The SIN3 deacetylase complex represses genes encoding mitochondrial proteins: implications for the regulation of energy metabolism.
Deacetylation of histones by the SIN3 complex is a major mechanism utilized in eukaryotic organisms to repress transcription. Presumably, developmental and cellular phenotypes resulting from mutations in SIN3 are a consequence of altered transcription of SIN3 target genes. Therefore, to understand the molecular mechanisms underlying SIN3 mutant phenotypes in Drosophila, we used full-genome oligonucleotide microarrays to compare gene expression levels in wild type Drosophila tissue culture cells versus SIN3-deficient cells generated by RNA interference. Of the 13,137 genes tested, 364 were induced and 35 were repressed by loss of SIN3. The approximately 10-fold difference between the number of induced and repressed genes suggests that SIN3 plays a direct role in regulating these genes. The identified genes are distributed throughout euchromatic regions but are preferentially excluded from heterochromatic regions of Drosophila chromosomes suggesting that the SIN3 complex can only access particular chromatin structures. A number of cell cycle regulators were repressed by loss of SIN3, and functional studies indicate that repression of string, encoding the Drosophila homologue of the yeast CDC25 phosphatase, contributes to the G2 cell cycle delay of SIN3-deficient cells. Unexpectedly, a substantial fraction of genes induced by loss of SIN3 is involved in cytosolic and mitochondrial energy-generating pathways and other genes encode components of the mitochondrial translation machinery. Increased expression of mitochondrial proteins in SIN3-deficient cells is manifested in an increase in mitochondrial mass. Thus, SIN3 may play an important role in regulating mitochondrial respiratory activity.


Assessment of 100% Rapid Review as an Effective Tool for Internal Quality Control in Cytopathological Services.
The aim of this study was to evaluate the 100% rapid review (100%-RR) as an effective tool for internal quality control (IQC) in gynecological cytopathology services. A total of 8,677 swabs were analyzed; the negative results were submitted to 100%-RR. Divergent cases were discussed in a consensus meeting to reach a conclusion on the final diagnosis. The data were entered into SAS statistical software, and the agreement of the 100%-RR results with the final diagnosis was tested with the weighted kappa statistic. Of the 8,155 smears characterized as negative, 255 (3.13%) were abnormal smears, and 552 (6.77%) unsatisfactory smears were deemed negative. Regarding the results on the 8,155 smears subjected to 100%-RR when compared with the final diagnosis, there was agreement in 7,063 (86.60%) of them, and there were 1,092 (13.40%) discordant results (65.6%, unsatisfactory; 5.47%, atypical squamous cells of undetermined significance [ASC-US]). The κ index had an agreement of 0.867, with κ = 0.734 (p < 0.0001). Compared with the final diagnosis, the sensitivity of 100%-RR was 99.91% and its specificity was 99.4% for severe abnormalities. The sensitivity for high-grade squamous intraepithelial lesions was 88.2%, with a specificity of 100.00%. For abnormalities considered borderline, such as ASC-US, the sensitivity was 94.50% and the specificity was 99.5%. The 100%-RR was considered efficient when used as an IQC method.


The anterior medial hippocampus contributes to both recall and familiarity-based memory for scenes.
The hippocampus is usually associated with recall memory, whereas its contribution to familiarity-based memory is debated. Growing evidence support the idea that this structure participates to any cognitive process performed on scene representations. In parallel, differences in functional specialisation and cortical connectivity were found across the longitudinal and transverse axes of the hippocampus. Here we reanalysed functional MRI data from 51 participants showing stronger engagement of the hippocampus in recall, familiarity-based recognition and rejection, and visual discrimination, of scenes compared to single objects. A conjunction analysis between these four tasks revealed a set of occipital, medial temporal, posterior cingulate, and parietal regions, matching the scene construction network described in the literature. Crucially, we found that the anterior medial part of the hippocampus was consistently involved in all tasks investigated for scene stimuli. These findings support that the hippocampus can contribute to both recall and familiarity-based memory, depending on stimulus type. More generally, this bolsters the recent proposal that circumscribed regions within the hippocampus may underpin specific cognitive mechanisms.


Identification of an animal sucrose transporter.
According to a classic tenet, sugar transport across animal membranes is restricted to monosaccharides. Here, we present the first report of an animal sucrose transporter, SCRT, which we detected in Drosophila melanogaster at each developmental stage. We localized the protein in apical membranes of the late embryonic hindgut as well as in vesicular membranes of ovarian follicle cells. The fact that knockdown of SCRT expression results in significantly increased lethality demonstrates an essential function for the protein. Experiments with Saccharomyces cerevisiae as a heterologous expression system revealed that sucrose is a transported substrate. Because the knockout of SLC45A2, a highly similar protein belonging to the mammalian solute carrier family 45 (SLC45) causes oculocutaneous albinism and because the vesicular structures in which SCRT is located appear to contain melanin, we propose that these organelles are melanosome-like structures and that the transporter is necessary for balancing the osmotic equilibrium during the polymerization process of melanin by the import of a compatible osmolyte. In the hindgut epithelial cells, sucrose might also serve as a compatible osmolyte, but we cannot exclude the possibility that transport of this disaccharide also serves nutritional adequacy.


Exploration and high adventure: the legacy of Grey Walter.
Although many people feel themselves to be familiar with Grey Walter's ideas, and with the design principles of his tortoises, most of the published sources are lacking in detail. This paper gathers together images and written material from a variety of published and unpublished sources to set both the man and his work in a richer context than has been possible for many decades. Grey Walter emerges as a fascinating and far-seeing figure whose work has not dated, perhaps because it was explicitly based on similar principles to those used today in biologically inspired robotics.


Surveillance for rejection by echocardiographically guided endomyocardial biopsy in the infant heart transplant recipient.
Echocardiographically guided endomyocardial biopsy via percutaneous right internal jugular vein puncture has been performed 98 times in six patients 5-16 years of age at our institutions. The use of this approach was extended for rejection surveillance in seven infants transplanted at 2 weeks to 15 months of age (median, 2 months; mode, 2 weeks). A total of 35 consecutive biopsies were performed under heavy sedation in these infants (lowest weight, 3.0 kg) with the use of a 5F semirigid bioptome through a 5.0-cm 5F sheath. There was no case of entrance failure. A median of four biopsies was performed on each child (range, one to 14). Four to seven tissue pieces per biopsy were obtained using an apical four-chamber view for bioptome guidance. Ten instances of clinically suspected rejection were not confirmed by biopsy, and two cases of unsuspected rejection were found. The only complication was one instance of new mild tricuspid regurgitation in this group compared with one instance of increased tricuspid regurgitation after biopsy in the older child group. These preliminary results suggest that echocardiographically guided endomyocardial biopsy from the right internal jugular approach is a reliable and safe means for rejection surveillance in the infant and young child.


Neutrality of foreign complex subunits in an experimental model of lateral gene transfer.
Lateral gene transfer (LGT) is a powerful force in microbial evolution. However, the barriers that restrict this evolutionary phenomenon are not fully understood. It has long been observed that genes that encode subunits of complexes exhibit relatively compatible phylogenies, implying mostly vertical evolution. This may be explained by the failure of a new gene product to effectively interact with preexisting protein subunits, making its acquisition neutral--a theory termed the "complexity hypothesis." On the other hand, such genes may reduce the fitness of the host by disturbing the stoichiometric balance between complex subunits, resulting in purifying selection against gene retention. To examine these 2 alternative scenarios, we designed an experimental system that mimics the transfer of genes encoding homologs of essential complex subunits into the model bacterium Escherichia coli. In addition, we overexpressed the native E. coli gene in order to examine the contribution of gene dosage effects. We show that accumulation of native or foreign complex subunits in the cell does not result in loss of fitness, except for a minor fitness reduction observed for a single foreign homolog. Indeed, a series of genetic and biochemical assays failed to detect any interaction between the foreign subunits and the native polypeptides of the complex, implying an inability of such transfer events to generate positive selection for gene retention. We conclude that LGT of complex subunits may be mostly neutral and that forces operating against gene retention appear to be moderate.


Optimizing irradiation treatment of shell eggs using simulation.
Accurate dose calculation is needed to ensure proper irradiation process control to maintain the freshness of the product. Our objective was to establish the best irradiation treatment for shell eggs taking into account their different components (shell, albumen, yolk). Computer tomography (CT) data were used to generate a 3-D geometry to simulate dose distributions within 1 egg using a radiation transport code (MCNP5). Radiation energies used for simulation were 10 MeV (high-energy) and 1.35 MeV (low-energy) for electron beam, 5 MeV for X-rays, and 1.25 MeV for a gamma-rays source such as Co-60. Low-energy (surface) e-beam simulation indicated that electrons only penetrate up to the thin albumen (0.6 cm). Because of their irregular shape, shell eggs should be irradiated from the side (rather than from top or bottom) for better dose distribution. For high-energy e-beam simulation, the entire egg was irradiated and the best results were obtained when the egg was irradiated from both sides, showing a dose uniformity ratio (D(max)/D(min)) of 1.42. X- or gamma-ray source simulation from one side only, the dose uniformity ratio was 3.38 and 3.12, respectively. For surface-only irradiation, a low-energy e-beam provides a uniform dose distribution. To irradiate the entire egg, 2-sided high-energy e-beam sources are required for an efficient treatment. Unless the product rotates in front of the source, the dose uniformity ratio for X-ray or gamma ray is not adequate for shell egg treatment for pathogen decontamination purposes. Practical Application: Proper control of irradiation treatment of foods such as shell eggs is critical to ensure pathogen inactivation while maintaining product freshness. Simulation allows for accurate calculation of dose distribution within the egg to further establish the best irradiation scheme.


Hippocampal long-term potentiation and spatial learning in the rat: effects of GABAB receptor blockade.
This series of experiments assessed the role of GABAB receptors in the induction of long-term potentiation in the dentate gyrus in vivo, and spatial learning and memory in three different tasks. In urethane-anesthetized rats, the GABAB receptor antagonist CGP 46381 was injected intraperitoneally at a dose which effectively suppressed GABAB-mediated paired pulse disinhibition. Theta-burst stimulation reliably produced long-term potentiation in control rats. However, GABAB receptor blockade significantly suppressed the induction of long-term potentiation in the dentate gyrus. To compare the results of the long-term potentiation experiments with behavior, we assessed the performance of rats on several spatial learning and memory tasks in the presence of CGP 46381. We found that the working memory performance of highly trained rats on the eight-arm radial maze was unaffected by CGP 46381. There was also no effect of GABAB receptor blockade on learning in the eight-arm maze using a five-trial repeated acquisition paradigm. However, when we tested spatial learning in naive rats using a mildly stressful water maze task, we found that CGP 46381 substantially impaired both the latency to find the platform and the path-length travelled in the maze during acquisition. CGP 46381-treated rats took longer to learn the location of the escape platform and travelled a greater distance over the acquisition trials. These data demonstrate that GABAB receptor blockade results in a suppression of hippocampal long-term potentiation in vivo and impairs spatial learning in a task where stress may be a component of performance.


