Spitz Tumor With SQSTM1::NTRK2 Fusion: A Clinicopathological Study of 5 Cases.
Spitz tumors are melanocytic neoplasms characterized by specific, mutually exclusive driver molecular events, namely genomic rearrangements involving the threonine kinase BRAF and the tyrosine kinase receptors ALK , NTRK1 , NTRK2 , NTRK3 , MET , RET , ROS1 , and MAP3K8 or less commonly, mutations in HRAS or MAP2K1 . We hereby report 5 Spitz tumors with a SQSTM1::NTRK2 fusion. All patients were woman with the ages at diagnosis ranging from 30 to 50 years. Locations included the lower extremity (n = 3), forearm, and back (one each). All the neoplasms were superficial melanocytic proliferation with a flat to dome-shaped silhouette, in which junctional spindled and polygonal dendritic melanocytes were mainly arranged as horizontal nests associated with conspicuous lentiginous involvement of the follicular epithelium. Only one case showed heavily pigmented, vertically oriented melanocytic nests resembling Reed nevus. A superficial intradermal component observed in 2 cases appeared as small nests with a back-to-back configuration. In all lesions, next-generation sequencing analysis identified a SQSTM1::NTRK2 fusion. A single case studied with fluorescence in situ hybridization for copy number changes in melanoma-related genes proved negative. No further molecular alterations were detected, including TERT-p hotspot mutations.


Baker's Cyst Filled with Hematoma at the Lower Calf.
Baker's cyst is a distension of the gastrocnemius-semimembranosus bursa of the knee, which communicates with the posterior portion of the joint capsule. Baker's cyst is commonly located in the inferomedial or superficial layers of the knee joint and rarely extends laterally or proximally. Complications of Baker's cysts are dissection, rupture, pseudothrombophlebitis, leg ischemia, nerve entrapment, and compartment syndrome. However, hematomas in the Baker's cyst have not been reported in Korea. We report a rare case of hematoma in the Baker's cyst with subfascial extension into the calf. The hematoma was demonstrated by magnetic resonance imaging and removed by mass excision.


Definitions and clinical impact of revascularization completeness.
The completeness of revascularization in patients with multivessel coronary artery disease (CAD) remains an unanswered question. Despite 20 years of investigation there are still major doubts in this topic, reaching as far as to the lack of a standardized definition. The employment of different definition and the multiplicity of confounding variables that in general favor patients who receive a complete revascularization (CR) are the reason of difficult comparisons between studies. The complexity of coronary anatomy diseases and the clinical features play important role in the revascularization strategy. However, the clinical impact of CR is different in particular clinical subsets, such as diabetes, ST-segment elevation myocardial infarction, cardiogenic shock, ischemic heart failure. The CR is a desirable objective, but it is not mandatory and sometimes a reasonable incomplete revascularization (IR) offers comparable results. Clinical variables, including patient's age, life expectancy, the severity of symptoms at presentation, comorbidities (particularly diabetes mellitus), left ventricular function and myocardial viability, as well as coronary anatomy should be considered in the decision making whether to attempt CR or to follow a reasonable IR strategy, for both percutaneous coronary intervention and coronary artery bypass graft surgery, in patients with multivessel CAD.


Missed and delayed diagnoses in the emergency department: a study of closed malpractice claims from 4 liability insurers.
Diagnostic errors in the emergency department (ED) are an important patient safety concern, but little is known about their cause. We identify types and causes of missed or delayed diagnoses in the ED. This is a review of 122 closed malpractice claims from 4 liability insurers in which patients had alleged a missed or delayed diagnosis in the ED. Trained physician reviewers examined the litigation files and the associated medical records to determine whether an adverse outcome because of a missed diagnosis had occurred, what breakdowns were involved in the missed diagnosis, and what factors contributed to it. Main outcome measures were missed diagnoses, process breakdowns, and contributing factors. A total of 79 claims (65%) involved missed ED diagnoses that harmed patients. Forty-eight percent of these missed diagnoses were associated with serious harm, and 39% resulted in death. The leading breakdowns in the diagnostic process were failure to order an appropriate diagnostic test (58% of errors), failure to perform an adequate medical history or physical examination (42%), incorrect interpretation of a diagnostic test (37%), and failure to order an appropriate consultation (33%). The leading contributing factors to the missed diagnoses were cognitive factors (96%), patient-related factors (34%), lack of appropriate supervision (30%), inadequate handoffs (24%), and excessive workload (23%). The median numbers of process breakdowns and contributing factors per missed diagnosis were 2 and 3, respectively. Missed diagnoses in the ED have a complex cause. They are typically the result of multiple breakdowns in the diagnostic process and several contributing factors.


Neural correlates of spontaneous percept switches in ambiguous stimuli: an event-related functional magnetic resonance imaging study.
When ambiguous visual stimuli are being looked at, perception alternates spontaneously between two competing interpretations of the same sensory input. One major issue in understanding the underlying neural process is whether spontaneous percept switches result from fluctuations at the level of sensory processes or whether they are initiated by higher-order areas. To further study this question, we developed an ambiguous apparent motion paradigm that specifically focused on the generation of percept switches. The percept switches occurred either spontaneously or were experimentally triggered. The differential analysis of spontaneous and triggered percept switches was aimed at disentangling the causes and effects of percept switches. Spontaneous percept switches were associated with stronger activations at the right occipitotemporal junction, whereas prefrontal, superior temporal and inferior parietal regions showed greater activations during experimentally triggered percept switches. We propose that complex networks including both sensory and higher-order areas are involved in percept switches, whereas stimulus-specific sensory processes are crucial for the initiation of spontaneous percept switches.


Peripheral hypertrophic subepithelial corneal degeneration.
To describe the clinical features, clinical course, and response to therapy of an atypical peripheral corneal opacification. Retrospective case series review. Six patients are described with similar findings of bilateral, fairly symmetric, peripheral, hypertrophic, subepithelial corneal opacification. All patients were female and had no concurrent systemic conditions. All six patients complained of ocular irritation. Three patients complained of blurred vision, and one patient had monocular diplopia. In three patients followed up for more than 30 months, the corneal opacification remained stable in one patient and enlarged in the other two patients. The other three patients were examined once or twice, so the evaluation of disease progression was precluded. Two patients were treated surgically with superficial keratectomy followed by 2-minute intraoperative application of 0.02% mitomycin-C. Pathologic examination of bilateral keratectomy specimens from one patient showed subepithelial fibrosis without inflammation. The clinical findings are reminiscent but atypical of Salzmann nodular degeneration.


Sex differences in somatic and sensory motor development after neonatal anoxia in Wistar rats.
Currently, one of the important causes of brain injury in new-borns is the neonatal anoxia which impacts the perinatology services worldwide. Animal models of anoxia have been used to assess its effects at cellular and behavioural levels in all ages, but few studies focus on sex differences. This study aimed to investigate some physical parameters of development, sensorimotor alterations, early neurological reflexes as well as the density of cells in motor and sensorimotor cerebral cortex of adolescent rats submitted to neonatal anoxia. The results presented significant differences in most of the evaluated parameters, such as body weight and lenght, medio-lateral head axis, eruption of superior incisor, palmar grasp, auditory startle, negative geotaxis, showing that neonatal anoxia affects physical parameters and neurological development, with sex differences. Cellular analysis revealed decreased amount of neurons in motor cortex and primary sensory hind limb and forelimb regions in anoxic group, along with gender difference, as compared to control groups. There is an important rationale for performing early assessment of sensorimotor deficits as there is similarity of the model with high risk human neonates and the sequelae in later life periods, which can be inferred from the present results with suggestion of a possible correlation between sensorimotor development delay and cellular changes in sensorimotor cortex. Furthermore, these observed sex dependent alterations certainly will address further studies and should be considered especially in treatments and strategies to avoid or minimize the neonatal anoxic effects.


Encoding with frames in MRI and analysis of the signal-to-noise ratio.
Recently, many new encoding techniques have been suggested for magnetic resonance imaging and an important image reconstruction problem has been raised in order to fully exploit the advantages promised by these new encoding techniques. In terms of frames in an L2 (R) space, we treat these encoding techniques in a unified perspective and propose a solution for this image reconstruction problem. We first develop a matrix form of frame theory and apply it to numerically construct the duals of the encoding functions, which are the transverse excitation profiles generated by radio-frequency pulses along a linear magnetic field gradient. An analysis of the signal-to-noise ratio (SNR) is also presented. Simulations have been carried out and they show that our image reconstruction algorithm minimizes the mean square error between the original and reconstructed images. The SNRs evaluated from simulations agree with our theoretical predictions.


The Edinburgh human metabolic network reconstruction and its functional analysis.
A better understanding of human metabolism and its relationship with diseases is an important task in human systems biology studies. In this paper, we present a high-quality human metabolic network manually reconstructed by integrating genome annotation information from different databases and metabolic reaction information from literature. The network contains nearly 3000 metabolic reactions, which were reorganized into about 70 human-specific metabolic pathways according to their functional relationships. By analysis of the functional connectivity of the metabolites in the network, the bow-tie structure, which was found previously by structure analysis, is reconfirmed. Furthermore, the distribution of the disease related genes in the network suggests that the IN (substrates) subset of the bow-tie structure has more flexibility than other parts.


Niobium-silica catalysts for the selective epoxidation of cyclic alkenes: the generation of the active site by grafting niobocene dichloride.
Niobium-containing silica materials obtained by deposition via liquid-phase grafting or dry impregnation of niobocene(iv) dichloride are active and selective catalysts in the epoxidation of alkenes in the presence of aqueous hydrogen peroxide. The generation of the catalytically-active Nb species was followed step-by-step, and investigated using a combined DR-UV-Vis, NIR, Raman, XRD, XANES and EXAFS analyses. At the end of the grafting procedure, the nature of the surface active species can be described as an oxo-Nb(v) site, tripodally grafted onto the silica surface in close proximity to other Nb(v) centres. The liquid-phase methodology provides a better dispersion of the metal sites onto the siliceous support than the dry-impregnation approach. The niobium-silica catalysts were then tested in the epoxidation of cyclohexene and 1-methylcyclohexene, as model substrates.


