Anion substitution induced vacancy regulating of cobalt sulfoselenide toward electrocatalytic overall water splitting.
Anion substitution is a valid strategy to modulate the active sites of the transition metal dichalcogenides (TMDs). Herein, a series of cobalt sulfoselenide nanomeshes (CoS2(1-x)Se2x@NC) were synthesized by calcining S/Se power with ultrathin metal-organic framework (MOFs) nanosheets. The vacancy concentration of CoS2(1-x)Se2x@NC could be adjusted through changing the ratio of S/Se precursor. Interestingly, CoS1.25Se0.75@NC electrocatalyst possesses the largest vacancy concentration as well as the optimal electrocatalytic performance. CoS1.25Se0.75@NC delivers an overpotential as low as 134 mV for hydrogen evolution reaction (HER) and 270 mV for oxygen evolution reaction (OER) at the current density of 10 mA cm -2, respectively. Furthermore, CoS1.25Se0.75@NC affords a low cell voltage of 1.67 V (at 10 mA cm-2) and outstanding cycling stability for overall water splitting reaction (more than 55 h). For HER process, theoretical calculations prove that anion vacancy not only lower the free energy barrier of H2O dissociation step but also favor the desorption step of intermediate H*. For OER process, the anion vacancies could modulate the adsorption/desorption free energy of oxygen-containing intermediates. The present work demonstrates a practical approach to modulate the vacancy concentration of cobalt sulfoselenide and provides new ideas for design of efficient non-metal electrocatalysts.


Sucrose transporters of resistant grapevine are involved in stress resistance.
The whole promoter regions of SUTs in Vitis were firstly isolated. SUTs are involved in the adaptation to biotic and abiotic stresses. The vulnerability of Vitis vinifera to abiotic and biotic stresses limits its yields. In contrast, Vitis amurensis displays resistance to environmental stresses, such as microbial pathogens, low temperatures, and drought. Sucrose transporters (SUTs) are important regulators for plant growth and stress tolerance; however, the role that SUTs play in stress resistance in V. amurensis is not known. Using V. amurensis Ruper. 'Zuoshan-1' and V. vinifera 'Chardonnay', we found that SUC27 was highly expressed in several vegetative organs of Zuoshan-1, SUC12 was weakly expressed or absent in most organs in both the species, and the distribution of SUC11 in source and sink organs was highest in Zuoshan-1. A search for cis-regulatory elements in the promoter sequences of SUTs revealed that they were regulated by light, environmental stresses, physiological correlation, and hormones. The SUTs in Zuoshan-1 mostly show a higher and rapid response than in Chardonnay under the induction by Plasmopara viticola infection, cold, water deficit, and dark conditions. The induction of SUTs was associated with the upregulation of key genes involved in sucrose metabolism and the biosynthesis of plant hormones. These results indicate that stress resistance in Zuoshan-1 is governed by the differential distribution and induction of SUTs by various stimuli, and the subsequent promotion of sucrose metabolism and hormone synthesis.


Modeling Chronic Coccidioidomycosis in Mice.
Coccidioidomycosis, caused by the dimorphic pathogens Coccidioides posadasii and C. immitis, is a fungal disease endemic to the southwestern United States, Mexico, and some regions of Central and South America. The mouse is the primary model for studying pathology and immunology of disease. Mice in general are extremely susceptible to Coccidioides spp., which creates challenges in studying the adaptive immune responses that are required for host control of coccidioidomycosis. Here, we describe how to infect mice to model asymptomatic infection with controlled, chronic granulomas and a slowly progressive but ultimately fatal infection that has kinetics more similar to the human disease.


Effectiveness of antihypertensive treatment in chronic renal failure: to what extent and with which drugs do patients treated by nephrologists achieve the recommended blood pressure?
Adequate control of blood pressure (BP) is important to slow the progression of chronic renal failure (CRF). The Joint National Committee (JNC) VI recommends BP <130/85 mmHg, or <125/75 mmHg if urinary protein excretion exceeds 1 g/d. Angiotensin converting enzyme inhibitors (ACE-I) are considered as first-line agents. The current study is a survey of the degree of goal achievement and prescription patterns of antihypertensive (AHT) medication according to the JNC guidelines in clinical nephrology practice. All patients with CRF, not on renal replacement therapy, treated by nephrologists at the University Hospital of North-Norway were included in this retrospective cross-sectional study. Data on protein:creatinine ratio (PC ratio), BP and AHT drugs prescribed were extracted from the hospital's databases and medical records. A total of 144 patients were included. The patients' age was 62+/-16 years and the serum creatinine value was 210+/-92 micromol/l (mean+/-s.d.). In all, 74 patients (51%) had PC ratio < or =1, 36 (25%) >1, and for 34 (24%) PC ratio had not been measured; 23 (31%) of the patients with PC ratio < or =1 had BP < or =130/85 (139+/-21/78+/-12), and 5 (14%) of those with PC ratio >1 had BP < or =125/75 (145+/-22/85+/-14). Failure to achieve the goal was most commonly due to elevated SBP. In all, 55 % of the patients were prescribed ACE-I or angiotensin receptor blocker (ARB). In conclusion, the recommended BP goals may be difficult to achieve for a high proportion of patients in clinical practice due to difficulty in lowering SBP. There is a potential for improved treatment of hypertension in CRF patients, including increased prescription of ACE-I and ARB.


Protocol to analyze antitumor immunity of orthotopic injection and spontaneous murine high-grade glioma models using flow cytometry and single-cell RNA sequencing.
Despite the recognized importance of antitumor immunity, our understanding of brain tumor immunity is poor. Orthotopic injection models have been widely used for immunological analyses. However, these models have limitations in analysis of antitumor immunity because the approach involves drilling skulls and injecting tumor cells, which can induce adverse effects. We describe a protocol for the induction of spontaneous brain tumor model, isolation of single cells from brain tumor microenvironment, and analysis of the immune responses using scRNA-seq and flow cytometry. For complete details on the use and execution of this protocol, please refer to Park et al. (2021).


Iron assimilation and utilization in anaerobic ammonium oxidizing bacteria.
The most abundant transition metal in biological systems is iron. It is incorporated into protein cofactors and serves either catalytic, redox or regulatory purposes. Anaerobic ammonium oxidizing (anammox) bacteria rely heavily on iron-containing proteins - especially cytochromes - for their energy conservation, which occurs within a unique organelle, the anammoxosome. Both their anaerobic lifestyle and the presence of an additional cellular compartment challenge our understanding of iron processing. Here, we combine existing concepts of iron uptake, utilization and metabolism, and cellular fate with genomic and still limited biochemical and physiological data on anammox bacteria to propose pathways these bacteria may employ.


Association between thyroid-stimulating hormone and maternal hemodynamics in hypertensive disorders of pregnancy: an observational study.
Hypertensive disorders of pregnancy (HDP) are characterized by hemodynamic disturbances. Altered thyroid function is a risk factor for poor outcomes of pregnancy. However, the associations between thyroid function biomarkers and maternal hemodynamics during pregnancy in HDP remain unclear. From January 2016 to January 2018, pregnant women diagnosed with HDP admitted to the Nanjing Maternity and Child Health Care Hospital were prospectively enrolled in the third trimester. Normally distributed variables were expressed as mean ± standard deviation and skewed variables were expressed as median (25th percentile, 75th percentile). Correlations between thyroid-stimulating hormone (TSH) or free thyroxine (FT4) and maternal hemodynamic parameters were assessed by Pearson's correlation coefficient and 95% confidence interval (95%CI). Bonferroni's correction for multiple correlations was performed. Logistic regression models with odd ratio (OR) and 95%CI were applied to confirm the associations. A total of 163 third-trimester pregnant women with HDP with a mean gestational age of 35.62 ± 2.83 weeks were recruited. The infant birth weight of patients with elevated TSH levels was lower than that of patients with normal TSH levels (2635 ± 867 g vs. 3037 ± 673 g, p = 0.002). Reduced cardiac output (CO) was defined as CO < 3.5 L/min. The infant birth weight of patients with reduced CO was lower than that of patients with normal CO (2250 ± 510 g vs. 2890 ± 774 g, p = 0.002). TSH levels were significantly and negatively correlated with CO (r = - 0.260, 95%CI: - 0.392- -0.103, p < 0.001). FT4 levels were not significantly correlated with any of the maternal hemodynamic parameters (all p > 0.05). TSH level (OR = 1.371, 95%CI: 1.086-1.733, p = 0.008) was confirmed associated with reduced CO in the logistic regression analysis. Elevated TSH levels are associated with reduced CO in HDP during the third trimester.


Acquired Gerbode defect following endocarditis of the tricuspid valve: a case report and literature review.
The Gerbode's defect is a communication between the left ventricle and right atrium. It is usually congenital, but rarely is acquired, as a complication of endocarditis, myocardial infarction, trauma, or after previous cardiac surgery. The acquired Gerbode defect with involvement of the tricuspid valve acquired after bacterial endocarditis can be challenging to repair. We present a rare case of young woman, with endocarditis of the tricuspid valve and acquired Gerbode defect without previous cardiac surgery. She underwent successful surgical closure of the Gerbode defect and reconstruction of the septal leaflet of the tricuspid valve using a an autologous pericardial patch. A total of 20 other cases were reported with acquired Gerbode defect due to endocarditis in patients without previous cardiac surgery. Three other cases presented acquired Gerbode defect due to myocardial infarction and two due to chest trauma. Another series of 62 patients presented acquired Gerbode defect after previous cardiac surgery. Surgical treatment is always feasible with excellent outcome. However the percutanous transcatheter closure remains an excellent option especially in high risk patients.


Comparison of survival times of mice inoculated with brain tissue from various neurological diseases.
Mice inoculated intracerebrally before the age of 5 days with homogenates of autopsied brain tissue from patients with Creutzfeldt-Jakob (C-J), Alzheimer's, or Pick's diseases showed highly significant decreases in life span when compared with sham-inoculated control mice. With C-J disease there was strong indication of horizontal transmission of the agent to uninoculated mice caged with the inoculated mice. While the results with C-J disease were not unexpected in view of the known infectious etiology of the disease, the results obtained with Alzheimer's and Pick's diseases suggest that previously undetermined infectious or toxic agents may be associated with these two diseases, which currently have unresolved etiologies. Mice inoculated with autopsied brain tissue from patients with multiple sclerosis or subacute sclerosing panencephalitis had life spans similar to those of the control mice.


