The molecular basis of nonmelanoma skin cancer: new understanding.
Nonmelanoma skin cancers, including basal cell carcinomas and squamous cell carcinomas, represent the most common malignant neoplasms in humans. Although many environmental and genetic factors contribute to the development of skin cancers, the most important is chronic exposure to UV radiation in sunlight. We now appreciate that the role of UV in the development of nonmelanoma skin cancers is 2-fold. First, UV radiation causes mutations in cellular DNA. Failure to repair these genetic alterations ultimately leads to unrestrained growth and tumor formation. Second, UV radiation has profound effects on the cutaneous immune system, inducing a state of relative immunosuppression that prevents tumor rejection. The purpose of this review is to educate clinical dermatologists about the recent developments in molecular biology and immunology that have greatly enhanced our understanding of how skin cancers arise. The clinical implications of this new knowledge are far-reaching and likely to soon impact the diagnosis, treatment, and prevention of a variety of benign and malignant skin conditions. It will be important for the clinician to understand the biological mechanisms underlying these new therapeutic developments to implement them effectively.


Exit slit mirrors for the ebert spectrometer.
The use of a very long straight entrance slit in an Ebert grating spectrometer with two plane mirrors at the shorter exit slit to increase the energy density is described. This system has been employed in a far uv rocket spectrometer to provide higher sensitivity than has been achieved previously. The imaging properties and required slit and mirror adjustments are presented. Experimental results are included.


Activation of Content-Schemata for Scaffolding L2 Writing: Voices from a Turkish Context.
It has been observed that Turkish university students suffer in L2 writing when they lack background knowledge about the writing topic. Triggered by this observation, this study intended to explore effectiveness of content-schemata activation for scaffolding Turkish students in their challenging L2 writing practices. Study participants, students studying at an English-medium university in Turkey, were asked to write an essay on a specific topic at the beginning of the week before participating in any activities and then they were asked to write a second essay on the same topic after being engaged in various skills activities designed to activate their content-schemata. The same procedure was repeated for seven weeks with a different topic each week. To gather data, students' first and second essays were compared and students' and teachers' perceptions regarding their experiences in English writing classes were elicited through questionnaires. As study findings reveal that content-schemata activation leads to the production of better essays in terms of content and that both students and teachers are positive about the use of skills activities for idea generation prior to essay writing, integration of activities that would activate students' content-schemata into the language curriculum in other ESL/EFL educational contexts is highly recommended.


The effect of small tumor volumes on studies of intratumoral heterogeneity of tracer uptake.
The number of studies in the literature involving quantification of the metabolic heterogeneity seen in (18)F-FDG PET images has increased sharply over recent years. We hypothesized that inclusion of very small regions of interest as unique data points will have deleterious effects on these studies. Using a combination of probability theory and clinical (18)F-FDG PET data, we numerically calculated the curve describing the probability a given tumor volume is large enough to adequately sample the underlying tumor biology assayed via a PET/CT scanner at a planar resolution of 4 mm and transaxial resolution of 4 mm (64 mm(3) voxel size). We then used a computer simulation to isolate the effects of tumor volume on the image local entropy. We computed the underlying global intensity distribution for 70 cervical cancer tumors ranging from 4 to 248 cm(3)), which were ensemble-averaged over the same intensity scale. From this distribution, we determined that about 700 total voxels (45 cm(3)) are required to give 95% certainty that the global intensity distribution has been sufficiently sampled for common statistical comparisons of individual tumor intensity distributions to be made canonically. We demonstrated that one previously suggested measure of heterogeneity is dependent on tumor volume and that measurement of heterogeneity is about 5 times more sensitive to volume changes for volumes below the proposed minimum than for those above it. Inclusion of tumor volumes below 45 cm(3) can profoundly bias comparisons of intratumoral uptake heterogeneity metrics derived from data from the current generation of whole-body (18)F-FDG PET scanners.


Risk Factors Associated with Nursing Home COVID-19 Outbreaks: A Retrospective Cohort Study.
The coronavirus disease 2019 (COVID-19) pandemic had a devastating impact on nursing homes/long-term care facilities. This study examined the relationship between geography, size, design, organizational characteristics, and implementation of infection prevention and control (IPC) measures and the extent of COVID-19 outbreaks in nursing homes in the Autonomous Province of Trento (Italy) during the time frame of March-May 2020. The analysis included 57 nursing homes (5145 beds). The association between median cumulative incidence of COVID-19 cases among residents and characteristics of nursing homes was assessed by Mann-Whitney U test, Kruskal-Wallis test or Spearman rho. To evaluate the potential confounding of geographical area, a 2-level random intercept logistic model was fitted, with level 1 units (patients in nursing homes) nested into level 2 units (nursing homes), and "being a COVID-19 case" as the dependent variable. Median cumulative incidence was not significantly associated with any of the variables, except for geographical region (p = 0.002). COVID-19 cases clustered in the part of the province bordering the Italian region most affected by the pandemic (Lombardy) (45.2% median cumulative incidence). Structural/organizational factors and standard IPC measures may not predict the epidemiology of COVID-19 outbreaks and be sufficient alone to protect nursing homes against them.


Human plasma alpha-cysteine proteinase inhibitor. Purification by affinity chromatography, characterization and isolation of an active fragment.
Human plasma alpha-cysteine proteinase inhibitor (alpha CPI) was purified by a two-stage method: affinity chromatography on S-carboxymethyl-papain-Sepharose, and high-resolution anion-exchange chromatography. The protein was obtained as a form of Mr about 64 000 and material of higher Mr (about 100 000). In sodium dodecyl sulphate/polyacrylamide-gel electrophoresis with reduction, both forms showed a major component of Mr 64 000. An antiserum was raised against alpha CPI, and 'rocket' immunoassays showed the mean concentration in sera from 19 individuals to be 35.9 mg/dl. Both low-Mr and high-Mr forms of alpha CPI were confirmed to be sialoglycoproteins by the decrease in electrophoretic mobility after treatment with neuraminidase. alpha CPI was shown immunologically to be distinct from antithrombin III and alpha 1-antichymotrypsin, two serine proteinase inhibitors from plasma with somewhat similar Mr values. alpha CPI was also distinct from cystatins A and B, the two intracellular low-Mr cysteine proteinase inhibitors from human liver. Complexes of alpha CPI with papain were detectable in immunoelectrophoresis, but dissociated to free enzyme and intact inhibitor in sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. The stoichiometry of binding of papain was close to 1:1 for both low-Mr and high-Mr forms. alpha CPI was found to be a tight-binding inhibitor of papain and human cathepsins H and L (Ki 34 pM, 1.1 nM and 62 pM respectively). By contrast, inhibition of cathepsin B was much weaker, Ki being about 35 microM. Dipeptidyl peptidase I also was weakly inhibited. Digestion of alpha CPI with bromelain gave rise to an inhibitory fragment of Mr about 22 000, which was isolated.


Anemia, myopathy, and pansteatitis in vitamin E-deficient captive marmosets (Callithrix spp.).
Five young adult pet marmosets (Callithrix spp.) were presented with weight loss (5/5); fecal retention (3/5); diarrhea (2/5); impaired locomotion (3/5); anemia (4/4); hypoproteinemia or hypoalbuminemia (3/4); elevations of creatine phosphokinase, lactic dehydrogenase, and alanine aminotransferase (3/4); and renal failure with hypercholesterolemia (2/4). All anemic marmosets had low serum vitamin E levels. The anemia responded to vitamin E and selenium therapy in two marmosets. One of the five marmosets died before presentation, and two others died despite therapy. The two marmosets necropsied had degenerative myopathy, pyogranulomatous pansteatitis, and increased erythrophagocytosis and hemosiderosis. The striated muscle and adipose tissue of both marmosets were negative for coxsackievirus ribonucleic acid by in situ hybridization. These findings suggest that vitamin E deficiency may be involved in the development of anemia, myopathy, and steatitis in callitrichids; however, in some marmosets, underlying diseases such as chronic colitis may have influenced the development of anemia and impaired vitamin E status.


Hepatitis C virus infection mediates cholesteryl ester synthesis to facilitate infectious particle production.
Cholesterol is a critical component of the hepatitis C virus (HCV) life cycle, as demonstrated by its accumulation within infected hepatocytes and lipoviral particles. To cope with excess cholesterol, hepatic enzymes ACAT1 and ACAT2 produce cholesteryl esters (CEs), which are destined for storage in lipid droplets or for secretion as apolipoproteins. Here we demonstrate in vitro that cholesterol accumulation following HCV infection induces upregulation of the ACAT genes and increases CE synthesis. Analysis of human liver biopsy tissue showed increased ACAT2 mRNA expression in liver infected with HCV genotype 3, compared with genotype 1. Inhibiting cholesterol esterification using the potent ACAT inhibitor TMP-153 significantly reduced production of infectious virus, but did not inhibit virus RNA replication. Density gradient analysis showed that TMP-153 treatment caused a significant increase in lipoviral particle density, suggesting reduced lipidation. These data suggest that cholesterol accumulation following HCV infection stimulates the production of CE, a major component of lipoviral particles. Inhibition of CE synthesis reduces HCV particle density and infectivity, suggesting that CEs are required for optimal infection of hepatocytes.


