Cells on biomaterials--some aspects of elemental analysis by means of electron probes.
Electron probe X-ray microanalysis enables concomitant observation of specimens and analysis of their elemental composition. The method is attractive for engineers developing tissue-compatible biomaterials. Either changes in element composition of cells or biomaterial can be defined according to well-established preparation and quantification procedures. However, the qualitative and quantitative elemental analysis appears more complicated when cells or thin tissue sections are deposited on biomaterials. X-ray spectra generated at the cell/tissue-biomaterial interface are modelled using a Monte Carlo simulation of a cell deposited on borosilicate glass. Enhanced electron backscattering from borosilicate glass was noted until the thickness of the biological layer deposited on the substrate reached 1.25 μm. It resulted in significant increase in X-ray intensities typical for the elements present in the cellular part. In this case, the mean atomic number value of the biomaterial determines the strength of this effect. When elements are present in the cells only, the positive linear relationship appears between X-ray intensities and cell thickness. Then, spatial dimensions of X-ray emission for the particular elements are exclusively in the range of the biological part and the intensities of X-rays become constant. When the elements are present in both the cell and the biomaterial, X-ray intensities are registered for the biological part and the substrate simultaneously leading to a negative linear relationship of X-ray intensities in the function of cell thickness. In the case of the analysis of an element typical for the biomaterial, strong decrease in X-ray emission is observed in the function of cell thickness as the effect of X-ray absorption and the limited excitation range to biological part rather than to the substrate. Correction procedures for calculations of element concentrations in thin films and coatings deposited on substrates are well established in materials science, but little is known about factors that have to be taken into account to accurately quantify bioelements in thin and semi-thick biological samples. Thus thorough tests of currently available quantification procedures are required to verify their applicability to cells or tissues deposited on the biomaterials.


Effect of angiotensin-converting enzyme inhibition by captopril on cardiac output, coronary blood flow, and systemic arterial blood pressure in the intact and in the bilaterally nephrectomized rabbit.
The purpose of this study was to investigate the hemodynamic responses, mainly cardiac output and regional blood flow, to converting enzyme inhibition by captopril in the intact and nephrectomized rabbit. Twenty-one New Zealand white rabbits anesthetized with pentobarbital has systemic arterial blood pressures measured and cardiac output and regional blood flow determined by the microsphere method. Captopril (1--3 mg/kg) significantly reduced cardiac output in the intact but not in nephrectomized rabbits. In both the intact and nephrectomized animals, captopril was associated with small but not significant decreases in blood pressure and no significant change in total peripheral vascular resistance or heart rate. Regional blood flow was reduced, but the fractional distribution of cardiac output to the myocardial, lung (bronchial), hepatic, and splanchnic (small intestine) circulations was unchanged after captopril. These data suggest that the reduction in cardiac output induced by converting enzyme inhibition may be attributed to a fall in venous return that in turn may be dependent on renal factors.


Effects of an amino acid carbohydrate drink on exercise performance after consecutive-day exercise bouts.
This study examined the effect of amino acids in a carbohydrate beverage on cycling performance. Twelve male athletes (28.5 +/- 2.1 yr) cycled at 75% VO2peak for 90 min followed by a ride to exhaustion at 85% VO2peak, before (T1) and on 2 consecutive days (T2 and T3) after 2 weeks of supplementation with 3.6% carbohydrate plus 1% amino acids (AA) or 4.6% carbohydrate-only (CHO) isocaloric beverages. Muscle damage was assessed by plasma creatine kinase (CK), and muscle fatigue by changes in vertical jump pre- to postexercise. Muscle soreness, overall fatigue, and changes in mood state were assessed using questionnaires. Plasma CK was lower for AA in T3 (214.0 +/- 13.5 vs. 485.9 +/- 191.4 U/L immediately post, 213.9 +/- 13.1 vs. 492.0 +/- 199.4 U/L 5 hr post, and 194.9 +/- 17.9 vs. 405.9 +/- 166.6 U/L 24 hr postexercise in AA and CHO, respectively). Time to exhaustion decreased from T2 to T3 only in CHO (10.9 +/- 2.5 to 12.6 +/- 3.2 vs. 13.8 +/- 2.8 to 7.8 +/- 1.5 min in AA and CHO, respectively). Vertical-jump change from pre- to postexercise was greater in T3 for the CHO treatment. Total fatigue score and mood disturbance decreased significantly only with AA in T3. The addition of AA to a carbohydrate beverage after consecutive-day exercise bouts reduced muscle damage as indicated by CK levels, decreased fatigue, and maintained exercise performance compared with consuming carbohydrate alone.


Improved long-term stability of blood cocaine in evacuated collection tubes.
A study was undertaken to determine if a relatively minor modification of our existing specimen collection tubes could enhance the long-term stability of blood cocaine. We added cocaine, benzoylecgonine (BE) and ethanol to whole sheep blood in glass tubes that were prepared to contain one of several combinations of preservatives and anticoagulant. On day 1 and at intervals of up to one year, the drugs were measured by gas chromatography-mass spectrometry (cocaine and BE) or headspace gas chromatography (ethanol). Storage of blood containing 200 ng/mL cocaine at 4 degrees C for one year resulted in 100% loss of the drug using our normal 10 mL specimen collection tubes containing 100 mg sodium fluoride and 20 mg potassium oxalate. The substitution of oxalic acid for potassium oxalate reduced this loss to 76% without any significant effect on the benzoylecgonine or ethanol concentrations. Further addition of 10 mg echothiophate iodide, a quaternary ammonium compound, brought the cocaine loss down to 60% of the original concentration by one year. Further work will be required to determine if oxalic acid and/or echothiophate iodide could be used in blood collection vials intended for forensic toxicological purposes without any detrimental effect on other assays.


Catharsis: an investigation of its meaning and nature.
Nurses commonly use catharsis and cathartic techniques as part of their clinical practice to enable clients and themselves to release emotion, to feel better and to facilitate coping. However, the literature does not provide clinical nursing evidence for its use. The main purpose of the investigation is to examine the beliefs about and understanding of catharsis which two groups of nurses hold: one group of nurse teachers and one group of nursing students. One hundred and forty-two respondents completed self-administered questionnaires asking about their understanding of and beliefs about catharsis as being beneficial, social, negative or psychotherapeutic in nature. The possible relationship of their answers to age, sex, philosophical orientation and qualifications was deemed to be important. The results suggest nurses understand that catharsis is related to emotion and has a psychotherapeutic purpose. However, there appear to be gaps in their understanding. Nurses also seem to believe that the release and expression of emotions is more acceptable for women than for men. There is also evidence that the more experienced nurses think differently from less experienced nurses, placing more emphasis on behaviour rather than emotion as they grow older. The problems associated with catharsis are discussed along with the implications for research and practice.


Re-entrant nematic behavior in the 7OCB+9OCB mixtures: evidence for multiple nematic-smectic tricritical points.
The metastable phase diagram of the two-component system heptyloxycyanobiphenyl (7OCB)+nonyloxycyanobiphenyl (9OCB) was determined by means of modulated differential scanning calorimetry (MDSC) and optical microscopy measurements. It was experimentally established that the 7OCB+9OCB two-component system exhibits a monotropic re-entrant nematic behavior. A complete quantitative thermodynamic analysis, through Oonk's equal G analysis, was performed, allowing for the calculation of the monotropic re-entrant behavior and the prediction of two tricritical points, one of them experimentally accessible for the SmAd-to-N transition and the other non-experimentally accessible for the RN-to-SmAd transition. From specific-heat measurements, latent heats were obtained for those mixtures displaying a first-order SmAd-to-N transition. Additionally, for some mixtures, the specific-heat critical exponents (alpha), through the second-order SmAd-to-N transition, were obtained. Both batches of data enable us to access to the experimental tricritical temperature for the SmAd-to-N transition.


Ensuring the reliability of brominated flame retardant data on food and feed occurrence through harmonised analytical criteria and proficiency testing.
The volume of occurrence data on food and animal feed contaminants such as polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecanes (HBCDDs) is slowly increasing as more laboratories develop analytical capability. This data allows an evaluation of current background levels in different countries and regions and is also useful for estimating the health risk through dietary exposure and as evidence for the formulation of future control strategies. Existing data varies in the number of analytes reported and the quality measures applied. In order to ensure reliability and comparability, guidance on analytical criteria such as precision and trueness, limits of quantitation, recovery, positive identification, etc. is provided. These parameters are based on several years of collective experience and allow validation and regular quality control of analysis of individual PBDE congeners and HBCDD stereoisomers. The criteria-based approach also allows laboratories the flexibility to use different analytical methodologies and techniques for generating data. The effectiveness of this approach has been demonstrated by a successful proficiency testing scheme that has been used for a number of years and has attracted an increasing number of participants. The majority of participating laboratories (>80%) have been able to demonstrate performance within the 95% confidence interval (│z-score│≤ 2) and a further 10% of laboratories demonstrated performance with a z-score of (2 <│z-score│< 3). The combined support of these guidance criteria backed by successful proficiency testing will ensure the reliability and comparability of results, in particular, to refine risk assessments and to help the formulation of regulatory policy.


Physician-assisted death: doctrinal develoment vs. Christian tradition.
Physician-assisted suicide offers a moral and theological Rorschach test. Foundational commitments regarding morality and theology are disclosed by how the issue is perceived and by what moral problems it is seen to present. One of the cardinal differences disclosed is that between Western and Orthodox Christian approaches to theology in general, and the theology of dying and suicide in particular. Confrontation with the issue of suicide is likely to bring further doctrinal development in many of the Western Christian religions, so as to be able to accept physician-assisted suicide and euthanasia.


Concordance about childhood sexual abuse among depressed patients 50 and over and their family and friends.
In post-mortem studies of suicide, informant sources are often relied upon to provide information to identify correlates of suicide and suicidal behavior. While previous research has shown that informants can supply reliable information about patients' recent stressful life events, it is unknown whether informants and patients provide concordant data about adverse early life experiences such as childhood sexual abuse. This study examined concordance between patient and informant reports of childhood sexual abuse in a sample of depressed patients 50 years and older. Patients and informants (n=88 pairs) independently responded to items from the Childhood Trauma Questionnaire. Informants' reports of patients' severe sexual abuse histories were in high agreement with patients' reports; concordance was significantly lower, however, for milder forms of sexual abuse. These findings demonstrate the feasibility and limitations of collecting sensitive information about patients' early life experiences in research designs utilizing informant report, including postmortem studies of suicide that use psychological autopsy methodology.