[Atmospheric air pollution and the incidence of lung cancer among urban population].
The article presents results of investigations of ambient air pollution and smoking related cancer morbidity of the population in 26 cities of the USSR. To reveal the relationship with lung cancer morbidity of the urban population a number of techniques are approved for the determination of levels of ecological tension of the atmosphere and consumption of cigarettes per capita in the cities under study is analysed. Correlation analysis results suggest the presence of a common etiological factor for lung cancer for both sexes--smoking. Ambient air pollution influences lung cancer morbidity to a significantly less degree, which is indicated by a weak correlation of this parameter with the morbidity of women.


The use of videos for diabetes patient education: A systematic review.
Diabetes prevalence is rising worldwide, calling for public health concerns and interventions to improve prevention and management. Self-care is an important component in reducing the incidence of complications from diabetes, but it must be taught. This systematic review aims to synthesise the evidence for education videos for people with diabetes. Electronic databases, including Ovid (Medline, Embase, EmCare), PsychInfo, CINAHL, Web of Science and Scopus, were searched for studies on educational videos for patients with diabetes that met the inclusion criteria. A total of 36 studies met the inclusion criteria. Data extracted were synthesised through narrative synthesis. Studies examined outcomes including biological (i.e., glycated haemoglobin (HbA1C), weight, BMI), non-biological (health literacy, self-efficacy) and subjective feedback (i.e., acceptability, cultural appropriateness). The most common length of video was ≤10 min. Online dissemination was the most common method of video distribution. A statistically significant decrease (ranging from -0.1% to -2.1%) in HbA1C was noted in 7 of 12 studies examining this outcome. Other studies also found evidence of improvement in health literacy, self-efficacy, physical activity, medication adherence and other outcomes. Feedback from participants was generally positive, and emphasis was placed on the need for cultural appropriateness and representation in the educational videos.


Novel bladder preservation therapy with Osaka Medical College regimen.
We investigated the effect of balloon occluded arterial infusion of an anticancer agent (cisplatin/gemcitabine), used concomitantly with hemodialysis, which delivers an extremely high concentration of anticancer agent to the tumor site without systemic adverse effects, along with concurrent radiation (referred to as the Osaka Medical College regimen) in patients with advanced bladder cancer. A total of 329 patients (TisN0 16, T2N0 174, T3N0 77, T4N0 22 and TxN+ 40) were assigned to receive the Osaka Medical College regimen. Patients who did not achieve complete response underwent total cystectomy or secondary balloon occluded arterial infusion with an increased amount of cisplatin and/or gemcitabine. The Osaka Medical College regimen allowed 83.6% (276 of 329) of patients in total and 93.6% (250 of 267) of patients with organ confined disease (including T3b) to achieve complete response. Of the patients with a complete response 96% (240 of 250) survived with a functional bladder without evidence of recurrent disease within a mean followup of 159 weeks. Although lymph node involvement, especially N2 stage, was selected as a significant risk factor for treatment failure and survival, it was noteworthy that 61.9% of patients with N1 disease achieved complete response and that the 5-year overall survival rate was 72.2%. No patients had grade III or more severe toxicities. The Osaka Medical College regimen, a new bladder preservation strategy, can be curative not only in patients for whom cystectomy is indicated, but also in patients whose condition is not amenable to curative treatment because of disease stage, age or other factors, and for whom merely palliative therapy would otherwise seem the only option.


[A method for the continuos recording of intracraneal pressure].
91 patients with acute head injuries, hydrocephalus, cerebral infarction, subarachnoid hemorrhage, encephalitis, intracerebral hemorrhage, or carbon monoxide intoxication have been so monitored by using the Numoto pressure switch by a method herein described. The main advantage has been the knowledge of the level of intracranial pressure at any given time and the early detection of a rising pressure when this phenomenon occurred. There were no complications except for 3 cases of infection. Two of these cases were minor purulent collections only at the site of exit of the tube in the scalp. One patient with a compound wound, cerebral laceration, and intracerebral hematoma developed a wound infection and brain abscess which required drainage.


Liquid chromatography/tandem mass spectrometry methods for quantitation of mevalonic acid in human plasma and urine: method validation, demonstration of using a surrogate analyte, and demonstration of unacceptable matrix effect in spite of use of a stable isotope analog internal standard.
Selective, accurate, and reproducible liquid chromatography/tandem mass spectrometry (LC/MS/MS) methods were developed and validated for the determination of mevalonic acid, an intermediate in the biosynthesis of cholesterol and therefore a useful biomarker in the development of cholesterol lowering drugs, in human plasma and urine. A hepta-deuterated analog of mevalonic acid was used as the internal standard. For both methods, calibration standards were prepared in water, instead of human plasma and urine, due to unacceptably high levels of endogenous mevalonic acid. The lower quality control (QC) samples were prepared in water while the higher QC samples were prepared in the biological matrices. For the isolation/purification of mevalonic acid from the plasma and urine matrices, the samples were first acidified to convert the acid analyte into its lactone form. For the plasma samples, the lactone analyte was retained on and then eluted off a polymeric solid-phase extraction (SPE) sorbent. For the urine method, the sample containing the lactone analyte was passed through a C-18 SPE column, which did not retain the analyte, with the subsequent analyte retention on and then elution off a polymeric SPE sorbent. Chromatographic separation was achieved isocratically on a polar-endcapped C-18 analytical column with a water/methanol mobile phase containing 0.5 mM formic acid. Detection was by negative-ion electrospray tandem mass spectrometry. The standard curve range was 0.500-20.0 ng/mL for the plasma method and 25.0-1,000 ng/mL for the urine method. Excellent accuracy and precision were obtained for both methods at all concentration levels tested. It was interesting to note that for certain batches of urine, when a larger sample volume was used for analysis, a high degree of matrix effect was observed which resulted not only in the attenuation of the absolute response, but also in a change of analyte/internal standard response ratio. This demonstrated that, under certain conditions, the use of a stable isotope analog internal standard does not, contrary to conventional thinking, guarantee the constancy of the analyte/internal response ratio, which is a prerequisite for a rugged bioanalytical method. On the other hand, under conditions where the sample matrix does not have such a deleterious effect, we have found that a stable isotope analog could serve as a surrogate (substitute) analyte. Thus, we have shown that using calibration standards prepared by spiking plasma with tri-deuterated or tetra-deuterated mevalonic acid, instead of mevalonic acid itself (the analyte), plasma QC samples that contain mevalonic acid can be successfully analyzed for the accurate and precise quantitation of mevalonic acid. The use of a surrogate analyte provides the opportunity to gauge the daily performance of the method for the low concentration levels prepared in the biological matrix, which otherwise is not achievable because of the endogenous concentrations of the analyte in the biological matrices.


Does sputum culture affect the management and/or outcome of community-acquired pneumonia?
This prospective study was conducted in 6 hospitals in Edmonton, Canada to determine the factors associated with obtaining sputum for culture and the effect of sputum culture on the management of patients with community-acquired pneumonia (CAP). Participants were 1362 adults who were hospitalized with CAP. Sputum was obtained from 539 (39.6%) patients, of which 507 (94.1%) were good quality, acceptable for culture; 171 (33.7%) of these had a positive sputum culture. Levofloxacin, cefuroxime and azithromycin were the most common antibiotics prescribed for the groups with positive sputum culture and no sputum collection. Positive sputum culture was demonstrated in only a small number of patients with CAP; this did not affect antimicrobial therapy or mortality.


Gabapentin-Induced Myokymia: A Case Report.
Gabapentin is a commonly used medication for neuropathic pain and epilepsy that is prescribed by a wide range of medical specialties. Adverse effects including asterixis and myoclonus have been described in patients with chronic kidney disease, but myokymia has not been previously reported. A 69-year-old man with a history of traumatic brain injury, peripheral neuropathy, amnesia, and posttraumatic stress disorder presented to the hospital after multiple falls attributed to acute onset muscle spasms. He reported taking a total daily dose of 9600 mg of gabapentin, as prescribed. Physical examination demonstrated stimulus-sensitive myoclonus, painful muscle spasms in all extremities, and myokymia in his bilateral calves. Diffuse action tremors, as well as tongue tremors, were also observed.Initial workup, including basic laboratory investigations, brain imaging, and electroencephalogram, was unrevealing. Gabapentin toxicity was suspected, and a gabapentin holiday was initiated with the improvement of myokymia by hospital day 3. The patient was found to have a high gabapentin level (25.8 μg/mL; reference range, 2.0-20.0 μg/mL) measured the morning after hospital presentation. After restarting on a lower dose of gabapentin with multimodal pain control, the patient continued to improve with diminution of his myoclonus, tremor, and gait instability. Myokymia is a newly described motor symptom associated with gabapentin toxicity. The mechanism of gabapentin-associated myokymia is currently unknown. A brief medication holiday resulted in the resolution of motor symptoms without significant withdrawal symptoms. Knowledge of this newly reported adverse manifestation can aid physicians in the diagnosis of gabapentin toxicity and prompt treatment, as gabapentin levels are not widely or immediately available.


Does urethral-sparing prostatectomy risk residual prostate cancer?
Urethral length after radical prostatectomy has correlated positively with postoperative urinary continence. Because sparing the prostatic urethra may improve continence after prostatectomy, we evaluated anatomic and pathologic consequences of urethral-sparing surgery. From February to October 1999, 12 patients with clinically localized prostate cancer received a bladder neck-sparing radical retropubic prostatectomy by one surgeon. At the time of operation, the prostatic urethra was anatomically dissected from the prostatectomy specimen and sent separately to pathology to evaluate for the presence of adenoma or prostate cancer. All patients had clinically localized prostate cancer with routine preoperative evaluations, including negative bone scans for prostate-specific antigen (PSA) greater than 10 or Gleason score higher than 7. Pathologic specimens confirmed localized prostate cancer in 7 of 12 specimens. Positive margins were identified in 5, including 2 patients with locally advanced disease. All 12 urethral specimens showed residual prostate adenoma but no prostate cancer. Follow-up ranged from 8 to 16 months with a zero PSA for all evaluated. Residual prostate adenoma is found on dissected urethral specimens during radical retropubic prostatectomy. Although urethral-sparing prostatectomy may improve continence after radical prostatectomy, residual adenoma may confound follow-up PSA results. Furthermore, the malignant potential of the benign periurethral adenoma is unknown. The patient and clinician must understand the implications of residual prostatic tissue when performing urethral-sparing radical retropubic prostatectomy.


