The Association Between Pressure Ulcer/Injury Development and Short-term Mortality in Critically Ill Patients: A Retrospective Cohort Study.
Pressure ulcers/injuries (PU/Is) affect the social, mental, and physical well-being of patients; increase treatment costs; prolong hospital stays; increase patient risk for infections; and may independently decrease life expectancy. The aim of this retrospective study was to examine the association between PU/I development and mortality in a large cohort of consecutively admitted critically ill patients. Data from adult patients ( >18 years of age) admitted to an intensive care unit (ICU) between 2010 and 2013 were extracted from the ICU electronic clinical information system. Patients were excluded if they had a PU/I present on admission, no recorded admission modified Jackson/Cubbin (mJ/C) or Sequential Organ Failure Assessment (SOFA) score, or their ICU outcome was undetermined. The mJ/C risk scale (score range 9-48) was used to assess the PU/I risk (the lower the score, the higher the PU/I risk), the SOFA score (score range 0-24; the higher the SOFA score, the sicker the patient, with a higher risk of death) was used to assess the severity of the condition and outcome. ICU outcome was defined as 1) moved from the ICU to a ward/recovering or 2) no response to ICU treatment/deceased. All data were transferred to statistical software for analysis. Logistic regression analysis was used to examine the outcome related to PU/I development, SOFA, and mJ/C scores. Descriptive contingency tables of different scenarios were used to further evaluate relationships among different risk factors related to mortality; the Wald χ2 test was used to assess the statistical significance of the contingency tables. Of the 6582 patients admitted, 6089 were included for analysis. Two hundred, one (201) had a PU/In on admission, 212 had missing mJ/C or SOFA scores, and ICU outcome was undetermined in 80 patients. Patient mean age was 61.1 ± 15.8 (range 18-94) years; 3891 (63.9%) were male, average length of stay (LOS) was 3.6 days, denoted by quartile (Q) (median 1.58 days; Q1: 0.9, Q3: 3.9 days), and 1589 (26.1%) stayed 3 days or more in the ICU. The incidence of PU/I was 6.9% (423 patients), and ICU mortality rate was 9.1% (n=553). The mean LOS of patients with PU/I was 13.35 ± 15.56 days (median 8.95, Q1: 4.88, Q3: 16.2) and 2.84 ± 3.87 days for patients with no PU/I (median: 1.20, Q1: 0.90, Q3: 3.17; P <.0001). Mean LOS was 3.42 ± 5.95 days (median: 1.30, Q1: 0.90, Q3: 3.70) among recovering and 5.00 ± 7.17 days among deceased patients (median 2.56, Q1: 1.26, Q3: 6.40; P <.0001). The proportion of patients with an admission mJ/C score of 29 or less ranged from 48.8% to 51.5%, and the mean SOFA score was 7.0 ± 3.2. PU/I development and SOFA or mJ/C scores were independent predictors of mortality. The probability of a negative outcome was higher in persons with PU/Is compared to persons with no PU/Is. Persons with lower SOFA scores (ie, less severely ill patients) and higher mJ/C scores for each factor separately (ie, at low risk of PU/I development) each factor separately had a lower mortality risk. PU/I development in critically ill patients treated at an ICU is an independent predictor of mortality, even though the PU/I incidence and hospital mortality were relatively low. The ICU admission SOFA and mJ/C score also were independent prognosticators of ICU mortality. Future research could focus on the role of different steps in the cascade of PU/I development, especially to the role of inflammation.


Ocular Adnexal Lymphoma Presenting with Visual Loss.
Elderly patients with visual loss often have age-related macular degeneration, diabetic retinopathy, glaucoma, and cataract as common causes of visual loss. Other less common etiologies should be considered, especially in those presenting with systemic associations. The patient discussed in our review is an 80-year-old female, with a history of diabetic retinopathy and macular degeneration who presented with a sudden deterioration of vision. While this was initially attributed to diabetic retinopathy, she was eventually noted to have a salmon patch lesion in her conjunctiva, diagnosed on biopsy to be a diffuse large B-cell lymphoma. Because of the significant rate of disseminated disease among patients with lymphomas in the orbit that carries a worse prognosis, early diagnosis is essential to promote better overall survival of these patients. We describe here a patient diagnosed with conjunctival lymphoma associated with pronounced visual loss and review the literature on this subject.


Fluorination effects on the thermodynamic, thermophysical and surface properties of ionic liquids.
This paper reports the thermal, thermodynamic, thermophysical and surface properties of eight ionic liquids with fluorinated alkyl side chain lengths equal or greater than four carbon atoms. Melting and decomposition temperatures were determined together with experimental densities, surface tensions, refractive indices, dynamic viscosities and ionic conductivities in a temperature interval ranging from 293.15 to 353.15 K. The surface properties of these fluorinated ionic liquids were discussed and several thermodynamic functions, as well as critical temperatures, were estimated. Coefficients of isobaric thermal expansion, molecular volumes and free volume effects were calculated from experimental values of density and refractive index and compared with previous data. Finally, Walden plots were used to evaluate the ionicity of the investigated ionic liquids.


Simple deterministically constructed cycle reservoirs with regular jumps.
A new class of state-space models, reservoir models, with a fixed state transition structure (the "reservoir") and an adaptable readout from the state space, has recently emerged as a way for time series processing and modeling. Echo state network (ESN) is one of the simplest, yet powerful, reservoir models. ESN models are generally constructed in a randomized manner. In our previous study (Rodan & Tiňo, 2011), we showed that a very simple, cyclic, deterministically generated reservoir can yield performance competitive with standard ESN. In this contribution, we extend our previous study in three aspects. First, we introduce a novel simple deterministic reservoir model, cycle reservoir with jumps (CRJ), with highly constrained weight values, that has superior performance to standard ESN on a variety of temporal tasks of different origin and characteristics. Second, we elaborate on the possible link between reservoir characterizations, such as eigenvalue distribution of the reservoir matrix or pseudo-Lyapunov exponent of the input-driven reservoir dynamics, and the model performance. It has been suggested that a uniform coverage of the unit disk by such eigenvalues can lead to superior model performance. We show that despite highly constrained eigenvalue distribution, CRJ consistently outperforms ESN (which has much more uniform eigenvalue coverage of the unit disk). Also, unlike in the case of ESN, pseudo-Lyapunov exponents of the selected optimal CRJ models are consistently negative. Third, we present a new framework for determining the short-term memory capacity of linear reservoir models to a high degree of precision. Using the framework, we study the effect of shortcut connections in the CRJ reservoir topology on its memory capacity.


Tamlana agarivorans sp. nov., isolated from seawater off Jeju Island in Korea.
A Gram-negative, non-motile, rod-shaped, agarolytic bacterial strain, designated JW-26T, was isolated from seawater off Jeju Island in Korea, and was subjected to a polyphasic taxonomic investigation. Strain JW-26T grew optimally at pH 7.0-8.0, at 30 degrees C and in the presence of approximately 2 % (w/v) NaCl. Phylogenetic analyses based on 16S rRNA gene sequences revealed that strain JW-26T joins Tamlana crocina HST1-43T, with which it exhibited a 16S rRNA gene sequence similarity value of 95.5 %. Strain JW-26T contained MK-6 as the predominant menaquinone and iso-C15:0, C15:0 and iso-C15:1 as the major fatty acids. The DNA G+C content was 36.8 mol%. There were no distinct phenotypic and, particularly, chemotaxonomic properties to differentiate strain JW-26T from the genus Tamlana. DNA-DNA relatedness data and differential phenotypic properties, together with the phylogenetic distinctiveness, demonstrated that strain JW-26T is distinguishable from the type strain of T. crocina. On the basis of phenotypic, phylogenetic and genetic data, therefore, strain JW-26T represents a novel species within the genus Tamlana, for which the name Tamlana agarivorans sp. nov. is proposed. The type strain is JW-26T (=KCTC 22176T =CCUG 55327T).


A simplified technique for intestinal reanastomosis after the Hartmann procedure.
The technique described herein is simple, fast and provides a secure anastomosis. Mobilization and extensive dissection of either the Hartmann pouch or the stump of the sigmoid colon is avoided. In addition, there is no need for pursestring sutures, which may be difficult to place in patients with short rectal stumps.


Focal electrical stimulation of human retinal ganglion cells for vision restoration.
Objective. Vision restoration with retinal implants is limited by indiscriminate simultaneous activation of many cells and cell types, which is incompatible with reproducing the neural code of the retina. Recent work has shown that primate retinal ganglion cells (RGCs), which transmit visual information to the brain, can be directly electrically activated with single-cell, single-spike, cell-type precision - however, this possibility has never been tested in the human retina. In this study we aim to characterize, for the first time, direct in situ extracellular electrical stimulation of individual human RGCs.Approach. Extracellular electrical stimulation of individual human RGCs was conducted in three human retinas ex vivo using a custom large-scale, multi-electrode array capable of simultaneous recording and stimulation. Measured activation properties were compared directly to extensive results from macaque.Main results. Precise activation was in many cases possible without activating overlying axon bundles, at low stimulation current levels similar to those used in macaque. The major RGC types could be identified and targeted based on their distinctive electrical signatures. The measured electrical activation properties of RGCs, combined with a dynamic stimulation algorithm, was sufficient to produce an evoked visual signal that was nearly optimal given the constraints of the interface.Significance. These results suggest the possibility of high-fidelity vision restoration in humans using bi-directional epiretinal implants.


A low-toxicity IL-2-based immunocytokine retains antitumor activity despite its high degree of IL-2 receptor selectivity.
The goal of the study was to engineer a form of interleukin 2 (IL-2) that, when delivered as a tumor-specific antibody fusion protein, retains the ability to stimulate an antitumor immune response via interaction with the high-affinity IL-2 receptor but has lower toxicity because of the reduced activation of the intermediate-affinity IL-2 receptor. We investigated changes in the proposed toxin motif of IL-2 by introducing a D20T mutation that has little effect on the activity of free IL-2. We expressed this IL-2 variant as a fusion protein with an antibody (NHS76) that targets the necrotic core of tumors and characterized this molecule (NHS-IL2LT) in vitro and in vivo. NHS-IL2LT was shown to have near normal biological activity in vitro by using T-cell lines expressing the high-affinity IL-2 receptor, but little or no activity by using cell lines expressing only the intermediate IL-2 receptor. Relative to the control antibody fusion protein containing wild-type IL-2, NHS-IL2LT retained antitumor activity against established neuroblastoma and non-small cell lung cancer metastases in syngeneic mouse tumor models but was much better tolerated in immune-competent mice and in cynomolgus monkeys. The qualities of low toxicity and single-agent efficacy shown suggest that NHS-IL2LT is a good candidate for therapeutic approaches combining standard cytotoxic and immune therapies. In fact, this molecule (also known as Selectikine or EMD 521873) is currently in phase I clinical trial.


