Deep learning pose estimation for multi-cattle lameness detection.
The objective of this study was to develop a fully automated multiple-cow real-time lameness detection system using a deep learning approach for cattle detection and pose estimation that could be deployed across dairy farms. Utilising computer vision and deep learning, the system can analyse simultaneously both the posture and gait of each cow within a camera field of view to a very high degree of accuracy (94-100%). Twenty-five video sequences containing 250 cows in varying degrees of lameness were recorded and independently scored by three accredited Agriculture and Horticulture Development Board (AHDB) mobility scorers using the AHDB dairy mobility scoring system to provide ground truth lameness data. These observers showed significant inter-observer reliability. Video sequences were broken down into their constituent frames and with a further 500 images downloaded from google, annotated with 15 anatomical points for each animal. A modified Mask-RCNN estimated the pose of each cow to output 5 key-points to determine back arching and 2 key-points to determine head position. Using the SORT (simple, online, and real-time tracking) algorithm, cows were tracked as they move through frames of the video sequence (i.e., in moving animals). All the features were combined using the CatBoost gradient boosting algorithm with accuracy being determined using threefold cross-validation including recursive feature elimination. Precision was assessed using Cohen's kappa coefficient and assessments of precision and recall. This methodology was applied to cows with varying degrees of lameness (according to accredited scoring, n = 3) and demonstrated that some characteristics directly associated with lameness could be monitored simultaneously. By combining the algorithm results over time, more robust evaluation of individual cow lameness was obtained. The model showed high performance for predicting and matching the ground truth lameness data with the outputs of the algorithm. Overall, threefold lameness detection accuracy of 100% and a lameness severity classification accuracy of 94% respectively was achieved with a high degree of precision (Cohen's kappa = 0.8782, precision = 0.8650 and recall = 0.9209).


Acid-base equilibria of various oxidation states of aqua-ruthenium complexes with 1,10-phenanthroline-5,6-dione in aqueous media.
Syntheses and pH dependent electrochemical properties of aqua-ruthenium(II) complexes, [Ru(trpy)(PDA-N,N')(OH2)](ClO4)2 ([1](ClO4)2) and [Ru(trpy)(PD-N,N')(OH2)](ClO4)2 ([2](ClO4)2) (trpy = 2,2':6',2''-terpyridine, PDA = 6-acetonyl-6-hydroxy-1,10-phenanthroline-5-one, PD = 1,10-phenanthroline-5,6-dione) are presented. Treatment of [Ru(trpy)(PD-N,N')Cl](PF6) with AgClO4 in a mixed solvent of acetone and H2O selectively produced the acetonyl-PD complex [1](ClO4)2, and the similar treatment in a mixed solvent of 2-methoxyethanol and H2O gave the PD complex [2](ClO4)2. The molecular structures of both complexes were determined by X-ray structural analysis. The proton dissociation constants of various oxidations state of [1]2+ and [2]2+ were evaluated by simulation of E(1/2) values of those redox potentials depending on pH. The simulation revealed that the acetonyl-PD complex [1]2+ underwent successive Ru(II)/Ru(III) and Ru(III)/Ru(IV) redox couples though the two redox reactions were not separated in the cyclic voltammograms. The redox behavior of [2]2+ in H2O is reasonably explained by not only the similar successive metal-centered redox reactions but also simultaneous two-electron quinone/catechol redox couple of the PD ligand including the contribution of hydration on a carbonyl carbon.


[Aging, health and family income].
The Survey of Health, Ageing and Retirement in Europe (SHARE) has completed its second step, having interviewed some 25,000 Europeans aged 55 years and over about their income and health. SHARE is an interdisciplinary study that answers questions on the relation between family income and disease, which, like education level and disease, are correlated. Prevention can reduce future health expenditures, and SHARE can help in calculating the extent of such reduction.


Canine parasitoses in north Patagonia (Argentina): comparison between different social and environmental factors.
In many countries, urban areas are commonly contaminated with canine feces that spread parasites, a situation related to the natural and social environment. Dogs having free access to public areas therefore constitutes a health risk. Because in Patagonia there are no records of city comparisons that consider the number of free-roaming dogs and the local environmental and socioeconomic characteristics, in this study we analyse and compare canine parasitoses in two cities of Rio Negro province, Argentina. Canine feces were collected from public areas of El Bolsón and Cipolletti cities and examined using enrichment methods, Kinyoun stain and immunoassay (Copro-Elisa). The total percentage of positive feces in El Bolsón was 68.95% and 16 parasite taxa being identified, whereas in Cipolletti the total positive feces was 41.1%, with 11 taxa. Both cities presented more helminth species than protozoans. The variables that explained the occurrence of all parasites were rainfall and socioeconomic stratum with the highest values being found in low-income areas.Soil moisture is conditioned by rainfall. This study highlights the presence of the zoonotic Echinococcus sp. in dogs in urban areas of the Rio Negro province. The occurrence of this parasite in Cipolletti is unexpected, given that this city is not considered an endemic zone for this disease, which is not included in local monitoring and control plans.