Smartphone based colorimetric approach for quantitative determination of uric acid using Image J.
Recently, significant attention has been directed towards digital image colorimetry DIC using mobile applications or available software programs, which offer the advantage of analyzing samples without the need for sophisticated instruments. One such image processing program is Image J, widely used for obtaining quantitative information from scientific images. Image J could measure the color intensities by quantifying of the RGB (red-green-blue) gray levels across the images of colored substances. These values are correlated to the color intensities through conversion to CMY (cyan-magenta-yellow) values which are proportional to the color intensities. The objective of this study is to develop an innovative analytical method for the quantitative determination of uric acid using Image J for color quantification. Image J was utilized to analyze images captured by smart phone for successive concentrations of uric acid that were previously treated with phosphotungstate to develop a blue color. The proposed method has been applied for determination of uric acid in real urine using standard addition method and the results were compared with UV/VIS spectrophotometry as a reference method. In this research, we will also assess the effectiveness of quantitative analysis using Image J in comparison to a mobile application, namely RGB Color Detector.


Computer-assisted measurement of retinal vascular width and tortuosity in retinopathy of prematurity.
To validate the accuracy of ROPtool software in measuring retinal vascular width and tortuosity in a large image set compared with expert diagnoses. Tortuosity and dilation indexes generated by ROPtool were compared with 3 expert consensus grades of normal, pre-plus, or plus disease for 368 quadrants in 92 RetCam (Clarity Medical Systems, Pleasanton, California) fundus images. Sensitivity and specificity of ROPtool software in diagnosing tortuosity and dilation sufficient for plus and pre-plus disease were calculated. These measures were compared with individual accuracies of 3 experienced pediatric ophthalmologists. The mean tortuosity indexes for expert-diagnosed categories of normal, pre-plus, and plus disease were 7.04, 18.73, and 34.62, respectively (P < .001), and the mean dilation indexes were 9.63, 12.05, and 13.61, respectively (P < .001). When optimal tortuosity and dilation index thresholds (from receiver operating characteristic curves) were applied, resultant sensitivity and specificity were 0.913 and 0.863, respectively, for plus tortuosity and 0.782 and 0.840, respectively, for plus dilation. These values were comparable to the performance of examiners judged against the same expert panel. ROPtool version 2.1.5 accurately measures tortuosity and dilation of posterior pole blood vessels in RetCam images, corresponding well with expert diagnostic categories of normal, pre-plus, and plus disease and performing comparably to experienced examiners.


Spatial analysis of human and livestock anthrax in Lai Chau province, Vietnam (2004-2021).
Anthrax is reported globally with varying disease intensity and seasonality among countries. In Vietnam, anthrax epidemiology and ecology remain understudied. We used historical data of human and livestock anthrax from 2004 to 2021 in Lai Chau province, to identify spatial clusters of human and livestock anthrax, describe epidemiological characteristics, and compare livestock anthrax vaccine coverage to human and livestock disease incidence. Local Moran's I (LISA) using spatial Bayes smoothed commune-level cumulative incidence (per 10,000) for the study period, epidemiological descriptive statistics, livestock vaccine coverage data, and annual incidence rates (per 10,000) at provincial level were used. LISA identified a human anthrax hotspot (high-high) in the southeast which did not overlap spatially with livestock anthrax hotspots in southeastern and northeastern communes. Most human cases were male, aged 15-59 years, handled sick animals, and/or consumed contaminated meat. Almost all cases were reported by grassroot health facilities with a delay of 6.3 days between exposure and case notification to the national surveillance system. 80 % of human cases were reported from June-October. The increase in disease incidence occurred shortly after livestock anthrax vaccine coverage decreased. This study informs vaccination strategy and targeted surveillance and control measures in newly identified high-risk areas and seasons of anthrax.


Fiber-based wearable electronics: a review of materials, fabrication, devices, and applications.
Fiber-based structures are highly desirable for wearable electronics that are expected to be light-weight, long-lasting, flexible, and conformable. Many fibrous structures have been manufactured by well-established lost-effective textile processing technologies, normally at ambient conditions. The advancement of nanotechnology has made it feasible to build electronic devices directly on the surface or inside of single fibers, which have typical thickness of several to tens microns. However, imparting electronic functions to porous, highly deformable and three-dimensional fiber assemblies and maintaining them during wear represent great challenges from both views of fundamental understanding and practical implementation. This article attempts to critically review the current state-of-arts with respect to materials, fabrication techniques, and structural design of devices as well as applications of the fiber-based wearable electronic products. In addition, this review elaborates the performance requirements of the fiber-based wearable electronic products, especially regarding the correlation among materials, fiber/textile structures and electronic as well as mechanical functionalities of fiber-based electronic devices. Finally, discussions will be presented regarding to limitations of current materials, fabrication techniques, devices concerning manufacturability and performance as well as scientific understanding that must be improved prior to their wide adoption.


[Influenza vaccination of elderly persons: state of the art].
Influenza is a major health problem among elderly people in industrialized countries. Elderly individuals suffering from chronic illnesses are more prone to suffer complications from influenza infection. In institutions, the outbreaks of influenza may touch about 60% of residents and induce life-threatening complications in more than 25% of cases. In this population--generally very old and handicapped by several chronic physical and mental diseases--the mortality associated with infections is very high. Influenza vaccination has been shown to be effective in 33% of vaccinated elderly persons for preventing clinical infection and in 74% for preventing mortality. This efficacy seems to be age-related. The other factors implicated in the immune response are discussed. A better understanding of these relationships is of great importance for public health and could improve the immune responses after influenza vaccination.


Increasing access to fertility care through private foundations.
To characterize the available support for infertility treatment and populations served by private foundations across the United States. Web-based cross-sectional survey. Not applicable. Not applicable. None. Geographies and populations served, dollar-amount and scope of financial assistance provided by private foundations for individuals seeking financial assistance for infertility treatment. Thirty-seven private foundations were identified, 25 responded (68% response rate). More than one-half of the foundations had awarded grants to lesbian, gay, and transgender individuals, as well as single men and women. Forty percent of the foundations serve only a single state or geographic region. Foundations have provided 9,996 grants for infertility treatment, 1,740 in 2016 alone, with an average value of $8,191 per grant. The Livestrong foundation has provide more than 90% of these grants, and only to patients with a history of cancer. Twelve percent of foundations provide assistance for fertility preservation in patients with cancer, and 20% provide assistance for elective oocyte cryopreservation. Private foundations significantly increase access to infertility care for individuals and couples affected by cancer who could otherwise not afford treatment. Significant heterogeneity exists regarding the populations served and the services available for grant support by these foundations, and the landscape of options for patients unaffected by cancer is severely limited.


The impact of the nursing hours per patient day (NHPPD) staffing method on patient outcomes: a retrospective analysis of patient and staffing data.
In March 2002 the Australian Industrial Relations Commission ordered the introduction of a new staffing method - nursing hours per patient day (NHPPD) - for implementation in Western Australia public hospitals. This method used a "bottom up" approach to classify each hospital ward into one of seven categories using characteristics such as patient complexity, intervention levels, the presence of high dependency beds, the emergency/elective patient mix and patient turnover. Once classified, NHPPD were allocated for each ward. The objective of this study was to determine the impact of implementing the NHPPD staffing method on 14 nursing-sensitive outcomes: central nervous system complications, wound infections, pulmonary failure, urinary tract infection, pressure ulcer, pneumonia, deep vein thrombosis, ulcer/gastritis/upper gastrointestinal bleed, sepsis, physiologic/metabolic derangement, shock/cardiac arrest, mortality, failure to rescue and length of stay. The research design was an interrupted time series using retrospective analysis of patient and staffing administrative data from three adult tertiary hospitals in metropolitan Perth over a 4-year period. All patient records (N=236,454) and nurse staffing records (N=150,925) from NHPPD wards were included. The study found significant decreases in the rates of nine nursing-sensitive outcomes when examining hospital-level data following implementation of NHPPD; mortality, central nervous system complications, pressure ulcers, deep vein thrombosis, sepsis, ulcer/gastritis/upper gastrointestinal bleed shock/cardiac arrest, pneumonia and average length of stay. At the ward level, significant decreases in the rates of five nursing-sensitive outcomes; mortality, shock/cardiac arrest, ulcer/gastritis/upper gastrointestinal bleed, length of stay and urinary tract infections occurred. The findings provide evidence to support the continuation of the NHPPD staffing method. They also add to evidence about the importance of nurse staffing to patient safety; evidence that must influence policy. This study is one of the first to empirically review a specific nurse staffing method, based on an individual assessment of each ward to determine staffing requirements, rather than a "one-size-fits-all" approach.


Validation of the Muscularity Bias Internalization Scale in Chinese women.
The Muscularity Bias Internalization Scale (MBIS) captures an individual's endorsement of stereotypical beliefs about muscularity and engagement in self-stigmatizing evaluations about their muscularity. The MBIS has been validated in Chinese men and Lebanese men and women, showing strong internal consistency reliability and construct validity. Because muscularity-related body image concerns are present in Chinese women, there is a need for research to validate the MBIS in Chinese women. The present study examined the factor structure and psychometric properties of the MBIS in a sample of Chinese women. Exploratory factor analysis (n = 300) identified a two-factor structure which showed adequate model fit in confirmatory factor analysis (n = 300), with χ2(76) = 294.63 (p < .001), CFI = 0.98, TLI = 0.98, and SRMR = 0.05. Results also showed that the MBIS in women had adequate internal consistency, two-week test-retest reliability, and good construct validity. Findings suggest that the MBIS is a useful tool for assessing muscularity bias internalization, a potentially important risk factor for muscularity-oriented eating and body image disturbances.