Larotrectinib for paediatric solid tumours harbouring NTRK gene fusions: phase 1 results from a multicentre, open-label, phase 1/2 study.
Gene fusions involving NTRK1, NTRK2, or NTRK3 (TRK fusions) are found in a broad range of paediatric and adult malignancies. Larotrectinib, a highly selective small-molecule inhibitor of the TRK kinases, had shown activity in preclinical models and in adults with tumours harbouring TRK fusions. This study aimed to assess the safety of larotrectinib in paediatric patients. This multicentre, open-label, phase 1/2 study was done at eight sites in the USA and enrolled infants, children, and adolescents aged 1 month to 21 years with locally advanced or metastatic solid tumours or CNS tumours that had relapsed, progressed, or were non-responsive to available therapies regardless of TRK fusion status; had a Karnofsky (≥16 years of age) or Lansky (<16 years of age) performance status score of 50 or more, adequate organ function, and full recovery from the acute toxic effects of all previous anticancer therapy. Following a protocol amendment on Sept 12, 2016, patients with locally advanced infantile fibrosarcoma who would require disfiguring surgery to achieve a complete surgical resection were also eligible. Patients were enrolled to three dose cohorts according to a rolling six design. Larotrectinib was administered orally (capsule or liquid formulation), twice daily, on a continuous 28-day schedule, in increasing doses adjusted for age and bodyweight. The primary endpoint of the phase 1 dose escalation component was the safety of larotrectinib, including dose-limiting toxicity. All patients who received at least one dose of larotrectinib were included in the safety analyses. Reported here are results of the phase 1 dose escalation cohort. Phase 1 follow-up and phase 2 are ongoing. This trial is registered with ClinicalTrials.gov, number NCT02637687. Between Dec 21, 2015, and April 13, 2017, 24 patients (n=17 with tumours harbouring TRK fusions, n=7 without a documented TRK fusion) with a median age of 4·5 years (IQR 1·3-13·3) were enrolled to three dose cohorts: cohorts 1 and 2 were assigned doses on the basis of both age and bodyweight predicted by use of SimCyp modelling to achieve an area under the curve equivalent to the adult doses of 100 mg twice daily (cohort 1) and 150 mg twice daily (cohort 2); and cohort 3 was assigned to receive a dose of 100 mg/m2 twice daily (maximum 100 mg per dose), regardless of age, equating to a maximum of 173% of the recommended adult phase 2 dose. Among enrolled patients harbouring TRK fusion-positive cancers, eight (47%) had infantile fibrosarcoma, seven (41%) had other soft tissue sarcomas, and two (12%) had papillary thyroid cancer. Adverse events were predominantly grade 1 or 2 (occurring in 21 [88%] of 24 patients); the most common larotrectinib-related adverse events of all grades were increased alanine and aspartate aminotransferase (ten [42%] of 24 each), leucopenia (five [21%] of 24), decreased neutrophil count (five [21%] of 24), and vomiting (five [21%] of 24). Grade 3 alanine aminotransferase elevation was the only dose-limiting toxicity and occurred in one patient without a TRK fusion and with progressive disease. No grade 4 or 5 treatment-related adverse events were observed. Two larotrectinib-related serious adverse events were observed: grade 3 nausea and grade 3 ejection fraction decrease during the 28-day follow-up after discontinuing larotrectinib and while on anthracyclines. The maximum tolerated dose was not reached, and 100 mg/m2 (maximum of 100 mg per dose) was established as the recommended phase 2 dose. 14 (93%) of 15 patients with TRK fusion-positive cancers achieved an objective response as per Response Evaluation Criteria In Solid Tumors version 1.1; the remaining patient had tumour regression that did not meet the criteria for objective response. None of the seven patients with TRK fusion-negative cancers had an objective response. The TRK inhibitor larotrectinib was well tolerated in paediatric patients and showed encouraging antitumour activity in all patients with TRK fusion-positive tumours. The recommended phase 2 dose was defined as 100mg/m2 (maximum 100 mg per dose) for infants, children, and adolescents, regardless of age. Loxo Oncology Inc.


Association between insulin-like growth factor status and physical activity levels in rheumatoid arthritis.
To determine if the altered insulin-like growth factor (IGF) status in rheumatoid arthritis (RA) is due to inflammation, altered body composition, or lack of exercise. Subjects included 73 patients with RA, 54 patients with other rheumatic diseases, both inflammatory and noninflammatory, and 28 healthy, physically active controls. Serum levels of IGF-I, IGF-II, and IGF binding protein-3 (IGFBP-3) were measured by radioimmunoassay. Body composition was estimated by bioelectrical impedance analysis, and habitual exercise level approximated by questionnaire. Statistical analysis was performed by 2 and 3 way ANOVA and moderated hierarchical regression. Serum IGF-I (p < 0.001), IGFBP-3 (p < 0.001), and the BP-3:total IGF molar ratio (p < 0.001) were depressed in both patient groups relative to controls. In contrast, IGF-II levels were depressed only in patients with RA (p < 0.01). Differences in the IGF proteins between patients and controls could not be attributed to inflammation. Habitual exercise level, but not body composition, was shown to be a significant predictor for IGF-I, IGFBP-3, and BP-3:total IGF molar ratio (p < 0.001). Our results indicate that the reduction in circulating IGF proteins observed in our patients is more related to their sedentary lifestyle than to the inflammatory process. This conclusion is in agreement with reports that show that highly active individuals typically exhibit higher levels of systemic IGF proteins than age matched sedentary controls.


Anti-inflammatory and antiapoptotic effect of interleukine-18 binding protein on the spinal cord ischemia-reperfusion injury.
We investigated the anti-inflammatory and antiapoptotic effects of interleukin-18 binding protein (IL-18BP) on spinal cord ischemia/reperfusion (I/R) injury in rats. Twenty-one adult male rats were divided into three groups: sham, I/R, and I/R+IL-18BP. Proinflammatory cytokines were determined in rat blood samples by using ELISA, while apoptosis was immunohistochemically evaluated in spinal cord tissue using caspase 3. Both IL-18 and TNF-α were significantly decreased in the IL-18BP group compared to that in the sham group. The highest caspase 3 levels were observed in the I/R group, while the lowest levels were found in the sham group. The mean Tarlov score of the I/R group was significantly lower than that of the sham group. However, the mean Tarlov score of the IL-18BP group was significantly higher than that of the I/R group. The results of the current study demonstrate that IL-18BP plays both anti-inflammatory and antiapoptotic roles in spinal cord I/R injury.


The curious characteristics of pyrazinamide: a review.
Pyrazinamide (PZA) is an important sterilising tuberculosis drug that helps to shorten the duration of current chemotherapy regimens for tuberculosis. When first discovered, it had activity in murine tuberculosis but no apparent in vitro activity, and its subsequent use in treatment depended largely on classic experiments at Cornell University, which showed its requirement for an acid pH for activity and its sterilising activity in the mouse. Recent studies have shown that PZA enters Mycobacterium tuberculosis by passive diffusion, is converted to pyrazinoic acid (POA) by nicotinamidase/pyrazinamidase (PZase) and is then excreted by a weak efflux pump. Protonated POA (HPOA) is reabsorbed into the bacilli under acid conditions and accumulates because the efflux pump is inefficient, causing cellular damage. Unlike other antibacterials, PZA has no defined target of action. PZA is more active against old than against actively growing cultures, probably because the energy production and efflux pump would be slowed down by low bacterial metabolism. This review deals with the activity of PZA in vitro, in macrophages and in animal models. It describes the evidence from clinical trials that it is an effective sterilising drug that acts synergistically with rifampicin. The highly diverse mutations in the PZase gene (pncA) that lead to loss of PZase activity cause PZA resistance. Methods for susceptibility determination either as tests against PZA or nicotinamide in liquid and solid media, as tests for PZase activity or for mutations in pncA, are reviewed.


Peripheral prepositioning and local CXCL9 chemokine-mediated guidance orchestrate rapid memory CD8+ T cell responses in the lymph node.
After an infection, the immune system generates long-lived memory lymphocytes whose increased frequency and altered state of differentiation enhance host defense against reinfection. Recently, the spatial distribution of memory cells was found to contribute to their protective function. Effector memory CD8+ T cells reside in peripheral tissue sites of initial pathogen encounter, in apparent anticipation of reinfection. Here we show that within lymph nodes (LNs), memory CD8+ T cells were concentrated near peripheral entry portals of lymph-borne pathogens, promoting rapid engagement of infected sentinel macrophages. A feed-forward CXCL9-dependent circuit provided additional chemotactic cues that further increase local memory cell density. Memory CD8+ T cells also produced effector responses to local cytokine triggers, but their dynamic behavior differed from that seen after antigen recognition. These data reveal the distinct localization and dynamic behavior of naive versus memory T cells within LNs and how these differences contribute to host defense.


Altered default mode network connectivity in older adults with cognitive complaints and amnestic mild cognitive impairment.
Default mode network (DMN) disruption has been reported in Alzheimer's disease (AD), yet the specific pattern of altered connectivity over the course of prodromal AD remains to be characterized. The aim of this study was to assess DMN connectivity in older adults with informant-verified cognitive complaints (CC) but normal neuropsychological performance compared to individuals with mild cognitive impairment (MCI) and healthy controls (HC). DMN maps were derived from resting-state fMRI using independent component analysis. Group comparisons of DMN connectivity were performed between older adults with MCI (n = 18), CC (n = 23), and HC (n = 16). Both CC and MCI showed decreased DMN connectivity in the right hippocampus compared to HC, with the CC group showing greater connectivity than MCI. These differences survived atrophy correction and correlated with cognitive performance. DMN connectivity appears sensitive to early prodromal neurodegenerative changes associated with AD, notably including pre-MCI individuals with cognitive complaints.


Molecular modeling of 2-alkyloxy- and 2-aralkyloxy-adenosine A1- and A2-agonists.
The C2-region of adenosine A1- and A2-receptors by a molecular modeling technique has been extended and applied to a series of 2-substituted adenosines reported by Olsson, et al. The similarity and dissimilarity of the structure maps obtained by molecular modeling have been used as a basis for the mapping of the analysed receptor domain. The proposed model of the C2-region of the A1-receptor consists of a narrow and sterically limited area that interacts well electrostatically with small and electron rich moieties. Olsson's provisional model of the C2-region of the A2-receptor has been extended with two subsites, as well as with a forbidden area near the C2-position of the purine ring. The conformational analysis performed in the study does not support the hypothesis of Olsson et al. that adenosine C2 substituents may partly occupy the same receptor domain as the N6 substituents of the A1-receptor. The occupation of the cycloalkyl subsite increases the receptor selectivity while the occupation of the other subsite by aryl rings, fixed at a parallel position to the purine system, highly enhances the receptor affinity.


Transient Circulation Event near the Deep Ocean Floor.
On 24 January 1968, a transient deep-circulation event was recorded by a triangular array of autonomous current recorders installed 3 meters above the bottom at two of the three positions and at intervals of 3 to 1000 meters above the bottom at the third position in a depth of 3950 meters above the relatively smooth floor of the eastern North Pacific. The event interrupted a 24-hour record of relatively steady but peculiar conditions, lasted for about 1(1/2) hours, and was followed by current directions and speeds that greatly differed from those of the initial period. The event occurred over a volume of the sea of at least 2 kilometers in horizontal dimensions and 1 kilometer thick. Associated with the event were many small clockwise-rotating features extending from 3 to at least 1000 meters above the bottom and a rapidly increasing current velocity at 1000 meters. The event was probably local and may have involved convective motion, internal waves, and the passage of front. Some of the changes in horizontal velocity may have resulted from the combined effects of upwelling and the earth's rotation.