The spiral flap for fingertip resurfacing: short-term and long-term results.
We describe a homodigital neurovascular island flap for reconstructing large pulp defects of the fingertips and review the short-term and long-term appearance and function of the reconstructed fingertips. The spiral flap is a homodigital neurovascular island flap with a unique spiral advancement and transposition design that allows pulp reconstruction using sensate glabrous skin while restricting donor morbidity to the injured digit. Thirty-two fingertips were resurfaced using this flap. All had large pulp defects averaging 1.2 cm wide x 2.0 cm long (1.0-2.0 cm x 1.5-2.5 cm). Short-term results (<18 months) for all patients at a minimum of 6 months and long-term results (>5 years) for 10 patients with a mean follow-up of 13 years were reviewed. Objective outcome measures included static 2-point discrimination, degree of nail deformity (beaking), total active motion, and hypersensitivity or cold intolerance. Subjective outcome measures included patient satisfaction with function and aesthetics, using a visual analog scale. All flaps achieved primary healing with no complications. There was initially mild extension deficit in the proximal interphalangeal and distal interphalangeal joints, which improved to full range of motion in the long term. Sensory recovery was excellent, with an average 2-point discrimination of 5 mm initially, improving to 4 mm in the long term. Nail beaking was minimal initially but increased significantly in the long term. These results may be explained by soft tissue remodeling. All patients on long-term follow-up were highly satisfied with both aesthetic and functional outcome. There was no hypersensitivity or cold intolerance at either the short-term or long-term follow-up assessments. The spiral advancement-transposition flap is suitable for resurfacing large pulp defects with excellent short-term and long-term functional and aesthetic results and high patient satisfaction. Therapeutic IV.


Methods to recognize work-related cancer in workplaces, the general population, and by experts in the clinic, a Norwegian experience.
In most countries, the numbers of work-related cancer identified are much lower than are the estimated total burden of cancer caused by exposure at work. Therefore, there is a great need to use all available practical as well as epidemiological methods for identification as well as to develop new methods of recognizing cases of work-related cancers. Primarily based on practical experiences from Norway, methods to identify cases of possible work-related cancers in the general population and at workplaces as well as methods to recognize more specific cases after referral to specialized clinics are reviewed in this publication. Countries applying a number of the available methods to detect work-related cancer reach a reporting rate of 60 such cases per million, while other countries that do not employ such methods hardly identify any cases. As most subjects previously exposed to cancer causing agents and substances at work are gradually recruited out of work, methods should be versatile for identification of cases in the general population, as well as at work. Even in countries using a number of the available methods for identification, only a limited fraction of the real number of work-related cancer are notified to the labour inspectorate. Clinicians should be familiar with the methods and do the best to identify work-related cancer to serve prevention.


A pyramidal approach for automatic segmentation of multiple sclerosis lesions in brain MRI.
Quantitative assessment of Magnetic Resonance Imaging (MRI) lesion load of patients with multiple sclerosis (MS) is the most objective approach for a better understanding of the history of the pathology, either natural or modified by therapies. To achieve an accurate and reproducible quantification of MS lesions in conventional brain MRI, an automatic segmentation algorithm based on a multiresolution approach using pyramidal data structures is proposed. The systematic pyramidal decomposition in the frequency domain provides a robust and flexible low level tool for MR image analysis. Context-dependent rules regarding MRI findings in MS are used as high level considerations for automatic lesion detection.


Intensive combination chemotherapy for cancer of the oral cavity.
Thirty advanced cases of cancer of the oral cavity were treated by intensive combination chemotherapy using bleomycin, methotrexate, 5-fluorouracil, cyclophosphamide, and Oncovin administered over a period of 48 hours. Bleomycin was given as a continuous infusion and Oncovin was administered six hours prior to the administration of other drugs. A clinical response was obtained in 73.3% of the cases, a complete response in 33.3%, and a partial response in 40%. The toxicity was within acceptable limits.


Bone growth accelerated by stimulation of the epiphyseal plate with electric current.
The effect of stimulation with continuous small amounts (20 microA) of electric current on the distal epiphyseal plate of rabbit femurs was examined. In contrast to control animals 6 weeks after the operation 18 of the 20 experimental animals showed an increased lengthening or broadening of the femur on the operated side. In 14 cases the increased growth resulted in varus or valgus deformities.


Natural mega disturbances drive spatial and temporal changes in diversity and genetic structure on the toadfish Aphos porosus.
Natural disturbances can modify extinction-colonization dynamics, driving changes in the genetic diversity and structure of marine populations. Along Chilean coast (36°S, 73°W), a strong hypoxic-upwelling event in 2008, and a mega earthquake-tsunami in 2010 caused mass mortality within the Aphos porosus population, which is a vulnerable species with low dispersal potential. We evaluated the effects of these two major disturbances on the diversity and spatial-temporal genetic structure of Aphos porosus in two neighboring areas that were impacted on different levels (High level: Coliumo Bay; Low level: Itata Shelf). Thirteen microsatellites (from 2008 to 2015) amplified in individuals collected from both locations were used to evaluate the effects of the two disturbances. Results showed that after the strong hypoxic-upwelling event and the mega earthquake-tsunami, Aphos porosus populations exhibited lower genetic diversity and less effective population sizes (Ne < 20), as well as asymmetries in migration and spatial-temporal genetic structure. These findings suggest a rise in extinction-recolonization dynamics in local Aphos porosus populations after the disturbances, which led to a loss of local genetic diversity (mainly in Coliumo Bay area impacted the most), and to greater spatial-temporal genetic structure caused by drift and gene flow. Our results suggest that continuous genetic monitoring is needed in order to assess potential risks for Aphos porosus in light of new natural and anthropogenic disturbances.


Hydraulic basis for the evolution of photosynthetic productivity.
Clarifying the evolution and mechanisms for photosynthetic productivity is a key to both improving crops and understanding plant evolution and habitat distributions. Current theory recognizes a role for the hydraulics of water transport as a potential determinant of photosynthetic productivity based on comparative data across disparate species. However, there has never been rigorous support for the maintenance of this relationship during an evolutionary radiation. We tested this theory for 30 species of Viburnum, diverse in leaf shape and photosynthetic anatomy, grown in a common garden. We found strong support for a fundamental requirement for leaf hydraulic capacity (Kleaf) in determining photosynthetic capacity (Amax), as these traits diversified across this lineage in tight coordination, with their proportionality modulated by the climate experienced in the species' range. Variation in Kleaf arose from differences in venation architecture that influenced xylem and especially outside-xylem flow pathways. These findings substantiate an evolutionary basis for the coordination of hydraulic and photosynthetic physiology across species, and their co-dependence on climate, establishing a fundamental role for water transport in the evolution of the photosynthetic rate.


Efficient Enhancement of Electron Transport and Collection Capability in PTB7:PC71 BM-based Solar Cells Enabled by Sulforhodamine Cathode Interlayers.
Development of low-cost water-/alcohol-soluble interfacial materials is a crucial issue to promote the commercialization of polymer solar cells (PSCs). Herein, two derivatives of low-cost rhodamine, called sulforhodamine 101 (SR101) and sulforhodamine B (SRB), are applied as cathode interfacial layers (CILs) to effectively improve the charge-carrier transportation and collection, reduce the work function (WF) of Al counter electrode, and decrease the series resistance and charge recombination in the PSCs. As a result, SR101-based devices show excellent performance with the highest power conversion efficiency (PCE) of 9.10 %, superior to that of both the control devices with MeOH/Al and Ca/Al. Notably, sulforhodamine is commercially available with low cost and great solution-processability. This work demonstrates that sulforhodamine has a great potential as a CIL material,which is suitable for the large-area fabrication process and commercialization of highly efficient PSCs.


The comparative tissues distribution of platinum and 14C in mice receiving 14C-labelled carboplatin.
Since the reactivity of carboplatin depends on the rate of removal of the 1,1-cyclobutanedicarboxylate ligand, the time course of this dissociation has been determined in various tissue and body fluids using 14C-labelled carboplatin (cis-diammine[1,1-cyclobutane-1-14C-dicarboxylate]platinum II). Mice received 14C-carboplatin (80 mg/kg; 1.1 mCi/kg, i.v.), and tissue was removed at times ranging from 5 min to 5 days posttreatment. Following solubilization, tissue aliquots were analyzed for platinum and 14C contents. Carboplatin remained intact for up to 2 h posttreatment, since the ratio of 14C: Pt in tissues (nmol/g) was unity. Thereafter, the 14C ligand was released from the molecule and preferentially removed from tissues, indicated by decreasing 14C: Pt ratios. The elimination half-lives for Pt varied between tissues (40-156 h). In contrast, the corresponding half-lives for the 14C species were similar in most types of tissue (18-35 h), although those in the liver and spleen were exceptional (210 and 90 h, respectively). At 5 days a maximum of 4%-24% of the total Pt in tissue might exist as intact drug. Thus, the metabolic handling of carboplatin varies according to the tissue, since the elimination of the 14C cyclobutane dicarboxylate species from most tissue was similar and Pt elimination was slower and tissue-dependent.


Automatic differentiation of ruptured and unruptured intracranial aneurysms on computed tomography angiography based on deep learning and radiomics.
Rupture of intracranial aneurysm is very dangerous, often leading to death and disability. In this study, deep learning and radiomics techniques were used to automatically detect and differentiate ruptured and unruptured intracranial aneurysms. 363 ruptured aneurysms and 535 unruptured aneurysms from Hospital 1 were included in the training set. 63 ruptured aneurysms and 190 unruptured aneurysms from Hospital 2 were used for independent external testing. Aneurysm detection, segmentation and morphological features extraction were automatically performed with a 3-dimensional convolutional neural network (CNN). Radiomic features were additionally computed via pyradiomics package. After dimensionality reduction, three classification models including support vector machines (SVM), random forests (RF), and multi-layer perceptron (MLP) were established and evaluated via area under the curve (AUC) of receiver operating characteristics. Delong tests were used for the comparison of different models. The 3-dimensional CNN automatically detected, segmented aneurysms and calculated 21 morphological features for each aneurysm. The pyradiomics provided 14 radiomics features. After dimensionality reduction, 13 features were found associated with aneurysm rupture. The AUCs of SVM, RF and MLP on the training dataset and external testing dataset were 0.86, 0.85, 0.90 and 0.85, 0.88, 0.86, respectively, for the discrimination of ruptured and unruptured intracranial aneurysms. Delong tests showed that there was no significant difference among the three models. In this study, three classification models were established to distinguish ruptured and unruptured aneurysms accurately. The aneurysms segmentation and morphological measurements were performed automatically, which greatly improved the clinical efficiency. Our fully automatic models could rapidly process the CTA data and evaluate the status of aneurysms in one minute.


