Evidence for recent intergeneric transfer of a new tetracycline resistance gene, tet(W), isolated from Butyrivibrio fibrisolvens, and the occurrence of tet(O) in ruminal bacteria.
We have previously reported high-frequency transfer of tetracycline resistance between strains of the rumen anaerobic bacterium Butyrivibrio fibrisolvens. Donor strains were postulated to carry two TcR genes, one of which is transferred on a novel chromosomal element. It is shown here that coding sequences within the non-transmissible gene in B. fibrisolvens 1.230 are identical to those of the Streptococcus pneumoniae tet(O) gene. This provides the first evidence for genetic exchange between facultatively anaerobic bacteria and rumen obligate anaerobes. In contrast, the product of the transmissible TcR gene shares only 68% amino acid sequence identity with the TetO and TetM proteins and represents a new class of ribosome protection tetracycline resistance determinant, designated Tet W. The tet(W) coding region shows a higher DNA G + C content (53%) than other B. fibrisolvens genes or other ribosome protection-type tet genes, suggesting recent acquisition from a high G + C content genome. Tet(W) genes with almost identical sequences are also shown to be present in TcR strains of B. fibrisolvens from Australian sheep and in TcR strains of two other genera of rumen obligate anaerobes, Selenomonas ruminantium and Mitsuokella multiacidus. This provides compelling evidence for recent intergeneric transfer of resistance genes between ruminal bacteria. Tet(W) is not restricted to ruminal bacteria, as it was also present in a porcine strain of M. multiacidus.


Audio-visual speech perception in schizophrenia: an fMRI study.
Abnormalities in the integration of auditory and visual language inputs could underlie many core psychotic features. Perceptual confusion may arise because of the normal propensity of visual speech perception to evoke auditory percepts. Recent functional neuroimaging studies of normal subjects have demonstrated activation in auditory-linguistic brain areas in response to silent lip-reading. Three functional magnetic resonance imaging experiments were carried out on seven normal volunteers, and 14 schizophrenia patients, half of whom were actively psychotic. The tasks involved listening to auditory speech, silent lip-reading (visual speech), and perception of meaningless lip movements (visual non-speech). Subjects also undertook a behavioural study of audio-visual word identification designed to evoke perceptual fusions. Patients and controls both showed susceptibility to audio-visual fusions on the behavioural task. The patient group as a whole showed less activation relative to controls in superior and inferior posterior temporal areas while performing the silent lip-reading task. Attending to visual non-speech, the patients activated less posterior (occipito-temporal) and more anterior (frontal, insular and striatal) brain areas than controls. This difference was accounted for largely by the psychotic subgroup. Insular and striatal areas were also activated in both subject groups in the auditory speech perception condition, thus demonstrating the bimodal sensitivity of these regions. The results suggest that schizophrenia patients with psychotic symptoms respond to visually ambiguous stimuli (non-speech) by activation of polysensory structures. This could reflect particular processing strategies and may increase susceptibility to certain paranoid and hallucinatory symptoms.


[Antiphospholipid syndrome. The use of transesophageal echocardiography].
Antiphospholipid syndrome (APS) is defined by the presence of arterial and venous thromboses, recurrent fetal death, cerebrovascular accidents, hemolytic anaemia, thrombocytopenia and various other manifestations in different organs. APS is a clinical entity that can appear commonly alongside systemic lupus erithemathous on it can occur as a primary disease. The syndrome is defined by the presence of antiphospholipid antibodies in serum, a group of immunoglobulins (IgG, IgM, IgA or an mixture of them) that adopt an hexagonal configuration when they are incubated at 37grades C. In APS, it is rather common to find cardiac lesions such as non-verrucous endocarditis, valvular lesions (especially of the mitral valve), microvascular cardiac disease and more risk of thrombosis at this level, myxomas that could be the cause of a systemic inflammation in relation to the production of antiphospholipid antibodies, intracardiac thrombii and congenital heart disease. We present the case of a woman with APS associated with interauricular communication whose initial diagnosis were pulmonary thromboembolism and cerebrovascular stroke. We were able to diagnose the cardiac abnormality by the use of transesophagic echocardiography. We propose the use of this imaging technique for patients with APS even though the transthoracic Doppler echocardiography was found to be normal. In this way we will be able to rule out cardiac lesions which could also be the cause of embolic manifestations.


Prognostic and predictive value of the Immunoscore in stage III colon cancer patients treated with oxaliplatin in the prospective IDEA France PRODIGE-GERCOR cohort study.
The Immunoscore (IS), which prognostically classifies stage I-III colon cancer (CC) patients, was evaluated in the International Duration Evaluation of Adjuvant Therapy (IDEA) France cohort study investigating 3 versus 6 months of oxaliplatin-based adjuvant chemotherapy in stage III CC patients. Densities of CD3+ and CD8+ T cells in the tumor and invasive margin were determined by immunohistochemistry, quantified by digital pathology, and converted to IS. Mismatch repair status was determined by immunohistochemistry or by pentaplex PCR. Prediction of disease-free survival (DFS) by IS was analyzed by a multivariable Cox regression model in each study arm. Harrell's C-statistics were used to investigate the IS performance. Samples of 1322 patients were available. IS Low, Intermediate (Int), and High were observed in 43.6%, 47.0%, and 9.4% of patients, respectively. IS Low identified patients at higher risk of relapse or death compared with Int + High [hazard ratio (HR) = 1.54; 95% confidence interval (CI) 1.24-1.93, P = 0.0001]. The 3-year DFS was 66.80% (95% CI 62.23-70.94) for IS Low and 77.14% (95% CI 73.50-80.35) for IS Int + High. In multivariable analysis, IS remained significantly independently associated with DFS (P = 0.003) when adjusted for sex, histological grade, T/N stage, and microsatellite instability. For mFOLFOX6-treated patients (91.6% of the cohort), a statistical significant interaction was observed for the predictive value of IS for treatment duration (3 versus 6 months) in terms of DFS (P = 0.057). IS Int + High significantly predicted benefit of 6 months of treatment (HR = 0.53; 95% CI 0.37-0.75; P = 0.0004), including clinically low- and high-risk stage III CC (all P < 0.001). Conversely, patients with IS Low (46.4%) did not significantly benefit from the 6-month mFOLFOX6 versus the 3-month mFOLFOX6. The prognostic value of IS for DFS was confirmed in patients with stage III CC treated with oxaliplatin-based chemotherapy. Its predictive value for DFS benefit of longer duration of mFOLFOX6 adjuvant treatment was found in IS Int + High. These results will be validated in an external independent cohort. CLINICALTRIALS. NCT03422601; EudraCT Number: 2009-010384-16.


Development of visual system - comparison of monkey and man.
In Golgi preparations of the lateral geniculate nucleus of adult humans and monkeys several types of neuron are described. Multipolar neurons have a "radiate" or "tufted" dendritic arbor. The next commonest class is the bipolar neuron with two or three thick dendrites arising from opposite poles of the soma. A few examples of rare medium-sized neurons with beaded dendrites are found. There are also small neurons with fine "axon-like" dendritic processes. Some have long, untapered dendrites and others shorter dendritic arbors. A class of large, capsular neurons is found in the circumgeniculate capsule. Maturation of lateral geniculate nucleus neurons in baby humans and monkeys was studied in Golgi preparations. They pass through post-natal stages characterised by dendritic growth cones and a profusion of spine-like protuberances on dendrites and somata. The mature form is found by the second month in monkey and about one year in man. The morphological changes in the thalamus are paralleled by synaptogenesis in the visual cortex. In man synaptic density reaches a maximum at about one year of age, declines later in childhood and stabilises at adult levels by about 11 years of age. In both monkey and man the period of morphological maturation in the visual pathways corresponds to a time of increasing visual acuity when visual deprivation is most likely to have permanent harmful effects.


Selective bundle reconstruction in partial ACL tears leads to excellent long-term functional outcomes and a low percentage of failures.
The optimal treatment of partial anterior cruciate ligament (ACL) tears continues to be debatable. Short-term results of selective bundle reconstruction have already been widely shown. The purpose of this study was to assess functional outcomes, subjective satisfaction and the failure rate of selective bundle reconstructions for partial ACL tears over a five to nine year follow-up period. Patients who underwent ACL selective bundle reconstruction between October 2008 and October 2012 were studied. Functional assessment was performed with the objective International Knee Documentation Committee (IKDC) ligament evaluation form, the Lysholm knee scale and the Tegner activity level scale. Cumulative failure and level of satisfaction have also been investigated. Seventy-six patients were included. The average follow-up period was 85 months (range 65-110). Thirty-four had AMB tear and 42 had PLB tears. An overall statistically significant improvement (p < 0.001) was obtained in terms of the subjective IKDC and the Lysholm questionnaire between preoperative and last follow-up. The same or no more than one level lower Tegner score was restored in 97.3% of the cases. Cumulative failure was observed in two patients (2.6%). Dissatisfied patient percentage was 15% (4/76). Selective bundle reconstruction in partial ACL tears leads to excellent long-term functional outcomes, a low percentage of failures and a high degree of subjective satisfaction in patients. Therapeutic case series; level 4.


The intracellular region of Notch ligands Dll1 and Dll3 regulates their trafficking and signaling activity.
Genetic studies have shown that ubiquitination and endocytosis of the Drosophila ligand Delta in signal-sending cells are required for activation of Notch signaling, but how these events promote Notch activation remains poorly understood. Here, we show that an ubiquitination-defective mutant of the murine Delta-homologue Dll1 is endocytosed but, in contrast to the wild-type Dll1, is unable to subsequently recycle back to the cell surface or to bind Notch1 efficiently. These results demonstrate that ubiquitination, although not required for endocytosis, is essential for Dll1 recycling and that recycling is required to acquire affinity for the receptor. On the other hand, a chimeric molecule encompassing the extracellular domain of Dll1 and the transmembrane/intracellular domain of Dll3, which contains no lysine, is endocytosed, recycled, and interacts with Notch1 but is unable to induce transendocytosis of the extracellular region of Notch1 or to signal. These observations suggest that the chimera uses an ubiquitination-independent signal to recycle, allowing it to acquire affinity for Notch1. Our results support the idea that ligand recycling determines its competence to bind efficiently to the receptor but that this is insufficient to allow it to perform transendocytosis, an event required for activation of Notch signaling. Finally, the present study indicates that Dll1 partially localizes to lipid microdomains, whereas both ubiquitination-defective Dll1 and the Dll1-3 chimera are excluded from these compartments, suggesting that these microdomains provide the environment necessary for Dll1 to activate Notch signaling.