[Value of EEG in the characterization and prognosis of neurological diseases in premature infants].
The importance of the EEG for the investigation of neurological diseases in the neonatal period has been largely discussed, since it is often the only way to approach cerebral function in newborns with severe pathologies or under drug effect. The present study was carried out with 85 newborns (NB) who presented perinatal dysfunctions and were submitted to neurological and electroencephalogram (EEG) or polysomnography (PS) evaluation. EEG/PS alterations, pathologies and prognosis were reported. The EEG were classified according to basal activity alterations, presence of paroxysmal activity and sleep stages organization and maturity. The most frequent pathology was perinatal asphyxia (40%) followed by intraventricular hemorrhage (HIV, 16%). The most frequent complaint for exam indication was apnea (71%) followed by convulsion (19%). Fifty-five percent of the exams exclusively required because apnea complaint were considered normal and out of all exams required because seizures only 31% were normal. The EEG alteration most frequently related to perinatal asphyxia, HIV and intrauterine growth delay was immaturity and in the NB with seizures immature EEG and abnormal paroxysms. Many different alterations were registered in the NB with nervous system infection. The EEG findings more correlated with unfavorable prognosis were isoelectricity and abnormal paroxysmal activity including positive sharp waves (100%).


Primary Ewing's sarcoma of the talus.
Ewing's sarcoma is a malignant round cell tumour of bones and soft tissues that usually arises from the diaphyseal or meta-diaphyseal parts of long bones and less commonly from flat bones. It occurs rarely in the foot and if occurs, the calcaneus and the metatarsals are commonly involved. We present a case of a young woman diagnosed with primary Ewing's sarcoma of the talus with local spread to adjacent tarsals and the ankle joint. Ewing's sarcoma of feet, if present with even a trivial suspicion of spread either locally or distant, makes limb salvage surgery difficult. So, the treatment with radical surgery or by combined chemotherapy and radiotherapy should be considered-keeping in mind the complex anatomy of the foot and the difficulty in achieving tumour-free margins. Based on this experience, she underwent below-knee amputation. The patient received adjuvant chemotherapy and survived with a disease-free survival at the latest follow-up of 1 year.


The role of head and body cues in visual individual recognition in grey parrots (Psittacus erithacus).
Individual recognition underlies social behaviors in many species and is essential for complex social interactions commonly occurring between conspecifics. Focusing on visual perception, we explored this process in African grey parrots (Psittacus erithacus) using the matching-to-sample (MTS) method commonly used in primate research. We used cards made from photographs of familiar conspecific in four consecutive experiments, first testing the ability of our subjects (two male and one female adult) to match the photographs of familiar individuals and then creating modified stimuli cards to determine which visual aspects and features were crucial for successful recognition of a familiar conspecific. All three subjects were able to successfully match different photographs of familiar conspecifics in Experiment 1. Experiments 2-4 showed that modification of the facial area in the photograph had only a weak effect on subjects' success rates in MTS tasks. On the other hand, changes in the plumage color or obscuring of abdominal cues impaired their ability to successfully match conspecifics' photographs in some tasks. This study implies that African grey parrots process visual information holistically. Moreover, the process of individual recognition in this species differs from what we find in primates, including humans, where faces play a crucial role. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


The medial ganglionic eminence gives rise to a population of early neurons in the developing cerebral cortex.
During development of the neocortex, the marginal zone (layer I) and the subplate (layer VII) are the first layers to form from a primordial plexiform neoropil. The cortical plate (layers II-VI) is subsequently established between these superficial and deep components of the primordial plexiform neuropil. Neurons in the early zones are thought to play important roles in the formation of the cortex: the Cajal-Retzius cells of the marginal zone are instrumental in neuronal migration and laminar formation, and cells of the subplate are involved in the formation of cortical connections. Using the fluorescent tracer 1,1'-dioctodecyl-3,3,3', 3'-tetramethylindocarbocyanine (DiI), we have shown here that a substantial proportion of neurons of the marginal zone, including cells with features of Cajal-Retzius cells, and of the subplate and lower intermediate zone are not born in the ventricular neuroepithelium but instead originate in the medial ganglionic eminence (MGE), the pallidal primordium. These neurons follow a tangential migratory route to their positions in the developing cortex. They express the neurotransmitter GABA but seem to lack the calcium binding protein calretinin; some migrating cells found in the marginal zone express reelin. In addition, migrating cells express the LIM-homeobox gene Lhx6, a characteristic marker of the MGE. It is suggested that this gene uniquely or in combination with other transcription factors may be involved in the decision of MGE cells to differentiate in situ or migrate to the neocortex.


Item responsiveness of a rhinitis and asthma symptom score during a pollen season.
Twenty-one asthma patients with allergic rhinitis completed a series of self-administered questionnaires (21-item symptom score for rhinosinusitis and asthma, bother scale, McMaster Asthma Quality of Life Questionnaire [MAQOL] and Euroqol) at 2-week intervals from August to November 1994. Relative responsiveness of the instruments was assessed in reference to the maximum and minimum average scores for MAQOL, with area under the curve (AUC) and correlation coefficients between the different instruments. Symptom score, MAQOL, and bother scale provided similar results for both extreme values and AUC, whereas Euroqol utilities were less responsive. These results suggest that the symptom scores and bother scales are responsive and valid, and might prove valuable in everyday practice, clinical trials, and quality assurance programs.


[Phospholipid level and activity of lipid peroxidation in the myocardium of rabbits with a chronic inflammatory bronchopulmonary process].
The changes were examined in the content and spectrum of phospholipids and lipid peroxidation in right heart tissue during chronic inflammatory bronchopulmonary process. The content of phosphatidylcholines, phosphatidylserines, diphosphatidylglycerins in the myocardium decreased and lysophosphatidylcholines appeared in the spectrum of total phospholipids, which was accompanied by dramatic activation of lipid peroxidation.


Stepped wedge cluster randomized controlled trial designs: a review of reporting quality and design features.
The stepped wedge (SW) cluster randomized controlled trial (CRCT) design is being used with increasing frequency. However, there is limited published research on the quality of reporting of SW-CRCTs. We address this issue by conducting a literature review. Medline, Ovid, Web of Knowledge, the Cochrane Library, PsycINFO, the ISRCTN registry, and ClinicalTrials.gov were searched to identify investigations employing the SW-CRCT design up to February 2015. For each included completed study, information was extracted on a selection of criteria, based on the CONSORT extension to CRCTs, to assess the quality of reporting. A total of 123 studies were included in our review, of which 39 were completed trial reports. The standard of reporting of SW-CRCTs varied in quality. The percentage of trials reporting each criterion varied to as low as 15.4%, with a median of 66.7%. There is much room for improvement in the quality of reporting of SW-CRCTs. This is consistent with recent findings for CRCTs. A CONSORT extension for SW-CRCTs is warranted to standardize the reporting of SW-CRCTs.


Early prediction of spontaneous Patent Ductus Arteriosus (PDA) closure and PDA-associated outcomes: a prospective cohort investigation.
Patent ductus arteriosus (PDA), the most commonly diagnosed cardiovascular condition in preterm infants, is associated with increased mortality and harmful long-term outcomes (chronic lung disease, neurodevelopmental delay). Although pharmacologic and/or interventional treatments to close PDA likely benefit some infants, widespread routine treatment of all preterm infants with PDA may not improve outcomes. Most PDAs close spontaneously by 44-weeks postmenstrual age; treatment is increasingly controversial, varying markedly between institutions and providers. Because treatment detriments may outweigh benefits, especially in infants destined for early, spontaneous PDA closure, the relevant unanswered clinical question is not whether to treat all preterm infants with PDA, but whom to treat (and when). Clinicians cannot currently predict in the first month which infants are at highest risk for persistent PDA, nor which combination of clinical risk factors, echocardiographic measurements, and biomarkers best predict PDA-associated harm. Prospective cohort of untreated infants with PDA (n=450) will be used to predict spontaneous ductal closure timing. Clinical measures, serum (brain natriuretic peptide, N-terminal pro-brain natriuretic peptide) and urine (neutrophil gelatinase-associated lipocalin, heart-type fatty acid-binding protein) biomarkers, and echocardiographic variables collected during each of first 4 postnatal weeks will be analyzed to identify those associated with long-term impairment. Myocardial deformation imaging and tissue Doppler imaging, innovative echocardiographic techniques, will facilitate quantitative evaluation of myocardial performance. Aim1 will estimate probability of spontaneous PDA closure and predict timing of ductal closure using echocardiographic, biomarker, and clinical predictors. Aim2 will specify which echocardiographic predictors and biomarkers are associated with mortality and respiratory illness severity at 36-weeks postmenstrual age. Aim3 will identify which echocardiographic predictors and biomarkers are associated with 22 to 26-month neurodevelopmental delay. Models will be validated in a separate cohort of infants (n=225) enrolled subsequent to primary study cohort. The current study will make significant contributions to scientific knowledge and effective PDA management. Study results will reduce unnecessary and harmful overtreatment of infants with a high probability of early spontaneous PDA closure and facilitate development of outcomes-focused trials to examine effectiveness of PDA closure in "high-risk" infants most likely to receive benefit. ClinicalTrials.gov NCT03782610. Registered 20 December 2018.


Bis-(5'-guanosyl) tetraphosphatase in rat tissues.
The occurrence and distribution of bis-(5'-guanosyl) tetraphosphatase activity towards dinucleoside tetraphosphates between the 27 000 g supernatant and sedimented fraction were studied in liver, kidney, brain, muscle and intestinal mucosa from rat. The p1p4-bis-(5'-guanosyl) tetraphosphate-hydrolysing activities found in total homogenates were 0.77, 1.44, 0.39, 0.36 and 2.14 units (mumol/min)/g respectively. The activities found in the 27000 g-sedimented fractions were 74, 49, 11, 4 and 96% of those present in the homogenates respectively. The properties of the soluble enzymes were investigated. All of them have low Km values for p1p4-bis-(5'-guanosyl) tetraphosphate (from 2 to 50 microM), are competitively inhibited by guanosine 5'-tetraphosphate with K1 values from 10 to 160 nM, have molecular weights of about 21 000, require Mg2+ or Mn2+ and are inhibited by Ca2+. These properties show that bis-(5'-guanosyl) tetraphosphatase (EC 188.8.131.52), an enzyme previously characterized in Artemia salina and rat liver [Warner & Finamore (1965) Biochemistry 4, 1568-1575; Vallejo, Sillero & Sillero (1974) Biochim, Biophys. Acta 358, 117-125; Lobatón, Vallejo, Sillero & Sillero (1975) Eur. J. Biochem. 50, 495-501], is present in all the rat tissues examined. The inhibition of the enzyme by Ca2+ could be related to the effect of p1p4-bis-(5'-adenosyl) tetraphosphate as a trigger of DNA synthesis [Grummt, Waltl, Jantzen, Hamprecht, Huebscher & Kuenzle (1979) Proc. Natl. Acad. Sci. U.S.A. 76, 6081-6085].