Whole body exposure of rats to microwaves emitted from a cell phone does not affect the testes.
The objective of this study was to investigate the effects of radiofrequency radiation emitted from cellular phones on the lipid composition, malondialdehyde concentration, p53 immune reactivity, sperm count, morphology, histological structure of testes, and on rectal temperature of rats exposed to microwave radiation emitted from cellular phones. Sixteen Spraque-Dawley rats were separated into two groups of eight, sham exposed (control) and experimental. The rats were confined in plexiglas cages specially designed for this study, and cellular phones were placed 0.5 cm under the cages. For the experimental group, cellular phones were activated 20 min per day (7 days a week) for 1 month. For the control group, the cellular phones were placed beneath the cages for 20 min a day, but the phones were turned off. Rectal temperatures were measured weekly. For 250 mW radiated power, the whole body average SAR (rms) is 0.52 W/kg and 1 g averaged peak SAR (rms) is 3.13 W/kg. The Mann-Whitney U-test was used for statistical comparisons of groups. No statistically significant alteration in any of the endpoints was noted. This study found no evidence suggesting an adverse effect of cell phone exposure on measures of testicular function or structure.


When should a trial of fluoxetine for major depression be declared failed?
Although the newer antidepressants are widely used, little is known about how long it takes to see their full effect. The authors sought to determine how many weeks a fluoxetine trial with no improvement should continue before treatment is changed. The data involved 840 patients in a 12-week open trial of fluoxetine, 20 mg/day, followed by a blinded, placebo-controlled discontinuation study. Outcomes at 4, 6, 8, 10, and 12 weeks were classified as nonresponse, partial response, response, and remission and were based on Hamilton Depression Rating Scale scores. The rate of remission at week 12 was calculated for each group of patients without remission at the earlier time points. The time to relapse during weeks 13-26 of the discontinuation study was examined in patients taking placebo and fluoxetine in relation to status at week 6. Patients unimproved at week 6 had a remission rate at week 12 of 31%-41%. For patients with remission at week 12, level of improvement at week 6 did not affect prognosis in weeks 13-26. Of the unimproved patients at week 8, 23% had remissions by week 12. The week 12 remission rate for unimproved patients at week 4 was clearly high enough to justify continued treatment; the rate for unimproved patients at week 10 was too low. These data suggest that nonresponse to fluoxetine should not be declared until 8 weeks of treatment have elapsed. Practitioners should discuss trial length with patients at the beginning of treatment.


Morphometric analysis of differentiation in human breast carcinoma. Tumor heterogeneity.
The assumption that tumor grading is best performed in the region having the least differentiation was tested in a series of mammary ductal carcinomas by quantitating the relative amounts of neoplastic cells that remain within ducts (intraductal tumor [IN]) or participate in glandular formations (differentiated infiltrating tumor [DI]). Field-to-field variation in these two elements displayed a linear correlation with their overall level in each tumor. Since having less than 10% DI + IN is a marker for recurrence among breast cancer patients, this marker was applied to find variant regions of potential biological importance. Such regions were common, but their distribution was random, and they varied so much within themselves that they were not significantly different from the remainder of the tumor. Furthermore, the existence of such poorly differentiated regions did not correlate with a poor prognosis. Grading should be performed on a sample that is representative of the entire tumor, rather than its least differentiated part.


The paradox of teaching wellness: Lessons from a national obstetrics and gynaecology resident curriculum.
In response to high rates of burnout among trainees, educators in obstetrics and gynaecology introduced a six-session wellness curriculum that improved professional fulfilment and resident burnout in participants with greater attendance. The implementation of the curriculum varied based on local variables and contextual factors. To analyse the reactions of participants and curriculum leaders across the diverse settings of the pilot experience in order to identify the best practices for implementation of a wellness curriculum. Twenty-five US OBGYN residency programmes completed the curriculum in the 2017-2018 academic year. OBGYN residents in all the years of training participated. Faculty members and fellows were workshop facilitators and course leaders. All participants completed post-intervention surveys. A qualitative, descriptive thematic analysis explored free-text responses from residents and workshop facilitators. Among 592 eligible resident participants, 387 (65%) responded to the post-intervention survey. Workshop facilitators submitted 65 surveys (47% response) on curriculum elements, rating the activities as 'good' or 'excellent' in 90.8% of cases. Qualitative analysis of workshop facilitators' and resident comments pointed to three themes, namely disagreement about the purpose of the curriculum, the social value of the curriculum in the residency programme and the need to open a broader discussion and take action to address structural barriers to wellness. Residents and faculty members involved in a wellness curriculum pilot had polarised reactions. While participants found value in learning skills and connecting to colleagues, efforts to promote wellness skills should be accompanied by communication and action to address drivers of burnout.


A Short Form of the Chinese Version of the Weinstein Noise Sensitivity Scale through Optimal Test Assembly.
This study developed a short form of the traditional Chinese version of the Weinstein Noise Sensitivity Scale (WNSS) through optimal test assembly (OTA). A total of 1069 Chinese adults (64.8% female) completed the territory-wide cross-sectional study. We first removed Items 12 and 5 which had negative factor loading and gender-related differential item functioning (DIF), respectively. The optimal length was then determined as the minimal one that reasonably resembled the reliability and validity of the scale without DIF items. OTA identified an 8-item WNSS (WNSS-8) which retained 67.2% of the test information of the original 21-item scale and had a Cronbach's alpha of 0.83. It also showed significant correlations of 0.272 and -0.115 with the neuroticism and extraversion scales of Chinese NEO-Five Factor Inventory, respectively. Adequate model fit of the WNSS-8 was demonstrated by the confirmatory factor analysis. The Chinese WNSS-8 can be used to assess noise sensitivity without compromising reliability and validity.


ANTIBODY PLAQUE FORMATION BY NORMAL MOUSE SPLEEN CELL CULTURES EXPOSED IN VITRO TO RNA FROM IMMUNE MICE.
Suspensions of normal spleen cells from nonimmune mice were treated in vitro with RNA extracted from spleen cells from donor mice immunized 4 days previously with sheep erythrocytes. Subsequent incubation of the RNA-treated cells in tissue culture medium at 37 degrees C for several days resulted in a marked increase in the number of localized zones of hemolysis ("antibody plaques") in relation to the number of viable cells plated in agar containing sheep erythrocytes and complement. Nonimmune cells maintained in tisse, culture medium did not form plaques after incubation with either RNA from Immune mice or ribonuclease-treated RNA from immune mice, or with RNA from non-immune donor mice, or from donors immunized with chicken erythrocytes or bovine serum albumin.


[The management of thyroid well-differentiated carcinoma invading the upper aerodigestive tract].
To investigate the management and prognosis of thyroid well-differentiated carcinoma invading the upper aerodigestive tract. A retrospective analysis of the management was performed done 62 patients with thyroid well-differentiated carcinoma invading the upper aerodigestive tract. The main method of surgery was shaving excision, and the other means including partial thyrochondrectomy, total laryngectomy, sleeve tracheal resection, sternocleidomastoid myoperiosteal flap and myodermal flap reconstruction, or simply palliative excision. Some patients received postoperative radioactive isotope therapy and radiotherapy. All patients were followed-up for 2 to 15 years with an average of 6.5 years. The best curative effect was proved in the patients with local invasion, with the lumen uninvolved and their locoregional control rate was 100.0% (17/17). And the second choice was in patients with more extensive involvement of the upper aerodigestive tract structures. For them, extensive surgical management was done attempting to remove all gross disease followed by reconstruction, their locoregional control rate was 87.5% (7/8). And the third place was designated to patients with local invasion for which shaving excision was performed even though minor residual disease was left, their locoregional control rate was 55.6% (5/9). The poorest result went to simple palliative excision. For 17 patients with minor residual tumor, the locoregional control rate of those who were given postoperative radioactive isotope therapy was significantly higher than those without. According to the limits and degree of invasion in the upper aerodigestive tract by thyroid well-differentiated carcinoma, different ways of surgery is indicated. For patients with residual disease, radioactive isotope therapy should be used to improve the result and life quality. Advanced lesions should be given postoperative radio therapy.


The transcription factor repertoire of Flt3+ hematopoietic stem cells.
Hematopoietic stem cells maintain the development of all mature blood cells throughout life due to their sustained self-renewal capacity and multilineage differentiation potential. During development into specific cell lineages, the options of stem cells and multipotent progenitor cells become increasingly restricted concomitant with a successive decline in self-renewal potential. Here we describe an Flt3+CD11b+ multipotent progenitor that can be amplified in vitro with a specific combination of cytokines to yield homogeneous populations in high cell numbers. By employing gene expression profiling with DNA microarrays, we studied the transcription factor repertoire of Flt3+CD11b+ progenitors and related it to the transcription factor repertoire of hematopoietic stem cells and embryonic stem cells. We report here on overlapping and nonoverlapping expression patterns of transcription factors in these cells and thus provide novel insights into the dynamic networks of transcriptional regulators in embryonic and adult stem cells. Additionally, the results obtained open the perspective for elucidating lineage and 'stemness' determinants in hematopoiesis.


Novel IRF6 mutations in Honduran Van der Woude syndrome patients.
Van der Woude syndrome (VWS) is an autosomal dominant inherited disease characterized by lower lip pits, cleft lip and/or cleft palate. Missense, nonsense and frameshift mutations in IRF6 have been revealed to be responsible for VWS in European, Asian, North American and Brazilian populations. However, the mutations responsible for VWS have not been studied in Central American populations. Here, we investigated the role of IRF6 in patients with VWS in a previously unstudied Honduran population. IRF6 mutations were identified in four out of five VWS families examined, which strongly suggests that mutations in IRF6 are responsible for VWS in this population. We reported three novel mutations and one previously described mutation. In the first family, a mother and daughter both exhibited a p.N88I mutation in the DNA-binding region of IRF6 that was not present in unaffected family members. In the second, we found a unique p.K101QfsX15 mutation in the affected patient, leading to a frameshift and early stop codon. In the third, we identified a p.Q208X mutation occurring in exon 6. In the fourth, we found a nonsense mutation in exon 9 (p.R412X), previously described in Brazilian and Northern European populations. In the fifth, we did not identify any unique exonic missense, nonsense or frameshift mutations. This study reports the first cases of IRF6 mutations in VWS patients in a Central American population, further confirming that the causal link between IRF6 and VWS is consistent across multiple populations.