Diet and colorectal cancer mortality: results from the Japan Collaborative Cohort Study.
The relationship between diet and colorectal cancer mortality was analyzed in a prospective study of 45,181 men and 62,643 women aged 40-79 yr enrolled in the Japan Collaborative Cohort Study. Between 1988 and 1990, subjects completed a self-administered questionnaire on their sociodemographic characteristics, diet, and other lifestyle habits. During the follow-up period (average 9.9 yr), 284 colon cancer deaths (138 men and 146 women) and 173 rectal cancer deaths (116 men and 57 women) were confirmed. The only significant association of colorectal cancer mortality with vegetable intake was observed between male rectal cancer mortality and green leafy vegetable consumption [hazard ratio (HR) using Cox proportional hazard models = 0.6; 95% confidence interval (CI) = 0.3-0.9; P for trend = 0.02]. Yogurt intake was also inversely associated with male rectal cancer mortality (HR = 0.5; 95% CI = 0.2-1.0; P for trend = 0.04). Egg consumption was positively associated with male colon cancer mortality (P for trend = 0.04). Women with high fruit consumption had increased colon cancer mortality (HR = 1.6; 95% CI = 1.0-2.6; P for trend = 0.04). It should be noted that this study lacked statistical power due to small sample size and measurement error in the food-frequency questionnaire. Further investigation is therefore necessary to confirm the association between diet and colorectal cancer, especially by subsites and gender.


To let go or not to let go: how ParA can impact the release of the chromosomal anchoring in Caulobacter crescentus.
Chromosomal maintenance is vital for the survival of bacteria. In Caulobacter crescentus, chromosome replication initiates at ori and segregation is delayed until the nearby centromere-like region parS is replicated. Our understanding of how this sequence of events is regulated remains limited. The segregation of parS has been shown to involve multiple steps including polar release from anchoring protein PopZ, slow movement and fast ParA-dependent movement to the opposite cell pole. In this study, we demonstrate that ParA's competing attractions from PopZ and from DNA are critical for segregation of parS. Interfering with this balance of attractions-by expressing a variant ParA-R195E unable to bind DNA and thus favoring interactions exclusively between ParA-PopZ-results in cell death. Our data revealed that ParA-R195E's sole interactions with PopZ obstruct PopZ's ability to release the polar anchoring of parS, resulting in cells with multiple parS loci fixed at one cell pole. We show that the inability to separate and segregate multiple parS loci from the pole is specifically dependent on the interaction between ParA and PopZ. Collectively, our results reveal that the initial steps in chromosome segregation are highly regulated.


Expansion of human midbrain floor plate progenitors from induced pluripotent stem cells increases dopaminergic neuron differentiation potential.
Human induced pluripotent stem cells (hiPSCs) are invaluable to study developmental processes and disease mechanisms particularly in the brain. hiPSCs can be differentiated into mature and functional dopaminergic (DA) neurons. Having robust protocols for the generation of differentiated DA neurons from pluripotent cells is a prerequisite for the use of hiPSCs to study disease mechanisms, for drug discovery, and eventually for cell replacement therapy. Here, we describe a protocol for generating and expanding large numbers of homogeneous midbrain floor plate progenitors (mFPPs) that retain efficient DA neurogenic potential over multiple passages and can be cryobanked. We demonstrate that expanded mFPPs have increased DA neuron potential and differentiate more efficiently and rapidly than progenitors generated by standard protocols. In addition, this novel method results in increased numbers of DA neurons that in vitro show characteristic electrophysiological properties of nigrostriatal DA neurons, produce high levels of dopamine, and integrate into host mice when grafted in vivo. Thus, we describe a robust method for producing human mesencephalic DA neurons from hiPSCs.


Influence of arsenate and arsenite on signal transduction pathways: an update.
Arsenic has been a recognized contaminant and toxicant, as well as a medicinal compound throughout human history. Populations throughout the world are exposed to arsenic and these exposures have been associated with a number of human cancers. Not much is known about the role of arsenic as a human carcinogen and more recently its role in non-cancerous diseases, such as cardiovascular disease, hypertension and diabetes mellitus have been uncovered. The health effects associated with arsenic are numerous and the association between arsenic exposure and human disease has intensified the search for molecular mechanisms that describe the biological activity of arsenic in humans and leads to the aforementioned disease states. Arsenic poses a human health risk due in part to the regulation of cellular signal transduction pathways and over the last few decades, some cellular mechanisms that account for arsenic toxicity, as well as, signal transduction pathways have been discovered. However, given the ubiquitous nature of arsenic in the environment, making sense of all the data remains a challenge. This review will focus on our knowledge of signal transduction pathways that are regulated by arsenic.


Multi-scale Gaussian representation and outline-learning based cell image segmentation.
High-throughput genome-wide screening to study gene-specific functions, e.g. for drug discovery, demands fast automated image analysis methods to assist in unraveling the full potential of such studies. Image segmentation is typically at the forefront of such analysis as the performance of the subsequent steps, for example, cell classification, cell tracking etc., often relies on the results of segmentation. We present a cell cytoplasm segmentation framework which first separates cell cytoplasm from image background using novel approach of image enhancement and coefficient of variation of multi-scale Gaussian scale-space representation. A novel outline-learning based classification method is developed using regularized logistic regression with embedded feature selection which classifies image pixels as outline/non-outline to give cytoplasm outlines. Refinement of the detected outlines to separate cells from each other is performed in a post-processing step where the nuclei segmentation is used as contextual information. We evaluate the proposed segmentation methodology using two challenging test cases, presenting images with completely different characteristics, with cells of varying size, shape, texture and degrees of overlap. The feature selection and classification framework for outline detection produces very simple sparse models which use only a small subset of the large, generic feature set, that is, only 7 and 5 features for the two cases. Quantitative comparison of the results for the two test cases against state-of-the-art methods show that our methodology outperforms them with an increase of 4-9% in segmentation accuracy with maximum accuracy of 93%. Finally, the results obtained for diverse datasets demonstrate that our framework not only produces accurate segmentation but also generalizes well to different segmentation tasks.


Allergic conditions and brain tumor risk.
An inverse association between allergic conditions and glioma risk has been reported previously. In this large population-based case-control study, the authors identified cases diagnosed with glioma or meningioma in Denmark, Norway, Finland, Sweden, and southeast England between 2000 and 2004. Detailed information on self-reported physician-diagnosed allergic conditions was collected from 1,527 glioma cases, 1,210 meningioma cases, and 3,309 randomly selected controls. Logistic regression showed an odds ratio of 0.70 (95% confidence interval: 0.61, 0.80) for glioma associated with a diagnosis of any of asthma, hay fever, eczema, or other type of allergy. The risk estimates for glioma were around 0.65 for each allergic condition (asthma, eczema, hay fever, and food allergy), and the 95% confidence intervals were equally consistent, at around 0.55, 0.80. The reduced risks of glioma related to eczema, hay fever, and allergy overall, but not asthma, were confined to current rather than past conditions. Meningioma risk was not associated with allergic conditions, except for eczema (odds ratio = 0.74, 95% confidence interval: 0.60, 0.91). Our results show a reduced risk for glioma associated primarily with current allergic conditions. If this is etiologic, it has implications for the understanding of how allergic conditions might reduce the tumor risk.


[Nucleotide control of ionic transport and ATP synthesis in mitochondria].
It was demonstrated that under certain experimental conditions the P/O ratio of oleate-treated mitochondria in hypotonic media at low pH values is sharply decreased irrespective of high ADP/O values. This is probably due to a drastic fall in the ionic permeability of membranes induced by ADP. The effect observed is due to ADP (ATP) interaction with nucleotide translocase, since atractyloside eliminates the effect of ADP on the ionic permeability. It was demonstrated that nucleotide translocase is immediately involved in regulation of the functioning of the oxidative phosphorylation system of mitochondria.


Prospective evaluation of renal allograft dysfunction with 99mtechnetium-diethylenetriaminepentaacetic acid renal scans.
A prospective, single-blinded study was done to determine the ability of serial 99mtechnetium-diethylenetriaminepentaacetic acid scans to diagnose renal allograft rejection. Among 28 transplant recipients 111 renal scans were obtained 1 day postoperatively and every 3 to 4 days thereafter for 3 weeks in all patients retaining an allograft. Computer-generated time-activity blood flow curves were analyzed semiquantitatively for the 1) interval between curve peaks of the allograft and iliac artery, 2) renal transit time and 3) renal washout of radionuclide. Excretory function was assessed by degree and interval to appearance of radionuclide in the calices and bladder. Deterioration of renal blood flow and excretion compared to the initial scan was considered rejection. Of 52 scans performed during clinical rejection 47 (90.4 per cent) were interpreted as showing rejection (sensitivity). Of 53 scans interpreted as showing rejection 47 (88.7 per cent) were positive for clinical rejection. The remaining 6 patients (initial false positive results) suffered clinical rejection within 24 to 72 hours. We conclude that 99mtechnetium-diethylenetriaminepentaacetic acid renal scans are useful in the differential diagnosis of renal allograft dysfunction.


Elimination of beta-hexachlorocyclohexane in occupationally exposed persons.
The elimination of beta-hexachlorocyclohexane (beta-HCH) in humans was investigated in a group of 40 former workers of a lindane-producing plant by analyzing at least 2 blood specimens (3 specimens in 3 workers) from different time points. Assuming a first-order kinetic model for excretion, the median half-life of beta-HCH is 7.2 yr calculated by concentrations in whole blood and 7.6 yr calculated by concentrations in extractable lipids. In univariate analyses an influence of age, percent body fat, and liver disease (additionally in whole blood an influence of contents of extractable lipids) on clearance was observed. All factors show a positive correlation with half-life. According to a multiple regression model, influence of percent body fat calculated according to Deurenberg et al. (1991) is an important covariate in the description of the variations of the clearance rate (calculated on the basis of extractable lipids) of beta-HCH. The data support the assumption of first-order kinetics.


Hypervalence in monoxides and dioxides of superalkali clusters.
F2Li3, a superalkali cluster, is characterized as having a lower adiabatic ionization energy than its elemental alkali counterpart and, coupled with the presence of complex molecular orbitals, suggests promise for novel bonding possibilities. CBS-QB3 composite method was used to study three distinct cluster isomers, as well as their cationic (+1) and anionic (-1) species, to identify energetic trends and observe geometric changes. Oxides were then generated from these clusters, of which three distinct monoxides and nine dioxides were obtained upon structure optimization. Identical calculations were performed for the oxide species and their charged counterparts. Some of the most stable oxides produced appear to possess hypervalent lithium and oxygen atoms, forming unique structures with exceptional stability.