Image reconstruction through dynamic scattering media based on deep learning.
Under complex scattering conditions, it is very difficult to capture clear object images hidden behind the media by modelling the inverse problem. With regard to dynamic scattering media, the challenge increases. For solving the inverse problem, we propose a new class-specific image reconstruction algorithm. The method based on deep learning classifies blurred scattering images according to scattering conditions and then recovers to clear images hidden behind the media. The deep learning network is used to learn the mapping relationship between the object and the scattering image rather than characterizing the scattering media explicitly or parametrically. 25000 scattering images are obtained under five sets of dynamic scattering condition to verify the feasibility of the proposed method. In addition, the generalizability of the method has been verified successfully. Compared with common CNN method, it's confirmed that our algorithm has better performance in reconstructing higher-quality images. Furthermore, for a given scattering image with unknown scattering condition, the closest scattering condition information can be given by classification network, and then the corresponding clear image is restored by reconstruction network.


Granulicella paludicola gen. nov., sp. nov., Granulicella pectinivorans sp. nov., Granulicella aggregans sp. nov. and Granulicella rosea sp. nov., acidophilic, polymer-degrading acidobacteria from Sphagnum peat bogs.
Five strains of strictly aerobic, heterotrophic bacteria that form pink-red colonies and are capable of hydrolysing pectin, xylan, laminarin, lichenan and starch were isolated from acidic Sphagnum peat bogs and were designated OB1010(T), LCBR1, TPB6011(T), TPB6028(T) and TPO1014(T). Cells of these isolates were Gram-negative, non-motile rods that produced an amorphous extracellular polysaccharide-like substance. Old cultures contained spherical bodies of varying sizes, which represent starvation forms. Cells of all five strains were acidophilic and psychrotolerant, capable of growth at pH 3.0-7.5 (optimum pH 3.8-4.5) and at 2-33°C (optimum 15-22°C). The major fatty acids were iso-C(15 : 0), C(16 : 0) and summed feature 3 (C(16 : 1)ω7c and/or iso-C(15 : 0) 2-OH). The major menaquinone detected was MK-8. The pigments were carotenoids. The genomic DNA G+C contents were 57.3-59.3 mol%. The five isolates were found to be members of subdivision 1 of the phylum Acidobacteria and displayed 95.3-98.9 % 16S rRNA gene sequence similarity to each other. The closest described relatives to strains OB1010(T), LCBR1, TPB6011(T), TPB6028(T), and TPO1014(T) were members of the genera Terriglobus (94.6-95.8 % 16S rRNA gene sequence similarity) and Edaphobacter (94.2-95.4 %). Based on differences in cell morphology, phenotypic characteristics and hydrolytic capabilities, we propose a novel genus, Granulicella gen. nov., containing four novel species, Granulicella paludicola sp. nov. with type strain OB1010(T) (=DSM 22464(T) =LMG 25275(T)) and strain LCBR1, Granulicella pectinivorans sp. nov. with type strain TPB6011(T) (=VKM B-2509(T) =DSM 21001(T)), Granulicella rosea sp. nov. with type strain TPO1014(T) (=DSM 18704(T) =ATCC BAA-1396(T)) and Granulicella aggregans sp. nov. with type strain TPB6028(T) (=LMG 25274(T) =VKM B-2571(T)).


Post-transplant diabetes mellitus: Findings in nutritional status and body composition.
Weight gain and changes in body composition are associated with the onset of diabetes after kidney transplantation, and detailing these changes can help prevent this situation. The study aimed to assess the prevalence of diabetes mellitus after kidney transplantation and changes in the nutritional status and body composition in patients with diabetes one year from surgery. This survey was a single-center, prospective cohort study. Twenty-nine patients over 18 years old who underwent isolated kidney transplantation, without diabetes, were included and followed up for one year. At hospital discharge after transplantation and one year later, anthropometric (weight, height and abdominal circumference), body composition (electrical bioimpedance), routine biochemical and dietary intake assessments were performed. Most of the patients were male (75%), and the mean age was 48.0±11.8 years old. In the first-year post-surgery 27.6% of patients had DM and the diagnosis was made, on average, 4 months after transplantation. The group with diabetes had, from the beginning to the end of the study, greater weight and body fat, especially abdominal fat. The non-diabetic group, after one year, showed an increase in phase angle, body weight and body masses, more pronounced of fat-free mass, when compared with fat mass gain. Both groups showed weight gain, but in the non-diabetic group these changes can be interpreted as an improvement in the nutritional profile. Metabolic abnormalities associated with immunosuppression and eating habits, combination that maintains increased the risk for diabetes for long time, keeping this group with priority in nutritional care.


Predictors of mortality in autoimmune disease patients with concurrent cytomegalovirus infections detected by quantitative real-time PCR.
Cytomegaloviruses (CMV) can have a significant impact on the prognosis of immunocompromised patients. Unlike in the transplantation and AIDS fields, only a few studies on CMV infections have been published in the field of autoimmunity. In this study, we examined the clinical outcomes of CMV infections in patients with autoimmune diseases at a single tertiary medical institution. A retrospective study was performed to identify the mortality risk factors associated with CMV infections in patients with autoimmune diseases. We reviewed the medical records of patients with autoimmune diseases who were diagnosed with CMV infections using real-time quantitative polymerase chain reaction between December 2005 and March 2016. Clinical and laboratory parameters as well as treatment outcomes were analyzed. Seventy-three CMV infected patients were separated into survivors and non-survivors. Non-survivors had significantly higher median CMV-DNA copy numbers than survivors (95,500 vs 6,700 copies/mL, p = 0.005) and demonstrated significantly more frequent incidents of CMV pneumonitis (69.2 vs 36.2%, p = 0.007). After adjusting for multiple confounding covariates, the log CMV-DNA copies/mL (hazard ratio, 1.48; 95% confidence interval, 1.14-1.92; p = 0.003) and the presence of concurrent infections (hazard ratio, 22.00; 95% confidence interval, 2.75-175.97, p = 0.004) were identified as independent mortality risk factors. Furthermore, patients with high CMV copy numbers (> 60,000 copies/mL) had higher in-hospital mortality than those with low CMV copy numbers (p < 0.05). CMV-DNA copy numbers and concurrent infections are predictors of in-hospital mortality in CMV-infected patients with autoimmune diseases. Therefore, serial measurements of CMV-DNA copy numbers and close observation for signs of other infections are recommended for patients with autoimmune diseases who have concurrent CMV infection.


Hematologic effects of the high-energy endocardial ablation technique.
Ablation of atrioventricular conduction is now widely accepted in the management of supraventricular arrhythmias. Reports of high temperatures, high pressures, and gas production suggest that there may be adverse effects on the blood, the electrode, and the cardiovascular system. In this investigation, using samples of fresh, heparinized pig blood, we measured hemolytic damage, the liberated gas volume and composition, and electrode erosion associated with high-energy electrical ablation. The blood was tested in a 10 liter tank at room temperature. Impulses of 10 to 400 J were applied to new USCI No. 6F bipolar pacing electrodes using both positive and negative polarities. Voltage and current waveforms were recorded. The volume of gas liberated with cathodal electrodes was 0.50 microliter/J up to 50 J and 0.29 microliter/J above 100 J. It was composed predominantly of hydrogen and nitrogen, with carbon dioxide and oxygen. With positive electrodes, the gas volume was linearly related to energy at 4.34 microliter/J up to 200 J and also contained carbon monoxide. The hemolysis was directly proportional to impulse energy for both cathodal and anodal electrodes, being 1.37 microliter/J and 4.48 microliters/J, respectively. Electrode erosion was substantial but clinically acceptable. We conclude that there are marked differences in the energy conversion processes and, where the same energy can achieve a comparable clinical effectiveness, there are advantages in using a cathodal electrode polarity. It is also advisable to use lower energies.


Review of nutrition guidelines relevant for adolescents in low- and middle-income countries.
The economic and social well-being of any country will one day depend on its current adolescent population. To provide a good foundation for healthy adolescent development, healthy diet, along with physical activity and adequate nutrients, is necessary. Therefore, addressing the nutrition needs of adolescents could be an important step toward breaking the vicious cycle of intergenerational malnutrition, chronic diseases, and poverty. These problems could be addressed with timely recognition and appropriately delivered interventions. Our aim here is to review the existing guidelines on various aspects of nutrition interventions for adolescents and young women. We review all of the major existing guidelines on adolescent nutrition. We were able to find 18 guideline bodies that covered some form of nutritional advice in guidelines that targeted adolescents. Although the guidelines that focus specifically on this age group are limited in scope, we also extrapolated recommendations from guidelines focused on adults, women of reproductive age, and pregnant women, which were based on evidence that included populations of adolescent girls. We were able to extract and synthesize specific directives for nutrition in adolescents, macro- and micronutrient supplementation, exercise, obesity, and nutrition during preconception, pregnancy, and the postconception period.


Explaining illness with evil: pathogen prevalence fosters moral vitalism.
Pathogens represent a significant threat to human health leading to the emergence of strategies designed to help manage their negative impact. We examined how spiritual beliefs developed to explain and predict the devastating effects of pathogens and spread of infectious disease. Analysis of existing data in studies 1 and 2 suggests that moral vitalism (beliefs about spiritual forces of evil) is higher in geographical regions characterized by historical higher levels of pathogens. Furthermore, drawing on a sample of 3140 participants from 28 countries in study 3, we found that historical higher levels of pathogens were associated with stronger endorsement of moral vitalistic beliefs. Furthermore, endorsement of moral vitalistic beliefs statistically mediated the previously reported relationship between pathogen prevalence and conservative ideologies, suggesting these beliefs reinforce behavioural strategies which function to prevent infection. We conclude that moral vitalism may be adaptive: by emphasizing concerns over contagion, it provided an explanatory model that enabled human groups to reduce rates of contagious disease.


A multifunctional online research portal for facilitation of simulation-based research: a report from the EXPRESS pediatric simulation research collaborative.
Simulation-based research requires the coordinated effort of research teams to design projects, recruit subjects, and carry out performance assessments of individuals or teams. These efforts can often be labor intensive, time consuming, and logistically challenging, especially in the context of multicenter simulation-based research trials. We have developed a multifunctional, internet-based research portal for facilitation of simulation-based research. This free portal, accessible from www.cesei.org, is capable of managing the research process by helping researchers to design their project, setup data collection using customized assessment tools, upload videos for performance assessment, and finally, download data-filled spreadsheets for statistical analysis. The research portal has been used successfully to manage the first major project of the EXPRESS research collaborative, a multicenter research study involving 15 recruitment sites and more than 400 subjects. The use of the research portal has enabled us to simplify and streamline the management of our multicenter research studies. We envision that this portal will permit novice and expert researchers alike to carry out their simulation-based research projects in a coordinated and time-efficient fashion, thus ultimately helping to enhance their overall research productivity.


