present study examines the health status and socioeconomic characteristics of United States patients, the role of for-profit versus not-for-profit status of dialysis facilities, and the likelihood of transplant wait-listing and transplantation rates. Analyses of transplantation rates were based on 5267 randomly selected DOPPS I patients in dialysis units in the United States, Europe, and Japan who received chronic hemodialysis therapy for at least 90 days in 2000. Left-truncated Cox regression was used to assess time to kidney transplantation. Logistic regression determined the odds of being transplant wait-listed for a cross-section of 1323 hemodialysis patients in the United States in 2000. Furthermore, kidney transplant wait-listing was determined in 12 countries from cross-sectional samples of DOPPS II hemodialysis patients in 2002 to 2003 (N= 4274). Transplantation rates varied widely, from very low in Japan to 25-fold higher in the United States and 75-fold higher in Spain (both P values <0.0001). Factors associated with higher rates of transplantation included younger age, nonblack race, less comorbidity, fewer years on dialysis, higher income, and higher education levels. The likelihood of being wait-listed showed wide variation internationally and by United States region but not by for-profit dialysis unit status within the United States. DOPPS I and II confirmed large variations in kidney transplantation rates by country, even after adjusting for differences in case mix. Facility size and, in the United States, profit status, were not associated with varying transplantation rates. International results consistently showed higher transplantation rates for younger, healthier, better-educated, and higher income patients.


Edge orientation signals in tactile afferents of macaques.
The orientation of edges indented into the skin has been shown to be encoded in the responses of neurons in primary somatosensory cortex in a manner that draws remarkable analogies to their counterparts in primary visual cortex. According to the classical view, orientation tuning arises from the integration of untuned input from thalamic neurons with aligned but spatially displaced receptive fields (RFs). In a recent microneurography study with human subjects, the precise temporal structure of the responses of individual mechanoreceptive afferents to scanned edges was found to carry information about their orientation. This putative mechanism could in principle contribute to or complement the classical rate-based code for orientation. In the present study, we further examine orientation information carried by mechanoreceptive afferents of Rhesus monkeys. To this end, we record the activity evoked in cutaneous mechanoreceptive afferents when edges are indented into or scanned across the skin. First, we confirm that information about the edge orientation can be extracted from the temporal patterning in afferent responses of monkeys, as is the case in humans. Second, we find that while the coarse temporal profile of the response can be predicted linearly from the layout of the RF, the fine temporal profile cannot. Finally, we show that orientation signals in tactile afferents are often highly dependent on stimulus features other than orientation, which complicates putative decoding strategies. We discuss the challenges associated with establishing a neural code at the somatosensory periphery, where afferents are exquisitely sensitive and nearly deterministic.


Extracellular deposition of eosinophil granule major basic protein in lymph nodes of patients with Hodgkin's disease.
Lymph nodes from each of the four histologic types of Hodgkin's disease were examined for the presence of eosinophils and for eosinophil degranulation by immunofluorescent localization of eosinophil granule major basic protein (MBP). Eosinophil degranulation shown by MBP deposition outside of eosinophils was found in six of eight nodes from patients with nodular sclerosing disease and in two of eight nodes from patients with lymphocyte depletion-type disease. Three nodes of the mixed cellularity type, one node of the lymphocyte predominance type, and one lymph node of the lymphocyte depletion type showed one or two small foci of extracellular MBP deposition. Lymph nodes from patients without Hodgkin's disease showed no extracellular deposition of MBP. Large numbers of eosinophils were found in seven of eight nodes of the nodular sclerosing variant, but were less frequently seen among the other types of Hodgkin's disease. The presence of extracellular MBP in lymph nodes of patients with Hodgkin's disease indicates that eosinophil degranulation commonly occurs and suggests that the released eosinophil granule proteins may participate in the inflammatory reaction in this disorder more extensively than is presently appreciated.


