Tumor M2-pyruvate kinase in lung cancer patients: immunohistochemical detection and disease monitoring.
Lung cancer is one of the main causes for cancer death. A reliable diagnosis and follow-up of patients is important support for a successful therapy. The diagnostic efficiency of a new marker Tumor M2-pyruvate kinase (Tumor M2-PK) is evaluated. In this report immunohistochemical detection of pyruvate kinase M2 in tissue sections of lung cancer specimens is presented. Furthermore Tumor M2-PK was quantified in EDTA plasma of lung cancer patients in order to monitor the disease, especially under chemotherapy. Immunohistochemical detection of pyruvate kinase M2 in tissue sections of lung cancer specimens showed selective staining of tumor cells, independent of the histological classification of the tumor. In EDTA plasma of lung cancer patients, the marker concentrations correlated well with the tumor load during follow-up, showing significantly increasing concentrations with progressive tumor stages and decreased concentrations during tumor remission. Again, this effect was independent of the histological tumor type. The present data indicate that Tumor M2-PK in EDTA-plasma could be a valuable tumor marker for monitoring lung cancer.


Endothelin receptors: binding and phosphoinositide breakdown in human myometrium.
Endothelin (ET) binding sites and phosphoinositide hydrolysis induced by ET peptides were studied in the nonpregnant human myometrium. Saturation binding experiments revealed that the proportion of [125I]ET-1 binding sites was 4-fold higher than that of [125I]ET-3 binding sites, whereas Kd values were not significantly different. In competition binding studies, unlabeled peptides displaced [125I]ET-1 binding with the following order of affinity ET-1 > sarafotoxin 6b > ET-3 >> sarafotoxin 6c, whereas very similar Ki values were obtained with the four peptides for the displacement of [125I]ET-3 binding. Approximately 75% of [125I]ET-1 binding sites exhibited high affinity to BQ 123 ([cyclo(D-Trp,D-Asp,L-Pro,D-Val,L-Leu)]), an ETA selective antagonist. ET-1 elicited a time-dependent accumulation of [3H]inositol phosphates in myometrial explants prelabeled with myo-[3H]inositol. All the peptides examined, ET-1, ET-3, sarafotoxin 6b and sarafotoxin 6c were able to induce phosphoinositide hydrolysis in a dose-dependent manner, ET-1 being more potent than ET-3 with corresponding EC50 values of 32 +/- 12 and 441 +/- 37 nM, respectively. Sarafotoxin 6c induced a moderate stimulation of inositol phosphates accumulation. ET-1- and ET-3-induced accumulation of [3H]inositol phosphates was (40-45%) inhibited in part by 100 microM BQ 123, whereas sarafotoxin 6c response was not affected by the ETA-antagonist. All these results indicate the presence of ETA and ETB receptors coupled to phospholipase C in human myometrium. Although ET-1 and ET-3 bind to both subtypes, sarafotoxin 6c only interacts with the ETB subtype.


Cognitive programs: software for attention's executive.
What are the computational tasks that an executive controller for visual attention must solve? This question is posed in the context of the Selective Tuning model of attention. The range of required computations go beyond top-down bias signals or region-of-interest determinations, and must deal with overt and covert fixations, process timing and synchronization, information routing, memory, matching control to task, spatial localization, priming, and coordination of bottom-up with top-down information. During task execution, results must be monitored to ensure the expected results. This description includes the kinds of elements that are common in the control of any kind of complex machine or system. We seek a mechanistic integration of the above, in other words, algorithms that accomplish control. Such algorithms operate on representations, transforming a representation of one kind into another, which then forms the input to yet another algorithm. Cognitive Programs (CPs) are hypothesized to capture exactly such representational transformations via stepwise sequences of operations. CPs, an updated and modernized offspring of Ullman's Visual Routines, impose an algorithmic structure to the set of attentional functions and play a role in the overall shaping of attentional modulation of the visual system so that it provides its best performance. This requires that we consider the visual system as a dynamic, yet general-purpose processor tuned to the task and input of the moment. This differs dramatically from the almost universal cognitive and computational views, which regard vision as a passively observing module to which simple questions about percepts can be posed, regardless of task. Differing from Visual Routines, CPs explicitly involve the critical elements of Visual Task Executive (vTE), Visual Attention Executive (vAE), and Visual Working Memory (vWM). Cognitive Programs provide the software that directs the actions of the Selective Tuning model of visual attention.


Acylphosphatase overexpression triggers SH-SY5Y differentiation towards neuronal phenotype.
An acylphosphatase (AcPase) overexpression study was carried out on SH-SY5Y neuroblastoma cells, using a green fluorescent fusion protein (AcP-GFP), with GFP acting as a reporter protein. The cellular proliferation rate was significantly reduced by overexpression of AcPase by a factor of ten. In contrast, clones transfected with two inactive AcPase mutants showed a growth rate comparable to control cells. This suggests that AcPase catalyzes the proliferative down-regulation. AcPase-overexpressing clones showed a physiological mortality rate as assessed by an MTT reduction test and by evaluation of necrotic markers. DNA fragmentation analysis and assays of caspase-3 and poly (ADP-ribose) polymerase (PARP)-active fragments showed no evidence of any apoptotic pattern. AcPase overexpression led to a marked increase in PARP activity as well as Bcl-2 content; these are commonly up-regulated during differentiative processes in neuronal cells. In fact, the typical differentiation marker, growth-associated-protein 43, was significantly up-regulated. Microscopic observations also showed a clear increase in the differentiative phenotype in AcPase-overexpressing cells. Our results clearly show that AcPase plays a primary causative role in neuronal differentiation.


Neurologic outcome score for infants and children.
To develop and validate a practical outcome instrument applicable to a broad range of neurologic deficits in children. Reliability testing of a draft version of the Neurologic Outcome Scale for Infants and Children (NOSIC) in 100 children with a wide range of ages and levels of neurologic function was performed. After review of the reliability data by a panel of experts, the NOSIC was revised. Validity and reliability testing of the final NOSIC was performed in a new population of 157 children, 52 with cerebral palsy, motor delay, or language delay. Interrater reliability was assessed using Spearman rank correlation coefficients of two investigators' scores. NOSIC scores were correlated with scores on criterion-standard neuropsychological tests to assess validity. The median NOSIC score for normal children was 98, interquartile range 96-100; the median score for abnormal children was 87, interquartile range 58-96. Interrater reliability of the NOSIC scores of 84 patients rated by both raters demonstrated excellent reliability (rho = 0.77, 95% confidence interval [CI] = 0.62 to 0.88). Correlation of the NOSIC scores of the 127 patients who had neuropsychological testing with applicable criterion standards was rho = 0.63, 95% CI = 0.50 to 0.74. The NOSIC is a practical, reliable, valid, instrument applicable to infants and children with a broad range of neurologic deficits. It should be a useful research tool when neurologic function is an important outcome measure.


Linking perception to neural activity as measured by visual evoked potentials.
Linking propositions have played an important role in refining our understanding of the relationship between neural activity and perception. Over the last 40 years, visual evoked potentials (VEPs) have been used in many different ways to address questions of the relationship between neural activity and perception. This review organizes and discusses this research within the linking proposition framework developed by Davida Teller, and her colleagues. A series of examples from the VEP literature illustrates each of the five classes of linking propositions originally proposed by Davida Teller. The related concept of the bridge locus-the site at which neural activity can be said to first be proscriptive of perception-is discussed and a suggestion is made that the concept be expanded to include an evolution over time and cortical area.


Derivation of a prognostic equation to predict in-hospital mortality and requirement of invasive mechanical ventilation in patients with acute exacerbation of chronic obstructive pulmonary disease.
Predicting in-hospital mortality and formulating a scoring system derived from predictors of mortality may aid prognostication. One hundred and fifty-one consecutive patients admitted with a diagnosis of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) were followed to discharge or death in hospital stay. Secondary variables studied were duration of hospital stay, and need for and duration of mechanical ventilation (MV). Mean (SD) age of patients was 60.5 (11.4) years; 65.6% were mechanically ventilated, and 25.2% died in hospital. Independent predictors of mortality at admission were serum creatinine (odds ratio [OR] 2.1, 95% Confidence intervals [CI] 1.03 to 4.30; p = 0.04), and serum sodium (OR 0.94, 95% CI 0.90 to 0.99; p = 0.03). An equation derived [Score = 8+ (0.74 x creatinine) = (0.015 x sodium)] to predict mortality, had an area under receiver operating characteristic (ROC) curve of 73%, with a cut-off of 6.74 having sensitivity, specificity, positive and negative predictive values for predicting death of 71%, 64%, 40% and 87%, respectively. Glasgow coma scale (GCS), partial pressure of oxygen in arterial blood (PaO2) and partial pressure of carbon dioxide in arterial blood (PaCO2) at admission independently predicted need for invasive ventilation. An equation derived [Score = 2.36+(0.02 x PaO2)+(0.05 x PaCO2)-(0.47 x GCS)] to predict need for MV, had an area under ROC curve of 85%, with a cut-off of 0.54 having sensitivity, specificity, positive and negative predictive values for predicting need for MV of 82%, 81%, 89% and 70%, respectively. Serum creatinine and sodium at admission are independent predictors of mortality for patients admitted with AECOPD. The equation derived from these two variables is a simple and useful method for predicting outcome.


The presence of depression in women who are victims of violence. The experiences of Anti Violence centers in the region of Calabria.
As is clear from research accredited by the ONU, the violence suffered by the partner, husband or other family members is the leading cause of death and disability for women aged 15 to 44 years. The WHO has also shown that at least one in five women suffers a beating or any form of violence in herl lifetime. Gender-based violence is undoubtedly a widespread phenomenon on a worldwide scale regardless of ethnicity, religion, social class,or level of education. It is a traumatic experience that produces different effects depending on the type of violence and the person who is the victim. There is a close relationship of cause and effect between violence and health status of women. They are in fact relevant primary effects related to the consequences of direct physical violence on the body and the side effects associated with mental and physical damage to repetitive exposure and situations of traumatic impact. The health consequences can be of different nature,rainging from Physical, Psychological and Behavioral, Sexual and Reproductive, to Death. The first important Psychological consequences are Depressive Disorder and Anxiety. The objective of this study was to analyze, through the administration of diagnostic tests, the methods of the links of the subjects on the one hand, attachment and relationships on the other; grouped in practice to detect if there is a close relationship between a Depressive Disorder and Violence suffered. 20 women aged between 23 and 50 years who have experienced various forms of violence, were randomly selected and followed by the three anti-violence centers of Calabria. The Separation Anxiety Depressive trait that explains the current Depression is not the result of the violence, but it is due to lack of self-confidence, difficulty im being identified and ability to plan for their lives. These difficulties are established in the woman through an enmeshed relationship with her partner, in fact, what has emerged is the establishment of an Insecure Attachment. Women who have been raped are traumatized individuals, who have not recovered from trauma, and therefore are vulnerable to pain. In relationships that have established themselves they feel responsible for what they have now (guilt, lack self-confidence, difficulty in separating); denying Separation Anxiety and remaining trapped in a violent relationship. The term Separation Anxiety denotes an aspect of behaviour, considered as a pathological form as well as clarified by the DSM V (even in adults); In fact, this is the separation anxiety which is manifested by extreme anxiety and those who suffer from it are tied more to the partner and/or parents that are the very cause of the symptom. This discomfort is related to childhood, therefore, the evidence suggests that there is a close relationship between what one has lived in that era and adult life. Women victims of violence, must overcome the separation anxiety that has been established as a result of trauma, the latter if not processed coincides with the shame and the guilt. This will be possible if they are given valid support, which is psychological / psychotherapeutic and pharmacological , to accompany and support them towards a new lease of life.