[Respiratory diseases and obesity: special phenotype or independent events: Review].
A combination of factors, including Western European eating habits, physical inactivity and genetic predisposition, lead to a dramatic increase in adipose tissue mass. A special place is occupied by abdominal obesity, in which there is an accumulation of adipose tissue in the mesentery of the small intestine and the omentum. Developing in conditions of visceral obesity, insulin resistance, dyslipidemia and systemic inflammation are one of the key components of the pathogenesis of type 2 diabetes mellitus, cardiovascular diseases, non-alcoholic fatty liver and pancreas disease, polycystic ovary disease, some forms of cancer (breast cancer, endometrial cancer, colonic and direct intestines). At the same time, the pathogenetic role of adipose tissue is not limited to its participation in the formation of the cardiometabolic continuum and oncogenesis. The most important role of metabolically active fat in the pathogenesis of many respiratory diseases is known, including bronchial asthma, obstructive sleep apnea and pulmonary hypertension. This paper presents an overview of current data on immunological, pathophysiological and clinical features of the phenotype of the combination of respiratory diseases with overweight and obesity.


Effects of oral administration of furosemide and torsemide in healthy dogs.
To investigate the diuretic effects, tolerability, and adverse effects of furosemide and torsemide after short- and long-term administration in healthy dogs. 8 mixed-breed dogs. In a crossover study, furosemide (2 mg/kg), torsemide (0.2 mg/kg), or placebo (bifidobacterium [1 mg/kg]) was administered orally to each dog every 12 hours for 14 days. Blood and urine samples were collected before the study (baseline data) and at intervals on the 1st (short-term administration) and 14th day (long-term administration) of treatment for assessment of urine volume and specific gravity and selected clinicopathologic variables including BUN, creatinine, and aldosterone concentrations, and creatinine clearance. Compared with the baseline value, short-term administration of furosemide or torsemide immediately increased urine volume significantly; after long-term administration of either drug, urine specific gravity decreased significantly. Compared with the effect of placebo, the 24-hour urine volume was significantly increased after short-term administra-tion of furosemide or torsemide. In addition, it was significantly increased after long-term administration of torsemide, compared with that of short-term administration. Long-term administration of furosemide or torsemide increased the BUN and plasma creatinine con-centrations, compared with the baseline value. Compared with the baseline value, plasma aldosterone concentration was significantly increased after long-term administration of either drug and was significantly higher after torsemide treatment than after furosemide treatment. In dogs, diuretic resistance developed after 14 days of furosemide, but not torsemide, administration; however, both loop diuretics were associated with increased BUN and plasma creatinine concentrations, compared with values before treatment.


Treatment options for androgen-independent prostate cancer.
Patients with recurrent prostate cancer may be treated with androgen deprivation strategies, but most patients will develop androgen-independent prostate cancer (AIPC). Current strategies for treatment of patients who develop AIPC have shown significant palliation, but no definitive increase in survival to date. The results of large chemotherapy trials with survival endpoints are expected soon. In addition, several novel drugs have proceeded through preclinical testing into early clinical trials. These drugs-either alone or in combination-are designed to target strategic pathways to improve survival and quality of life in patients. This article summarizes standard treatment options and promising new drugs and combination therapies under investigation for AIPC.


Analysis of the distinct features of metastasis male breast cancer and its effect on overall survival based on the SEER database compared with female breast cancer.
Male breast cancer (MBC) is a rare disease and differs from female breast cancer (FBC) in clinicopathological and immune tissue types. Given the limited research on MBC due to its rarity, an understanding of the shared and distinct features of MBC and FBC is vital for formulating efficacious treatment strategies. Data of patients diagnosed with metastatic breast cancer in the Surveillance, Epidemiology, and End Results (SEER) database from 2012 to 2017 were analysed. Chi-square test was used to compare clinicopathological characteristics between male and female patients. Kaplan-Meier analysis was utilized to compare differences in overall survival (OS). A total of 2,858 patients with MBC were studied, 134 of whom had distant metastasis. Compared with 8,698 patients with metastatic FBC, a higher proportion of metastatic MBC patients had tumors located in the center of the breast, received surgical treatment, and had bone + lung metastasis. Survival analysis revealed no difference in OS between metastatic MBC and FBC patients (P=0.27), but there was a significant difference in OS between metastatic and nonmetastatic MBC (P=0.004). Compared with metastatic FBC, MBC patients with bone metastasis alone, lung metastasis alone, liver metastasis alone, and bone + lung metastasis also had worse prognosis (P=0.021, 0.019, 0.024, 0.011, respectively). Metastatic MBC has unique clinicopathological disease features and patterns of metastasis. No significant difference between the survival of metastatic MBC and FBC patients was observed. Distant metastasis was an independent risk factor impacting the prognosis of MBC patients.


Essential updates 2021/2022: Perioperative and surgical treatments for gastric and esophagogastric junction cancer.
In recent years, important clinical trials for gastric cancer (GC) and esophagogastric junction cancer (EGJC) have been reported, changing the strategies of surgical and perioperative treatment. Although laparoscopic gastrectomy has already been shown to be effective for early-stage cancer, recent evidence from both Asia (JLSSG0901, CLASS-01 and KLASS-02) and Europe (LOGICA and STOMACH trials) has demonstrated that it is useful for advanced GC. Robotic surgery has been rapidly gaining popularity in recent years, and randomized controlled trials are ongoing to evaluate its efficacy. A prospective nationwide multicenter study mapped sites with frequent metastasis and revealed lymphatic flow specific to EGJC, thus establishing the optimal lymph node dissection area and surgical approach based on esophageal involvement. Perioperative chemotherapy, the mainstay of treatment in Europe, also has been established in Asia by the PRODIGY and RESOLVE studies. New clinical trials have been conducted to evaluate the efficacy of combining immunotherapy or molecular-targeted therapy with perioperative chemotherapy or chemoradiotherapy. In this review, we present important recent clinical trials regarding the treatment of GC and EGJC published in 2021 or 2022.


Neural induction and patterning by fibroblast growth factor, notochord and somite tissue in Xenopus.
Two natural neural inducing sources have been used, the notochord and the somites together with the growth factor bFGF, to investigate the anterior/posterior patterning of neural tissue in an animal cap explant model in Xenopus laevis. Notochord and somite tissue from stages 12.5/13 and 16, respectively, were manually isolated, and combined heterochronically with responding animal cap ectoderm aged to gastrula stages. Somite recombinants were also constructed with animal caps injected with noggin mRNA. The responses of the ectoderm were analyzed by reverse transcription polymerase chain reaction (RT-PCR) detection of marker gene expression, and in some cases by in situ hybridization. The requirement for FGF receptor function was analyzed using the dominant negative FGF receptor (XFD). The experiments showed that bFGF is capable of direct neural induction in caps aged to stage 10.5. It was also shown that notochords are capable of inducing anterior neural tissue in gastrula stage animal cap ectoderm, and this induction is sensitive to XFD in the responding tissue. Injection of noggin mRNA results in the induction of anterior neural differentiation, and it was demonstrated that this induction was insensitive to the expression of XFD in the responding tissue. It was also shown that somite tissue recombined with gastrula stage animal cap ectoderm, can induce both anterior and posterior nervous tissue and can also posteriorize noggin-induced anterior neural tissue when combined with noggin-injected animal cap ectoderm. This response is partially sensitive to XFD expression. The results shed light on the role of competence of animal cap ectoderm and the signals from postgastrulation axial and paraxial mesoderm in the patterning of the amphibian nervous system.


Effects of high potassium concentration and dihydropyridine Ca2(+)-channel agonists on cytoplasmic Ca2+ and aldosterone production in rat adrenal glomerulosa cells.
The aldosterone secretory response of isolated rat adrenal glomerulosa cells to potassium was studied in a cell-perifusion system. Increasing the potassium concentration from 3.6 to 5.4 mM in the perifusion medium caused a rapid 40-fold stimulation of aldosterone production which was maintained during the 2 h period of stimulation. A dose of 8.4 mM potassium elicited a 100-fold increase of hormone production with rapid onset and a slowly decreasing plateau. When the potassium concentration was further increased to 18 mM, there was a rapid stimulation of aldosterone production comparable to that evoked by 8.4 mM potassium; however, the response declined very rapidly to levels still above basal. The dihydropyridine-agonist BAY-K 8644 (100 nM) greatly enhanced the aldosterone response to 5.4 mM potassium but did not significantly modify the response evoked by 8.4 mM potassium. The effect of BAY-K 8644 on the aldosterone response was inhibitory at 18 mM potassium concentration, suggesting that the character of dihydropyridine modulation of the secretory response was voltage dependent, showing reversal at relatively negative potentials. When the cytoplasmic Ca2+ concentration was monitored in glomerulosa cells by the fluorescent Ca2(+)-probe Fura-2, potassium evoked a rapid dose-dependent increase in free Ca2+, with elevated steady-state Ca2(+)-levels throughout stimulation, even at potassium concentrations higher than 18 mM. Moreover, BAY-K 8644 (100 nM) enhanced the cytoplasmic Ca2+ response to all potassium concentrations tested up to 30 mM. The initial 30 sec 45Ca2+ uptake, an indicator of potassium-stimulated voltage-sensitive Ca2+ influx into these cells, showed a fast increase and only an initial inactivation in response to 18 mM potassium. This response was enhanced by 100 nM BAY-K 8644, with no sign of enhanced inactivation or inhibition caused by the dihydropyridine agonist. These results indicate that the correlation between Ca2+ influx, cytoplasmic Ca2+ levels, and the secretory response in adrenal glomerulosa cells is lost at potassium concentrations higher than 8 mM, especially in the presence of the dihydropyridine agonist, BAY-K 8644.


Progress in acetylcholinesterase reactivators and in the treatment of organophosphorus intoxication: a patent review (2006-2016).
organophosphorus compounds act as irreversible inhibitors of the vital enzyme acetylcholinesterase (AChE). this leads in the accumulation of acetylcholine (ACh) leading to cholinergic crisis and death. The main therapeutic approach is based on immediate administration of an ache reactivator as an antidote enabling recovery of the ache function. Areas covered: This review covers the development of AChE reactivators in order to introduce a new efficient drug that will overcome significant failures of common antidotes. Further options together with methods of detection are also discussed in order to assure a complete insight into the treatment of intoxication. Expert opinion: Since organophosphates belong to the most toxic chemical warfare agents, efficient antidotes are a matter of importance. The solution of how to limit the basic drawbacks of clinically used reactivators remained a spotlight for many researches worldwide. Recent strategies of the treatment of OP exposure bring us new possibilities which may overcome classic antidotes. The importance of detection of OP also has to be taken into consideration. Especially, with the fast spreading toxic effect when death can occur within minutes.