Membranoproliferative Glomerulonephritis Associated with Nivolumab Therapy.
Nivolumab is an immune checkpoint inhibitor that targets programmed death-1 on T cells and is designed to amplify an immunologic reaction against cancer cells. However, upregulation of the immune system with checkpoint inhibition is nonspecific, and it can be associated with certain renal side effects, the best documented of which is acute tubulointerstitial nephritis. We present a unique case of a patient with acute kidney injury associated with nephrotic syndrome shortly after starting nivolumab therapy for metastatic anal carcinoma. Subsequent renal biopsy revealed membranoproliferative glomerulonephritis (MPGN). We believe this represents the first reported direct case of nivolumab-associated MPGN. As immunotherapy becomes more widely used in cancer treatment, particular attention must be paid to possible consequences of immune checkpoint inhibitors.


[A young man with acute, generalised oedema].
Ménétrier disease is an uncommon, idiopathic disease characterized by development of chronic protein loss from marked gastric foveolar hyperplasia. A literature search identified several reports of self-limiting, cytomegalovirus-associated Ménétrier disease in children. Some cases have also been reported in adults. A formerly healthy man was admitted to hospital with a serum albumin level of 11 g/l and generalised oedema. Transabdominal ultrasound and endoscopy revealed a folded thickening of the (abdominal) ventricular wall; indications of Ménétrier disease. Histological examination of endoscopic biopsies showed moderate hyperplasia in foveolar epithelium, but also suggested an infectious cause. Intranucleal inclusion bodies, CMV-specific immunology, PCR and special stains all supported cytomegalovirus infection. The patient recovered quickly on antiviral treatment. Our case demonstrates that cytomegalovirus may cause severe, Ménétrier-like gastritis with protein loss in non-immune-compromised adults.


Negative gating modulation by (R)-N-(benzimidazol-2-yl)-1,2,3,4-tetrahydro-1-naphthylamine (NS8593) depends on residues in the inner pore vestibule: pharmacological evidence of deep-pore gating of K(Ca)2 channels.
Acting as a negative gating modulator, (R)-N-(benzimidazol-2-yl)-1,2,3,4-tetrahydro-1-naphthylamine (NS8593) shifts the apparent Ca(2+)-dependence of the small-conductance Ca(2+)-activated K(+) channels K(Ca)2.1-2.3 to higher Ca(2+) concentrations. Similar to the positive K(Ca) channel-gating modulators 1-ethyl-2-benzimidazolinone (1-EBIO) and cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methylpyrimidin-4-yl]-amine (CyPPA), the binding site for NS8593 has been assumed to be located in the C-terminal region, in which these channels interact with their Ca(2+) sensor calmodulin. However, by using a progressive chimeric approach, we were able to localize the site-of-action of NS8593 to the K(Ca)2 pore. For example, when we transferred the C terminus from the NS8593-insensitive intermediate-conductance K(Ca)3.1 channel to K(Ca)2.3, the chimeric channel remained as sensitive to NS8593 as wild-type K(Ca)2.3. In contrast, when we transferred the K(Ca)2.3 pore to K(Ca)3.1, the channel became sensitive to NS8593. Using site-directed mutagenesis, we subsequently identified two specific residues in the inner vestibule of K(Ca)2.3 (Ser507 and Ala532) that determined the effect of NS8593. Mutation of these residues to the corresponding residues in K(Ca)3.1 (Thr250 and Val275) made K(Ca)2.3 insensitive to NS8593, whereas introduction of serine and alanine into K(Ca)3.1 was sufficient to render this channel highly sensitive to NS8593. It is noteworthy that the same two residue positions have been found previously to mediate sensitivity of K(Ca)3.1 to clotrimazole and 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34). The location of Ser507 in the pore-loop near the selectivity filter and Ala532 in an adjacent position in S6 are within the region predicted to contain the K(Ca)2 channel gate. Hence, we propose that NS8593-mediated gating modulation occurs via interaction with gating structures at a position deep within the inner pore vestibule.