SENSITIVE TO PROTON RHIZOTOXICITY1, CALMODULIN BINDING TRANSCRIPTION ACTIVATOR2, and other transcription factors are involved in ALUMINUM-ACTIVATED MALATE TRANSPORTER1 expression.
In Arabidopsis (Arabidopsis thaliana) the root apex is protected from aluminum (Al) rhizotoxicity by excretion of malate, an Al chelator, by ALUMINUM-ACTIVATED MALATE TRANSPORTER1 (AtALMT1). AtALMT1 expression is fundamentally regulated by the SENSITIVE TO PROTON RHIZOTOXICITY1 (STOP1) zinc finger protein, but other transcription factors have roles that enable Al-inducible expression with a broad dynamic range. In this study, we characterized multiple cis-elements in the AtALMT1 promoter that interact with transcription factors. In planta complementation assays of AtALMT1 driven by 5' truncated promoters of different lengths showed that the promoter region between -540 and 0 (the first ATG) restored the Al-sensitive phenotype of atalm1 and thus contains cis-elements essential for AtALMT1 expression for Al tolerance. Computation of overrepresented octamers showed that eight regions in this promoter region contained potential cis-elements involved in Al induction and STOP1 regulation. Mutation in a position around -297 from the first ATG completely inactivated AtALMT1 expression and Al response. In vitro binding assays showed that this region contained the STOP1 binding site, which accounted for the recognition by four zinc finger domains of the protein. Other positions were characterized as cis-elements that regulated expression by repressors and activators and a transcription factor that determines root tip expression of AtALMT1. From the consensus of known cis-elements, we identified CALMODULIN-BINDING TRANSCRIPTION ACTIVATOR2 to be an activator of AtALMT1 expression. Al-inducible expression of AtALMT1 changed transcription starting sites, which increased the abundance of transcripts with a shortened 5' untranslated region. The present analyses identified multiple mechanisms that regulate AtALMT1 expression.


Six year incidence and progression of diabetic retinopathy: results from the Mauritius diabetes complication study.
To determine the incidence, progression and risk factors for diabetic retinopathy in the multiethnic population of Mauritius. A longitudinal, population-based study was conducted in Mauritius, during 1987, 1992 and 1998. Participants identified through the study as having diabetes (both known and newly diagnosed, by self-report and oral glucose tolerance test) and one in four participants with impaired glucose tolerance (IGT) underwent complications screening in 1992 and 1998. Retinal photographs were taken using a TRC-50VT retinal camera in three fields of the right eye (centred on the optic disc; macula (temporal to the optic disc); and nasal to disc). Photographs were graded according to a simplified version of the Wisconsin grading system. The 6-year incidence of diabetic retinopathy was 23.8% (sight-threatening in 0.4%). Among those with known diabetes mellitus (KDM) and free of retinopathy at baseline the incidence of non-proliferative diabetic retinopathy (NPDR) was 29.2% and proliferative diabetic retinopathy (PDR) was 1.0%. Among those with newly diagnosed diabetes mellitus (NDM) at baseline the incidence of NPDR was 19.1% (no incident cases of PDR were found). Independent risk factors for retinopathy using the baseline population characteristics were duration of diabetes and fasting plasma glucose. This is one of the few recent population-based studies of diabetic retinopathy undertaken in a developing nation. The incidence of retinopathy in Mauritius was high among those with NDM at baseline, with one in five developing retinopathy over 6 years. These results support the concept that screening for diabetes is important.


The inhibitory effects of K+ channel-blocking agents on T lymphocyte proliferation and lymphokine production are "nonspecific".
The effect of K+ channel-blocking agents, tetraethylammonium (TEA) and 4-aminopyridine (4AP), on the responses of cloned murine helper and cytolytic T lymphocytes stimulated with mitogen, anti-T cell receptor monoclonal antibody, or interleukin 2 was examined. The addition of TEA and 4AP reduced [3H]thymidine incorporation and lymphokine production to levels observed in unstimulated cells. However, thymidine incorporation by the tumor cell lines P-815 and SP2/0, which replicate autonomously, also was inhibited by these drugs. Treatment of cloned murine helper T lymphocyte, L2, with TEA appeared to inhibit uptake of [3H]thymidine and [3H]phenylalanine after stimulation with interleukin 2. These results suggest that the inhibitory effects of the K+ channel-blocking agents TEA and 4AP may not be specific for the sequence of events that are initiated by activation of T lymphocytes through the antigen receptor. Instead, the observed inhibitory effects by these agents may result from inhibition of transport of thymidine, amino acids, and other essential metabolites across the cell membrane.


Interrogating the Contested Spaces of Rural Aging: Implications for Research, Policy, and Practice.
Informed by a critical turn underway in rural gerontology, this article explores how the intersection of global and local trends relating to population aging and rural change create contested spaces of rural aging. The aim is to build our understanding of rural as a dynamic context within which the processes, outcomes, and experiences of aging are created, confronted, and contested by older adults and their communities. A review of key developments within gerontology and rural studies reveals how competing policies, discourses, and practices relating to healthy aging and aging in place, rural citizenship and governmentality, and social inclusion and inequality combine in particular ways to empower or disempower a diverse range of older rural adults aging in a diverse range of rural communities. The article provides a contextually sensitive perspective on potential sources of conflict and exclusion for older adults in dynamic rural spaces and further enhances our understanding of how rural physical and social environments are constructed and experienced in older age. A framework for interrogating emergent questions about aging in rural contexts is developed and implications for advancing research, policy, and practice are discussed.


[Clinical thinking and decision making in practice. A student with sudden headache].
A previously healthy man aged 18 years suddenly developed a severe headache, followed by nausea, vomiting, fever. During the following weeks a left-sided hemiparesis developed. CT of the brain revealed a pansinusitis and a frontal epidural empyema. A few days after surgical drainage his condition deteriorated and subsequent CT showed a right-sided subdural empyema. This was surgically evacuated and followed by long-term high-dose intravenous antibiotic therapy. The patient made a complete recovery. A sudden severe headache can be caused by an intracranial infection and intracranial pus collections can occur in the subdural as well as in the epidural space. Epidural empyema is a limited disease with relatively mild symptoms and a favourable prognosis, whereas subdural empyema may rapidly spread and cause severe disease with a poor prognosis. Quick antibiotic treatment and surgical drainage are required.


Characterizing Normal Variant [68Ga]Ga-FAPI-46 Uptake in the Epididymis.
The biodistribution of fibroblast activation protein inhibitor (FAPI) PET tracers includes the kidneys, bladder, uterus, breast, muscles, and bone marrow. We describe its occasional uptake patterns in the epididymis. Methods: Epididymal [68Ga]Ga-FAPI-46 uptake was retrospectively analyzed in 55 PET/CT studies of 55 men. Uptake intensity (SUV), pattern (diffuse, focal, or multifocal), laterality, and location (epididymal head with or without body/tail) were analyzed. Electronic medical records were reviewed to determine the presence of epididymis-related disease. Results: Epididymal [68Ga]Ga-FAPI-46 uptake was observed in 8 of 55 (15%) subjects, with bilateral epididymal head uptake in all cases and epididymal body/tail uptake in 6 of 8 (75%) cases, 5 of 6 (83%) bilaterally and 1 of 6 (17%) unilaterally. The average SUVmax was greater in the epididymal heads than in the epididymal bodies/tails, with an SUVmax of 4.1 versus 3.0 (P < 0.001). No subject had epididymal disease related to the uptake. Conclusion: [68Ga]Ga-FAPI-46 uptake in the epididymis occurs occasionally and does not appear related to epididymal disease.


Different effects of short- and long-term recombinant hGH administration on ghrelin and adiponectin levels in GH-deficient adults.
To evaluate circulating levels of ghrelin and adiponectin (ApN) in GH-deficient (GHD) adults before and after short- and long-term recombinant human GH (rhGH) administration. Twenty-three patients were studied. Seventeen subjects (Group A, 12 men, five women) were evaluated at baseline and after 1 year rhGH therapy (dose mean +/- SD: 0.3 +/- 0.1 mg/day) with the assessment of serum IGF-I, ghrelin, ApN, leptin, insulin and glucose levels, percentage of body fat (BF%), HOMA-IR and QUICKI. Seventeen age-, sex- and body mass index (BMI)-matched healthy subjects were recruited for comparisons. Six patients (Group B, three men, three women) underwent IGF-I generation test (rhGH 0.025 mg/kg/day for 7 days), blood sampled at baseline and on day 8 for determination of IGF-I, ghrelin and ApN levels. Group A: at baseline GHD patients showed low IGF-I levels and BF% significantly higher than controls (31.4 +/- 2.5 vs. 26.4 +/- 1.3, P < 0.05). Glucose, insulin, leptin, tryglicerides, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels, as well as HOMA-IR and QUICKI values were similar in the two series, while total cholesterol levels were higher in GHD. In GHD, ghrelin levels were significantly lower than in controls (193.9 +/- 27.1 vs. 298.1 +/- 32.5 pmol/l, respectively, P = 0.02), while ApN levels were similar (10.2 +/- 1.1 and 9 +/- 1 mg/l, respectively, P = ns). After 1 year of rhGH therapy, BF%, BMI, serum total and LDL cholesterol significantly decreased, serum leptin levels showed a trend to decrease, while HOMA-IR and QUICKI did not change. Ghrelin and ApN levels significantly increased from 193.9 +/- 27.1 to 232.4 +/- 26.3 pmol/l (P < 0.01) and from 8.6 +/- 0.8 to 10.3 +/- 1.1 mg/l (P < 0.05), respectively. In group B, the expected increase in IGF-I levels was associated with a significant decrease in ghrelin levels, while ApN did not change. GHD patients showed serum ghrelin lower than controls, probably due to the higher BF%. No difference in ApN was observed. Ghrelin and ApN increments induced by long-term treatment may be related to the significant BMI and BF% reduction that is the predominant metabolic effect of rhGH therapy. Conversely, the decrease in ghrelin levels observed after short-term rhGH administration may be consistent with an inhibitory feedback of GH and/or IGF-I on ghrelin release.


Oxygen-dependent killing of Staphylococcus aureus by human neutrophils.
Luminol-dependent chemiluminescence was used as a monitor of reactive oxidant generation during phagocytosis of Staphylococcus aureus by human neutrophils. Reactive oxidants play a crucial role in the killing of this organism because: (a) S. aureus was killed most rapidly when the rate of increase of chemiluminescence was greatest; (b) neutrophils which had been activated to generate reactive oxidants by re-aeration of anaerobic suspensions killed this bacterium more efficiently than control suspensions; and (c) neutrophils from a patient with chronic granulomatous disease could neither generate reactive oxidants nor kill S. aureus.