[Application of the analogy in the connotation of reinforcing and reducing principle and method in traditional acupuncture].
Analogy is the significant thinking method in TCM and it has been recorded abundantly in ancient literature of TCM. The analogy idea had been adopted in the connotation of the reinforcing and reducing principle and method of traditional acupuncture, such as the reinforcing and reducing manipulation techniques, the timing of the reinforcing and reducing method and the effects of deqi. In view of the analogy idea, the relevant reinforcing and reducing principles andmethods of traditional acupuncture were collated and analyzed in the article. It is anticipated that the origin and essence of reinforcing and reducing principles and methods can be better identified and this thinking characteristic of ancient acupuncture theory be widely understood and fully emphasized.


Validation of Peptide Identification Results in Proteomics Using Amino Acid Counting.
The efficiency of proteome analysis depends strongly on the configuration parameters of the search engine. One of the murkiest and nontrivial among them is the list of amino acid modifications included for the search. Here, an approach called AA_stat is presented for uncovering the unexpected modifications of amino acid residues in the protein sequences, as well as possible artifacts of data acquisition or processing, in the results of proteome analyses. The approach is based on comparing the amino acid frequencies of different mass shifts observed using the open search method introduced recently. In this work, the proposed approach is applied to publicly available proteomic data is applied and its feasibility for discovering unaccounted modifications or possible pitfalls of the identification workflow is demonstrated. The algorithm is implemented in Python as an open-source command-line tool available at https://bitbucket.org/J_Bale/aa_stat/.


Construction and evaluation of a predictive model for compassion fatigue among emergency department nurses: A cross-sectional study.
Compassion fatigue is a syndrome resulting from long-term work-related traumatic event stress exposure of medical staff. The emergency department is considered to be a high-risk, high-intensity and high-stress work environment, with a high prevalence of trauma and violence. Nurses in the emergency department are more prone to compassion fatigue than nurses in other departments. Compassion fatigue not only affects the physical and mental health, and job satisfaction of emergency department nurses, but also causes serious consequences for patients, such as poor patient outcome, medical errors, and increased patient mortality during hospitalization. Our study aims to develop and evaluate a predictive model for compassion fatigue among emergency department nurses. A cross-sectional study. The emergency department nurses (N = 1014) were recruited from 21 tertiary hospitals (from Chengdu, Chongqing, Guiyang, Guangzhou and Shanghai) in central, southwestern, southern, and eastern China from July 25, 2022 to October 30, 2022. Univariate and multiple logistic regression analyses were used to determine the potential predictive factors associated with compassion fatigue in emergency department nurses. A nomogram was built based on the predictive factors and internally evaluated using a bootstrap resampling method (1000 bootstrap resamples). The performance of the predictive model was evaluated by measuring the Hosmer-Lemeshow goodness of fit test and calibration curve. The prevalence of compassion fatigue among emergency department nurses was 75.9 %. The multiple logistic regression analysis revealed that the independent predictive factors for compassion fatigue among emergency department nurses were working position, job satisfaction, diet habit, sleep hours per day, occupational stress, physical harassment and the level of workplace violence, all of which were identified to create the nomogram. The Hosmer-Lemeshow goodness of fit test indicated that the predictive model was well calibrated (χ2 = 11.520, P = 0.174). The bootstrap-corrected concordance index of nomogram was 0.821 (95 % CI: 0.791-0.851). The calibration curve of the nomogram showed good consistency between the predicted and actual probabilities. A predictive model of compassion fatigue among emergency department nurses has been developed, based on the general demographic, work-related and lifestyle characteristics, occupational stress, and workplace violence, with satisfactory predictive ability. This model can identify emergency department nurses who are at high risk of compassion fatigue. Our study provides an empirical basis for early detection, early diagnosis and early intervention of emergency department nurses at high risk of compassion fatigue.


Latinx adolescents' ethnic-racial discrimination and expected future barriers over time.
Expecting discrimination in one's future occupation is known to have negative implications for adolescents' career pathways. However, little is known about how such discriminatory expectations emerge. The current contentious sociopolitical climate toward immigrants, especially those of Latinx heritage, has contributed to heightened discrimination against adolescents in this group. The present study examined how experiences of discrimination over time relate to youths' expectations of future occupational barriers among 148 Latinx adolescents at 3 annual waves (82% U.S.-born; 53% female; Mage = 13.54 at Wave 1). Results suggest that Latinx youth report increasing exposure to ethnic-racial discrimination and objectification as a perceived foreigner over time. Moreover, as Latinx youth perceived more ethnic-racial discrimination and foreigner objectification over the course of adolescence they increasingly expected to face racial and ethnic barriers in their future occupations. Implications of these findings for an increasing Latinx youth and working-age population in the United States are discussed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Validation and applicability of an alternative method for dialysis water and dialysate quality analysis.
In hemodialysis, patients are exposed to a large volume of water, which may lead to fatal risks if not meeting quality standards. This study aimed to validate an alternative method for monitoring microbiological quality of treated water and assess its applicability in dialysis and dialysate analysis, to allow corrective actions in real-time. Validation and applicability were analyzed by conventional and alternative methods. For validation, E. coli standard endotoxin was diluted with apyrogenic water in five concentrations. For the applicability analysis, treated water for dialysis was collected from different points in the treatment system (reverse osmosis, drainage canalization at the storage tank bottom, reuse, and loop), and dialysate was collected from four machines located in different rooms in the hemodialysis sector. The validation results were in accordance with the Brazilian Pharmacopoeia acceptance criteria, except for the last two concentrations analyzed. In addition, the ruggedness criterion performed under the US Pharmacopoeia was in agreement with the results. A limiting factor in the applicability analysis was the absence of the endotoxin maximum permitted level in dialysate by the Brazilian legislation. When comparing the analysis time, the alternative method was more time-consuming than the conventional one. This suggests that the alternative method is effective in the case of few analyses, that is, real-time analyses, favoring corrective actions promptly. On the other hand, it does not support the implementation of the alternative method in a laboratory routine due to the high demand for analyses.


[Age-related cognitive impairment: conceptual changes and diagnostic strategies].
The actual field of dementia encompasses also the pre-symptomatic phase, which may evolve for decades. Early detection and appropriate diagnosis decrease patient's and family's anxiety, improve patient's global care and allow better legal patient's protection. General Practitioners have at hand several available tools to screen a neurocognitive disorder, with up to 80% of sensitivity and specificity, to complete their clinical evaluation. An accurate diagnosis requires then a complete medical, neurological neuropsychological and neuroradiological evaluation in a Memory Clinic. Other investigations, such as functional cerebral imagery and spinal tap can be critical in unusual situations. Despite mood improvement after diagnostic announcement, increased suicidal risk in the 3 first months should be screened.


Anticonvulsants containing the N-(3-aryl-2-propenoyl) amido pharmacophore.
A series of 1-(3-aryl-2-propenoyl)-4-oxopiperidines (1) as well as some related semicarbazones (2) and thiosemicarbazones (3) were prepared in order to determine whether the relative locations of aryl rings and amidic groups would lead to novel anticonvulsant agents. Initially the compounds were administered intraperitoneally to mice and examined in the maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ) and neurotoxicity (NT) screens. The biodata revealed that anticonvulsant properties were displayed by most of the compounds in series (1), in half of the semicarbazones (2) while protection was absent by members of series (3). Molecular modeling was utilized in order to compare the positions of a phenyl ring in relation to amidic groups in representative compounds in series (1-3) with previously reported anticonvulsant agents. Molecular simplification of 4-oxo-1-(3-phenyl-2-propenoyl)piperidine (la) led to 1-(3-phenyl-2-propenoyl)piperidine (7) and N,N-diethylcinnamamide (8) with retention of anticonvulsant properties. Both (la) and (8) afforded protection in the hippocampal kindling screen in rats. When administered orally to rats, (la) and (8) demonstrated activity in the MES screen and in the case of (8), a huge protection index was observed revealing it to be an important lead compound. The IC50 values of all of the compounds towards murine P388 cells were in excess of 50 microM while several compounds displayed cytotoxicity towards Mycobacterium tuberculosis.


National Planetary Health learning objectives for Germany: A steppingstone for medical education to promote transformative change.
Physicians play an important role in adapting to and mitigating the adverse health effects of the unfolding climate and ecological crises. To fully harness this potential, future physicians need to acquire knowledge, values, skills, and leadership attributes to care for patients presenting with environmental change-related conditions and to initiate and propel transformative change in healthcare and other sectors of society including, but not limited to, the decarbonization of healthcare systems, the transition to renewable energies and the transformation of transport and food systems. Despite the potential of Planetary Health Education (PHE) to support medical students in becoming agents of change, best-practice examples of mainstreaming PHE in medical curricula remain scarce both in Germany and internationally. The process of revising and updating the Medical Licensing Regulations and the National Competency-based Catalog of Learning Objectives for Medical Education in Germany provided a window of opportunity to address this implementation challenge. In this article, we describe the development and content of national Planetary Health learning objectives for Germany. We anticipate that the learning objectives will stimulate the development and implementation of innovative Planetary Health teaching, learning and exam formats in medical schools and inform similar initiatives in other health professions. The availability of Planetary Health learning objectives in other countries will provide opportunities for cross-country and interdisciplinary exchange of experiences and validation of content, thus supporting the consolidation of Planetary Health learning objectives and the improvement of PHE for all health professionals globally.


[Thoracoscopic esophagectomy].
The current roles of thoracoscopic esophagectomy in the treatment of cancer in Japan are described. Lymphadenectomy of the same quality as open surgery should be performed thoracoscopically to obtain good oncological outcomes. The indications for thoracoscopic esophagectomy are 1) no extensive pleural adhesions; 2) pulmonary function sufficient for single-lung ventilation; and 3) tumor not invading other organs. Hand-assisted or mini-thoracotomy facilitates the dissection of lymph nodes, especially on the left side of the trachea. However, for any type of procedure, a good en-face view is essential for safe and accurate lymphadenectomy. The magnifying effect of video, with the camera in close proximity, is important to maintain a proper dissecting plane. Although sufficient experience is necessary to master the learning curve, lymphadenectomy of the same quality as open surgery can be performed with mini-thoracotomy in a feasible time period. Thoracoscopic esophagectomy contributes to reducing postoperative pain and constrictive pulmonary dysfunction. It may be too soon to assert that the thoracoscopic approach can provide oncological outcomes comparable to those after open surgery because long-term follow up is not yet sufficient. Thoracoscopic esophagectomy, however, has the potential to improve the postoperative quality of life of patients with esophageal cancer.