A microarray-based method to perform nucleic acid selections.
This method describes a microarray-based platform to perform nucleic acid selections. Chemical ligands to which a nucleic acid binder is desired are immobilized onto an agarose microarray surface; the array is then incubated with an RNA library. Bound RNA library members are harvested directly from the array surface via gel excision at the position on the array where a ligand was immobilized. The RNA is then amplified via RT-PCR, cloned, and sequenced. This method has the following advantages over traditional resin-based Systematic Evolution of Ligands by Exponential Enrichment (SELEX): (1) multiple selections can be completed in parallel on a single microarray surface; (2) kinetic biases in the selections are mitigated since all RNA binders are harvested from an array via gel excision; (3) the amount of chemical ligand needed to perform a selection is minimized; (4) selections do not require expensive resins or equipment; and (5) the matrix used for selections is inexpensive and easy to prepare. Although this protocol was demonstrated for RNA selections, it should be applicable for any nucleic acid selection.


Present status of endovascular brachytherapy in peripheral arteries.
Peripheral artery disease based on atherosclerosis is one of the major problems in angiology. Endovascular brachytherapy has shown to be a promising new treatment method for prevention of restenosis after femoropopliteal angioplasty. Brachytherapy for peripheral arteries is performed by using an iridium-192 gamma source delivered with a remote controlled afterloading unit. Semiflexible 5F radiation catheter without centering possibility and specially designed 7F centering radiation delivery catheter with segmented balloons are available. After angioplasty patient is transported to the brachytherapy unit equipped with specific shielded walls. For treatment planning the whole length of intervention (interventional length = IL) plus safety margins is assumed to be the target. Dose should be related to a certain radial depth (2 mm) from the vessel lumen into vessel wall as proposed in the EVA GEC ESTRO Recommendations. Treatment planning is performed based on the vessel lumen diameter, IL safety margins and reference isodose length (RIL). First clinical experience with endovascular brachytherapy was obtained in Frankfurt and showed significant improvement of arterial patency even after a long follow-up period. The Vienna-2 study was the first prospective, randomized trial proofing 48% relative reduction of restenosis in the brachytherapy arm. The results of ongoing trials using centering catheter (Vienna-3, PARIS) are soon expected and will definitely determine the role of endovascular brachytherapy for restenosis prevention after angioplasty.


Derivation of an induced pluripotent stem cell line (GWCMCi001-A) from PBMCs of a four-year-old male patient with Immunoglobulin A nephropathy.
Immunoglobulin A nephropathy (IgAN) is a common primary glomerular disease contributing to end-stage renal failure. In this study, the induced pluripotent stem cell line GWCMCi001-A from PBMCs of a 4-year-old male patient with IgAN using the episomal plasmids was established, which is an ideal in vitro model to understand the exact pathogenesis of IgAN.


Psychiatric diagnosis in self-poisoning patients.
The Present State Examination was administered to 539 patients who attended a casualty department after an act of self-poisoning during the course of a year. Computer analysis by means of the Catego program showed that 30% of the patients had insufficient symptoms to be considered as psychiatric 'cases'. Fewer than 4% had symptoms of functional psychosis. About 60% of the patients were classed as depressed: on several indices this group was less severely ill than a group of depressives feceiving psychiatric treatment. It is suggested that psychiatric treatment is essential for only a small proportion of self-poisoning patients. The effectiveness of psychiatric treatment for the large group of patients with depressive disorders of minor severity and probably short duration has still to be evaluated.


Influence of the medical treatment schedule in new diagnoses patients with heart failure and reduced ejection fraction.
Heart failure (HF) guidelines recommend treating all patients with HF and reduced ejection fraction (HFrEF) with quadruple therapy, although they do not establish how to start it. This study aimed to evaluate the implementation of these recommendations, analyzing the efficacy and safety of the different therapeutic schedules. Prospective, observational, and multicenter registry that evaluated the treatment initiated in patients with newly diagnosed HFrEF and its evolution at 3 months. Clinical and analytical data were collected, as well as adverse reactions and events during follow-up. Five hundred and thirty-three patients were included, selecting four hundred and ninety-seven, aged 65.5 ± 12.9 years (72% male). The most frequent etiologies were ischemic (25.5%) and idiopathic (21.1%), with a left ventricular ejection fraction of 28.7 ± 7.4%. Quadruple therapy was started in 314 (63.2%) patients, triple in 120 (24.1%), and double in 63 (12.7%). Follow-up was 112 days [IQI 91; 154], with 10 (2%) patients dying. At 3 months, 78.5% had quadruple therapy (p < 0.001). There were no differences in achieving maximum doses or reducing or withdrawing drugs (< 6%) depending on the starting scheme. Twenty-seven (5.7%) patients had any emergency room visits or admission for HF, less frequent in those with quadruple therapy (p = 0.02). It is possible to achieve quadruple therapy in patients with newly diagnosed HFrEF early. This strategy makes it possible to reduce admissions and visits to the emergency room for HF without associating a more significant reduction or withdrawal of drugs or significant difficulty in achieving the target doses.


Anatomy and white matter connections of the lateral occipital cortex.
White matter tracts link different regions of the brain, and the known functions of those interconnected regions may offer clues about the roles that white matter tracts play in information relay. The authors of this report discuss the structure and function of the lateral occipital lobe and how the lateral occipital lobe communicates with other regions via white matter tracts. The authors used generalized q-sampling imaging and cadaveric brain dissections to uncover the subcortical white matter connections of the lateral occipital lobe. The authors created GQI of ten healthy controls and dissected ten cadaveric brains. The middle longitudinal fasciculus, vertical occipital fasciculus, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, optic radiations, and a diverse array of U-shaped fibers connect the lateral occipital lobe to itself, parts of the temporal, parietal, and medial occipital cortices. The complex functional processes attributed to the lateral occipital lobe, including object recognition, facial recognition, and motion perception are likely related to the subcortical white matter tracts described within this study. There was good concordance between the white matter tracts generated using GQI and the white matter tracts that were found after dissection of the cadaveric brains. This article presents the anatomic connections of the lateral occipital lobe and discusses the associated functions.


Cues to solution, restructuring patterns, and reports of insight in creative problem solving.
While the subjective experience of insight during problem solving is a common occurrence, an understanding of the processes leading to solution remains relatively uncertain. The goal of this study was to investigate the restructuring patterns underlying solution of a creative problem, and how providing cues to solution may alter the process. Results show that both providing cues to solution and analyzing problem solving performance on an aggregate level may result in restructuring patterns that appear incremental. Analysis of performance on an individual level provides evidence for insight-like solution patterns. However, no evidence is found for a relationship between an individual's restructuring pattern and their subjective experience of insight during problem solving.


Changes over time in papanicolaou cytology test and HPV test in a large women's academic center laboratory.
In the past 2 decades, cervical cancer screening guidelines in the United States have undergone numerous revisions with recent greater emphasis on primary high-risk human papillomavirus (hrHPV) testing. We examine the trends of Papanicolaou test and hrHPV testing at our large academic center across 4 years (2006, 2011, 2016, and 2021) over a 15-year period. The number of ThinPrep Papanicolaou and hrHPV tests, as well as the triggers for HPV testing, were retrospectively analyzed. A total of 308,355 Papanicolaou tests and 117,477 hrHPV tests were reported across the 4 years. The number of Papanicolaou tests performed decreased nearly 3-fold over the study period, with only 43,230 Papanicolaou tests performed in 2021. The HPV test to Papanicolaou test ratio increased: 17% of Papanicolaou tests had an associated HPV test in 2006, whereas 72% of Papanicolaou tests ordered in 2021 had a companion hrHPV. The use of co-testing also increased. Overall, 73% were co-tests and 27% were reflexively ordered in the 4 one-year time periods. Co-tests constituted only 46% of HPV tests in 2006, but this increased to 93% in 2021. The percentage of positive hrHPV results decreased; in 2006, 18.3% of cases were positive, dropping to 8.6% in 2021 due to the marked increase in co-testing. Stratifying by diagnostic category, hrHPV results have remained relatively constant. With the numerous recent revisions of cervical screening guidelines, screening strategies at our institution reflected these changes in clinical practice. Papanicolaou and HPV co-testing became the most common screening method for women 30 to 65 years of age in our cohort.


[3-Meth-oxy-5-(meth-oxy-carbon-yl)isoxazol-4-yl](4-meth-oxy-phen-yl)iodo-nium 2,2,2-tri-fluoro-acetate.
A new isoxazole-based iodo-noium salt, C13H13INO5 +·C2F3O2 -, has been synthesized and structurally characterized. In the crystal, ions are linked by short I⋯O contacts to form a neutral tetra-ion aggregate. These combine with C-H⋯F and C-H⋯O inter-actions to form double-layered two-dimensional sheets in the (001) plane.


The novel cyclopropapyrroloindole(CPI) bisalkylators bearing 3,3'-(1,4-phenylene)diacryloyl group as a linker.
The novel cyclopropapyrroloindole(CPI) bisalkylators were synthesized and their antitumor activity was evaluated. Among these derivatives, AT-760 (5a) in which the two 3-methoxycarbonyl-2-trifluoromethylCPI (MCTFCPI) moieties are connected with a 3,3'-(1,4-phenylene)diacryloyl group, was found to exhibit more prominent cytotoxicity and antitumor activity than U-77,779 (bizelesin) (1).


Hydralazine Promotes Central Nervous System Recovery after Spinal Cord Injury by Suppressing Oxidative Stress and Inflammation through Macrophage Regulation.
This study aims to investigate the effects of hydralazine on inflammation induced by spinal cord injury (SCI) in the central nervous system (CNS) and its mechanism in promoting the structural and functional recovery of the injured CNS. A compressive SCI mouse model was utilized for this investigation. Immunofluorescence and quantitative real-time polymerase chain reaction were employed to examine the levels of acrolein, acrolein-induced inflammation-related factors, and macrophages at the injury site and within the CNS. Western blotting was used to evaluate the activity of the phosphoinositide 3-kinase (PI3K)/AKT pathway to study macrophage regulation. The neuropathic pain and motor function recovery were evaluated by glutamic acid decarboxylase 65/67 (GAD65/67), vesicular glutamate transporter 1 (VGLUT1), paw withdrawal response, and Basso Mouse Scale score. Nissl staining and Luxol Fast Blue (LFB) staining were performed to investigate the structural recovery of the injured CNS. Hydralazine downregulated the levels of acrolein, IL-1β, and TNF-α in the spinal cord. The downregulation of acrolein induced by hydralazine promoted the activation of the PI3K/AKT pathway, leading to M2 macrophage polarization, which protected neurons against SCI-induced inflammation. Additionally, hydralazine promoted the structural recovery of the injured spinal cord area. Mitigating inflammation and oxidative stress by hydralazine in the animal model alleviated neuropathic pain and altered neurotransmitter expression. Furthermore, hydralazine facilitated motor function recovery following SCI. Nissl staining and LFB staining indicated that hydralazine promoted the structural recovery of the injured CNS. Hydralazine, an acrolein scavenger, significantly mitigated SCI-induced inflammation and oxidative stress in vivo, modulated macrophage activation, and consequently promoted the structural and functional recovery of the injured CNS.