Myocardial viability: known and unknown.
The assessment of myocardial viability has gained a lot of attention over the past few years. Various imaging techniques, mainly nuclear and echocardiographic approaches, have been developed for this purpose. From the existing data, it has become clear that the presence of dysfunctional yet viable myocardium can predict improvement of regional and global left ventricular (LV) function after revascularization. This issue is most relevant in patients with severely depressed LV function, since in these patients revascularization carries a high (peri-)procedural risk on the one hand, but may substantially improve LV function in some patients. Besides the improvement of resting LV function after revascularization, other end-points may also be clinically relevant, including the response during stress, improvement of exercise capacity, the quality of life and the prevention of LV remodeling. These issues have not been studied extensively thusfar. Finally, several retrospective studies have shown the prognostic value of viability assessment; patients with viable but jeopardized myocardium were significantly more prone to experience cardiac events than patients with viability who underwent revascularization. The different aspects of viability assessment (including pathophysiology, available techniques, current implications and unresolved issues) will be addressed in this manuscript.


Saving the gorillas (Gorilla g. gorilla) and chimpanzees (Pan t. troglodytes) of the Congo Basin.
The forests of the Congo Basin in equatorial Africa are home to significant populations of gorillas and chimpanzees. However, numbers are declining owing to hunting and to alteration of their habitat. Gorillas and chimpanzees are particularly vulnerable for biological reasons: slow reproduction, prolonged developmental periods and complex social behaviour. In addition, their capacity to recover from disturbance is limited and the reinforcement of wild populations with captive-born individuals is rarely an option. Compared with the critically endangered mountain gorillas and the beleaguered chimpanzees in forest fragments in West Africa, there are some reasons for optimism about the future of the Congo Basin apes: levels of threat remain relatively low; and conservation of tropical rainforests has become a priority of the international community. At the same time, knowledge of the ecological needs of wild apes has increased and non-invasive techniques now exist to monitor population health. Sadly, no animals remain truly 'wild', as their survival depends to a greater or lesser extent on management. Protected areas and laws that forbid hunting of vulnerable species are classic tools of management, but broader landscape visions are now emerging that may allow the Congo Basin to avoid the fragile scenario of larger animals persisting only in 'island' parks.


Identifying and Breaking Scaling Relations in Molecular Catalysis of Electrochemical Reactions.
Improving molecular catalysis for important electrochemical proton-coupled electron transfer (PCET) reactions, such as the interconversions of H+/H2, O2/H2O, CO2/CO, and N2/NH3, is an ongoing challenge. Synthetic modifications to the molecular catalysts are valuable but often show trade-offs between turnover frequency (TOF) and the effective overpotential required to initiate catalysis (ηeff). Herein, we derive a new approach for improving efficiencies-higher TOF at lower ηeff-by changing the concentrations and properties of the reactants and products, rather than by modifying the catalyst. The dependence of TOF on ηeff is shown to be quite different upon changing, for instance, the pKa of the acid HA versus the concentration or partial pressure of a reactant or product. Using the electrochemical reduction of dioxygen catalyzed by iron porphyrins in DMF as an example, decreasing [HA] 10-fold lowers ηeff by 59 mV and decreases the TOF by a factor of 10. Alternatively, a 10-fold decrease in Ka(HA) also lowers ηeff by 59 mV but only decreases the TOF by a factor of 2. This approach has been used to improve a catalytic TOF by 104 vs the previously reported scaling relationship developed via synthetic modifications to the catalyst. The analysis has the potential to predict improved efficiency and product selectivity of any molecular PCET catalyst, based on its mechanism and rate law.