Metabonomic assessment of physiological disruptions using 1H-13C HMBC-NMR spectroscopy combined with pattern recognition procedures performed on filtered variables.
Metabonomic characterization of long-lasting although weak physiological events such as anabolic disruptions remains poorly investigated. We have validated 1H-13C HMBC-NMR as a suitable generator of instrumental variables that are strongly linked to the concentration of endogenous metabolites in biological fluids. This method is interfaced to multivariate pattern recognition procedures. Fingerprints established from urine sample collected on cattle treated with anabolic steroids were used to validate this method. Four main results arise from this study. (i) 2D NMR is as informative as 1D NMR. (ii) 2D NMR variable clustering highlights successfully a contingent redundancy of variables, although a relevant hierarchical model of statistical correlations covering from structural relationships to physiologic links can also be evidenced. (iii) To enhance pattern recognition performances, we have validated a variable selection algorithm for accurate prediction of unknown individuals belonging to predetermined groups achieved by linear discriminant analysis (LDA). This algorithm synthesizes the whole information contained in the data set by selecting preferentially nonredundant variables. Parameters generating variable subsets are validated by predicted variance efficiency obtained when minimizing error rates calculated by cross-validation methods. (iv) Provided variables are correctly filtered, LDA fairly competes with partial least-squares methods for both classification of individuals and statistical interpretation of metabolic responses obtained in such a physiological disruption context.


Formation of functional centromeric chromatin is specified epigenetically in Candida albicans.
In the pathogenic yeast Candida albicans, the 3-kb centromeric DNA regions (CEN) of each of the eight chromosomes have different and unique DNA sequences. The centromeric histone CaCse4p (CENP-A homolog) occurs only within these 3-kb CEN regions to form specialized centromeric chromatin. Centromere activity was maintained on small chromosome fragments derived in vivo by homologous recombination of a native chromosome with linear DNA fragments containing a telomere and a selectable marker. An in vivo derived 85-kb truncated chromosome containing the 3-kb CEN7 locus on 69 kb of chromosome 7 DNA was stably and autonomously maintained in mitosis, indicating that preexisting active CEN chromatin remains functional through many generations. This same 85-kb chromosome fragment, isolated as naked DNA (devoid of chromatin proteins) from C. albicans and reintroduced back into C. albicans cells by standard DNA transformation techniques, was unable to reform functional CEN chromatin and was mitotically unstable. Comparison of active and inactive CEN chromatin digested with micrococcal nuclease revealed that periodic nucleosome arrays are disrupted at active centromeres. Chromatin immunoprecipitation with antibodies against CaCse4p confirmed that CEN7 introduced into C. albicans cells as naked DNA did not recruit CaCse4p or induce its spread to a duplicate region only 7 kb away from active CEN7 chromatin. These results indicate that CaCse4p recruitment and centromere activation are epigenetically specified and maintained in C. albicans.


Statistical significance of combinatorial regulations.
More than three transcription factors often work together to enable cells to respond to various signals. The detection of combinatorial regulation by multiple transcription factors, however, is not only computationally nontrivial but also extremely unlikely because of multiple testing correction. The exponential growth in the number of tests forces us to set a strict limit on the maximum arity. Here, we propose an efficient branch-and-bound algorithm called the "limitless arity multiple-testing procedure" (LAMP) to count the exact number of testable combinations and calibrate the Bonferroni factor to the smallest possible value. LAMP lists significant combinations without any limit, whereas the family-wise error rate is rigorously controlled under the threshold. In the human breast cancer transcriptome, LAMP discovered statistically significant combinations of as many as eight binding motifs. This method may contribute to uncover pathways regulated in a coordinated fashion and find hidden associations in heterogeneous data.


Personal glucose sensor for point-of-care early cancer diagnosis.
Early POC diagnosis of cancer is demonstrated by using multi-invertase conjugated microsphere labels and a personal glucose sensor (PGS) transducer. The invertase, which catalyzes the hydrolysis of sucrose to glucose, enables the PGS to detect target analytes beyond glucose, and the numerous invertase labels involved in each antibody-antigen binding event lead to significantly amplified PGS readings for sensitive protein detection.


Genomic organization of mouse orexin receptors: characterization of two novel tissue-specific splice variants.
In humans and rat, orexins orchestrate divergent actions through their G protein-coupled receptors, orexin-1 (OX1R) and orexin-2 (OX2R). Orexins also play an important physiological role in mouse, but the receptors through which they function are not characterized. To characterize the physiological role(s) of orexins in the mouse, we cloned and characterized the mouse orexin receptor(s), mOX1R and mOX2R, using rapid amplification of cDNA (mouse brain) ends, RT-PCR, and gene structure analysis. The mOX1R cDNA encodes a 416-amino acid (aa) receptor. We have identified two alternative C terminus splice variants of the mOX2R; mOX2 alpha R (443 aa) and mOX2 beta R (460 aa). Binding studies in human embryonic kidney 293 cells transfected with mOX1R, mOX2 alpha R, and the mOX2 beta R revealed specific, saturable sites for both orexin-A and -B. Activation of these receptors by orexins induced inositol triphosphate (IP(3)) turnover. However, human embryonic kidney 293 cells transfected with mOXRs demonstrated no cAMP response to either orexin-A or orexin-B challenge, although forskolin and GTP gamma S revealed a dose-dependent increase in cAMP. Although, orexin-A and -B showed no difference in binding characteristics between the splice variants; interestingly, orexin-B led to an increase in IP(3) production at all concentrations in the mOX2 beta R variant. Orexin-A, however, showed no difference in IP(3) production between the two variants. Additionally, in the mouse, we demonstrate that these splice variants are distributed in a tissue-specific manner, where OX2 alpha R mRNA was undetectable in skeletal muscle and kidney. Moreover, food deprivation led to a greater increase in hypothalamic mOX2 beta R gene expression, compared with both mOX1R and mOX2 alpha R. This potentially implicates a fundamental physiological role for these splice variants.


Modeling Endometrial Cancer: Past, Present, and Future.
Endometrial cancer is the most common type of cancer of the female reproductive tract. Although prognosis is generally good for patients with low-grade and early-stage diseases, the outcomes for high-grade and metastatic/recurrent cases remain poor, since traditional chemotherapy regimens based on platinum and taxanes have limited effects. No targeted agents have been approved so far, although several new drugs have been tested without striking results in clinical trials. Over the last decades, many efforts have been made towards the establishment and development of preclinical models, aiming at recapitulating the structural and molecular determinants of the disease. Here, we present an overview of the most commonly used in vitro and in vivo models and discuss their peculiar features, describing their main applications and the value in the advancement of both fundamental and translational endometrial cancer research.


Dispersant and Protective Roles of Amphiphilic Poly(ethylene phosphate) Block Copolymers in Polyester/Bone Mineral Composites.
Composites of synthetic bone mineral substitutes (BMS) and biodegradable polyesters are of particular interest for bone surgery and orthopedics. Manufacturing of composite scaffolds commonly uses mixing of the BMS with polymer melts. Melt processing requires a high homogeneity of the mixing, and is complicated by BMS-promoted thermal degradation of polymers. In our work, poly(L-lactide) (PLLA) and poly(ε-caprolactone) (PCL) composites reinforced by commercial β-tricalcium phosphate (βTCP) or synthesized carbonated hydroxyapatite with hexagonal and plate-like crystallite shapes (hCAp and pCAp, respectively) were fabricated using injection molding. pCAp-based composites showed advanced mechanical and thermal characteristics, and the best set of mechanical characteristics was observed for the PLLA-based composite containing 25 wt% of pCAp. To achieve compatibility of polyesters and pCAp, reactive block copolymers of PLLA or PCL with poly(tert-butyl ethylene phosphate) (C1 and C2, respectively) were introduced to the composite. The formation of a polyester-b-poly(ethylene phosphoric acid) (PEPA) compatibilizer during composite preparation, followed by chemical binding of PEPA with pCAp, have been proved experimentally. The presence of 5 wt% of the compatibilizer provided deeper homogenization of the composite, resulting in a marked increase in strength and moduli as well as a more pronounced nucleation effect during isothermal crystallization. The use of C1 increased the thermal stability of the PLLA-based composite, containing 25 wt% of pCAp. In view of positive impacts of polyester-b-PEPA on composite homogeneity, mechanical characteristics, and thermal stability, polyester-b-PEPA will find application in the further development of composite materials for bone surgery and orthopedics.


Loss and hope: strategies for coping with aphasia.
Speaking from almost 30 years of experience living with aphasia, the author offers suggestions for health care professionals who relate to persons with this disorder. Persons with aphasia should be involved in meaningful activities, learn to accept limitations, build trusting relationships, strengthen social support, and find tools that facilitate communication.


Suppression of the vacuum space-charge effect in fs-photoemission by a retarding electrostatic front lens.
The performance of time-resolved photoemission experiments at fs-pulsed photon sources is ultimately limited by the e-e Coulomb interaction, downgrading energy and momentum resolution. Here, we present an approach to effectively suppress space-charge artifacts in momentum microscopes and photoemission microscopes. A retarding electrostatic field generated by a special objective lens repels slow electrons, retaining the k-image of the fast photoelectrons. The suppression of space-charge effects scales with the ratio of the photoelectron velocities of fast and slow electrons. Fields in the range from -20 to -1100 V/mm for Ekin = 100 eV to 4 keV direct secondaries and pump-induced slow electrons back to the sample surface. Ray tracing simulations reveal that this happens within the first 40 to 3 μm above the sample surface for Ekin = 100 eV to 4 keV. An optimized front-lens design allows switching between the conventional accelerating and the new retarding mode. Time-resolved experiments at Ekin = 107 eV using fs extreme ultraviolet probe pulses from the free-electron laser FLASH reveal that the width of the Fermi edge increases by just 30 meV at an incident pump fluence of 22 mJ/cm2 (retarding field -21 V/mm). For an accelerating field of +2 kV/mm and a pump fluence of only 5 mJ/cm2, it increases by 0.5 eV (pump wavelength 1030 nm). At the given conditions, the suppression mode permits increasing the slow-electron yield by three to four orders of magnitude. The feasibility of the method at high energies is demonstrated without a pump beam at Ekin = 3830 eV using hard x rays from the storage ring PETRA III. The approach opens up a previously inaccessible regime of pump fluences for photoemission experiments.