Neutralization of mouse xenotropic virus by lipoproteins involves binding to the virions.
We examined the properties of the mouse serum lipoprotein responsible for specific neutralization of the endogenous mouse xenotropic (X-tropic) type C retrovirus. The anti-X-tropic virus activity of the mouse lipoprotein neutralizing factor (NF) could not be blocked by sugars or lectins. Moreover, neutralization did not involve rupture of the virion core. Sucrose density gradient analysis of X-tropic virus mixed with various lipoprotein preparations demonstrated that the binding of complete virions to NF is associated with the neutralization.


Can T1 mapping be an alternative of post-contrast magnetic resonance sequences in patients with surgically corrected tetralogy of Fallot?
The objective of this study is to investigate the ability of native T1 mapping in the determination of myocardial fibrosis in patients with surgically corrected tetralogy of Fallot (TOF). We included 35 patients with surgically corrected TOF who underwent cardiac magnetic resonance imaging in this study. Additionally, we added pre- and post-contrast T1 mapping sequences at the right ventricular outflow tract (RVOT) and short-axis planes to the routine protocol. We visually evaluated the pre-contrast native T1 mapping images to determine the presence of areas with higher T1 times that indicate focal fibrosis. We compared the findings with the findings of post-contrast images. In 22 of the 35 cases, RVOT enhancement was observed in the delayed enhancement images; however, none of these cases could be distinguished on the native T1 maps. When compared to post-contrast imaging, 28 of the 30 contrast enhancements at right ventricle insertion points and 14 of the 17 contrast enhancements at the remaining left ventricle walls were visually observed on the color-coded native T1 maps. The sensitivity, specificity, positive and negative predictive values of native T1 mapping for the detection of focal fibrosis at the right ventricle insertion points were found to be 93.3%, 100%, 100%, and 71.4%, respectively, whereas these values were found to be 82.4%, 100%, 100%, and 85.8% in the detection of fibrosis in the remaining left ventricle walls. Native T1 mapping is valuable in the detection of focal fibrosis at the right ventricle insertion points and the remaining left ventricle walls; however, it was not possible to visually detect RVOT fibrosis by native T1 mapping. Hence, T1 mapping may not replace the contrast-enhanced imaging in patients with surgically corrected TOF.


Comprehensive approach to the management and prevention of early childhood caries.
Dental caries is the most common disease of childhood that does not resolve spontaneously or respond to a course of antibiotic therapy. Tragically, children in Hawaii experience the highest incidence of tooth decay in the United States. This manuscript briefly explains the etiology of Early Childhood Caries (ECC), describes the consequences of this insidious disease process and outlines a comprehensive, multidisciplinary, preventive approach for Hawaii's health care providers.


Removal of polyvinylpyrrolidone from wastewater using different methods.
Polyvinylpyrrolidone (PVP) is a frequently used polymer in the pharmaceutical and foodstuff industries. Because it is not subject to metabolic changes and is virtually nondegradable, trace concentrations of PVP are often found in community wastewaters. The literature finds that the partial removal of PVP in wastewater treatment plants probably occurs through sorption. The primary objective of this study was to find an effective method to remove PVP from wastewaters. In this regard, the literature indicates the theoretical potential to use specific enzymes (e.g., gamma-lactamases, amidases) to gradually degrade PVP molecules. Polyvinylpyrrolidone biodegradability tests were conducted using suitable heterogeneous cultures (activated sludge) collected from a conventional wastewater treatment plant, treatment plants connected to a pharmaceutical factory, and using select enzymes. Aerobic biodegradation of PVP in a conventional wastewater environment was ineffective, even after adaptation of activated sludge using the nearly identical monomer 1-methyl-2-pyrrolidone. Another potential method for PVP removal involves pretreating the polymer prior to biological degradation. Based on the results (approximately 10 to 15% biodegradation), pretreatment was partially effective, realistically, it could only be applied with difficulty at wastewater treatment plants. Sorption of PVP to an active carbon sorbent (Chezacarb S), which corresponded to the Langmuir isotherm, and sorption to activated sludge, which corresponded to the Freundlich isotherm, were also evaluated. From these sorption tests, it can be concluded that the considerable adsorption of PVP to activated sludge occurred primarily at low PVP concentrations. Based on the test results, the authors recommend the following methods for PVP removal from wastewater: (1) sorption; (2) application of specific microorganisms; and (3) alkaline hydrolysis, which is the least suitable of the three for use in wastewater treatment plants.


[Parent's perception of vaccination].
The purpose of this study was to analyze the attitude and grade of knowledge of the parents of children concerning the vaccination of their children, as well as to know their opinion about a program destine to diminish their anxiety. The subjects of the study were parents of children of our county that began their immunizations in 1994. The method utilized was realization of a survey with closed questions. The statistical analysis was carried out by means of the R-SIGMA program. There were 115 surveys registered. Of these 71% has adequate knowledge of the illness against which their child had been vaccinated. Anxiety and fear was seen in 60% before beginning the vaccination process, descending to 30% once the process of immunization began. Only 54.5% perceived the vaccination as inoffensive and 66% considered that the illness against which their child was being protected were very grave. The principal secondary effect seen in the children was fever (70.4%). Forty-one percent of those surveyed considered that the illness of the vaccination program were typical of a low socioeconomic class. Only 7% gave an opinion that the vaccine should be voluntary and in 100% of the cases was it considered that it was an advance in medicine. Only 25% of the population surveyed had access to previous information and their attitude was reinforced positively. The data most valued by those surveyed, referring to the vaccination program, was the informative interview previous to the program and the presence of the pediatrician. The vaccine is considered as something dangerous, but necessary. Better education of the parents, on the part of the sanitary authorities and those responsible of ordering and administering vaccines, would result in a modification in the attitude of the population in regards to vaccinations.


Direct Measurements of Magnetic Polarons in Cd1-xMnxSe Nanocrystals from Resonant Photoluminescence.
In semiconductors, quantum confinement can greatly enhance the interaction between band carriers (electrons and holes) and dopant atoms. One manifestation of this enhancement is the increased stability of exciton magnetic polarons in magnetically doped nanostructures. In the limit of very strong 0D confinement that is realized in colloidal semiconductor nanocrystals, a single exciton can exert an effective exchange field Bex on the embedded magnetic dopants that exceeds several tesla. Here we use the very sensitive method of resonant photoluminescence (PL) to directly measure the presence and properties of exciton magnetic polarons in colloidal Cd1-xMnxSe nanocrystals. Despite small Mn2+ concentrations (x = 0.4-1.6%), large polaron binding energies up to ∼26 meV are observed at low temperatures via the substantial Stokes shift between the pump laser and the resonant PL maximum, indicating nearly complete alignment of all Mn2+ spins by Bex. Temperature and magnetic field-dependent studies reveal that Bex ≈ 10 T in these nanocrystals, in good agreement with theoretical estimates. Further, the emission line widths provide direct insight into the statistical fluctuations of the Mn2+ spins. These resonant PL studies provide detailed insight into collective magnetic phenomena, especially in lightly doped nanocrystals where conventional techniques such as nonresonant PL or time-resolved PL provide ambiguous results.


Sympathetic system in potassium homeostasis.
The extrarenal disposal of potassium was studied in nephrectomized and adrenalectomized rats by measuring the rise in serum potassium produced during an infusion of 3 meq KCl/kg over 90 min. Adrenalectomy alone did not alter the volume of distribution of infused potassium in nephrectomized animals. When nephrectomy and adrenalectomy were combined with either insulin deficiency produced by streptozotocin or chemical sympathectomy induced by injection of 6-hydroxydopamine, potassium tolerance was significantly impaired. Hyperkalemia produced in chemically sympathectomized animals by potassium infusion was minimized by simultaneous infusion of epinephrine, an effect blocked by the beta-antagonist propranolol but not by the alpha-blocker phenoxybenzamine. These results suggest that extra renal uptake of potassium, in addition to being influenced by insulin and circulating catecholamines, is modulated by peripheral sympathetic activity.


The pigtail macaque (Macaca nemestrina) model of COVID-19 reproduces diverse clinical outcomes and reveals new and complex signatures of disease.
The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 disease, has killed over five million people worldwide as of December 2021 with infections rising again due to the emergence of highly transmissible variants. Animal models that faithfully recapitulate human disease are critical for assessing SARS-CoV-2 viral and immune dynamics, for understanding mechanisms of disease, and for testing vaccines and therapeutics. Pigtail macaques (PTM, Macaca nemestrina) demonstrate a rapid and severe disease course when infected with simian immunodeficiency virus (SIV), including the development of severe cardiovascular symptoms that are pertinent to COVID-19 manifestations in humans. We thus proposed this species may likewise exhibit severe COVID-19 disease upon infection with SARS-CoV-2. Here, we extensively studied a cohort of SARS-CoV-2-infected PTM euthanized either 6- or 21-days after respiratory viral challenge. We show that PTM demonstrate largely mild-to-moderate COVID-19 disease. Pulmonary infiltrates were dominated by T cells, including CD4+ T cells that upregulate CD8 and express cytotoxic molecules, as well as virus-targeting T cells that were predominantly CD4+. We also noted increases in inflammatory and coagulation markers in blood, pulmonary pathologic lesions, and the development of neutralizing antibodies. Together, our data demonstrate that SARS-CoV-2 infection of PTM recapitulates important features of COVID-19 and reveals new immune and viral dynamics and thus may serve as a useful animal model for studying pathogenesis and testing vaccines and therapeutics.


An event-related fMRI study of implicit phrase-level syntactic and semantic processing.
Most neuroimaging studies of language function to date use a block-subtraction paradigm in which images acquired during relatively long periods of target stimuli are compared to those acquired during a control period. These studies typically require an overt response on the part of the subject, usually some type of discrimination or grammatical judgment by button press, or silent word generation. Results from studies of syntactic and semantic processing have generally been compatible with the classical correlation to Broca's area and Wernicke's area, respectively. Recently, functional magnetic resonance imaging (fMRI) studies departing from the block-subtraction paradigm in favor of event-related fMRI paradigms have been reported. We have extended the use of this approach to examine implicit (i.e., without an explicit task on the part of the subject) syntactic and semantic processing at the phrasal level, using visually presented verb phrases. Left BA 44 is more strongly activated for the syntactic condition than the semantic condition. BA 45, 10, and 46 show laterality differences: mostly left-lateralized for the syntactic condition and right-lateralized for the semantic condition. We also find activations of the inferior parietal lobe, consistent with a visual oddball response reported previously, and the anterior cingulate gyrus (BA 32), implicated for attention and memory-related processes in numerous studies.