Jointly Optimized Spatial Histogram UNET Architecture (JOSHUA) for Adipose Tissue Segmentation.
Objective. We aim to develop a machine learning algorithm to quantify adipose tissue deposition at surgical sites as a function of biomaterial implantation. Impact Statement. To our knowledge, this study is the first investigation to apply convolutional neural network (CNN) models to identify and segment adipose tissue in histological images from silk fibroin biomaterial implants. Introduction. When designing biomaterials for the treatment of various soft tissue injuries and diseases, one must consider the extent of adipose tissue deposition. In this work, we analyzed adipose tissue accumulation in histological images of sectioned silk fibroin-based biomaterials excised from rodents following subcutaneous implantation for 1, 2, 4, or 8 weeks. Current strategies for quantifying adipose tissue after biomaterial implantation are often tedious and prone to human bias during analysis. Methods. We used CNN models with novel spatial histogram layer(s) that can more accurately identify and segment regions of adipose tissue in hematoxylin and eosin (H&E) and Masson's trichrome stained images, allowing for determination of the optimal biomaterial formulation. We compared the method, Jointly Optimized Spatial Histogram UNET Architecture (JOSHUA), to the baseline UNET model and an extension of the baseline model, attention UNET, as well as to versions of the models with a supplemental attention-inspired mechanism (JOSHUA+ and UNET+). Results. The inclusion of histogram layer(s) in our models shows improved performance through qualitative and quantitative evaluation. Conclusion. Our results demonstrate that the proposed methods, JOSHUA and JOSHUA+, are highly beneficial for adipose tissue identification and localization. The new histological dataset and code used in our experiments are publicly available.


A Comparative Analysis of Microscopy, Culture, and the Xpert Mycobacterium tuberculosis/Rifampicin Assay in Diagnosing Pulmonary Tuberculosis in Human Immunodeficiency-Positive Individuals.
Individuals with human immunodeficiency virus (HIV) infection have an increased likelihood of developing tuberculosis (TB). The primary objective of this study was to compare the diagnostic accuracy of microscopy, culture, and the Xpert Mycobacterium tuberculosis/Rifampicin (MTB/RIF) assay in the diagnosis of pulmonary TB in sputum samples of HIV-infected patients. The secondary objectives were to evaluate the sensitivity and specificity of these three methods along with a comparison of diagnostic approaches for detecting drug-resistant strains. This prospective, laboratory-based study was done in the Microbiology Department of IGIMS, Patna. The study included sputum samples of 102 individuals who were HIV-positive and exhibited symptoms indicative of tuberculosis. Out of 102 individuals suspected of having tuberculosis, 18 tested positive for M. tuberculosis. Male individuals between the ages of 31 and 40 were more affected by both HIV and tuberculosis, and in most of these cases, their CD4 cell count was below 200 cells/µl. Among the 102 sputum samples collected, 18% (18 samples) were found to be positive using the Mycobacterium Growth Indicator Tube (MGIT) 960 liquid culture method. Two samples were contaminated, and 14.7% (15 cases) tested positive using the cartridge-based nucleic acid amplification test (CBNAAT) method. Additionally, 3.92% (four samples) were positive using the ZN staining method. The study found that Xpert MTB/RIF outperformed other methods in identifying resistance to RIF, showed better agreement with gene sequencing results for RIF resistance, and had higher accuracy in detecting tuberculosis cases, including both smear-positive and smear-negative cases.


CD147 expression in uterine smooth muscle tumors, and its potential role as a diagnostic and prognostic marker in patients with leiomyosarcoma.
To investigate the role of CD147 expression in uterine smooth muscle neoplasms, as a potential diagnostic and prognostic marker in patients with leiomyosarcoma (LMS). We investigated CD147 protein expression in uterine smooth muscle tumor samples from patients diagnosed with leiomyoma (n = 22), atypical leiomyoma (BLM) (n = 5), smooth muscle tumor of uncertain malignant potential (STUMP) (n = 14), and LMS (n = 22). The intensity and extensity of immunohistochemical staining were compared to determine its potential role in differential diagnosis. Spearman's rank correlation tests were performed to determine the relationship between CD147 expression and prognostic clinical and pathological criteria in the patients with LMS. CD147 was strongly expressed in 81.8% (n = 18) of the LMS tissue samples. In fact expression of CD147 in LMS tissues was significantly higher than that of the three other uterine smooth muscle tumor types (p = 0.000). However, high CD147 expression was found in only one BLM sample and one STUMP sample. Furthermore, CD147 percent expression positively correlated with Ki67 percent expression (r = 0.466, p<0.05) and mitotic index (r = 0.554, p<0.05), respectively. Our results suggest that immunohistochemistry may be a helpful tool in determining whether CD147 is a useful marker in the differential diagnosis of certain uterine smooth muscle tumors. CD147 may also have prognostic value for patients with LMS. Yet, in order to determine the extent of this potential marker's utility as a diagnostic and prognostic indicator, a larger randomized multicenter study must be performed.