Genomic signatures of strain selection and enhancement in Bacillus atrophaeus var. globigii, a historical biowarfare simulant.
Despite the decades-long use of Bacillus atrophaeus var. globigii (BG) as a simulant for biological warfare (BW) agents, knowledge of its genome composition is limited. Furthermore, the ability to differentiate signatures of deliberate adaptation and selection from natural variation is lacking for most bacterial agents. We characterized a lineage of BGwith a long history of use as a simulant for BW operations, focusing on classical bacteriological markers, metabolic profiling and whole-genome shotgun sequencing (WGS). Archival strains and two "present day" type strains were compared to simulant strains on different laboratory media. Several of the samples produced multiple colony morphotypes that differed from that of an archival isolate. To trace the microevolutionary history of these isolates, we obtained WGS data for several archival and present-day strains and morphotypes. Bacillus-wide phylogenetic analysis identified B. subtilis as the nearest neighbor to B. atrophaeus. The genome of B. atrophaeus is, on average, 86% identical to B. subtilis on the nucleotide level. WGS of variants revealed that several strains were mixed but highly related populations and uncovered a progressive accumulation of mutations among the "military" isolates. Metabolic profiling and microscopic examination of bacterial cultures revealed enhanced growth of "military" isolates on lactate-containing media, and showed that the "military" strains exhibited a hypersporulating phenotype. Our analysis revealed the genomic and phenotypic signatures of strain adaptation and deliberate selection for traits that were desirable in a simulant organism. Together, these results demonstrate the power of whole-genome and modern systems-level approaches to characterize microbial lineages to develop and validate forensic markers for strain discrimination and reveal signatures of deliberate adaptation.


The role of hyperhomocysteinemia in nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF)-mediated vasodilatation.
Hyperhomocysteinemia (HHcy) is associated with impaired endothelial-dependent vasodilatation and increased risk of atherosclerosis and thrombosis. Here, we summarize some of our previous work on the effect of HHcy on pathways involved in endothelium-dependent vasodilatation, and present new data concerning the endothelium-derived hyperpolarizing factor (EDHF)-mediated vasodilatation. We showed that the 894 G>T single-nucleotide polymorphism in the human endothelial nitric oxide synthase gene (eNOS) increased the risk of recurrent venous thrombosis in individuals with elevated homocysteine levels, indicating that the pathophysiological mechanism in HHcy involves impaired NO-mediated vasodilatation. In addition, the EDHF-mediated vasodilatation of the renal artery was disturbed in diet-induced hyperhomocysteinemic rats. Interestingly, we demonstrated that pretreatment of rats with periodate-oxidized adenosine (Adox), which is an inhibitor of S-adenosylhomocysteine hydrolase, prevented the methionine-induced rise in plasma total Hcy (tHcy) levels but not the inhibition of the EDHF pathway. Furthermore, we demonstrated that S-adenosylhomocysteine (AdoHcy) and S-adenosylmethionine (AdoMet) levels were increased in the kidneys of diet-induced HHcy rats, resulting in a decreased AdoMet:AdoHcy ratio. In addition, we demonstrated that mRNA expression of Connexin 40, which is one of the structural subunits of gap-junctions, was down-regulated in endothelial cells of HHcy rats, and correlated with elevated AdoHcy levels in kidney of these rats. These finding suggest a key role for AdoHcy in relation to decreased Cx40 mRNA expression and impaired EDHF-mediated vasodilatation of HHcy rats.