Effect of Music Therapy on Pain Perception, Anxiety, and Opioid Use During Dressing Change Among Patients With Burns in India: A Quasi-experimental, Cross-over Pilot Study.
The effectiveness of music therapy for relieving pain and anxiety during burn dressing changes has not been reported from India. This study was conducted to assess the effect of music therapy on pain, anxiety, opioid use, and hemodynamic variables during burn dressing change. Patients in a tertiary care burn unit who were >10 years old, conscious, able to respond, and oriented to time, place, and person participated in a 2-month, quasi-experimental, cross-over pilot study. Each served as his/her own control. Dressings were changed every other day alternating between the control (standard pain management) and experimental (control plus patient-selected music) intervention. Pain was assessed using a numerical rating scale, anxiety was scored using the State Trait Anxiety Test (higher scores indicated more pain and anxiety), and hemodynamic parameters and analgesics were recorded. Wilcoxon Test and chi-squared tests were utilized for statistical analysis. Median pain scores (5, interquartile range [IQR] IQR: 3-7; and 6, IQR: 5-8) and median anxiety scores (12, IQR: 8-17; and 14, IQR: 10-19) were significantly lower during the experimental than during the standard dressing change, respectively (P <.001), and opioids were used significantly less frequently during the experimental change (P = .002). Music therapy helps reduce anxiety, pain, and opioid use during burn dressing change.


Novel insights from live-imaging in shoot meristem development.
Microscopic imaging of fluorescent reporters for key meristem regulators in live tissues is emerging as a powerful technique, enabling researchers to observe dynamic spatial and temporal distribution of hormonal and developmental regulators in living cells. Aided by time-lapse microphotography, new types of imaging acquisition and analysis software, and computational modeling, we are gaining significant insights into shoot apical meristem (SAM) behavior and function. This review is focused on summarizing recent advances in the understanding of SAM organization, development, and behavior derived from live-imaging techniques. This includes the revelation of mechanical forces in microtubule-controlled anisotropic growth, the role of the CLV-WUS network in the specification of peripheral zone and central zone cells, the multiple feedback loops involving cytokinin in controlling WUS expression, auxin dynamics in determining the position of new primordia, and, finally, sequence of regulatory events leading to de novo assembly of shoots from callus in culture. Future studies toward formulating "digital SAM" that incorporates multi-dimensional data ranging from images of SAM morphogenesis to a genome-scale expression map of SAM will greatly enhance our ability to understand, predict, and manipulate SAM, containing the stem cells that give rise to all above ground parts of a plant.


Regulation of the temporal synthesis of proteins in bacteriophage BF23-infected cells.
Regulation of temporal synthesis of pre-early, early, and late proteins in bacteriophage BF23-infected cells has been studied by using five amber mutants defective in genes 1, 2, 10, 14, and 19. The synthesis of pre-early proteins is negatively regulated by the actions of gene 1, a pre-early gene. The switch from pre-early to early protein synthesis is mainly regulated by the second-step DNA transfer reaction, which is controlled by at least genes 1 and 2. Early proteins can be kinetically and genetically divided into two regulatory classes, designated Ea and Eb. The shutoff of Eb-early protein synthesis is associated with the turn-on of late protein synthesis. This step is controlled by genes 10, 14, and 19. Gene 10 also regulates negatively the synthesis of Ea-early proteins, indicating that this gene has a dual function in the regulation of early protein synthesis. The temporal synthesis of phage-encoded proteins is regulated mainly at the transcriptional level. Evidence is presented indicating that the host RNA polymerase is modified by the interaction with the gene products of genes 2, 10, and 14 (gp2, gp10, and gp14, respectively). gp2 interacts with the enzyme in the earlier stage of infection but is replaced by gp10 in the later stage. This exchange reaction depends on the presence of gp14 and gp19 and is related to the switch from Eb to late protein synthesis. Thus, the regulation of BF23 gene expression occurs in a coordinated manner throughout the development of this phage.


Review of Sexuality Studies in Africa: Setting a New Post-2015 Research Agenda.
At the nexus between reproductive health, population and development is the subject of sexuality which has generated extensive discourse in the past two decades. In this paper, we review Africa sexuality studies published between 1994 and 2015 with the aim of synthesizing the available evidence and suggesting a new research agenda for post-2015. Review findings showed that previous studies covered the five components of sexuality - practices, partners, pleasure/pressure/pain, procreation and power to different extents. Risky sexual behaviour was prevalent from adolescence till older ages. Literature on pleasure, pain, procreation and power reflect the complex diversity driven by traditional norms, gender roles and attitudes across the continent. Knowledge gaps were highlighted and new agenda suggested for sexuality research.


Identification of a new HLA-DRB1 allele in three members of an Italian family.
Abstract A new human leucocyte antigen (HLA)-DRB1 allele, HLA-DRB1*1149, has been identified in three members of an Italian family during routine sequence based typing. This new allele differs from HLA-DRB1*110101 only for a single nucleotide substitution at position 113 of exon 2 resulting in an amino acid change from Valine (GTG) to Alanine (GCG) at codon 38.


Arteriovenous Fistula of the Filum Terminale: A Case Report and Review of the Literature.
Fistulas of the filum terminale are rare lesions that result from a fistulous connection between the artery and vein of the filum terminale. These lesions often present as progressive thoracic myelopathy secondary to venous hypertension that is transmitted to the coronal venous plexus of the spinal cord. Frequently, filum fistulas will be associated with lumbar stenosis and likely form as a result of chronic inflammation and compression. However, owing to the relative rarity of filum fistulas and the commonality of lumbar stenosis, the presence of a filum fistula could be overlooked or misdiagnosed. We have presented the case of a 62-year-old man with severe lumbar stenosis who had presented with progressive thoracic myelopathy. The evaluation, including spinal angiography, identified a low-flow arteriovenous fistula within the filum terminale that was successfully treated with microsurgical obliteration. The patient tolerated the procedure well, with good functional recovery within 1 month. Just as was the case with our patient, these lesions demonstrate a high association with lumbar stenosis and tethered or tight cord syndrome. We reviewed the clinical presentation, imaging findings, surgical management, and possible mechanisms of development for these rarely encountered fistulas.


Analysis of the fate and transport of nC₆₀ nanoparticles in the subsurface using response surface methodology.
Predicting the distribution of engineered nanomaterials (ENMs) in the environment will provide critical information for risk assessment and policy development to regulate these emerging contaminants. The fate and transport of ENMs in natural subsurface environments are complicated by various factors, such as hydraulic gradient, initial release concentration, nanoparticle size, and collision efficiency factor. Based on advanced statistical methodologies (i.e., response surface methodology (RSM)), we explore simple relationships between key factors that control ENM transport (collision efficiency factor, particle size, hydraulic gradient, and initial release concentration) and key parameters that describe the ENM concentration distribution in porous media (maximum standardized concentration, the mass percentage of injected nanoparticle attached in the aquifer, the x-centroid of aqueous phase nC₆₀ plume, and the x-centroid of attached phase nC₆₀ distribution). Hypothetical scenarios for the release of nanoparticles into an aquifer were simulated numerically with randomly generated permeability fields that were based on mildly and highly heterogeneous sites. RSM was used to develop polynomial regression equations based on a statistical experimental design. High R-squared values (greater than 0.9) of the regression equations were obtained for all the models developed based on the mildly heterogeneous site. On the highly heterogeneous site, the R-squared value of the regression equation for the percentage of nanoparticles attached (by mass) was more than 0.9. The ability to accurately estimate aqueous phase ENM concentration distribution using simple regression equations is particularly critical for risk assessment. Even though the correlations developed in this study were site and scenario specific, this work represents a first effort of applying RSM for predicting the distribution of engineered nanomaterials in porous media.


[Cardiac imaging: specific clinical role of newly developed non invasive techniques. Part II: functional evaluation].
The non-invasive evaluation of myocardial ischemia is a priority in cardiology. The preferred initial non-invasive test is exercise ECG, because of its high accessibility and its low cost. Stress radionuclide myocardial perfusion imaging or stress echocardiography are now routinely performed, and new non-invasive techniques such as perfusion-MRI, dobutamine stress-MRI or 82rubidium perfusion PET have recently gained acceptance in clinical practice. In the same time, an increasing attention has been accorded to the concept of myocardial viability in the decisional processes in case of ischemic heart failure. In this indication, MRI with late enhancement after intravenous injection of gadolinium and 18F-FDG PET showed an excellent diagnostic accuracy. This article will present these new imaging modalities and their accepted indications.


Strigolactones: new plant hormones in the spotlight.
The development and growth of plants are regulated by interplay of a plethora of complex chemical reactions in which plant hormones play a pivotal role. In recent years, a group of new plant hormones, namely strigolactones (SLs), was discovered and identified. The first SL, strigol, was isolated in 1966, but it took almost 20 years before the details of its structure were fully elucidated. At present, two families of SLs are known, one having the stereochemistry of (+)-strigol and the other that of (-)-orobanchol, the most abundant naturally occurring SL. The most well-known bioproperty of SLs is the germination of seeds of the parasitic weeds Striga and Orobanche. It is evident that SLs are going to play a prominent role in modern molecular botany. In this review, relevant molecular and bioproperties of SLs are discussed. Items of importance are the effect of stereochemistry, structure-activity relationships, design and synthesis of analogues with a simple structure, but with retention of bioactivity, introduction of fluorescent labels into SLs, biosynthetic origin of SLs, mode of action in plants, application in agriculture for the control of parasitic weeds, stimulation of the branching of arbuscular mycorrhizal (AM) fungi, and the control of plant architecture. The future potential of SLs in molecular botany is highlighted.