Single-Molecule Study of Thermomyces lanuginosus Lipase in a Detergency Application System Reveals Diffusion Pattern Remodeling by Surfactants and Calcium.
Lipases comprise one of the major enzyme classes in biotechnology with applications within, e.g., baking, brewing, biocatalysis, and the detergent industry. Understanding the mechanisms of lipase function and regulation is therefore important to facilitate the optimization of their function by protein engineering. Advances in single-molecule studies in model systems have provided deep mechanistic insights on lipase function, such as the existence of functional states, their dependence on regulatory cues, and their correlation to activity. However, it is unclear how these observations translate to enzyme behavior in applied settings. Here, single-molecule tracking of individual Thermomyces lanuginosus lipase (TLL) enzymes in a detergency application system allowed real-time direct observation of spatiotemporal localization, and thus diffusional behavior, of TLL enzymes on a lard substrate. Parallelized imaging of thousands of individual enzymes allowed us to observe directly the existence and quantify the abundance and interconversion kinetics between three diffusional states that we recently provided evidence to correlate with function. We observe redistribution of the enzyme's diffusional pattern at the lipid-water interface as well as variations in binding efficiency in response to surfactants and calcium, demonstrating that detergency effectors can drive the sampling of lipase functional states. Our single-molecule results combined with ensemble activity assays and enzyme surface binding efficiency readouts allowed us to deconvolute how application conditions can significantly alter protein functional dynamics and/or surface binding, both of which underpin enzyme performance. We anticipate that our results will inspire further efforts to decipher and integrate the dynamic nature of lipases, and other enzymes, in the design of new biotechnological solutions.


Status of marine turtle rehabilitation in Queensland.
Rehabilitation of marine turtles in Queensland has multifaceted objectives. It treats individual animals, serves to educate the public, and contributes to conservation. We examined the outcome from rehabilitation, time in rehabilitation, and subsequent recapture and restranding rates of stranded marine turtles between 1996 and 2013 to determine if the benefits associated with this practice are cost-effective as a conservation tool. Of 13,854 marine turtles reported as stranded during this 18-year period, 5,022 of these turtles were stranded alive with the remainder verified as dead or of unknown condition. A total of 2,970 (59%) of these live strandings were transported to a rehabilitation facility. Overall, 1,173/2,970 (39%) turtles were released over 18 years, 101 of which were recaptured: 77 reported as restrandings (20 dead, 13 alive subsequently died, 11 alive subsequently euthanized, 33 alive) and 24 recaptured during normal marine turtle population monitoring or fishing activities. Of the turtles admitted to rehabilitation exhibiting signs of disease, 88% of them died, either unassisted or by euthanasia and 66% of turtles admitted for unknown causes of stranding died either unassisted or by euthanasia. All turtles recorded as having a buoyancy disorder with no other presenting problem or disorder recorded, were released alive. In Queensland, rehabilitation costs approximately $1,000 per animal per year admitted to a center, $2,583 per animal per year released, and $123,750 per animal per year for marine turtles which are presumably successfully returned to the functional population. This practice may not be economically viable in its present configuration, but may be more cost effective as a mobile response unit. Further there is certainly benefit giving individual turtles a chance at survival and educating the public in the perils facing marine turtles. As well, rehabilitation can provide insight into the diseases and environmental stressors causing stranding, arming researchers with information to mitigate negative impacts.


Vertigo in postoperative follow-up of otosclerosis.
Causes of vertigo after otosclerosis surgery were studied postoperatively and in long-term follow-up examinations. Pressure and mobility changes in the posterior labyrinth fluids, enzymatic process, and decrease in blood supply at the time of operation appear to be the major causes. Methods of detection, avoiding, and managing vertigo are presented.


Theophylline abolishes the light peak in perfused cat eyes.
Theophylline, a phosphodiesterase inhibitor, was applied to the arterially perfused cat eye in vitro. At a concentration of 850 microM, theophylline abolished the light peak of the DC-ERG and led to a 20% increase in perfusate flow to the eye. The effects were reversible. An experimentally-induced increase in flow per se by 20% resulted in a slight enhancement of the light peak. The data suggest the involvement of cyclic nucleotides in the generation of the light peak. Theophylline also caused a decrease in the standing potential of the eye, an increase in the b-wave amplitude, and a decrease in the c-wave amplitude in a dose-dependent and reversible manner.


Stakeholder engagement: a model for tobacco policy planning in Oklahoma Tribal communities.
Oklahoma law pre-empts local governments from enacting smoking restrictions inside public places that are stricter than state law, but the sovereign status of Oklahoma's 38 Tribal nations means they are uniquely positioned to stand apart as leaders in the area of tobacco policy. To provide recommendations for employing university-Tribal partnerships as an effective strategy for tobacco policy planning in tribal communities. Using a community-based participatory research approach, researchers facilitated a series of meetings with key Tribal stakeholders in order to develop a comprehensive tobacco policy plan. Ongoing engagement activities held between January 2011 and May 2012, including interdepartmental visits, facility site tours, interviews, and attendance at tribal activities, were critical for fostering constructive and trusting relationships between all partners involved in the policy planning process. The 17-month collaborative engagement produced a plan designed to regulate the use of commercial tobacco in all Tribally owned properties. The extended period of collaboration between the researchers and Tribal stakeholders facilitated: (1) levels of trust between partners; and (2) a steadfast commitment to the planning process, ensuring completion of the plan amid uncertain political climates and economic concerns about tobacco bans. Extended engagement produced an effective foundation for policy planning that promoted collaboration between otherwise dispersed Tribal departments, and facilitated communication of diverse stakeholder interests related to the goal of tobacco policies. The findings of this study provide useful strategies and best practices for those looking to employ Tribal-university partnerships as strategies for tobacco control planning and policy-based research.