Avoiding litigation after a reduction in workforce.
Healthcare organizations can avoid litigation after a reduction in workforce by observing Federal and state laws that protect employees, by documenting why and how the reduction will be carried out, and by training healthcare managers to terminate employment properly. Careful planning and scrupulous execution of a reduction-in-workforce plan can prevent costly lawsuits.


Mutual coherence function for a double-passage retroreflected optical wave in atmospheric turbulence.
The mutual coherence function in the source-receiver plane of a reflected Gaussian beam wave from a retroreflector is calculated and analyzed for two refractive-index spectral models and compared with similar results for the case of a plane mirror. Specific expressions are calculated for the mean irradiance and spatial coherence radius based on a Gaussian model for the finite reflector. Results that we obtained here using a modified spectrum with a high wave-number rise and inner scale generally show greater amplitude enhancements in the reflected wave than predicted by the pure power-law spectrum of Kolmogorov. In contrast, a finite outer scale in the spectral model leads to a reduction in the amount of beam spreading caused by turbulence and, in the case of a retroreflector, also leads to a reduction in the peak amplitude enhancement on the optical axis. This last result is in contrast with a plane mirror reflector, in which outer scale effects tend to increase the peak amplitude enhancement on the optical axis. The theory also predicts that, except for small reflectors, the coherence radius associated with a retroreflector can be as much as 1.4 times larger than that associated with a plane mirror, and 1.2 times that of a bistatic configuration for a plane mirror. All calculations are based on weak fluctuation theory and generalized spectral representations that use complex ABCD ray matrices.


[Prognosis of surviving children with neurologic complications in the intensive phase of leukemia treatment].
32 children survived neurological complications during the treatment of ALL, AML or NHL (intracranial bleeding, convulsions, infections, severe neuropathy, severe EEG-slowing). Neurological, electroencephalographic and psychological examinations were performed 6 months to 6 years after the end of maintenance therapy. Findings were normal or borderline in about 70% of the patients. 20% presented with neurological signs, due to localised cerebral or peripheral lesions. However, these generally did not interfere to high degree with the daily living skills. The frequencies of school problems and of abnormal psychological findings were similar to these found in ALL patients without neurological complications.


Partial purification and zinc dependence of human red cell pyrimidine-5'-nucleotidase.
Human red cell pyrimidine-5'-nucleotidase (EC 18.104.22.168) was partially purified from the blood of normal subjects by ion-exchange and affinity chromatography. Red cells were lysed in 50 mmol/l Tris-Cl buffer at pH 7.5 containing 1.0 mmol/l dithiothreitol and 0.5 mmol/l EDTA. The lysate was centrifuged and introduced onto a column of Sephadex A-50. After washing, the pyrimidine-5'-nucleotidase activity was eluted from the column with a NaCl gradient from 0 to 200 mmol/l in Tris buffer at pH 7.5. The pyrimidine-5'-nucleotidase was then desalted on Sephadex G-25 and introduced onto a UDP agarose column with a Tris buffer at pH 6.5 containing 150 mmol/l NaCl. This partial purification resulted in an approximately 80,000-fold increase in enzyme concentration. The Km for the partially purified enzyme was 0.32 mmol/l for UMP, 0.16 mmol/l for CMP and 0.11 mmol/l for OMP with a pH maximum of 7.5. This partially purified pyrimidine-5'-nucleotidase was then dialyzed in 50 mmol/l Tris-Cl buffer at pH 7.5 with 0.01 mmol/l CaCl2 and NaCl against 2 X 10(-3) mol/l 1,10-phenanthroline for 24 h at 4 degrees C. This incubation resulted in 73% decrease in enzyme activity which could be restored by the addition of zinc into the mixture, but not by the addition of other divalent metal ions.


"If You Let Them, They Will Be on It 24 Hours a Day": Qualitative Study Conducted in the United States Exploring Brazilian Immigrant Mothers' Beliefs, Attitudes, and Practices Related to Screen Time Behaviors of Their Preschool-Age Children.
The increasing prevalence of excessive screen time (ST) among children is a growing public health concern, with evidence linking it to an increased risk of overweight and obesity among children. This study aimed to explore the beliefs, attitudes, and practices of Brazilian immigrant mothers living in the United States related to their preschool-age children's ST behaviors. A qualitative study comprising 7 focus group discussions (FGDs) was conducted with Brazilian immigrant mothers living in the United States. All FGDs were audio-recorded and professionally transcribed verbatim. The Portuguese transcripts were analyzed using thematic analysis. In total, 37 women participated in the FGDs. Analyses revealed that although most mothers expressed concerns for their preschool-age children's ST, nearly all viewed ST as an acceptable part of their children's daily lives. Furthermore, mothers perceived that ST has more benefits than disadvantages. The mothers' positive beliefs about (eg, educational purposes and entertainment) and perceived functional benefits of ST (eg, ability to keep children occupied so tasks can be completed and facilitation of communication with family outside the United States) contributed to their acceptance of ST for their preschool-age children. Nevertheless, most mothers spoke of needing to balance their preschool-age children's ST with other activities. Mothers reported using several parenting practices including monitoring time and content, setting limits and having rules, and prompting their children to participate in other activities to manage their preschool-age children's ST. This study provides new information on the beliefs, attitudes, and practices of Brazilian immigrant mothers living in the United States related to their preschool-age children's ST. Study findings revealed several potentially modifiable maternal beliefs and parenting practices that may provide important targets for parenting- and family-based interventions aimed at limiting preschool-age children's ST.


Practical Considerations before Installing Ground-Based Geodetic Infrastructure for Integrated InSAR and cGNSS Monitoring of Vertical Land Motion.
Continuously operating Global Navigation Satellite Systems (cGNSS) can be used to convert relative values of vertical land motion (VLM) derived from Interferometric Synthetic Aperture Radar (InSAR) to absolute values in a global or regional reference frame. Artificial trihedral corner reflectors (CRs) provide high-intensity and temporally stable reflections in SAR time series imagery, more so than naturally occurring permanent scatterers. Therefore, it is logical to co-locate CRs with cGNSS as ground-based geodetic infrastructure for the integrated monitoring of VLM. We describe the practical considerations for such co-locations using four case-study examples from Perth, Australia. After basic initial considerations such as land access, sky visibility and security, temporary test deployments of co-located CRs with cGNSS should be analysed together to determine site suitability. Signal to clutter ratios from SAR imagery are used to determine potential sites for placement of the CR. A significant concern is whether the co-location of a deliberately designed reflecting object generates unwanted multipath (reflected signals) in the cGNSS data. To mitigate against this, we located CRs >30 m from the cGNSS with no inter-visibility. Daily RMS values of the zero-difference ionosphere-free carrier-phase residuals, and ellipsoidal heights from static precise point positioning GNSS processing at each co-located site were then used to ascertain that the CR did not generate unwanted cGNSS multipath. These steps form a set of recommendations for the installation of such geodetic ground-infrastructure, which may be of use to others wishing to establish integrated InSAR-cGNSS monitoring of VLM elsewhere.


Proximity of jupiter-like planets to low-mass stars.
The sensitivities of astrometric and radial velocity searches for extrasolar planets are strongly dependent on planetary masses and orbits. Because most nearby stars are less massive than the sun, the first detection is likely to be of a Jupiter-mass planet orbiting a low-mass star, with a possible theoretical expectation being that Jupiter-like planets will be found much closer [inside the Earth-sun separation of 1 astronomical unit (AU)] to these low-luminosity stars than Jupiter is to the sun (5.2 AU). However, radiative hydrodynamic models of protoplanetary disks around low-mass stars (of 0.1 to 1 solar mass) show that Jupiter-like planets should form at distances (approximately 4 to 5 AU) that are only weakly dependent on the stellar mass.


Post-endocytic sorting of calcitonin receptor-like receptor and receptor activity-modifying protein 1.
Calcitonin receptor-like receptor (CLR) and the receptor activity-modifying protein 1 (RAMP1) comprise a receptor for calcitonin gene-related peptide (CGRP). Although CGRP induces endocytosis of CLR/RAMP1, little is known about post-endocytic sorting of these proteins. We observed that the duration of stimulation with CGRP markedly affected post-endocytic sorting of CLR/RAMP1. In HEK and SK-N-MC cells, transient stimulation (10(-7) M CGRP, 1 h), induced CLR/RAMP1 recycling with similar kinetics (2-6 h), demonstrated by labeling receptors in living cells with antibodies to extracellular epitopes. Recycling of CLR/RAMP1 correlated with resensitization of CGRP-induced increases in [Ca(2+)](i). Cycloheximide did not affect resensitization, but bafilomycin A(1), an inhibitor of vacuolar H(+)-ATPases, abolished resensitization. Recycling CLR and RAMP1 were detected in endosomes containing Rab4a and Rab11a, and expression of GTPase-defective Rab4aS22N and Rab11aS25N inhibited resensitization. After sustained stimulation (10(-7) M CGRP, >2 h), CLR/RAMP1 trafficked to lysosomes. RAMP1 was degraded approximately 4-fold more rapidly than CLR (RAMP1, 45% degradation, 5 h; CLR, 54% degradation, 16 h), determined by Western blotting. Inhibitors of lysosomal, but not proteasomal, proteases prevented degradation. Sustained stimulation did not induce detectable mono- or polyubiquitination of CLR or RAMP1, determined by immunoprecipitation and Western blotting. Moreover, a RAMP1 mutant lacking the only intracellular lysine (RAMP1K142R) internalized and was degraded normally. Thus, after transient stimulation with CGRP, CLR and RAMP1 traffic from endosomes to the plasma membrane, which mediates resensitization. After sustained stimulation, CLR and RAMP1 traffic from endosomes to lysosomes by ubiquitin-independent mechanisms, where they are degraded at different rates.