The role of self-help in the treatment of mild anxiety disorders in young people: an evidence-based review.
Anxiety disorders are the most common mental health problems experienced by young people, and even mild anxiety can significantly limit social, emotional, and cognitive development into adulthood. It is, therefore, essential that anxiety is treated as early and effectively as possible. Young people are unlikely, however, to seek professional treatment for their problems, increasing their chance of serious long-term problems such as impaired peer relations and low self-esteem. The barriers young people face to accessing services are well documented, and self-help resources may provide an alternative option to respond to early manifestations of anxiety disorders. This article reviews the potential benefits of self-help treatments for anxiety and the evidence for their effectiveness. Despite using inclusive review criteria, only six relevant studies were found. The results of these studies show that there is some evidence for the use of self-help interventions for anxiety in young people, but like the research with adult populations, the overall quality of the studies is poor and there is need for further and more rigorous research.


Impact of indinavir on the quality of life in patients with advanced HIV infection treated with zidovudine and lamivudine.
In AIDS Clinical Trial Group (ACTG) study 320, triple-combination antiretroviral therapy including indinavir significantly slowed progression to acquired immunodeficiency syndrome or death, compared with treatment with dual nucleoside reverse-transcriptase inhibitors (NRTIs) alone, in zidovudine-experienced patients with advanced human immunodeficiency virus (HIV) infection. We examined the impact of indinavir on quality of life in participants from this study. A total of 1156 protease inhibitor- and lamivudine-naive patients stratified by CD4 cell count (<or=50 and 51-200 cells/mm(3)) were randomized to receive zidovudine (or stavudine) and lamivudine, with or without indinavir. Health-related quality of life was measured using the ACTG QoL601-602 questionnaire, which assesses general health status measured on a visual analogue scale and 8 specific health-related domains. Quality-adjusted survival time was estimated using the visual analogue scale for general health. Mean changes in general health scores after 24 weeks were +2.9 in the triple-therapy group versus -0.2 in the dual-therapy group (P=.018). By week 24, scores in all specific domains were higher with triple-drug therapy than dual-drug therapy, with statistically significant differences in role function, energy, and pain scores. Benefits of triple-drug therapy were largely confined to patients with CD4 cell counts of <or=50 cells/mm(3). Quality-adjusted survival time did not differ significantly between the 2 treatment groups. Triple-drug therapy with indinavir and 2 NRTIs resulted in a significant improvement in general health status after 24 weeks, especially in patients with low CD4 cell counts. Patients receiving triple-drug therapy also had significantly better role function, energy, and pain scores than did patients treated with dual-drug therapy.


Establishment and characterization of a human lung cancer cell line NCI-H460-LNM35 with consistent lymphogenous metastasis via both subcutaneous and orthotopic propagation.
Lymphogenous metastasis is a common feature of human lung cancers, but very little is known about the underlying mechanism. In the present study, in vivo selection was carried out to obtain a highly lymphogenous metastatic subline of a human large cell carcinoma of the lung, NCI-H460. The resulting subline, termed NCI-H460-LNM35 (LNM35), was shown to metastasize to regional lymph nodes with a 100% incidence not only as a result of orthotopic intrabronchial (i.b.) implantation, but also as a result of conventional s.c. implantation. LNM35 has a short latency period, allowing for the collection of experimental data within 28 days after i.b. inoculation and 45 days after s.c. inoculation. It was noted that orthotopically i.b.-propagated LNM35 closely mimicked the clinical manifestations of human lung cancer patients by infiltrating into lymphatic vessels and metastasizing to the mediastinal lymph nodes. The LNM35 cell line is, to the best of our knowledge, the first human lung cancer cell line to be reported as having lymphogenous metastatic properties, and the observed 100% incidence by s.c. inoculation gives LNM35 a significant advantage even over previously reported human cancer cell lines of other origins. Comparisons between LNM35 and its parental NCI-H460 cell lines were also made with regard to expression levels and/or activities of various molecules that are thought to play a part in the metastatic process. We show here that the expression of cyclooxygenase 2 is increased in LNM35 and that a specific cyclooxygenase 2 inhibitor, nimesulide, can inhibit the invasion of LNM35 in vitro through Matrigel containing basement membrane components.


Individual-level sterility: a new method of estimation with application to sub-Saharan Africa.
This paper extends work on measures of population proportions sterile to propose a new estimator of an individual woman's age at sterility and consequently her sterility status at given ages. Accuracy and reliability, examined in a simulation study, appear satisfactory. From World Fertility Survey data for five African countries, the proportions sterile by age estimated by the individual measure and by the population estimator are almost identical. Cameroon and Kenya show substantial variation in prevalence and incidence of sterility across ethnic groups and by number of marriages. Unexpectedly, the evidence suggests that sterility increased from 1960 on in Kenya and remained unchanged in Cameroon.


Anti-transglutaminase antibody assay of the culture medium of intestinal biopsy specimens can improve the accuracy of celiac disease diagnosis.
We measured anti-transglutaminase (anti-tTG) antibody in the culture medium of intestinal biopsy specimens from patients with suspected celiac disease (CD) and evaluated the relationship between antibody production and severity of intestinal mucosal damage. We performed diagnostic testing for CD on 273 consecutive patients. In addition to routine histologic evaluation of duodenal biopsy specimens, we assayed anti-tTG antibodies in serum and in the culture medium of duodenal biopsy specimens. CD was diagnosed in 191 of the 273 patients. Sensitivity and specificity of the serum anti-endomysium (EmA) and anti-tTG assays were 83% and 85% and 99% and 95%, respectively, and both had 88% diagnostic accuracy. EmA and anti-tTG assayed in the culture medium had 98% sensitivity, 100% specificity, and 98% diagnostic accuracy (vs serum assays; P <0.0001). Twenty-nine CD patient specimens (16%) were negative for serum anti-tTG and EmA; for 24 of these patients, anti-tTG assay of the culture medium was positive. The CD patients whose biopsy specimens were positive for serum antibodies showed the following intestinal histologies: total villous atrophy, 35%; severe villous atrophy, 25%; mild atrophy, 25%; villi with no atrophy but with increased intraepithelial lymphocytes, 15%. None of the CD patients whose specimens were negative for serum antibodies showed total or severe villous atrophy; 77% had mild villous atrophy, and 23% had no villous atrophy but had increased intraepithelial lymphocyte counts. Mild villous atrophy was also seen in specimens from approximately 15% of patients without CD. Anti-tTG assay of the culture medium of biopsy specimens can improve the accuracy of CD diagnosis in patients negative for serum antibodies.


Harvesting energy from the marine sediment-water interface II. Kinetic activity of anode materials.
Here, we report a comparative study on the kinetic activity of various anodes of a recently described microbial fuel cell consisting of an anode imbedded in marine sediment and a cathode in overlying seawater. Using plain graphite anodes, it was demonstrated that a significant portion of the anodic current results from oxidation of sediment organic matter catalyzed by microorganisms colonizing the anode and capable of directly reducing the anode without added exogenous electron-transfer mediators. Here, graphite anodes incorporating microbial oxidants are evaluated in the laboratory relative to plain graphite with the goal of increasing power density by increasing current density. Anodes evaluated include graphite modified by adsorption of anthraquinone-1,6-disulfonic acid (AQDS) or 1,4-naphthoquinone (NQ), a graphite-ceramic composite containing Mn2+ and Ni2+, and graphite modified with a graphite paste containing Fe3O4 or Fe3O4 and Ni2+. It was found that these anodes possess between 1.5- and 2.2-fold greater kinetic activity than plain graphite. Fuel cells were deployed in a coastal site near Tuckerton, NJ (USA) that utilized two of these anodes. These fuel cells generated ca. 5-fold greater current density than a previously characterized fuel cell equipped with a plain graphite anode, and operated at the same site.


Verification, characterization and tissue-specific expression of UreG, a urease accessory protein gene, from the amphioxus Branchiostoma belcheri.
UreG genes have been found in bacteria, fungi and plants but have not yet identified in animals, although a putative UreG-like gene has been documented in sea urchin. In the course of a large-scale sequencing of amphioxus gut cDNA library, we have identified a cDNA with high similarity to UreG genes. Both reverse transcription-polymerase chain reaction and nested polymerase chain reaction, as well as in situ hybridization histochemistry, verified that the cDNA represented an amphioxus UreG gene (AmphiUreG) rather than a microbial contaminant of the cDNA library. This is further supported by the presence of urease activity in amphioxus gut, gill and ovary. AmphiUreG encodes a deduced protein of 200 amino acid residues including a highly conserved P-loop, bearing approximately 46%-49%, 44%-48%, and 29%-37% similarity to fungal, plant and bacterial UreG proteins, respectively. It shows a tissue-specific expression pattern in amphioxus, and is especially abundant in the digestive system. This is the first UreG gene identified in animal species.


Suppression of intermixing in strain-relaxed epitaxial layers.
Misfit strain plays a crucial role in semiconductor heteroepitaxy, driving alloy intermixing or the introduction of dislocations. Here we predict a strong coupling between these two modes of strain relaxation, with unexpected consequences. Specifically, strain relaxation by dislocations can suppress intermixing between the heterolayer and the substrate. Monte Carlo simulations and continuum modeling show that the suppression, though not absolute, can be surprisingly large, even at high temperatures. The effect is strongest for a large misfit (e.g., InAs on GaAs) or for thin substrates (e.g., Ge on silicon on insulator).


Strange Cases: Jekyll & Hyde Narratives as Rhetorical Strategy in Sir Alexander Morison's Physiognomy of Mental Diseases.
Sir Alexander Morison's Physiognomy of Mental Diseases (1838) was created as a didactic tool for physicians, depicting lunatics in both the active and dormant states of disease. Through the act of juxtaposition, Morison constituted his subjects as their own Jekylls and Hydes, capable of radical transformation. In doing so, he marshaled artistic and clinical, visual and textual approaches in order to pose a particular argument about madness as a temporally manifested, visually distinguishable state defined by its contrast with reason. This argument served a crucial function in legitimizing the emergent discipline of psychiatry by applying biomedical methodologies to the observation and classification of distinctly physical symptoms. Robert Louis Stevenson's "quintessentially Victorian parable" serves as a metaphor for the way 19th-century alienists conceptualized insanity, while the theme of duality at the core of Stevenson's story serves as a framework for conceptualizing both psychiatry and the subjects it generates. It was (and is) a discipline formulated around narrative as the primary organizing structure for its particular set of paradoxes, and specifically, narratives of the self as a fluid, dynamic, and contradictory entity.