CaMKIIδ-mediated inflammatory gene expression and inflammasome activation in cardiomyocytes initiate inflammation and induce fibrosis.
Inflammation accompanies heart failure and is a mediator of cardiac fibrosis. CaMKIIδ plays an essential role in adverse remodeling and decompensation to heart failure. We postulated that inflammation is the mechanism by which CaMKIIδ contributes to adverse remodeling in response to nonischemic interventions. We demonstrate that deletion of CaMKIIδ in the cardiomyocyte (CKO) significantly attenuates activation of NF-κB, expression of inflammatory chemokines and cytokines, and macrophage accumulation induced by angiotensin II (Ang II) infusion. The inflammasome was activated by Ang II, and this response was also diminished in CKO mice. These events occurred prior to any evidence of Ang II-induced cell death. In addition, CaMKII-dependent inflammatory gene expression and inflammasome priming were observed as early as the third hour of infusion, a time point at which macrophage recruitment was not evident. Inhibition of either the inflammasome or monocyte chemoattractant protein 1 (MCP1) signaling attenuated macrophage accumulation, and these interventions, like cardiomyocyte CaMKIIδ deletion, diminished the fibrotic response to Ang II. Thus, activation of CaMKIIδ in the cardiomyocyte represents what we believe to be a novel mechanism for initiating inflammasome activation and an inflammatory gene program that leads to macrophage recruitment and ultimately to development of fibrosis.


Inositol trisphosphate mediates cloned muscarinic receptor-activated conductances in transfected mouse fibroblast A9 L cells.
1. The mechanism by which cloned m1 and m3 muscarinic receptor subtypes activate Ca2+-dependent channels was investigated with whole-cell and cell-attached patch-clamp recording techniques and with Fura-2 Ca2+ indicator dye measurements in cultured A9 L cells transfected with rat m1 and m3 cDNAs. 2. The Ca2+-dependent K+ and Cl- currents induced by muscarinic receptor stimulation were dependent on GTP. Responses were reduced when GTP was excluded from the intracellular recording solution or when GDP-beta-S was added. Intracellular GTP-gamma-S activated spontaneous fluctuations and permitted only one acetylcholine-(ACh) induced current response. These results implicate GTP-binding proteins (G protein) in the signal transduction pathway. This G protein is probably not pertussis toxin-sensitive as the ACh-induced electrical response was not abolished by pertussis toxin treatment. 3. Cell-attached single-channel recordings revealed activation of ion channels within the patch during application of ACh outside the patch, implying that second messengers might be involved in the ACh-induced response. Two types of K+ channel were activated, a discrete channel of 36 pS and channel activity calculated to be about 5 pS. 4. Application of 8-bromo cyclic AMP or 1-oleoyl-1,2-acetylglycerol (OAG) produced no electrical response and did not affect the ACh-induced responses. Phorbol myristic acetate (PMA) evoked no electrical response, but reduced the ACh-induced responses. 5. Inclusion of inositol 1,4,5-trisphosphate (IP3) in the intracellular pipette solution activated outward currents at -50 mV associated with an increase in conductance. The IP3-induced current response reversed polarity at -65 mV and showed a dependence on K+. Increasing the intracellular free Ca2+ concentration ([Ca2+]i) from 20 nM to 1 microM also induced an outward current response associated with an increase in conductance. Inclusion of inositol 1,3,4,5-tetrakisphosphate (IP4) in the intracellular solution had no effect on the A9 L cells. 6. Fura-2 measurements revealed ACh-induced increases in Cai2+. The Ca2+ responses were abolished by atropine showing that they were muscarinic in nature. Removal of extracellular Ca2+ did not affect the initial ACh-induced increase in Cai2+ but subsequent Cai2+ responses to ACh were depressed, suggesting depletion of Ca2+ intracellular stores. Residual though small responses continued to be elicited by ACh. Barium (5 mM) had little effect and cobalt slightly reduced the ACh-induced Ca2+ response. 7. The ACh-induced currents recorded at -50 mV were unaffected by removal of extracellular Ca2+.(ABSTRACT TRUNCATED AT 400 WORDS)


Trophic structure of a nektobenthic community exploited by a multispecific bottom trawling fishery in Northeastern Brazil.
We used complementary stable isotope (SIA) and stomach content (SCA) analyses to investigate feeding relationships among species of the nektobenthic communities and the potential ecological effects of the bottom trawling of a coastal ecosystem in northeastern Brazil. Carbon (δ13C) and nitrogen (δ15N) compositions were determined for five basal sources and 28 consumers, from zooplankton to shrimp and fish species. Fishes and basal sources showed a broad range of δ15N (fishes: 6.49-14.94‰; sources: 2.58-6.79‰) and δ13C values (fishes: -23.86 to -13.71‰; sources: -24.32 to -13.53‰), while shrimps and crabs exhibited similar nitrogen and carbon ratios. Six trophic consumer groups were determined among zooplankton, crustaceans and fishes by SIA, with trophic pathways associated mostly with benthic sources. SCA results indicated a preference for benthic invertebrates, mainly worms, crabs and shrimps, as prey for the fish fauna, highlighting their importance in the food web. In overall, differences between SCA and the SIA approaches were observed, except for groups composed mainly for shrimps and some species of high δ15N values, mostly piscivorous and zoobenthivores. Given the absence of regulation for bottom trawling activities in the area, the cumulative effects of trawling on population parameters, species composition, potentially decreasing the abundance of benthic preys (e.g., shrimps, worms and crabs) may lead to changes in the trophic structure potentially affect the food web and the sustainability of the fishery.


Comparison of the protective effect amongst anticholinergic drugs on methacholine-induced bronchoconstriction in asthma.
The protective effect of inhaled anticholinergic drugs in the methacholine-induced bronchospasm is well-known. The objective of this study was to assess if any possible differences may be found among Ipratropium (IB), Oxitropium (OXI) and Tiotropium (TIO) pre-treatments to obtain the protective effect. Forty-four patients with intermittent bronchial asthma and PD(20)FEV(1) < 200 microg were selected (24 M, 20 F; mean age 32 +/- 8.8). On the baseline, they had mean FEV(1)%: 98.8 +/- 8.54 of theoretical and mean PD(15)FEV(1) 111.8 +/- 61.04 microg. After 72 hours, all patients underwent a second methacholine challenge and were given Ipratropium (40 microg by MDI in 14 pts) or Oxitropium (200 microg by MDI in 14 pts) or Tiotropium (18 microg by Handihaler in 16 pts) sixty minutes before the test. Sixty minutes after the bronchodilator inhalation, the FEV(1)% increase was higher (p < 0.05) in OXI (6.7 +/- 4.83%) and TIO groups (6.11 +/- 2.54%) than in the IB group (3.8 +/- 1.96%). In the IB group PD(15)FEV(1) and PD(20)FEV(1) were obtained in all patients, while in the OXI group they were obtained in 12 and 5 pts respectively and in the TIO group in 14 and 5 pts respectively. Normal hyperreactivity was obtained in 2 patients, in both OXI and TIO groups. In OXI and TIO, the PD(15) obtained after drug pre-medication, was similar (respectively 1628 +/- 955.7 and 1595.5 +/- 990 microg), but higher (p < 0.0001) in comparison to the PD(15) measured in the IB group (532.2 +/- 434.8 microg). Also, the dose-response slope (decline percentage of FEV(1)/cumulative methacholine dose) after PD(15) was similar in both OXI and TIO groups but different in the IB group. A significant relationship (p < 0.01) was found between PD(15)FEV(1) (obtained in 40 pts) and the increase in FEV(1)% obtained 60 minutes after bronchodilator inhalations (r = 0.53). In conclusion, with a standard dose, both Oxitropium and Tiotropium seem to have the same protective effect in bronchial asthma but higher than Ipratropium. It's probable that the best dose of Ipratropium should be a higher one than the usual dose taken.


Mother-to-child transmission of human immunodeficiency virus.
Transmission of HIV virus from an infected mother to her offspring is becoming the leading cause of spreading in the pediatric population. This is particularly burdensome in the pattern II countries where HIV infection has reached epidemic proportions and infection rates affect more women of childbearing age than men. During the last few years considerable effort has been directed at defining the optimal methods for identifying infants of HIV-infected mothers who will themselves prove to be infected because conventional serological assessment is impaired due to placental transfer of maternal IgG. At present, detection of specific IgA to HIV proteins, evaluation of autochthonous antibody production in vitro from infants' lymphocytes, and gene amplification of HIV DNA/RNA by polymerase chain reaction are the most promising procedures for early diagnosis within the first 6 months of life. Nevertheless all these techniques are cumbersome when evaluating specimens from the newborn child. Many studies have been performed to identify those maternal factors affecting the risk of vertical transmission. So far, none of them has shown real prognostic value. However, evaluation of maternal antibody response to functional epitopes of HIV envelope proteins such as the principal neutralizing domain, in some epidemiological settings, seems to correlate to a reduced rate of mother-to-child transmission.


Malignancies in Patients with Inflammatory Bowel Disease: Results from 20 Years of Follow-up in the IBSEN Study.
Whether patients with inflammatory bowel diseases [IBDs] have increased risk of developing cancer has been debated. The aims of the study were to determine the prevalence of intestinal/extraintestinal cancers in an IBD cohort 20 years after diagnosis and to assess whether these patients had an increased cancer-specific risk compared with a matched control population. Patients with ulcerative colitis [UC] and Crohn's disease [CD] diagnosed 1990-1993 have been prospectively followed up for 20 years. Follow-up visits were carried out 1, 5, 10, and 20 years after inclusion. Data on all cancer cases, deaths, and causes of death were collected from the Cancer Registry of Norway and from the Norwegian Cause of Death Registry. In all, 756 patients [519 UC and 237 CD] were diagnosed with IBD. Increased risk of cancer was seen in UC patients (hazard ratio [HR] = 1.40, 95% confidence interval [CI] 1.08-1.81, p < 0.01), but not in CD patients [HR = 1.23, 95% CI 0.80-2.03, p = 0.30]. Stratified by gender, our data revealed a statistically increased risk for all cancers only in male UC patients compared with the controls [HR = 1.51, 95% CI 1.08-2.11, p = 0.017]. In both groups breast cancer was seen more often than expected. Male UC patients display an increased risk of development of colorectal cancer and, also all cancers combined, compared with the controls. In both UC and CD, standardized incidence ratio for breast cancer was increased.