Immunological effects of treatment with sequential administration of recombinant interferon gamma and alpha in patients with metastatic renal cell carcinoma during a phase I trial.
Many anticancer mechanisms of the interferons have been proposed but none have been associated with clinical response to date. The biological activities of the interferons in vivo have included effects upon the natural killer cell, T- and B-lymphocytes, and macrophages. This report details a prospective study of the immunological effects on peripheral blood mononuclear cells of sequentially administered recombinant (r) interferon (IFN) gamma and rIFN alpha in 28 patients with metastatic renal cell carcinoma. Natural killer cell activity, T-cell phenotype (CD4, CD8, CD56, CD16, CD4/HLA-DR, CD8/HLA-DR, CD56/HLA-DR) and 2',5'-oligoadenylate synthetase were measured prior to therapy, during therapy, and following completion of treatment. Statistical analysis of all parameters was performed for the entire group, by individual patient, by dosage, by time, and by clinical response. An overall significant depression in natural killer cell activity and in the percentage of circulating CD56, CD16, and CD8+ cells were noted. Significant increases in 2',5'-oligoadenylate synthetase and in the percentage of circulating CD4 cells were also noted. Although an association between the magnitude of change in percentage of CD16+ cells and 2',5'-oligoadenylate synthetase and dosage of rIFN gamma and rIFN alpha, respectively, was observed, optimal biological dose of this sequence of rIFNs could not be determined due to the limited number of patients. A decrease in the percentage of circulating CD8+ cells was observed among patients with objective clinical response (partial and complete). Sequentially administered rIFN gamma and rIFN alpha can modulate immunological parameters in vivo in patients with metastatic renal cell carcinoma. A fall in percentage of circulating CD8+ cell is associated with response and suggests that this sequence of rIFN alpha and rIFN gamma might influence T-cell mediated antitumor activity.


Perception of current and ideal body size in preschool age children.
25 girls and 25 boys between the ages of 5 and 7 years indicated their current and desired body size on Collins' figures. The children's weight and height were measured, and the Body Mass Index was calculated. 52% of girls and 44% of boys expressed a wish to become thinner in relation to perception of their own body. Significant sex differences were found in selection of the ideal figure: girls showed greater preferences for a thinner figure than boys. There was a significant correlation between perception of current figure and Body Mass Index for boys but not for girls.


Acupuncture in De Quervain's disease: a treatment proposal.
De Quervain's disease is a painful stenosing tenosynovitis of the first dorsal compartment of the hand affecting the tendons of the abductor pollicis longus and extensor pollicis brevis, caused mainly by overuse. Conventional treatments include rest, immobilisation, oral anti-inflammatory drugs, corticosteroid injection and even surgery, but none of these is established as clearly effective. Acupuncture is rarely mentioned and the points suggested are rather general-regional, tender and ah shi points. Tendinopathy is almost always associated with problems in the relevant muscles and this paper calls attention to the correct identification and needling of the affected muscles, in order to increase the specificity of acupuncture treatment.


Highly sensitive fluorometric method based on nitrogen-doped carbon dot clusters for tartrazine determination in cookies samples.
Nitrogen-doped carbon nanodots (CDs) were prepared via the solvothermal method, using urea and triethylene glycol as the starting materials. The as-prepared CDs had individual diameters of approximately 100 nm and were in clusters of different sizes. The surface composition and optical properties of the as-prepared CDs were characterized. They exhibited multicolor emission properties in the visible range when excited with a wide wavelength range. The aqueous solution of the CDs was used in highly sensitive tartrazine determination. The fluorescence quenching of the CDs was in a linear relationship with the concentrations of tartrazine in the range of 0.5-30.0 μM. The detection limit of the assay was 0.18 μM. Acceptable recovery results were obtained via spike-recovery experiments on cookie samples.


Increase in posterior alpha activity during rehearsal predicts successful long-term memory formation of word sequences.
It is becoming increasingly clear that demanding cognitive tasks rely on an extended network engaging task-relevant areas and, importantly, disengaging task-irrelevant areas. Given that alpha activity (8-12 Hz) has been shown to reflect the disengagement of task-irrelevant regions in attention and working memory tasks, we here ask if alpha activity plays a related role for long-term memory formation. Subjects were instructed to encode and maintain the order of word sequences while the ongoing brain activity was recorded using magnetoencephalography (MEG). In each trial, three words were presented followed by a 3.4 s rehearsal interval. Considering the good temporal resolution of MEG this allowed us to investigate the word presentation and rehearsal interval separately. The sequences were grouped in trials where word order either could be tested immediately (working memory trials; WM) or later (LTM trials) according to instructions. Subjects were tested on their ability to retrieve the order of the three words. The data revealed that alpha power in parieto-occipital regions was lower during word presentation compared to rehearsal. Our key finding was that parieto-occipital alpha power during the rehearsal period was markedly stronger for successfully than unsuccessfully encoded LTM sequences. This subsequent memory effect demonstrates that high posterior alpha activity creates an optimal brain state for successful LTM formation possibly by actively reducing parieto-occipital activity that might interfere with sequence encoding.


[Social background in recruitment of medical students].
The questions raised in this article is whether the social background of Norwegian medical students has changed over time, and whether changes in admission procedures have influenced recruitment. The analysis is based on the total population of Norwegian students who qualified for university admission between 1980 and 2003, including those who entered medical school. The proportion of medical students who qualified for admission to medicine through private-school tutoring is estimated for the whole period, so is the degree to which medical students read other university subjects prior to entering medical school in order to get in. The impact of social origin is studied by estimates of the proportions of university-qualified students from various social strata who went to medical school, as well as by logistic regression analysis. The use of private-school tutoring has decreased in recent years, while the proportion who read other university subject prior to admission has increased. The impact of social background has not changed. Those who have physicians as parents are particularly likely to go to medical school; the relative difference between them and students with parents with other university degrees or a lower educational attainments tends to be stable over time. This also holds true when we compare students with the same grade level in school. Three explanations are offered for the stable social recruitment, and especially for the high proportion of physicians' children recruited: physicians have ample financial means to support their children, their children develop an interest in medicine because of their parents' line of work, and they wish to avoid social degradation.


Chitosan and β-Cyclodextrin-epichlorohydrin Polymer Composite Film as a Plant Healthcare Material for Carbendazim-Controlled Release to Protect Rape against Sclerotinia sclerotiorum (Lib.) de Bary.
The influence of β-cyclodextrin-epichlorohydrin (β-CD-EP) polymers on the improvement of the solubility and antifungal activity of carbendazim has been investigated. Meanwhile, the potential of the chitosan and β-CD-EP composite film used as a plant healthcare material for carbendazim-controlled release to protect rape against Sclerotinia sclerotiorum (Lib.) de Bary has been evaluated. β-CD-EP-1 and 2 (β-CD content, 750 mg/g and 440 mg/g, respectively) were found to significantly improve the solubility of the guest molecule carbendazim (17.9 and 18.5 times, respectively) and the 1:1 stoichiometry of the host-guest was confirmed by the Job's plot. A slight synergism was observed for the β-CD-EP/carbendazim complex against S. sclerotiorum (Lib.) de Bary, indicating an enhancement to the bioavailability of carbendazim. The in vitro release studies revealed that β-CD-EP polymers could efficiently modulate carbendazim release behaviors, such as the release retard and rate. The in vivo efficacy experiments demonstrated that the β-CD-EP/carbendazim and chitosan composite film could significantly prolong the effective duration of carbendazim at a concentration of 100 μg/mL compared with spraying carbendazim at 500 μg/mL. Thereby, a highly useful and strategic concept in plant disease control by a plant healthcare material-the chitosan and polymeric β-CD-EP composite film-is provided, which could also serve as a concept for related plant diseases.


Eosinophilic vacuolated tumor (EVT) of kidney demonstrates sporadic TSC/MTOR mutations: next-generation sequencing multi-institutional study of 19 cases.
A distinct renal tumor has recently been described as "high-grade oncocytic renal tumor" and "sporadic renal cell carcinoma with eosinophilic and vacuolated cytoplasm". The Genitourinary Pathology Society (GUPS) consensus proposed a unifying name "eosinophilic vacuolated tumor" (EVT) for this emerging entity. In this multi-institutional study, we evaluated 19 EVTs, particularly their molecular features and mutation profile, using next-generation sequencing. All cases were sporadic and none of the patients had a tuberous sclerosis complex. There were 8 men and 11 women, with a mean age of 47 years (median 50; range 15-72 years). Average tumor size was 4.3 cm (median 3.8 cm; range 1.5-11.5 cm). All patients with available follow-up data (18/19) were alive and without evidence of disease recurrence or progression during the follow-up, ranging from 12 to 198 months (mean 56.3, median 41.5 months). The tumors were well circumscribed, but lacked a well-formed capsule, had nested to solid growth, focal tubular architecture, and showed ubiquitous, large intracytoplasmic vacuoles, round to oval nuclei, and prominent nucleoli. Immunohistochemically, cathepsin K, CD117, CD10, and antimitochondrial antigen were expressed in all cases. Other positive stains included: PAX8, AE1/AE3 and CK18. CK7 was typically restricted only to rare scattered cells. Vimentin, HMB45, melan-A, and TFE3 were negative in all cases. All tumors showed retained SDHB. All cases (19/19) showed non-overlapping mutations of the mTOR pathway genes: TSC1 (4), TSC2 (7), and MTOR (8); one case with MTOR mutation showed a coexistent RICTOR missense mutation. Low mutational rates were found in all samples (ranged from 0 to 6 mutations/Mbp). Microsatellite instability and copy number variations were not found in any of the 17 analyzable cases. EVT represents an emerging renal entity that shows a characteristic and readily identifiable morphology, consistent immunohistochemical profile, indolent behavior, and mutations in either TSC1, TSC2, or MTOR genes.


Using a monotone single-index model to stabilize the propensity score in missing data problems and causal inference.
The augmented inverse weighting method is one of the most popular methods for estimating the mean of the response in causal inference and missing data problems. An important component of this method is the propensity score. Popular parametric models for the propensity score include the logistic, probit, and complementary log-log models. A common feature of these models is that the propensity score is a monotonic function of a linear combination of the explanatory variables. To avoid the need to choose a model, we model the propensity score via a semiparametric single-index model, in which the score is an unknown monotonic nondecreasing function of the given single index. Under this new model, the augmented inverse weighting estimator (AIWE) of the mean of the response is asymptotically linear, semiparametrically efficient, and more robust than existing estimators. Moreover, we have made a surprising observation. The inverse probability weighting and AIWEs based on a correctly specified parametric model may have worse performance than their counterparts based on a nonparametric model. A heuristic explanation of this phenomenon is provided. A real-data example is used to illustrate the proposed methods.