Crohn's disease: are enteroenteral fistulas an indication for surgery?
Currently many physicians consider enteroenteral fistulas an indication for surgery in Crohn's disease. In an attempt to document the natural history of these fistulas, the courses of 64 patients with Crohn's disease complicated by enteroenteral fistulas were reviewed. The fistulas were diagnosed radiologically in 48 patients (75%) and at operation or by examination of the resected specimen in 16 (25%). Twenty-four of the 48 patients whose fistulas were diagnosed radiologically underwent early operation. The remaining 24 initially had nonoperative management and thus provided information about the natural history of enteroenteral fistulas. Ten of these 24 patients had nonoperative treatment for less than 1 year. All required surgery because of intestinal obstruction, enterovesical fistula, or failed response to medical therapy. Fourteen patients were managed nonoperatively for a mean period of 3.5 years (range 1 to 9 years). Eight of these patients eventually required operation, but the remaining six have to date not needed surgery. In two of these patients the fistulas can no longer be demonstrated radiographically. Patients who initially received nonoperative therapy and later required operation did not have any increased mortality or morbidity as compared with those treated with early surgery. Enteroenteral fistulas are frequently associated with and are the result of active inflammatory disease. The fistulas are usually asymptomatic and are by themselves not considered an indication for operation.


Shifting the set of stimulus selection when switching between tasks.
Switching between tasks associated with different requirements of stimulus selection may suffer interference from persisting attentional settings or processes of reconfiguration, possibly constituting a source of task switch costs (i.e., impaired performance in task switch trials compared to task repetition trials). To explore the processes involved in task switching with and without a switch in stimulus selection requirements, we administered a task-switching paradigm that involved task-unique sets of hierarchical (Navon) stimuli, preventing stimulus-related proactive interference (i.e., impaired responding to a stimulus that was previously processed in the context of a different task), and varied, between groups of participants, whether the target stimulus level (i.e., global vs. local) was held constant or varied between the tasks. Mixing target levels impaired performance overall and increased the task switch costs. Moreover, (within-task) global-local congruency effects were larger when target levels were mixed, particularly in task switch trials, suggesting relatively stronger stimulus processing according to the attentional set of the other task. In a second phase of the experimental session, the target level was changed persistently for either one or for both tasks, presumably evoking stimulus-related proactive interference. This change yielded large task switch costs and global-local congruency effects when it resulted in mixed target levels, but not when it resulted in a constant target level. These results are consistent with the notion that stimulus-related proactive interference is reduced by constant withdrawal of attention from the perceptual dimension of the interference-eliciting stimuli.


Impact of COVID-19 on rehabilitation experiences of physiotherapists.
As the COVID-19 pandemic progressed, pressures on almost all health sectors in many countries increased, and physiotherapy interventions were canceled for various reasons. The aim of this study was to determine the status of physiotherapists who interrupted their services due to the pandemic and investigate procedures adopted by physiotherapists during face-to-face practice. The measuring tool was an online survey administered via Google Forms between January 27 and February 27, 2021. In this descriptive cross-sectional study, the sample consisted of 558 physiotherapists, questions about their clinical experience during the pandemic were answered, and descriptive statistics were examined. Of the physiotherapists, 351 (62.9%) suspended their services due to pandemic, while 207 (37%) of all participants worked without suspending their services since the beginning of the process. Among participants, 303 (54.3%) needed education to use telerehabilitation methods, and 315 (56.5%) monitored their patients with remote communication methods. Hand washing (86.6%), disinfectant (85.3%), gloves (76.5%) and masks (86.6%) were the most common protective measures. Most physiotherapists had their face-to-face practice interrupted for a short time due to the COVID-19 outbreak, but they continue to treat all disease conditions in spite of inherent physical intimacy and increased risk of infection.


Effect of Donor Nephrectomy Technique on Recipient Lymphatic Drainage.
We sought to evaluate the postoperative recipient lymphatic drainage depending on open donor nephrectomy (ODN) or laparoscopic (LDN) techniques. Between March 2012 and August 2014, 58 patients underwent renal transplantation from living-related donors. Thirty donors underwent ODN (group 1), and 28 LDN (group 2). Operations were performed by the same surgeons. Both cranial and caudal drainage catheters for lymphatic leakage were placed preoperatively and all the recipients received tacrolimus, mycophenolate mofetil, and steroid as immunosuppressive regimen. None of the patients had coagulation abnormalities. All grafts were functioning during the early postoperative period and diuresis was ensured. No difference was observed on early postoperative period regarding to acute rejection (P = .329) or infection (P = .546). No difference was seen concerning mycophenolate mofetil and mycophenolate sodium regimens among the 2 groups (P = .227). In groups 1 and 2, the cranial drainage catheters were not taken out until postoperative days 5.5 ± 2.5 (range, 0-11) and 6.4 ± 3.8 (range, 0-14) and the caudal catheters stayed in place until days 8.8 ± 3.5 (range, 1-16) and 9.9 ± 5.9 (range, 3-22), respectively. No difference was found when comparing the cranial (P = .308) and caudal (P = .426) drainage periods. However, during clinical acute rejection episodes the cranial drainage period was longer in group 1 (P = .003). Three patients developed lymphoceles, 1 requiring drainage, in group 2. There seems to be no difference in recipient lymphatic drainage by donor nephrectomy technique. A laparoscopic procedure may be advantageous owing to shorter lymphatic drainage during clinical acute rejection episodes.


Diagnostic Value of Serum lncRNA HOTAIR Combined with Galectin-3 in Benign and Papillary Thyroid Carcinoma.
Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. LncRNA HOTAIR (HOx Transcript AntIsense RNA) and Galectin-3 are involved in PTC. This study explored the clinical effect of lncRNA HOTAIR/Galectin-3 on PTC patients. Subjects were assigned into PTC (160 cases) and benign thyroid tumor groups (150 cases). Fasting peripheral venous blood was collected. LncRNA HOTAIR/Galectin-3 expressions in serum were detected. Subjects were assigned into HOTAIR/Glactin-3 high/low expression groups and their correlation with age, gender, BMI, tumor size, pathological stage, TSH, TPO-Ab, and TG-Ab in PTC was analyzed. Receiver operating characteristic (ROC) curve was conducted on diagnostic efficacy of HOTAIR or/and Galectin-3. The difference of area under the curve (AUC) was compared and analyzed. HOTAIR and Glactin-3 were higher in PTC group and correlated with tumor pathological stage. Higher HOTAIR/Glactin-3 expression indicated a more advanced TNM stage. LncRNA HOTAIR was positively correlated with TPO-Ab and TG-Ab. AUC of HOTAIR for PTC diagnosis was 0.895, with 96.00% specificity and 80.63% sensitivity. AUC of Glactin-3 for PTC diagnosis was 0.817, with 66.67% specificity and 78.75% sensitivity. AUC of HOTAIR combining with Glactin-3 for PTC diagnosis was 0.969 with 96.00% specificity and 87.50% sensitivity. AUC of lncRNA HOTAIR was higher than that of Glactin-3, while AUC of the combination was higher than that of lncRNA HOTAIR or Glactin-3. LncRNA HOTAIR and Glactin-3 were highly expressed in PTC. The combination detection of lncRNA HOTAIR/Glactin-3 had higher diagnostic efficiency on the differential diagnosis of benign thyroid tumor and PTC.


Taxonomic reference libraries for environmental barcoding: a best practice example from diatom research.
DNA barcoding uses a short fragment of a DNA sequence to identify a taxon. After obtaining the target sequence it is compared to reference sequences stored in a database to assign an organism name to it. The quality of data in the reference database is the key to the success of the analysis. In the here presented study, multiple types of data have been combined and critically examined in order to create best practice guidelines for taxonomic reference libraries for environmental barcoding. 70 unialgal diatom strains from Berlin waters have been established and cultured to obtain morphological and molecular data. The strains were sequenced for 18S V4 rDNA (the pre-Barcode for protists) as well as rbcL data, and identified by microscopy. LM and for some strains also SEM pictures were taken and physical vouchers deposited at the BGBM. 37 freshwater taxa from 15 naviculoid diatom genera were identified. Four taxa from the genera Amphora, Mayamaea, Planothidium and Stauroneis are described here as new. Names, molecular, morphological and habitat data as well as additional images of living cells are also available electronically in the AlgaTerra Information System. All reference sequences (or reference barcodes) presented here are linked to voucher specimens in order to provide a complete chain of evidence back to the formal taxonomic literature.


Neurobiology of simian and feline immunodeficiency virus infections.
Experimental and clinical evidence indicates that all lentiviruses of animals and humans are neurotropic and potentially neurovirulent. The prototypic animal lentiviruses, visna virus in sheep and caprine arthritis encephalitis virus in goats have been known for decades to induce neurologic disease. More recently, infection of the brain with the human immunodeficiency virus (HIV) has been linked to an associated encephalopathy and cognitive/motor complex. While the visna virus and caprine arthritis encephalitis virus are important models of neurologic disease they are not optimal for the study of HIV encephalitis because immune deficiency is only a minor component of the disease they induce. By contrast, the recently isolated lentiviruses from monkeys and cats, the simian and feline immunodeficiency viruses (SIV and FIV respectively), are profoundly immunosuppressive as well as neurotropic. SIV infection of the central nervous system of macaques now provides the best animal model for HIV infection of the human brain due to the close evolutionary relationship between monkeys and man, the genetic relatedness of their respective lentiviruses, and the similarities in the neuropathology. This chapter will compare and contrast the neurobiology of SIV and FIV with HIV.