Microstructural characterization of myocardial infarction with optical coherence tractography and two-photon microscopy.
Myocardial infarction leads to complex changes in the fiber architecture of the heart. Here, we present a novel optical approach to characterize these changes in intact hearts in three dimensions. Optical coherence tomography (OCT) was used to derive a depth-resolved field of orientation on which tractography was performed. Tractography of healthy myocardium revealed a smooth linear transition in fiber inclination or helix angle from the epicardium to endocardium. Conversely, in infarcted hearts, no coherent microstructure could be identified in the infarct with OCT Additional characterization of the infarct was performed by the measurement of light attenuation and with two-photon microscopy. Myofibers were imaged using autofluorescence and collagen fibers using second harmonic generation. This revealed the presence of two distinct microstructural patterns in areas of the infarct with high light attenuation. In the presence of residual myofibers, the surrounding collagen fibers were aligned in a coherent manner parallel to the myofibers. In the absence of residual myofibers, the collagen fibers were randomly oriented and lacked any microstructural coherence. The presence of residual myofibers thus exerts a profound effect on the microstructural properties of the infarct scar and consequently the risk of aneurysm formation and arrhythmias. Catheter-based approaches to segment and image myocardial microstructure in humans are feasible and could play a valuable role in guiding the development of strategies to improve infarct healing.


Effects of earthworm invasion on plant species richness in northern hardwood forests.
The invasion of non-native earthworms (Lumbricus spp.) into a small number of intensively studied stands of northern hardwood forest has been linked to declines in plant diversity and the local extirpation of one threatened species. It is unknown, however, whether these changes have occurred across larger regions of hardwood forests, which plant species are most vulnerable, or with which earthworm species such changes are associated most closely. To address these issues we conducted a regional survey in the Chippewa and Chequamegon national forests in Minnesota and Wisconsin (U.S.A.), respectively. We sampled earthworms, soils, and vegetation, examined deer browse in 20 mature, sugar-maple-dominated forest stands in each national forest, and analyzed the relationship between invasive earthworms and vascular plant species richness and composition. Invasion by Lumbricus was a strong indicator of reduced plant richness in both national forests. The mass of Lumbricus juveniles was significantly and negatively related to plant-species richness in both forests. In addition, Lumbricus was a significant factor affecting plant richness in a full model that included multiple variables. In the Chequamegon National Forest earthworm mass was associated with higher sedge cover and lower cover of sugar maple seedlings and several forb species. The trends were similar but not as pronounced in Chippewa, perhaps due to lower deer densities and different earthworm species composition. Our results provide regional evidence that invasion by Lumbricus species may be an important mechanism in reduced plant-species richness and changes in plant communities in mature forests dominated by sugar maples.


General versus Neuraxial Anesthesia on Clinical Outcomes in Patients Receiving Hip Fracture Surgery: An Analysis of the ACS NSQIP Database.
Whether the use of neuraxial anesthesia or general anesthesia leads to more favorable postoperative outcomes in patients receiving hip fracture surgery remains unclear. We used data from the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) Data Files between 2016 and 2020 to investigate the association of neuraxial anesthesia and general anesthesia with morbidity and mortality after hip fracture surgery. Inverse probability of treatment weighting (IPTW) was used to balance the baseline characteristics, and multivariable Cox regression models were used to estimate the hazard ratio (HR) with a 95% confidence interval (CI) for postoperative morbidity and mortality among the different anesthesia groups. A total of 45,874 patients were included in this study. Postoperative adverse events occurred in 1087 of 9864 patients (11.0%) who received neuraxial anesthesia and in 4635 of 36,010 patients (12.9%) who received general anesthesia. After adjustment for IPTW, the multivariable Cox regressions revealed that general anesthesia was associated with increased risks of postoperative morbidity (adjusted HR, 1.19; 95% CI, 1.14-1.24) and mortality (adjusted HR, 1.09; 95% CI, 1.03-1.16). The results of the present study suggest that, compared with general anesthesia, neuraxial anesthesia is associated with lower risks of postoperative adverse events in patients undergoing hip fracture surgery.


Rottlerin impairs the formation and maintenance of psychostimulant-supported memory.
Since brain proteins such as protein kinase C (PKC), brain-derived neurotrophic factor (BDNF), and mammalian target of rapamycin (mTOR) are involved in the establishment and maintenance of psychostimulant memory, we sought to determine if systemic treatment with rottlerin, a natural compound affecting all these proteins, may modulate stimulant-supported memory. Stimulant-induced conditioned place preference (CPP) was used in modeling stimulant-supported memory. Three cocaine (10 mg/kg; COC) or three methamphetamine (1 mg/kg; MA) conditioning trials reliably established the drug-induced CPP in male C57BL/6 mice. An intra-peritoneal rottlerin injection (5 mg/kg) at least 24 h prior to the first COC or first MA conditioning trial prevented the establishment of CPP. Following the establishment of the COC- or MA-induced CPP, saline conditioning trial was used to extinguish the CPP. Rottlerin (5 mg/kg, intra-peritoneal (i.p.)) administered 20 h prior to the first saline conditioning trial diminished subsequent drug- and stressor-primed reinstatement of the extinguished CPP. Rottlerin (5 mg/kg, i.p.) produced a fast-onset and long-lasting increase in hippocampal BDNF levels. However, treatment with a BDNF tropomyosin receptor kinase B (TrkB) receptor antagonist, K252a (5 μg/kg), did not affect rottlerin's suppressing effect on COC-induced CPP and treatment with 7,8-dihydroxyflavone (10 mg/kg x 6, 7,8-DHF), a selective TrkB agonist, prior to each conditioning trial did not affect COC-induced CPP. These results suggest that systemic rottlerin treatment may impair the formation of COC- and MA-supported memory. Importantly, such a treatment may advance our understanding of the underlying mechanism through which extinction training resulted in the "forgetting" of the COC- and MA-supported memory.


Food-group and nutrient-density intakes by Hispanic and Latino backgrounds in the Hispanic Community Health Study/Study of Latinos.
Hispanics are a heterogeneous group of individuals with a variation in dietary habits that is reflective of their cultural heritage and country of origin. It is important to identify differences in their dietary habits because it has been well established that nutrition contributes substantially to the burden of preventable diseases and early deaths in the United States. We estimated the distribution of usual intakes (of both food groups and nutrients) by Hispanic and Latino backgrounds by using National Cancer Institute methodology. The Hispanic Community Health Study/Study of Latinos is a population-based cohort study that recruited participants who were 18-74 y of age from 4 US cities in 2008-2011 (Miami, Bronx, Chicago, and San Diego). Participants who provided at least one 24-h dietary recall and completed a food propensity questionnaire (n = 13,285) were included in the analyses. Results were adjusted for age, sex, field center, weekend, sequencing, and typical amount of intake. Overall, Cubans (n = 2128) had higher intakes of total energy, macronutrients (including all subtypes of fat), and alcohol than those of other groups. Mexicans (n = 5371) had higher intakes of vitamin C, calcium, and fiber. Lowest intakes of total energy, macronutrients, folate, iron, and calcium were reported by Dominicans (n = 1217), whereas Puerto Ricans (n = 2176) had lowest intakes of vitamin C and fiber. Food-group servings reflected nutrient intakes, with Cubans having higher intakes of refined grains, vegetables, red meat, and fats and Dominicans having higher intakes of fruit and poultry, whereas Puerto Ricans had lowest intakes of fruit and vegetables. Central and South Americans (n = 1468 and 925, respectively) were characterized by being second in their reported intakes of fruit and poultry and the highest in fish intake in comparison with other groups. Variations in diet noted in this study, with additional analysis, may help explain diet-related differences in health outcomes observed in Hispanics and Latinos.


Respiratory symptoms and farming practices in farmers associated with an acute febrile illness after organic dust exposure.
To conduct a preliminary study of occupational respiratory complaints in farmers who have experienced organic dust toxic syndrome (ODTS) symptoms. Cross-sectional. An agricultural trade show. None. Two hundred ninety-seven people (204 men, 93 women) completed a questionnaire about agricultural practices, respiratory health (including history of febrile episodes while handling grain), and use of respirators. Spirometry was also performed. ODTS symptoms were described by 107 of the people (36%). A strong significant association was found between ODTS and cough or chest tightness after handling grain (odds ratio [OR], 7.5; 95% confidence ratio [CI], 4.2 to 13.5). People who experienced cough or chest tightness after handling grain were more likely to report handling grain sorghum than people who had not experienced cough or chest tightening after handling grain (OR, 2.1; 95% CI, 1.3 to 3.5). The strong association seen between ODTS and frequent use of a respirator while working in grain bins (OR, 3.9; 95% CI, 1.6 to 9.4) may indicate that farmers began using respirators after respiratory symptoms developed. Having a history consistent with ODTS exposure was very common in the farmers surveyed. Farmers who had a history consistent with ODTS were more likely to report cough or chest tightness with handling grain. Exposure to grain sorghum was more likely to be associated with respiratory symptoms than was exposure to other types of grain. There is a need for additional studies to further examine the relationship between ODTS and respiratory symptoms with grain dust exposure in farmers.


Candida die-off: Adverse effect and neutralization with phytotherapy approaches.
Candida albicans is the main species that causes 3rd most common bloodstream infection candidiasis in hospitalization. Once it has been diagnosed and treated with antifungal medications accurately, large amounts of Candida cells are killed off rapidly known as Candida die-off or Jarisch-Herxheimer reactions. When Candida cells are killed off quickly, a large no. of toxic substances are released simultaneously. This flood of endotoxins is noxious (harmful) and causes the kidneys and liver to work overtime to try and remove them which causes worsening of symptoms in patients. As a complementary and holistic approach to addressing Candida die-off and its associated symptoms, plant-based remedies i.e., phytotherapy have been gaining increased attention. In this review paper, we have discussed major factors involved in provoking Candida die-off, their management by phytotherapy, challenges associated with the toxic effects due to die-off, and neutralization of Candida die-off through phytotherapy to manage this problem and challenges. In conclusion, this article serves as a meticulous compilation of knowledge on the intriguing subject of Candida die-off, presenting a distinct and informative perspective that has the potential to pave the way for new insights in the realm of plant-based antifungal therapeutics.


Chicken heart ubiquinol: cytochrome c reductase--isolation by affinity chromatography and resolution of enzyme into subunits.
Chicken heart mitochondrial ubiquinol: cytochrome c reductase has been isolated as a monodisperse form by solubilization with Triton X-100 in low ionic strength and subsequent affinity chromatography. The enzyme complex contains less than 0.15 mumol ubiquinone and 12 mumol phospholipid per mumol enzyme. The spectrum of cytochrome b in the reduced exhibited two maximum alpha-absorption bands at 558 nm and 562 nm; a shoulder at 553 nm for c1. The purified enzyme complex consists of at least 9 subunits with apparent molecular weight of 47 K, 44 K, 36 K, 31 K, 25 K, 17 K, 15 K, 12 K and 9 K. The enzyme complex has been dissociated into subdomains of subunits in the presence of increasing concentration of salt and Triton X-100. Three subunits carrying the redox centers (cytochrome b, cytochrome c1 and Fe-S protein) have been further isolated.