[Parenteral-enteral feeding and monitoring of patients with protein-calorie malnutrition in pharyngeal-laryngeal tumors].
The authors nourished artificially patients with stage III.--IV. pharyngeal and laryngeal tumors in the preoperative phase at the Department of Head and Neck Surgery, Postgraduate Medical School. The courses were monitored with biochemical and antropometrical measurements. The good results of wound healing advocate the use of the described method.


Stretch-induced triphosphorylation of myosin light chain and myogenic tone in canine basilar artery.
The relationship between phosphorylation of 20,000 Da myosin light chain (MLC20) and contraction in response to mechanical stretch was investigated in the canine basilar artery. A slow stretch (at a rate of 1 mm/s and a stimulus period for 15 min) increased triphosphorylated MLC20 despite lowered intracellular calcium concentration and mechanical activities, such as myogenic tone, shortening velocity and stiffness of the artery. Nicardipine, a Ca2+ channel blocker, and ML-9, a myosin light chain kinase (MLCK) inhibitor, partially inhibited the stretch-induced MLC20 phosphorylation. The remained phosphorylation was further reduced by calphostin C, a protein kinase C (PKC) inhibitor. Y-27632, a Rho-kinase inhibitor, inhibited phosphorylation of myosin light chain phosphatase and attenuated MLC20 phosphorylation. These results suggest that slow stretch induces triphosphorylation of MLC20, which is mediated by MLCK, PKC, and Rho-kinase, and that the triphosphorylation of MLC20 does not result in myogenic contraction, rather seems to counteract it.


Estimating drug delivery using hybrid system for simultaneous dynamic MRI and fluorescence tomography.
Optical tomography is often coupled with high resolution imaging modality like MRI to provide functional information associated with specific anatomical structure noninvasively. MRI-coupled paired agent fluorescence molecular tomography (MRI-PAFT) is a hybrid imaging modality capable of noninvasively quantifying drug-target engagement in vivo utilizing a targeted and an untargeted fluorescence agent. This study compares the uptake kinetics of MRI contrast agent and fluorescence agents in tumor and normal tissue, and demonstrates the potential of utilizing MRI contrast agent kinetic and targeted fluorescence agent kinetics to quantify targeted tumor receptor concentration in glioma tumor model.


Perceptual learning with odors: implications for psychological accounts of odor quality perception.
After two odors have been experienced in a mixture, the pair are subsequently rated as sharing more qualities and smelling more alike than equally exposed controls. These effects may result from the retrieval of a common mixture memory when either component is sniffed alone. If correct, odor pairs experienced together in a mixture should also be less discriminable than those experienced an equal number of times but in different mixtures. This was tested here by exposing participants to two odor mixtures (either AX, BY or AY, BX) and then testing their ability to discriminate between the components. As predicted, odors previously experienced together as a mixture were less discriminable than controls. These and related findings noted above suggest that learning and memory play an important role in odor quality perception.


Stereotype or grammar? The representation of gender when two-year-old and three-year-old French-speaking toddlers listen to role nouns.
Using a preferential looking paradigm, the current study examined the role that grammatical gender plays when preschool French-speaking toddlers process role nouns in the masculine form (e.g., chanteurs masculine 'singers'). While being auditorily prompted with "Look at the 'a role noun'!", two- and three-year-olds were presented with two pictures of two characters ('boy-boy' versus 'girl-boy') with attributes of the given role noun (e.g., singers with microphone and music notes). All role nouns were presented in the masculine plural form, which, despite its use to refer to mixed-gender groups, can be interpreted as referring to men. We expected toddlers to be biased by stereotypes, yet when non-stereotypical role nouns were presented, toddlers were not influenced by grammatical gender, but by their own sex (even more so for three-year-old toddlers). The absence of sensitivity to grammatical cues for either age group is discussed in terms of the developmental awareness of grammatical gender.


High incidence of urological complications in men dying from prostate cancer.
The incidence and clinical characteristics of urological adverse events suffered by patients with lethal prostate cancer (PCa) toward the end of life are not fully understood. A search of our hospital medical registry identified 3816 individuals diagnosed with PCa, among whom 243 died from the disease and 144 died from other causes (n = 387). We retrospectively reviewed the 387 patients who had died to determine the incidence of PCa-related urological complications, associated factors, and subsequent palliative interventions. Major urological complications that required therapeutic intervention were observed in 28.4 % of PCa patients dying from the disease itself, whereas such complications were much less frequent (4.3 %) in PCa patients dying from other causes. Urological complications were associated with local recurrence in men who underwent prostatectomy, lower irradiation dose in men who underwent radiotherapy, and pretreatment higher T stage and absence of metastasis in men who underwent androgen deprivation therapy (ADT) as the primary treatment. Patients who received long-term ADT for localized disease had the highest risk for urological complications. Therapeutic intervention was highly effective for palliation. Urological adverse events are very common in PCa patients who are dying from the disease. Prevention or early palliation should be considered in patients at high risk of PCa-related urological complications.


Perceptions of Older People Regarding Their Vision and Incident Causation.
It is widely known that visual impairment (VI) is a risk factor for falls, but patients or their eye care practitioners may not recognize other kinds of incidents as being problematic because of their vision. Consequently, older people with VI may have unmet needs for advice on how to carry out activities of daily living safely. Therefore, the purpose of this study was to understand whether older people with VI consider their vision as a causative factor of incidents they experience and their perceptions regarding the prevention of future incidents. If sample size permitted, a secondary aim was to evaluate whether quantitative findings supported their perceptions. The study design was a prospective cohort study evaluating injurious and damaging incidents and related near misses using open questions in a written 2-weekly large-print diary with active follow-up over 8 weeks in older people (>60 years, n = 80) with and without VI. Baseline measures included habitual binocular visual acuity, contrast sensitivity, visual fields, 3-m walk test, and Short Form 12 physical and mental component scores. Participants' diary entries were coded. Factor analysis and binary logistic analysis were used to investigate whether baseline measures were predictive of incident occurrence. Risk and preventative factors identified were compared. Participants perceived that their vision was implicated in bump and fall incidents. Quantitative analysis indicated that contrast sensitivity and fitness were significant predictors of incident occurrence. Six vision-related and five non-vision-related causative factors were identified by participants as contributing factors. Participants frequently stated "don't know" when asked to identify solutions to prevent incident recurrence. Participants had unmet needs for advice in relation to incident prevention. It would be prudent for eye care practitioners to raise incident prevention in eye care consultations regardless of voiced patient concerns.


Invasive pulmonary and cerebral aspergillosis in a patient with Weil's disease.
We describe the successful medical treatment of invasive aspergillosis in a patient suffering from Weil's disease with a combined therapy based on amphotericin B lipid complex and voriconazole.


Free tissue transfers for reconstruction of weight-bearing heel defects: Flap selection, ulceration management, and contour revisions.
Soft tissue defects in the weight-bearing heel represent a reconstructive challenge because of tissue complexity and lack of local/regional coverage. This study presents our reconstruction outcomes of different defect aetiologies, reconstruction timing, and flap selection. Patients with weight-bearing heel defects who underwent free tissue transfer from 2003 to 2014 and with at least 6 months of follow-up were retrospectively reviewed. Flap types (fasciocutaneous vs muscle/musculocutaneous), timing of reconstruction (early vs subacute vs delayed), and defect aetiology were compared in terms of flap failure, vascular complications, and ulceration. Seventy-four flaps were used to reconstruct weight-bearing heel defects in 70 patients. Defect aetiology included trauma in 53 patients (75%), chronic wound in 12 patients (17%), and tumour resection in 6 patients (8%). Flap survival was 97% (72/74). There was no significant difference in flap failures between muscle and fasciocutaneous flaps. The timing of reconstruction showed no difference in flap survival. There was a significant difference in ulceration rate between the trauma and non-trauma groups (p = 0.001). Twenty-eight ulcers (39%) developed, 12 (43%) of which presented 3 years postoperatively, while only 6 cases (21%) presented within one year postoperatively. Our experience represents one of the highest survival rates reported regarding free flap weight-bearing heel reconstruction. The anterolateral thigh flap was our first choice for extensive heel defects. Ulceration incidence was directly related to trauma and tends to develop 3 years after reconstruction. Delayed reconstruction was at least as safe as early or subacute reconstruction though with less need for debulking.


Melatonin supplementation combats nickel-induced phytotoxicity in Trigonella foenum-graecum L. plants through metal accumulation reduction, upregulation of NO generation, antioxidant defence machinery and secondary metabolites.
Nickel (Ni) at a toxic level (80 mg kg-1 of soil) adversely affects the crop performance of fenugreek (Trigonella foenum-graecum L.). Melatonin (MEL), a potent plant growth regulator, is ascribed to offer promising roles in heavy metal stress alleviation. In this study, different doses viz. 0, 25, 50, 75 and 100 μM of MEL were administered to plants through foliage under normal and Ni-stress conditions. The experiment unveiled positive roles of MEL in enhancing root-shoot lengths, fresh-dry weights, seed yield and restoring photosynthetic efficiency assessed in terms of higher Fv/Fm, YII, qP, and lower NPQ values in plants exposed to Ni (80 mg kg-1). MEL supplementation (at 75 μM) effectively restricted Ni accumulation and regulated oxidative stress via modulation of MDA, O2-, H2O2 and NO generation, most prominently. Besides, MEL at 75 μM more conspicuously perked up the activities of antioxidant enzymes like SOD, POX, CAT and APX by 15.7, 20.0, 14.5 and 16.5% higher than the Ni-exposed plants for effective ROS scavenging. Likewise, MEL at 75 μM also efficiently counteracted Ni-generated osmotic stress, through an upscaled accumulation of proline (19.6%) along with the enhancement in the concentration of total phenols (13.6%), total tannins (11.2%), total flavonoids (25.5%) and total alkaloids (19.2%) in plant's leaves. Furthermore, under 80 mg kg-1 Ni stress, MEL at 75 μM improved the seed's trigonelline content by 40.1% higher compared to Ni-disturbed plants, upgrading the pharmacological actions of the plant. Thus, the present study deciphers the envisaged roles of MEL in the alleviation of Ni stress in plants to enhance overall crop productivity.