The regenerative activity of interleukin-6.
Interleukin-6 (IL-6) is a cytokine which is involved in many inflammatory processes and in the development of cancer. In addition, IL-6 has been shown to be important for the induction of hepatic acute-phase proteins, for the regeneration of the liver and for the stimulation of B-cells. IL-6 binds to a transmembrane IL-6 receptor (IL-6R), which is present on hepatocytes and some leukocytes. The complex of IL-6 and IL-6R associates with a second protein, gp130, which is expressed on all cells of the body. Since neither IL-6 nor IL-6R has a measurable affinity for gp130, cells, which do not express IL-6R, are not responsive to the cytokine IL-6. It could be shown, however, that a naturally occurring soluble IL-6R (sIL-6R) in complex with IL-6 can bind to gp130 on cells with no IL-6R expression. Therefore, cells shedding the sIL-6R render cells, which only express gp130, responsive to the cytokine. This process has been called trans-signaling. In the present chapter, we summarize the known activities of IL-6 with a special emphasis on regenerative activities, which often depend on the sIL-6R. A designer cytokine called Hyper-IL-6, which is a fusion protein of IL-6 and the sIL-6R, can mimic IL-6 trans-signaling responses in vitro and in vivo with considerably higher efficacy than the combination of the natural proteins IL-6 and sIL-6R. We present recent examples from animal models in which the therapeutic potential of Hyper-IL-6 has been evaluated. We propose that Hyper-IL-6 can be used to induce potent regeneration responses in liver, kidney, and other tissues and therefore will be a novel therapeutic approach in regenerative medicine.


Vegetation development and floristical diversity of newly created sown and unsown field margin strips on ex arable land during the first 3 successional years.
Early succesion of newly created sown/unsown margin strips on ex arableland, managed by two cuttings per year with/without removal of cuttings was characterised by the replacement of annuals in favour of perennials, a steadily increase in the importance of monocots and a decrease in non N-fixing dicots. Mowing with removal of cuttings delayed this succession pattern. Sorenson's qualitative similarity index (based solely on species occurrence) revealed that species composition of the sown communities (in terms of species occurrence) became increasingly similar to the unsown plots. Furthermore convergence in vegetation composition between sown and unsown plots occurred also in terms of species importance as assessed by Sorenson's quantitative index (based on the combination of species occurrence and importance). Similarity in species importance (but not of species occurrence) was significantly enhanced by cutting with removal of cuttings. During the first 3 successional years, species diversity of sown and unsown communities converged in time, irrespective of mowing regime or location. The decrease in species diversity, number of sown wildflower species and wildflower density of sown communities was more pronounced under a mowing regime without removal of cuttings. The annual addition of mown roadside herbage significantly enhanced species richness but not the importance of dicots.


[Types of immunocompetent cell reactions in in vitro loading tests in healthy children].
Lymphocyte reactivity was assessed with various surface antigens detectable by Russian monoclonal antisera by indirect immunofluorescence in peripheral blood samples from 40 healthy children in vitro in loading tests. Values of a coefficient reflecting individual reactivity of immunocompetent cells with surface antigens CD5, CD4, and CD8 corresponding to type II reaction were found characteristic of children whatever their age or sex. The results may be used as reference values in examinations of children with various diseases.


The origin of the Drosophila subretinal pigment layer.
Optical insulation plays a critical role in the fine visual acuity of the Drosophila compound eye. Screening pigments expressed by a number of cell types contribute to this phenomenon. They provide optical insulation that prevents extraneous light rays from inappropriately activating the photoreceptors. This optical insulation can be divided into two categories; the insulation of the individual ommatidia, and the insulation of the compound eye as a whole. The whole-eye insulation is provided by two sources. The sides of the eye are optically insulated by the pigment rim, a band of pigment cells that circumscribes the eye. The base of the eye is insulated by the subretinal pigment layer; a thick layer of pigment that lies directly underneath the retina. How this subretinal pigment layer is generated has not been clearly described. Here, experiments that manipulate pigment expression during eye development suggest that the subretinal pigment layer is directly derived from pigment cells in the overlying retina.


[Adenoid cystic carcinoma].
Adenoid cystic carcinoma is an uncommon tumor of the head and neck. Although it is mainly located in the salivary gland, a skin location has also been described. Metastases are rare, but 50 % of the cases relapse. A 65-year-old male patient had a lesion in the upper lip. After resection, the histological diagnosis was adenoid cystic carcinoma. Treatment was completed with radiotherapy. Ten years later, a nodule was detected in the neck. Its histological diagnosis was lymphatic metastasis due to adenoid cystic carcinoma. Primary cutaneous adenoid cystic carcinoma is a very uncommon tumor in which treatment consists in extensive local excision with free margins. Radiotherapy is not curative and should be reserved for palliative treatments. Multicenter, prospective studies are necessary to determine the best treatment and especially the adjuvant treatment for adenoid cystic carcinoma.


Characterization of canine anti-mouse antibodies highlights that multiple strategies are needed to combat immunoassay interference.
Immunoassays are widely used for detection and quantification of analytes in biological samples, but are vulnerable to analytical errors caused by interfering sample substances. Of particular interest are endogenous anti-animal antibodies that may bind to the immunoassay antibodies and cause erroneous test results. This phenomenon is a hazard to patient safety in both human and veterinary medicine. Here, we demonstrate that anti-mouse antibodies in dogs bind selectively to different regions of the murine IgG molecule, cross-react with IgG from different species, and consist of all major antibody classes present in canine serum (IgA, IgG and IgM). The antibody characteristics varied among individuals and their prevalence differed between two dog breeds. The selective binding to different IgG regions suggests that the antibodies might not originate from immunization through exposure to mice or other species. These findings show that canine anti-mouse antibodies are highly heterogeneous in nature and therefore require a combination of strategies to be counteracted.


Do the urban poor want household taps? Community preferences and willingness to pay for household taps in Accra, Ghana.
In Sub-Saharan Africa, only 35% of the urban population has piped water on premises despite the economic (time savings) and public health benefits that household taps offer. In the urban informal settlements, even fewer people own household taps. However, while there is extensive literature on everyday urban water insecurity in the region, far less attention has focused on whether the urban poor are interested in private taps, and if so, what service attributes are important to them. We implemented a choice experiment in Nima, an urban settlement in Accra, Ghana, to investigate community preferences and willingness to pay (WTP) for household taps. We used a comprehensive set of system attributes including days of service, service hours, water pressure, water quality, connection fees, monthly payment, and management, an attribute very few WTP studies have explored. Results from the choice experiment show that residents are more sensitive to time (not day) of service delivery, quality of water, connection fees, and monthly water bills. Households had no preference between a 24-h supply and 12-h supply during the day. Households preferred Accra Metropolitan Assembly (AMA) to Ghana Water Company Limited (GWCL) as the service provider and were willing to pay more for a system managed by AMA, an indication of declining trust in GWCL. The findings provide valuable information that policymakers and water utilities can use to assess the feasibility and cost effectiveness of extending household taps to poor urban settlements.


Capacitive Removal of Fluoride Ions via Creating Multiple Capture Sites in a Modulatory Heterostructure.
Fluoride pollution has become a major concern because of its adverse effects on human health. However, the removal capacity of defluorination agents in traditional methods is far from satisfactory. Herein, capacitive removal of F- ions via creating multiple capture sites in a modulatory heterostructure has been originally demonstrated. The heterostructure of uniformly dispersed Al2O3 coating on hollow porous nitrogen-doped carbon frameworks was precisely synthesized by atomic layer deposition. An exceptional F- ion removal efficiency at 1.2 V (95.8 and 92.9% in 5 and 10 mg/L F- solutions, respectively) could be finally achieved, with a good regeneration ability after 20 consecutive defluorination cycles. Furthermore, we investigated the removal mechanisms of F- ions by in situ Raman, in situ X-ray diffraction, and ex situ X-ray photoelectron spectroscopy measurements. The promotional removal capacity was realized by the multiple capture sites of the reversible conversion of Al-F species and the insertion of F- ions into the carbon skeleton. This work offers an important new pathway and deep understanding for efficient removal of F- ions from wastewater.


The retinoic acid receptor beta (Rarb) region of Mmu14 is associated with prion disease incubation time in mouse.
In neurodegenerative conditions such as Alzheimer's and prion disease it has been shown that host genetic background can have a significant effect on susceptibility. Indeed, human genome-wide association studies (GWAS) have implicated several candidate genes. Understanding such genetic susceptibility is relevant to risks of developing variant CJD (vCJD) in populations exposed to bovine spongiform encephalopathy (BSE) and understanding mechanisms of neurodegeneration. In mice, aspects of prion disease susceptibility can be modelled by examining the incubation period following experimental inoculation. Quantitative trait linkage studies have already identified multiple candidate genes; however, it is also possible to take an individual candidate gene approach. Rarb and Stmn2 were selected as candidates based on the known association with vCJD. Because of the increasing overlap described between prion and Alzheimer's diseases we also chose Clu, Picalm and Cr1, which were identified as part of Alzheimer's disease GWAS. Clusterin (Clu) was considered to be of particular interest as it has already been implicated in prion disease. Approximately 1,000 heterogeneous stock (HS) mice were inoculated intra-cerebrally with Chandler/RML prions and incubation times were recorded. Candidate genes were evaluated by sequencing the whole transcript including exon-intron boundaries and potential promoters in the parental lines of the HS mice. Representative SNPs were genotyped in the HS mice. No SNPs were identified in Cr1 and no statistical association with incubation time was seen for Clu (P = 0.96) and Picalm (P = 0.91). Significant associations were seen for both Stmn2 (P = 0.04) and Rarb (P = 0.0005), however, this was only highly significant for Rarb. This data provides significant further support for a role for the Rarb region of Mmu14 and Stmn2 in prion disease.