Cold reacting antinuclear antibody in Henoch-Schönlein Purpura.
Although the etiology is unknown, a number of features of Henoch-Schönlein Purpura (HSP) suggest an immune pathogenesis. Using indirect immunofluorescence, we evaluated 19 patients with HSP for the presence of cold reacting antinuclear antibody (ANA). Eighteen of 19 patients demonstrated cold reacting ANA of the IgG class when human epithelial cells were utilized as substrate. The immunofluorescent pattern was speckled in all. One patient demonstrated ANA when tested at room temperature, while the remaining 18 were negative at room temperature. Cold reacting ANA persisted for periods of 6 months to 6 years in 10 patients, regardless of concomitant disease activity. None of the HSP patients demonstrated cold reacting ANA when mouse kidney sections were employed as substrate. Moreover, none demonstrated antibody to DNA or to extractable nuclear antigen. Sera from 20 normal adults, 10 normal children, and 7 children with juvenile rheumatoid arthritis were all negative when tested for cold reacting ANA. Cold incubation altered neither the ANA titer nor the immunofluorescent pattern in 5 patients with systemic lupus erythematosus. These results indicate that patients with HSP elaborate a cold reacting ANA which is substrate dependent.


Effect of position on selected hemodynamic parameters in postoperative cardiac surgery patients.
Indirect/noninvasive blood pressure, heart rate and central venous pressure are frequently monitored hemodynamic parameters in postoperative cardiac surgery patients. No previous studies have explored the effect of lateral position on these variables in this population. To determine differences in (1) blood pressure, central venous pressure, or heart rate measurements among postoperative cardiac surgery patients due to position (supine, 45 degrees right lateral, and 45 degrees left lateral), (2) responses to position between patients having cardiac surgery in which the myocardium was opened (valvular replacement) and those in which it was not (coronary artery bypass graft), and (3) responses to position between cardiac surgery patients having preoperatively diagnosed lung disease and those without lung disease. Phlebostatic axis in lateral positions was determined by echocardiography and geometric diagrams prior to the initiation of data collection. Postoperative cardiac surgery patients (N = 120) were studied in the three positions in random sequences. In each position, simultaneous blood pressure measurements were obtained from each arm, and central venous pressure and heart rate were recorded. Statistically significant differences were found in response to position in systolic and diastolic blood pressure, central venous pressure, and heart rate. Certain positions produced greater changes in selected variables, both in the total group and within specific subgroups. No differences were found between coronary artery bypass graft and valve (closed or opened myocardium) subgroups or between subgroups with and without lung disease. Lateral positioning of postoperative cardiac surgery patients appears to cause no detrimental effects on indirect/noninvasive blood pressure or heart rate measurements. However, significant differences in central venous pressure may occur and supine positioning for determination of central venous pressure is recommended.


Otitis media.
The spectrum of otitis media includes acute and chronic forms, each of which can be either suppurative of nonsuppurative. In the usual clinical setting distinctions between these several forms can be difficult. Determination of accurate incidence figures is impeded by the unavailability of universally accepted diagnostic criteria. Risk factors include season of the year, genetic factors, race, preceding respiratory tract infections, cleft palate, and others. The effect of household size and allergy are uncertain. The most common infecting organisms are Streptococcus pneumoniae and Hemophilus influenzae, although in a significant number of cases either the fluid is nonpathogenic or no organisms can be isolated. The effects of several therapies are reviewed, including antibiotics, myringotomy, steroids, and middle-ear ventilating tubes.


Abrupt Structural Transformation in Asymmetric ABPO4F (A = K, Rb, Cs).
An asymmetric structure is the necessary requirement for second-order nonlinear-optical (NLO) materials, which have important applications in modern science and technology. Here we report two isostructural asymmetric compounds, RbBPO4F and CsBPO4F. Both compounds crystallize in cubic space group P213 (No. 198) with three-dimensional (3D) gismondine-like structures. Remarkably, in spite of the same basic structural units BO3F and PO4, both structures are distinct from the previously reported derivative KBPO4F, which crystallizes in a monoclinic space group Cc (No. 9) with a two-dimensional (2D)-layered structure. Careful structural analysis reveals that this structural transformation (from a monoclinic 2D structure to cubic 3D structures) should be aroused by the different alkaline ionic radii. To the best of our knowledge, such an abrupt structural transformation by alkaline elements is reported in all-inorganic asymmetric compounds for the first time. The structural transformation from 2D to 3D structures is favorable to eliminate the layered growth habit. This study will shed deep insight in the structural modulation of asymmetric compounds.


Serum titer of neutralizing antibodies after COVID-19 vaccination in Japanese patients with inflammatory bowel disease.
Vaccination is an important strategy to reduce the infection rate and adverse events of coronavirus disease 2019 (COVID-19). However, the effect of COVID-19 vaccination for Japanese patients with inflammatory bowel disease (IBD) has not been fully elucidated. In the present study, we investigated the serum titer of neutralizing antibodies after COVID-19 vaccination in patients with IBD, treated with and without immunosuppressive therapy. The study consisted of 108 patients with IBD [76 with ulcerative colitis (UC) and 32 with Crohn's disease (CD)] from the gastroenterology outpatient clinic at the Hospital of the Kyoto Prefectural University of Medicine who underwent anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. The control group included 64 healthy subjects who received the anti-SARS-CoV-2 vaccine. When 10 AU/ml of neutralizing antibodies was used as cut-off value, the positive rates of neutralizing antibodies of patients with UC, patients with DC, and the control group were 97.3%, 84.3%, and 100%, respectively. The neutralizing antibody titer showed no difference between patients treated with and without immunosuppressive therapy. These results indicate that COVID-19 vaccination may be useful in patients with IBD, treated with or without immunosuppressive therapy.


Gastrointestinal stromal tumor after tyrosine kinase inhibition therapy: a review of biopsies of 34 patients with clinically suspected relapse and/or progression of the tumor.
Implementation of combined surgical and targeted therapy strategies using tyrosine kinase inhibitors improved the prognosis of patients with aggressive GISTs. The therapeutic answer may be individually different, some patients do not respond properly, or even progress in spite of the therapy. This together with intratumoral heterogeneity and possible development of secondary phenotypical and genetical changes represents a challenge for pathologists examining a biopsy of relapsed tumors and/or their metastases. For this study biopsy files of the national Slovak GIST registry were reviewed to identify patients examined bioptically both prior the therapy and during the TKI treatment due to suspected tumor relapse and/or progression. All the GIST biopsies were analyzed using a standardized algorithm of histological, immunohistochemical and molecular analyses of exon 7, 9, 11, 13 of c-KIT and exons 12, 14, and 18 of PDGFRA genes, with the aim to identify posttherapeutical changes of these parameters. From 34 patients fulfilling the criteria of selection, all were histologically examined during their clinically suspicious first GIST relaps, eight during the 2nd, three during 3rd and one during 4th and 5th relapse resp. All but one posttherapeutical biopsies showed "viable" GIST tissue and so 44 relapses of 33 patients could be evaluated in comparison with identical parameters of diagnostic biopsies. Distinguishing three major histological types (spindle-, epitheloid-cell and mixed cell type), a change of the GIST type was identified in 1/3 of 1st relapse and ¼ of all relapse biopsies. Evaluation of three phenotypical GIST parameters CD117, CD34 and DOG-1, showed that phenotype alteration was always represented by a single change. The most common was either a gain or loss of CD34 positivity appearing in 1/3 of 1st relapse biopsies, while a loss of CD117 positivity was identified in one patient´s biopsy only. Altogether, the phenotypical changes were in ¼ of all relapses. A changed mutational profile was recognized in 38,2% first relaps biopsies and in 33% of all relapses, the change was mostly isolated (in 10/45 relapses) and less often (in 4/45 relapses) it represented a gain of a new mutation in association with persisting original one. In conclusion, the biopsies of patients showing relapse and/or progression on TKI treatment show predominance of viable GIST cells with limited or even absent signs of scaring, as well as relatively low incidence of morphological, pheno- and genotypical changes.


[Tako-Tsubo syndrome (transient antero-apical dyskinesia): first case reported in Latin America and review of the literature].
Tako-Tsubo syndrome (TTS) is a recently described entity that can mimic an acute myocardial infarction. It is characterized by anginal chest pain with ST-T elevation in precordial leads, no coronary obstruction on angiography, and as its distinctive feature, a reversible left ventricular antero-apical ballooning with basal hyperkinesis. TTS is more frequent in female and elderly patients and in an article published in 2001 it was mentioned that only two cases had been reported outside Japan. We describe a typical case of recurrent TTS triggered by intense emotional stress. This is the first case reported from Latin America. A review of the literature suggests that TTS is more frequent than previously thought but apparently due to lack of awareness of this entity it can go unrecognized. Identification of TTS is of clinical importance because its management and prognosis differs significantly from that of an acute myocardial infarction that results from the thrombotic occlusion of a coronary atherosclerotic plaque.