Trends in heart failure hospitalizations, patient characteristics, in-hospital and 1-year mortality: A population study, from 2000 to 2012 in Lombardy.
This study was undertaken to evaluate trends in heat failure hospitalizations (HFHs) and 1-year mortality of HFH in Lombardy, the largest Italian region, from 2000 to 2012. Hospital discharge forms with HF-related ICD-9 CM codes collected from 2000 to 2012 by the regional healthcare service (n=699797 in 370538 adult patients), were analyzed with respect to in-hospital and 1-year mortality; Group (G) 1 included most acute HF episodes with primary cardiac diagnosis (70%); G2 included cardiomyopathies without acute HF codes (17%); and G3 included non-cardiac conditions with HF as secondary diagnosis (13%). Patients experiencing their first HFH since 2005 were analyzed as incident cases (n=216782). Annual HFHs number (mean 53830) and in-hospital mortality (9.4%) did not change over the years, the latter being associated with increasing age (p<0.0001) and diagnosis Group (G1 9.1%, G2 5.6%, G3 15.9%, p<0.0001). Incidence of new cases decreased over the years (3.62 [CI 3.58-3.67] in 2005 to 3.13 [CI 3.09-3.17] in 2012, per 1000 adult inhabitants/year, p<0.0001), with an increasing proportion of patients aged ≥85y (22.3% to 31.4%, p<0.0001). Mortality lowered over time in <75y incident cases, both in-hospital (5.15% to 4.36%, p<0.0001) and at 1-year (14.8% to 12.9%, p=0.0006). The overall burden and mortality of HFH appear stable for more than a decade. However, from 2005 to 2012, there was a reduction of new, incident cases, with increasing age at first hospitalization. Meanwhile, both in-hospital and 1-year mortality decreased in patients aged <75y, possibly due to improved prevention and treatment.


Interferon antagonists encoded by SARS-CoV-2 at a glance.
The innate immune system is a powerful barrier against invading pathogens. Interferons (IFNs) are a major part of the cytokine-mediated anti-viral innate immune response. After recognition of a pathogen by immune sensors, signaling cascades are activated that culminate in the release of IFNs. These activate cells in an autocrine or paracrine fashion eventually setting cells in an anti-viral state via upregulation of hundreds of interferon-stimulated genes (ISGs). To evade the anti-viral effect of the IFN system, successful viruses like the pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolved strategies to counteract both IFN induction and signaling. In fact, more than half of the about 30 proteins encoded by SARS-CoV-2 target the IFN system at multiple levels to escape IFN-mediated restriction. Here, we review recent insights into the molecular mechanisms used by SARS-CoV-2 proteins to suppress IFN production and the establishment of an anti-viral state.


A case of sclerosing angiomatoid nodular transformation:the correlation between imaging and pathological findings.
A 53-year-old woman was referred to our hospital with a 40-mm splenic tumor, which was detected incidentally on abdominal computed tomography during hospitalization for pyelonephritis. The tumor was hypointense on T2-weighted imaging and gradually enhanced on dynamic study. The tumor increased in size over a six-month period. Since we could not exclude splenic malignancy, we performed laparoscopic partial splenectomy. Histological examination revealed multiple angiomatoid nodules with three distinct vessel types. Pathologically, the tumor was diagnosed as a sclerosing angiomatoid nodular transformation (SANT). We then examined the correlation between the imaging and pathological findings, and performed a review of previous reports, concluding that contrast-enhanced MRI was the most useful modality for diagnosing SANT.


SEAT CHOICE AND DISTANCE JUDGMENT IN PUBLIC SPACES (1).
This research assessed whether public space users will adopt a least-effort approach and choose a less suitable seat nearby or seek the most suitable seat, even if it is farther away from them when the decision is made. How distance assessment affects seat choice was investigated through an observational survey, which allowed the identification of behavioral patterns. Those behavioral patterns were then tested in a paired comparison experiment with 40 participants. The results showed that the effect of distance on seat choice is related to the difference in distance between the options and that a sufficient difference can cause trade-offs between distance and seat properties. The necessary difference in distance is conditioned by the activity and the seat properties.


Structure of the cytoplasmic ring of the Xenopus laevis nuclear pore complex by cryo-electron microscopy single particle analysis.
The nuclear pore complex (NPC) exhibits structural plasticity and has only been characterized at local resolutions of up to 15 Å for the cytoplasmic ring (CR). Here we present a single-particle cryo-electron microscopy (cryo-EM) structure of the CR from Xenopus laevis NPC at average resolutions of 5.5-7.9 Å, with local resolutions reaching 4.5 Å. Improved resolutions allow identification and placement of secondary structural elements in the majority of the CR components. The two Y complexes in each CR subunit interact with each other and associate with those from flanking subunits, forming a circular scaffold. Within each CR subunit, the Nup358-containing region wraps around the stems of both Y complexes, likely stabilizing the scaffold. Nup205 connects the short arms of the two Y complexes and associates with the stem of a neighboring Y complex. The Nup214-containing region uses an extended coiled-coil to link Nup85 of the two Y complexes and protrudes into the axial pore of the NPC. These previously uncharacterized structural features reveal insights into NPC assembly.


The structure and function of centriolar rootlets.
To gain a holistic understanding of cellular function, we must understand not just the role of individual organelles, but also how multiple macromolecular assemblies function collectively. Centrioles produce fundamental cellular processes through their ability to organise cytoskeletal fibres. In addition to nucleating microtubules, centrioles form lesser-known polymers, termed rootlets. Rootlets were identified over a 100 years ago and have been documented morphologically since by electron microscopy in different eukaryotic organisms. Rootlet-knockout animals have been created in various systems, providing insight into their physiological functions. However, the precise structure and function of rootlets is still enigmatic. Here, I consider common themes of rootlet function and assembly across diverse cellular systems. I suggest that the capability of rootlets to form physical links from centrioles to other cellular structures is a general principle unifying their functions in diverse cells and serves as an example of how cellular function arises from collective organellar activity.


Suzuki-Miyaura Cross-Coupling of Amides by N-C Cleavage Mediated by Air-Stable, Well-Defined [Pd(NHC)(sulfide)Cl2] Catalysts: Reaction Development, Scope, and Mechanism.
The Suzuki-Miyaura cross-coupling of amides by selective N-C acyl bond cleavage represents a powerful tool for constructing biaryl ketones from historically inert amide bonds. These amide bond activation reactions hinge upon efficient oxidative addition of the N-C acyl bond to Pd(0). However, in contrast to the well-researched activation of aryl halides by C(sp2)-X oxidative addition, very few studies on the mechanism of C(acyl)-N bond oxidative addition and catalyst effect have been reported. Herein, we report a study on [Pd(NHC)(sulfide)Cl2] catalysts in amide N-C bond activation. These readily prepared, well-defined, air- and moisture-stable Pd(II)-NHC catalysts feature SMe2 (DMS = dimethylsulfide) or S(CH2CH2)2 (THT = tetrahydrothiophene) as ancillary ligands. The reaction development, kinetic studies, and reaction scope are presented. Extensive DFT studies were conducted to gain insight into the mechanism of C(acyl)-N bond oxidative addition and catalyst activation. We expect that [Pd(NHC)(sulfide)Cl2] precatalysts featuring sulfides as well-defined, readily accessible ancillary ligands will find application in C(acyl)-X bond activation in organic synthesis and catalysis.


Development and validation of a prognostic nomogram for early HER2-positive and lymph node-negative breast cancer.
Dual-targeted therapy is currently the standard adjuvant treatment for human epidermal growth factor receptor 2-positive (HER2+) and lymph node-positive (LN+) breast cancer. However, the optimal therapeutic strategy for patients with HER2+ and lymph node-negative (LN-) breast cancer remains unclear. This population-based study aimed to explore the factors associated with survival in patients with HER2+ and LN- breast cancer, and develop a survival-predicting nomogram in the era of trastuzumab-based single-targeted therapy. We collected the clinicopathological information of HER2+ and LN- breast cancer patients who underwent chemotherapy and surgery from The Surveillance, Epidemiology, and End Results (SEER) database (2010-2016, the Trastuzumab-based single-targeted therapy era). We subsequently explored the risk factors for breast cancer-specific survival (BCSS) and overall survival (OS) using a Cox proportional hazards regression model, aiming to identify subgroups with worse prognosis, which would indicate potential demand for dual-targeted therapy. Three- and 5-year survival probability-predictive nomograms were established and subjected to bootstrap internal validation. The concordance index (C-index) and calibration curve were applied to evaluate the performance of the model. After data cleansing, a total of 13,755 patients were included in the current analysis. Using univariate and multivariate Cox proportional hazards regression, higher clinical T stage, hormone receptors-negative (HR-), and partial mastectomy without radiotherapy were identified as independent risk factors for BCSS and OS in patients with HER2+ and LN- breast cancer. Nomograms for 3- and 5-year BCSS and OS incorporating the selected prognostic factors were established. Calibration curves verified good consistency between the actual and nomogram-predicted survival probability. The C-index values of the BCSS and OS predictions and 95% confidence interval (CI) were 0.773 (0.740-0.806) and 0.764 (0.737-0.791), respectively. Higher clinical T stage, HR-, and partial mastectomy without radiotherapy predicted worse prognosis in patients with HER2+ and LN- breast cancer. In clinical practice, patients can be recommended for single-targeted or dual-targeted therapy according to the individualized factors.


[Endoscopic endonasal anterior extended transsphenoidal approach in craniopharyngioma surgery].
The paper describes results of treatment of 56 patients with suprasellar craniopharyngioma (stem, intra-extraventricular) who were operated in Burdenko Neurosurgical Institute using endoscopic endonasal anterior extended transsphenoidal approach. Assessed dynamics of major clinical syndromes (neuro-ophthalmological symptoms, neurological and hormonal status), radicality of surgery, incidence and nature of postoperative complications, postoperative mortality. A comparative analysis of the results obtained in previous studies of our Institute, as well as with those of foreign authors is performed. Obtained data show that endoscopic endonasal anterior extended transsphenoidal approach in craniopharyngioma surgery is an efficient and non-traumatic technique, capable of providing a radical removal of the tumor along with a high quality of life after surgery, and relatively low rates of postoperative complications and mortality.