Work capacity and left ventricular function during rehabilitation after myocardial revascularization surgery.
A prospective randomized trial was conducted to evaluate the effects of exercise-based cardiac rehabilitation after myocardial revascularization surgery (MRS) on work capacity (measured in mets) and left ventricular function as determined from ejection fraction (LVEF). Twenty-eight patients undergoing MRS were randomly assigned to experimental (aerobic exercise, n = 19) or control (muscle relaxation and low-level exercise, n = 9) groups. Patients were studied before surgery (T1) and 2 (T2), 8 (T3), and 24 (T4) weeks after surgery with first-pass radionuclide angiography both while they were at rest and during maximal upright cycle ergometric exercise. Subsets of patients were also studied at T2, T3, and T4 at a standard workload of 75 W, and during maximal exercise 1 year after surgery (T5). Work capacity improved in both groups although significantly more so in the experimental group (3.9, 3.8, 6.0, and 7.3 mets and 3.7, 3.7, 4.9, and 5.7 mets at T1, T2, T3, and T4 in the experimental and control groups, respectively). The differences between groups were significant by T3. Peak exercise LVEF increased significantly in both groups from T1 to T2 then decreased at T3 and remained unchanged through T5. Peak exercise LVEF at T3 to T5 remained significantly above that observed at T1. LVEF responses were not related to the exercise program. During a standard workload, heart rate decreased, blood pressure increased, and LVEF did not change in either group. After conclusion of the formal protocol (T4), work capacity and LVEF did not change for either group throughout an additional 6 months (T5).(ABSTRACT TRUNCATED AT 250 WORDS)


Prevalence of dental caries and treatment needs among the orphan children and adolescents of Udaipur district, Rajasthan, India.
The study was to examine the prevalence of dental caries and treatment needs among the orphan children and adolescents of Udaipur district, Rajasthan, India. A descriptive cross-sectional study was conducted to assess the oral health status and treatment needs of orphan children. The lists obtained comprised of 13 orphanages consisting of 923 inmates including both sexes. The survey proforma was prepared using a self-administered structured questionnaire written in English validated through a pretested survey. The statistical software namely SPSS 15.0 was used for the analysis of the data. The prevalence of dental caries in primary teeth was found to be 49.6% and in permanent teeth was 41%. Most of the children need one surface filling followed by pulp care. The unmet needs for decayed teeth were also found to be high indicating a very poor accessibility and availability of any oral health care. Clearly, it can be concluded that this community has experienced a low utilization of preventive or therapeutic oral health services. Orphanage children in India are usually taken care by NGOs or social workers who do not realize that dental care and oral health forms an integral part of children well-being. So, this paper enlighten the prevalence of dental caries and treatment needs among the orphan children and adolescents.


Hemodynamic Impact of Superior Vena Cava Placement in the Y-Graft Fontan Connection.
A Fontan Y-shaped graft using a commercially available aortoiliac graft has been used to connect the inferior vena cava (IVC) to the pulmonary arteries. This modification of the Fontan procedure seeks to improve hepatic flow distribution (HFD) to the lungs. However, patient-specific anatomical restrictions might limit the space available for graft placement. Altering the superior vena cava (SVC) positioning is hypothesized to provide more space for an optimal connection, avoiding caval flow collision. Computational modeling tools were used to retrospectively study the effect of SVC placement on Y-graft hemodynamics. Patient-specific anatomies (N = 10 patients) and vessel flows were reconstructed from retrospective cardiac magnetic resonance (CMR) images after Fontan Y-graft completion. Alternative geometries were created using a virtual surgery environment, altering the SVC position and the offset in relation to the Y-graft branches. Geometric characterization and computational fluid dynamics simulations were performed. Hemodynamic factors (power loss and HFD) were computed. Patients with a higher IVC return showed less sensitivity to SVC positioning. Patients with low IVC flow showed varied HFD results, depending on SVC location. Balanced HFD values (50% to each lung) were obtained when the SVC lay completely between the Y-graft branches. The effect on power loss was patient specific. SVC positioning with respect to the Y-graft affects HFD, especially in patients with lower IVC flow. Careful positioning of the SVC at the time of a bidirectional Glenn (BDG) procedure based on patient-specific anatomy can optimize the hemodynamics of the eventual Fontan completion.


The potential value of immunoperoxidase techniques in diagnostic cytology.
A slightly modified immunoperoxidase method was developed in our laboratory and applied to a variety of aspiration and exfoliative cytologic material. Our aims were: (1) to explore the applicability of the immunoperoxidase procedure to diagnostic cytology, (2) to attempt to define the histogenesis of neoplastic cells when morphology alone proved insufficient, and (3) to investigate the possibility of differentiating reactive from neoplastic lymphoreticular disorders by studying their immunoglobulin patterns. Our findings indicate that the immunoperoxidase technique is applicable to cytologic material. The simplicity of the procedure, combined with its high sensitivity and excellent morphology, merits wider application of this technique to routine diagnostic cytology.


Celecoxib mitigates genotoxicity induced by ionizing radiation in human blood lymphocytes.
Ionizing radiation causes DNA damage and chromosome abbreviations on normal cells. The radioprotective effect of celecoxib (CLX) was investigated against genotoxicity induced by ionizing radiation in cultured human blood lymphocytes. Peripheral blood samples were collected from human volunteers and were incubated at different concentrations at 1, 5, 10 and 50 μM of CLX for two hours. At each dose point, the whole blood was exposed in vitro to 150 cGy of X-ray, and then the lymphocytes were cultured with mitogenic stimulation to determine the micronucleus frequency in cytokinesis blocked binucleated lymphocytes. Incubation of the whole blood with CLX exhibited a significant decrease in the incidence of micronuclei in lymphocytes induced by ionizing radiation, as compared with similarly irradiated lymphocytes without CLX treatment. The maximum reduction on the frequency of micronuclei was observed at 50 μM of CLX (65% decrease). This data may have an important possible application for the protection of human lymphocytes from the genetic damage induced by ionizing irradiation in human exposed to radiation.


Anti-invasive activities of anthocyanins through modulation of tight junctions and suppression of matrix metalloproteinase activities in HCT-116 human colon carcinoma cells.
Claudins are a family of proteins that are the most important components of the tight junctions. Recently it has been reported that these proteins are overexpressed in cancers and there is a positive correlation between suppression of the expression of these proteins and anti-invasive activity. Matrix metalloproteinases (MMPs) have been implicated as important mediators in cancer invasion. Here, we investigated the effects of anthocyanins on tight junctions (TJs) and the expression of claudins as well as MMPs. The inhibitory effects of the anthocyanins on cell proliferation, motility and invasiveness were found to be associated with tightening TJs, which was demonstrated by an increase in transepithelial electrical resistance (TER). The expression of claudin proteins was suppressed by anthocyanins. Furthermore, the activities of MMP-2 and -9 were dose-dependently suppressed by anthocyanin treatment. These effects were related to activation of 38-MAPK and suppression of the PI3K/Akt pathway in HCT-116 human colon cancer cells.


[The milking machine as a cause of severe agitation in cows (and the farmer) during milking].
A dairy farmer had complaints about uneasiness of the cows during milking. The problems started after changing some parts of the milking machine. Therefore a dynamic milking machine test was carried out to detect the cause of the problems. This test showed that the drainage ability of the milking machine was insufficient in cows with a high milkability (> 4.0 kg/min). The cyclic variations in the short milk tube and the drop of the mean vacuum in the short milk tube did not comply with the standards in cows with a high milkability. Moreover, in these cows, the mean vacuum in the beginning of the long milk tube was too low. Beside, the vacuum in the mouthpiece of the teat cup liner in cows with small teats was far above the standards and the shut off valves in the claws, which must lock the exit to the long milk tube nipple when the cluster is taken off automatically, did not function anymore. The way these deviations disturbed the milking procedure, is discussed. The farmer was advised (i) to replace the automatic cluster remover system by an electronically controlled one. (ii) and to replace the milking claws by claws with a larger volume (iii) and to replace the teat cup liners by teat cup liners with a smaller diameter. After the implementations of all advises, the cows were at ease again.


Low-density lipoprotein receptor-related protein 1 is a novel modulator of radial glia stem cell proliferation, survival, and differentiation.
The LDL family of receptors and its member low-density lipoprotein receptor-related protein 1 (LRP1) have classically been associated with a modulation of lipoprotein metabolism. Current studies, however, indicate diverse functions for this receptor in various aspects of cellular activities, including cell proliferation, migration, differentiation, and survival. LRP1 is essential for normal neuronal function in the adult CNS, whereas the role of LRP1 in development remained unclear. Previously, we have observed an upregulation of LewisX (LeX) glycosylated LRP1 in the stem cells of the developing cortex and demonstrated its importance for oligodendrocyte differentiation. In the current study, we show that LeX-glycosylated LRP1 is also expressed in the stem cell compartment of the developing spinal cord and has broader functions in the developing CNS. We have investigated the basic properties of LRP1 conditional knockout on the neural stem/progenitor cells (NSPCs) from the cortex and the spinal cord, created by means of Cre-loxp-mediated recombination in vitro. The functional status of LRP1-deficient cells has been studied using proliferation, differentiation, and apoptosis assays. LRP1 deficient NSPCs from both CNS regions demonstrated altered differentiation profiles. Their differentiation capacity toward oligodendrocyte progenitor cells (OPCs), mature oligodendrocytes and neurons was reduced. In contrast, astrocyte differentiation was promoted. Moreover, LRP1 deletion had a negative effect on NSPCs proliferation and survival. Our observations suggest that LRP1 facilitates NSPCs differentiation via interaction with apolipoprotein E (ApoE). Upon ApoE4 stimulation wild type NSPCs generated more oligodendrocytes, but LRP1 knockout cells showed no response. The effect of ApoE seems to be independent of cholesterol uptake, but is rather mediated by downstream MAPK and Akt activation. GLIA 2016 GLIA 2016;64:1363-1380.