Different classes of antibiotics given to women routinely for preventing infection at caesarean section.
Caesarean section increases the risk of postpartum infection for women and prophylactic antibiotics have been shown to reduce the incidence; however, there are adverse effects. It is important to identify the most effective class of antibiotics to use and those with the least adverse effects. To determine, from the best available evidence, the balance of benefits and harms between different classes of antibiotic given prophylactically to women undergoing caesarean section. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 September 2014) and reference lists of retrieved papers. We included randomised controlled trials comparing different classes of prophylactic antibiotics given to women undergoing caesarean section. We excluded trials that compared drugs with placebo or drugs within a specific class; these are assessed in other Cochrane reviews. Two review authors independently assessed the studies for inclusion, assessed risk of bias and carried out data extraction. We included 35 studies of which 31 provided data on 7697 women. For the main comparison between cephalosporins versus penicillins, there were 30 studies of which 27 provided data on 7299 women. There was a lack of good quality data and important outcomes often included only small numbers of women.For the comparison of a single cephalosporin versus a single penicillin (Comparison 1 subgroup 1), we found no significant difference between these classes of antibiotics for our chosen most important seven outcomes namely: maternal sepsis - there were no women with sepsis in the two studies involving 346 women; maternal endometritis (risk ratio (RR) 1.11, 95% confidence interval (CI) 0.81 to 1.52, nine studies, 3130 women, random effects, moderate quality of the evidence); maternal wound infection (RR 0.83, 95% CI 0.38 to 1.81, nine studies, 1497 women, random effects, low quality of the evidence), maternal urinary tract infection (RR 1.48, 95% CI 0.89 to 2.48, seven studies, 1120 women, low quality of the evidence) and maternal composite adverse effects (RR 2.02, 95% CI 0.18 to 21.96, three studies, 1902 women, very low quality of the evidence). None of the included studies looked for infant sepsis nor infant oral thrush.This meant we could only conclude that the current evidence shows no overall difference between the different classes of antibiotics in terms of reducing maternal infections after caesarean sections. However, none of the studies reported on infections diagnosed after the initial postoperative hospital stay. We were unable to assess what impact, if any, the use of different classes of antibiotics might have on bacterial resistance. Based on the best currently available evidence, cephalosporins and penicillins have similar efficacy at caesarean section when considering immediate postoperative infections. We have no data for outcomes on the baby, nor on late infections (up to 30 days) in the mother. Clinicians need to consider bacterial resistance and women's individual circumstances.


Our VOICE: an interdisciplinary approach to shared governance.
The authors' purpose was to make public to other healthcare executives the demonstrated success of an interdisciplinary shared governance process benefiting any healthcare organization. Main components of a successful model include a conducive work environment free of distractions, available resources in order to gather information to complete a project, and committees chosen focused on high priority for patient and staff satisfaction, quality, and safety. An essential piece of the puzzle is that grassroots staff needs to own the process. The authors share the current model and discuss outcomes, success, and lessons learned throughout their decade-long journey.


A model for immunological correlates of protection.
Immunological assays measure characteristics of the immune system, such as antibody levels, specific to certain diseases. High assay values are often associated with protection from disease. A question of interest is how the relationship between assay values and subsequent development of disease should be quantitatively modelled. Existing approaches successfully model the relationship for high assay values, where the probability of developing disease is low. However at low assay values, the probability of developing disease is more closely associated with factors such as disease prevalence rates and an individual's chance of exposure to infection; these are less well captured by existing models. This paper presents a model that accommodates both assay values and factors independent of assay values, enabling protection from disease to be modelled over the whole range of assay values and proposing a method for predicting the efficacy of a vaccine from the assays of vaccinees and non-vaccinees.


Epidemiology, major outcomes, risk factors, prevention and management of chronic kidney disease in China.
Chronic kidney disease (CKD) is common in China. In residents older than 40 years in Beijing, China, 11.3% of subjects had at least one indicator of kidney damage. The primary cause of chronic renal failure in China was glomerulonephritis, which was followed by diabetic nephropathy and hypertensive nephrosclerosis. Renal failure, cardiovascular disease and infection were important complications. IgA nephropathy (IgAN) is the most common CKD in China. The prevalence of hypertension, intrarenal artery lesions and tubulointerstitial lesions in patients with IgAN at the time of renal biopsy was approximately 40, 55 and 85%, respectively. The genetic variation in Megsin confers susceptibility to IgAN in Chinese. The patients with SL/LL genotypes of the MUC20 gene, the 38AA genotype of uteroglobin and DD genotype of the angiotensin-converting enzyme gene had a higher risk of progression. Chinese prospective clinical trials showed that benazepril (BZ) conferred substantial renal benefits in patients with advanced renal insufficiency. The combined therapy with urokinase and BZ was more effective than with BZ alone in reducing proteinuria and protecting renal function in Chinese patients with severe IgAN. Lupus nephritis (LN) is a common form of secondary renal disease diagnosed by renal biopsy in China. Chinese multicenter clinical trials showed that mycophenolate mofetil or leflunomide combined with steroids was effective as induction therapy for proliferative LN.


[Immunology in clinical practice. XIII. Immune diseases of the eye].
The eye has a special relationship with the immune system; normally, there appears to be intraocular suppression of inflammatory responses. Studies of the immunological principles of intraocular inflammation (uveitis) are mostly done in animal models. Although very complicated, uveitis appears in any case to be T-cell mediated. Uveitis is classified according to anatomical location as anterior, intermediate, posterior and pan-uveitis. Other immunological disorders are the sicca syndrome, keratitis and scleritis. All these disorders may or may not be associated with systemic autoimmune diseases. The chronic and recurring characteristics make uveitis a serious threat to vision. A rapid diagnosis and adequate treatment are therefore very important.


Vaginal infection with Ureaplasma urealyticum accounts for preterm delivery via induction of inflammatory responses.
U. urealyticum, a member of the family Mycoplasmataceae, is often detected in the vagina of pregnant women. In this study, the possible association of ureaplasmal infection with preterm delivery was examined, as was the capacity of ureaplasmal LP to stimulate monocytes in vitro to produce pro-inflammatory cytokines relevant to preterm delivery. A hundred cases of normal delivery and 45 cases of preterm delivery were randomly selected. A mAb against U. urealyticum urease, that selectively and positively stained it in vaginal secretions of infected women but not in those of uninfected women, was generated. The preterm delivery group showed a significantly higher incidence of vaginal infection with this bacteria than the normal delivery group. Since the LP of Mycoplasma has potent biological activity, ureaplasmal LP was extracted. THP-1 cells, and human monocytic cells, produced IL-8, a potent pro-inflammatory cytokine associated with preterm delivery, and showed apoptotic cell death in response to the LP in vitro. These results suggest that U. urealyticum infection might play a causative role in preterm delivery via LP-induced IL-8 production and apoptosis.


Culturally-Relevant Online Education Improves Health Workers' Capacity and Intent to Address Cancer.
To address a desire for timely, medically-accurate cancer education in rural Alaska, ten culturally-relevant online learning modules were developed, implemented, and evaluated with, and for, Alaska's Community Health Aides/Practitioners (CHA/Ps). The project was guided by the framework of Community-Based Participatory Action Research, honored Indigenous Ways of Knowing, and was informed by Empowerment Theory. Each learner was invited to complete an end-of-module evaluation survey. The survey asked about changes in intent to share cancer information with patients as a result of the module. In 1 year, August 1, 2016-July 31, 2017, 459 surveys were completed by 79 CHA/Ps. CHA/Ps reported that, because of the modules, they felt more knowledgeable about cancer, and more comfortable, confident, and prepared to talk about cancer with their patients, families, and communities. All learners shared that because of the modules, they intended to talk with their patients more often about cancer screenings, tobacco cessation, physical activity, or nutrition. These findings suggest that the application of this collaboratively developed, culturally-relevant, health promotion intervention has supported increased CHA/P capacity and intent to interact with patients about cancer. In the words of a learner: "Doing all these courses makes me a ton times more comfortable in talking about cancer with anyone. I didn't know too much about it at first but now I know a whole lot. Thank you".


A scoping review of the knowledge base in WORK that addresses work related outcomes for individuals with chronic pain.
Chronic pain such as arthritis has a significant impact on occupational performance in the workplace that contributes to decreased productivity, reduced rates of employment, personal and societal economic costs. In commemoration of the 20th anniversary of WORK, a scoping review was conducted to understand the knowledge base on chronic pain. The purpose of this was to examine and describe WORK's contribution to the literature relevant for rehabilitation professionals such as occupational therapists to improve work related outcomes for persons experiencing chronic pain. The method employed the use of historical, citation and dimension analyses of assessment and intervention articles. Of the 30 articles identified in WORK, the historical analysis of their scope indicated an international representation of authors and a greater emphasis on quantitative study designs. The citation analysis revealed that the articles in WORK drew heavily on medical literature to inform their studies. The dimensional analysis of the assessment and intervention articles applied an occupational lens of self-care, productivity and leisure, to draw upon the Occupational Competence Model and identified that the majority of papers focused on 2 or more dimensions of the person, environment and occupation. WORK has contributed to the knowledge base of assessment and intervention approaches that inform work rehabilitation strategies for individuals with chronic pain. To advance its knowledge base for the rehabilitation and management of chronic pain, WORK is encouraged to include more prevention and multidimensional interventions articles, as well as articles that contain multidimensional assessment tools that address both clinical and outcome assessments of chronic pain. Additionally internal dialogue should be encouraged within WORK so that new authors build on previous submissions and increase the impact and quality of research on chronic pain as it pertains to work.


Slow inactivation in Shaker K channels is delayed by intracellular tetraethylammonium.
After removal of the fast N-type inactivation gate, voltage-sensitive Shaker (Shaker IR) K channels are still able to inactivate, albeit slowly, upon sustained depolarization. The classical mechanism proposed for the slow inactivation observed in cell-free membrane patches--the so called C inactivation--is a constriction of the external mouth of the channel pore that prevents K(+) ion conduction. This constriction is antagonized by the external application of the pore blocker tetraethylammonium (TEA). In contrast to C inactivation, here we show that, when recorded in whole Xenopus oocytes, slow inactivation kinetics in Shaker IR K channels is poorly dependent on external TEA but severely delayed by internal TEA. Based on the antagonism with internally or externally added TEA, we used a two-pulse protocol to show that half of the channels inactivate by way of a gate sensitive to internal TEA. Such gate had a recovery time course in the tens of milliseconds range when the interpulse voltage was -90 mV, whereas C-inactivated channels took several seconds to recover. Internal TEA also reduced gating charge conversion associated to slow inactivation, suggesting that the closing of the internal TEA-sensitive inactivation gate could be associated with a significant amount of charge exchange of this type. We interpreted our data assuming that binding of internal TEA antagonized with U-type inactivation (Klemic, K.G., G.E. Kirsch, and S.W. Jones. 2001. Biophys. J. 81:814-826). Our results are consistent with a direct steric interference of internal TEA with an internally located slow inactivation gate as a "foot in the door" mechanism, implying a significant functional overlap between the gate of the internal TEA-sensitive slow inactivation and the primary activation gate. But, because U-type inactivation is reduced by channel opening, trapping the channel in the open conformation by TEA would also yield to an allosteric delay of slow inactivation. These results provide a framework to explain why constitutively C-inactivated channels exhibit gating charge conversion, and why mutations at the internal exit of the pore, such as those associated to episodic ataxia type I in hKv1.1, cause severe changes in inactivation kinetics.