A brief history of corneal transplantation: From ancient to modern.
This review highlights many of the fundamental concepts and events in the development of corneal transplantation - from ancient times to modern. Tales of eye, limb, and even heart transplantation appear in ancient and medieval texts; however, in the scientific sense, the original concepts of corneal surgery date back to the Greek physician Galen (130-200 AD). Although proposals to provide improved corneal clarity by surgical interventions, including keratoprostheses, were better developed by the 17(th) and 18(th) centuries, true scientific and surgical experimentation in this field did not begin until the 19(th) century. Indeed, the success of contemporary corneal transplantation is largely the result of a culmination of pivotal ideas, experimentation, and perseverance by inspired individuals over the last 200 years. Franz Reisinger initiated experimental animal corneal transplantation in 1818, coining the term "keratoplasty". Subsequently, Wilhelmus Thorne created the term corneal transplant and 3 years later Samuel Bigger, 1837, reported successful corneal transplantation in a gazelle. The first recorded therapeutic corneal xenograft on a human was reported shortly thereafter in 1838-unsurprisingly this was unsuccessful. Further progress in corneal transplantation was significantly hindered by limited understanding of antiseptic principles, anesthesiology, surgical technique, and immunology. There ensued an extremely prolonged period of debate and experimentation upon the utility of animal compared to human tissue, and lamellar versus penetrating keratoplasty. Indeed, the first successful human corneal transplant was not performed by Eduard Zirm until 1905. Since that first successful corneal transplant, innumerable ophthalmologists have contributed to the development and refinement of corneal transplantation aided by the development of surgical microscopes, refined suture materials, the development of eye banks, and the introduction of corticosteroids. Recent developments, including the replacement of selected corneal layers rather than full-thickness keratoplasty, have the potential to improve or transform corneal transplant surgery in the future.


Aging without Dementia is Achievable: Current Evidence from Epidemiological Research.
Both the incidence and the prevalence of dementia increase exponentially with increasing age. This raises the question of whether dementia is an inevitable consequence of aging or whether aging without dementia is achievable. In this review article, we sought to summarize the current evidence from epidemiological and neuropathological studies that investigated this topic. Epidemiological studies have shown that dementia could be avoided even at extreme old ages (e.g., centenarians or supercentenarians). Furthermore, clinico-neuropathological studies found that nearly half of centenarians with dementia did not have sufficient brain pathology to explain their cognitive symptoms, while intermediate-to-high Alzheimer pathology was present in around one-third of very old people without dementia or cognitive impairment. This suggests that certain compensatory mechanisms (e.g., cognitive reserve or resilience) may play a role in helping people in extreme old ages escape dementia syndrome. Finally, evidence has been accumulating in recent years indicating that the incidence of dementia has declined in Europe and North America, which supports the view that the risk of dementia in late life is modifiable. Evidence has emerged that intervention strategies that promote general health, maintain vascular health, and increase cognitive reserve are likely to help preserve cognitive function till late life, thus achieving the goal of aging without dementia.


Efficacy and safety of sublingual immunotherapy in children.
Allergen immunotherapy (AIT) is currently the only available disease-modifying and aetiological treatment of IgE-mediated diseases. Sublingual allergen immunotherapy (SLIT) constitutes the preferred route of administration of AIT for respiratory allergies in Europe. Recently it has also been approved in the US. Further applications are currently under evaluation, such as IgE-mediated food allergy and IgE-mediated atopic dermatitis. The SLIT safety profile is overall favourable, although local adverse events, usually mild, are described. Most of the meta-analyses confirmed the efficacy of SLIT in reducing symptoms and medication intake in children with allergic diseases. AIT, as an immune-modulating treatment, can modify the natural history of the allergic diseases: reduction of the risk of development of asthma and bronchial hyperreactivity in patients with allergic rhinitis, and reduction of the onset of new sensitizations. A great interest is now devoted to the preventive effects of AIT and, consequently, to the optimal time of initiation.


[Developing and validating of patient-reported questionnaires - part 2].
Patient-reported outcome measurements (PROMs) are often questionnaires which provide and rate the patient's point of view in the measurement of subjective clinical phenomena such as pain or quality of life. In the second of two articles we describe field-testing, the psychometric theories Classical Test Theory and Item Response Theory, psychometric validation and the measurement properties of a PROM. The latter is based on the COSMIN (consensus-based standards for the selection of health measurement instruments) guidelines, which are developed to assist in development and evaluation of PROMs.


Room Decontamination Using Ionized Hydrogen Peroxide Fog and Mist Reduces Hatching Rates of Syphacia obvelata Ova.
This study evaluated the efficacy of ionized hydrogen peroxide (iHP) fog and mist for environmental and surface decontaminationof Syphacia obvelata ova in rodent rooms. Ova were collected by perianal tape impression from S. obvelata infectedmice. In experiment 1, ova were exposed to iHP using a whole-room fogging decontamination system with a 15 min initialfog application cycle in unoccupied rodent rooms. Ova were removed from the fogged environment after a 15 min, 30 min, 90min, or 240 min iHP exposure time. In experiment 2, a second cohort of ova were exposed to iHP using the whole-room foggingdecontamination system. Ova were removed after 3, 4 or 6 continuous fog application cycles with 45 min dwelling timebetween each cycle and 15 h dwelling time for the last time point. In experiment 3, a third set of ova was exposed to an iHPsurface misting unit with 1, 2, or 3 iHP mist applications. A 7 min contact time followed each application. After exposure, ovawere incubated in a hatching medium for 6 h. Control ova were maintained at room temperature without iHP exposure beforeincubation in the hatching medium. After incubation, the number of ova hatched was assessed by microscopic examination.For experiment 1, results ranged from 46% to 57% of exposed ova hatched. For experiment 2, results ranged from 43% to 49%of ova hatched. For experiment 3, 37% to 46% of exposed ova hatched. Conversely, for the control groups above 80% of ovahatched for all 3 experiments. These data suggest that exposure to iHP fog and mist has variable effectiveness in reducingviability of S. obvelata ova at the time points tracked. Further studies are needed to identify iHP exposures that will furtherreduce or eliminate the hatching of rodent pinworm ova.


A case of ambiguous external genitalia in a Thoroughbred male horse with the 63,XO/64,XY mosaic karyotype.
A Thoroughbred colt with ambiguous external genitalia was presented for clinical and histological examinations. The colt had a short penis that faced backward between his hind limbs. The measurements of luteinizing hormone, follicle stimulating hormone, testosterone and ir-inhibin showed a tendency to increase gradually from April. Both the sex-determining region of the Y chromosome and amelogenin gene fragments were detected by the PCR method. A cytogenetic analysis revealed the 63,XO/64,XY mosaic karyotype (ratio 83:17). In autopsy, immature symmetrical subcutaneous testes were found in the inguinal regions. The testes and other accessory sex organs were histologically normal. These results add to our knowledge of chromosomal abnormality and information concerning disorders of sex development in the horse.


Translational tests involving non-reward: methodological considerations.
This review is concerned with methods for assessing the processing of unrewarded responses in experimental animals and the mechanisms underlying performance of these tasks. A number of clinical populations, including Parkinson's disease, depression, compulsive disorders, and schizophrenia demonstrate either abnormal processing or learning from non-rewarded responses in laboratory-based reinforcement learning tasks. These effects are hypothesized to result from disturbances in modulatory neurotransmitter systems, including dopamine and serotonin. Parallel work in experimental animals has revealed consistent behavioral patterns associated with non-reward and, consistent with the human literature, modulatory roles for specific neurotransmitters. Classical tests involving an important reward omission component include appetitive extinction, ratio schedules of responding, reversal learning, and delay and probability discounting procedures. In addition, innovative behavioral tests have recently been developed leverage probabilistic feedback to specifically assay accommodation of, and learning from, non-rewarded responses. These procedures will be described and reviewed with discussion of the behavioral and neural determinants of performance. A final section focusses specifically on the benefits of trial-by-trial analysis of responding during such tasks, and the implications of such analyses for the translation of findings to clinical studies.


What do high school students say when they talk to their friends about substance use? Exploring the content of substance-use-specific communication with friends.
In this study, we examined the content of adolescents' conversations with their friends about substance use, adolescents' reactions to such conversations, and reasons why some adolescents did not engage in such conversations. Based on 25 semistructured interviews with high school students, we identified three themes: informational, persuasive, and relational messages. Informational messages included discussing how many peers use substances and clarifying rumors about a friend's substance use. Persuasive messages involved direct anti-substance-use messages (e.g., warning), direct pro-substance-use messages (e.g., legalizing marijuana), indirect anti-substance-use messages (e.g., disliking their substance-use experience), and indirect pro-substance-use messages (e.g., intentions to use substances). Relational messages included joking about substance use and establishing code words for use. Adolescents reacted to their conversations in several ways, such as shock and increased relational closeness. When adolescents did not talk about substance use with their friend, they offered several reasons, including low response efficacy and fear of ruining the friendship.


[Correlation between single nucleotide polymorphisms of neurotrophic factors and executive function characteristics in children with attention deficit hyperactivity disorder].
To investigate the correlation between the polymorphisms of(brain derived neurotrophic factor, BDNF)BDNF gene rs11030104 and rs2030324 and executive function in children with attention deficit hyperactivity disorder(ADHD). A total of 206 ADHD children and 212 control children were enrolled in the study. Five mL peripheral venous blood was extracted from each subject and genomic DNA was extracted. The genotypes of rs11030104 and rs2030324 loci were genotyped by PCR/sequencing. The selection was tested by Wisconsin Classification Card Test, Stroop Color-Word Task, Reaction/Nonresponse Task and Stop Signal Task. The distribution of rs2030324 locus gene frequency was different between ADHD group and control group. G allele was the risk factor of ADHD(χ~2=4. 481, P=0. 034; OR=1. 520, 95%CI 1. 031-2. 243); rs11030101 locus gene frequency distribution and genotype distribution had statistical significance between the two groups, and A allele was related to ADHD susceptibility(OR=1. 601, 95%CI 1. 052-2. 436). The error interference score of Stroop test in ADHD group was higher than that in control group(P<0. 05), but there was no significant difference in response time interference score between the two groups(P>0. 05). The SCWT scores of different genotypes of BDNF rs2030324 in ADHD group were different. Compared with AA type and AG type, the SCWT error interference scores of GG type ADHD patients were higher. There was no significant difference among rs11030101 genotypes. The WCST scores of ADHD group were lower than those of control group. The variation of Go/no-go scores in ADHD group was higher than that of control group in missed count, mistaken count and correct reaction time. The variation of SST and correct reaction time in ADHD group were higher than that of control group, but the genotype distribution of rs11030104 and rs2030324 loci had no significant correlation with WCST, Go/no-go and SST scores. Children with ADHD have executive dysfunction. ADHD children with BDNF rs2030324 GG genotype showed poor Stroop executive function.