Effect of training and anabolic-androgenic steroids on drug metabolism in rat liver.
The effects of anabolic-androgenic steroid administration and exercise training on various aspects of hepatic function were investigated in sedentary and trained (treadmill for 12 wk) male and female rats treated orally with fluoxymesterone or methylandrostanolone (2 mg.kg-1 body weight, 5 d.wk-1 for 8 wk). The mean values of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total and direct bilirubin, and total- and high-density lipoprotein-cholesterol remained within normal range in all groups of male animals. The same is true for female rats, except for an increase in alkaline phosphatase activity in the steroid-treated groups. Hepatic microsomal aniline p-hydroxylase activity was reduced in male and increased in female rats by either steroid, whereas no significant effect was detected on 7-ethoxycoumarin deethylase activity. The levels of cytochrome P-450 and cytochrome b5 were markedly decreased by the anabolic-androgenic steroid treatment in male rat microsomes, but neither the steroid administration nor exercise training induced significant changes in the cytochrome levels of female rat livers. Taking into account the significant increase in microsomal protein yield elicited by fluoxymesterone or methylandrostanolone treatment both in males and females, it is noteworthy that the total monooxygenase activities and cytochrome P-450 content, expressed on a per gram liver basis, were significantly increased in female whereas they were apparently unchanged in male rats. In conclusion, the present data show that the prolonged ingestion of high doses of anabolic-androgenic steroids, either with or without concurrent exercise training, can modify in a sex-dependent manner the capacity of rat liver to metabolize drugs without affecting classical serum indicators of hepatic function.


Drug Conjugates of Antagonistic R-Spondin 4 Mutant for Simultaneous Targeting of Leucine-Rich Repeat-Containing G Protein-Coupled Receptors 4/5/6 for Cancer Treatment.
LGR4-6 (leucine-rich repeat-containing G-protein-coupled receptors 4, 5, and 6) are three related receptors with an upregulated expression in gastrointestinal cancers to various extents, and LGR5 is enriched in cancer stem cells. Antibody-drug conjugates (ADCs) targeting LGR5 showed a robust antitumor effect in vivo but could not eradicate tumors due to plasticity of LGR5-positive cancer cells. As LGR5-negative cancer cells often express LGR4 or LGR6 or both, we reasoned that simultaneous targeting of all three LGRs may provide a more effective approach. R-spondins (RSPOs) bind to LGR4-6 with high affinity and potentiate Wnt signaling. We identified an RSPO4 furin domain mutant (Q65R) that retains potent LGR binding but no longer potentiates Wnt signaling. Drug conjugates of a peptibody comprising the RSPO4 mutant and IgG1-Fc showed potent cytotoxic effects on cancer cell lines expressing any LGR in vitro and suppressed tumor growth in vivo without inducing intestinal enlargement or other adverse effects.


Modification of cellular protein sulfhydryl groups by activated soluble immune response suppressor.
Soluble immune response suppressor (SIRS), a product of murine Ly-2+ T lymphocytes, is activated to SIRSox by H2O2 produced by macrophages: SIRSox directly inhibits cell division by normal and neoplastic cells and antibody secretion by B lymphocytes. To examine the mechanism of SIRSox-mediated inhibition, a variety of cellular functions were measured after treatment of cells with SIRSox. These included respiration, glucose transport, microtubule content, glutathione content, production of H2O2 or superoxide anion, and the activities of a variety of different enzymes. Several cellular activities or measurements were inhibited or lowered after SIRSox-treatment, including cell division, microtubule content, glutathione reductase activity, and thioredoxin reductase activity; inhibition was partially reversed by the sulfhydryl reducing agent dithiothreitol. Protein sulfhydryl content of P815 mastocytoma cells and several other cell types was lowered by 35 to 45% after exposure to SIRSox. Protein sulfhydryl loss was also partially restored after incubation with dithiothreitol. Sulfhydryl loss was not due to cell lysis. In addition, treatment of crude cellular particulate fractions with SIRSox resulted in protein sulfhydryl loss and formation of protein sulfenyl derivatives. A comparison of the amount of SIRS and H2O2 present to the number of protein sulfhydryls lost or sulfenyl derivatives formed suggests that SIRSox acts catalytically, serves as a co-factor in protein sulfhydryl oxidation, or that it activates a second pathway that is directly responsible for sulfhydryl oxidation.


The heterodisulfide reductase from Methanobacterium thermoautotrophicum contains sequence motifs characteristic of pyridine-nucleotide-dependent thioredoxin reductases.
The genes hdrA, hdrB and hdrC, encoding the three subunits of the iron-sulfur flavoprotein heterodisulfide reductase, have been cloned and sequenced. HdrA (72.19 kDa) was found to contain a region of amino acid sequence highly similar to the FAD-binding domain of pyridine-nucleotide-dependent disulfide oxidoreductases. Additionally, 110 amino acids C-terminal to the FAD-binding consensus, a short polypeptide stretch (VX2CATID) was detected which shows similarity to the region of thioredoxine reductase that contains the active-site cysteine residues (VX2CATCD). These findings suggest that HdrA harbors the site of heterodisulfide reduction and that the catalytic mechanism of the enzyme is similar to that of pyridine-nucleotide-dependent thioredoxin reductase. HdrA was additionally found to contain four copies of the sequence motif CX2CX2CX3C(P), indicating the presence of four [4Fe-4S] clusters. Two such sequence motifs were also present in HdrC (21.76 kDa), the N-terminal amino acid sequence of which showed sequence similarity to the gamma-subunit of the anaerobic glycerol-3-phosphate dehydrogenase of Escherichia coli. HdrC is therefore considered to be an electron carrier protein that contains two [4Fe-4S] clusters. HdrB (33.46 kDa) did not show sequence similarity to other known proteins, but appears to possess a C-terminal hydrophobic alpha-helix that might function as a membrane anchor. Although hdrB and hdrC are juxtaposed, these genes are not near hdrA.


Identification of virus components in circulating immune complexes isolated during hepatitis A virus infection.
Circulating immune complexes were isolated by conglutinin affinity chromatography during the course of hepatitis A virus infection in a chimpanzee. Characterization of circulating immune complexes showed that most of the hepatitis A virus-specific antibody was IgM, that IgG was present and that C3d and fibronectin were also present. Hepatitis A virus capsid polypeptides were identified in the circulating immune complexes and polypeptides in the molecular weight range of 63 to 67 kDa having immunological determinants common to both C3d and hepatitis A virus. Hepatitis A virus-RNA was detected in these circulating immune complexes using the polymerase chain reaction for in vitro amplification of nucleic acid and suggests the circulating immune complexes contain intact virus.


Effects of a nicotine warning label and vaping cessation resources on young adults' perceptions of pro-vaping instagram influencer posts.
Exposure to social media content promoting e-cigarette use ("vaping") is associated with subsequent tobacco use among young adults. Adding features to pro-vaping Instagram influencer posts, such as a nicotine warning label and vaping cessation resources, could help counteract posts' negative influence. Young adults (N = 2,179; Mage = 22.6 [SD = 0.4]; 53.0 % cisgender women, 45.1 % Hispanic) completed an online experiment in 2021-2022 through an ongoing prospective cohort study. Participants viewed three simulated pro-vaping Instagram influencer posts in a four-group, between-subjects design. Post features differed by experimental condition: "label-only" (nicotine warning label on post), "link-only" (link to vaping cessation resources under post), "L&L" (label and link), or "control" (neither). Participants rated each influencer's traits (honest, trustworthy, informed, smart, attractive, popular; 0-100 %). After viewing all three posts, participants reported use intentions, susceptibility, positive and negative expectancies, and harm perceptions around the fictitious advertised vaping product. Past-month vapers additionally reported their desire and self-efficacy for quitting. L&L (versus control and link-only) participants viewed influencers as more honest, trustworthy, and informed. L&L (versus control) participants had lower odds of susceptibility to using the advertised product, lower positive expectancies, and greater negative expectancies. The label and link did not significantly affect participants' intentions to use the product, perceived harm of the product, or desire or self-efficacy for quitting vaping. Providing a nicotine warning label and link to vaping cessation resources on influencers' Instagram posts may have the unintended effect of increasing positive perceptions of the influencer. However, they may reduce susceptibility to product use.


Self-reported medication and lifestyle adherence in Hungarian patients with Type 2 diabetes.
Type 2 diabetes is a complex disorder that requires the patient to pay constant attention to diet, physical activity, glucose monitoring and medication. To evaluate the medication, lifestyle adherence and factors associated to these in Type 2 diabetes in Hungarian patients. Fourteen community pharmacies in Hungary between March and May 2004. A questionnaire was given to every tenth Type 2 diabetic patient who presented to one of the 14 pharmacies included in this study with a prescription for oral antidiabetics, oral antidiabetics and insulin or exclusively insulin. For the latter two groups, the prerequisite for inclusion in the study was also that their diabetes had developed after the age of 35 and that at some in their treatment regimen they had taken only oral antidiabetics. These latter two criteria were controlled in the patient's general practitioners' (GP) database. General and diabetes-related data were collected in the questionnaire, and the adherence and lifestyle of the participant were assessed. An adapted and validated Hungarian version of the EQ-5D (EuroQol Group, 1993) quality-of-life questionnaire was also included. Descriptive and chi(2) test statistical methods and two sample t-test were used. A significance level of P<0.05 was considered to be significant. Patient self-reported adherence to diet, physical activity, self monitoring of blood glucose, purchasing of drug(s), drug regimen, association of demographic factors, treatment, lifestyle and quality of life on adherence. Of the 220 questionnaires distributed to diabetic patients, 151 were returned, of which 142 were evaluated (nine did not satisfy the above-mentioned inclusion criteria). With respect to the factors assessed, sub-optimal adherence was assessed for: diet (76.8%), physical activity (33.8%), self-monitoring of blood glucose (81%), drug purchasing (20.4%) and drug taking (52.1%). Smokers comprised 14.8% of the respondents, while 8.5% were heavy drinkers. Fewer than five meals a day were eaten by 46.5% of the patients, and about 43.6% of the patients did not self-monitor blood glucose. The results indicate few significant associations between at least one of the four main areas of adherence (diet, physical activity, purchasing of drug(s), drug regimen) and body mass index, GP consultation frequency, quality-of-life parameters and EQ-5D index. The adherence of Hungarian Type 2 diabetics in some areas does not reach optimal levels, especially for diet, self-monitoring, drug purchasing and adherence to drug taking.