[Acute rheumatic fever: problems and outlooks].
The issue related with acute rheumatic fever still remains to be topical at the present stage, which is accentuated by a high prevalence of rheumatic heart diseases. The results of multiple studies point out at the presence of "rheumatogenetic" A-streptococcal strains possessing certain biological properties. Although there were no changes in the disease semiotics, the intensity degree of clinical signs went down, due to which an early diagnosis of the disease became more complicated. The issues related with the nosological classification of post-streptococcal reactive arthritis and with PANDAS syndrome need to be solved. There is also an urgent necessity in creating high-technological domestic benzathine-penicillins intended for secondary prevention of the disease.


Nonthrombotic Pulmonary Embolism Associated With Non-Hodgkin Lymphoma.
Nonthrombotic pulmonary embolism (NTPE) challenges the medical community with its diverse etiologies and potential life-threatening implications. The classification section delves into the multifaceted nature of NTPE, which includes various embolic agents that traverse the vascular system. From air and fat emboli to tumor and amniotic fluid emboli, this exploration of diverse etiologies sheds light on the complexity of NTPE. Diagnostic methods play a crucial role in the effective management of NTPE. This article describes a range of traditional and cutting-edge diagnostic techniques, from computed tomography angiography to novel biomarkers, enabling the accurate and timely identification of NTPE. NTPE treatment options are diverse and patient-specific, requiring customized approaches to address varying embolic sources. Anticoagulation, embolus removal, and emerging interventions under study are discussed, providing clinicians with a comprehensive understanding of management strategies. This article uncovers the rare but captivating association between NTPE and non-Hodgkin lymphoma. Although rare, documented cases have sparked curiosity among researchers and medical practitioners. We explore potential pathophysiological connections, discussing challenges and considerations when encountering this unique scenario. In conclusion, this captivating review encapsulates the multifaceted realm of NTPE, covering its classification, diagnostics, and treatment modalities. Moreover, it presents a fascinating connection with non-Hodgkin lymphoma. This article offers a comprehensive and concise review of NTPE, guiding readers through its intricate classification, diagnostic approaches, and therapeutic interventions.


Community activism as a strategy to reduce intimate partner violence (IPV) in rural Rwanda: Results of a community randomised trial.
There is considerable interest in community organising and activism as a strategy to shift patriarchal gender norms, attitudes and beliefs and thus reduce intimate partner violence (IPV). Yet there is limited insight into how activism actually translates into reduced violence, including how aspects of programme implementation or cultural context may affect impact. This study evaluates the community activism/mobilisation portion of Indashyikirwa, a multi-component, IPV prevention programme implemented in rural Rwanda. The activism part of Indashyikirwa was based on SASA!, a promising program model from Uganda with demonstrated effectiveness. We implemented two separate cross-sectional surveys as part of a larger community randomised controlled trial to assess the impact of the community portion of Indashyikirwa on preventing physical and/or sexual IPV and other secondary outcomes at a community level. The survey consisted of a random household-based sample of 1400 women and 1400 men at both waves. Surveys were conducted before community-level activities commenced and were repeated 24 months later with a new cross-sectional sample. Longitudinal, qualitative data were collected as part of an embedded process evaluation. There was no evidence of an intervention effect at a community level on any of the trial's primary or secondary outcomes, most notably women's experience of physical and/or sexual IPV from a current male partner in the past 12 months (adjusted odds ratio (aOR) = 1.25; 95% confidence interval (CI) = 0.92-1.70, P = 0.16), or men's perpetration of male-to-female physical and/or sexual IPV (aOR = 1.02; 95% CI = 0.72-1.45, P = 0.89). Process evaluation data suggest that delays due to challenges in adapting and implementing SASA!-style activites in rural Rwanda may account for the trial's failure to measure an effect. Additionally, the intervention strategy of informal activism was not well suited to the Rwandan context and required considerable modification. Failure to reduce violence when implementing an adaptation of SASA! in rural Rwanda highlights the importance of allowing sufficient time for adapting evidence-based programming (EBP) to ensure cultural appropriateness and fidelity. This evaluation held little chance of demonstrating impact since the project timeline forced endline evaluation only months after certain elements of the programme became operational. Donors must anticipate longer time horizons (5 to 7 years) when contemplating evaluations of novel or newly-adapted programmess for reducing IPV at a population level. These findings also reinforce the value of including embedded process evaluations when investing in rigorous trials of complex phenomena such as community activism. ClinicalTrials.gov, NCT03477877.


ERM/ETV5 up-regulation plays a role during myometrial infiltration through matrix metalloproteinase-2 activation in endometrial cancer.
We have described recently the Ets family transcription factor, ERM/ETV5, specifically up-regulated in endometrioid endometrial carcinoma (EEC) and associated with myometrial infiltration. Ets family members have been correlated to tumor progression by up-regulating the expression of matrix-degrading proteases. In the present study, we investigated the possibility that in EEC, ERM/ETV5 may act by inducing the expression of genes involved in extracellular matrix remodeling. Unraveling the molecular events associated with the initiation of tumor invasion would represent an obvious improvement for EEC patients. The overexpression of ERM/ETV5 induced scattering in the endometrial cancer cell line Hec-1A, correlating to increased matrix metalloproteinase-2 (MMP-2) gelatinase activity. Both chromatin immunoprecipitation and reversion experiments with RNA interference and specific MMP-2 inhibitor showed a functional link between ERM/ETV5 overexpression and MMP-2 activation. The increased MMP-2 activity associated with overexpressed ERM/ETV5 in a mouse model conferred invasive capacity to endometrial tumors. Orthotopically implanted overexpressing ERM/ETV5 tumors presented a more aggressive and infiltrative pattern of myometrial invasion. Finally, the specific localization of ERM/ETV5 and MMP-2 at the invasive front of myometrial infiltrating human endometrial carcinomas further reinforced the hypothesis of a role for ERM/ETV5 in the early steps of endometrial dissemination. Taken together, these results lead us to propose that in EEC, ERM/ETV5 acts through MMP-2 gelatinolytic activity to confer invasive capabilities, associated with an initial switch to myometrial infiltration. They also postulate ERM/ETV5 as a valuable marker for patient stratification and a transcription pathway that should be evaluated for therapies specifically targeting the initial steps of EEC dissemination.


Discovery of CTCF-sensitive Cis-spliced fusion RNAs between adjacent genes in human prostate cells.
Genes or their encoded products are not expected to mingle with each other unless in some disease situations. In cancer, a frequent mechanism that can produce gene fusions is chromosomal rearrangement. However, recent discoveries of RNA trans-splicing and cis-splicing between adjacent genes (cis-SAGe) support for other mechanisms in generating fusion RNAs. In our transcriptome analyses of 28 prostate normal and cancer samples, 30% fusion RNAs on average are the transcripts that contain exons belonging to same-strand neighboring genes. These fusion RNAs may be the products of cis-SAGe, which was previously thought to be rare. To validate this finding and to better understand the phenomenon, we used LNCaP, a prostate cell line as a model, and identified 16 additional cis-SAGe events by silencing transcription factor CTCF and paired-end RNA sequencing. About half of the fusions are expressed at a significant level compared to their parental genes. Silencing one of the in-frame fusions resulted in reduced cell motility. Most out-of-frame fusions are likely to function as non-coding RNAs. The majority of the 16 fusions are also detected in other prostate cell lines, as well as in the 14 clinical prostate normal and cancer pairs. By studying the features associated with these fusions, we developed a set of rules: 1) the parental genes are same-strand-neighboring genes; 2) the distance between the genes is within 30kb; 3) the 5' genes are actively transcribing; and 4) the chimeras tend to have the second-to-last exon in the 5' genes joined to the second exon in the 3' genes. We then randomly selected 20 neighboring genes in the genome, and detected four fusion events using these rules in prostate cancer and non-cancerous cells. These results suggest that splicing between neighboring gene transcripts is a rather frequent phenomenon, and it is not a feature unique to cancer cells.


[Expression of bcl-2, bax and p53 protein in the basal cell carcinoma].
The expression of bcl-2, bax and p53 protein was studied in the basal cell carcinoma with 32 patients by immunohistochemical method. The results showed that bcl-2 protein was positive in 26 patients (81.2%), bax protein was positive in 9 patients(28.1%), and p53 protein was positive in 13 patients (40.6%); there is a negative correlation between the expression of bcl-2 and bax protein(P < 0.05). These findings suggest that apoptosis is suppressed which might cause the production of basal cell carcinoma.


BSA and fibrinogen adsorption on chitosan/κ-carrageenan polyelectrolyte complexes.
PECs of chitosan/κ-carrageenan are prepared in three different volumetric rations. The complex formation is characterized in order to evaluate the blending formation. Blood compatibility is evaluated by protein adsorption (BSA and fibrinogen) and PEC toxicities are determined with fibroblast cell viability and proliferation. The swelling degree of PECs decreases when the amount of chitosan increases. Due to the linked film formation, PECs decrease BSA adsorption and increase fibrinogen adsorption when compared to the pristine chitosan and κ-carrageenan films. Although pristine chitosan and κ-carrageenan films produced similar cell expansion and viability, the PEC 50:50 vol% chitosan/κ-carrageenan PEC may be acceptable as a new scaffold for cell therapies, due to their effect on cell survival.


How RNase HI (Escherichia coli) promoted site-selective hydrolysis works on RNA in duplex with carba-LNA and LNA substituted antisense strands in an antisense strategy context?
A detailed kinetic study of 36 single modified AON-RNA heteroduplexes shows that substitution of a single native nucleotide in the antisense strand (AON) by locked nucleic acid (LNA) or by diastereomerically pure carba-LNA results in site-dependent modulation of RNase H promoted cleavage of complementary mRNA strands by 2 to 5 fold at 5'-GpN-3' cleavage sites, giving up to 70% of the RNA cleavage products. The experiments have been performed using RNase HI of Escherichia coli. The 2nd best cleavage site, being the 5'-ApN-3' sites, cleaves up to 23%, depending upon the substitution site in 36 isosequential complementary AONs. A comparison of the modified AON promoted RNA cleavage rates with that of the native AON shows that sequence-specificity is considerably enhanced as a result of modification. Clearly, relatively weaker 5'-purine (Pu)-pyrimidine (Py)-3' stacking in the complementary RNA strand is preferred (giving ∼90% of total cleavage products), which plays an important role in RNase H promoted RNA cleavage. A plausible mechanism of RNase H mediated cleavage of the RNA has been proposed to be two-fold, dictated by the balancing effect of the aromatic character of the purine aglycone: first, the locally formed 9-guanylate ion (pKa 9.3, ∼18-20% N1 ionized at pH 8) alters the adjoining sugar-phosphate backbone around the scissile phosphate, transforming its sugar N/S conformational equilibrium, to preferential S-type, causing preferential cleavage at 5'-GpN-3' sites around the center of 20 mer complementary mRNA. Second, the weaker nearest-neighbor strength of 5'-Pu-p-Py-3' stacking promotes preferential 5'-GpN-3' and 5'-ApN-3' cleavage, providing ∼90% of the total products, compared to ∼50% in that of the native one, because of the cLNA/LNA substituent effect on the neighboring 5'-Pu-p-Py-3' sites, providing both local steric flexibility and additional hydration. This facilitates both the water and water/Mg2+ ion availability at the cleavage site causing sequence-specific hydrolysis of the phosphodiester bond of scissile phosphate. The enhancement of the total rate of cleavage of the complementary mRNA strand by up to 25%, presented in this work, provides opportunities to engineer a single modification site in appropriately substituted AONs to design an effective antisense strategy based on the nucleolytic stability of the AON strand versus RNase H capability to cleave the complementary RNA strand.