Multilineage differentiation potential in the infant adipose- and umbilical cord-derived mesenchymal stem cells.
This study aims to compare the biological properties of infant adipose-derived mesenchymal stem cells (infant ADSCs) from excised polydactyly fat tissue and umbilical cord-derived mesenchymal stem cells (UCSCs) in terms of proliferation and differentiation capabilities. The proliferation of infant ADSCs and UCSCs was analyzed by determining the fold changes of cell numbers and doubling time periods. The state of senescence and replicative stress was compared by analyzing the expression of age-related genes, senescence-associated β-galactosidase (SA-β-gal) staining, and phosphorylated histone variant H2AX (γH2AX) immunofluorescence staining. The expression levels of superoxide dismutase ( SODs ) and genes related to multilineage differentiation were analyzed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Differentiation levels were determined using histochemical staining, immunohistochemical staining, and immunofluorescence staining. Infant ADSCs exhibited higher proliferation rates and expression levels of SOD1 , SOD2 , and SOD3 at passages 3-5 compared with UCSCs. Senescence related genes ( p16 , p21 , and p53 ), SA-β-gal staining, and replicative stress analysis were reduced in infant ADSCs. The expression levels of chondrogenic genes ( COL2 and COL10 ), osteogenic genes ( RUNX2 and ALP ), adipogenic genes ( LPL ), and hepatogenic genes ( ALB and TAT ) in infant ADSC-differentiated cells were significantly higher than those in UCSCs. Histochemical and immunofluorescence staining confirmed these results. Only the expression levels of tenogenic genes ( MMP3 , DCN , and COL3 ) in infant ADSC-differentiated cells were lower than those in UCSCs. Infant ADSCs exhibit higher proliferation rates, reduced cellular senescence and replicative stress, better antioxidative activity, and higher differentiation potential toward chondrogenic, osteogenic, adipogenic and hepatogenic lineages than UCSCs.


New Diagnostic Possibilities for Early Onset Neonatal Sepsis: Red Cell Distribution Width to Platelet Ratio.
Aims: Red cell distribution width to platelet ratio (RPR) has been reported as a useful inflammatory marker and prognostic indicator of adult inflammatory diseases. In the present study, red cell distribution width (RDW) and RPR parameters, which are parts of a complete blood count analysis, were compared to the traditional C reactive protein (CRP) and procalcitonin (PCT) parameters to investigate the potential to predict early onset sepsis (EOS) in neonates with or without positive blood cultures. Methods: An observational, retrospective cohort study was conducted to evaluate newborns born in our hospital. Results: RDW, RPR, CRP, PCT, Immature to total neutrophil ratio (I/T), and white blood cell (WBC) counts were higher in suspected and proven EOS compared to control group. Conclusion: We believe that RPR may be used in diagnosis of early onset neonatal sepsis and may be a good alternative to other tools as a readily available biomarker.


Impact of red blood cell transfusion dose density on progression-free survival in patients with lower-risk myelodysplastic syndromes.
Progression-free survival (PFS) of patients with lower-risk myelodysplastic syndromes (MDS) treated with red blood cell transfusions is usually reduced, but it is unclear whether transfusion dose density is an independent prognostic factor. The European MDS Registry collects prospective data at 6-monthly intervals from newly diagnosed lower-risk myelodysplastic syndromes patients in 16 European countries and Israel. Data on the transfusion dose density - the cumulative dose received at the end of each interval divided by the time since the beginning of the interval in which the first transfusion was received - were analyzed using proportional hazards regression with time-varying co-variates, with death and progression to higher-risk MDS/acute myeloid leukemia as events. Of the 1,267 patients included in the analyses, 317 died without progression; in 162 patients the disease had progressed. PFS was significantly associated with age, EQ-5D index, baseline World Health Organization classification, bone marrow blast count, cytogenetic risk category, number of cytopenias, and country. Transfusion dose density was inversely associated with PFS (P<1×10-4): dose density had an increasing effect on hazard until a dose density of 3 units/16 weeks. The transfusion dose density effect continued to increase beyond 8 units/16 weeks after correction for the impact of treatment with erythropoiesis-stimulating agents, lenalidomide and/or iron chelators. In conclusion, the negative effect of transfusion treatment on PFS already occurs at transfusion densities below 3 units/16 weeks. This indicates that transfusion dependency, even at relatively low dose densities, may be considered as an indicator of inferior PFS. This trial was registered at www.clinicaltrials.gov as #NCT00600860.


Concordance among Measurements Obtained by Three Pulse Oximeters Currently Used by Health Professionals.
Oxygen saturation is considered as the 5(th) vital sign. Presently, there exist fixed and wireless pulse oximeters, being the latter most widely used in the last years. Some of them have no possibility of calibration. This situation leads the health staff to adopt therapeutic attitudes which can be wrong. Therefore, it is extremely important to know if these wireless oximeters show a right concordance as regards measurements, since it is of great interest in daily clinical practice. To evaluate concordance among measurements obtained by three different pulse oximeters currently used by health professionals. This is an observational, descriptive and cross-sectional study related to the concordance of the results obtained in measurements collected by three different pulse oximeters (one monitor and two wireless oximeters) which are available and in use in this hospital unit. The sample size calculation was performed for a concordance above 0.81 and an estimation error which did not exceed 0.20. The intraclass correlation index (ICI) was used to establish the concordance whereas the Landis-Koch criteria were used to interpret the results. Systematic errors were analyzed using the Bland-Altman plot. The overall concordance among the three pulse oximeters analyzed resulted in 0.88, a value considered as "good" according to the Landis-Koch criteria. The results obtained show that in daily clinical practice both wireless pulse oximeters analyzed can be used with a certain reliability, taking into account the limitations of this research.


Mesenchymal stem cell-derived microRNAs: Friends or foes of tumor cells?
Mesenchymal stem cell (MSC)-dependent biological effects in the tumor microenvironment mainly rely on the activity of MSC-sourced microRNAs (MSC-miRNAs) which modulate protein synthesis in target tumor cells, endothelial cells and tumor-infiltrated immune cells, regulating their phenotype and function. Several MSC-sourced miRNAs (miR-221, miR-23b, miR-21-5p, miR-222/223, miR-15a miR-424, miR-30b, miR-30c) possess tumor-promoting properties and are able to enhance viability, invasiveness and metastatic potential of malignant cells, induce proliferation and sprouting of tumor endothelial cells and suppress effector functions of cytotoxic tumor-infiltrated immune cells, crucially contributing to the rapid growth and progression of tumor tissue. On the contrary, MSCs also produce "anti-tumorigenic" miRNAs (miR-100, miR-222-3p, miR-146b miR-302a, miR-338-5p, miR-100-5p and miR-1246) which suppress tumor growth and progression by: Up-regulating expression of chemoresistance-related genes in tumor cells, by suppressing neo-angiogenesis and by inducing generation of tumorotoxic phenotypes in tumor-infiltrated lymphocytes. In this review article, we summarize the current knowledge about molecular mechanisms that are responsible for MSC-miRNA-dependent alterations of intracellular signaling in tumor and immune cells and we discuss different insights regarding the therapeutic potential of MSC-derived miRNAs in cancer treatment.


Cost-effectiveness of collaborative care including PST and an antidepressant treatment algorithm for the treatment of major depressive disorder in primary care; a randomised clinical trial.
Depressive disorder is currently one of the most burdensome disorders worldwide. Evidence-based treatments for depressive disorder are already available, but these are used insufficiently, and with less positive results than possible. Earlier research in the USA has shown good results in the treatment of depressive disorder based on a collaborative care approach with Problem Solving Treatment and an antidepressant treatment algorithm, and research in the UK has also shown good results with Problem Solving Treatment. These treatment strategies may also work very well in the Netherlands too, even though health care systems differ between countries. This study is a two-armed randomised clinical trial, with randomization on patient-level. The aim of the trial is to evaluate the treatment of depressive disorder in primary care in the Netherlands by means of an adapted collaborative care framework, including contracting and adherence-improving strategies, combined with Problem Solving Treatment and antidepressant medication according to a treatment algorithm. Forty general practices will be randomised to either the intervention group or the control group. Included will be patients who are diagnosed with moderate to severe depression, based on DSM-IV criteria, and stratified according to comorbid chronic physical illness. Patients in the intervention group will receive treatment based on the collaborative care approach, and patients in the control group will receive care as usual. Baseline measurements and follow up measures (3, 6, 9 and 12 months) are assessed using questionnaires and an interview. The primary outcome measure is severity of depressive symptoms, according to the PHQ9. Secondary outcome measures are remission as measured with the PHQ9 and the IDS-SR, and cost-effectiveness measured with the TiC-P, the EQ-5D and the SF-36. In this study, an American model to enhance care for patients with a depressive disorder, the collaborative care model, will be evaluated for effectiveness in the primary care setting. If effective across the Atlantic and across different health care systems, it is also likely to be an effective strategy to implement in the treatment of major depressive disorder in the Netherlands.


Adolescent and mid-life diet: risk of colorectal cancer in the NIH-AARP Diet and Health Study.
Colorectal cancer has a natural history of several decades; therefore, the diet consumed decades before diagnosis may aid in understanding this malignancy. The objective was to investigate diet during adolescence and 10 y before baseline (ages 40-61 y) in relation to colorectal cancer. Participants in the NIH-AARP Diet and Health Study (n = 292,797) completed a 124-item food-frequency questionnaire (FFQ) about diet in the past 12 mo and two 37-item FFQs about diet at ages 12-13 y and 10 y previously. Cox regression was used to estimate multivariate HRs and 95% CIs for colon (n = 2794) and rectal (n = 979) cancers within quintiles of exposures. Colon cancer risk was lower in the highest than in the lowest quintile of vitamin A (HR: 0.82; 95% CI: 0.72, 0.92) and vegetable (HR: 0.81, 0.70, 0.92) intakes during adolescence. Those in the highest intake category 10 y previously for calcium (HR: 0.83; 95% CI: 0.73, 0.94), vitamin A (HR: 0.81; 95% CI: 0.71, 0.92), vitamin C (HR: 0.83; 95% CI: 0.72, 0.95), fruit (HR: 0.84; 95% CI: 0.73, 0.97), and milk (HR: 0.78; 95% CI: 0.67, 0.90) had a lower risk of colon cancer, but a higher risk was observed for total fat (HR: 1.15; 95% CI: 1.01, 1.30), red meat (HR: 1.31; 95% CI: 1.12, 1.53), and processed meat (HR: 1.24; 95% CI: 1.06, 1.45). For rectal cancer, milk was inversely associated (HR: 0.75; 95% CI: 0.58, 0.96) with risk. Adolescent and midlife diet may play a role in colorectal carcinogenesis.