Estrogen stimulates adenosine receptor expression subtypes in human breast cancer MCF-7 cell line.
Estrogen is a steroid hormone that plays a key role in the development and regulation of reproductive system. It has been shown that estrogen is related to breast cancer development through binding to its receptors. In order to uncover the estrogen effects on adenosine receptor expression, estrogen-positive MCF-7 cells were used to treat with agonist and antagonist of estrogen and then the mRNA expression of adenosine receptor subtypes were evaluated. Estrogen-positive MCF-7 cells were treated with various concentrations of 17β estradiol (E2) as an estrogen agonist, and ICI 182,780 as an estrogen antagonist. The gene expression of adenosine receptor subtypes were detected by real time RT-PCR. The results of MTT assay showed that E2 increased cell viability in a dose dependent manner. The expression pattern of all adenosine receptor subtypes are as follow; A2b > A1 > A2a > A3 in untreated MCF-7 cells. Obtained results showed that E2 incubation at 0.001-0.01 μM led to up-regulation of A1ARs, A2aARs and A3ARs dose dependently. E2 at 0.001 μM also had no significant effect on A2bARs expression but, at higher doses induced a considerable decrease in mRNA A2bARs expression. Treatment with antagonist confirmed that up-regulation of these receptors is mediated by estrogen receptor. Taken together, our results indicate that treatment of MCF-7 cells with E2 led to up-regulation of adenosine receptors. However, these effects were partially restored by treatment with antagonist suggesting that such effects are mediated by estrogen receptors.


Critical Role of Semiquinones in Reductive Dehalogenation.
Quinones and products of their redox reactions (hydroquinones and semiquinones) have been suggested as important players in the reductive dehalogenation of organohalogens mediated by natural and pyrogenic organic matter, although based on limited direct evidence. This study focused on the reductive dehalogenation of a model organohalogen (triclosan) by 1,4-benzohydroquinone (H2Q). In the presence of H2Q only, degradation of triclosan does not occur within the experimental period (up to 288 h); however, it takes place in the presence of H2Q and FeCl3 under anoxic conditions at pH 5 and 7 (above the pKa of SQ = 4.1) only to be halted in the presence of dissolved oxygen. Kinetic simulation and thermodynamic calculations indicated that benzosemiquinone (SQ-) is responsible for the reductive degradation of triclosan, with the fitted rate constant for the reaction between SQ- and triclosan being 317 M-2 h-1. The critical role of semiquinones in reductive dehalogenation can be relevant to a wide range of quinones in natural and engineering systems based on the reported oxidation-reduction potentials of quinones/semiquinones and semiquinones/hydroquinones and supported by experiments with additional model hydroquinones.


Neighborhood social environments and the distribution of low birthweight in Chicago.
This study examined the socioeconomic precursors of disparities in maternal health by measuring the associations of nine neighborhood-level indicators of social phenomena with low infant birthweight. Vital records and census data for the Chicago metropolitan area in 1990 were merged (n = 112,327); a logistic regression model predicting low birthweight was estimated by backward elimination. With individual-level variables held constant, six neighborhood-level indicators predicted low birthweight, together contributing to a variation in rate of 5.5%. Community economic hardship and housing costs were positively associated with low birthweight, while community socioeconomic status, crowded housing, and high percentages of young and African-American residents were negatively associated with low birthweight. Maternal health inequalities should be explored in the context of historical segregation, social stratification, the dynamics of social support, and resource sharing among communities. Several community characteristics associated with poverty are negatively associated with low birthweight. The traditional focus on individual risk factors for low birthweight limits our understanding.


Myocardium of hypothermic rats with and without administration of dextran. Electrocardiographic and electron microscopic studies.
Electrocardiographic and electron microscopic alterations in the myocardium were investigated in rats subjected to hypothermia with and without injection of dextran. Twenty-two animals were divided into four groups and studied. The first group of five rats served as the control group. The second group of six rats, which were subjected to total body hypothermia developed arrhythmia (from first degree atrioventricular block to complete heart block) at a mean rectal temperature of 18 degrees C., with prolongation of P,P-R, and QRS duration, as well as a marked separation of intercalated discs, articularly at the level of the fascia adherens. The third group of six rats was subjected to hypothermia and to an injection of dextran. The resulting threshold temperature tthe temperature at which the arrhythmia appeared) was lower (16 degrees C.) than in the preceding group (p less than 0.005), but neither advanced atrioventricular block nor remarkable subcellular structural changes developed. The fourth group of five rats was sacrificed 18 to 24 hours following recovery from hypothermia and, at that time, showed no significant electrocardiographic or electron microscopic alterations.


Roles of TraI protein with activities of cleaving and rejoining the single-stranded DNA in both initiation and termination of conjugal DNA transfer.
The plasmid R100 encodes the TraI protein, which is required for conjugal DNA transfer. TraI has the activity of site- and strand-specific nicking of the supercoiled plasmid DNA. The molecular mechanism of this specific nicking, which is supposed to be the initiation reaction of DNA transfer, is not understood. We have demonstrated that TraI has the ability to cleave the single-stranded DNA at the same site as the nicking site (nic) in a region, which we here refer to as sbi. The product contained the TraI protein which was covalently linked to the newly generated 5' end of the nicking reaction. Both the cleaving and nicking reactions took place under almost the same conditions and required the presence of the sbi region. DNase I-footprinting analysis revealed that the TraI bound to the single-stranded DNA of the sbi region. TraI did not cleave the double-stranded DNA fragment, but it did cleave the double-stranded DNA with a single-stranded DNA portion in the sbi region. KMnO4 mapping analysis revealed that TraI can melt the sbi region in the supercoiled DNA to generate a single-stranded portion. We have also demonstrated that TraI was able to rejoin the cleaved products. The rejoining reaction required the 5' end of one cleaved product with the TraI covalently attached and the 3' end of the other product containing the sbi region. Our results demonstrate that the nicking reaction-the initiation reaction of DNA transfer-is actually the cleaving reaction of the single-stranded DNA. TraI, which has both cleaving and rejoining activities, is thought to be involved in the termination of DNA transfer, to give a copy of the conjugative plasmid by joining the 5' end, which is generated by the initiation reaction, with the 3' end, which will be generated upon cleavage of the sbi region appearing after one round of the rolling circle replication of the plasmid.


A study of the nurse tutor's role.
The aim of the study was to determine how British nurse tutors and nurse learners perceive the role of the nurse tutor in the field of general nursing. A survey by questionnaire was the method of inquiry used. The sample was drawn from eleven schools of nursing in one Regional Health Authority in England, and comprised 317 nurse learners and 93 nurse teachers. Data from the questionnaires were analysed using the statistical technique of factor analysis. In particular the learners' data were used to derive factor scales relating to aspects of the role of the nurse tutor. Twelve such factor scales emerged from the factor analysis of the data. Agreement was found between the learners and the teachers on four of these factor scales and disagreement was found relating to the remaining eight. It is suggested that the areas of agreement might form the basis for the systematic description of the role of the nurse tutor. Conversely, the areas of disagreement could provide a basis for further research into this subject.


Assessment of dietary intake of cadmium, lead and mercury via foods of the plant and animal origin in Slovenia.
Due to lack of data the Slovene Ministry of Health--Department of Health Inspection initiated a study of dietary intake of contaminants at the national level. The Institute of Public Health Celje conducted two phases of the study: The assessment of dietary intake of cadmium, lead and mercury in foods of the plant (1st phase) and animal origin (2nd phase). 1583 samples from 17 groups of plant and 11 groups of animal origin foods were taken in total. Sampling was implemented in nine Slovene regions, and thus at least 6 randomly composed samples of foods from the particular group were taken in each region. For assessment of dietary intake of different food items national food consumption data were applied. The estimated weekly intake of cadmium with foods of plant and animal origin that represent 84.6% of total food intake is 91.7 ig (18.8% of PTWI for cadmium. The weekly lead intake with foods of plant and animal origin is 422.3 g (24.2% PTWI for lead). The mercury content in foods disposable in Slovenia is low, therefore, the quantity of mercury consumed with analysed foods is 12.3% of PTWI for mercury.


[The key issues and corresponding strategy of acupoint medicated catgut embedding therapy].
Acupoint medicated catgut embedding therapy is a new type of acupuncture combined with medicine,which has great potential in the prevention and treatment of chronic diseases. This paper describes the clinical application of acupoint medicated catgut embedding in the treatment of common disease, medicated thread productionmethods and acupoints selection.To analyze the problems of the unclear mechanism, the lack of standardization of medicated thread production, the lag of the embedding tool, and the unclear adverse reaction. It is expected to promote the further development of acupoint medicated catgut embedding therapy by strengthening the mechanism of action, optimizing medicated catgut thread, rational design experiments, standardizing medicated thread production, innovating embedding tools, rational formulation, and optimizing acupoint selection.


Dissociation and Posttraumatic Symptoms in Maltreated Preschool Children.
This study examines dissociation and posttraumatic symptomatology in a sample of maltreated preschool-age children in foster care. Analyses compared Child Behavior Checklist subscale scores for the foster care sample and a community sample, and also examined differences between maltreatment subtypes. Exposure to any type of maltreatment was associated with greater dissociation and posttraumatic symptomatology in this sample. Preschool-age children with documented sexual abuse displayed high levels of posttraumatic symptoms, whereas children with documented physical abuse tended to use dissociation as a primary coping mechanism. The finding that physically abused children had high levels of dissociation confirms previous research with preschoolers.