Adverse Childhood Experiences Are Not Associated With Patient-reported Outcome Measures in Patients With Musculoskeletal Illness.
Adverse childhood experiences (ACEs) affect adult mental health and tend to contribute to greater symptoms of depression and more frequent suicide attempts. Given the relationship between symptoms of depression and patient-reported outcomes (PROs), adversity in childhood might be associated with PROs in patients seeking care for musculoskeletal problems, but it is not clear whether in fact there is such an association among patients seeking care in an outpatient, upper extremity orthopaedic practice. (1) Are ACE scores independently associated with variation in physical limitations measured among patients seen by an orthopaedic surgeon? (2) Are ACE scores independently associated with variations in pain intensity? (3) What factors are associated with ACE scores when treated as a continuous variable or as a categorical variable? We prospectively enrolled 143 adult patients visiting one of seven participating orthopaedic surgeons at three private and one academic orthopaedic surgery offices in a large urban area. We recorded their demographics and measured ACEs (using a validated 10-item binary questionnaire that measured physical, emotional, and sexual abuse in the first 18 years of life), magnitude of physical limitations, pain intensity, symptoms of depression, catastrophic thinking, and health anxiety. There were 143 patients with a mean age of 51 years, 62 (43%) of whom were men. In addition, 112 (78%) presented with a specific diagnosis and most (n = 79 [55%]) had upper extremity symptoms. We created one logistic and three linear regression models to test whether age, gender, race, marital status, having children, level of education, work status, insurance type, comorbidities, body mass index, smoking, site of symptoms, type of diagnosis, symptoms of depression, catastrophic thinking, and health anxiety were independently associated with (1) the magnitude of limitations; (2) pain intensity; (3) ACE scores on the continuum; and (4) ACE scores categorized (< 3 or ≥ 3). We calculated a priori that to detect a medium effect size with 90% statistical power and α set at 0.05, a sample of 136 patients was needed for a regression with five predictors if ACEs would account for ≥ 5% of the variability in physical function, and our complete model would account for 15% of the overall variability. To account for 5% incomplete responses, we enrolled 143 patients. We found no association between ACE scores and the magnitude of physical limitations measured by Patient-Reported Outcomes Measurement Information System Physical Function (p = 0.67; adjusted R = 0.55). ACE scores were not independently associated with pain intensity (Pearson correlation [r] = 0.11; p = 0.18). Greater ACE scores were independently associated with diagnosed mental comorbidities both when analyzed on the continuum (regression coefficient [β] = 1.1; 95% confidence interval [CI], 0.32-1.9; standard error [SE] 0.41; p = 0.006) and categorized (odds ratio [OR], 3.3; 95% CI, 1.2-9.2; SE 1.7; p = 0.024), but not with greater levels of health anxiety (OR, 1.1; 95% CI, 0.90-1.3; SE 0.096; p = 0.44, C statistic = 0.71), symptoms of depression (ACE < 3 mean ± SD = 0.73 ± 1.4; ACE ≥ 3 = 1.0 ± 1.4; p = 0.29) or catastrophic thinking (ACE < 3 = 3.6 ± 3.5; ACE ≥ 3 = 4.9 ± 5.1; p = 0.88). ACEs may not contribute to greater pain intensity or magnitude of physical limitations unless they are accompanied by greater health anxiety or less effective coping strategies. Adverse events can contribute to anxiety and depression, but perhaps they sometimes lead to development of resilience and effective coping strategies. Future research might address whether ACEs affect symptoms and limitations in younger adult patients and patients with more severe musculoskeletal pathology such as major traumatic injuries. Level II, prognostic study.


Bioinspired Universal Monolayer Coatings by Combining Concepts from Blood Protein Adsorption and Mussel Adhesion.
Despite the increasing need for universal polymer coating strategies, only a few approaches have been successfully developed, and most of them are suffering from color, high thickness, or high roughness. In this paper, we present for the first time a universal monolayer coating that is only a few nanometers thick and independent of the composition, size, shape, and structure of the substrate. The coating is based on a bioinspired synthetic amphiphilic block copolymer that combines two concepts from blood protein adsorption and mussel adhesion. This polymer can be rapidly tethered on various substrates including both planar surfaces and nanosystems with high grafting density. The resulting monolayer coatings are, on the one hand, inert to the adsorption of multiple polymer layers and prevent biofouling. On the other hand, they are chemically active for secondary functionalization and provide a new platform for selective material surface modification.


Yoga for metabolic syndrome: A systematic review and meta-analysis.
Background Metabolic syndrome is the most important risk factor for developing cardiovascular disease and type 2 diabetes. The aim of this review was to systematically assess and perform a meta-analysis of the effects of yoga on the parameters of metabolic syndrome. Methods MEDLINE/PubMed, Scopus, the Cochrane Central Register of Controlled Trials and IndMED were searched and screened from their inception through to 8 March 2016 for randomised controlled trials on yoga for patients with metabolic syndrome. Risk of bias was assessed using the Cochrane risk of bias tool. Results Seven trials with a total of 794 participants were included. No effects of yoga on resolution of metabolic syndrome, diastolic blood pressure, triglycerides, high-density lipoprotein cholesterol and fasting plasma glucose were found, but yoga was superior to usual care for waist circumference (standardised mean difference (SMD) = -0.35; 95% confidence interval (CI) = -0.57 to -0.13; p < 0.01) and systolic blood pressure (SMD = -0.29; 95% CI = -0.51 to -0.07; p = 0.01). However, these effects were not robust against selection bias. No intervention-related adverse events were reported. Conclusion Based on the results of this meta-analysis, no recommendation can be made for or against yoga in order to influence the parameters of metabolic syndrome. Despite methodological drawbacks, and until further research is undertaken, yoga can be preliminarily considered as a safe and effective intervention for reducing waist circumference and systolic blood pressure in individuals with metabolic syndrome who are not adhering to conventional forms of exercise.


A study of Class III treatment: orthodontic camouflage vs orthognathic surgery.
To evaluate the differences in pretreatment and post-treatment characteristics of Class III patients treated with orthodontic camouflage or orthognathic surgery, and to compare the range of skeletal, dental and soft tissue changes that are likely to occur with treatment, with particular reference to the influence of extractions on the resultant incisor angulations. Pretreatment and post-treatment cephalograms of 31 Class III orthodontically-camouflaged patients and 36 Class III surgical patients (without genioplasty) were obtained from one specialist practice. From the surgical group, 26 pre-surgical lateral cephalograms were also obtained. Inclusion criteria for the two groups were at least three of the following: (1) an ANB angle of 1 degree or less, (2) a Wits appraisal less than -4 mm, (3) an incisal overjet ≤ 0 mm, and (14) a Class III molar relationship. All lateral cephalograms were traced and digitised and a number of skeletal, dental and soft tissue variables were measured. The camouflage and surgical groups were also divided into premolar extraction and non-extraction subgroups to allow for a specific analysis of extraction effects. Before treatment, the surgical group demonstrated, on average, a more severe skeletal discrepancy and increased dental compensations, compared with the orthodontically camouflaged group. After treatment, the mean SNA angle was greater, the ANB angle was more positive, the Wits appraisal was closer to ideal and the lower incisors were less retroclined in the surgery group. There was a small mean reduction in horizontal chin projection in the surgery group compared with a small increase in the camouflage group. The mentolabial fold and the lower lip curve were deeper, on average, and the lips less retrusive after surgery. There was a mean increase in upper incisor proclination during treatment in both the surgical and camouflage groups with a greater increase in the camouflage group. There was a significant reduction in upper incisor proclination and a subsequent greater increase in the ANB angle associated with upper premolar extractions in the surgical group compared with the non-extraction group. Lower premolar extractions in the camouflage group resulted only in a deeper mentolabial fold compared with those treated without lower extractions. Class III patients selected for surgical treatment are likely to have more severe pretreatment dental and skeletal discrepancies than those selected for camouflage treatment. Surgical treatment is associated with significant decompensation of the lower incisors but, ultimately, not the upper incisors. Class III patients treated with either camouflage or surgery treatment are likely to finish with slightly proclined upper incisors. Generally, surgical treatment results in greater skeletal change, involving normalisation of the skeletal base relationship, a reduction in chin prominence, fuller lips, and a more favourable lip and chin contour.


Surgical treatment of lymph nodes with metastatic melanoma from unknown primary site.
To determine the prognosis of patients with lymph node metastases from an unknown primary melanoma, we retrospectively reviewed the clinicopathologic features of 188 such patients treated from 1971 through 1986 and compared their records with those of patients with clinical stage II melanoma with known primary lesions. Patients with lymph node metastases from an unknown primary melanoma represented 4.6% of all patients with melanoma treated during that period. The five- and ten-year survival rates were 42% and 40%, respectively (median, 37 months). When stratified by number of tumor-containing lymph nodes, there was no significant difference in survival between patients with an unknown primary melanoma and lymph node metastases and those with clinical stage II melanoma and known primary sites. The prognosis of the former patients is no worse than that of patients with lymph node metastases from a known primary site and should be treated in a comparable manner.