Distinct Roles of Wnt/β-Catenin Signaling in the Pathogenesis of Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis.
Wnt signaling pathways are tightly controlled under a physiological condition, under which they play key roles in many biological functions, including cell fate specification and tissue regeneration. Increasing lines of evidence recently demonstrated that a dysregulated activation of Wnt signaling, particularly the Wnt/β-catenin signaling, was involved in the pathogenesis of chronic pulmonary diseases, such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). In this respect, Wnt signaling interacts with other cellular signaling pathways to regulate the initiation and pathogenic procedures of airway inflammation and remodeling, pulmonary myofibroblast proliferation, epithelial-to-mesenchymal transition (EMT), and development of emphysema. Intriguingly, Wnt/β-catenin signaling is activated in IPF; an inhibition of this signaling leads to an alleviation of pulmonary inflammation and fibrosis in experimental models. Conversely, Wnt/β-catenin signaling is inactivated in COPD tissues, and its reactivation results in an amelioration of airspace enlargement with a restored alveolar epithelial structure and function in emphysema models. These studies thus imply distinct mechanisms of Wnt/β-catenin signaling in the pathogenesis of these two chronic pulmonary diseases, indicating potential targets for COPD and IPF treatments. This review article aims to summarize the involvement and pathogenic roles of Wnt signaling pathways in the COPD and IPF, with a focus on the implication of Wnt/β-catenin signaling as underlying mechanisms and therapeutic targets in these two incurable diseases.


Research at a Distance: Replicating Semantic Differentiation Effects Using Remote Data Collection With Children Participants.
Remote data collection procedures can strengthen developmental science by addressing current limitations to in-person data collection and helping recruit more diverse and larger samples of participants. Thus, remote data collection opens an opportunity for more equitable and more replicable developmental science. However, it remains an open question whether remote data collection procedures with children participants produce results comparable to those obtained using in-person data collection. This knowledge is critical to integrate results across studies using different data collection procedures. We developed novel web-based versions of two tasks that have been used in prior work with 4-6-year-old children and recruited children who were participating in a virtual enrichment program. We report the first successful remote replication of two key experimental effects that speak to the emergence of structured semantic representations (N = 52) and their role in inferential reasoning (N = 40). We discuss the implications of these findings for using remote data collection with children participants, for maintaining research collaborations with community settings, and for strengthening methodological practices in developmental science.


Psychostimulant effects of fencamfamine in healthy volunteers.
The effects of fencamfamine (25 and 50 mg po) were studied on acute psychophysiological and psychomotor performance in six healthy male volunteers. Stimulant effects, such as greater increases of critical flicker-fusion threshold, heart rate, blood pressure and stimulation assessed by self-rating, were more pronounced with the higher dose of fencamfamine. Paradoxical sedative effects were obtained with the 25 mg dose. Fencamfamine should not be considered only as an energizing agent, but also as an agent having a psychostimulant profile of effects.


Neonatal pulmonary hypoplasia after prolonged leakage of amniotic fluid.
The clinical, radiological, and pathological features of the 'oligohydramnios tetrad' (Potter's facies, limb malpositions, pulmonary hypoplasia, and growth retardation) resulting from chronic amniotic fluid leakage are described in 2 infants who died of respiratory failure within 12 hours of delivery. A third infant with a partial form of the syndrome had prolonged respiratory symptoms and survived the neonatal period: the course of the disease and the radiological findings were compatible with a hypothetical diagnosis of partial pulmonary hypoplasia. Pulmonary hypoplasia should be recognized as a cause of chronic respiratory symptoms in viable infants.