Investigation and analytical application of the reactions of eriochrome cyanine R with fluvoxamine and fluoxetine.
Eriochrome cyanine R (ECR) reacts with fluvoxamine (FXM) and fluoxetine (FXT) forming coloured ion-association compounds. The composition of the compounds, studied by spectrophometric methods showed that the molar ratio ECR:FXM = 1:2 and ECR:FXT = 1:2. The formation and extraction conditions of the compounds were established. The compounds were characterised by UV, VIS, and IR spectrometry. It was found that the compounds are insoluble in water but quantitatively extracted into buthanol. Under the optimal experimental conditions fluvoxamine and fluoxetine were determined in the range 2-40 microg/ml and 2-20 microg/ml, respectively. The relative standard deviation is about +/- 2%.


Minimally invasive compared to open microdiscectomy for lumbar disc herniation.
Before the advent of minimally invasive surgery for microdiscectomy, an open microdiscectomy had been the standard surgical intervention. Minimally invasive techniques have recently become more popular based upon the premise that smaller, less traumatic incisions should afford better recovery times and outcomes. From 2005 to 2008 we analyzed the outcomes of 25 patients who received an open microdiscectomy compared to 20 patients who received a minimally invasive microdiscectomy by the senior author (DC) in the lumbar region for disc herniation. A retrospective analysis was performed by carefully reviewing medical records for perioperative and immediate postoperative outcomes, and clinical follow-up was obtained either in the clinic or by telephone. There were no statistically significant differences between the minimally invasive and open groups in terms of operative time, length of stay, neurological outcome, complication rate, or change in pain score (pain improvement).


The Persian version of the Berg Balance Scale: inter and intra-rater reliability and construct validity in elderly adults.
As a well-known measure for quantifying functional mobility in elderly persons, Berg Balance Scale (BBS) was used in the present study to evaluate its psychometric properties among a sample of 106 elderly individuals speaking Persian language. After forward-backward translation process, videotapes were recorded from all participants while performing 14 tasks of the BBS. The volunteers were also asked to perform the Timed Up and Go (TUG) test at the same session. To determine inter and intra-rater reliability, the videotapes were viewed by two experienced therapists while one of the raters assessed the videotaped performance of the subjects on a second occasion. Intraclass correlation coefficients (95% confidence interval) of 0.93 (0.87 0.96) and 0.95 (0.92 0.97) were obtained for inter and intra-rater reliability, respectively. Cronbach's alpha was 0.62 which is marginally lower than the cut-off point of 0.70. Furthermore, there were no ceiling and floor effects for the Persian version. In terms of construct validity, the BBS had a negative and strong correlation with the TUG (r = -0.74, p < 0.001). Acceptable levels of intra and inter-rater reliability with a moderate internal consistency and high validity were demonstrated for the Persian version of BBS.


Effectiveness of the SYSTEM 1E Liquid Chemical Sterilant Processing System for reprocessing duodenoscopes.
A troubling number of health care-acquired infection outbreaks and transmission events, some involving highly resistant microbial pathogens and resulting in serious patient outcomes, have been traced to reusable, high-level disinfected duodenoscopes in the United States. The Food and Drug Administration (FDA) requested a study be conducted to verify liquid chemical sterilization efficacy of SYSTEM 1E(®) Liquid Chemical Sterilant Processing System (STERIS Corporation, Mentor, OH) with varied duodenoscope designs under especially arduous conditions. Here, we describe the system's performance under worst case SYSTEM 1E(®) processing conditions. The test protocol challenged the system's performance by running a fractional cycle to evaluate reduction of recoverable test spores from heavily contaminated endoscopes, including all channels and each distal tip, under worst case SYSTEM 1E(®) processing conditions. All devices were successfully liquid chemically sterilized, showing greater than a 6 log10 reduction of Geobacillus stearothermophilus spores at every inoculation site of each duodenoscope tested, in less than half the exposure time of the standard cycle. The successful outcome of the additional efficacy testing reported here indicates that the SYSTEM 1E(®) is an effective low-temperature liquid chemical sterilization method for duodenoscopes and other critical and semicritical devices. It offers a fast, safe, convenient processing alternative while providing the assurance of a system expressly tested and cleared to achieve liquid chemical sterilization of specific validated duodenoscope models.


Influence of subcutaneous injection of essential fatty acids on the stress-induced modifications of rat platelet aggregation and membrane lipid composition.
Membrane lipids play an important role in the function of blood platelets but the mechanisms by which the lipid composition of the platelet membrane is adjusted remain unclear. It has been shown that stress and poly-unsaturated fatty acids modified the lipid composition of blood plasma and platelet lipids, but very little is known about the effect of stress and fatty acids on membrane platelet lipid composition. The purpose of the present investigation was to study the influence of the essential fatty acids: linoleic, linolenic and arachidonic acids on the composition of the platelet membrane lipids of rats assigned to heat and restraint stress. It was shown that injections of polyunsaturated fatty acids decrease or suppress the stress-induced increase in platelet aggregation, suppress the stress-induced modification of the composition of the platelet membrane lipids and modify the fatty acid composition of the platelet membrane phospholipids.


On the pathogenesis of diabetic retinopathy.
Recent investigations of retinal vascular cells in tissue culture, animal models, and diabetic human subjects suggest several potential pathogenetic mechanisms for diabetic retinopathy. These include the enzyme aldose reductase, which appears to be responsible for basement membrane thickening in galactosemic rats (since the lesion is prevented by an aldose reductase inhibitor), and a picture, in galactosemic dogs, that closely resembles early, background diabetic retinopathy; insulin, which stimulates, and elevated glucose levels, which inhibit in vitro proliferation of retinal pericytes. Various hormones, including the sex hormone, the insulin-like growth factors and, perhaps independently, growth hormones, may influence the later stages of diabetic retinopathy. Chronic hyperglycemia appears to be the primary pathogenetic agent in diabetic retinopathy as well as in other complications of diabetes, but the different rates of onset and progression of these complications suggest that glucose acts through different biochemical pathways that are probably under different genetic control. Finally, the locus of the primary biochemical lesion in diabetic retinopathy may reside in the neuronal or glial cells of the retina, with the retinal blood vessels only secondarily involved.


A 77-year-old woman with sudden onset of blue discolouration of right third toe.
We report on a 77-year-old woman with a history of peripheral vascular disease who presented with an acute-onset tender blue toe and deteriorating renal function. A clinical diagnosis of blue toe syndrome was made but the patient deteriorated rapidly and died. This case illustrates the rapidly devastating nature and fatality of blue toe syndrome. There is no effective treatment for this condition.


Biomimetic electrical stimulation induces rat bone marrow mesenchymal stem cells to differentiate into cardiomyocyte-like cells via TGF-beta 1 in vitro.
Electrical conductance is one of the factors of the microenvironment of cardiomyocytes, and electrical stimulation (ES) has been shown to modulate the differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) toward a cardiomyogenic fate. Transforming growth factor-beta 1 (TGF-β1) stimulates the cardiomyogenic marker expression in BMSCs. Herein, we promoted the differentiation of BMSCs into cardiomyocyte-like cells using ES to confirm if TGF-β1 mediates this event in vitro. ES increased protein levels of TGF-β1 in BMSCs, and this effect was better than that observed with 5-azacytidine (5-Aza). The effect of ES on promoting cardiomyogenic marker expression in BMSCs was enhanced by TGF-β1. Furthermore, the protein expression levels of Connexin43 (Cx43) and Alpha-actinin 2 (ACTN2) induced by ES in BMSCs were significantly decreased by pirfenidone. These results show that ES promotes cardiomyocyte-like cells differentiation in rat BMSCs and is possibly mediated by TGF-β1 in vitro.


Osteoid osteoma of the shoulder and elbow: from diagnosis to minimally invasive removal.
Musculoskeletal tumours are rare in the daily practice of an orthopaedic surgeon or even a shoulder and elbow specialist. Patient complaints are often related to secondary changes to the underlying disease making the correct diagnosis challenging. The goal of this study is to identify key symptoms and findings which should give rise to suspicion of an osteoid osteoma. This retrospective study analyses the diagnostic pathway, surgical treatment and clinical outcome of six patients who underwent resection of an osteoid osteoma of the shoulder or elbow joint. Average follow-up was 24 months (range 16-36 months). The neoplasm was often associated with synovitis mimicking a frozen joint causing marked delay in tumour identification. Misdiagnosis led to surgery without addressing the tumour in two cases, making further surgical intervention necessary. Once the tumour was identified and removed the pain resolved rapidly. In cases of chronic shoulder or elbow pain without an adequate clinical history an underlying cause including rarities such as an osteoid osteoma or other musculoskeletal tumours should be taken into consideration. Particularly in young patients, a magnetic resonance imaging (MRI)-proven hot spot of unknown origin should prompt a computed tomography examination to further clarify the source of pain and stiffness. IV, case series.


Acinetobacter species as a cause of catheter-related infections.
In recent years, Acinetobacter species have emerged as clinically important pathogens. Though these organisms are widely prevalent in nature, most human infections are hospital-acquired. Acinetobacter baumannii is the predominant species. Nosocomial Acinetobacter baumannii infections such as respiratory tract infections, urinary tract infections, meningitis following neurosurgical procedures, and bacteremia mainly affect patients with severe underlying disease in the ICU and often, in the setting of nosocomial outbreak. The occurrence of multiresistant strains often limits therapeutic options. A substantial part of Acinetobacter baumannii bacteremia cases represent catheter-related infections that usually carry a favorable prognosis. Acinetobacter species other than Acinetobacter baumannii are less frequently reported as a cause of infection in humans. Bacteremia due to these organisms is mostly sporadic and almost exclusively related to intravascular devices. The underlying diseases are often less severe than those of patients affected by Acinetobacter baumannii infections. The clinical course is usually benign and the infection responds readily to catheter removal irrespective of the appropriateness of antimicrobial therapy.