Participation of osteoclastogenic factors in immunopathogenesis of human chronic periapical lesions.
Chronic periapical lesions (CPLs) are common lesions of the oral cavity and are the result of caries, tooth fracture, iatrogenic causes, or factors causing contamination and pulp necrosis. Inflammatory cells participate in the expansion of CPLs by releasing factors that stimulate or inhibit osteolytic activity. The objective of this study was to investigate the participation of RANKL, TNF-α, cathepsin K, IL-33, and OPG in the development of radicular cysts (RCs) and periapical granulomas (PGs). Paraffin-embedded sections of 30 RCs and 22 PGs were submitted to immunohistochemistry. Immunoexpression of the proteins studied was observed in the epithelium and capsule of RCs, as well as in connective tissue of PGs. The expression of the osteoclastogenic factors studied differed significantly in RCs and PGs (P < .001), with lower expression of OPG in RCs. In PGs, the lowest expression was observed for cathepsin K. Comparison of the 2 lesions showed a similar participation of RANKL and IL33, while a significant difference was observed for OPG (P < .001), TNF-α (P = .002), and cathepsin K (P = .016). No association of the expression of the proteins with lesions size was observed. This study demonstrated the participation of RANKL, TNF-α, IL-33, cathepsin K, and OPG in the development of RCs and PGs, with emphasis on the highest immunoreactivity of cathepsin in RCs and TNF-α and OPG in PGs. OPG possibly determines the slower growth of PGs compared to RCs.


Pulmonary Involvement in Patients with Guillain-Barré Syndrome in Subacute Phase.
To evaluate the pulmonary function in Guillain-Barre syndrome (GBS) patients in subacute phase and find clinical correlates of pulmonary dysfunction. This was a single-center, prospective, cross-sectional, hospital-based study in GBS patients performed in Department of Neurological Rehabilitation at a tertiary care institute. Clinical examination for pulmonary function was done by measuring chest expansion. The pulmonary function tests were carried out by Spirometry kit Microquark Cosmed, Italy. Fatigue was assessed by Fatigue Severity Scale, disability status by Hughes Disability Scale (HDS), and muscle weakness by Medical Research Council sum scores. Statistical analysis was performed by Stata 11. The significance of P value was adjudged against an alpha of 0.05. Twenty-eight patients were included with 17 (61%) men and mean age of 31 years. Median duration of symptoms was 16.5 days. There were 10 (36%) demyelinating and 18 (64%) axonal variants. Twenty-six (93%) patients scored more than 2 on HDS. All study participants reported fatigue. Twenty-two (78.6%) patients had chest expansion of <2.5 cm. Spirometry showed restrictive pulmonary dysfunction in 23 (79%) patients. Significant correlation was found between abnormal pulmonary function test and chest expansion (P = 0.003). Pulmonary dysfunction in GBS is common even during subacute phase. It needs to be identified and managed appropriately for better clinical outcome.


Ovarian intratumoral 21-hydroxylase deficiency in a postmenopausal hirsute woman.
Virilising ovarian tumours are a rare cause of hyperandrogenism in women, accounting for less than 5% of all ovarian neoplasms. It occurs most often in - and postmenopausal women. We report a case of a 64 year-old woman with signs of virilisation that had started 3 years before. Blood hormone analysis revealed increased levels of testosterone, and 17-hydroxyprogesterone. The tetracosactin test revealed 21-hydroxylase deficiency. Radiological imaging demonstrated a nodule in her left ovary. The patient was submitted to bilateral laparoscopic oophorectomy, and histopathological examination revealed a luteoma of the left ovary. Postoperative serum testosterone level and 17-hydroxyprogesterone returned to normal levels in one month. Virilism regressed within six months. Our patient also showed an elevation in 17-OHP serum levels. Normalization of 17-OHP after oophorectomy suggests a case of intratumoral 21-hydroxylase deficiency. To our knowledge, this is the first description of ovarian intratumoral 21-hydroxylase deficiency in a postmenopausal woman.


Complete Genome Sequence of Seoul Virus Strain Tchoupitoulas.
Seoul virus (genus Hantavirus; family Bunyaviridae) is an emerging pathogen associated with cases of acute kidney injury in several countries across the globe. We report here the whole-genome sequence of the Tchoupitoulas strain of Seoul virus isolated in New Orleans, LA.


Evaluation of pH and calcium ion diffusion from calcium hydroxide pastes and MTA.
The aim of this ex vivo study was to evaluate changes in pH and calcium ion diffusion through root dentin from calcium hydroxide (Ca (OH) 2) and mineral trioxide aggregate (MTA) pastes at 7, 30 and 60 days; and the relationship between pH and ion diffusion. Thirty-two human premolars were used. Crowns were sectioned and root canals instrumented and filled in with the following preparations: 1) Ca(OH) 2 + distilled water (n=7); 2) Ca(OH) 2 + 0.1% chlorhexidine gluconate (n=7); 3) MTA + distilled water (n=7); 4) MTA + 0.1% chlorhexidine gluconate (CHX) (n=7); 5) distilled water (n=2) (control); 6) 0.1% chlorhexidine gluconate (n=2) (control). The apex and coronary opening were sealed with IRM. Roots were placed in Eppendorf tubes with 1 ml distilled water at 37°C and 100% humidity. At baseline, 7, 30 and 60 days, pH was measured with pH meter, and calcium ion content in the solution was analyzed by atomic absorption spectrophotometry. The data were statistically analyzed using ANOVA, simple linear regression analysis and Pearson's correlation test. The highest pH values were achieved with calcium hydroxide pastes at 60 days (p ≤ 0.05). Calcium ions were released in all groups. The calcium hydroxide paste with distilled water at 60 days had the highest calcium ion value (p ≤ 0.01). There was a positive correlation between calcium and pH values.


Quantitative optical coherence tomography analysis for late in-stent restenotic lesions.
Coronary optical coherence tomography (OCT) has the potential to identify in-stent neoatherosclerosis, which is a possible risk factor for late acute coronary events after drug-eluting stent implantation. The purpose of this study was to investigate differences between mid-term and late in-stent restenosis after stent implantation by quantitative and semiautomated tissue property analysis using OCT. In total, 1063 OCT image frames of 16 lesions in 15 patients were analyzed. This included 346 frames of 6 lesions in late in-stent restenosis, which was defined as restenosis that was not detected at 6 to 12 months but ≥ 12 months after follow-up coronary angiography. Signal attenuation was circumferentially analyzed using a dedicated semiautomated software. Attenuation was assessed along 200 lines delineated radially for analysis of the in-stent restenotic lesions (between the lumen and stent contours). All lines were anchored by the image wire to avoid artifacts resulting from wire location. Stronger signal attenuation at the frame level (2.46 ± 0.78 versus 1.47 ± 0.32, P < 0.001) and higher maximum signal intensity at the lesion level (9.19 ± 0.19 versus 8.84 ± 0.32, P = 0.018) were observed in late in-stent restenotic lesions than in mid-term in-stent restenotic lesions. OCT demonstrated stronger signal attenuation and higher maximum signal intensity in late in-stent restenotic lesions than in mid-term in-stent restenotic lesions, indicating the possibility of neoatherosclerosis.


NADP-dependent isocitrate dehydrogenase from the halophilic archaeon Haloferax volcanii: cloning, sequence determination and overexpression in Escherichia coli.
A gene encoding NADP-dependent Ds-threo-isocitrate dehydrogenase was isolated from Haloferax volcanii genomic DNA by using a combination of polymerase chain reaction and screening of a lambda EMBL3 library. Analysis of the nucleotide sequence revealed an open reading frame of 1260 bp encoding a protein of 419 amino acids with 45837 Da molecular mass. This sequence is highly similar to previously sequenced isocitrate dehydrogenases. In the alignment of the amino acid sequences with those from several archaeal and mesophilic NADP-dependent isocitrate dehydrogenases, the residues involved in dinucleotide binding and isocitrate binding are well conserved. We have developed methods for the expression in Escherichia coli and purification of the enzyme from H. volcanii. This expression was carried out in E. coli as inclusion bodies using the cytoplasmic expression vector pET3a. The enzyme was refolded by solubilisation in 8 M urea followed by dilution into a buffer containing EDTA, MgCl(2) and 3 M NaCl. Maximal activity was obtained after several hours incubation at room temperature.


Big Data Analyses in Health and Opportunities for Research in Radiology.
This article reviews examples of big data analyses in health care with a focus on radiology. We review the defining characteristics of big data, the use of natural language processing, traditional and novel data sources, and large clinical data repositories available for research. This article aims to invoke novel research ideas through a combination of examples of analyses and domain knowledge.


ACTN1-related Macrothrombocytopenia: A Novel Entity in the Progressing Field of Pediatric Thrombocytopenia.
The most common cause of thrombocytopenia in children is immune thrombocytopenia. Nevertheless, some atypical cases should evoke the hypothesis of genetic thrombocytopenia. Indeed, in the past years, 30 new genes had been described in the field of inherited thrombocytopenia. We report a series of 11 cases of a newly diagnosed entity: ACTN1-related macrothrombocytopenia. Mutations in the gene ACTN1 cause mild macrothrombocytopenia characterized by elevated mean platelet volume and elevated immature platelet fraction, and low bleeding tendency. Its transmission is autosomal dominant. Molecular diagnosis is made by sequencing the ACTN1 gene. Its potential role in hematological malignancy predisposition remains unclear and should be clarified. We identified 11 patients with ACTN1-related macrothrombocytopenia diagnosed through pediatric probands. The aim was to underline the specificities of this entity, especially in children, and bring it to the knowledge of pediatricians.