Acute lymphoblastic leukemia in children and SALL4 and BMI-1 gene expression.
Sal-like protein 4 transcription factor (SALL4) and B cell-specific Moloney murine leukemia virus integration site 1 (BMI-1) gene were reported to cause treatment failure and relapse in several malignancies. We aimed to evaluate the prognostic value of SALL4 and BMI-1 in children with acute lymphoblastic leukemia (ALL). This prospective cohort study was carried out on 60 children with ALL as the patient group and 60 age- and sex-matched children as the control group. We evaluated the expression pattern of both SALL4 and BMI-1 genes in the peripheral blood using real-time reverse transcriptase-polymerase chain reaction in children with ALL at initial diagnosis before chemotherapy. We followed up with the patient group for 2 years for relapse or death. Both SALL4 and BMI-1 were overexpressed in ALL children compared to the control group. Moreover, the expression of SALL4 and BMI-1 in patients with relapse was significantly higher than those with complete remission. The best cut-off of SALL4 and BMI-1 to predict relapse were >2.21 and 0.55 yielding sensitivity of 92.3% and 84.6%, respectively. Patients with overexpression of SALL4 and BMI-1 had significantly shorter overall and disease-free survival. SALL4 and BMI-1 could be useful prognostic markers in children with ALL to predict relapse.


Precursors of murine B lymphocytes. Physical and functional characterization, and distinctions from myeloid stem cells.
The emergence of functional B cells was monitored in irradiated or unirradiated CBA/N recipients of either adult bone marrow or fetal liver from CBA/HT6T6 donors. The cells that are primarily responsible for the generation of B lymphocytes, at least during the first 6 wk, are rapidly sedimenting (4.5-6 mm/h), lack surface immunoglobulin, and are found in both the adult bone marrow and the fetal liver from day 12 onward. These pre-B cells are distinct from the colony-forming unit spleen (CFU-s) as demonstrated by the following criteria: (a) absence from yolk sac (19), (b) lack of correlation between CFU-s number and the ability to generate B cells in fetal liver populations of different ages of gestation, and (c) hybridoma antibodies that significantly inhibited B cell reconstitution but have no effect on CFU-s numbers. The antigen detected by this antiserum is present on both the fetal liver and bone marrow B cell progenitor, although its expression is not restricted to the B lineage. The pre-B cells that we monitor are not homogeneous, however, as both physical and functional differences are found. These observations reinforce our thesis that committed progenitor cells for the humoral immune system are formed early in development and thereafter constitute the major precursor pool for the generation of B lymphocytes.


Cognitive orientation to daily occupational performance (CO-OP) approach as telehealth for a child with developmental coordination disorder: a case report.
This study aimed to propose a possible interventional form of occupational therapy through a case study report of the applied Cognitive Orientation to daily Occupational Performance (CO-OP) approach as telehealth for a child with developmental coordination disorder (DCD). The intervention method was CO-OP-based tele-occupational therapy for a boy with DCD and his mother; 10 sessions were conducted using a video-conferencing system. This study used the Canadian Occupational Performance Measure (COPM) and the Performance Quality Rating Scale (PQRS) as assessment tools. The PQRS evaluated each occupational performance based on videos recorded during the online sessions and videos taken by the mother of the child. The CO-OP approach improved COPM performance and satisfaction as well as PQRS scores in the following five goals: (1) handwriting, (2) column addition, (3) jumping rope, (4) playing on the bar, and (5) riding a bicycle. An online approach based on the CO-OP was realistic and effective, to some extent. Continuing to develop telehealth interventions in the future is recommended.


[Hygienic characteristics of the influence of anthropogenic and natural geochemical factors on the population health in the South Ural].
The natural and technogenic factors of the industrial towns and rural localities in the Orenburg Region were differentially analyzed. The modifying effects of xenobiotics and their complex action on man are considered. The study showed the high pollution of the atmosphere, the blanket of snow, soil, the trace composition imbalance of drinking water, foodstuffs, a reduction in biogenic elements and an increase in toxic elements in the children's substrates (blood, hair) and high morbidity among the children suggest the presence of the formed technogenic biogeochemical province in the Eastern zone and, those in terms of some xenobiotics, in the Central area of the Orenburg Region.


Differences in DNA Binding Specificity of Floral Homeotic Protein Complexes Predict Organ-Specific Target Genes.
Floral organ identities in plants are specified by the combinatorial action of homeotic master regulatory transcription factors. However, how these factors achieve their regulatory specificities is still largely unclear. Genome-wide in vivo DNA binding data show that homeotic MADS domain proteins recognize partly distinct genomic regions, suggesting that DNA binding specificity contributes to functional differences of homeotic protein complexes. We used in vitro systematic evolution of ligands by exponential enrichment followed by high-throughput DNA sequencing (SELEX-seq) on several floral MADS domain protein homo- and heterodimers to measure their DNA binding specificities. We show that specification of reproductive organs is associated with distinct binding preferences of a complex formed by SEPALLATA3 and AGAMOUS. Binding specificity is further modulated by different binding site spacing preferences. Combination of SELEX-seq and genome-wide DNA binding data allows differentiation between targets in specification of reproductive versus perianth organs in the flower. We validate the importance of DNA binding specificity for organ-specific gene regulation by modulating promoter activity through targeted mutagenesis. Our study shows that intrafamily protein interactions affect DNA binding specificity of floral MADS domain proteins. Differential DNA binding of MADS domain protein complexes plays a role in the specificity of target gene regulation.


Effect of NaCl on nitrate removal from ion-exchange spent brine in the membrane biofilm reactor (MBfR).
The H(2)-based membrane biofilm reactor was used to remove nitrate from synthetic ion-exchange brine at NaCl concentrations from ∼3 to 30 g/L. NaCl concentrations below 20 g/L did not affect the nitrate removal flux as long as potassium was available to generate osmotic tolerance for high sodium, the H(2) pressure was adequate, and membrane fouling was eliminated. Operating pHs of 7-8 and periodic citric acid washes controlled membrane fouling and enabled reactor operation for 650 days. At 30 psig H(2) and high nitrate loading rates of 15 to 80 g/m(2) d, nitrate removal fluxes ranged from 2.5 to ∼6 g/m(2) d, which are the highest fluxes observed when treating 30 g/L IX brine. However, percent removals were low, and the H(2) pressure probably limited the removal flux.


Experimental and computational study of the conrotatory ring opening of various 3-chloro-2-azetines.
A combined experimental and theoretical study is presented on 2-azetines, a class of azaheterocyclic compounds, which are difficult to access but have shown a unique reactivity as strained cyclic enamines. New highly substituted 2-azetines bearing aryl substituents at the 2- and 4-position were synthesized from 3,3-dichloroazetidines. Whereas 2-aryl-3,3-dichloroazetidines gave stable 2-aryl-3-chloro-2-azetines upon treatment with sodium hydride in DMSO, 2,4-diaryl-3,3-dichloroazetidines showed a remarkably different reactivity in that they afforded benzimidoyl-substituted alkynes under similar mild treatment with base. The formation of the alkynes involves electrocyclic ring opening of intermediate 2,4-diaryl-3-chloro-2-azetines and elimination of hydrogen chloride. Ab initio theoretical calculations confirmed the experimental findings and demonstrated that the 4-aryl substituent is responsible for this remarkably enhanced reactivity of 2-azetines toward electrocyclic conrotatory ring opening by a significant decrease in reaction barrier of about 30 kJ/mol. This activation effect by an aryl group in the allylic position toward electrocyclic ring opening of unsaturated four-membered rings is of general importance since a similar increased reactivity of 4-aryloxetes, 4-arylthiete-1,1-dioxides, and 3-arylcyclobutenes has been reported in literature as well.


Suppression and enhancement of emotional responses to unpleasant pictures.
Despite the prominence of emotional dysfunction in psychopathology, relatively few experiments have explicitly studied emotion regulation in adults. The present study examined one type of emotion regulation: voluntary regulation of short-term emotional responses to unpleasant visual stimuli. In a sample of 48 college students, both eyeblink startle magnitude and corrugator activity were sensitive to experimental manipulation. Instructions to suppress negative emotion led to both smaller startle eyeblinks and decreased corrugator activity. Instructions to enhance negative emotion led to larger startle eyeblinks and increased corrugator activity. Several advantages of this experimental manipulation are discussed, including the use of both a suppress and an enhance emotion condition, independent measurement of initial emotion elicitation and subsequent regulation of that emotion, the use of a completely within-subjects design, and the use of naturalistic emotion regulation strategies.


Function of a calmodulin in postsynaptic densities. III. Calmodulin-binding proteins of the postsynaptic density.
A method has been developed for binding calmodulin, radioiodinated by the lactoperoxidase method, to denaturing gels and has been used to attempt to identify the calmodulin-binding proteins of cerebral cortex postsynaptic densities (PSDs). Calmodulin primarily bound to the major 51,000 Mr protein in a saturatable manner; secondarily bound to the 60,000 Mr region, 140,000 Mr region, and 230,000 Mr protein; and bound in lesser amounts to a number of other proteins. The major 51,000 Mr calmodulin-binding protein is one of unknown identity. Binding of iodinated calmodulin to these proteins was blocked by EDTA, EGTA, chlorpromazine, and preincubation with unlabeled calmodulin. Calmodulin iodinated by the chloramine-T method, which inactivates calmodulin did not bind to the PSD but bound nonspecifically to histone. Calmodulin did not bind to proteins from a variety of sources for which calmodulin interactions have not been found. Except for three proteins, all of the proteins of synaptic membranes that bind calmodulin could be accounted for by proteins of the PSD which are a part of the synaptic membrane fraction. The major 51,000 M, protein and the corresponding iodinated calmodulin binding were greatly reduced in cerebellar PSDs and this difference between cerebral cortex and cerebellar PSDs is discussed in light of the possible function of calmodulin in synaptic excitatory responses.


Postseismic relaxation along the San Andreas fault at Parkfield from continuous seismological observations.
Seismic velocity changes and nonvolcanic tremor activity in the Parkfield area in California reveal that large earthquakes induce long-term perturbations of crustal properties in the San Andreas fault zone. The 2003 San Simeon and 2004 Parkfield earthquakes both reduced seismic velocities that were measured from correlations of the ambient seismic noise and induced an increased nonvolcanic tremor activity along the San Andreas fault. After the Parkfield earthquake, velocity reduction and nonvolcanic tremor activity remained elevated for more than 3 years and decayed over time, similarly to afterslip derived from GPS (Global Positioning System) measurements. These observations suggest that the seismic velocity changes are related to co-seismic damage in the shallow layers and to deep co-seismic stress change and postseismic stress relaxation within the San Andreas fault zone.