The comparison of the effects of hepatic regeneration after partial hepatectomy, silybum marinaum, propofol, N-acetylcysteine and vitamin E on liver.
We investigated the comparison of the effects of N-acetylcysteine, silybum marinaum, propofol, and vitamin E on liver hepatic regeneration after partial hepatectomy. Forty-eight rats were randomized into 6 different groups of the same age and weight. After partial hepatectomy, all animals were resuscitated with 5 ml of isotonic sodium chloride solution administered subcutaneously while group 1 (sham) did not receive any injection, group 2 (control) received serum physiologic intraperitoneally, group 3 received 25 mg /kg of propofol intraperitoneally, group 4 received 20 mg/kg of N-acetylcysteine intraperitoneally, group 5 received 400 mg/kg of vitamin E intraperitoneally, and group 6 received 10 mg/kg of silybum intraperitoneally. None of these groups were given antibitotics. On the third day, a half of the rats, and on the seventh day, the other half of rats were reoperated and sacrificed. Blood samples were used for biochemical parameters (AST, ALT). Ki-67 proliferation index was used for histopathologic parameters. A statistically meaningful difference was detected in silybum, vitamin E, N-acetylcysteine, and propofol groups for AST, ALT levels when compared to control and sham groups (p<0.05). Ki-67 regeneration proliferation index of all groups, which were given agents on the third and seventh days were statistically higher than the control and sham groups (p<0.05). During the evaluation, AST, ALT, Ki-67, Ro (regeneration value) levels of silybum group displayed a statistically significant difference according to other groups (p<0.05). Our experimental study indicates that hepatic regeneration after partial hepatectomy was meaningful and significant in groups with intraperitoneal administration of silybum marinaum,vitamin E, N-acetylcysteine and propofol. Hepatic regeneration rate was particularly higher in silybum group compared to other groups (Fig. 16, Ref. 26).


Immediate loss of cell-mediated immunity to murine cytomegalovirus upon treatment with immunosuppressive agents.
Splenic lymphocytes from cytomegalovirus-infected mice lost their in vitro proliferative responses to cytomegalovirus antigen within 3 h after in vivo treatment with antilymphocyte globulin and prednisolone. The response was inhibited when the agents were administered separately or together, and inhibition persisted through a 2-week course of immunosuppression. Circulating specific antibodies were depressed by multiple injections of antilymphocyte globulin alone or with prednisolone, but not by prednisolone alone. Mitogen-induced blast transformation was immediately depressed by immunosuppression with both agents. Although the response to lipopolysaccharide returned briefly, it declined with continuing treatment. Cytomegalovirus infection augmented the depressive effect of immunosuppression on the lipopolysaccharide proliferative response. Prednisolone treatment of infected animals did not affect the concanavalin A response, and lipopolysaccharide stimulation decreased more slowly and to a lesser extent than it did in mice treated with antilymphocyte globulin or both agents. Loss of specific cell-mediated immunity and simultaneous depression of humoral immunity indicated that immunosuppression immediately created an inability to respond to an active cytomegalovirus infection.


Caring for the children.
KwaZulu Natal has the highest rates of HIV/AIDS in South Africa. Teams of British nurses and doctors visit the province regularly to help staff there learn about antiretroviral therapy.


Expression of connexin-26, -32, and -43 gap junction proteins in the porcine cervix and uterus during pregnancy and relaxin-induced growth.
Connexin (CX) proteins participate in growth, differentiation, and tissue remodeling. Relaxin-stimulated reproductive tissue growth and remodeling may be facilitated by enhanced intracellular communication. This study was an examination of the effects of relaxin in vivo on expression of CX-26, CX-32, and CX-43 in the cervix and uterus of prepubertal pigs. In addition, expression of these proteins was monitored in the sow uterus during pregnancy. Relaxin was administered to prepubertal gilts every 6 h for 54 h. CX expression was characterized by immunoblotting and localized by immunofluorescence. Significant increases in all three CXs were observed in the cervix following relaxin treatment (P < 0.05). Uterine CX proteins were also significantly higher (P < 0.05) in relaxin-treated animals compared to controls. The CX protein level in relaxin-treated animals was similar to that observed during the second half of pregnancy, but below levels found in mature, nonpregnant sows. This is the first evidence for specific CX expression in the porcine cervix, and the first study to show that relaxin increases the expression of CX proteins in the porcine uterus and cervix. The data show that CX proteins are differentially regulated in the uterus of the pig during pregnancy. These data support a role for CX-mediated communication during relaxin-induced reproductive tissue growth and remodeling.


Analysis of prognostic factors for postoperative complications and reinterventions after open surgical repair and endovascular aneurysm repair in patients with abdominal aortic aneurysm.
A definitive treatment for patients with abdominal aortic aneurysm considering age and comorbidities has not been identified. In the present study, we retrospectively validated treatment outcomes in Japanese patients and proposed the treatment strategy of open surgical repair (OSR) and endovascular aneurysm repair (EVAR). We retrospectively analyzed data for patients undergoing EVAR or OSR between 2006 and 2017. Patients with ruptured abdominal aortic aneurysm were excluded. We examined post-operative complications, operative mortality, re-intervention and prognosis. Throughout the study period, 405 patients underwent EVAR and 176 patients underwent OSR. The percentage of patients with post-operative complications was 35.8% in the OSR group, compared with 13.1% in the EVAR group (P < 0.01). The operative mortality rate was 0.49% in the EVAR group and 0.57% in the OSR group (P = 1.00). With a multivariate analysis, age, hemodialysis, modified Frailty Index (mFI), and OSR were risk factors for post-operative complications. The 5-year re-intervention free survival rate was 63.0 % with hostile neck EVAR compared with 83.1 % with favorable neck EVAR and 86.1 % with OSR group (P < 0.01). With a multivariate analysis, hemodialysis, mFI, and hostile neck EVAR were risk factors for re-intervention. The 5-year overall survival rate was 51.9 % with hostile neck EVAR compared with 73.2 % with favorable neck EVAR and 79.0 % with OSR group (P < 0.01). With a multivariate analysis, age, mFI, and hostile neck EVAR were poor prognostic factors. Age, mFI, hemodialysis and hostile neck anatomy are useful predictors of post-operative complications, re-intervention and overall survival, and could be useful for informing treatment selection between OSR and EVAR.


Treatment of hypertension in the elderly.
We have evaluated the effectiveness of antihypertensive therapy for predominant systolic hypertension in 55 patients, aged 61 to 76 years, with untreated systolic blood pressures of at least 160 mm Hg and diastolic blood pressures less than 100 mm Hg. In this retrospective analysis, 41 of the patients had been treated with the centrally acting agent guanabenz (average dose 24 +/- 14 [SD] mg daily) given alone, and 14 had received a combination of guanabenz (17 +/- 10 mg daily) and hydrochlorothiazide (60 +/- 30 mg daily). After six months of therapy, each regimen significantly decreased both systolic and diastolic blood pressures. Moreover, there were no differences between the two treatment regimens in their antihypertensive efficacy, and there was no evidence of orthostatic effects. In both treatment groups, approximately 50% of the patients had excellent therapeutic responses (decrease in supine systolic blood pressure of at least 20 mm Hg). The main side effects of treatment were drowsiness and dry mouth, though these tended to be mild and of short duration. Thus, in predominant systolic hypertension in elderly patients, guanabenz, either alone or in combination with a diuretic, appears to be an effective and well tolerated form of treatment.


Effect of O6-alkylguanine pretreatment on the sensitivity of human colon tumor cells to the cytotoxic effects of chloroethylating agents.
Two human colon carcinoma cell lines which differ greatly in their content of O6-alkylguanine-DNA alkyltransferase were analyzed for their response to 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) and 2-chloroethyl(methylsulfonyl)methanesulfonate (ClEtSoSo) before and after treatment with O6-alkylguanines. HT29 cells contained about 17 times more alkyltransferase activity than BE cells. The alkyltransferase activity of HT29 cells was reduced by 60-80% by treatment for 24 h with 0.05-0.4 mM O6-methylguanine or O6-n-butylguanine. Such pretreatment prior to exposure to CCNU or ClEtSoSo increased the sensitivity of HT29 cells to these drugs. The exposure to O6-alkylguanines gave a greater enhancement of the toxic effects of ClEtSoSo than of CCNU. There was no significant increase in the toxicity of these agents towards the BE cells which contained much lower levels of the alkyltransferase. When added alone neither O6-methylguanine nor O6-n-butylguanine showed any toxicity towards HT29 or BE cells at the doses used. These results provide strong evidence that the formation of adducts at the O6-position of guanine by these agents contributes significantly to their lethality and that this reaction is more critical for ClEtSoSo than CCNU. The enhancement of the activity of chloroethylating agents by pretreatment with nontoxic doses of O6-alkylguanines may be clinically useful in terms of increasing their therapeutic efficacy towards cells containing high levels of alkyltransferase.


Antitumor properties of two traditional aromatic rice genotypes (Kalijira and Chinigura).
Methanol extract of bran and unpolished grain of two traditional aromatic rice genotypes viz. Kalijira and Chinigura were assayed for their activity on the growth and initiation of crown-gall tumors on potato disks. Three Agrobacterium tumefaciens (A. tumefaciens) strain AtSl0105, AtTa0112, and AtAc0114 were used as the tumor forming agent. Collected rice was separated to bran and unpolished grain by different milling processes and made into fine powder before extracting using methanol. Antitumor assay of plant extracts was performed according to standard potato disc bioassay. Disc diffusion assay (Kirby-Bauer Method) was used to screen A. tumefaciens sensitivity test. The results demonstrated a high correlation between the ability of aromatic rice to inhibit the initiation and growth of crown-gall tumors on potato disks. Maximum tumor inhibitions were observed against the strain AtSl0105 by Kalijira bran (73.91%) and Chinigura bran (69.56%). Both unpolished grains showed significant effect (Kalijira 57.43%, Chinigura 55.53%) to inhibit the tumor. It can be concluded that aromatic rice (Kalijira and Chinigura) might be a potential source of antitumor agent that can be used for further drug development for tumor treatment.


Admissible mixing distributions for a general class of mixture survival models with known asymptotics.
Statistical analysis of data on the longest living humans leaves room for speculation whether the human force of mortality is actually leveling off. Based on this uncertainty, we study a mixture failure model, introduced by Finkelstein and Esaulova (2006) that generalizes, among others, the proportional hazards and accelerated failure time models. In this paper we first, extend the Abelian theorem of these authors to mixing distributions, whose densities are functions of regular variation. In addition, taking into account the asymptotic behavior of the mixture hazard rate prescribed by this Abelian theorem, we prove three Tauberian-type theorems that describe the class of admissible mixing distributions. We illustrate our findings with examples of popular mixing distributions that are used to model unobserved heterogeneity.