Younger age and prognosis in diverticulitis: a nationwide retrospective cohort study.
Traditionally regarded as a disease of the elderly, the incidence of diverticulitis of the colon has been on the rise, especially in younger cohorts. These patients have been found to experience a more aggressive disease course with more frequent hospitalization and greater need for surgical intervention. To characterize factors that portend a poor prognosis in patients diagnosed with diverticulitis; in particular, to evaluate the role of demographic variables on disease course. Using the Canadian Institute for Health Information Discharge Abstract Databases, readmission rates, length of stay, colectomy rates and mortality rates in patients hospitalized for diverticulitis were examined. Data were stratified according to age, sex and comorbidity (as defined by the Charlson index). In the cohort ≤30 years of age, a clear male predominance was apparent. Colectomy rate in the index admission, stratified according to age, demonstrated a J-shaped curve, with the highest rate in patients ≤30 years of age (adjusted OR 2.3 [95% CI 1.62 to 3.27]) compared with the 31 to 40 years of age group. In-hospital mortality increased with age. Cumulative rates of readmission at six and 12 months were 6.8% and 8.8%, respectively. In the present nationwide cohort study, younger patients (specifically those ≤30 years of age) were at highest risk for colectomy during their index admission for diverticulitis. It is unclear whether this observation was due to more virulent disease among younger patients, or surgeon and patient preferences.


Relationship between activity of silica thin films and density of cells occupation.
The SiO2 thin films (STFs) were deposited on the surfaces of stainless steel tapes and their activity was particularly investigated from the aspect of the number density of hydroxyl groups on their surfaces. The calculation procedure of density of active OH groups includes determination of average length of silica chains that constitute silica sol particles with almost uniform size, on the base of thermogravimetric analysis. The size of SiO2 particles is analyzed by transmission electron microscopy and dynamic light scattering method. Fibroblast (L929) cell densities on the surfaces of these films were investigated using phase contrast microcopy. It was shown that there is a relationship between OH group densities and density of attached cells. Besides, the cytotoxicity effect was studied and compared for various thermally treated STFs.


Human cytomegalovirus tegument protein ppUL35 is important for viral replication and particle formation.
The tegument proteins ppUL35 and ppUL82 (pp71) of human cytomegalovirus (HCMV) physically interact and cooperatively activate the major immediate-early transcription. While an HCMV mutant lacking UL82 displayed a multiplicity of infection (MOI)-dependent growth, the biological significance of ppUL35 has not been addressed so far. We generated a mutant virus with a deletion of the UL35 gene. Using an MOI of 0.1, the progeny virus yield of this mutant was reduced by a factor of 1,000; however, when infected at a low MOI (0.01), the gene was essential. Characterization of the replication cycle showed that the mutant virus had two defects: when virus inoculum was standardized by the amount of viral DNA, a reduced immediate-early gene expression was observed, leading to a strongly delayed expression of lytic genes. A second defect was apparent in the virus assembly, as fewer enveloped particles and no dense bodies were present in cells infected with the mutant virus. However, the particles produced by wild-type and mutant viruses did not show significant ultrastructural differences. These results suggest an important role for ppUL35 in immediate-early gene expression and virus assembly.


Evaluation of Same-Day versus Next-Day Implantation of Intracanalicular Dexamethasone for the Control of Postoperative Inflammation and Pain Following Cataract Surgery.
To evaluate the safety and efficacy of a sustained-release intracanalicular dexamethasone insert for postoperative inflammation and pain implanted in a clinical setting preoperatively or on postoperative day 1. Single-site, retrospective, contralateral eye study of patients undergoing cataract surgery. Included were subjects with a dexamethasone intracanalicular insert implanted in the clinic immediately prior to surgery in one eye (same-day) and on postoperative day 1 (POD1) in the contralateral eye. The primary outcome measure was the resolution of anterior chamber inflammation at 1 week postoperative. Secondary outcome measures included proportion of eyes requiring additional therapy for pain and inflammation through 1 month as well as the number of eyes with IOP spikes above baseline. Safety measures included adverse events through 1 month postoperative. Sixty-two eyes of 31 subjects were included in the case series. At 1 week postoperative, 52% of the eyes (n = 16) achieved complete resolution of inflammation in the same-day group and 58% (n = 18) met this endpoint at 1 week in the POD1 group. One subject in the same-day group required additional therapy for rebound inflammation and no eyes required additional therapy in the POD1 group. There were no reports of pain at 1 week or 1 month in either group. There were no implant-related adverse events in either group. The favorable results of this study indicate that the sustained-release dexamethasone insert can be safely implanted in the clinic either preoperatively on the day of surgery or on postoperative day 1 for the control of pain and inflammation following cataract surgery.


Experimental and analytical study of anisotropic strength properties of bovine cortical bone.
This paper is focused on specification of conditions at failure in bovine cortical bone. Both experimental and analytical studies are conducted. The experimental part includes a series of novel direct shear tests which examine the sensitivity of shear strength to the applied normal stress for different orientations of the sample microstructure. These experiments are supplemented by standard axial compression and tension tests in order to define and quantify a general form of failure criterion. The analytical part examines two different methodologies, viz. critical plane approach and microstructure tensor approach, for defining the anisotropic strength criterion. A procedure for identification of material parameters is outlined which is based on the results of the performed material tests.


Activation of Torpedo acetylcholine receptors expressed in mouse fibroblasts. Single channel current kinetics reveal distinct agonist binding affinities.
The experiments described examine single channel currents recorded through Torpedo acetylcholine receptor channels stably expressed by a mouse fibroblast cell line. Closed-duration histograms were constructed from currents elicited by 0.5-300 microM acetylcholine (ACh). The concentration dependence of closed durations is well described by a four-state linear scheme with the addition of open-channel block by ACh. Analysis of closed durations measured at low concentrations gives estimates of the rate of opening of doubly liganded receptors, beta, the rate of dissociation of ACh from doubly liganded receptors, k-2, and the rate of channel closing, alpha. The rate of ACh dissociation from singly liganded receptors, k-1, is then deduced from closed-duration histograms obtained at intermediate ACh concentrations. With k-1, k-2 and beta determined, the rates of ACh association, k+1 and k+2, are estimated from fitting closed-duration histograms obtained over a range of high ACh concentrations. A complete set of rate constants is presented for three experimental conditions: (a) Ca2(+)-free extracellular solution containing 1 mM free Mg2+ at 22 degrees C, (b) Ca2(+)-free solution at 12 degrees C, and (c) extracellular Ca2+ and Mg2+, both at 0.5 mM, at 22 degrees C. For all three conditions the dissociation constant for the first agonist binding site is approximately 100-fold lower than that for the second site. The different affinities are due primarily to different dissociation rates. Both the association and dissociation rates depend strongly on temperature. At 22 degrees C ACh associates at diffusion-limited rates, whereas at 12 degrees C association is 30- to 60-fold slower. Also slowed at 12 degrees C are beta (4-fold), k-2 (3-fold), k-1 (25-fold), and alpha (15-fold). In contrast to the activation rate constants, those for ACh-induced block decrease only twofold between 22 and 12 degrees C. Changing from a Ca2(+)-free to a Ca2(+)-containing extracellular solution does not affect k+1 and k+2, but increases beta (twofold) and decreases k-2, k-1, and alpha (all twofold). Spectral analysis of single channel currents supports the parameter estimates obtained from fitting the open- and closed-duration histograms, and improves resolution of brief channel blockages produced by ACh.


[Effects of hypoxia and anisodamine on products of TXA2 and PGI2 in cultured intra-pulmonary arteriolar smooth muscle cells].
The changes of contents of TXB2 and 6-Keto-PGF1a were studied in severely acute hypoxic cultured intra-pulmonary arteriolar smooth muscle cells (PASMCs) under the action of anisodamine. The results demonstrated that the contents of TXB2 and 6-Keto-PGF1a and their ratio were significantly increased in severe acute hypoxic PASMCs' medium. The content of TXB2 decreased significantly, but the content of 6-Keto-PGF1a was hardly affected by anisodamine under normoxia and hypoxia. These findings suggest that acute and severe hypoxia results in pulmonary vascular constriction through increased production of PASMCs and liberation of TXA2, or PGI2, and increased TXA2/PGI2 ratio. The latter effect of hypoxia could be prevented by anisodamine, which antagonized the effect of hypoxia induced pulmonary vasoconstriction.


Goal adjustment capacities, coping, and subjective well-being: the sample case of caregiving for a family member with mental illness.
This study examined the associations between goal adjustment capacities, coping, and indicators of subjective well-being in 2 waves of data from individuals who provide care for a family member with mental illness. We hypothesized that goal adjustment capacities would predict higher levels of subjective well-being by facilitating coping with caregiving stress. Results showed that goal disengagement was associated with effective care-specific coping (e.g., less self-blame and substance use). Goal reengagement was also associated with effective care-specific coping (e.g., positive reframing), but at the same time it predicted the use of less effective strategies (e.g., venting and self-distraction). Moreover, goal disengagement predicted lower levels of caregiver burden and depressive symptoms and buffered the longitudinal effect of caregiver burden on increases in depressive symptoms. Goal reengagement, by contrast, predicted higher levels of caregiver burden and purpose in life and buffered the cross-sectional association between caregiver burden and depressive symptoms. Finally, effective (and less useful) care-specific coping statistically explained the adaptive (and maladaptive) effects of goal adjustment capacities on participants' well-being.


Effect of MON810 Bt field corn on Helicoverpa zea (Lepidoptera: Noctuidae) cannibalism and its implications to resistance development.
Pairs of Helicoverpa zea (Boddie) larvae reared on diet-incorporated MON810 transgenic leaf tissue of field corn (Zea mays L.) were observed in the laboratory to characterize effects of sublethal levels of Bacillus thuringiensis variety kurstaki (Bt) Cry1Ab endotoxins on cannibalistic behavior and mortality. Feeding on sublethal levels of Bt corn reduced the frequency of cannibalistic behaviors exhibited by H. zea when uneven instars were paired together. Exposure to the Bt endotoxin had no significant effect on when cannibalistic mortality occurred or the level of mortality as a result of cannibalism. Assuming that H. zea larvae reared on nonBt corn tissue behaved in a similar way that resistant larvae would if feeding on Bt tissue, sublethal effects of Cry1Ab intoxication may reduce the chances of successful cannibalism by susceptible larvae and thus play a disproportionate role in the survival of multiple ear infestations. Furthermore, cannibalistic encounters could result in partially resistant larvae feeding on nontoxic food, thus temporarily providing an escape from exposure to the Bt endotoxin. These behavior alterations could increase the selective differential between susceptible individuals and those carrying resistance genes.