Hyperhomocysteinemia prevalence among patients with venous thromboembolism.
The aim of this study is to evaluate the plasma total homocysteine level in patients with venous thromboembolism (VTE) and to investigate the effect of different risk factors on plasma levels. Ninety-three-patients with VTE and 37-control participants diagnosed with other than VTE were included in the study. Plasma homocysteine levels and the factors affecting plasma homocysteine levels were evaluated. Plasma homocysteine level was higher among patients with VTE compared to the controls independent from vitamin B12 and folate levels. The prevalence of hyperhomocysteinemia in VTE was 63%. Plasma homocysteine level was higher in patients with PE than deep venous thrombosis (DVT; 23 ± 13.7 vs 16 ± 5.8 μmol/L, P = .018). With regression analysis hyperhomocysteinemia was found to be associated with a 4.8-fold increased risk of VTE. Hyperhomocysteinemia is a common and possibly modifiable risk factor that should be considered when screening patients with VTE. Secondary causes of hyperhomocysteinemia especially vitamin B12 deficiency should be monitored in patients with VTE to prevent recurrences.


Downregulation of CD45 Signaling in COVID-19 Patients Is Reversed by C24D, a Novel CD45 Targeting Peptide.
CD45, the predominant transmembrane tyrosine phosphatase in leukocytes, is required for the efficient induction of T cell receptor signaling and activation. We recently reported that the CD45-intracellular signals in peripheral blood mononuclear cells (PBMCs) of triple negative breast cancer (TNBC) patients are inhibited. We also reported that C24D, an immune modulating therapeutic peptide, binds to CD45 on immune-suppressed cells and resets the functionality of the immune system via the CD45 signaling pathway. Various studies have demonstrated that also viruses can interfere with the functions of CD45 and that patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are immune-suppressed. Given the similarity between the role of CD45 in viral immune suppression and our findings on TNBC, we hypothesized that the C24D peptide may have a similar "immune-resetting" effect on PBMCs from COVID-19 patients as it did on PBMCs from TNBC patients. We tested this hypothesis by comparing the CD45/TCR intracellular signaling in PBMCs from ten COVID-19 patients vs. PBMCs from ten healthy volunteers. Herein, we report our findings, demonstrating the immune reactivating effect of C24D via the phosphorylation of the tyrosine 505 and 394 in Lck, the tyrosine 493 in ZAP-70 and the tyrosine 172 in VAV-1 proteins in the CD45 signaling pathway. Despite the relatively small number of patients in this report, the results demonstrate that C24D rescued CD45 signaling. Given the central role played by CD45 in the immune system, we suggest CD45 as a potential therapeutic target.


Association of SARS-CoV-2 Spike Protein Antibody Vaccine Response With Infection Severity in Patients With Cancer: A National COVID Cancer Cross-sectional Evaluation.
Accurate identification of patient groups with the lowest level of protection following COVID-19 vaccination is important to better target resources and interventions for the most vulnerable populations. It is not known whether SARS-CoV-2 antibody testing has clinical utility for high-risk groups, such as people with cancer. To evaluate whether spike protein antibody vaccine response (COV-S) following COVID-19 vaccination is associated with the risk of SARS-CoV-2 breakthrough infection or hospitalization among patients with cancer. This was a population-based cross-sectional study of patients with cancer from the UK as part of the National COVID Cancer Antibody Survey. Adults with a known or reported cancer diagnosis who had completed their primary SARS-CoV-2 vaccination schedule were included. This analysis ran from September 1, 2021, to March 4, 2022, a period covering the expansion of the UK's third-dose vaccination booster program. Anti-SARS-CoV-2 COV-S antibody test (Elecsys; Roche). Odds of SARS-CoV-2 breakthrough infection and COVID-19 hospitalization. The evaluation comprised 4249 antibody test results from 3555 patients with cancer and 294 230 test results from 225 272 individuals in the noncancer population. The overall cohort of 228 827 individuals (patients with cancer and the noncancer population) comprised 298 479 antibody tests. The median age of the cohort was in the age band of 40 and 49 years and included 182 741 test results (61.22%) from women and 115 737 (38.78%) from men. There were 279 721 tests (93.72%) taken by individuals identifying as White or White British. Patients with cancer were more likely to have undetectable anti-S antibody responses than the general population (199 of 4249 test results [4.68%] vs 376 of 294 230 [0.13%]; P < .001). Patients with leukemia or lymphoma had the lowest antibody titers. In the cancer cohort, following multivariable correction, patients who had an undetectable antibody response were at much greater risk for SARS-CoV-2 breakthrough infection (odds ratio [OR], 3.05; 95% CI, 1.96-4.72; P < .001) and SARS-CoV-2-related hospitalization (OR, 6.48; 95% CI, 3.31-12.67; P < .001) than individuals who had a positive antibody response. The findings of this cross-sectional study suggest that COV-S antibody testing allows the identification of patients with cancer who have the lowest level of antibody-derived protection from COVID-19. This study supports larger evaluations of SARS-CoV-2 antibody testing. Prevention of SARS-CoV-2 transmission to patients with cancer should be prioritized to minimize impact on cancer treatments and maximize quality of life for individuals with cancer during the ongoing pandemic.


High Density Lipoproteins: Metabolism, Function, and Therapeutic Potential.
High Density Lipoproteins (HDLs) have long been considered as "good cholesterol," beneficial to the whole body and, in particular, to cardio-vascular health. However, HDLs are complex particles that undergoes dynamic remodeling through interactions with various enzymes and tissues throughout their life cycle, making the complete understanding of its functions and roles more complicated than initially expected. In this review, we explore the novel understanding of HDLs' behavior in health and disease as a multifaceted class of lipoprotein, with different size subclasses, molecular composition, receptor interactions, and functionality. Further, we report on emergent HDL-based therapeutics tested in small and larger scale clinical trials and their mixed successes.


Changes in cell shape correlate with collagenase gene expression in rabbit synovial fibroblasts.
Induction of the neutral proteinase, collagenase, is a marker for a specific switch in gene expression observed in rabbit synovial fibroblasts. A variety of agents, including 12-O-tetradecanoylphorbol-13-acetate, cytochalasins B and D, trypsin, chymotrypsin, poly(2-hydroxyethylmethacrylate), and trifluoperazine induced this change in gene expression. Induction of collagenase by these agents was always correlated with a marked alteration in cell morphology, although the cells remained adherent to the culture dishes. The amount of collagenase induced was positively correlated with the degree of shape change produced by a given concentration and, to some extent, with the duration of treatment. Altered cell morphology was required only during the first few hours of treatment with inducing agents; after this time collagenase synthesis continued for up to 6 d even when agents were removed and normal flattened cell morphology was regained. All agents that altered cell morphology also produced a characteristic switch in protein secretion phenotype, characterized by the induction of procollagenase (Mr 53,000 and 57,000) and a neutral metalloproteinase (Mr 51,000), which accounted for approximately 25% and 15% of the protein secreted, respectively. Secretion of another neutral proteinase, plasminogen activator, did not correlate with increased collagenase secretion. In contrast, synthesis and secretion of a number of other polypeptides, including the extracellular matrix proteins, collagen and fibronectin, were concomitantly decreased. That changes in cell shape correlated with a program of gene expression manifested by both degradation and synthesis of extracellular macromolecules may have broad implications in development, repair, and pathologic conditions.


Attitudes to carrier screening for cystic fibrosis: a survey of health care professionals, relatives of sufferers and other members of the public.
The gene which is mutated in cystic fibrosis has now been identified, thus permitting the detection of carriers in the general population. This paper reports pilot surveys in the North West Thames region of the health service to assess knowledge of people about cystic fibrosis and their attitudes towards screening. Three groups were surveyed: a group of relatives of those with cystic fibrosis (n = 268), a sample of the community (school pupils and family planning clinic attenders, n = 363), and a group of health care professionals (general practitioners and family planning clinic staff, n = 227). The relatives of cystic fibrosis sufferers were unanimously in favour of the introduction of cystic fibrosis screening, and the results indicate that there is likely to be support from the relevant health professionals: approximately 75% of respondents in the group of health care professionals believe the introduction of screening would be worthwhile. Data from the community sample suggest that, although knowledge of cystic fibrosis within the general community is low (less than 50% of respondents realized that cystic fibrosis affects the lungs and that no cure is available), there is likely to be considerable demand for carrier testing from the general public. Approximately 75% of the community sample indicated that they would like to be tested. There was no clear consensus, either from the professionals or the public, as to the best time to offer screening.


Clinicopathological and prognostic significance of H3K27 methylation status in malignant peripheral nerve sheath tumor: correlation with skeletal muscle differentiation.
Malignant peripheral nerve sheath tumor (MPNST) is a very aggressive peripheral nerve sheath-derived sarcoma, which is one of the most difficult tumors to diagnose due to its wide spectrum of histological findings and lack of specific immunohistochemical markers. Recently, it has been reported that losses of expression of H3K27me3 and H3K27me2 caused by PRC2 dysfunction may be useful diagnostic markers for MPNST, but there is no consensus on their clinicopathological significance. Here, we investigated the relationship between loss of H3K27 methylation and various parameters and clarified the clinicopathological significance of such loss. We analyzed the clinicopathological and immunohistochemical features in 84 MPNST cases. Complete losses of H3K27me3 and H3K27me2 were observed in 37 (44%) and 29 (35%) cases, respectively. Losses of H3K27me3 and H3K27me2 were significantly correlated with myogenic immunopositivity (H3K27me3 vs. desmin, P = 0.0051; H3K27me3 vs. myogenin, P = 0.0009; H3K27me2 vs. myogenin, P = 0.042). Meanwhile, there were significant correlations between preservation of immunohistochemical neurogenic markers and intact H3K27me3 and H3K27me2 (H3K27me3 vs. S-100 protein, P = 0.0019; H3K27me3 vs. SOX10, P = 0.014; H3K27me2 vs. S-100 protein, P = 0.0011; H3K27me2 vs. SOX10, P = 0.0087). In multivariate analysis, local recurrence, distant metastasis, high FNCLCC grade, and loss of SOX10 expression were independent prognostic factors for overall survival. H3K27me3 and H3K27me2 expression was retained in all 26 cases of rhabdomyosarcoma non-alveolar subtype. In conclusion, we suggest that H3K27me3 and H3K27me2 immunonegativity is useful but not definitive for diagnosing MPNST. Complete loss of H3K27 methylation may be involved in aggressive transdifferentiation from neural differentiation to skeletal muscle differentiation in MPNST.