Model selection analysis of temporal variation in benefit for an ant-tended treehopper.
Recent studies of mutualism have emphasized both that the net benefit to participants depends on the ecological context and that the density-dependent pattern of benefit is key to understanding the population dynamics of mutualism. Indeed, changes in the ecological context are likely to drive changes in both the magnitude of benefit and the density-dependent pattern of benefit. Despite the close linkage between these two areas of research, however, few studies have addressed the factors underlying variation in the density-dependent pattern of benefit. Here I use model selection to evaluate how variation in the benefits of a mutualism drives temporal variation in the density-dependent pattern of net benefit for the ant-tended treehopper Publilia concava. In the interaction between ants and treehoppers in the genus Publilia, ants collect the sugary excretions of treehoppers as a food resource, and treehoppers benefit both directly (e.g., by feeding facilitation) and indirectly (e.g., by predator protection). Results presented here show that temporal changes in the relative magnitude of direct and indirect benefit components of ant tending, especially the effectiveness of predator protection by ants, qualitatively change the overall pattern of density-dependent benefit between years with maximum benefit shifting from treehoppers in small to large aggregations. These results emphasize the need for empirical studies that evaluate the long-term dynamics of mutualism and theoretical studies that consider the population dynamics consequences of variation in the density-dependent pattern of benefit.


Valvular-ventricular interaction: importance of the mitral apparatus in canine left ventricular systolic performance.
As the mitral valvular apparatus tenses during systole, forces transmitted along the chordae tendineae to the left ventricular chamber may influence left ventricular performance. To test this hypothesis, 10 dogs anesthetized with fentanyl were studied during cardiopulmonary bypass. The importance of the mitral apparatus in left ventricular systolic function was assessed independent of load by means of the slope of the contractile state-dependent left ventricular peak isovolumetric pressure-volume relationship (Emax), which was measured at constant heart rate and aortic pressure with a micromanometer inside a left ventricular intracavitary balloon before and immediately after all chordae tendineae were severed. Herniation of the balloon was prevented by a disk secured to the mitral anulus. Emax decreased from 11.97 +/- 3.35 (+/- SD) to 6.38 +/- 0.96 mm Hg/ml (p less than .001) with chordal severing. The volume intercept (Vo) was unchanged. Fluoroscopic studies of the balloon contour in eight additional dogs revealed dyskinesia in the area of the papillary muscle insertion and substantial alterations in chamber geometry during systole after the chordae were severed. Accordingly, we conclude that global left ventricular systolic performance is impaired when chordal attachments of the mitral valve are disrupted. Changes in left ventricular geometry or loss of inward force normally transmitted to the left ventricular wall as the valve tense may underlie these changes. These findings suggest that postoperative left ventricular dysfunction after mitral valve replacement may be attributable, in part, to excision of the native mitral apparatus at the time of surgery and support efforts to spare chordae during mitral valve surgery.


Fabrication of rigidity and space variable protein oligomers with two peptide linkers.
Supramolecular protein assemblies have garnered considerable interest due to their potential in diverse fields with unrivaled attainable functionalities and structural accuracy. Despite significant advances in protein assembly strategies, inserting long linkers with varied lengths and rigidity between assembling protein building blocks remains extremely difficult. Here we report a series of green fluorescent protein (GFP) oligomers, where protein building blocks were linked via two independent peptide strands. Assembling protein units for this two-peptide assembly were designed by flopped fusion of three self-assembling GFP fragments with two peptide linkers. Diverse flexible and rigid peptide linkers were successfully inserted into high-valent GFP oligomers. In addition, oligomers with one flexible linker and one rigid linker could also be fabricated, allowing more versatile linker rigidity control. Linker length could be varied from 10 amino acids (aa) even up to 76 aa, which is the longest among reported protein assembling peptide linkers. Discrete GFP oligomers containing diverse linkers with valencies between monomers to decamers were monodispersely purified by gel elution. Furthermore, various functional proteins could be multivalently fused to the present GFP oligomers. Binding assays, size exclusion chromatography, dynamic light scattering, circular dichroism, differential scanning calorimetry, and transmission electron microscopy suggested circular geometries of the GFP oligomers and showed distinct characteristics of GFP oligomers with length/rigidity varied linkers. Lastly, a surface binding study indicated that more spaced oligomeric binding modules offered more effective multivalent interactions than less spaced modules.