Psychotic depression: a review and clinical experience.
We review research literature on psychotic (delusional) depression, including demographic, illness pattern, clinical, biological marker and treatment issues. Secondly, we report a study of a consecutive sample of 137 patients meeting criteria for DSM-III melancholia, RDC definite endogenous depression and our "clinical" criteria for endogenous depression, of whom there were 35 "psychotic depressives" (PDs). The PDs were contrasted with the remaining 76 depressives (EDs) and with an age and sex-matched subset (MEDs). The PDs were distinctly older than the EDs at assessment and at initial onset of any affective disorder. Compared to the MEDs, they tended to have longer illnesses, were more likely to be hospitalised (and to have longer stays), to receive (in the past and for the current episode) combination antipsychotic/antidepressant medication and/or ECT, and to have a poorer course over the following year. They were no more likely to have a bipolar pattern, a family history of depressive disorder, schizophrenia or alcoholism, or vegetative depressive features. Developmental psychosocial stressors and antecedent life event stressors were not over-represented. Most of the PDs had delusions, one-fifth reported hallucinations and psychomotor disturbance was marked. Other differential clinical findings were sustained mood disturbance, constipation, and the absence of a diurnal variation in mood and energy.


Self-assembled graphene-dextran nanohybrid for killing drug-resistant cancer cells.
A nanohybrid based on nanoscale graphene oxide (NGO) and dextran has been designed and employed for effectively killing drug-resistant MCF-7/ADR cells. This graphene-based nanohybrid was readily prepared through π-π interaction of NGO and hematin-terminated dextran (HDex), being denoted as NGO-HDex. It revealed an improved stability in physiological conditions as compared to native NGO. Besides, NGO-HDex could efficiently load doxorubicin (DOX), an anticancer drug, with drug loading capacity of 3.4 mg/mg NGO and liberate the drug with a pH-dependent profile. Cell viability assay indicated that the NGO-HDex displayed lower cytotoxicity against MCF-7/ADR cells as compared to native NGO. DOX-loaded NGO-HDex, however, revealed more efficient killing effect in the cells than free DOX because the nanohybrid caused a higher amount of DOX accumulated in the cells. The results of this study highlight that the NGO-HDex has high potential for killing drug-resistant cancer cells.


Effects of Exogenous Melatonin on Methyl Viologen-Mediated Oxidative Stress in Apple Leaf.
Oxidative stress is a major source of damage of plants exposed to adverse environments. We examined the effect of exogenous melatonin (MT) in limiting of oxidative stress caused by methyl viologen (MV; paraquatin) in apple leaves (Malus domestica Borkh.). When detached leaves were pre-treated with melatonin, their level of stress tolerance increased. Under MV treatment, melatonin effectively alleviated the decrease in chlorophyll concentrations and maximum potential Photosystem II efficiency while also mitigating membrane damage and lipid peroxidation when compared with control leaves that were sprayed only with water prior to the stress experiment. The melatonin-treated leaves also showed higher activities and transcripts of antioxidant enzymes superoxide dismutase, peroxidase, and catalase. In addition, the expression of genes for those enzymes was upregulated. Melatonin-synthesis genes MdTDC1, MdT5H4, MdAANAT2, and MdASMT1 were also upregulated under oxidative stress in leaves but that expression was suppressed in response to 1 mM melatonin pretreatment during the MV treatments. Therefore, we conclude that exogenous melatonin mitigates the detrimental effects of oxidative stress, perhaps by slowing the decline in chlorophyll concentrations, moderating membrane damage and lipid peroxidation, increasing the activities of antioxidant enzymes, and changing the expression of genes for melatonin synthesis.


Changes in biliary and fecal bile acids in mice after treatments with diosgenin and beta-sitosterol.
Diosgenin and beta-sitosterol (1% in diet) were administered to CRJ:CD-1 male mice for 15 days, in order to examine the changes in bile acid metabolism. There were some differences between diosgenin and beta-sitosterol in their effects on diet intake, liver weight, and plasma cholesterol level. However, both phytosterols caused no statistically significant changes in body weight gain, decreased cholesterol absorption to about one-third that observed in control mice, decreased liver cholesterol level, increased fecal excretion of cholesterol, and decreased fecal excretion of bile acids. Most of the increase in fecal excretion of cholesterol occurred 2 days after the start of feeding of phytosterols and gradually declined thereafter, but the levels on day 15 were nevertheless higher than those in the control mice. The fecal excretion of bile acids decreased progressively after the treatment with phytosterols. The decrease of bile acid derived from chenodeoxycholic acid was more predominant than the decrease of those derived from cholic acid, resulting in an increase of the cholic acid/chenodeoxycholic acid ratio. The biliary cholesterol, phospholipid, and bile acid mole % ratios and the lithogenic index were not changed, but the percentages of cholic acid and its related bile acids (the cholic acid group) to the total bile acids increased and those of the chenodeoxycholic acid group decreased after the treatments. The pool size of bile acids decreased in the mice given diosgenin but not in those given beta-sitosterol. Distribution of bile acids between the gallbladder and intestine was not altered by either phytosterol.(ABSTRACT TRUNCATED AT 250 WORDS)