The LupusQoL and associations with demographics and clinical measurements in patients with systemic lupus erythematosus.
Having developed and validated a disease-specific health-related quality of life (HRQOL) measure for patients with systemic lupus erythematosus (SLE), the LupusQoL, we determined its relationship to demographic and clinical measurements in a group of patients with SLE. A group of 322 outpatients completed the LupusQoL. Demographic (age, sex, marital status, ethnicity) and clinical variables (disease duration, disease activity, damage) were recorded. Associations between the 8 LupusQoL domains and age, disease duration, disease activity, and damage were explored using Spearman's correlation coefficients. Differences in LupusQoL scores were examined for sex and marital status using the Mann-Whitney U test. Ethnic groups were compared using ANOVA. All domains of LupusQoL were impaired, with fatigue (56.3) being the worst affected and body image (80.0) the least. The correlations between the LupusQoL domain scores and age (r = -0.01 to -0.22) and disease duration (r = 0 to 0.16) were absent or weak. Similarly, there were no significant differences in the LupusQoL scores regarding sex, marital status, or the 3 main ethnic groups (Black-Caribbean, Asian, White). Although there were statistically significant correlations between the scores of the LupusQoL domains and some scores of the British Isles Lupus Assessment Group index (r = -0.22 to 0.09) and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (r = -0.29 to 0.21), these were weak. HRQOL was impaired in this cohort of outpatients with SLE as assessed by the validated lupus-specific LupusQoL. There were no clinically important associations between the 8 domains of the LupusQoL and clinical or demographic variables in this group of patients. Thus, the LupusQoL is a relatively independent outcome measure in patients with SLE.


Water stress induced by polyethylene glycol 6000 and sodium chloride in two maize cultivars.
Responses of growth and germination to water stress induced by PEG 6000 and NaCl in two maize (Zea mays L.) cultivars 704 and 301 were studied. Water stress was generated by additions of PEG 6000 or sodium chloride to the root medium. Water potentials were: zero as control and -0.15, -0.49, -1.03 and -1.76 MPa as treatments. After 24 h treatment, the roots and shoots length and dry weight were of plants determined. In water stress, roots and shoots length and dry weight decreased at both treatments in both varieties. The germination is inversely proportional to the NaCl and PEG concentrations, it means that 704 and 301 cultivars of maize showed a reduction in germination with an increasing in NaCl or PEG concentrations induced water deficit, but this reduction in NaCl treatment were higher than PEG treatment. At treatment by PEG, the germination was severely decreased at -1.03 MPa. At treatment by NaCl no germination occurred at -1.03 in 301 var. and germination was very low at -1.03 MPa in 704 var., no germination occurred at -1.76 MPa in both varieties at both treatments. Decrease of germination in 704 variety was higher than 301 variety.


Risk factors for mortality and cost implications of complicated intra-abdominal infections in critically ill patients.
To assess risk factors for 28-day mortality and cost implications in intensive care unit (ICU) patients with complicated intra-abdominal infections (cIAIs). Single-center retrospective cohort study of prospectively collected data analysing ICU patients with a microbiologically confirmed complicated intra-abdominal infections. 137 complicated intra-abdominal infections were included and stratified according to the adequacy of antimicrobial therapy (initial inadequate antimicrobial therapy [IIAT], n = 44; initial adequate antimicrobial therapy [IAAT], n = 93). The empirical use of enterococci/methicillin-resistant Staphylococcus aureus active agents and of carbapenems was associated with a higher rate of therapeutic adequacy (p = 0.016 and p = 0.01, respectively) while empirical double gram-negative and antifungal therapy did not. IAAT showed significantly lower mortality at 28 and 90 days and increased clinical cure and microbiological eradication (p < 0.01). In the logistic and Cox-regression models, IIAT and inadequate source control were the unique predictors of 28-day mortality. No costs differences were related to the adequacy of empirical therapy and source control. The empirical double gram-negative and antifungal therapy (p = 0.03, p = 0.04) as well as the isolation of multidrug-resistant (MDR) bacteria and the microbiological failure after targeted therapy were drivers of increased costs (p = 0.004, p = 0.04). IIAT and inadequate source control are confirmed predictors of mortality in ICU patients with complicated intra-abdominal infections. Empirical antimicrobial strategies and MDR may drive hospital costs.


Levodopa-carbidopa intestinal gel in a subgroup of patients with dyskinesia at baseline from the GLORIA Registry.
To evaluate long-term effects of levodopa-carbidopa intestinal gel on dyskinesia burden. Posthoc analysis of the GLORIA registry assessed subgroups of advanced Parkinson's disease patients with <4 and ≥4 h/day of levodopa-induced dyskinesia at baseline. Mean dyskinesia duration significantly (p < 0.0001) decreased by 3.5 h in patients with ≥4 h baseline dyskinesia; conversely, dyskinesia duration increased by 1.6 h in patients with <4 h baseline dyskinesia. Quality of life improved in both subgroups. Adverse drug reactions occurred at similar rates in both subgroups. Despite increases in levodopa dose, levodopa-carbidopa intestinal gel treatment led to significant and sustained reductions in dyskinesia time, severity and associated pain in advanced Parkinson's disease patients with high baseline dyskinesia burden.


[Clonogenic stromal cell count in the bone marrow of mice].
The number of fibroblast colonies in bone marrow cultures depends on FCFC concentration in explanted cells and FCFC cloning efficiency. For mouse bone marrow the efficiency of fibroblast colony formation increases in the presence of the feeder (irradiated bone marrow of spleen cells). Colony-stimulating feeder activity does not depend on the presence of phagocytic and stromal cells in the feeder cell population. Trypsinization of the bone marrow leads to the release of additional FCFC and the increase of their concentration in bone marrow cell suspensions.


"You are here": Missing links, chains of being, and the language of cartoons.
Evolution cartoons served polemical and satirical purposes even before Darwin published On the Origin of Species, and they proliferated afterward. Yet even though Victorian evolution cartoons often pictured Darwin himself as a personification of his theory, by the time of the Scopes trial controversy in the 1920s cartoons about evolution had come to popularize ironically non-Darwinian views of evolution. Cartoons repeated, reflected, and perpetuated teleological views of evolution and often implicitly associated evolution with prevalent attitudes about race, gender, and social hierarchies. Cartoons drew on old iconographic traditions, expanding them to fit changing historical circumstances, forming a lasting cartoon lexicon. Though adaptable and protean, the language of evolution cartoons, like any language, carries its history with it, and in them we can read the history of the cultural context of evolution controversies.


Unrestricted weight bearing and intensive physiotherapy after uncemented total hip arthroplasty.
The effectiveness of partial weightbearing after hip surgery has been questioned as well as the need of intensive physiotherapy. 36 patients (average age 54.4, 19 women) operated with uncemented hip arthroplasty were randomized either to unrestricted weightbearing (UWB) combined with intensive physiotherapy or to partial weightbearing (PWB) for 3 months combined with a short self-training program. The load during walking and the muscle strength (MS) in abduction was measured preoperative and subsequent up to 12 months. The average peak load on the operated leg at one week was 39.0 kg for the UWB and 25.8 for the PWB group (P = 0.009) while at three months 70.0 and 31.7 (P = 0.001) respectively. At 6 and 12 months there were no differences between the groups. The muscle strength increased in both groups up to six months but there were no differences between the groups. Even though patients applied more load than the recommended 15 kg most patients were able to comply with partial weightbearing fairly well. The effect of intensive physiotherapy on the muscle strength after hip arthroplasty is questionable.


Who comes back with what: a retrospective database study on reasons for emergency readmission to hospital in children and young people in England.
To determine the proportion of children and young people (CYP) in England who are readmitted for the same condition. Retrospective cohort study. National administrative hospital data (Hospital Episode Statistics). CYP (0-year-olds to 24-year-olds) discharged after an emergency admission to the National Health Service in England in 2009/2010. Coded primary diagnosis classified in six broad groups indicating reason for admission (infection, chronic condition, injury, perinatal related or pregnancy related, sign or symptom or other). We grouped readmissions as ≤30 days or between 31 days and 2 years after the index discharge. We used multivariable logistic regression to determine factors at the index admission that were predictive of readmission within 30 days. 9% of CYP were readmitted within 30 days. Half of the 30-day readmissions and 40% of the recurrent admissions between 30 days and 2 years had the same primary diagnosis group as the original admission. These proportions were consistent across age, sex and diagnostic groups, except for infants and young women with pregnancy-related problems (15-24 years) who were more likely to be readmitted for the same primary diagnostic group. CYP with underlying chronic conditions were readmitted within 30 days twice as often (OR: 1.93, 95% CI 1.89 to 1.99) compared with CYP without chronic conditions. Financial penalties for readmission are expected to incentivise more effective care of the original problem, thereby avoiding readmission. Our findings, that half of children come back with different problems, do not support this presumption.


A randomized controlled trial comparing quantitative informed consent formats.
Informed consent has been indirectly studied only in settings that do not replicate the actual consent process. We designed a sham study and randomly allocated adult ambulatory patients to receive one of two consent forms: Consent A (n = 52) described a randomized trial of usual treatment vs a new medication that "may work twice as fast as the usual treatment"; or Consent B (n = 48) that described a randomized trial of a new medication that "may work half as fast as the usual treatment". Patients randomized to Consent A were more likely to consent than those randomized to Consent B (consent rate A = 67%, consent rate B = 42%, p less than 0.01). Among patients who cited quantitative information, the difference in consent rate was even more marked (95% vs 36%, p less than 0.001); patients who did not cite quantitative information had equivalent consent rates. Patients who perceived minimal or severe symptoms had lower consent rates than those with mid-range symptom scores (chi 2(2) = 8.35, p = 0.015). Patients who recognize quantitative information will use it to make informed consent decisions.


An essential mesenchymal function for miR-143/145 in intestinal epithelial regeneration.
Downregulation of the miR-143/145 microRNA (miRNA) cluster has been repeatedly reported in colon cancer and other epithelial tumors. In addition, overexpression of these miRNAs inhibits tumorigenesis, leading to broad consensus that they function as cell-autonomous epithelial tumor suppressors. We generated mice with deletion of miR-143/145 to investigate the functions of these miRNAs in intestinal physiology and disease in vivo. Although intestinal development proceeded normally in the absence of these miRNAs, epithelial regeneration after injury was dramatically impaired. Surprisingly, we found that miR-143/145 are expressed and function exclusively within the mesenchymal compartment of intestine. Defective epithelial regeneration in miR-143/145-deficient mice resulted from the dysfunction of smooth muscle and myofibroblasts and was associated with derepression of the miR-143 target Igfbp5, which impaired IGF signaling after epithelial injury. These results provide important insights into the regulation of epithelial wound healing and argue against a cell-autonomous tumor suppressor role for miR-143/145 in colon cancer.