Involvement of adenosine in retinal ischemia. Studies on the rat.
The aim of this study was to determine whether adenosinergic agents can be used to slow down the changes seen in the rat retina after ischemia-reperfusion. Ischemia-reperfusion injury to the rat retina was induced by raising the intraocular pressure above the systolic blood pressure for 45 minutes, followed by reperfusion for 3 days. This insult caused a reduction of the b-wave of the electroretinogram (54% +/- 5%, n = 23) relative to the contralateral control retina, an expression of glial fibrillary acidic protein (GFAP) in the Müller cells, and an alteration in the "staining" pattern of the calretinin immunoreactivity. The normal two to three bands of calretinin immunoreactivity in the inner plexiform layer appeared as a single band. Elevation of the intraocular pressure for 60 minutes, followed by reperfusion of 2 weeks, caused a 40% reduction in the thickness of the inner nuclear and plexiform layers. No statistically significant changes in the other retinal layers were recorded. When the adenosine deaminase inhibitor erythro-9-(2-hydroxyl-3-nonyl)adenine (EHNA) was injected into the eye just before ischemia, the ischemia-reperfusion changes in the b-wave and calretinin immunoreactivity were largely prevented. Similar results were observed when the adenosine A1 receptor agonist, R-N6-(2-phenylisopropyl)adenosine (R-PLA), was administered intraperitoneally just before ischemia. Injection of adenosine deaminase into the eye before ischemia seemed to potentiate the ischemia-reperfusion effect because the reduction of the b-wave was almost complete (8% +/- 4%, n = 6). The ischemia-reperfusion-induced expression of GFAP in the Müller cells was not reduced by any of the adenosinergic agents tested. This suggests that GFAP expression in the Müller cells is not related to a reduction in the b-wave. An injection of EHNA into the eye before ischemia reduced the thinning of the inner plexiform and nuclear retinal layers so that no significant difference between them and the control retinas existed. However, an injection of R-PIA just before ischemia did not reduce the thinning of the retinal layers in a statistically significant way, possibly because the R-PIA protective effect is less than that of EHNA and is difficult to detect when thickness of the retinal layers is measured. It may be necessary to use higher concentrations of R-PIA to observe a protective effect. The combined data show that substances resulting in the activation of adenosine A1 receptors protect the retina against changes induced by ischemia-reperfusion.


The sagittal diameter of the lumbar vertebral canal in normal adult Nigerians.
An osteometric study of the anteroposterior diameter of the lumbar vertebral canal and intervertebral foramina of normal adult Nigerians is reported. The results show that the midsagittal diameter of the canal is subject to racial variations, and is determined primarily by the thickness and orientation of the lamina and to a lesser extent by the height of the pedicle. The significance of the findings is discussed.


Serum Procalcitonin Predicts Anastomotic Leaks in Colorectal Surgery
Background: Anastomotic leaks in colorectal surgery results in a high morbidity and mortality rate. Serum procalcitonin levels is known as a sensitive and specific marker of sepsis and could be use as a marker for early detection of a leak allowing early intervention. It may help a clinician decide to perform a CT scan even earlier especially when the diagnosis of a leak is uncertain. The aim of this study is to determine whether serum procalcitonin is a good predictor of anastomotic leak in colorectal surgery. Methodology: Between July 2014 until October 2015, 70 patients undergoing colorectal surgery were prospectively analyzed in a single-center tertiary teaching hospital. Demographic and surgical data were obtained. Serum procalcitonin was taken before surgery and at day 3 (72 hours) postoperatively. During the postoperative period, the patients were observed in the ward for features of anastomotic leak and if present, it was managed accordingly. The primary outcome was to prospectively determine an association between serum procalcitonin levels and an anastomotic leak in patients who underwent colorectal surgery with a primary anastomosis. Result: The rate of anastomotic leak was 4.5% (3 patients) with a mortality rate of 4.3% (3 patients). A rise in serum procalcitonin was statistically significant among patients with anastomotic leak. The optimal procalcitonin cut-off level at postoperative day 3 was 5.27 ng/mL, resulting in 100% sensitivity, 85% specificity, 23% positive predictive value and 100% negative predictive value. Nevertheless, none of the variables showed statistical significance with an anastomotic leak. Conclusion: Procalcitonin is a reliable biochemical marker to help diagnose anastomotic leak in colorectal surgery. Our study has shown that a level of 5 times beyond normal is statistically significant and a value of more than 5.27 ng/mL is confirmatory of a leak.


Mental Health Among Latina Farmworkers and Other Employed Latinas in North Carolina.
The mental health of Latinas with manual occupations, particularly those employed in agriculture, is a public health concern. The goals of this analysis were to describe the mental health of Latina farmworkers, and to compare their mental health with that of other Latina manual workers. Participants included 35 employed Latina farmworkers, 35 employed non-farmworkers, and 25 unemployed non-farmworkers who completed interviews in 2012. Measures included stress, anxiety, depressive symptoms, elevated depressive symptoms, and risk for alcohol dependence. Farmworkers had greater stress and anxiety than did employed and unemployed non-farmworkers. Employed Latinas, whether farmworkers or in other occupations, had greater stress and anxiety than unemployed Latinas. Depressive symptoms, although high, did not differ significantly by occupation and employment. Few were at risk for alcohol dependence. Concrete steps are needed to address the mental health of Latina farmworkers, and to continue documentation of mental health concerns and their causes in this population.


Intractable depression successfully treated with a combination of autogenic training and high-dose antidepressant in department of otorhinolaryngology: a case report.
Patients suffering from ear discomfort are commonly encountered in the department of otolaryngology. If various clinical examinations do not reveal any objective findings, then the patients are referred to the department of internal medicine or psychiatry. Psychotherapy is recommended in some cases. This paper describes the successful administration of autogenic training in a patient suffering from ear discomfort due to major depression. We present a case of intractable depression that was successfully treated with a combination of psychotherapy, administered by a clinical psychologist, and high-dose antidepressant. The patient was a 36-year-old female with hearing discomfort in her left ear. In 2003, she experienced insomnia and an appetite loss, and her condition was diagnosed as major depression along with an avoidant personality disorder. Her depression has not been improved with antidepressant treatment for 3 years in department of psychosomatic medicine. She was referred to our department because of ear discomfort in her left ear. There was no abnormality in her physical examinations. She wanted to be treated in department of otorhinolaryngology. We increased the dose of fluvoxamine maleate up to 200 mg/day, and introduced cognitive therapy and autogenic training by a clinical psychologist. Eventually, her depressive state as well as the hearing complaint was markedly alleviated. Autogenic training can be a viable and acceptable treatment option for patients who fail to respond to other therapies. This case emphasizes the importance of autogenic training as a method to control physical symptom of depression.


[Assessment of the cellular immune response induced in Balb/C mice with dengue virus 2 envelope protein].
The cellular immune response to dengue type 2 virus envelope protein was studied. To this end, the lympho-proliferative capacity of T-lymphocytes obtained from splenocytes of animals immunized with the protein when they were stimulated by such protein and dengue 2 virus. It was realized that splenocytes proliferated significantly in response to both types of viral antigens and that the values of stimulation indexes were higher in response to the whole virus than to the protein alone. Based on the above-mentioned, it was concludes that purified dengue 2 virus envelope protein was capable of generating specific and memory responses of antigen T-cell to dengue 2 type virus.


A connectionist approach to generating oblique decision trees.
Neural networks and decision tree methods are two common approaches to pattern classification. While neural networks can achieve high predictive accuracy rates, the decision boundaries they form are highly nonlinear and generally difficult to comprehend. Decision trees, on the other hand, can be readily translated into a set of rules. In this paper, we present a novel algorithm for generating oblique decision trees that capitalizes on the strength of both approaches. Oblique decision trees classify the patterns by testing on linear combinations of the input attributes. As a result, an oblique decision tree is usually much smaller than the univariate tree generated for the same domain. Our algorithm consists of two components: connectionist and symbolic. A three-layer feedforward neural network is constructed and pruned, a decision tree is then built from the hidden unit activation values of the pruned network. An oblique decision tree is obtained by expressing the activation values using the original input attributes. We test our algorithm on a wide range of problems. The oblique decision trees generated by the algorithm preserve the high accuracy of the neural networks, while keeping the explicitness of decision trees. Moreover, they outperform univariate decision trees generated by the symbolic approach and oblique decision trees built by other approaches in accuracy and tree size.


A qualitative investigation of a prenatal yoga intervention to prevent excessive gestational weight gain: A thematic analysis of interviews.
To describe pregnant women's experiences and perceived facilitators/barriers of a prenatal yoga intervention to prevent excessive gestational weight gain (EGWG). Pregnant women (N = 13) were interviewed after participation in a 12-week prenatal yoga intervention to prevent EGWG. Interviews were summarized using thematic analysis. Twelve themes were identified and organized into four categories: 1) experiences of prenatal yoga (positive experience/enjoyment, pain relief, connecting to body), 2) prenatal yoga and weight (increased mindfulness/self-awareness, increased physical activity, weight management), 3) barriers to prenatal yoga (physical body, commute/traffic, schedule), and 4) facilitators of prenatal yoga (healthy pregnancy, support from other pregnant women, the feeling from prenatal yoga). Prenatal yoga may relieve pain and help women be more connected to their bodies. Prenatal yoga may also help women become more aware of their health behaviors and increases their physical activity which may have important implications for reducing EGWG.


Cometabolism of m-chlorobenzoate by an Arthrobacter.
Twenty isolates representing nine bacterial genera were obtained from enrichment cultures and were shown to cometabolize one or more of 22 substituted benzoates. One of the isolates, an Arthrobacter sp., cometabolized m-chlorobenzoate to a product identified as 4-chlorocatechol by thin-layer chromatography and ultraviolet and infrared spectroscopy. The data indicate that cometabolism by the arthrobacter results from the formation of products by its benzoate-oxiding enzyme system that are not acted upon by the catechol-metabolizing enzymes of the bacterium.


Comparison study on the complete sequence of hepatitis B virus identifies new mutations in core gene associated with hepatocellular carcinoma.
Mutations in the hepatitis B virus (HBV) genome may influence the activity of liver disease. The aim of this study was to identify new viral variations associated with hepatocellular carcinoma (HCC). We carried out a comparison study on the complete sequence of HBV isolated from 20 HCC and 35 non-HCC patients in Qidong, China, an area with a high incidence of HCC. We compared the HBV sequences in a consecutive series of plasma samples from four HCC cases before and after the occurrence of HCC. In addition, we selected four mutations in the HBV core (C) gene to verify their relationships to HCC in an independent set of 103 HCC cases and 103 sex- and age-matched non-HCC controls. The pre-S deletion and 12 point mutations, namely, the pre-S2 start codon mutation, T53C in the pre-S2 gene, T766A in the S gene, G1613A, C1653T, A1762T, G1764A in the X gene, and G1899A, C2002T, A2159G, A2189C, and G2203W (A or T) in the pre-C/C gene, showed close associations with HCC. In the validation study, A2159G, A2189C, and G2203W showed consistent associations with HCC by univariate analysis. Multivariate analysis showed that A2189C and G2203W were independent risk factors for HCC. The odds ratios (95% confidence interval) were 3.99 (1.61-9.92) and 9.70 (1.17-80.58), respectively, for A2189C and G2203W. These results implicate A2189C and G2203W as new predictive markers for HCC. The complete genome analysis of HBV provided pilot data for the identification of novel mutations that could serve as markers for HCC.