Theoretical insight into the photodegradation of a disulfide bridged cyclic tetrapeptide in solution and subsequent fast unfolding-refolding events.
We report the photoinduced peptide bond (C-N) of an amide unit and S-S bond fission mechanisms of the cyclic tetrapeptide [cyclo(Boc-Cys-Pro-Aib-Cys-OMe)] in methanol solvent by using high-level CASSCF/CASPT2/Amber quantum mechanical/molecular mechanical (QM/MM) calculations. The subsequent energy transport and unfolding-refolding events are characterized by using a semiempirical QM/MM molecular dynamics (MD) simulation methodology that is developed in the present work. In the case of high-energy excitation with <193 nm light, the tetrapeptide molecule in the (1)n pi* surface overcomes two barriers with approximately 10.0 kcal/mol, respectively, and uses energy consumption for breaking the hydrogen bond as well as the N-C bond in the amide unit, ultimately leading to the ground state via a conical intersection of CI (S(NP)/S(0)) by structural changes of an increased N-C distance and a O-C-C angle in the amide unit (a two-dimensional model of the reaction coordinates). Following this point, relaxation to a hot molecule with its original structure in the ground state is the predominant decay channel. A large amount of heat (approximately 110.0 kcal/mol) is initially accumulated in the region of the targeted point of the photoexcitation, and more than 60% of the heat is rapidly dissipated into the solvent on the femtosecond time scale. The relatively slower propagation of heat along the peptide backbone reaches a phase of equilibration within 3 ps. A 300 nm photon of light initiates the relaxation along the repulsive S(sigma sigma)((1)sigma sigma*) state and this decays to the CI (S(sigma sigma)/S(0)) in concomitance with the separation of the disulfide bond. Once cysteinyl radicals are generated, the polar solvent of methanol molecules rapidly diffuses around the radicals, forming a solvent cage and reducing the possibility of close contact in a physical sense. The fast unfolding-refolding event is triggered by S-S bond fission and powered by dramatic thermal motion of the methanol solvent that benefits from heat dissipation. The beta-turn opening (unfolding) can be achieved in about 120 ps without the inclusion of the time associated with the photochemical steps and eventually relaxes to a 3(10)-helix structural architecture (refolding) within 200 ps.


Controlled Gelation of Graphene Towards Unprecedented Superstructures.
Graphene exhibits a range of exceptional physical properties and holds great promise for development of novel bulk materials for widespread applications. Properly engineering of assembled structures of graphene at multiple length scales is essential to realize its full potential in bulk forms. In this Concept article, we highlight the unique colloidal and gelation behavior of a commonly used precursor for graphene, graphene oxide (GO), and discuss how the colloidal chemistry of GO and reduced GO can enable new scalable and cost-effective approaches to construct graphene-based soft superstructures with excellent properties.


Supporting breastfeeding of babies in neonatal units.
Breastmilk is invaluable for premature and sick babies. Recognition of the unique qualities of breastmilk has led to increasing encouragement to women to express breastmilk for their babies, if they are unable to feed directly from the breast. The National Childbirth Trust (NCT) had become increasingly concerned about the shortcomings in some areas in the practical and professional support available to women wanting to breastfeed when their babies are in neonatal units. The NCT therefore funded an investigation of the provision of facilities to express breastmilk in hospitals, including the availability of electric breast pumps for loan to mothers at home. We found that facilities for mothers in hospital were patchy, with only a third of neonatal units providing a separate room where mothers could express breastmilk or breastfeed in private. More than half the units on which we collected information had no specialist breastfeeding professional available. A quarter of units loaned out free electric breast pumps and a further 28% were able to provide some free breast pumps. 24% of hospitals did not provide any pumps to mothers who needed to express breastmilk at home while their babies were in hospital.


Roles of lipid modifications of transducin subunits in their GDP-dependent association and membrane binding.
Transducin is an unusually soluble and dissociable heterotrimeric G-protein, although its T alpha and T beta gamma subunits are N-acylated and farnesylated, respectively. These lipid modifications have been suggested to contribute directly to the GDP-dependent T alpha-T beta gamma association, through specific lipid recognition sites on both protein subunits. We studied the dependence of subunit association on their bound lipids and on the presence of different lipidic environments. Association of native N-acylated (nT alpha) or acyl-free recombinant (rT alpha) T alpha with farnesylated and carboxymethylated (fcT beta gamma), farnesylated (fT beta gamma), or farnesyl-free (dfT beta gamma) T beta gamma was analyzed by gradient centrifugation and gel filtration in the presence of detergent or phospholipid-cholate micelles and by cosedimentation with phospholipid vesicles. Without detergent, nT alpha GDP and fcT beta gamma associate only weakly in solution. The loss of T alpha acyl or T beta gamma farnesyl residues induces total dissociation. With detergent or lipids, isolated fcT beta gamma binds tightly to micelles or vesicles, while dfT beta gamma does not; nT alpha GDP binds weakly, while deacylated rT alpha GDP does not bind at all; and nT alpha GDP binds cooperatively with fcT beta gamma, while rT alpha GDP does not. Thus (i) the T alpha acyl chain binds weakly, whereas the T beta gamma farnesyl chain binds strongly to membrane lipids; (ii) there is no evidence for binding of the T alpha acyl chain to a polypeptide site in T beta gamma, nor for binding of the T beta gamma farnesyl chain to a polypeptidic site in T alpha, but the T alpha acyl chain seems to bind cooperatively with the T beta gamma farnesyl chain in the membrane lipids; (iii) the insertion of the two protein-attached lipids into the same membrane could contribute to the association of both subunits by favoring collision coupling of the properly oriented protein moieties on the membrane surface.


Hydrogen and Water Bonding between Glycosaminoglycans and Phospholipids in the Synovial Fluid: Molecular Dynamics Study.
Synovial fluid is a lubricant of the synovial joint that shows remarkable tribological properties. These properties originate in the synergy between its components, with two of its major components, glycosaminoglycans (GAGs) and phospholipids (PLs), playing a major role in boundary and mixed lubrication regimes. All-atom molecular dynamic simulations were performed to investigate the way these components bond. Hyaluronic acid (HA) and chondroitin sulphate (CS) bonding with three types of lipids was tested. The results show that both glycosaminoglycans bind lipids at a similar rate, except for 1,2-d-ipalmitoyl-sn-glycero-3-phosphoethanolamine lipids, which bind to chondroitin at a much higher rate than to hyaluronan. The results suggest that different synovial fluid lipids may play a different role when binding to both hyaluronan and chondroitin sulphate. The presented results may help in understanding a process of lubrication of articular cartilage at a nanoscale level.


Criminal offending among respondents to protective orders: crime types and patterns that predict victim risk.
Research has shown that respondents to protective orders have robust criminal histories and that criminal offending behavior often follows issuance of a protective order. Nonetheless, the specific nature of the association between protective orders and criminal offending remains unclear. This study uses two classes of statistical models to more clearly delineate that relationship. The models reveal factors and characteristics that appear to be associated with offending and protective order issuance and provide indications about when a victim is most at risk and when the justice system should be most ready to provide immediate protection.


How closely do the delta(13)C values of Crassulacean Acid metabolism plants reflect the proportion of CO(2) fixed during day and night?
The extent to which Crassulacean acid metabolism (CAM) plant delta(13)C values provide an index of the proportions of CO(2) fixed during daytime and nighttime was assessed. Shoots of seven CAM species (Aloe vera, Hylocereus monocanthus, Kalanchoe beharensis, Kalanchoe daigremontiana, Kalanchoe pinnata, Vanilla pauciflora, and Xerosicyos danguyi) and two C(3) species (teak [Tectona grandis] and Clusia sp.) were grown in a cuvette, and net CO(2) exchange was monitored for up to 51 d. In species exhibiting net dark CO(2) fixation, between 14% and 73.3% of the carbon gain occurred in the dark. delta(13)C values of tissues formed inside the cuvette ranged between -28.7 per thousand and -11.6 per thousand, and correlated linearly with the percentages of carbon gained in the light and in the dark. The delta(13)C values for new biomass obtained solely during the dark and light were estimated as -8.7 per thousand and -26.9 per thousand, respectively. For each 10% contribution of dark CO(2) fixation integrated over the entire experiment, the delta(13)C content of the tissue was, thus, approximately 1.8 per thousand less negative. Extrapolation of the observations to plants previously surveyed under natural conditions suggests that the most commonly expressed version of CAM in the field, "the typical CAM plant," involves plants that gain about 71% to 77% of their carbon by dark fixation, and that the isotopic signals of plants that obtain one-third or less of their carbon in the dark may be confused with C(3) plants when identified on the basis of carbon isotope content alone.


Radioimmunoassay of fragment E-related neoantigen: validation studies and clinical application.
Measurement of fibrinogen-fibrin degradation products (FDP) levels in plasma may provide a direct index of plasmin action, and increased levels of FDP would indicate coagulopathy. We have established an E-neoantigen radioimmunoassay ( Eneo RIA) that can determine normal and pathological plasma levels of E-related FDP. The assay employs rabbit antiserum produced against fragment E derived from a plasmin digest of fibrinogen and subsequently absorbed with fibrinogen. The absorbed antiserum contains antibodies which are equally reactive with fibrinogen derived E (Fg-E) and fibrin derived E (Fb-E) but not with fibrinogen at 1 mg/ml. The Eneo RIA was validated by assay parallelism and by recovery experiments. Plasma Eneo immunoreactivities in 14 normals were 4-22 ng/ml (mean 12.7 ng/ml). Plasma Eneo levels in 23 of 24 patients with neoplastic and haematological diseases were elevated above normal (range 27-2027 ng/ml). Unusually high Eneo values were observed with three patients whose diseases were complicated by either disseminated intravascular coagulation (DIC) or deep vein thrombosis. After heparin therapy, the Eneo level of a patient with chronic DIC declined. A pathological plasma was eluted from a Sephadex G-200 column and Eneo immunoreactivity was determined on the eluates. The gel filtration pattern of Eneo indicates that E-related FDP is a family of plasmic fragments derived from crosslinked fibrin.