Effect of adding Mycophenolate mofetil in paediatric renal transplant recipients with chronical cyclosporine nephrotoxicity.
Cyclosporine (CyA) has made a great impact on 1-year allograft survival, however, after years, renal function deteriorates, possibly due to chronic toxicity. Recently, Mycophenolate mofetil (MMF) was introduced as a non-nephrotoxic immunosuppressant that might be effective in chronical transplant arteriolopathy. We therefore started MMF at a dose of 600 mg/m2 b. i. d. in 18 pediatric renal transplant recipients (10.8 +/- 3.9 (SD) years of age at transplantation, 11/18 with a history of rejections) with biopsy-proven chronic arteriolopathy and other signs of CyA toxicity at a mean follow up time of 6.2 +/- 2.7 (range 2.3-11.8) years after transplantation. One month prior to conversion, mean serum creatinine was 171 +/- 96 micromol/l, lower than at the time of conversion (188 +/- 100 micromol/l, P = 0.003, paired t-test). At last follow-up (median 13.7 months, range 5.0 to 25.0 months) after conversion, mean serum creatinine decreased significantly to 127 +/- 69 micromol/l (P = 0,0003, paired t-test). The CyA dosage was reduced from a mean of 150 +/- 39 mg/ m2 per day to 59 +/- 13 mg/m2 per day in 7 patients, and CyA was discontinued in 11 patients after a median period of nine months (range 1-18 months). After a median period of 21 days, a pharmacokinetic profile was performed in all patients. The mean MMF dose was 1117 +/- 319 mg/m2 per day (range 675-1774 mg/m2 per day). The mean Mycophenolic acid (MPA) trough concentration was 4.0 +/- 2.0 microg/ml, range 1.4-7.9 microg/ml. Mean 12 h MPA AUC was 70.6 +/- 28.1 (range 31.9-127) microg x h/ml. Except for one patient with diarrhea associated with a high AUC, and for one patient with a steroid-sensitive rejection episode after 566 days, no other patient experienced side effects or a rejection episode. Prednisolone was left unaltered at 2-4 mg/m2 per day. We conclude that MMF allows safe reduction of CyA with markedly better graft function, suggesting that chronical CyA-toxicity partially accounts for deteriorating allograft function.


Combining chlorination and chloramination processes for the inhibition of biofilm formation in drinking surface water system models.
The aim of this study was to investigate the inhibition of biofilm formation on stainless steel (SS) and galvanized mild steel (MS) in chlorine (AFC(1)) and chlorine-monochloramine treated waters (AFC(2)M). Disinfection was carried out using 2.5 mg l(-1) free chlorine followed by 1.5 mg l(-1) monochloramine, with non-disinfected water used as control water. Results of the standard spread plate procedure, DAPI epifluorescence microscopy and scanning electron microscopy revealed bacterial colonization of SS and MS exposed to non-disinfected and chlorinated waters between 24 and 720 h, while no bacterial adhesion was detected on SS and MS exposed to AFC(2)M between 48 and 504 h. The inability of bacteria to grow on SS and MS was observed only when 0.35 mg l(-1) residual monochloramine was maintained throughout the system. This demonstrates the inability of chlorine alone to inhibit bacterial growth and suggests a combination of chlorine and monochloramine as a more effective treatment for drinking water, especially for rural communities with very poor source waters in Africa.


An overlooked parameter in coronary slow flow phenomenon: whole blood viscosity.
We aimed to assess the relationship between coronary slow flow phenomenon (CSFP) and whole blood viscosity (WBV). Two hundred patients with CSFP and 200 subjects with normal coronary arteries as control group were enrolled. WBV was calculated from hematocrit and plasma protein concentration at low shear rate (LSR) (0.5 s(-1)) and high shear rate (HSR) (208 s(-1)) by a validated equation. CSFP patients had significantly higher WBV for LSR and HSR. The mean corrected TIMI frame count was highest in the highest tertile group for both shear rates. Corrected TIMI frame count revealed a significant relationship with WBV for LSR (r = 0.562) and HSR (r = 0.611). At multivariate analysis, WBV at LSR and HSR were independent predictors of CSFP. WBV seemed to have a significant and an independent predictor of CSFP.


Intravenous glucose tolerance test in gestational diabetes and pregnancy: 'manual' versus computerized assessment.
In order to assess the reliability of 'manual' versus computerized interpretation of the intravenous glucose tolerance test (IVGTT), fifty-five women, aged 19 to 41, underwent an IVGTT. Fifteen subjects had overt diabetes mellitus, sixteen were evaluated for gestational diabetes and twenty-four were healthy controls, fourteen of whom were pregnant. Each IVGTT was analysed by two trained physicians independently and by a simple computerized program, and the k' values obtained were compared, using the Student t-test for paired data. Significant difference (p less than 0.005) was found comparing either the 'manual' assessments or the 'manual' versus computer calculations. It is concluded that the IVGTT test must be interpreted using a simple computerized program, especially in borderline cases of pregnancy where the traditional 'manual' analysis might result in misclassification or misdiagnosis of the patient.


The embryonic pineal gland of the chicken as a model for experimental jet lag.
The circadian clock in the chicken pineal model develops before hatching, at around the 17th embryonic day (ED17). By this stage, it runs in synchrony with environmental cues. To address if phase resetting mechanisms are comparable to those of post-hatched chicken, we investigated ED19 stage chicken embryos under 12h light:12h dark (LD), under constant darkness (DD), or under acute 4h phase delay of the LD condition (LD+4). The 24h mRNA-expression patterns of clock gene clock and of clock controlled genes Aanat and hiomt were analyzed with qRT-PCR. Under DD the rhythm of Aanat did not change significantly, however the 24h pattern of hiomt was altered. Clock shows a delayed response to DD with a phase-shift in its rhythm. After the first cycle under LD+4 conditions, the 24h patterns of Aa-nat and hiomt mRNA-s were phase delayed. Clock showed both acute and delayed changes in response to LD+4. These results show that the embryonic chicken pineal gland has a fully functioning clock mechanism, and that it is a good model for phase-change experiments. In addition it demonstrates that only one cycle of altered light schedule is sufficient to trigger changes within the molecular clock mechanisms of the chicken embryonic pineal model.


Leukocyte counting during process control of leukoreduced blood components.
To describe the characteristics of counting assays used for process control of leukoreduction. Literature review. Counting assays with good performance characteristics are an essential element of the process control of leukoreduction. A recent multicenter study by a Working Party of the ISBT has evaluated three widely used methods for counting low numbers of leukocytes in leukoreduced blood. Automated methods provide greater accuracy and better inter-laboratory precision than Nageotte hematocytometry. However, deterioration of performance as a result of prolonged sample shipment remains an obstacle to centralized testing services. Although several mathematical approaches have been used to model the distribution of residual leukocytes in leukoreduced blood, no single model has been shown to be clearly superior.


Neurogenomics of speech and language disorders: the road ahead.
Next-generation sequencing is set to transform the discovery of genes underlying neurodevelopmental disorders, and so offer important insights into the biological bases of spoken language. Success will depend on functional assessments in neuronal cell lines, animal models and humans themselves.


Effect of "helper lipid" on lipoplex electrostatics.
Lipoplexes, which are complexes between cationic liposomes (L+) and nucleic acids, are commonly used as a nucleic acid delivery system in vitro and in vivo. This study aimed to better characterize cationic liposome and lipoplex electrostatics, which seems to play a major role in the formation and the performance of lipoplexes in vitro and in vivo. We characterized lipoplexes based on two commonly used monocationic lipids, DOTAP and DMRIE, and one polycationic lipid, DOSPA--each with and without helper lipid (cholesterol or DOPE). Electrical surface potential (Psi0) and surface pH were determined using several surface pH-sensitive fluorophores attached either to a one-chain lipid (4-heptadecyl hydroxycoumarin (C17HC)) or to the primary amino group of the two-chain lipids (1,2-dioleyl-sn-glycero-3-phosphoethanolamine-N-carboxyfluorescein (CFPE) and 1,2-dioleyl-sn-glycero-3-phosphoethanolamine-N-7-hydroxycoumarin) (HC-DOPE). Zeta potentials of the DOTAP-based cationic liposomes and lipoplexes were compared with Psi0 determined using C17HC. The location and relatively low sensitivity of fluorescein to pH changes explains why CFPE is the least efficient in quantifying the differences between the various cationic liposomes and lipoplexes used in this study. The fact that, for all cationic liposomes studied, those containing DOPE as helper lipid have the least positive Psi0 indicates neutralization of the cationic charge by the negatively-charged phosphodiester of the DOPE. Zeta potential is much less positively charged than Psi0 determined by C17HC. The electrostatics affects size changes that occurred to the cationic liposomes upon lipoplex formation. The largest size increase (based on static light scattering measurements) for all formulations occurred at DNA-/L+ charge ratios 0.5-1. Comparing the use of the one-chain C17HC and the two-chain HC-DOPE for monitoring lipoplex electrostatics reveals that both are suitable, as long as there is no serum (or other lipidic assemblies) present in the medium; in the latter case, only the two-chain HC-DOPE gives reliable results. Increasing NaCl concentrations decrease surface potential. Neutralization by DNA is reduced in a NaCl-concentration-dependent manner.


Cellular prion protein in mammary gland and milk fractions of domestic ruminants.
The present study shows that PrP(c) is expressed in the mammary gland and milk fractions of domestic ruminants in a species-specific manner. By applying immunohistochemistry, Western blot and ELISA, clear expression differences between bovine, ovine and caprine mammary gland, skimmed milk, acid whey and cream could be demonstrated, the highest relative PrP(c) levels being associated with the cream fraction. In the bovine gland PrP(c) was preferentially detectable at the basolateral surface of mammary gland epithelial cells, whereas in ovine and caprine samples the prion protein was more homogeneously distributed. Moreover, in ovine and caprine bovine mammary gland epithelial cells, apocrine secretory vesicles were strongly stained. Ovine and caprine milk proved to contain PrP(c) in all fractions with an additional truncated form at 12kDa in Western blot. This truncated isoform is the predominate one in caprine acid whey. These results support the hypothesis that the apocrine secretion mode of milk fat globules is a major way of PrP(c) transport into the milk.


Cerebral toxoplasmosis in a patient with Hodgkin's disease.
A case is described of a patient presenting with enlarged lymph nodes and in whom a diagnosis of acute toxoplasmosis was made. The patient later developed Hodgkin's disease for which chemotherapy was started. Reactivation of the quiescent toxoplasma infection took place with devastating results. Prophylactic treatment in such cases is discussed.


Teroxirone inhibited growth of human non-small cell lung cancer cells by activating p53.
In this work, we demonstrated that the growth of human non-small-cell-lung-cancer cells H460 and A549 cells can be inhibited by low concentrations of an epoxide derivative, teroxirone, in both in vitro and in vivo models. The cytotoxicity was mediated by apoptotic cell death through DNA damage. The onset of ultimate apoptosis is dependent on the status of p53. Teroxirone caused transient elevation of p53 that activates downstream p21 and procaspase-3 cleavage. The presence of caspase-3 inhibitor reverted apoptotic phenotype. Furthermore, we showed the cytotoxicity of teroxirone in H1299 cells with stable ectopic expression of p53, but not those of mutant p53. A siRNA-mediated knockdown of p53 expression attenuated drug sensitivity. The in vivo experiments demonstrated that teroxirone suppressed growth of xenograft tumors in nude mice. Being a potential therapeutic agent by restraining cell growth through apoptotic death at low concentrations, teroxirone provides a feasible perspective in reversing tumorigenic phenotype of human lung cancer cells.