Air pollution and pregnancy.
Increased fossil fuel usage and extreme climate change events have led to global increases in greenhouse gases and particulate matter with 99% of the world's population now breathing polluted air that exceeds the World Health Organization's recommended limits. Pregnant women and neonates with exposure to high levels of air pollutants are at increased risk of adverse health outcomes such as maternal hypertensive disorders, postpartum depression, placental abruption, low birth weight, preterm birth, infant mortality, and adverse lung and respiratory effects. While the exact mechanism by which air pollution exerts adverse health effects is unknown, oxidative stress as well as epigenetic and immune mechanisms are thought to play roles. Comprehensive, global efforts are urgently required to tackle the health challenges posed by air pollution through policies and action for reducing air pollution as well as finding ways to protect the health of vulnerable populations in the face of increasing air pollution.


Effectiveness of spa therapy for patients with chronic low back pain: An updated systematic review and meta-analysis.
Low back pain (LBP) is a major health problem around the world. Two previous meta-analyses showed that the spa therapy has a positive effect on reducing pain among patients with LBP based on studies published before 2006 and studies published between 2006 and 2013. In recent years, more studies reported the effect of spa therapy on treating chronic low back pain (CLBP). Our study aimed to update the meta-analysis of randomized controlled trials (RCTs) about the effect of spa therapy on treating CLBP and to examine the effect of spa therapy based on different interventions. PubMed, Embase, Web of Science, and Cochrane Library were searched until May 2018 to identify RCTs about spa therapy among patients with CLBP. Summary effect estimates were calculated by using a random-effects model. The quality of each eligible study was evaluated by Jadad checklist. Twelve studies met the inclusion criteria for the systematic review and were included in meta-analysis. There was a significant decrease in pain based on visual analogue scale (VAS) (mean difference [MD] 16.07, 95% confidence interval [CI] [9.57, 22.57], P < .00001, I = 88%, n = 966), and lumbar spine function in Oswestry disability index (ODI) (MD 7.12, 95% CI [3.77, 10.47], P < .00001, I = 87%, n = 468) comparing spa therapy group to control group. Methodological assessment for included studies showed that the study's quality is associated with lacking blinding. This updated meta-analysis confirmed that spa therapy can benefit pain reliving and improve lumbar spine function among patients with CLBP. Physiotherapy of subgroup analysis indicated that it can improve lumbar spine function. However, these conclusions should be treated with caution due to limited studies. More high-quality RCTs with double-blind design, larger sample size, and longer follow-up should be employed to improve the validity of study results.


Enabling households to support successful migration of AIDS orphans in southern Africa.
Most southern African orphans are cared for by extended families but the implications of the spatial dispersal of such families are seldom recognized: orphans often have to migrate to new homes and communities. This paper, based on qualitative research conducted with children and guardians in urban and rural Lesotho and Malawi, examines orphans' migration experiences in order to assess how successful migration might best be supported. Most children found migration traumatic in the short term, but over time many settled into new environments. Although much AIDS policy in southern Africa stresses the role of communities, the burden of care lay with extended family households. Failed migrations, which resulted in renewed migration and trauma, were attributable to one of two household-level causes: orphans feeling ill-treated in their new families or changes in guardians' circumstances. Policy interventions to reduce disruption and trauma for young AIDS migrants should aim at facilitating sustainable arrangements by enabling suitable households to provide care. Reducing the economic costs of caring for children, particularly school-related costs, would: allow children to stay with those relatives (e.g. grandparents) best able to meet their non-material needs; reduce resentment of foster children in impoverished households; and diminish the need for multiple migrations.


Phase I clinical trial of fazarabine as a twenty-four-hour continuous infusion.
A phase I trial of fazarabine (ara-AC, 1-beta-D-arabinofuranosyl-5-azacytosine, NSC 281272) administered as a 24-h continuous infusion was performed in 24 adults with solid tumor malignancies. The majority of patients had received prior marrow-suppressive therapy. Level 7 (54.5 mg/m2/h for 24 h) was the maximum tolerated dose since during 6 evaluable first courses, 2 episodes of grade 4 granulocytopenia and 3 episodes of grade 3 occurred. Moderate thrombocytopenia also occurred at level 7 with 3 episodes of grade 1 and 1 episode of grade 4 thrombocytopenia during 6 first course treatments. Minimal myelosuppression, principally leukopenia, was seen prior to level 7. The nadir WBC through 47 courses had a linear relationship with plasma steady-state concentrations of ara-AC. The only other toxicity noted was moderate nausea/vomiting, which did not appear to be dose related. Plasma steady-state concentrations of ara-AC were reached in all patients within 4-6 h and ranged from 1.1 microM (11 mg/m2/h for 24 h) to 7.5 microM (54.5 mg/m2/h for 24 h). The mean total body clearance of ara-AC for 47 courses, levels 1-7, was 592 +/- 147 (SD) ml/min/m2 which is similar to prior pharmacokinetic data from the 24-h and 72-h infusion trials of the Pediatric and Medicine Branches, respectively. There were no objective disease responses during the trial. The recommended adult phase II dose for a 24-h infusion of ara-AC is 45-50 mg/m2/h.


Characterization of chloride-depleted human sulfite oxidase by electron paramagnetic resonance spectroscopy: experimental evidence for the role of anions in product release.
The Mo(V) state of the molybdoenzyme sulfite oxidase (SO) is paramagnetic and can be studied by electron paramagnetic resonance (EPR) spectroscopy. Vertebrate SO at pH <7 and >9 exhibits characteristic EPR spectra that correspond to two structurally different forms of the Mo(V) active center termed the low-pH (lpH) and high-pH (hpH) forms, respectively. Both EPR forms have an exchangeable equatorial OH ligand, but its orientation in the two forms is different. It has been hypothesized that the formation of the lpH species is dependent on the presence of chloride. In this work, we have prepared and purified samples of the wild type and various mutants of human SO that are depleted of chloride. These samples do not exhibit the typical lpH EPR spectrum at low pH but rather exhibit spectra that are characteristic of the blocked species that contains an exchangeable equatorial sulfate ligand. Addition of chloride to these samples results in the disappearance of the blocked species and the formation of the lpH species. Similarly, if chloride is added before sulfite, the lpH species is formed instead of the blocked one. Qualitatively similar results were observed for samples of sulfite-oxidizing enzymes from other organisms that were previously reported to form a blocked species at low pH. However, the depletion of chloride has no effect upon the formation of the hpH species.


Noninvasive molecular methods to identify live scarab larvae: an example of sympatric pest and nonpest species in New Zealand.
Despite the negative impact that many scarab larvae have on agro-ecosystems, very little attention has been paid to their taxonomy. Their often extremely similar morphological characteristics have probably contributed to this impediment, which has also meant that they are very difficult to identify in the field. Molecular methods can overcome this challenge and are particularly useful for the identification of larvae to enable management of pest species occurring sympatrically with nonpest species. However, the invasive collection of DNA samples for such molecular methods is not compatible with subsequent behavioural, developmental or fitness studies. Two noninvasive DNA sampling and DNA analysis methods suitable for the identification of larvae from closely related scarab species were developed here. Using the frass and larval exuviae as sources of DNA, field-collected larvae of Costelytra zealandica (White) and Costelytra brunneum (Broun) (Scarabaeidae: Melolonthinae) were identified by multiplex PCR based on the difference in size of the resulting PCR products. This study also showed that small quantities of frass can be used reliably even 7 days after excretion. This stability of the DNA is of major importance in ecological studies where timeframes rarely allow daily monitoring. The approach developed here is readily transferable to the study of any holometabolous insect species for which morphological identification of larval stages is difficult.


EVIDENCE FOR A PERSISTENT VIRAL INFECTION IN A CELL LINE DERIVED FROM BURKITT'S LYMPHOMA.
Henle, Gertrude (Children's Hospital of Philadelphia, Philadelphia, Pa.), and Werner Henle. Evidence for a persistent viral infection in a cell line derived from Burkitt's lymphoma. J. Bacteriol. 89:252-258. 1965.-Exposure of a cell line (EB2) derived from Burkitt's lymphoma to vesicular stomatitis (VSV) and certain other viruses revealed a marked resistance of the cultures to infection. Intact, but not disintegrated lymphoma cells induced resistance to VSV in human embryonic kidney, amnion and diploid, as well as in green monkey kidney cells employed as feeder layers. A line of rabbit kidney or Earle's strain L cells was not protected under similar conditions. Depending upon the number of EB2 cells initially transferred, resistance developed within 1 day or in more than 2 weeks. Cell-free media collected from cultures of EB2 cells in the presence or absence of feeder layers of human cells were capable of conferring rapid protection against VSV to human-cell cultures but not to L cells. The protective principle complies with present criteria for an interferon. The results are compatible with the suggestion that EB2 cultures are latently infected with an as yet unidentified virus.


Contradictory KRAS mutation test results in a patient with metastatic colon cancer: a clinical dilemma in the era of personalized medicine.
The KRAS oncogene is mutated in 40‒50% of colorectal cancers and confers resistance to EGFR-targeted therapy. In the clinic, agents such as cetuximab or panitumumab target the EGFR receptor for therapeutic benefit. Cetuximab was approved by the FDA in 2012 as first-line therapy for KRAS mutation-negative (wild-type), EGFR-expressing metastatic colorectal cancer, in combination with FOLFIRI (5-fluorouracil, irinotecan, leucovorin). Herein we report a case of metastatic colon cancer with conflicting testing results for the KRAS oncogene from two different reference laboratories. The discordant reports complicated the decision-making process regarding the administration of targeted anti-EGFR personalized therapy. As the second test result was wild-type from the same original pathological specimen, the patient was treated with cetuximab-containing combination chemotherapy and appeared to have a response after prior disease progression. It is unclear whether the observed response was fully due to regression of wild-type KRAS-containing tumor or any component of antibody-dependent cellular cytotoxicity to a heterogeneous tumor in this patient.