Utility of Bone Marrow Biopsy and Aspirate for Staging of Diffuse Large B Cell Lymphoma in the Era of Positron Emission Tomography With 2-Deoxy-2-[Fluorine-18]fluoro-deoxyglucose Integrated With Computed Tomography.
About one-third of patients with diffuse large B cell lymphoma (DLBCL) have lymphomatous bone marrow involvement (BMI) at the time of diagnosis, and bone marrow aspirate/biopsy (BMAB) is considered the gold standard to detect such involvement. [18F] fluorodeoxyglucose positron emission tomography combined with computed tomography (PET-CT), has become standard pretreatment imaging in DLBCL and may be a noninvasive alternative to BMAB to ascertain BMI. Prior studies have suggested that PET-CT scan may obviate the need for BMAB as a component for staging patients with newly diagnosed DLBCL, but this is not yet a standard of practice. The aim of this retrospective study was to determine the accuracy of PET-CT in detecting BMI in DLBCL and to define 2-year and 5-year overall survival based on BMI by BMAB versus PET-CT. We reviewed institutional records of all patients with newly diagnosed DLBCL between January 2004 and December 2013 who underwent pretreatment PET-CT and BMAB. PET-CT images were visually assessed for BMI, including the posterior iliac crest. Patients with primary mediastinal DLBCL, previous history or coexistence of another lymphoma subtype, and those with a nondiagnostic BMAB, and in whom the PET-CT did not show marrow signal abnormality, were excluded from the analysis. Ann Arbor stage was determined using PET-CT with and without the contribution of BMAB, and the proportion of stage IV cases by each method was measured. Among 99 eligible patients, the median age was 62 years (range, 24-88 years), 62 (63%) were male, 53 (53%) had elevated serum lactate dehydrogenase, and 17 (16%) had an Eastern Community Oncology Group performance status of > 2. Thirteen (12%) patients had more than 1 extra-nodal site of lymphoma involvement. Revised International Prognostic Index score was 1 in 39 (37%) patients, 2 in 42 (40%) patients, 3 in 20 (19%) patients, and 4 in 4 (4%) patients. A total of 38 (36%) patients had BMI established by either PET-CT (n = 24; 24%), BMAB (n = 14; 14%), or by both modalities (n = 12; 12%). Twelve (50%) of the 24 patients with positive PET-CT had BMI by DLBCL, whereas only 2 (3%) of the 75 patients with negative PET-CT showed BMI. BMAB upstaged 1 (2%) of the 53 stage I/II patients to stage IV. The sensitivity and specificity of PET-CT scan to detect BMI by DLBCL was 86% (95% confidence interval, 51.9%-95.7%) and 87% (95% confidence interval, 76%-92%), respectively. Eighty-five (86%) patients had concordant results between lymphomatous BMAB and PET-CT (12 patients were positive for both; 73 patients were negative for both), and 14 (14%) patients had a discordant interpretation (2 patients were positive by BMAB and negative by PET-CT, and 12 patients were negative by BMAB and positive by PET-CT). The positive predictive value of PET-CT was only 50%, whereas the negative predictive value was 98%. The accuracy of PET-CT was 86%. Although patients with positive BMAB had inferior 5-year overall survival estimates compared with those with negative BMAB (66% vs. 85%; P = .08), no such difference was demonstrated between PET-CT-positive and PET-CT-negative patients (79% vs. 83%; P = .30). In patients with newly diagnosed DLBCL, PET-CT is accurate in detecting BMI by DLBCL. Although PET-CT has a very high negative predictive value for BMI, it overestimates the number of cases with marrow involvement by DLBCL. In clinical practice, routine BMAB may no longer be necessary for all patients with DLBCL who are staged by PET-CT, unless the results would change both staging and therapy. The prognostic implication of BMI identified by PET-CT compared with BMAB remains unknown. Whether a PET-CT precludes the need for a BMAB in patients with DLBCL remains to be evaluated in a prospective study.


Characterization of bidirectional gene pairs in The Cancer Genome Atlas (TCGA) dataset.
The "bidirectional gene pair" indicates a particular head-to-head gene organization in which transcription start sites of two genes are located on opposite strands of genomic DNA within a region of one kb. Despite bidirectional gene pairs are well characterized, little is known about their expression profiles and regulation features in tumorigenesis. We used RNA-seq data from The Cancer Genome Atlas (TCGA) dataset for a systematic analysis of the expression profiles of bidirectional gene pairs in 13 cancer datasets. Gene pairs on the opposite strand with transcription end site distance within one kb or on the same strand with the distance of two genes between 1-10 kb and gene pairs comprising two randomly chosen genes were used as control gene pairs (CG1, CG2, and random). We identified and characterized up-/down-regulated genes by comparing the expression level between tumors and adjacent normal tissues in 13 TCGA datasets. There were no consistently significant difference in the percentage of up-/down-regulated genes between bidirectional and control/random genes in most of TCGA datasets. However, the percentage of bidirectional gene pairs comprising two up- or two down-regulated genes was significantly higher than gene pairs from CG1/2 in 12/11 analyzed TCGA datasets and the random gene pairs in all 13 TCGA datasets. Then we identified the methylation correlated bidirectional genes to explore the regulatory mechanism of bidirectional genes. Like the differentially expressed gene pairs, the bidirectional genes in a pair were significantly prone to be both hypo- or hyper-methylation correlated genes in 12/13 TCGA datasets when comparing to the CG2/random gene pairs despite no significant difference between the percentages of hypo-/hyper-methylation correlated genes in bidirectional and CG2/random genes in most of TCGA datasets. Finally, we explored the correlation between bidirectional genes and patient's survival, identifying prognostic bidirectional genes and prognostic bidirectional gene pairs in each TCGA dataset. Remarkably, we found a group of prognostic bidirectional gene pairs in which the combination of two protein coding genes with different expression level correlated with different survival prognosis in survival analysis for OS. The percentage of these gene pairs in bidirectional gene pair were significantly higher than the gene pairs in controls in COAD datasets and lower in none of 13 TCGA datasets.


Molecular understanding of ion specificity at the peptide bond.
The Hofmeister series has remained a mystery for more than a century. A detailed understanding of the interactions in ion-dissolved systems is still needed because the classical theories have failed to accommodate the specific ion effects. In this study, the interactions between ions, solvent and a model compound for proteins were explored using a direct nuclear magnetic resonance (NMR) approach along with density functional theory (DFT) calculations. It was found that the chaotropic anions caused increasing chemical shifts of the model compound, while kosmotropic anions resulted in decreasing shifts; this suggests that the kosmotropic anions were prevented from interacting with the model compound. The experimental results can be explained by a combination of local electrostatic interactions and hydrogen bonding. Although more effort are required to justify the NMR method applied in this study, the results could give a quantitative standard for defining kosmotropes/chaotropes and might provide a new way for predicting the effects of unfamiliar ions in the future.


Combining the hok/sok, parDE, and pnd postsegregational killer loci to enhance plasmid stability.
To enhance plasmid segregational stability in bacterial cells, two pairs of independent postsegregational killing loci (genes which induce host killing upon plasmid loss) isolated from plasmids R1, R483, or RP4 (hok+/sok+ pnd+ or hok+/sok+ parDE+) were cloned into a common site of the beta-galactosidase expression vector pMJR1750 (ptac::lacZ+) to form a series of plasmids in which the effect of one or two stability loci on segregational plasmid stability could be discerned. Adding two antisense killer loci (hok+/sok+ pnd+) decreased the specific growth rate by 50% though they were more effective at reducing segregational instability than hok+/sok+ alone. With the ptac promoter induced fully (2.0 mM isopropyl-beta-D-thiogalactopyranoside) and no antibiotic selection pressure, the combination of a proteic killer locus (parDE+) with antisense killer loci (hok+/sok+) had a negligible impact on specific growth rate, maintained high beta-galactosidase expression, and led to a 30 and 190% increase in segregational stability (based on stable generations) as compared to plasmids containing either hok+/sok+ or parDE+ alone, respectively. Use of hok+/sok+ or parDE+ alone with high cloned-gene expression led to ninefold and fourfold increases in the number of stable generations, respectively. Two convenient cloning cassettes have been constructed to facilitate cloning the dual hok+/sok+ parDE+ and hok+/sok+ pnd+ killer systems.


Improvement of Diet-induced Obesity by Ingestion of Mushroom Chitosan Prepared from Flammulina velutipes.
The anti-obesity effects of mushroom chitosan prepared from Flammulina velutipes were investigated using an animal model with diet-induced obesity. In this study, 5-week-old imprinting control region (ICR) mice were divided into six groups of 10 mice each and fed different diets based on the MF powdered diet (standard diet) for 6 weeks: standard diet control group, high-fat diet control group (induced dietary obesity) consisting of the standard diet and 20% lard, and mushroom chitosan groups consisting of the high-fat diet with mushroom chitosan added at 100, 500, 1,000, and 2,000 mg/kg body weight. On the final day of the experiment, mean body weight was 39.1 g in the high-fat control group and 36.3 g in the 2,000 mg/kg mushroom chitosan group, compared to 35.8 g in the standard diet control group. In the mushroom chitosan groups, a dose-dependent suppression of weight gain and marked improvements in serum triglycerides, total cholesterol, LDL-cholesterol, and HDL-cholesterol were found. The mushroom chitosan groups showed fewer and smaller fat deposits in liver cells than the high-fat diet control group, and liver weight was significantly reduced. Glutamic oxaloacetic transaminase (GOT) and glutamate pyruvic transaminase (GPT), which are indices of the hepatic function, all showed dose-dependent improvement with mushroom chitosan administration. These results suggested that mushroom chitosan acts to suppress enlargement of the liver from fat deposition resulting from a high-fat diet and to restore hepatic function. The lipid content of feces showed a marked increase correlated with the mushroom chitosan dose. These findings suggest the potential use of mushroom chitosan as a functional food ingredient that contributes to the prevention or improvement of dietary obesity by inhibiting digestion and absorption of fats in the digestive tract and simultaneously promotes lipolysis in adipocytes.


Effects of veratridine and cocaine on the kinetics of synaptosomal dopamine release.
Following preloading of striatal synaptosomes with 3H-dopamine (DA), the kinetics of release have been followed for a 60-min incubation period. DA appears to be totally releasable under both depolarizing (veratridine) and nondepolarizing conditions. Cocaine has no significant effect on release under either condition. Release is consistent with a model consisting of two parallel, linear compartments (when plotted as a log function). It is proposed that the slower compartment might represent the operation of the DA transporter, while the faster compartment might represent vesicular release.


Congenital syphilis presenting as swelling of fingers and toes.
Congenital syphilis has varied manifestations in first two years of life. A case of 4-month-old child who was presented with painless swelling of finger and toes is reported. Family history was suggestive of syphilis in parents and one sibling. VDRL test in serum was positive in 1:128 dilution. Treponema pallidum haemagglutination test was positive. The child was treated with crystalline penicillin and responded favourably.


Enhancement of DL-ethionine-induced liver carcinogenesis in rats fed a choline-devoid diet.
The effects of a choline-devoid (CD) or a choline-supplemented (CS) diet on the induction of liver tumors in rats by DL-ethionine were investigated. Groups of male outbred Sprague-Dawley rats were fed a plain CD or a plain CS diet, or the same diets containing 0.05% DL-ethionine. Hepatocellular carcinomas developed in 50% of the rats fed the CD+ethionine diet for 14 weeks and in about 80% of the rats fed the same diet for 22-30 weeks. No hepatocellular carcinomas developed in rats fed the CS+ethionine diet, the plain CD diet, or the plain CS diet up to 30 weeks. The findings suggest that a CD diet alters the response of rat liver to DL-ethionine and leads to an early and enhanced induction of hepatocellular carcinoma.