Genome editing and the next generation of antiviral therapy.
Engineered endonucleases such as homing endonucleases (HEs), zinc finger nucleases (ZFNs), Tal-effector nucleases (TALENS) and the RNA-guided engineered nucleases (RGENs or CRISPR/Cas9) can target specific DNA sequences for cleavage, and are proving to be valuable tools for gene editing. Recently engineered endonucleases have shown great promise as therapeutics for the treatment of genetic disease and infectious pathogens. In this review, we discuss recent efforts to use the HE, ZFN, TALEN and CRISPR/Cas9 gene-editing platforms as antiviral therapeutics. We also discuss the obstacles facing gene-editing antiviral therapeutics as they are tested in animal models of disease and transition towards human application.


Intestinal Myxoid Leiomyosarcoma in a Sambar Deer (Rusa unicolor).
A 9-year-old male sambar deer (Rusa unicolor) that died during sedation had a large and firm polypoid mass, which expanded the small intestinal wall and partially obstructed the duodenal lumen. Histopathology revealed a pleomorphic sarcoma composed of stellate to spindloid cells loosely arranged in an abundant myxoid matrix. The cytoplasm of the neoplastic cells was strongly immunopositive for vimentin and smooth muscle actin, but negative for c-KIT, desmin and myoglobin. The findings are consistent with intestinal myxoid leiomyosarcoma, which is rare in cervids and has not been described in the sambar deer, which is an endangered species.


Constitutive nuclear expression of the I kappa B kinase complex and its activation in human neutrophils.
A singular feature of human neutrophils is that they constitutively express substantial amounts of NF-kappaB/Rel proteins and IkappaB-alpha in the nucleus. In this study, we show that in these cells, IkappaB kinase alpha (IKKalpha), IKKbeta, and IKKgamma also partially localize to the nucleus, whereas IKK-related kinases (IKKepsilon, TANK-binding kinase-1) are strictly cytoplasmic, and the NF-kappaB-inducing kinase is strictly nuclear. Following neutrophil activation, IKKbeta and IKKgamma become transiently phosphorylated in both the cytoplasm and nucleus, whereas IKKalpha transiently vanishes from both compartments in what appears to be an IKKbeta-dependent process. These responses are paralleled by the degradation of IkappaB-alpha, and by the phosphorylation of RelA on serine 536, in both compartments. Although both proteins can be IKK substrates, inhibition of IKK prevented IkappaB-alpha phosphorylation, while that of RelA was mostly unaffected. Finally, we provide evidence that the nuclear IKK isoforms (alpha, beta, gamma) associate with chromatin following neutrophil activation, which suggests a potential role in gene regulation. This is the first study to document IKK activation and the phosphorylation of NF-kappaB/Rel proteins in primary neutrophils. More importantly, our findings unveil a hitherto unsuspected mode of activation for the IKK/IkappaB signaling cascade within the cell nucleus.


Analysis of epothilone B-induced cell death in normal ovarian cells.
We have investigated the mode of cell death induced by a new microtubule-stabilizing agent, epothilone B (EpoB, patupilone), and a clinically used medicine, paclitaxel (PTX), in normal ovarian cells. Using fluorescence microscopy, polyacrylamide gel electrophoresis preceding Western blot analysis, as well as spectrofluorimetric and colorimetric detection, we demonstrate that, compared to EpoB, PTX induced high time-dependent morphological and biochemical changes typical of apoptosis. Induction of apoptosis followed an early increase in p53 levels. Apoptosis reached its maximum at 24-48 h. At the same time, there was a significant increase in caspase-9 and -3 activity and PARP fragmentation, which suggests that an intrinsic path was involved. Apoptosis in MM14 cells was increased more by PTX than EpoB, and also induced more necrosis responsible for inflammation (1.4-fold) than EpoB.


Is severe right ventricular failure in left ventricular assist device recipients a risk factor for unsuccessful bridging to transplant and post-transplant mortality.
Bridging to transplant with a left ventricular assist device (LVAD) can be limited by severe right ventricular failure (RVF). The focus of this study was to ascertain whether early implantation (< 24 hours) of a right ventricular assist device (RVAD) in patients with severe RVF improved survival and whether severe RVF adversely affected post-transplant survival. We conducted a 10-year review of our bridge to transplant experience using the Heartmate device (Thoratec, Pleasanton, CA, USA), studying patients who required an Abiomed RVAD (Abiomed, Danvers, MA, USA). There were 243 patients who underwent LVAD implantation, of which 17 (7.0%) required an RVAD. Ten patients underwent early RVAD insertion (< 24 hours) while 7 underwent delayed insertion (> 24 hours). Bridging to transplant was successful in 11 (64.7%) RVAD patients versus 163 (72.1%) non-RVAD patients (p = 0.046). Of the 10 patients who underwent early RVAD insertion, 7 (70.0%) were successfully bridged. Of the 7 patients who underwent delayed RVAD insertion, 4 (57.1%) were successfully bridged (p < 0.001). There was no significant difference in post-transplant 1, 5, and 10-year survival between RVAD and non-RVAD patients (71.4%, 71.4%, and 71.4% for RVAD patients, vs 90.5%, 80.4%, and 78.5%, respectively, for non-RVAD patients; p = 0.366). Pretransplant RVAD support was not a risk factor for post-transplant mortality (p = 0.864). Severe RVF adversely impacted bridging to transplant, although survival was improved with early RVAD insertion. The trend toward worse post-transplant survival in the RVAD cohort raises the possibility that if additional patients were evaluated, a difference in survival might be observed, suggesting the need for a multicenter analysis.


Peripheral iris erosions associated with pediatric intraocular lens implants.
Eight children in whom 2-loop iridocapsular lenses or 2-loop iris suture lenses were implanted have exhibited peripheral iris erosion adjacent to the IOL haptic, through the iris stroma, and eventually through the iris pigment epithelium. The process appears to be very gradual and these patients have exhibited no signs of iris irritation of hyphema. No treatment has been instituted.


Peri-conceptional nutritional restriction alters transcriptomic profile in the peri-implantation pig embryos.
Restricted nutritional consumption during the peri-conceptional period affects the potential for DNA methylation and alters endometrial transcriptomic profile during the peri-implantation period. The restricted diet fed to females during the peri-conceptional period may affect the transcriptomic profile in peri-implantation embryos. In the present study, the transcriptome of embryos of normal-diet-fed gilts was determined and compared with that in embryos of restricted-diet-fed gilts during the peri-implantation period. The restricted-diet-fed gilts were fed forage, in which the dose of proteins and energy had been reduced by 30% compared to the normal diet (Polish Norms of Nutrition). To clarify the issue Agilent's Porcine (V2) Two-Color Gene Expression Microarray 4 × 44 was used. Analysis of the microarray data revealed that the expression of 787 genes with known biological function were consistently altered (496 up- and 291 down-regulated) in embryos. The accurately annotated genes were organized into five categories and 18 subcategories containing 62 biological pathways. The qPCR analysis of ten selected genes [i.e., 5 acid phosphatase, tartrate resistant (ACP5), high mobility group box 2 (HMGB2), prostaglandin-endoperoxide synthase 2 (PTGS2), arachidonate 12-lipoxygenase (ALOX12), adiponectin receptor 2 (ADIPOR2), DNA (cytosine-5)-methyltransferase 1 (DNMT1), steroidogenic acute regulatory protein (STAR), progesterone receptor membrane component 2 (PGRMC2), progestin and adipoQ receptor family member 7 (PAQR7) and serpin family A member 1 (SERPINA1)] confirmed altered gene expression in embryos of restricted-diet-fed gilts. The insight into embryonic transcriptome indicates that female under-nutrition during the peri-conceptional period may create alterations in the pattern of genes expressed in the peri-implantation embryos.


The effects of L-thyroxin replacement therapy on bone minerals and body composition in hypothyroid children.
Prolonged treatment with levothyroxine 4 (L-T4) is a well known risk factor for osteoporosis. Patients on L-T4 replacement occasionally have a subnormal TSH, which carries a risk of development of bone loss. Thyroid hormones directly affect bone cells, stimulating osteoclastic and osteoblastic activity with a predominance of bone resorption and decrease of bone mineral density (BMD). The study included 35 hypothyroid patients with mean age 11.57 ±5.06, while 26 age- and sex-matched children served as controls. Dual energy X-ray absorptiometry (DXA) was done to detect the bone mineral density (BMD), bone mineral content (BMC) and Z score in lumbar and femur neck regions. Body composition was also studied by DXA. Calcium, phosphorus, osteocalcin as a bone formation marker, osteoprotegerin as an indicator of osteoclast activity and urinary deoxypyridinoline as a bone collagen breakdown marker were assessed. No significant differences were detected in lumbar Z score (-0.12 ±0.66) and femur Z score (-0.17 ±0.58) compared to controls (-0.33 ±0.74 and -0.21 ±0.53 respectively). Bone mineral density and BMC were not significantly different from controls. No significant difference was detected between cases and controls in body composition. A positive correlation was detected between BMD and age (r=0.857, p<0.01), and with the period of treatment (r=0.766, p<0.01). A positive correlation was found between BMD and total body fat (r=0.693, p<0.01), and with abdominal fat (r=0.667, p<0.01). Levothyroxine 4 treatment in hypothyroid children does not alter bone metabolism and body composition.


Signaler-receiver-eavesdropper: Risks and rewards of variation in the dominant frequency of male cricket calls.
Signals are important for communication and mating, and while they can benefit an individual, they can also be costly and dangerous. Male field crickets call in order to attract female crickets, but gravid females of a parasitoid fly species, Ormia ochracea, are also attracted to the call and use it to pinpoint male cricket hosts. Conspicuousness of the call can vary with frequency, amplitude, and temporal features. Previous work with this system has only considered temporal variation in cricket calls, both large scale, that is, amount of calling and at what time of evening, and small scale, that is, aspects of chirp rate, pulse rate, and numbers of pulses per chirp. Because auditory perception in both crickets and flies relies on the matching of the peak frequency of the call with the peripheral sensory system, peak frequency may be subject to selection both from female crickets and from female flies. Here, we used field playbacks of four different versions of the same male Gryllus lineaticeps calling song that only differed in peak frequency (3.3, 4.3, 5.3, and 6.3 kHz) to test the relative attractiveness of the calls to female crickets and female flies. Our results clearly show that lower frequency calls enhance male safety from fly parasitism, but that the enhanced safety would come at a cost of reduced attraction of female crickets as potential mates. The results imply that eavesdropper pressure can disrupt the matched coevolution of signalers and receivers such that the common concept of matched male-female signaler-receiver coevolution may actually be better described as male-female-predator signaler-receiver-eavesdropper coevolution.