Peer support for people with severe mental illness versus usual care in high-, middle- and low-income countries: study protocol for a pragmatic, multicentre, randomised controlled trial (UPSIDES-RCT).
Peer support is an established intervention involving a person recovering from mental illness supporting others with mental illness. Peer support is an under-used resource in global mental health. Building upon comprehensive formative research, this study will rigorously evaluate the impact of peer support at multiple levels, including service user outcomes (psychosocial and clinical), peer support worker outcomes (work role and empowerment), service outcomes (cost-effectiveness and return on investment), and implementation outcomes (adoption, sustainability and organisational change). UPSIDES-RCT is a pragmatic, parallel-group, multicentre, randomised controlled trial assessing the effectiveness of using peer support in developing empowering mental health services (UPSIDES) at four measurement points over 1 year (baseline, 4-, 8- and 12-month follow-up), with embedded process evaluation and cost-effectiveness analysis. Research will take place in a range of high-, middle- and low-income countries (Germany, UK, Israel, India, Uganda and Tanzania). The primary outcome is social inclusion of service users with severe mental illness (N = 558; N = 93 per site) at 8-month follow-up, measured with the Social Inclusion Scale. Secondary outcomes include empowerment (using the Empowerment Scale), hope (using the HOPE scale), recovery (using Stages of Recovery) and health and social functioning (using the Health of the Nations Outcome Scales). Mixed-methods process evaluation will investigate mediators and moderators of effect and the implementation experiences of four UPSIDES stakeholder groups (service users, peer support workers, mental health workers and policy makers). A cost-effectiveness analysis examining cost-utility and health budget impact will estimate the value for money of UPSIDES peer support. The UPSIDES-RCT will explore the essential components necessary to create a peer support model in mental health care, while providing the evidence required to sustain and eventually scale-up the intervention in different cultural, organisational and resource settings. By actively involving and empowering service users, UPSIDES will move mental health systems toward a recovery orientation, emphasising user-centredness, community participation and the realisation of mental health as a human right. ISRCTN, ISRCTN26008944. Registered on 30 October 2019.


Evolutionarily new sequences expressed in tumors.
Earlier we suggested the concept of the positive evolutionary role of tumors. According to this concept, tumors provide conditions for the expression of evolutionarily new and/or sleeping genes in their cells. Thus, tumors are considered as evolutionary proving ground or reservoir of expression. To support this concept we have previously characterized in silico and experimentally a new class of human tumor-related transcribed sequences. In this article we describe results of further studies of previously described tumor-related sequences. The results of molecular phylogeny studies, Southern hybridization experiments and computational comparison with genomes of other species are presented. These results suggest that these previously described tumor-related human transcripts are also relatively evolutionarily new.


[Combined study of the vascular, duct and lobular-alveolar systems of the mammary gland].
A procedure is suggested for filling the vessels with Indian ink-gelatine followed by staining the total preparations of the mammary gland. The procedure enables one to observe simultaneously the vascular network, duct, and lobular-alveolar system of the organ under light and stereoscopic microscopes.


Identification of vascular progenitor cells in pulmonary arteries of patients with chronic obstructive pulmonary disease.
Progenitor cells of bone marrow origin migrate to injured vessels, where they may contribute to endothelial maintenance and vessel remodeling through vascular endothelial growth factor (VEGF)-related signals. To what extent progenitor cells may play a role in vascular changes occurring in patients with chronic obstructive pulmonary disease (COPD) remains undetermined. In this study we sought to identify vascular progenitor cells in pulmonary arteries of patients with COPD and to investigate whether the presence of these cells could be related to changes in endothelial function or the expression of VEGF. Pulmonary arteries of nine patients with COPD and six control subjects were studied. Scanning electron microscopy demonstrated areas of denuded endothelium in the arteries of patients with COPD. Vascular progenitor cells were identified by immunohistochemistry and immunogold using antibodies against AC133, CD34, and CD45. AC133+ cells were localized in the endothelial surface, close to denuded areas. The number of AC133+ and CD45+ cells in pulmonary arteries was greater in patients with COPD than in control subjects. The number of AC133+ cells correlated with the response of pulmonary artery rings to hypoxic stimulus. AC133+ and CD45+ cells were also identified in the intimal layer. The wall thickness correlated with the number of progenitor cells in the intima and with VEGF and VEGF receptor-2 mRNA expression. We conclude that patients with COPD show an increased number of bone marrow-derived progenitor cells in pulmonary arteries. These cells seem to contribute to ongoing endothelial repair, but they might also be involved in the pathogenesis of pulmonary vascular remodeling.


Finasteride for prostatic disease: an updated and comprehensive review.
The development and introduction in clinical practice of finasteride, the first potent inhibitor of steroid 5-alpha-reductase that inhibits the conversion of testosterone to its active form dihydroxytestosterone, has created the possibility to prevent and treat prostatic disorder by manipulating and lowering the androgens levels in the prostate. Randomised and placebo-controlled trials have demonstrated the benefit of finasteride in men with enlarged prostatic gland owing to benign prostatic hyperplasia in terms of symptoms and urinary flow rate improvements. The Prostate Cancer Prevention Trial has clearly stated the chemopreventive properties of finasteride for prostate cancer but the necessity to provide such preventive therapy to a specific group of men with a higher risk to develop a clinically significant disease is under discussion. Finasteride is administered orally as a single daily dose. We recommend a 5 mg dose.


Neural basis of sensorimotor learning: modifying internal models.
The neural basis of the internal models used in sensorimotor transformations is beginning to be uncovered. Sensorimotor learning involves the modification of such models. Different stages of sensory-motor processing have been explored with a continuum of experimental tasks, from learning arbitrary associations of sensory cues to movements, to adapting to altered kinematic and dynamic environments. Several groups have been studying changes in neuronal activity in cortical and subcortical areas that may be related to the acquisition and consolidation processes. We discuss the progress and challenges in understanding how these learning-related neural changes are involved in the modification of internal models, and offer future directions.


Sequence analysis and regulation of the htrA gene of Escherichia coli: a sigma 32-independent mechanism of heat-inducible transcription.
Previous work has established that the E. coli htrA gene product is essential for bacterial survival at temperatures above 42 degrees. We have sequenced the htrA gene region and found an open reading frame (ORF) coding for a protein of 491 amino acids with a calculated molecular weight of 51,163 daltons. This molecular weight corresponds well with that seen following electrophoresis on SDS-polyacrylamide gels. This protein has an amino-terminal sequence typical for a leader peptide and undergoes post-translational modification by cleavage of an amino-terminal portion. The insertional mutations which affect the function of the htrA gene map inside this ORF. The levels of htrA mRNA increase rapidly and transiently upon heat shock in a manner independent of the rpoH gene, which encodes the sigma 32 RNA polymerase subunit and is known to regulate transcription of typical heat shock genes. Using S1 mapping and RNA primer extension, we have identified the htrA promoter and found that it is similar to the P3 promoter of the rpoH gene. The P3 promoter is especially active at high temperatures and is recognized by a recently identified transcriptional factor, sigma E.


Reduction of scintillation in optical modulating retro-reflector links.
Optical modulating retro-reflectors enable free-space optical links that have greatly reduced pointing requirements and do not require a laser at one end of the link. However, these types of links can exhibit very high optical scintillation due to the double passage of the beam through the atmosphere. This high scintillation causes fades and surges that can lead to packet errors in the link. It is shown that scintillation can be greatly reduced through a combination of techniques including retro-reflector diversity, aperture averaging and bistatic optical interrogation. Improvements of 20 dB in link performance are demonstrated.


How Biomechanical Improvements in Running Economy Could Break the 2-hour Marathon Barrier.
A sub-2-hour marathon requires an average velocity (5.86 m/s) that is 2.5% faster than the current world record of 02:02:57 (5.72 m/s) and could be accomplished with a 2.7% reduction in the metabolic cost of running. Although supporting body weight comprises the majority of the metabolic cost of running, targeting the costs of forward propulsion and leg swing are the most promising strategies for reducing the metabolic cost of running and thus improving marathon running performance. Here, we calculate how much time could be saved by taking advantage of unconventional drafting strategies, a consistent tailwind, a downhill course, and specific running shoe design features while staying within the current International Association of Athletic Federations regulations for record purposes. Specifically, running in shoes that are 100 g lighter along with second-half scenarios of four runners alternately leading and drafting, or a tailwind of 6.0 m/s, combined with a 42-m elevation drop could result in a time well below the 2-hour marathon barrier.


Left atrial area index provides the best prediction of atrial fibrillation in ischemic stroke patients: results from the LAETITIA observational study.
Left atrial (LA) enlargement has been repeatedly shown to be associated with the diagnosis of atrial fibrillation (AF). In clinical practice, several parameters are available to determine LA enlargement: LA diameter index (LADI), LA area index (LAAI), or LA volume index (LAVI). We investigated the predictive power of these individual LA parameters for AF in patients with acute ischemic stroke or transient ischemic attack (TIA). LAETITIA is a retrospective observational study that reflects the clinical reality of acute stroke care in Germany. Consecutive patient cases with acute ischemic cerebrovascular event (CVE) in 2019 and 2020 were identified from the Mannheim stroke database. Predictive power of each LA parameter was determined by the area under the curve (AUC) of receiver operating characteristic curves. A cutoff value was determined. A multiple logistic regression analysis was performed to confirm the strongest LA parameter as an independent predictor of AF in patients with acute ischemic CVE. A total of 1,910 patient cases were included. In all, 82.0% of patients had suffered a stroke and 18.0% had a TIA. Patients presented with a distinct cardiovascular risk profile (reflected by a CHA2DS2-VASc score ≥2 prior to hospital admission in 85.3% of patients) and were moderately affected on admission [median NIHSS score 3 (1; 8)]. In total, 19.5% of patients had pre-existing AF, and 8.0% were newly diagnosed with AF. LAAI had the greatest AUC of 0.748, LADI of 0.706, and LAVI of 0.719 (each p < 0.001 vs. diagonal line; AUC-LAAI vs. AUC-LADI p = 0.030, AUC-LAAI vs. AUC-LAVI p = 0.004). LAAI, increasing NIHSS score on admission, and systolic heart failure were identified as independent predictors of AF in patients with acute ischemic CVE. To achieve a clinically relevant specificity of 70%, a cutoff value of ≥10.3 cm2/m2 was determined for LAAI (sensitivity of 69.8%). LAAI revealed the best prediction of AF in patients with acute ischemic CVE and was confirmed as an independent risk factor. An LAAI cutoff value of 10.3 cm2/m2 could serve as an inclusion criterion for intensified AF screening in patients with embolic stroke of undetermined source in subsequent studies.