Epitope mapping of the PreS1 domain of the hepatitis B virus large surface protein.
The large (L) surface glycoprotein of hepatitis B virus is an important component of the virion envelope derived from translation initiation at the 5' end of the PreS1 domain of the surface antigen open reading frame. Since key roles in virion assembly and infectivity have been postulated for this protein, further understanding of its structure and topology is important. To this end we have mapped the epitopes recognized by a panel of monoclonal antibodies specific for this polypeptide by examining their reactivity with a series of deletion mutants of the PreS1 region expressed in cultured cells. On the basis of this and other techniques, the antibodies fall into two groups mapping to two distinct epitopes spanning residues 27-35 and 72-78, respectively. Immunoprecipitation studies indicate that both regions are exposed on the surface of HBV-encoded particles.


Variability of myocardial blood flow measurements by magnetic resonance imaging in the multi-ethnic study of atherosclerosis.
Magnetic resonance imaging (MRI) allows the noninvasive assessment of absolute myocardial blood flow (MBF) in mL/min/g during rest, and hyperemia induced by intravenous adenosine, a powerful coronary vasodilator with short decay time. The longitudinal variability in healthy volunteers of the hemodynamic response to adenosine, and of the MBF response, remain largely unknown. The purpose of this study was to assess the longitudinal variability for resting and hyperemic MBFs in the Multi-Ethnic Study of Atherosclerosis. Thirty participants (19 women, 11 men, mean age 63.2 +/- 9.6; range 45-79 years) underwent 2 MRI exams with an average separation of 334 +/- 158 days (range: 20-645) between the 2 exams, using a rapid, multislice T1-weighted gradient-echo imaging technique at rest and during maximal vasodilation with intravenous adenosine. The absolute repeatability coefficient, corresponding to the 95% confidence intervals of the within subject differences, was 0.29 mL/min/g for rest studies, and 1.13 mL/min/g for hyperemic MBF. The relative repeatability coefficients, expressed as a percentage of the mean blood flow, averaged 30% at rest, and 41% during hyperemia. Differences in resting MBF between the 2 exams from 1.01 +/- 0.22 to 0.91 +/- 0.18 mL/min/g (P = 0.001) were associated with changes in hemodynamic conditions, but no such association was observed for hyperemic MBFs, which averaged 2.84 +/- 0.87 mL/min/g in the first examination, and 2.69 +/- 0.65 mL/min/g at follow-up. Over approximately 1 year of aging between perfusion studies there was no observable decline of the hyperemic response, but the variability of the hyperemic MBF response increased with the lag between baseline and follow-up measurements. The repeatability of MBF measurements by MRI at rest was similar to results from previous studies with positron emission tomography.


Triiodothyronine induces over-expression of alpha-smooth muscle actin, restricts myofibrillar expansion and is permissive for the action of basic fibroblast growth factor and insulin-like growth factor I in adult rat cardiomyocytes.
Effects of triiodothyronine (T3) on the expression of cytoskeletal and myofibrillar proteins in adult rat cardiomyocytes (ARC) were followed during two weeks of culture in the presence of 20% T3-depleted (stripped) FCS. Control cultures expressed mainly beta-myosin heavy chain (MHC) mRNA. T3 caused a switch to alpha-MHC expression and a dose-dependent increase of alpha-smooth muscle (alpha-sm) actin mRNA and protein. In parallel, the number of alpha-sm actin immunoreactive cells increased from 1% in controls to 29 and 62% in ARC treated with 5 and 100 nM T3. In the presence of T3, cells exhibited a higher beating rate than controls. The distribution of myofibrils in T3-treated cells was restricted to the perinuclear area with a sharp boundary. Only 5% of the control cells but 30 and 62% of the T3-treated (5 and 100 nM) ARC showed this restricted myofibrillar phenotype. Basic fibroblast growth factor (bFGF) which restricts myofibrillar growth and upregulates alpha-sm actin in ARC cultured with normal FCS had no effect on alpha-sm actin in ARC cultured in stripped FCS, but potentiated the effect of T3. In contrast, insulin-like growth factor I (IGF I), which suppresses alpha-sm actin and stimulates myofibrillogenesis in the presence of normal FCS suppressed T3-induced alpha-sm actin expression in stripped FCS. Thus, T3 appears to be permissive for the action of bFGF and IGF I on alpha-sm actin expression.