Multi-pathway on peroxymonosulfate activation by single cobalt atoms incorporated on CuO with enriched oxygen vacancies for high-efficient oxidation of tetracycline.
The development of single atom catalysts (SACs) with superior catalytic performance is a long-term goal for peroxymonosulfate (PMS) activation in advanced oxidation processes (AOPs). A novel SACs that single Co atoms anchored on CuO with enriched oxygen vacancies (Ov) is synthesized successfully by choosing a metal oxide as the carrier creatively. 100% of tetracycline (TC) can be removed by Co-CuO (Ov)/PMS system within 3 min. The corresponding reaction rate constant is 3.1068 min-1, which is much higher than that of CuO (Ov), ZIF-CoN4-C, Co-CuO (without Ov) and CoNP-CuO (Ov), respectively. Co(II) is the primary source of radical pathway (·OH and SO4·-), and its regeneration is promoted by Cu(Ⅰ). The enriched Ov is the major contribution to the nonradical pathway, which promotes the singlet oxygen (1O2) generation together with accelerates the electron transfer from TC to catalyst-PMS*. Besides, the Co-CuO (Ov) exhibits an excellent stability and anti-interference capability. This study highlights a novel strategy to promote PMS activation by incorporating the single metal atoms on a metal oxide carrier with defects to accelerate the redox of dominate metal and stabilize the metal atoms simultaneously, which may inform the design for the next generation of SACs in AOPs.


Cracking the code-Matching a proprietary algorithm for a low-cost sensor measuring PM1 and PM2.5.
Some manufacturers of low-cost particle sensors use proprietary algorithms to estimate particle mass concentrations such as PM2.5. Often little or no information is given regarding the calibration aerosol, how the algorithm was created or tested, or how the mass was estimated from the particle number counts. If the algorithm is faulty in some way, researchers have little ability to correct it in a fundamental way, although they can multiply the output by some calibration factor to match the particular aerosol combination they are studying. However, the adjustment still requires the use of the proprietary algorithm, which may have quirks that make it impossible to fix completely using a single calibration factor. It might be possible in some cases to avoid using the proprietary algorithm at all. That is the approach of this study. The low-cost sensor studied is the Plantower PMS 5003, and the algorithm is the CF_1 algorithm offered by the manufacturer. Data from a six-month study of four collocated PurpleAir PA-II monitors, each containing two independent Plantower PMS 5003 sensors, were collected. Two of these monitors had previously been calibrated against research-grade monitors. The best-fitting model for PM1 was found to be of the form PM1 = a*(N1 + N2) + d, where N1 and N2 are the particle numbers in the size categories 0.3-0.5 μm and 0.5-1 μm, and d is an additive constant. The best-fitting model for PM2.5 was of the form a*(N1 + N2) + b*N3 + d, where N3 is the number of particles in the third size fraction (1-2.5 μm). The individual models for all 8 sensors matched the reported CF_1 values for both PM1 and PM2.5 with R2 values exceeding 0.99, intercepts near zero, and slopes in the 0.99-1.01 range. The proposed models may also explain why the CF_1 algorithm reports values of zero for a substantial portion of PM1 and PM2.5 estimates. General models capable of being applied to other datasets were developed and estimated to have mean absolute errors (MAEs) <1 μg/m3.


Tumoral and paratumoral NK cells and CD8+ T cells of esophageal carcinoma patients express high levels of CD47.
In a limited number of human malignancies, anti-CD47 therapy leads to the rapid clearance of tumor cells by macrophages. In esophageal squamous cell carcinoma, anti-CD47 treatment has shown promising results in vitro. However, the CD47 expression pattern in tumor-infiltrating lymphocytes (TILs), which are associated with prolonged overall survival and serve as a positive prognostic factor, is largely unknown. In this study, a total of 36 tissue samples from the tumor, peritumoral tissue, and adjacent healthy esophageal tissue was obtained from 12 esophageal carcinoma (EC) patients, and the surface expression of CD47 was evaluated in natural killer (NK) cells, CD8+ T cells, and the nonlymphocyte cell fraction. We found that the proportions of the evaluated cells and their CD47-expressing populations were comparable across the analyzed tissue compartments. However, the proportions of CD47-expressing populations in the analyzed tissue compartments were significantly higher in NK cells and CD8+ T cells than in the nonlymphocyte cell fraction. Importantly, the intensity of CD47 staining was also significantly higher in the tested immune cells than in the nonlymphocyte cell fraction. High expression of CD47 in tissue-infiltrating NK cells and CD8+ T cells in EC patients can, therefore, affect the efficacy of anti-CD47 therapy in EC.


Matrix correlation tests support a single origin for modern humans.
The debate over human origins has focused on two competing theories. The single African origin model holds that anatomically modern Homo sapiens evolved in Africa 100,000-200,000 years ago. Members of this population migrated out of Africa, replacing archaic human groups through Asia and Europe, with racial differentiation occurring within the past 100,000 years. The alternative regional continuity model proposes continuous evolution over the past million years, with racial variation developing early, and similar modern human traits developing in all regions as the result of worldwide gene flow. The persistence of specific morphological features within regions over the past million years supports regional continuity, whereas the identification of anatomically modern fossil specimens from Africa and the Levant 50-60,000 years before they are found elsewhere, provides support for a single origin. I give here the first quantitative test of the fossil evidence for each of these models. Results support a single African and/or Levantine origin for modern humans.


Scaffold-Free Coculture Spheroids of Human Colonic Adenocarcinoma Cells and Normal Colonic Fibroblasts Promote Tumorigenicity in Nude Mice.
The aim of this study was to form a scaffold-free coculture spheroid model of colonic adenocarcinoma cells (CACs) and normal colonic fibroblasts (NCFs) and to use the spheroids to investigate the role of NCFs in the tumorigenicity of CACs in nude mice. We analysed three-dimensional (3D) scaffold-free coculture spheroids of CACs and NCFs. CAC Matrigel invasion assays and tumorigenicity assays in nude mice were performed to examine the effect of NCFs on CAC invasive behaviour and tumorigenicity in 3D spheroids. We investigated the expression pattern of fibroblast activation protein-α (FAP-α) by immunohistochemical staining. CAC monocultures did not form densely-packed 3D spheroids, whereas cocultured CACs and NCFs formed 3D spheroids. The 3D coculture spheroids seeded on a Matrigel extracellular matrix showed higher CAC invasiveness compared to CACs alone or CACs and NCFs in suspension. 3D spheroids injected into nude mice generated more and faster-growing tumors compared to CACs alone or mixed suspensions consisting of CACs and NCFs. FAP-α was expressed in NCFs-CACs cocultures and xenograft tumors, whereas monocultures of NCFs or CACs were negative for FAP-α expression. Our findings provide evidence that the interaction between CACs and NCFs is essential for the tumorigenicity of cancer cells as well as for tumor propagation.


Implication of brain cdc2 and MAP2 kinases in the phosphorylation of tau protein in Alzheimer's disease.
Brain tau protein is phosphorylated in vitro by cdc2 and MAP2 kinases, obtained through immunoaffinity purification from rat brain extracts. The phosphorylation sites are located on the tau molecule both upstream and downstream of the tubulin-binding motifs. A synthetic peptide comprising residues 194-213 of the tau sequence, which contains the epitope recognized by the monoclonal antibody tau-1, is also efficiently phosphorylated in vitro by cdc2 and MAP2 kinases. Phosphorylation of this peptide markedly reduces its interaction with the antibody tau-1, as it has been described for tau protein in Alzheimer's disease. Both cdc2 and MAP2 kinases are present in brain extracts obtained from Alzheimer's disease patients. Interestingly, the level of cdc2 kinase may be increased in patient brains as compared with non-demented controls. These results suggest a role for cdc2 and MAP2 kinases in phosphorylating tau protein at the tau-1 epitope in Alzheimer's disease.


Predicting adults likely to develop heart failure using readily available clinical information: An analysis of heart failure incidence using the NHEFS.
Heart failure is a heavy burden on the health care system in the United States. Once heart failure develops, the quality of life and longevity are dramatically affected. As such, its prevention is critical for the well-being of at risk patients. We evaluated the predictive ability of readily available clinical information to identify those likely to develop heart failure. We used a classification and regression tree (CART) model to determine the top predictors for heart failure incidence using the NHANES Epidemiologic Follow-up Study (NHEFS). The identified predictors were hypertension, diabetes, obesity, and myocardial infarction (MI). We evaluated the relationship between these variables and incident heart failure by the product-limit method and Cox models. All analyses incorporated the complex sample design to provide population estimates. We analyzed data from 14,407 adults in the NHEFS. Participants with diabetes, MI, hypertension, or obesity had a higher incidence of heart failure than those without risk factors, with diabetes and MI being the most potent predictors. Individuals with multiple risk factors had a higher incidence of heart failure as well as a higher hazard ratio than those with just one risk factor. Combinations that included diabetes and MI had the highest incidence rates of heart failure per 1000 person years and the highest hazard ratios for incident heart failure. Having diabetes, MI, hypertension or obesity significantly increased the risk for incident heart failure, especially combinations including diabetes and MI. This suggests that individuals with these conditions, singly or in combination, should be prioritized in efforts to predict and prevent heart failure incidence.


Evaluation of the EMG-force relationship of trunk muscles during whole body tilt.
The study was aimed at the identification of the electromyography (EMG)-force relationship of five different trunk muscles. EMG-force relationships differ depending on changes in firing rate and the concurrent recruitment of motor units, which are linear and S-shaped, respectively. Trunk muscles are viewed as belonging to either the local or global muscle systems. Based on such assumptions, it would be expected that these functionally assigned muscles use different activation strategies. Thirty-one healthy volunteers (16 women, 15 men) were investigated. Forces on the trunk were applied with the use of a device that gradually tilts the body to horizontal position. Rotation capability enabled investigation of forward and backward as well as right and left sideward tilt directions. Surface EMG (SEMG) of five trunk muscles was taken. Root mean square (rms) values were computed and relative amplitudes, according to the measured maximum amplitudes, were calculated individually. Back muscles were characterized by a linear SEMG-force relationship during forward tilt. Abdominal muscles showed an S-shaped polynomial SEMG-force relationship for backward tilt direction. Sideward tilt directions evoked lesser SEMG levels with polynomial curve characteristics for all investigated muscles. Therefore, the SEMG-force relationship possibly is also subject to force vector in relation to fiber direction.