Bodily Expression Support for Creative Dance Education by Grasping-Type Musical Interface with Embedded Motion and Grasp Sensors.
Dance has been made mandatory as one of the physical education courses in Japan because it can cultivate capacities for expression and communication. Among several types of dance education, creative dance especially contributes to the cultivation of these capacities. However, creative dance requires some level of particular skills, as well as creativity, and it is difficult to presuppose these pre-requisites in beginner-level dancers without experience. We propose a novel supporting device for dance beginners to encourage creative dance performance by continuously generating musical sounds in real-time in accordance with their bodily movements. It has embedded sensors developed for this purpose. Experiments to evaluate the effectiveness of the device were conducted with ten beginner-level dancers. Using the proposed device, the subjects demonstrated enhanced creative dance movements with greater variety, evaluated in terms of Laban dance movement description. Also, using the device, they performed with better accuracy and repeatability in a task where they produced an imagined circular trajectory by hand. The proposed interface is effective in terms of creative dance activity and accuracy of motion generation for beginner-level dancers.


Changes in vascular pattern of chicken chorioallantois after cartilaginous extract, chondroitin sulfate and dextran sulfate treatment.
Cartilaginous extract, chondroitin sulfate C as well as dextran sulfate in gelatin pellets have an inhibitory effect on the development of fine capillaries, in contrast to pure gelatin pellets or pellets with sucrose. These results suggest an unspecific inhibitory effect of anionic saccharidic polymers on the development of chorioallantoic membrane vessels, because the chemical structure of dextran sulfate is (except anionic groups) different from chondroitin sulfate in the pure form or in the form of proteoglycans (in cartilaginous extract).


Association between anemia and the risk and outcomes of diabetic foot in patients with type 2 diabetes mellitus.
The aim of the present study was to explore the association between anemia and the risks and outcomes of diabetic foot (DF) in patients with type 2 diabetes mellitus (T2DM). A total of 145 patients with T2DM were recruited between January and December 2021 and divided into the DF and non-DF groups according to whether they were diagnosed with DF. Individual patient data were extracted and blood samples were evaluated in a biochemical center for routine biochemical and blood-related indicators. The patients' survival rates were followed up until December 2022. An independent-samples t-test and χ2 test were used to compare the differences between the two groups. The association between the various clinical indicators for the DF and non-DF groups was evaluated using single-factor binary logistic regression analysis. Multi-factor binary logistic regression analysis was used to analyze the association between hemoglobin (Hb) and the risk for DF. A Kaplan-Meier survival curve was used to analyze the impact of anemia and DF on the 1-year survival rate. The diabetes duration, number of patients who smoked and consumed alcohol, and serum creatinine and C-reactive protein levels in the DF group were significantly higher than those in the non-DF group (P<0.05). By contrast, the estimated glomerular filtration rate (eGFR) and Hb, albumin (Alb) and total cholesterol levels, were lower in the DF group when compared with those in the non-DF group (P<0.05). All of the study participants were divided into two groups, according to their baseline eGFR [eGFR ≥90 or <90 ml/(min x 1.73 m²)]. It was found that, independently of renal function, lower Hb and Alb levels were associated with a higher incidence of DF. The 1-year survival rate for DF with anemia was significantly lower when compared with that in patients with DF without anemia (P<0.05). In conclusion, the Hb level in patients with T2DM is a protective factor against DF and anemia is an independent risk factor for DF. The present study suggested that anemia is associated with a decrease in the survival rate of patients with DF. This finding provided a theoretical basis for the clinical correction of anemia and improvement of DF prognosis (clinical trial no. 20220003).