Cognitive-behavioral group treatment for perinatal anxiety: a pilot study.
Along with physical and biological changes, a tremendous amount of upheaval and adjustment accompany the pregnancy and postpartum period of a woman's life that together can often result in what is commonly known as postpartum depression. However, anxiety disorders have been found to be more frequent than depression during pregnancy and at least as common, if not more so, during the postpartum period, e.g., Brockington et al., (Archieves Women's Ment Health 9:253-263, 2006; Wenzel et al. (J Anxiety Disord, 19:295-311, 2005). Cognitive-behavioral therapy (CBT) is a well-established psychological treatment of choice for anxiety; however, few studies have specifically examined a cognitive-behavioral intervention targeting perinatal anxiety. This pilot study examined the effectiveness of a cognitive-behavioral group treatment (CBGT) program specifically tailored to address perinatal anxiety in 10 women who were either pregnant or within 12 months postpartum. Participants were recruited from a women's clinic at an academic hospital setting, with anxiety identified as their principal focus of distress. Following a diagnostic interview confirming a primary anxiety disorder and completion of assessment measures, participants completed a 6-week CBGT program. There was a statistically significant reduction in anxiety and depressive symptoms following the CBGT program (all p < 0.05). Participants also reported high acceptability and satisfaction with this treatment for addressing their perinatal anxiety. These findings suggest that CBGT for perinatal anxiety is a promising treatment for both anxiety and depressive symptoms experienced during the perinatal period. Further studies are needed to evaluate the treatment efficacy through larger controlled trials.


[Tetracycline antibiotic interaction with the subcellular fractions of rat liver homogenate].
Binding of tetracyclines, i. e. tetracycline, oxytetracycline, morphocycline, methacycline and doxycycline by subcellular fractions of rat liver homogenates was studied on randombred albino rats. It was shown that the drugs lost their activity to a significant extent on contact with nuclei, mitochondria, microsomes and the fraction mixtures. The mitochondrial fraction bound the highest amounts of the drugs. The binding level of methacycline by the organoids was the highest, while that of morphocycline was the least. Binding of the tetracyclines with the subcellular fractions of the liver was to a certain extent reversible. Accumulation of the antibiotic in the cells may be advantageous from the viewpoint of its effect on the intracellular microbes if possible subsequent dissociation from its complex with organoids is considered. At the same time the mitochondriatropic properties of the tetracyclines may be the basis for their toxic effect on the host cells.


[Influence of low intensive laser irradiation on ultrastructural changes in kidney tissue in experimental colic].
This investigation aimed at estimation of the influence of low-intensive laser irradiation on ultrastructural changes in renal tissue according to electronic microscopy data in case of experimental renal colic. The experiment was made on twenty rabbits with a single or recurrent colic. Ten animals after a single colic were exposed to low intensive laser therapy. Electronic microscopy showed that single renal colic is associated with marked ultrastructural changes in the proximal tubules. In recurrent colic the edema and destruction were more expressed in all nephron parts. Low intensive laser irradiation suppresses pathological processes in nephrocytes both after a single renal colic and after a recurrent renal colic; has a systemic effect on the body; stimulates compensatory processes in the contralateral kidney.


Prevention and treatment of venous thromboembolism in pregnancy.
During pregnancy, women have a 4- to 5-fold increased risk of thromboembolism. Candidates for anticoagulation in pregnancy include women with current thrombosis, a history of thrombosis, risk factors for postpartum thrombosis, and some women with thrombophilia and a history of poor pregnancy outcome. Although, there are no large trials of anticoagulants in pregnancy and recommendations for their use are based on case series and the opinion of experts, observational studies demonstrate the benefit of heparins in reducing the risk of recurrent thromboembolism in pregnancy. A practical approach to the prevention and treatment of thromboembolism in pregnancy is outlined.