Environmental influence on the preclinical evaluation of substance use disorder therapeutics.
Substance use disorders (SUD) develop as a result of complex interactions between the environment, the subject, and the drug of abuse. Preclinical basic research investigating each of these tripartite components of SUD individually has resulted in advancements in our fundamental knowledge regarding the progression from drug abuse to SUD and severe drug addiction and the underlying behavioral and neurobiological mechanisms. How these complex interactions between the environment, the subject, and the drug of abuse impact the effectiveness of candidate or clinically used medications for SUD has not been as extensively investigated. The focus of this chapter will address the current state of our knowledge how these environmental, subject, and pharmacological variables have been shown to impact candidate or clinical SUD medication evaluation in preclinical research using drug self-administration procedures as the primary dependent measure. The results discussed in this chapter highlight the importance of considering environmental variables such as the schedule of reinforcement, concurrent availability of alternative nondrug reinforcers, and experimental housing conditions in the context of SUD therapeutic evaluation. The thesis of this chapter is that improved understanding of environmental variables in the context of SUD research will facilitate the utility of preclinical drug self-administration studies in the evaluation and development of candidate SUD therapeutics.


[Ultrasonic assessment of the ankle joint in supination trauma].
Comparing 20 healthy subjects to 31 injured patients in this study it is demonstrated that ultrasound examination appears to be a reliable tool in the diagnosis of ligamentous inversion force injuries of the ankle. The ultrasound diagnosis was confirmed by conventional standard and on the tension X-Rays. When lateral collateral ligaments were ruptured mean differences of 2.3 mm for the anterior talofibular ligament and 5.5 mm for the calcaneofibular ligament, respectively were obtained between X-Rays in standard and on the tension position. In comparison, the values in the control group (no ankle injury) were 1.4 mm and 2.2 mm respectively. The results shown in this study are mainly in keeping with the present literature.


Utility of the LigaSure vessel sealing system during major head and neck cancer surgery.
To evaluate the haemostatic efficacy and safety of the LigaSure vessel sealing system in major head and neck cancer surgery. This two-year, prospective study included 34 patients who underwent major head and neck cancer surgery at a university hospital. The LigaSure Precise handpiece and LigaSure 8 vessel sealing system were utilised as the primary means of haemostasis, except when sealing vessels larger than 7 mm in diameter. Surgical outcomes were evaluated. In addition, in each patient the diameter of the largest vein and artery sealed (all were >2 mm) was measured before sealing. In all cases except one (33/34 patients), a sutureless technique was performed. Post-operative bleeding was observed in two cases. Thirty veins and 22 arteries were measured. The mean diameter of the largest sealed vein was 3.8 mm, while that of the largest sealed artery was 2.7 mm. Our experience indicates that the surgical technique described is safe and effective. The main advantages of the LigaSure system are that it simplifies the procedure and eliminates the need for clips and suture ligations.


Effects of the odorant Hedione on the human stress response.
Olfactory cues can affect subjective and autonomic manifestations of the human stress response, but evidence of altered endocrine stress reactivity is inconclusive. In the present study, we investigated effects of the odorant Hedione on the human stress response. We exposed 56 women in their follicular phases to a stressor in a room scented with Hedione or no odor. Subjective stress was captured via repeated self-report measurements and the assessment of anticipatory appraisal. As physiological markers of stress, we assessed blood pressure, salivary cortisol and alpha-amylase. The odorant enhanced the cortisol and cardiovascular stress response while leaving subjective stress unaffected. Our results provide evidence for a modulation of the human response to acute psychosocial stress by Hedione. A potential mechanism underlying this effect is Hedione targeting the hypothalamus via binding to the VN1R1 receptor, which is expressed on the human nasal mucosa.


Lead Integrity Alert Triggered by T-wave Oversensing.
T-wave oversensing (TWOS) is a relatively common occurrence in pacemakers and defibrillators that can lead to pauses and inappropriate implantable cardioverter-defibrillator shocks. We present a case of TWOS that triggered the Lead Integrity Alert (Medtronic, Minneapolis, MN, USA) without evidence of actual lead failure.


Epithelial repair mechanisms in the lung.
The recovery of an intact epithelium following lung injury is critical for restoration of lung homeostasis. The initial processes following injury include an acute inflammatory response, recruitment of immune cells, and epithelial cell spreading and migration upon an autologously secreted provisional matrix. Injury causes the release of factors that contribute to repair mechanisms including members of the epidermal growth factor and fibroblast growth factor families (TGF-alpha, KGF, HGF), chemokines (MCP-1), interleukins (IL-1beta, IL-2, IL-4, IL-13), and prostaglandins (PGE(2)), for example. These factors coordinate processes involving integrins, matrix materials (fibronectin, collagen, laminin), matrix metalloproteinases (MMP-1, MMP-7, MMP-9), focal adhesions, and cytoskeletal structures to promote cell spreading and migration. Several key signaling pathways are important in regulating these processes, including sonic hedgehog, Rho GTPases, MAP kinase pathways, STAT3, and Wnt. Changes in mechanical forces may also affect these pathways. Both localized and distal progenitor stem cells are recruited into the injured area, and proliferation and phenotypic differentiation of these cells leads to recovery of epithelial function. Persistent injury may contribute to the pathology of diseases such as asthma, chronic obstructive pulmonary disease, and pulmonary fibrosis. For example, dysregulated repair processes involving TGF-beta and epithelial-mesenchymal transition may lead to fibrosis. This review focuses on the processes of epithelial restitution, the localization and role of epithelial progenitor stem cells, the initiating factors involved in repair, and the signaling pathways involved in these processes.


Multimodality imaging of spleen involvement in Erdheim-Chester disease mimicking splenic hemangioma: a unique case report.
Erdheim-Chester disease (ECD) is a rare and clinically heterogeneous non-Langerhans cell histiocytosis, and its diagnosis relies on established clinical, radiologic, histopathological criteria. ECD can be evaluated by whole-body preoperative imaging methods. Although 18F-FDG PET/CT shows negative findings in some splenic benign or borderline lesions, such as splenic inflammatory myofibroblastic tumors and hemangioendotheliomas, it can provide value in differentiating some malignant diseases, such as hemangiosarcoma and metastases. Here, we report the CT, MRI, and 18F-FDG PET/CT imaging performance of an ECD patient who presented with only spleen involvement. Even though some clinical and radiological descriptions can be found in the literature, ECD reports with only splenic involvement mimicking splenic hemangioma as the first presentation are rare, to the best of our knowledge. Histopathology and molecular analysis of this case confirmed the diagnosis of ECD. Clinicians should pay attention to the possibility of ECD occurrence in the spleen, while negative findings on 18F-FDG PET/CT of the spleen indicated a low risk for high-grade malignant splenic tumors and metastases.


Hepatoprotective effects of rice-derived peptides against acetaminophen-induced damage in mice.
Glutathione, the most abundant intracellular antioxidant, protects cells against reactive oxygen species induced oxidative stress and regulates intracellular redox status. We found that rice peptides increased intracellular glutathione levels in human hepatoblastoma HepG2 cells. Acetaminophen is a commonly used analgesic. However, an overdose of acetaminophen causes severe hepatotoxicity via depletion of hepatic glutathione. Here, we investigated the protective effects of rice peptides on acetaminophen-induced hepatotoxicity in mice. ICR mice were orally administered rice peptides (0, 100 or 500 mg/kg) for seven days, followed by the induction of hepatotoxicity via intraperitoneal injection of acetaminophen (700 mg/kg). Pretreatment with rice peptides significantly prevented increases in serum alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase levels and protected against hepatic glutathione depletion. The expression of γ-glutamylcysteine synthetase, a key regulatory enzyme in the synthesis of glutathione, was decreased by treatment with acetaminophen, albeit rice peptides treatment recovered its expression compared to that achieved treatment with acetaminophen. In addition, histopathological evaluation of the livers also revealed that rice peptides prevented acetaminophen-induced centrilobular necrosis. These results suggest that rice peptides increased intracellular glutathione levels and could protect against acetaminophen-induced hepatotoxicity in mice.


Analyzing transformation of myelodysplastic syndrome to secondary acute myeloid leukemia using a large patient database.
One-third of patients with myelodysplastic syndrome (MDS) progress to secondary acute myeloid leukemia (sAML), with its concomitant poor prognosis. Recently, multiple mutations have been identified in association with MDS-to-sAMLtransition, but it is still unclear whether all these mutations are necessary for transformation. If multiple independent mutations are required for the transformation, sAML risk should increase with time from MDS diagnosis. In contrast, if a single critical biological event determines sAML transformation; its risk should be constant in time elapsing from MDS diagnosis. To elucidate this question, we studied a database of 1079 patients with MDS. We classified patients according to the International Prognostic Scoring System (IPSS), using either the French-American-British (FAB) or the World Health Organization (WHO) criteria, and statistically analyzed the resulting transformation risk curves of each group. The risk of transformation after MDS diagnosis remained constant in time within three out of four risk groups, and in all four risk groups, when patients were classified according to FAB or to the WHO-determined criteria, respectively. Further subdivision by blast percentage or cytogenetics had no influence on this result. Our analysis suggests that a single random biological event leads to transformation to sAML, thus calling for the exclusion of time since MDS diagnosis from the clinical decision-making process.


IL-6, IL-10 and TNF-α gene polymorphisms in preeclampsia: a case-control study in a Mexican population.
We focused our study on examining the genotype and allele frequency of IL-6 (rs1800795), TNF-α (rs1800629) and IL-10 (rs1800872) single nucleotide polymorphisms (SNP) on preeclampsia (PE) diagnosed Mexican pregnant women. A case-control study was designed including 86 preeclampsia patients and 100 normotensives pregnancies from Women's Hospital of Culiacan, Mexico. Genotyping of IL-6, TNF-α and IL-10 was performed using TaqMan SNP Genotyping. Not significant association was found between development of PE and genotypic (p > 0.05) and allelic (p > 0.05) frequencies of IL-6, TNF-α and IL-10 SNPs. Genotype distributions of IL-6 (p = 0.599), TNF-α (p = 0.721) and IL-10 (p = 0.761) polymorphisms in the two groups were in agreement with Hardy-Weinberg equilibrium. According to the findings, the IL-6, TNF-α and IL-10 SNPs are not exponents of susceptibility to developing PE.