Predictors of disease severity in patients admitted to a cholera treatment center in urban Haiti.
Cholera, previously unrecognized in Haiti, spread through the country in the fall of 2010. An analysis was performed to understand the epidemiological characteristics, clinical management, and risk factors for disease severity in a population seen at the GHESKIO Cholera Treatment Center in Port-au-Prince. A comprehensive review of the medical records of patients admitted during the period of October 28, 2010-July 10, 2011 was conducted. Disease severity on admission was directly correlated with older age, more prolonged length of stay, and presentation during the two epidemic waves seen in the observation period. Although there was a high seroprevalence of human immunodeficiency virus (HIV), severity of cholera was not greater with HIV infection. This study documents the correlation of cholera waves with rainfall and its reduction in settings with improved sanitary conditions and potable water when newly introduced cholera affects all ages equally so that interventions must be directed throughout the population.


Targeting cytokine- and therapy-induced PIM1 activation in preclinical models of T-cell acute lymphoblastic leukemia and lymphoma.
T-cell acute lymphoblastic leukemia (T-ALL) and T-cell acute lymphoblastic lymphoma (T-LBL) are aggressive hematological malignancies that are currently treated with high-dose chemotherapy. Over the last several years, the search toward novel and less-toxic therapeutic strategies for T-ALL/T-LBL patients has largely focused on the identification of cell-intrinsic properties of the tumor cell. However, non-cell-autonomous activation of specific oncogenic pathways might also offer opportunities that could be exploited at the therapeutic level. In line with this, we here show that endogenous interleukin 7 (IL7) can increase the expression of the oncogenic kinase proviral integration site for Moloney-murine leukemia 1 (PIM1) in CD127+ T-ALL/T-LBL, thereby rendering these tumor cells sensitive to in vivo PIM inhibition. In addition, using different CD127+ T-ALL/T-LBL xenograft models, we also reveal that residual tumor cells, which remain present after short-term in vivo chemotherapy, display consistent upregulation of PIM1 as compared with bulk nontreated tumor cells. Notably, this effect was transient as increased PIM1 levels were not observed in reestablished disease after abrogation of the initial chemotherapy. Furthermore, we uncover that this phenomenon is, at least in part, mediated by the ability of glucocorticoids to cause transcriptional upregulation of IL7RA in T-ALL/T-LBL patient-derived xenograft (PDX) cells, ultimately resulting in non-cell-autonomous PIM1 upregulation by endogenous IL7. Finally, we confirm in vivo that chemotherapy in combination with a pan-PIM inhibitor can improve leukemia survival in a PDX model of CD127+ T-ALL. Altogether, our work reveals that IL7 and glucocorticoids coordinately drive aberrant activation of PIM1 and suggests that IL7-responsive CD127+ T-ALL and T-LBL patients could benefit from PIM inhibition during induction chemotherapy.


[Drug therapy of hyperkinetic diseases in adults].
Attention deficit hyperactivity disorder (ADHD) is often diagnosed in children. Some major studies proved that symptoms can persist until the patients are grown up and that the prevalence of adult ADHD is underestimated. The classification systems ICD-10 and DSM-IV allow a diagnosis for adults, they differ, however, from childhood regarding symptoms. The diagnostic procedure requires extensive exploration and information from parents and school. Diagnostic interview procedures and questionnaires for self and expert rating are available to date only for English speaking countries. Apart from counselling and psychotherapeutic intervention pharmacotherapy is a third option. Especially stimulants proved to be an efficient treatment. Alternatively tricyclic antidepressants can be considered, other agents play only a minor role. Clinical trials trying to evaluate the efficacy of different pharmacotherapeutic agents are lacking.


Pixel-based analysis of FRAP data with a general initial bleaching profile.
In Jonasson et al. (2008), we presented a new pixel-based maximum likelihood framework for the estimation of diffusion coefficients from data on fluorescence recovery after photobleaching (FRAP) with confocal laser scanning microscopy (CLSM). The main method there, called the Gaussian profile method below, is based on the assumption that the initial intensity profile after photobleaching is approximately Gaussian. In the present paper, we introduce a method, called the Monotone profile method, where the maximum likelihood framework is extended to a general initial bleaching profile only assuming that the profile is a non-decreasing function of the distance to the bleaching centre. The statistical distribution of the image noise is further assumed to be Poisson instead of normal, which should be a more realistic description of the noise in the detector. The new Monotone profile method and the Gaussian profile method are applied to FRAP data on swelling of super absorbent polymers (SAP) in water with a Fluorescein probe. The initial bleaching profile is close to a step function at low degrees of swelling and close to a Gaussian profile at high degrees of swelling. The results obtained from the analysis of the FRAP data are corroborated with NMR diffusometry analysis of SAP with a polyethylene glycol probe having size similar to the Fluorescein. The comparison of the Gaussian and Monotone profile methods is also performed by use of simulated data. It is found that the new Monotone profile method is accurate for all types of initial profiles studied, but it suffers from being computationally slow. The fast Gaussian profile method is sufficiently accurate for most of the profiles studied, but underestimates the diffusion coefficient for profiles close to a step function. We also provide a diagnostic plot, which indicates whether the Gaussian profile method is acceptable or not.


Forming and activating an internal facilitation group for successful implementation: A qualitative study.
This study focuses on an implementation facilitation strategy to improve the delivery of anticoagulation care within pharmacy-run clinics across 8 Veterans Health Administration (VA) medical centers. Other studies have explored various models of implementation facilitation, including external facilitation (EF), internal facilitation (IF), and blended facilitation (BF) combining both approaches. This study focuses on the use of an internal facilitation team of anticoagulation coordinators representing 8 VA anticoagulation clinics to enhance the implementation process. This study examines how the team became instrumental in the successful implementation of evidence-based practice change. Semi-structured interviews were conducted annually over 4 years with representatives from each site, the internal facilitators (site champions), at 8 VA hospitals (47 interviews). Additionally, five external facilitators, experts in quality improvement and anticoagulation care who guided the implementation, were interviewed. Analysis drew on a deductive approach based on the Promoting Action on Research Implementation in Health Services (PARIHS) model and emergent thematic analysis to identify factors related to effectiveness of the internal facilitation team. Key findings are that the following factors enhanced successful uptake of the anticoagulation initiative: 1) Regular participation by the site champion in the internal facilitation team; 2) Champion strongly committed to being an agent of change; and 3) Champion received greater support from their supervisors. The first and second factors are interrelated, as internal facilitators who actively and regularly participated in the internal facilitation team often became truly committed to the improvement project. Both factors relate to the third, as supervisor support not only facilitated changes in practice, but also facilitated regular team attendance and stronger participation. Our study adds to implementation science by detailing how internal facilitators learn their skills over time, and how a group of internal facilitators can help each other succeed. These findings can guide those who wish to incorporate internal facilitation teams as an implementation strategy, and demonstrate how sites can build capacity for implementation efforts. This study focuses on an implementation facilitation strategy to improve the delivery of anticoagulation care within pharmacy-run clinics across 8 Veterans Health Administration medical centers. Internal facilitators (IFs) guided by and supported by an external facilitators (EF), successfully implemented the clinical innovation. This study examines how the IF group became instrumental in the successful implementation of evidence-based practice change.


Two-dose ChAdOx1 nCoV-19 vaccine protection against COVID-19 hospital admissions and deaths over time: a retrospective, population-based cohort study in Scotland and Brazil.
Reports suggest that COVID-19 vaccine effectiveness is decreasing, but whether this reflects waning or new SARS-CoV-2 variants-especially delta (B.1.617.2)-is unclear. We investigated the association between time since two doses of ChAdOx1 nCoV-19 vaccine and risk of severe COVID-19 outcomes in Scotland (where delta was dominant), with comparative analyses in Brazil (where delta was uncommon). In this retrospective, population-based cohort study in Brazil and Scotland, we linked national databases from the EAVE II study in Scotland; and the COVID-19 Vaccination Campaign, Acute Respiratory Infection Suspected Cases, and Severe Acute Respiratory Infection/Illness datasets in Brazil) for vaccination, laboratory testing, clinical, and mortality data. We defined cohorts of adults (aged ≥18 years) who received two doses of ChAdOx1 nCoV-19 and compared rates of severe COVID-19 outcomes (ie, COVID-19 hospital admission or death) across fortnightly periods, relative to 2-3 weeks after the second dose. Entry to the Scotland cohort started from May 19, 2021, and entry to the Brazil cohort started from Jan 18, 2021. Follow-up in both cohorts was until Oct 25, 2021. Poisson regression was used to estimate rate ratios (RRs) and vaccine effectiveness, with 95% CIs. 1 972 454 adults received two doses of ChAdOx1 nCoV-19 in Scotland and 42 558 839 in Brazil, with longer follow-up in Scotland because two-dose vaccination began earlier in Scotland than in Brazil. In Scotland, RRs for severe COVID-19 increased to 2·01 (95% CI 1·54-2·62) at 10-11 weeks, 3·01 (2·26-3·99) at 14-15 weeks, and 5·43 (4·00-7·38) at 18-19 weeks after the second dose. The pattern of results was similar in Brazil, with RRs of 2·29 (2·01-2·61) at 10-11 weeks, 3·10 (2·63-3·64) at 14-15 weeks, and 4·71 (3·83-5·78) at 18-19 weeks after the second dose. In Scotland, vaccine effectiveness decreased from 83·7% (95% CI 79·7-87·0) at 2-3 weeks, to 75·9% (72·9-78·6) at 14-15 weeks, and 63·7% (59·6-67·4) at 18-19 weeks after the second dose. In Brazil, vaccine effectiveness decreased from 86·4% (85·4-87·3) at 2-3 weeks, to 59·7% (54·6-64·2) at 14-15 weeks, and 42·2% (32·4-50·6) at 18-19 weeks. We found waning vaccine protection of ChAdOx1 nCoV-19 against COVID-19 hospital admissions and deaths in both Scotland and Brazil, this becoming evident within three months of the second vaccine dose. Consideration needs to be given to providing booster vaccine doses for people who have received ChAdOx1 nCoV-19. UK Research and Innovation (Medical Research Council), Scottish Government, Research and Innovation Industrial Strategy Challenge Fund, Health Data Research UK, Fiocruz, Fazer o Bem Faz Bem Programme; Conselho Nacional de Desenvolvimento Científico e Tecnológico, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro. For the Portuguese translation of the abstract see Supplementary Materials section.