Nanoscale zero-valent iron/persulfate enhanced upflow anaerobic sludge blanket reactor for dye removal: Insight into microbial metabolism and microbial community.
This study investigated the efficiency of nanoscale zero-valent iron combined with persulfate (NZVI/PS) for enhanced degradation of brilliant red X-3B in an upflow anaerobic sludge blanket (UASB) reactor, and examined the effects of NZVI/PS on anaerobic microbial communities during the treatment process. The addition of NZVI (0.5 g/L) greatly enhanced the decolourization rate of X-3B from 63.8% to 98.4%. The Biolog EcoPlateTM technique was utilized to examine microbial metabolism in the reactor, and the Illumina MiSeq high-throughput sequencing revealed 22 phyla and 88 genera of the bacteria. The largest genera (Lactococcus) decreased from 33.03% to 7.94%, while the Akkermansia genera increased from 1.69% to 20.23% according to the abundance in the presence of 0.2 g/L NZVI during the biological treatment process. Meanwhile, three strains were isolated from the sludge in the UASB reactors and identified by 16 S rRNA analysis. The distribution of three strains was consistent with the results from the Illumina MiSeq high throughput sequencing. The X-ray photoelectron spectroscopy results indicated that Fe(0) was transformed into Fe(II)/Fe(III) during the treatment process, which are beneficial for the microorganism growth, and thus promoting their metabolic processes and microbial community.


Dissection of the functional structure of aptamer17, which specifically recognizes differentiated PC12 cells.
A specific single-stranded DNA (ssDNA) aptamer (aptamer17) that specifically recognizes differentiated PC12 cells had been previously obtained after 6 rounds of whole cell-based subtractive systematic evolution of ligands by exponential enrichment selection from a random ssDNA library. To further investigate the relationship between the structure and function of this aptamer, 3 truncated ssDNA aptamers were designed according to the predicted secondary structure of aptamer17. Our results show that the stem-loop is the core structure of the aptamers required for specific binding to differentiated PC12 cells, specifically loops I and II. Aptamer17 and the truncated aptamers with this basic structure could bind specifically to differentiated PC12 cells and identify these cells from a mixture of differentiated and undifferentiated PC12 cells. Therefore, truncated forms of aptamer17 may be useful in the clinic to identify undifferentiated and differentiated PC12 cells from a mixture of cells.


The Potential of a Saliva Test for Screening of Alveolar Bone Resorption.
Oral health screening is important for maintaining and improving quality of life. The present study aimed to determine whether patients with a certain level of alveolar bone resorption could be screened by salivary bacterial test along with their background information. Saliva samples were collected from 977 Japanese patients, and the counts of each red-complex, that is, Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia, were measured using quantitative polymerase chain reaction analysis. Mean bone crest levels (BCLs) were measured using a full-mouth periapical radiograph. Multiple logistic regression analysis was used to determine associations between BCLs (1.5-4.0 mm in 0.5 mm increments) and explanatory variables, such as the number of each red-complex bacteria and the patients' age, sex, number of teeth, stimulated saliva volume, and smoking habits. When the cutoff BCL value was set at 3.0 mm, the area under the curve, sensitivity, and specificity values were optimal at 0.86, 0.82, and 0.76, respectively. In addition, all tested explanatory variables, except sex and T. denticola count, were significantly associated with BCLs according to a likelihood ratio test (p < 0.05). Additionally, the odds ratio (OR) was substantially increased when a patient was >40 years old and the bacterial count of P. gingivalis was >107 cells/µL (OR: >6). Thus, P. gingivalis count and patients' background information were significantly associated with the presence of a certain amount of bone resorption, suggesting that it may be possible to screen bone resorption without the need for radiography or oral examination.


Nontoxic Levels of Se-Containing Compounds Increase Survival by Blocking Oxidative and Inflammatory Stresses via Signal Pathways Whereas High Levels of Se Induce Apoptosis.
Selenium is a main group element and an essential trace element in human health. It was discovered in selenocysteine (SeC) by Stadtman in 1974. SeC is an encoded natural amino acid hailed as the 21st naturally occurring amino acid (U) present in several enzymes and which exquisitely participates in redox biology. As it turns out, selenium bears a U-shaped toxicity curve wherein too little of the nutrient present in biology leads to disorders; concentrations that are too great, on the other hand, pose toxicity to biological systems. In light of many excellent previous reviews and the corpus of literature, we wanted to offer this current review, in which we present aspects of the clinical and biological literature and justify why we should further investigate Se-containing species in biological and medicinal contexts, especially small molecule-containing species in biomedical research and clinical medicine. Of central interest is how selenium participates in biological signaling pathways. Several clinical medical cases are recounted; these reports are mainly pertinent to human cancer and changes in pathology and cases in which the patients are often terminal. Selenium was an option chosen in light of earlier chemotherapeutic treatment courses which lost their effectiveness. We describe apoptosis, and also ferroptosis, and senescence clearly in the context of selenium. Other contemporary issues in research also compelled us to form this review: issues with CoV-2 SARS infection which abound in the literature, and we described findings with human patients in this context. Laboratory scientific studies and clinical studies dealing with two main divisions of selenium, organic (e.g., methyl selenol) or inorganic selenium (e.g., sodium selenite), are discussed. The future seems bright with the research and clinical possibilities of selenium as a trace element, whose recent experimental clinical treatments have so far involved dosing simply and inexpensively over a set of days, amounts, and time intervals.


Age-related differences in the error-related negativity and error positivity in children and adolescents are moderated by sample and methodological characteristics: A meta-analysis.
The error-related negativity (ERN) and the error positivity (Pe) are electrophysiological components associated with error processing that are thought to exhibit distinctive developmental trajectories from childhood to adulthood. To investigate the age and age moderation effects on the ERN and the Pe strength during development, we conducted a preregistered three-level meta-analysis synthesizing 120 and 41 effect sizes across 18 group comparison studies and 19 correlational studies, respectively. The meta-analysis included studies with mean age between 3.6 and 28.7 (min-max age range: 3.5 and 49.8) years for age-group comparisons and 6.1 to 18.7 (min-max age range: 4.0-35.7) years for age correlations. Results showed that age was associated with a more negative ERN (SMD = -.433, r = -.230). No statistically significant association between age and the Pe was found (SMD = .059, r = -.091), except for in a group comparison between younger and older adolescents. The age effects were not significantly moderated by whether a Flanker or a Go/No-Go task was used, whereas a probabilistic learning task moderated the age effect on the Pe. Moreover, the Fz and Cz electrode sites yielded stronger negative associations between age and the ERN and the Pe, respectively. The results confirm that the ERN and the Pe show differential development courses and suggest that sample and methodological characteristics influence the age effects, and lay the foundation for investigations of developmental patterns of the ERN and the Pe in relation to psychopathology and early genetic and environmental risk factors.


Expression and prognostic value of tumor stem cell markers ALDH1 and CD133 in colorectal carcinoma.
The identification of cancer stem cells (CSCs) has improved the understanding of tumor occurrence and development. According to CSC theory, colorectal carcinoma (CRC) may be derived from these few cells. Thus, markers for CSCs may lead to the identification of CSCs and investigation of the correlation with various clinicopathological features and survival time in human CRC patients. Aldehyde dehydrogenase 1 (ALDH1) and CD133 (also known as Prominin-1 or AC133) were involved in the current study. The aim of the present study was to identify CSCs through markers of CSCs and to explore the value of the CSC markers, ALDH1 and CD133, in human CRC. The correlation between ALDH1 and CD133 protein expression and the various clinicopathological parameters were investigated through immunohistochemistry (IHC). In addition, the Kaplan-Meier method was used to estimate patients' overall survival. Correlation of the survival differences between ALDH1- or CD133-positive expression and negative controls was analyzed by the log-rank test. Furthermore, the correlation between the expression of ALDH1 and CD133 was assessed by Spearman's rank correlation. A marked correlation between the differentiation degree and expression of ALDH1 in tumor cells was demonstrated, but not with CD133 expression. In addition, it was demonstrated that low-stage tumors exhibit a higher expression of ALDH1 or CD133 staining compared with high-stage tumors. Meanwhile, CD133 expression was associated with lymph node metastasis-positive cases, but ALDH1 expression was not. Furthermore, compared with negative cases, ALDH1-positive patients exhibited a poor prognosis. However, no significant difference was identified between CD133-positive and -negative cases in terms of survival time. Overall, the results of the present study indicated that ALDH1 and CD133 may serve as useful markers of CSC to predict disease prognosis and clinicopathological characteristics of human CRC.


Emergency care for people with epilepsy.
Epilepsy affects 1% of the UK population, with 40% of people with epilepsy having two or more seizures a year. One in five people who have epilepsy visits a hospital emergency department (ED) each year and three out of five do so more than once.


Detection of enzootic babesiosis in baboons (Papio cynocephalus) and phylogenetic evidence supporting synonymy of the genera Entopolypoides and Babesia.
Blood smear evaluation of two baboons (Papio cynocephalus) experiencing acute hemolytic crises following experimental stem cell transplantation revealed numerous intraerythrocytic organisms typical of the genus Babesia. Both animals had received whole-blood transfusions from two baboon donors, one of which was subsequently found to display rare trophozoites of Entopolypoides macaci. An investigation was then undertaken to determine the prevalence of hematozoa in baboons held in our primate colony and to determine the relationship, if any, between the involved species. Analysis of thick and thin blood films from 65 healthy baboons (23 originating from our breeding facility, 26 originating from an out-of-state breeding facility, and 16 imported from Africa) for hematozoa revealed rare E. macaci parasites in 31%, with respective prevalences of 39, 35, and 12%. Phylogenetic analysis of nuclear small-subunit rRNA gene sequences amplified from peripheral blood of a baboon chronically infected with E. macaci demonstrated this parasite to be most closely related to Babesia microti (97.9% sequence similarity); sera from infected animals did not react in indirect fluorescent-antibody tests with Babesia microti antigen, however, suggesting that they represent different species. These results support an emerging view that the genus Entopolypoides Mayer 1933 is synonymous with that of the genus Babesia Starcovici 1893 and that the morphological variation noted among intracellular forms is a function of alteration in host immune status. The presence of an underrecognized, but highly enzootic, Babesia sp. in baboons may result in substantial, unanticipated impact on research programs. The similarity of this parasite to the known human pathogen B. microti may also pose risks to humans undergoing xenotransplantation, mandating effective screening of donor animals.