Comparison of speech-language pathologists' and naive subjects' identification of synthesized /r-w/ continua.
Two 9-step continua varying in F2 and F3 frequencies between exemplary /r/ and /w/ were synthesized to represent child and adult talkers. Stimuli from the full and truncated versions of the continua were presented to naive subjects in Experiment 1 and to speech-language pathologists in Experiment 2. Shifts from full range continua category boundaries occurred in Experiment 1 for both truncated "R" and truncated "W" conditions and in a direction opposite to the truncated end of the continuum. The results of Experiment 2 indicated that the full-range category boundaries for speech-language pathologists differed from those for naive subjects but that the boundary shift for truncated "R" was as great as that for naive subjects and the boundary shift for truncated "W" was greater than that for naive subjects. These findings indicate that speech-language pathologists are more likely than naive individuals to judge ambiguous /r/ sounds as "W" and that the phonetic judgments of speech-language pathologists about /r/ sounds are no more stable than those of naive subjects.


Flow cytogenetics.
Applications of flow karyotype analysis and flow chromosome sorting are being developed and are becoming increasingly relevant to clinical research. Among these applications are the quantitative analysis of chromosomal DNA content changes enabling the detection of minute deletions or unbalanced translocations, the quantitative analysis of aneuploidy for trisomy screening, and the sorting of derivative chromosomes for mapping chromosome breakpoints. Flow karyotyping has been accomplished on samples with clinical relevance including peripheral blood from both children and cancer patients as well as amniotic cell cultures. New techniques in flow cytogenetics to resolve chromosomes by morphology or by DNA sequence hybridizations are assessed for their promise. Although flow karyotyping has not yet developed into an 'automated' karyotyping technique, when used in conjunction with classical cytogenetic techniques, new information of significance to the clinician can be produced.


Behavioural Differences Between Online Sexual Groomers Approaching Boys and Girls.
This study focused on the behavior of convicted offenders who had approached profiles of boys and girls online for offline sexual encounters. A detailed coding scheme was designed to code and analyze offenders' grooming behaviors in transcripts of conversational interactions between convicted offenders and 52 volunteer workers purporting to be girls and 49 volunteer workers who masqueraded as boys. Behavioral differences and commonalities associated with the gender of the groomed child decoys were examined. Results showed that offenders approaching boys were significantly older and pretended to be younger than offenders approaching girls. When compared to offenders grooming boy decoys, offenders grooming girl decoys typically built more rapport, were less sexually explicit, and approached sexual topics carefully and indirectly. Offenders also used more strategies to conceal contact with girls than with boys.


Red blood cell transfusions alter splanchnic oxygenation response to enteral feeding in preterm infants: an observational pilot study.
Preterm infants often require red blood cell (RBC) transfusions, which may impair splanchnic hemodynamics, thus predisposing to necrotizing enterocolitis (NEC). The aim of this study was to evaluate whether RBC transfusions alter splanchnic oxygenation patterns in response to enteral feeding in this population. Preterm neonates (gestational age < 32 weeks and/or birth weight < 1500 g) requiring RBC transfusions for anemia underwent a 12-hour Near Infrared Spectroscopy monitoring of splanchnic (SrSO2 ) and cerebral (CrSO2 ) oxygenation, including the transfusion period, one feed before and one after. Splanchnic-cerebral oxygenation ratio (SCOR) was also calculated. Patterns of CrSO2 , SrSO2 , and SCOR changes from baseline (Δ) in response to feed before and after transfusion were analyzed. Twenty neonates were enrolled; none of them developed any gastrointestinal complication within 48 hours after transfusion. Pre-transfusion ΔSrSO2 and ΔSCOR increased significantly in response to feeding; on the contrary, a significant post-prandial decrease of ΔSrSO2 and ΔSCOR occurred after transfusion (p < 0.05). No difference in pre- and post-transfusion ΔCrSO2 patterns was observed. In preterm infants, RBC transfusions may alter splanchnic oxygenation response to enteral feeds. Whether these changes are involved in the pathogenesis of transfusion-associated NEC has to be evaluated in further larger trials.


[Anesthetic Management of a Patient who Developed Intraoperative Paroxysmal Supraventricular Tachycardia with Pulseless Electric Activity].
A 75-year-old woman was scheduled to undergo an ileus operation under general combined with epidural anesthesia. Preoperative electrocardiogram (ECG) showed first-degree atrioventricular block. The patient received no preoperative antiarrhythmic medication. During surgery, paroxysmal supraventricular tachycardia (PSVT) occurred unexpectedly with radial artery pulsation disappearing, indicating pulseless electric activity (PEA). After a five-second episode of PSVT, her sinus rhythm recovered spontaneously. However, the patient had repeated short duration of PSVT with PEA. Continuous infusion of ultra-short-acting β-blocker landiolol successfully terminated the PSVT, and sinus rhythm was restored. Postoperative ECG showed sinus rhythm. This case report indicates that β-blocker can be a drug of choice in patients with PSVT associated with PEA.


[Calcium in aging, health, and anti-aging. Significance of calcium supplement for anti-aging].
For prevention of osteoporosis and debilitating bone fractures, poor calcium intake has long been a major public health problem in Japan. However, few randomized controlled studies have been conducted to clarify the relationship between calcium intake and bone mineral density, and the effect of the prevention of bone fractures. Therefore we reviewed the articles about the evidence for calcium intake and bone fracture incidence in European, American and Asian. We get the results that many articles supported the basis of current health guidelines for the prevention of osteoporosis that recommended increasing calcium intake to the recommended age-related daily allowance levels.


[Filtration of platelet concentrates. Technical aspects, quantitative results. Group PSL].
This work summarizes a multicentric study (20 Blood Transfusion Centers) concerning the use of different filters applied to platelet collection. The results are good with the different filters and platelets concentrates evaluation. Nevertheless, we have seen a great heterogeneity of platelet concentrates. This characteristic could explain the variability in filter performances. Maybe we have to adapt some type of filter with specific platelet concentrates. In conclusion, it is important to continue the evaluation of new platelet concentrate filters, in order to increase the performances and the filtration quality. Clinical trials seem to be useful in the future to appreciate the effects of filtered platelets on alloimmunization and CMV transmission.


Absence of TGF-β Receptor Activation by Highly Purified hCG Preparations.
Recently, several LH/human chorionic gonadotropin (hCG) receptor-independent activities for hCG have been described, including activation of the TGF-β receptor (TGFβR) by hyperglycosylated hCG and stimulation of trophoblast invasion. Because the hCG concentrations used in these studies have been rather high, reflecting physiological hCG levels in pregnancy, even a minor contamination with growth factors, which act at very low concentrations, may be significant. Several commercial hCG preparations have been found to contain significant amounts of epidermal growth factor (EGF), which we also confirmed here. Furthermore, we found that some hCG preparations also contain significant amounts of TGF-β1. These hCG preparations were able to activate ERK1/2 in JEG-3 choriocarcinoma cells or TGFβR in mink lung epithelial cells transfected with a reporter gene for TGFβR activation. No such activation was found with highly purified hCG or its free β-subunit (hCGβ), irrespective of whether they were hyperglycosylated or not. Taken together, our results suggest that the growth factor contaminations in the hCG preparations can cause activation of TGFβR and, at least in JEG-3 cells, MAPK signaling. This highlights the importance to carefully control for potential contaminations and that highly purified hCG preparations have to be used for biological studies.


Smooth muscle tumor of uncertain malignant potential (STUMP): a clinicopathologic analysis of 26 cases.
To investigate the clinicopathologic features, differential diagnosis, and factors associated with recurrence in patients with smooth muscle tumors of uncertain malignant potential (STUMP). The clinical and pathologic data of STUMP patients diagnosed in Mindong Hospital of Ningde City from 2017 to 2018 were collected and slides reviewed, the high-frequency color Doppler ultrasound and pathological characteristics were observed, and the literature was reviewed. All the STUMP diagnoses were confirmed by slide review. The age of onset was 23-61 years (mean 42.96 years). The main clinical symptoms were leiomyoma of uterus, prolonged menstruation, and increased menstruation. Color Doppler ultrasonography showed hypoechoic uterine wall nodules. The mean follow-up time was 62.9 months (range: 13-96 months). Smooth muscle tumors of undetermined malignant potential (STUMP) in the uterus are one of the rare gynecologic neoplasms. Although not malignant, they should be considered as low malignant potential tumors because they occasionally recur. Six of 13 recurrent tumors recurred in the years following hysterectomy with preservation. These six recurrent tumors are the only ones that had a strong immune response to p16 and p53. In support of early observation, these markers may help predict STUMP behavior. Patients diagnosed with STUMP should be monitored over time.


Investigating the performance of susceptibility-weighted images in Fricke gel dosimeter reading and optimizing the related imaging parameters.
Fricke gel dosimeters are especially useful in small-field dosimetry and validation of treatment delivery in three-dimensional space with features such as tissue equivalence, non-toxicity, high spatial resolution, non-dependence on energy, and dose rate. The use of basic Magnetic Resonance Imaging (MRI) protocols (T1- and T2-Weighted) for reading Fricke gel dosimeters has always been considered the dominant method in many studies. However, the development and application of advanced MRI techniques for more accurate readings of Fricke gel dosimeters can be useful. Considering that in the main structure of Fricke gel, there are conversions of iron ions to each other, this study aimed to investigate the performance of Susceptibility-Weighted Imaging (SWI) and Quantitative Susceptibility Mapping (QSM) based on magnetic susceptibility in the reading of Fricke gel dosimeters and to optimize the related imaging parameters. For this purpose, a Fricke-Xylenol orange-gelatin was made at five concentrations of iron ammonium sulfate. To obtain gel dosimeter calibration curves, vials containing gel were subjected to irradiation at three different doses by a linear accelerator. The reading of gel dosimeters was performed using MRI imaging in three protocols, T1W, T2W, and SWI, and analyzed with a method unique to each one. Finally, the results obtained from the three protocols were compared with each other. The comparison of calibration curves in three imaging protocols shows that the sensitivity of calibration curves in SWI was about three times its value in T2W, and on the other hand, the reported sensitivity in T1W was very small compared to the other two protocols. The linearity factor was similar between SWI and T1W protocols and higher in T2W. Therefore, it is concluded that in addition to the relaxometry techniques that have been used as a conventional method for reading Fricke gel dosimeter, SWI imaging has high sensitivity and specificity for reading dosimeter gel based on iron.