Food commercials do not affect energy intake in a laboratory meal but do alter brain responses to visual food cues in children.
Food commercials promote snack intake and alter food decision-making, yet the influence of exposure to food commercials on subsequent neural processing of food cues and intake at a meal is unclear. This study tested whether exposing children to food or toy commercials altered subsequent brain response to high- and low-energy dense food cues and influenced laboratory intake at a multi-item, ad libitum meal. Forty-one 7-9-year-old children (25 healthy weight; 16 with overweight/obesity) completed five visits as part of a within-subjects design where they consumed multi-item test-meals under three conditions: no exposure, food commercial exposure, and toy commercial exposure. On the fourth and fifth visits, functional magnetic resonance imaging (fMRI) was performed while children viewed low- and high-energy dense food images following exposure to either food or toy commercials. Linear mixed models tested for differences in meal energy intake by commercial condition. A whole-brain analysis was conducted to compare differences in response by commercial condition and child weight status. Meal intake did not differ by commercial condition (p = 0.40). Relative to toy commercials, food commercials reduced brain response to high-energy food stimuli in cognitive control regions, including bilateral superior temporal gyri, middle temporal gyrus, and inferior frontal gyrus. Commercial condition * weight status interactions were observed in orbitofrontal cortex, fusiform gyrus, and supramarginal gyrus. Children with overweight/obesity showed increased response in these regions to high-energy stimuli following food commercials. Food commercial exposure affected children's subsequent processing of food cues by reducing engagement of the prefrontal cortex, a region implicated in cognitive control. Even though food commercial exposure did not increase intake at a meal, the effect of reduced prefrontal cortical engagement on a broader range of consumption patterns warrants investigation.


[Treatment of thrombotic complications of surgical infrainguinal revascularizations].
Authors in the work analyse the patients hospitalized with thrombosis of the surgical infrainguinal reconstruction. They evaluate the causes of reconstructions occlusions, therapeutic options in the treatment and their experiences with treatment of these patients. It is the retrospective analysis of the patients hospitalized during years 2001-2006 at the Department of Vascular Surgery of the Teaching Hospital J. A. Reimana in Presov with thrombosis of the surgical infrainguinal reconstruction. During the study period 723 surgical infrainguinal revascularization procedures were performed. The basic therapeutic approach in the care of these patients is anticoagulation and digital subtraction angiography, then they decide between percutaneous endovascular treatment, surgical thrombectomy, reoperation with implantation of the new reconstruction or conservative treatment. In the phase of irreversible ischemia high amputation is indicated. Thrombosis of the reconstruction was occured in 109 subjects (15.8%). Prothesis was thrombosed in 71 subjects (65.14%), vein in 38 subjects (34.86%). Percutaneous endovascular treatment was indicated in 3 subjects (2.8%), surgical thrombectomy with correction of the stenosis in 23 subjects (21.1%), reoperation with implantation of the new reconstruction in 53 subjects (48.6%),conservative approach in 21 subjects (19.3%), high amputation in 9 subjects (8.2%). The secondary patency after 12 months according to the life table method analysis after percutaneous endovascular treatment was 75%, after surgical thrombectomy of the graft with correction of stenosis 37% and after reoperation with implantation of the new reconstruction 72%. Authors believe that the best treatment in the care of the patients with thrombosis of the surgical infrainguinal reconstruction and critical limb ischemia is implantation of the new secondary reconstruction with autologous vein.


Backbone-only protein solution structures with a combination of classical and paramagnetism-based constraints: a method that can be scaled to large molecules.
Herein, it is shown that a medium-resolution solution structure of a protein can be obtained with the sole assignment of the protein backbone and backbone-related constriants if a derivative with a firmly bound paramagnetic metal is available. The proof-of-concept is provided on calbindin D9k, a calcium binding protein in which one of the two calcium ions can be selectively substituted by a paramagnetic lanthanide ion. The constraints used are HN (and Ha) nuclear Overhauser effects (NOEs), hydrogen bonds, dihedral angle constriants from chemical shifts, and the following paramagnetism-based constraints: 1) pseudocontact shifts, acquired by substituting one (or more) lanthanide(s) in the C-terminal calcium binding site; 2) N-HN residual dipolar couplings due to self-orientation induced by the paramagnetic lanthanide(s); 3) cross-correlations between the Curie and internuclear dipole-dipole interactions; and 4) paramagnetism-induced relaxation rate enhancements. An upper distance limit for internuclear distances between any two backbone atoms was also given according to the molecular weight of the protein. For this purpose, the paramagnetism-based constraints were collectively implemented in the program CYANA for solution structure determinations, similarly to what was previously done for the program DYANA. The method is intrinsically suitable for large molecular weight proteins.


Minimally-invasive Sampling of Interleukin-1α and Interleukin-1 Receptor Antagonist from the Skin: A Systematic Review of In vivo Studies in Humans.
Interleukin-1α (IL-1α) and its receptor antagonist IL-1RA play a pivotal role in skin homeostasis and disease. Although the use of biopsies to sample these cytokines from human skin is widely employed in dermatological practice, knowledge about less invasive, in vivo sampling methods is scarce. The aim of this study was to provide an overview of such methods by systematically reviewing studies in Medline, EMBASE, Web of Science and Cochrane Library using combinations of the terms "IL-1α", IL-1RA", "skin", "human", including all possible synonyms. Quality was assessed using the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) checklist. The search, performed on 14 October 2016, revealed 10 different sampling methods, with varying degrees of invasiveness and wide application spectrum, including assessment of both normal and diseased skin, from several body sites. The possibility to sample quantifiable amounts of cytokines from human skin with no or minimal discomfort holds promise for linking clinical outcomes to molecular profiles of skin inflammation.


Exploring the SDSS Dataset with Linked Scatter Plots: I. EMP, CEMP, and CV Stars.
We present the results of a search for EMP, CEMP, and cataclysmic variable stars using a new exploration tool based on linked scatter plots (LSPs). Our approach is especially designed to work with very large spectrum data sets such as the SDSS, LAMOST, RAVE, and Gaia data sets and can be applied to stellar, galaxy, and quasar spectra. As a demonstration, we conduct a search for EMP, CEMP, and cataclysmic variable stars in the SDSS DR10 data set. We first created a 3326-dimensional phase space containing nearly 2 billion measures of the strengths of over 1600 spectral features in 569,738 SDSS stars. These measures capture essentially all the stellar atomic and molecular species visible at the resolution of SDSS spectra. We show how LSPs can be used to quickly isolate and examine interesting portions of this phase space. To illustrate, we use LSPs coupled with cuts in selected portions of phase space to extract EMP stars, C-rich EMP stars, and CV stars. We present identifications for 59 previously unrecognized candidate EMP stars and 11 previously unrecognized candidate CEMP stars. We also call attention to 2 candidate He II emission CV stars found by the LSP approach that have not yet been discussed in the literature.


[Surgical aspects of pediatric liver transplantation. Living donor liver transplant program in Hungary].
Because of the long waiting time for pediatric liver transplantation, new techniques of liver transplantation were invented. Split and living-donor related liver transplantation are common today and the Kaplan-Meier (3 years) overall survival is over 80%. By splitting the liver, two recipients can be transplanted. In general, the left lobe is used for the pediatric, the right lobe for the adult recipient. There are a lot of combinations depending on the donor and recipient weight. The accepted liver volume is approx. 1% of the recipient body weight. The results of the Hungarian pediatric program improve, 27 transplantations were done using 14 partial liver grafts and living donor program was started. Using strict protocols and improving surgical skills, the overall pediatric survival was over 80% in the last 5 years.


On the bound of the Lyapunov exponents for the fractional differential systems.
In recent years, fractional(-order) differential equations have attracted increasing interests due to their applications in modeling anomalous diffusion, time dependent materials and processes with long range dependence, allometric scaling laws, and complex networks. Although an autonomous system cannot define a dynamical system in the sense of semigroup because of the memory property determined by the fractional derivative, we can still use the Lyapunov exponents to discuss its dynamical evolution. In this paper, we first define the Lyapunov exponents for fractional differential systems then estimate the bound of the corresponding Lyapunov exponents. For linear fractional differential system, the bounds of its Lyapunov exponents are conveniently derived which can be regarded as an example for the theoretical results established in this paper. Numerical example is also included which supports the theoretical analysis.


Diazo-based assay for total bilirubin in a coated thin film evaluated.
We compared results for total bilirubin as measured on a coated thin film and by the Evelyn-Malloy and Jendrassik-Gróf methods. We examined serum samples from patients and studied the effects of protein, hemoglobin, and lipids on bilirubin measurement. Results from the thin-film assay compared favorably with those of the other methods. Total and within-day precision (CV), assessed over a one-year period, were better than 6% and 3%, respectively, at all concentrations. Analytical recovery was 99 +/- 3%. Samples from individuals having a wide range of liver diseases demonstrated, by linear regression, good correlation between the thin-film method and the two wet-chemistry methods (correlation coefficients of 0.990 and 0.994). We conclude that the thin-film method offers a valid alternative assay for total bilirubin.


Balloon angioplasty of native coarctation of the aorta in a local group of children: acute results and midterm angiographic re-assessment.
Balloon angioplasty of native coarctation of the aorta is gaining acceptance as an alternative to surgery in children. The aim of this study was to assess the acute and midterm effectiveness and safety of the procedure. During a 3-year period, nine patients with native coarctation underwent balloon angioplasty at a median age of 2.9 years (range: 4 mo - 12 y) and median weight of 11 kg (range: 3.1 - 51 kg). Balloon diameter selected was at least twice the diameter of the narrowed segment, but never more than the diameter of the aorta at diaphragmatic level. There was a significant improvement in the mean systolic gradient across the coarctation from 36 +/- 13mm Hg to 4 +/- 4 mm Hg (p < 0.001), and in the mean diameter of the narrowed segment from 4 +/- 1.3 mm to 7.2 +/- 2.7 mm (p < 0.001). There was no immediate mortality or complication. Follow-up catheterisation was done in eight patients, a mean of 2.7 years (range: 0.8 - 4 y) after the initial procedure. No evidence of restenosis was found, but one patient developed an aneurysm that was surgically resected. Balloon angioplasty is effective and safe for the treatment of native coarctation in children. Radiographic follow-up is advisable in the midterm. Balloon angioplasty offers an alternative to surgery in the treatment of selected children older than 3 months with native coarctation of the aorta.