Leptin knockout attenuates hypoxia-induced pulmonary arterial hypertension by inhibiting proliferation of pulmonary arterial smooth muscle cells.
Pulmonary arterial hypertension (PAH) is a fatal disease characterized by excessive vascular smooth muscle cells proliferation in small pulmonary arteries, leading to elevation of pulmonary vascular resistance with consequent right ventricular (RV) failure and death. Recently, emerging evidence has shown that leptin signaling is involved in different cardiac pathologies; however, the role of leptin remains limited in the setting of PAH. Thus, in this study, we tested the hypothesis of direct involvement of leptin in the development of PAH. Our data show that leptin activity in plasma and protein level in the lung were higher in hypoxia- and monocrotaline-induced PAH models compared with control animals. Wild-type (WT) and C57BL/6J-Lep(ob) (ob/ob) male mice were exposed to normobaric hypoxia (10% O(2)) or normoxia (21% O(2)). After 2 and 4 weeks of chronic hypoxia exposure, WT mice developed PAH as reflected by the increased values of RV systolic pressure, RV hypertrophy index, the medial wall thickness of pulmonary arterioles, and muscularization of pulmonary arterioles. And, all these alterations were attenuated in ob/ob mice treated with hypoxia. Leptin could stimulate the proliferation of pulmonary arterial smooth muscle cells (PASMCs) by activating extracellular signal-regulated kinase (ERK), signal transducer and activator of transcription 3 (STAT3), and Akt pathways. These data suggest that the leptin signaling pathway is crucial for the development of PAH. Leptin activates ERK, STAT, and Akt pathways and subsequently PASMCs proliferation, providing new mechanistic information about hypoxia-induced PAH.


MicroRNA-155 Downregulation Promotes Cell Cycle Arrest and Apoptosis in Diffuse Large B-Cell Lymphoma.
Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin's lymphoma in the adult population, and treatment of DLBCL is still unfavorable. Therefore, there is an urgent requirement to investigate the molecular mechanisms underlying DLBCL tumorigenesis. To study the potential function of microRNA-155 (miR-155) involved in the regulation of lymphoma, we monitored lymphoma cell behavior including proliferation, cell cycle, and apoptosis using CCK-8 and flow cytometry analysis. Real-time PCR was used to detect the expression levels of miR-155 in 118 lymphoma patients' tissues, and Western blot was also used to analyze the expression level of proteins correlated with cell cycle and apoptosis in lymphoma cells. miR-155 expression levels were higher in lymphoma tissues compared with adjacent tissues. Downregulation of miR-155 inhibited lymphoma cell progress by arresting cell cycle in the G0/G1 phase and promoting apoptosis. Cell cycle-correlated proteins (cyclin B1, cyclin D1, and CDK4) were inhibited by downregulation of miR-155. Apoptosis-correlated proteins level (Bax/Bcl-2 and caspase 3 activity) were increased by downregulation of miR-155. In addition, a significant inverse correlation between the level of miR-155 and transforming growth factor-β receptor 2 (TGFBR2) was observed, which has been demonstrated to be a novel tumor suppressor gene. A further in vivo tumor formation study in nude mice indicated that downregulation of miR-155 in lymphoma cells delayed the progress of tumor formation. These findings indicate that miR-155 may serve as a useful potential target for the treatment of lymphoma.


Implications for maintaining vascular access device patency and performance: Application of science to practice.
Vascular access devices are commonly inserted devices that facilitate the administration of fluids and drugs, as well as blood sampling. Despite their common use in clinical settings, these devices are prone to occlusion and failure, requiring replacement and exposing the patient to ongoing discomfort/pain, local vessel inflammation and risk of infection. A range of insertion and maintenance strategies are employed to optimize device performance; however, the evidence base for many of these mechanisms is limited and the mechanisms contributing to the failure of these devices are largely unknown. (1) To revisit existing understanding of blood, vessel physiology and biological fluid dynamics; (2) develop an understanding of the implications that different clinical practices have on vessel health, and (3) apply these understandings to vascular access device research and practice. Narrative review of biomedical and bioengineering studies related to vascular access practice. Current vascular access device insertion and maintenance practice and policy are variable with limited clinical evidence to support the theoretical assumptions underpinning these regimens. This review demonstrates the physiological response to vascular access device insertion, flushing and infusion on the vein, blood components and blood flow. These appear to be associated with changes in intravascular fluid dynamics. Variable forces are at play that impact blood componentry and the endothelium. These may explain the mechanisms contributing to vascular access failure. This review provides an update to our current knowledge and understanding of vascular physiology and the hemodynamic response, challenging some previously held assumptions regarding vascular access device maintenance, which require further investigation.


A case of reversible hypoparathyroidism in a patient with Riedel's thyroiditis treated with glucocorticoids.
A 48-year-old woman with a history of primary hypothyroidism, presented with compressive symptoms secondary to a rapid enlargement of a preexisting goiter. She had no clinical signs of hypocalcemia. Biological tests revealed hypoparathyroidism. Cervicothoracic computed tomography scan showed a heterogeneous compressive goiter. The patient was treated with levothyroxine, calcium, and alfacalcidol. A total thyroidectomy was not performed because of the hard adhesion to neighboring structures. Histopathological examination of the thyroid biopsy was consistent with the diagnosis of Riedel's thyroiditis (RT). The patient was treated with glucocorticoids. The outcome was marked by the resolution of compressive symptoms and the decrease of the thyroid gland volume. Serum calcium and parathyroid hormone levels reached normal ranges after the discontinuation of vitaminocalcic supplementation. Hypoparathyroidism may be clinically asymptomatic in a patient with RT as in our case. Early administration of glucocorticoids may be effective in reducing the fibrosclerotic process and lead to the recovery of parathyroid dysfunction.


Photolabile precursors of cyclic nucleotides with high aqueous solubility and stability.
Photolabile phosphotriester derivatives of cyclic AMP and cyclic GMP are described, where the additional group on the phosphate is a 2-nitrobenzyl that bears an electron-withdrawing and dianionic substituent. This confers high aqueous solubility and excellent resistance to hydrolysis of the phosphotriester (t(1/2) for hydrolysis at pH 7, 22 degrees C, is >3 months for the axial isomers 3a and 4a and >1 month for the equatorial isomers 3b and 4b). The photolysis quantum yields are in the range 0.15-0.24, and the product release rate upon flash photolysis is 1.7 s(-1) at pH 7.0, 20 degrees C.


Clock-Bmal1 mediates MMP9 induction in acrolein-promoted atherosclerosis associated with gut microbiota regulation.
Circadian rhythm is believed to play important roles in atherosclerosis. The gut microbiota is found to be closely related to atherogenesis, and shows compositional and functional circadian oscillation. However, it's still unclarified whether circadian clock and intestinal microbiota are involved in the progression of atherosclerosis induced by environmental pollutant acrolein. Herein, patients with atherosclerosis showed higher MMP9, a promising biomarker for atherosclerosis, and lower Bmal1 and Clock expression in the plasma. Interestingly, acrolein exposure contributed to the increased MMP9, decreased Clock and Bmal1, and activated MAPK pathways in human umbilical vein endothelial cells (HUVECs). We found that knockdown of Clock or Bmal1 lead to upregulation of MMP9 in HUVECs, and that Clock and Bmal1 expression was elevated while MAPK pathways were blocked. Atherosclerotic apolipoproteinE-deficient mice consumed a high-fat diet were used and treated with acrolein (3 mg/kg/day) in the drinking water for 12 weeks. Upregulation of MMP9, and downregulation of Clock and Bmal1 were also observed in plasma of the mice. Besides, acrolein feeding altered gut microbiota composition at a phylum level especially for an increased Firmicutes and a decreased Bacteroidetes. Additionally, gut microbiota showed correlation with atherosclerotic plaque, MMP9 and Bmal1 levels. Therefore, our findings indicated that acrolein increased the expression of MMP9 through MAPK regulating circadian clock, which was associated with gut microbiota regulation in atherosclerosis. Circadian rhythms and gut microbiota might be promising targets in the prevention of cardiovascular disease caused by environmental pollutants.


Epidemiological patterns of cervical human papillomavirus infection among women presenting for cervical cancer screening in North-Eastern Nigeria.
Sub-Saharan countries including Nigeria have the highest burden of Human Papillomavirus (HPV) infection in the world. Most studies on HPV surveillance in Nigeria were done in the southern part of the country. Geographical and socio-cultural diversity of Nigeria makes these data unlikely to be universally representative for the entire country. Northern Nigeria especially the North-East carries a higher prevalence of cervical cancer and many of its risk factors. The region may be harbouring a higher prevalence of HPV infection with a possibility of different genotypic distribution. This study was carried out to determine the burden and confirm the predominant HPV genotypes among women presenting for cervical cancer screening at the Federal Teaching Hospital Gombe (FTHG), North-eastern, Nigeria. The study was an observational hospital based cross sectional study among women who presented for cervical cancer screening in FTHG. A total of 209 consenting women were tested for cervical HPV infection using PCR. DNA sequencing was carried out on positive samples to determine the prevalent HPV genotypes. The prevalence of cervical HPV infection among the participants with mean age of 39.6 ± 10.4 years was 48.1 %. The five most predominant genotypes were 18, 16, 33, 31 and 35, with prevalence of 44.7 %, 13.2 %, 7.9 %, 5.3 % and 5.3 % respectively. Other genotypes observed were 38, 45, 56, 58, 82 and KC5. Multiple HPV infections were detected among 7.9 % of participants. Risk factors such as level of education (X (2) = 15.897; p = 0.007), age at sexual debut (X (2) = 6.916; p = 0.009), parity (X (2) = 23.767; p = 0.000), number of life time sexual partners (X (2) = 7.805; p = 0.005), age at first pregnancy (X (2) = 10.554; p = 0.005) and history of other malignancies (X (2) = 7.325; p = 0.007) were found to have a statistically significant association with HPV infection. This study identified a high burden of HPV infection in Northern Nigeria while also confirming HPV 18 and 16 as the most predominant genotypes. It further justifies the potential benefit of the currently available HPV vaccines in the area. A larger and community based study is however recommended for better representation of the area.