Pharmaceuticals and personal care products in archived U.S. biosolids from the 2001 EPA National Sewage Sludge Survey.
In response to the U.S. National Academies' call for a better assessment of chemical pollutants contained in the approximately 7 million dry tons of digested municipal sludge produced annually in the United States, the mean concentration of 72 pharmaceuticals and personal care products (PPCP) were determined in 110 biosolids samples collected by the U.S. Environmental Protection Agency (EPA) in its 2001 National Sewage Sludge Survey. Composite samples of archived biosolids, collected at 94 U.S. wastewater treatment plants from 32 states and the District of Columbia, were analyzed by liquid chromatography tandem mass spectrometry using EPA Method 1694. Thirty-eight (54%) of the 72 analytes were detected in at least one composite sample at concentrations ranging from 0.002 to 48 mg kg(-1) dry weight. Triclocarban and triclosan were the most abundant analytes with mean concentrations of 36 +/- 8 and 12.6 +/- 3.8 mg kg(-1) (n = 5), respectively, accounting for 65% of the total PPCP mass found. The loading to U.S. soils from nationwide biosolids recycling was estimated at 210-250 metric tons per year for the sum of the 72 PPCPs investigated. The results of this nationwide reconnaissance of PPCPs in archived U.S. biosolids mirror in contaminant occurrences, frequencies and concentrations, those reported by the U.S. EPA for samples collected in 2006/2007. This demonstrates that PPCP releases in U.S. biosolids have been ongoing for many years and the most abundant PPCPs appear to show limited fluctuations in mass over time when assessed on a nationwide basis. The here demonstrated use of five mega composite samples holds promise for conducting cost-effective, routine monitoring on a regional and national basis.


[Structure of acute and chronic pain syndromes in patients with gynecologic tumors].
Questionnaires on the nature of pain were distributed among 100 female postoperative and 29 incurable patients suffering from genital tumors. The structure of an acute and a chronic pain syndrome was established. The postoperative pain syndrome appeared to be determined, mainly, by the site and extent of surgical intervention while the chronic one by the pattern of tumor progression.


Pontibacter korlensis sp. nov., isolated from the desert of Xinjiang, China.
Two Gram-negative, rod-shaped, gliding and pink-pigmented bacterial strains, X14-1T and X19-1, were isolated from a mixture of sand samples collected from the desert of Xinjiang, China, and characterized by using a polyphasic taxonomic approach. Strains X14-1T and X19-1 contained MK-7 as the predominant menaquinone. The major cellular fatty acids included iso-C15 : 0, iso-C17 : 0 3-OH, summed feature 3 and summed feature 4. The DNA G+C contents of strains X14-1T and X19-1 were 48.2 and 48.9 mol%, respectively. 16S rRNA gene sequence analysis showed that the isolates were highly related to each other (99.2 %) and confirmed their placement in the genus Pontibacter. Strains X14-1T and X19-1 exhibited 16S rRNA gene similarity levels of 95.0-97.2 % to the type strains of the two Pontibacter species with validly published names. DNA-DNA hybridization experiments revealed a high level of relatedness between the two new isolates (82 %), but low levels of relatedness between strain X14-1T and the phylogenetically most closely related species Pontibacter actiniarum KMM 6156T (51 %). On the basis of genotypic and phenotypic evidence, strains X14-1T and X19-1 are considered to represent a novel species of the genus Pontibacter, for which the name Pontibacter korlensis sp. nov. is proposed. The type strain is X14-1T (=CCTCC AB 206081T=NRRL B-51097T).


Gender inequality and restrictive gender norms: framing the challenges to health.
Gender is not accurately captured by the traditional male and female dichotomy of sex. Instead, it is a complex social system that structures the life experience of all human beings. This paper, the first in a Series of five papers, investigates the relationships between gender inequality, restrictive gender norms, and health and wellbeing. Building upon past work, we offer a consolidated conceptual framework that shows how individuals born biologically male or female develop into gendered beings, and how sexism and patriarchy intersect with other forms of discrimination, such as racism, classism, and homophobia, to structure pathways to poor health. We discuss the ample evidence showing the far-reaching consequences of these pathways, including how gender inequality and restrictive gender norms impact health through differential exposures, health-related behaviours and access to care, as well as how gender-biased health research and health-care systems reinforce and reproduce gender inequalities, with serious implications for health. The cumulative consequences of structured disadvantage, mediated through discriminatory laws, policies, and institutions, as well as diet, stress, substance use, and environmental toxins, have triggered important discussions about the role of social injustice in the creation and maintenance of health inequities, especially along racial and socioeconomic lines. This Series paper raises the parallel question of whether discrimination based on gender likewise becomes embodied, with negative consequences for health. For decades, advocates have worked to eliminate gender discrimination in global health, with only modest success. A new plan and new political commitment are needed if these global health aspirations and the wider Sustainable Development Goals of the UN are to be achieved.


Replication of kinetoplast DNA of Crithidia acanthocephali. I. Density shift experiments using deuterium oxide.
The protozoan Crithidia acanthocephali contains, within a modified region of a mitochondrion, a mass of DNA known as kinetoplast DNA (kDNA). This DNA consists mainly of an association of approximately 27,000 covalently closed 0.8-mum circular molecules which are apparently held together in a definite ordered manner by topological interlocking. After culturing of C. acanthocephali cells for 25 generations in medium containing 75% deuterium oxide, both nuclear DNA (rhonative, nondeuterated=1.717 g/cm3) and kDNA (rhonative, nondeuterated=1.702 g/cm3) increased in buoyant density by 0.012 g/cm3. The replication of the two DNAs was studied by cesium chloride buoyant density analysis of DNAs from exponentially growing cells taken at 1.0, 1.4, 2.0, 3.0, and 4.0 cell doublings after transfer of cells from D2O-containing medium into medium containing only normal water. The results obtained from analysis of both native and denatured nuclear DNAs indicate that this DNA replicates semiconservatively. From an analysis of intact associations of kDNA, it appears that this DNA doubles once per generation and that the newly synthesized DNA does not segregate from parental DNA. Fractions of covalently closed single circular molecules and of open circular and unit length linear molecules were obtained from associations of kDNA by sonication, sucrose sedimentation, and cesium chloride-ethidium bromide equilibrium gradient centrifugation. Buoyant density profiles obtained from these fractions indicate that: (a) doubling of the kDNA results from the replication of each circular molecule rather than from repeated replication of a small fraction of the circular molecules; (b) replication of kDNA is semiconservative rather than conservative, but there is recombination between the circles at an undefined time during the cell cycle.


Transcriptome profiling of Bergenia purpurascens under cold stress.
Bergenia purpurascens is an important medicinal, edible and ornamental plant. It generally grows in high-altitude areas with complex climates. There have been no reports about how B. purpurascens survives under cold stress. Here, the B. purpurascens under low temperature were subjected to transcriptomics analysis to explore the candidate genes and pathways that involved in the cold tolerance of B. purpurascens. Compared with the control treatment, we found 9,600 up-regulated differentially expressed genes (DEGs) and 7,055 down-regulated DEGs. A significant number of DEGs were involved in the Ca2+ signaling pathway, mitogen-activated protein kinase (MAPK) cascade, plant hormone signaling pathway, and lipid metabolism. A total of 400 transcription factors were found to respond to cold stress, most of which belonged to the MYB and AP2/ERF families. Five novel genes were found to be potential candidate genes involved in the cold tolerance of B. purpurascens. The study provide insights into further investigation of the molecular mechanism of how B. purpurascens survives under cold stress.


A monoclonal antibody that identifies human peripheral blood monocytes recognizes the accessory- cells required for mitogen-induced T lymphocyte proliferation.
These studies were carried out to evaluate the functional characteristics of the cells identified by a monoclonal anti-human mononuclear phagocyte (M phi) antibody, 63D3. This antibody reacts specifically with all human peripheral blood M phi and not with normal human peripheral blood T or B cells. By using the fluorescence-activated cell sorter, human peripheral blood mononuclear cells (PBM) were sorted into 63D3-positive and 63D3-negative populations. Cell volume analysis indicated that 63D3-negative cells were identical to the non-adherent cells (NAC) in PBM, whereas 63D3-positive cells had a bimodal size distribution comparable to glass-adherent cells (AC). Neither 63D3-negative cells nor NAC were able to proliferate in response to mitogenic stimulation, whereas co-culture with either mitomycin C-treated AC or 63D3-positive cells restored mitogen responsiveness. Thus, the 63D3-positive population contains the relevant accessory cell required for mitogen-induced human lymphocyte proliferation.


Lunar Gravity via Apollo 14 Doppler Radio Tracking.
Gravity measurements at high resolution were obtained over a 100-kilometer band from + 70 degrees to -70 degrees of longitude during the orbits of low periapsis altitude (approximately 16 kilometers). The line-of-sight accelerations are plotted on Aeronautical Chart and Information Center mercator charts (scale 1 : 1,000,000) as contours at 10-milligal intervals. Direct correlations between gravity variations and surface features are easily determined. Theophilus, Hipparchus, and Ptolemaeus are negative features, whereas Mare Nectaris is a large positive region. The acceleration profiles over Mare Nectaris are suggestive of a broad disk near the surface rather than a deeply buried spherical body. These data are in good agreement with the short arc of Apollo 12 lunar module descent data.


Imaging Beam-Sensitive Materials by Electron Microscopy.
Electron microscopy allows the extraction of multidimensional spatiotemporally correlated structural information of diverse materials down to atomic resolution, which is essential for figuring out their structure-property relationships. Unfortunately, the high-energy electrons that carry this important information can cause damage by modulating the structures of the materials. This has become a significant problem concerning the recent boost in materials science applications of a wide range of beam-sensitive materials, including metal-organic frameworks, covalent-organic frameworks, organic-inorganic hybrid materials, 2D materials, and zeolites. To this end, developing electron microscopy techniques that minimize the electron beam damage for the extraction of intrinsic structural information turns out to be a compelling but challenging need. This article provides a comprehensive review on the revolutionary strategies toward the electron microscopic imaging of beam-sensitive materials and associated materials science discoveries, based on the principles of electron-matter interaction and mechanisms of electron beam damage. Finally, perspectives and future trends in this field are put forward.