MicroRNA-19a promotes glioma cell growth by repressing LRIG1.
Growing evidence indicates that deregulation of miRNAs contributes to the development of glioma. In present study, we found that the level of miRNA-19a was significantly elevated in glioma tissues and cell lines. Moreover, down-regulation of miRNA-19a dramatically repressed glioma cell growth in vitro and in vivo. Meanwhile, the expression of LRIG1, a tumor suppressor in glioma, was increased following miRNA-19a knockdown. Furthermore, luciferase reporter assay confirmed that LRIG1 was a direct target of miRNA-19a. In addition, silencing of LRIG1 could reverse the suppressive effect of miRNA-19a inhibitor. Taken together, our results demonstrated that down-regulation of miRNA-19a could suppress the growth of glioma cells, at least in part, through up-regulating LRIG1.


Cdk5rap1-mediated 2-methylthio modification of mitochondrial tRNAs governs protein translation and contributes to myopathy in mice and humans.
Transfer RNAs (tRNAs) contain a wide variety of posttranscriptional modifications that are important for accurate decoding. Mammalian mitochondrial tRNAs (mt-tRNAs) are modified by nuclear-encoded tRNA-modifying enzymes; however, the physiological roles of these modifications remain largely unknown. In this study, we report that Cdk5 regulatory subunit-associated protein 1 (Cdk5rap1) is responsible for 2-methylthio (ms(2)) modifications of mammalian mt-tRNAs for Ser(UCN), Phe, Tyr, and Trp codons. Deficiency in ms(2) modification markedly impaired mitochondrial protein synthesis, which resulted in respiratory defects in Cdk5rap1 knockout (KO) mice. The KO mice were highly susceptive to stress-induced mitochondrial remodeling and exhibited accelerated myopathy and cardiac dysfunction under stressed conditions. Furthermore, we demonstrate that the ms(2) modifications of mt-tRNAs were sensitive to oxidative stress and were reduced in patients with mitochondrial disease. These findings highlight the fundamental role of ms(2) modifications of mt-tRNAs in mitochondrial protein synthesis and their pathological consequences in mitochondrial disease.


A developmental study of risky decisions on the cake gambling task: age and gender analyses of probability estimation and reward evaluation.
Decision making, or the process of choosing between competing courses of actions, is highly sensitive to age-related change, showing development throughout adolescence. In this study, we tested whether the development of decision making under risk is related to changes in risk-estimation abilities. Participants (N = 93) between ages 8-30 performed a child friendly gambling task, the Cake Gambling task, which was inspired by the Cambridge Gambling Task (Rogers et al., 1999), which has previously been shown to be sensitive to orbitofrontal cortex (OFC) damage. The task allowed comparisons of the contributions to risk perception of (1) the ability to estimate probabilities and (2) evaluate rewards. Adult performance patterns were highly similar to those found in previous reports, showing increased risk taking with increases in the probability of winning and the magnitude of potential reward. Behavioral patterns in children and adolescents did not differ from adult patterns, showing a similar ability for probability estimation and reward evaluation. These data suggest that participants 8 years and older perform like adults in a gambling task, previously shown to depend on the OFC in which all the information needed to make an advantageous decision is given on each trial and no information needs to be inferred from previous behavior. Interestingly, at all ages, females were more risk-averse than males. These results suggest that the increase in real-life risky behavior that is seen in adolescence is not a consequence of changes in risk perception abilities. The findings are discussed in relation to theories about the protracted development of the prefrontal cortex.


Value of ultrasound elastography in the diagnosis and management of prostate carcinoma.
The aim of the paper is to review and illustrate the role of sonoelastography in the diagnostic and therapeutic approach of prostate cancer. The examination technique and normal appearance are presented. The paper describes and illustrates the appearance of prostate cancer and suggested diagnostic scores. Artifacts, causes for false results and limitations are discussed and also illustrated. The diagnostic influence of intraprostatic tumor location, tumor volume and Gleason score are presented. The paper also reviews the statistical diagnostic value of the method, the relation to prostate biopsy and magnetic resonance assessment. In the end, potential uses and future developments of the method are mentioned.


Characterization and valuing of hatchery waste from the broiler chicken productive chain.
Characterizing the waste generated from different agro-industrial segments enables the strategic management of residues, with the goal of maximizing recovery within the premises of a circular economy. This research aimed to determine the coefficient of waste generated in broiler chick hatcheries as well as to characterize the waste, taking into account the points of culling and the ages of the laying hens. Furthermore, the waste was used in composting with sheep manure (SM) at increasing inclusion rates (0:100, 10:90, 20:80, 30:70, 40:60, and 50:50). On average, 0.16 kg (DM) of hatchery waste is generated per kg of broiler chicks born. At the hatchery, at least 79% of the total disposal occurs at the hatcher stage. This value is impacted by chicken age (P < 0.05), with birds of a late laying age generating waste with higher contents of carbon (C), volatile solids (VS), ether extract (EE), and nitrogen (N). Culling during egg reception and the manual transfer process account for only 1.8% of the total waste generated on average and thus contribute little to the composition of the overall residues. However, the mechanical transfer process may represent up to 19.0% of the total waste generated by hens of an intermediate laying age. According to the average of all the composting stages, the maximum reduction in solids and C from the hatchery waste was reached when the waste accounted for 50% of the windrow composition. Such conditions resulted in organic fertilizer with the highest N content (2.8%), equivalent to 40.0% more than that in the treatment with no added hatchery waste. The compost resulting from 50% hatchery waste inclusion also had the highest humic acid to fulvic acid (HA:FA) ratio and the highest calcium content due to the higher proportion of eggshells. These findings lead to the recommendation for the inclusion of hatchery waste in composting with SM at a 50% rate by mass.


An outbreak of appreciation: A discursive analysis of tweets of gratitude expressed to the National Health Service at the outset of the COVID-19 pandemic.
The early stages of the coronavirus disease 2019 pandemic prompted unprecedented displays of gratitude to healthcare workers. In the United Kingdom, gratitude was a hotly debated topic in public discourse, catalysing compelling displays of civic togetherness but also attracting criticism for being an unhelpful distraction that authorized unrealistic expectations of healthcare workers. Expressions of thanks tend to be neglected as drivers of transformation, and yet, they are important indicators of qualities to which people attach significance. This study aimed to use discursive analysis to explore how the National Health Service (NHS) was constructed in attention-attracting tweets that expressed and/or discussed gratitude to the NHS. Having determined that Twitter was the most active site for traffic relating to gratitude and the NHS, we established a corpus of 834 most-liked tweets, purposively sampled from Twitter searches on a day-by-day basis over the period of the first lockdown in the United Kingdom (22 March-28 May 2020). We developed a typology for tweets engaging with gratitude as well as analysing what the NHS was thanked for. Our analysis, informed by a discursive psychology approach, found that the meanings attributed to gratitude were highly mobile and there were distinct patterns of activity. The NHS was predominantly-and sometimes idealistically-thanked for working, effort, saving and caring. Displays of gratitude were seen as incommensurable with failures of responsibility. The clap-for-carers campaign was a potent driver of affect, especially in the early parts of the lockdown. The social value of gratitude is implicated in the re-evaluation of the risks and rewards of healthcare and social care work in the wake of the pandemic. We caution against cynicism about gratitude overshadowing the well-being effects that expressing and receiving gratitude can engender, particularly given concerns over the detrimental effects of the pandemic on mental health. This study involves the analysis of data provided by the public and published on social media.


Lack of Conventional Acinar Cells in Parotid Salivary Gland of Patient Taking an Anti-PD-L1 Immune Checkpoint Inhibitor.
Background: Salivary glands (SGs) can be damaged by immune checkpoint inhibitor (ICI) therapy. In patients with ICI-induced SG dysfunction, 60% progress to fulfill classification criteria for primary Sjögren's syndrome (pSS), owing to immune foci in SGs and/or anti-SSA autoantibody positivity. We report the SG tissue analysis of a patient with SG dysfunction after treatment with a programmed death ligand-1 (PD-L1) inhibitor, compared to that of a dry mouth ("sicca") control and pSS patient. Case presentation: The patient received the PD-L1 inhibitor durvalumab (10 mg/kg, every 2 weeks by intravenous infusion) as adjuvant treatment for stage 3 non-small cell lung carcinoma, following concurrent chemo radiotherapy. At 43 weeks after 21 cycles of Durvalumab, the patient was not capable of producing unstimulated or stimulated parotid gland saliva, and a biopsy was taken. Immunohistochemical analysis showed no classical AQP5+ CK7- acinar cell clusters (CK7 marks intercalated ducts, IDs). In contrast, the parenchyma was dominated by hybrid epithelial "structures" with ID-like morphology, containing a mixture of AQP5+CK7-, AQP5-CK7+, and AQP5+CK7+ cells (30 structures/mm2). These structures were present at lower frequencies in sicca control (2/mm2) and pSS (10/mm2) tissue. Hybrid structures contained proliferating (Ki67+) cells and senescent (p16+) cells. Striated ducts showed no abnormal morphology post PD-L1 treatment, in contrast to pSS tissue. PD-L1 expression was detected in the SG parenchyma following anti-PD-L1 therapy. The SG post-PD-L1 therapy further demonstrated focal lymphocytic sialadentitis, harboring disperse, and focal CD4+ T cell-rich infiltrates. CD8+ T cells were also present. In this patient, these CD4+ and CD8+ T cells were observed in-between and inside hybrid structures. CD20+ B-cells were infrequently detected following PD-L1 blockade, in contrast to their preponderance in pSS SG tissue. Conclusion: This patient lacked conventional SG acinar cells following anti-PD-L1 therapy and demonstrated presence of hybrid intercalated duct-like structures. Understanding which mechanisms and dynamics underpinning this aberrant parenchyma may be crucial to understand how SG dysfunction post ICI therapy, and potentially other affected organs. Furthermore, although the patient treated with anti-PD-L1 antibody examined here fulfills the criteria for pSS and demonstrated focal lymphocytic sialadentitis, the further histopathological characteristics do not resemble pSS.


Impurity-assisted interlayer exchange coupling across a tunnel barrier.
Localized impurity or defect states in the insulating barrier layer separating two ferromagnetic films affect dramatically the interlayer exchange coupling (IEC), making it significantly stronger compared to perfect barriers. We demonstrate that the impurity-assisted IEC becomes antiferromagnetic if the energy of the impurity states matches the Fermi energy and that the coupling strength decreases with temperature. These results explain available experimental data on the IEC across tunnel barriers.