Molecular signatures for the phylum Aquificae and its different clades: proposal for division of the phylum Aquificae into the emended order Aquificales, containing the families Aquificaceae and Hydrogenothermaceae, and a new order Desulfurobacteriales ord. nov., containing the family Desulfurobacteriaceae.
We report here detailed phylogenetic and comparative analyses on 11 sequenced genomes from the phylum Aquificae to identify molecular markers that are specific for the species from this phylum or its different families (viz. Aquificaceae, Hydrogenothermaceae and Desulfurobacteriaceae). In phylogenetic trees based on 16S rRNA gene or concatenated sequences for 32 conserved proteins, species from the three Aquificae families formed distinct clades. These trees also supported a strong relationship between the Aquificaceae and Hydrogenothermaceae families. In parallel, comparative analyses on protein sequences from Aquificae genomes have identified 46 conserved signature indels (CSIs) in broadly distributed proteins that are either exclusively or mainly found in members of the phylum Aquificae or its different families and subclades. Four of these CSIs, which are found in all sequenced Aquificae species, provide potential molecular markers for this phylum. Twelve, six and thirteen other CSIs that respectively are specific for the sequenced Aquificaceae, Hydrogenothermaceae and Desulfurobacteriaceae species provide molecular markers and novel tools for the identification of members of these families and for genetic and biochemical studies on them. Lastly, these studies have identified 11 CSIs in divergent proteins that are uniquely shared by members of the Aquificaceae and Hydrogenothermaceae families providing strong evidence that these two groups of bacteria shared a common ancestor exclusive of all other Aquificae (bacteria). The species from these two families are also very similar in their metabolic and physiological properties and they consist of aerobic or microaerophilic bacteria, which generally obtain energy by oxidation of hydrogen or reduced sulfur compounds by molecular oxygen. Based upon their strong association in phylogenetic trees, unique shared presence of large numbers of CSIs in different proteins, and similarities in their metabolic and physiological properties, it is proposed that the order Aquificales should be emended to include only the members of the families Aquificaceae and Hydrogenothermaceae. The members of the family Desulfurobacteriaceae, which are obligate anaerobes that strictly use hydrogen as electron donor, are now transferred to a new order Desulfurobacteriales ord. nov. The emended descriptions of the phylum Aquificae and its three families incorporating information for different molecular signatures are also provided.


Bridge Therapy Outcomes in Patients With Mechanical Heart Valves.
Bridge therapy is associated with an increased risk of major bleeding in patients with atrial fibrillation and venous thromboembolism (TE) without a corresponding reduction in TE. The benefits of bridge therapy in patients with mechanical heart valve (MHV) prostheses interrupting warfarin for invasive procedures are not well described. A retrospective cohort study was conducted at an integrated health-care delivery system. Anticoagulated patients with MHV interrupting warfarin for invasive diagnostic or surgical procedures between January 1, 2006, and March 31, 2012, were identified. Patients were categorized according to exposure to bridge therapy during the periprocedural period and TE risk (low, medium, and high). Outcomes validated via manual chart review included clinically relevant bleeding, TE, and all-cause mortality in the 30 days following the procedure. There were 547 procedures in 355 patients meeting inclusion criteria. Mean cohort age was 65.2 years, and 38% were female. Bridge therapy was utilized in 466 (85.2%) procedures (95.2%, 77.3%, and 65.8% of high, medium, and low TE risk category procedures, respectively). The 30-day rate of clinically relevant bleeding was numerically higher in bridged (5.8%; 95% confidence interval [CI], 3.9%-8.3%) versus not bridged procedures (1.2%; 95% CI, <0.1%-6.7%; P = .102). No TEs or deaths were identified. The use of bridge therapy is common among patients with MHV and may be associated with increased bleeding risk. Further research is needed to determine whether bridge therapy reduces TE in patients with MHV interrupting warfarin for invasive procedures.


Changes in emulsifying properties of caseinate-Soy soluble polysaccharides conjugates by ultrasonication.
This research aimed to assess the impact of ultrasonication on the emulsifying ability of a conjugate system composed of sodium caseinate and soluble soy polysaccharides. The study analyzed the characteristics of the particles and evaluated the emulsions produced using nanoconjugates. The results showed that ultrasonication improved the contact angle (63.7°) and decreased particle size (75 nm), resulting in more effective emulsifying efficiency. At a 2 % concentration of the nanoconjugates, stable emulsions with a 50 % oil content were successfully formed through complete coverage of the droplets' surface, and no oil release was observed. Moreover, the emulsions' creaming index remained below 25 % even after 60 days of storage. The stability of the nanoconjugate-based emulsions depended on the concentration of nanoconjugates, with an optimal concentration of 4 %. These findings suggest that the nanoconjugates have great potential as a natural stabilizer for emulsion-based products.


Diagnosis of Acute Myocardial Infarction in Hemodialysis Patients With High-Sensitivity Cardiac Troponin T Assay.
Cardiac troponins have become the gold standard for diagnosing acute myocardial infarction (AMI) in the general population; however, their diagnostic accuracy for hemodialysis (HD) patients presenting with chest pain or dyspnea is uncertain. To examine the diagnostic accuracy of high-sensitivity cardiac troponin T (hs-cTnT) assay for AMI in HD patients. In this prospective study, we enrolled 670 consecutive stable HD patients presenting with chest pain or dyspnea on routine predialysis therapy in the nephrology department. Receiver operating characteristic (ROC) curves were used to examine the diagnostic accuracy of hs-cTnT levels at enrollment in HD patients presenting with chest pain or dyspnea, and the dynamic change in these levels after 3 hours. Acute myocardial infarction was the adjudicated final diagnosis in 12% of HD patients. Among patients with a final diagnosis other than AMI, 97% had a plasma hs-cTnT concentration above the 99th percentile. At the time of enrollment, the area under the ROC curve of hs-cTnT levels for diagnosis of AMI was 0.68 (95% confidence interval [CI], 0.62-0.74; P < .001) with a cutoff value of 107.7 ng/L; the relative change after 3 hours was 0.90 (95% CI, 0.82-0.96, P < .001) with a cutoff value of 24%, and the absolute change was 0.88 (95% CI, 0.82-0.94, P < .001) with a cutoff value of 32.6 ng/L. The prognostic value for 40-day mortality varied with the magnitude of elevation in hs-cTnT levels. Tracking the dynamic change in hs-cTnT levels during the short term significantly increased this measure's diagnostic accuracy for AMI in HD patients.


A synthetic stimulant never tested in humans, 1,3-dimethylbutylamine (DMBA), is identified in multiple dietary supplements.
A synthetic stimulant never before studied in humans, 1,3-dimethylbutylamine (DMBA), was suspected of being present in dietary supplements. DMBA is an analogue of the pharmaceutical stimulant, 1,3-dimethylamylamine (DMAA), which was recently banned by the US Food and Drug Administration. We obtained all dietary supplements sold by US distributors that listed an ingredient on the label, such as AMP Citrate, that might be a marketing name for DMBA. Supplements were analyzed for the presence and quantity of DMBA. Fourteen supplements met our inclusion criteria and were analyzed by two separate laboratories using ultra high performance liquid chromatography (UHPLC) - mass spectrometry and a reference standard. The identity of DMBA was confirmed in 12 supplements in the range of 13 to 120 mg DMBA per serving. Following recommendations on the supplement label for maximum daily intake, customers would consume from 26 to 320 mg of DMBA per day. Supplements containing DMBA were marketed to improve athletic performance, increase weight loss and enhance brain function. DMBA has never before been detected in supplements. The stimulant has never been studied in humans; its efficacy and safety are entirely unknown. Regulatory agencies should act expeditiously to warn consumers and remove DMBA from all dietary supplements.