Cyclam-Modified Polyethyleneimine for Simultaneous TGFβ siRNA Delivery and CXCR4 Inhibition for the Treatment of CCl4-Induced Liver Fibrosis.
Liver fibrosis is a chronic liver disease with excessive production of extracellular matrix proteins, leading to cirrhosis, hepatocellular carcinoma, and death. This study aimed at the development of a novel derivative of polyethyleneimine (PEI) that can effectively deliver transforming growth factor β (TGFβ) siRNA and inhibit chemokine receptor 4 (CXCR4) for TGFβ silencing and CXCR4 Inhibition, respectively, to treat CCl4-induced liver fibrosis in a mouse model. Cyclam-modified PEI (PEI-Cyclam) was synthesized by incorporating cyclam moiety into PEI by nucleophilic substitution reaction. Gel electrophoresis confirmed the PEI-Cyclam polyplex formation and stability against RNAase and serum degradation. Transmission electron microscopy and zeta sizer were employed for the morphology, particle size, and zeta potential, respectively. The gene silencing and CXCR4 targeting abilities of PEI-Cyclam polyplex were evaluated by luciferase and CXCR4 redistribution assays, respectively. The histological and immunohistochemical staining determined the anti-fibrotic activity of PEI-Cyclam polyplex. The TGFβ silencing of PEI-Cyclam polyplex was authenticated by Western blotting. The 1H NMR of PEI-Cyclam exhibited successful incorporation of cyclam content onto PEI. The PEI-Cyclam polyplex displayed spherical morphology, positive surface charge, and stability against RNAse and serum degradation. Cyclam modification decreased the cytotoxicity and demonstrated CXCR4 antagonistic and luciferase gene silencing efficiency. PEI-Cyclam/siTGFβ polyplexes decreased inflammation, collagen deposition, apoptosis, and cell proliferation, thus ameliorating liver fibrosis. Also, PEI-Cyclam/siTGFβ polyplex significantly downregulated α-smooth muscle actin, TGFβ, and collagen type III. Our findings validate the feasibility of using PEI-Cyclam as a siRNA delivery vector for simultaneous TGFβ siRNA delivery and CXCR4 inhibition for the combined anti-fibrotic effects in a setting of CCl4-induced liver fibrosis.


Bound to remember: Infants show superior memory for objects presented at event boundaries.
Following Event Segmentation Theory (EST) adult memory is enhanced at event boundaries (EB). The present study set out to explore this in infancy. Sixty-eight 21-month-olds watched a cartoon with one of two objects (counterbalanced) inserted for 3s either at EB or between EB. Ten minutes later they watched both objects (familiar and novel) in a 10s Visual Paired Comparison (VPC) test while being eye-tracked. Furthermore, they were asked to point to the previous object. Based on EST, we hypothesized that objects inserted at EB would be processed more fully, resulting in improved memory compared to objects inserted between EB. Only infants with objects at EB exhibited memory evidenced by a transient familiarity preference for the first 3s of the test. Only 18 infants completed the pointing test, but all infants presented with objects at EB (10/10) pointed to the correct (familiar) object, which was not the case for the infants presented with objects between EB (5/8).


Effects of Intron 1 Sequences on Human PLP1 Expression: Implications for PLP1-Related Disorders.
Alterations in the myelin proteolipid protein gene ( PLP1) may result in rare X-linked disorders in humans such as Pelizaeus-Merzbacher disease and spastic paraplegia type 2. PLP1 expression must be tightly regulated since null mutations, as well as elevated PLP1 copy number, both lead to disease. Previous studies with Plp1-lacZ transgenic mice have demonstrated that mouse Plp1 ( mPlp1) intron 1 DNA (which accounts for slightly more than half of the gene) is required for the mPlp1 promoter to drive significant levels of reporter gene expression in brain. However not much is known about the mechanisms that control expression of the human PLP1 gene ( hPLP1). Therefore this review will focus on sequences in hPLP1 intron 1 DNA deemed important for hPLP1 gene activity as well as a couple of "human-specific" supplementary exons within the first intron which are utilized to generate novel splice variants, and the potential role that these sequences may play in PLP1-linked disorders.


MiR-223-3p promotes cell proliferation and metastasis by downregulating SLC4A4 in clear cell renal cell carcinoma.
MicroRNAs (miRNAs) are known to affect the occurrence and progression of cancer. We therefore evaluated the involvement of miR-223-3p in renal cell cancer. MiR-223-3p was highly expressed in clear cell renal cell cancer tissues. Clear cell renal cell cancer patients with higher miR-223-3p expression had higher tumor stages and grades and poorer prognoses. In renal cancer cells, overexpression of miR-223-3p enhanced cell proliferation and metastasis, while inhibition of miR-223-3p reduced the malignant capacity of the cells. MiR-223-3p was found to bind directly to solute carrier family 4, member 4 (SLC4A4) mRNA, thereby reducing SLC4A4 mRNA and protein expression. SLC4A4 overexpression restrained cell proliferation and metastasis by suppressing Kirsten rat sarcoma viral oncogene (KRAS) expression in renal cancer cells. SLC4A4 expression correlated negatively with miR-223-3p expression in patient samples. Given that miR-223-3p suppressed the SLC4A4/KRAS axis, miR-223-3p gene therapy could be an effective treatment for renal cancer.


The role of urokinase plasminogen activator and plasminogen activator inhibitor-1 in follicle rupture during ovulation in the teleost medaka.
We previously reported that the serine protease plasmin plays a role in follicle rupture during ovulation in the teleost medaka. In this study, we showed that urokinase-type plasminogen activator 1 (Plau1) is a physiological activator of plasminogen. Morphological analyses revealed that in the preovulatory follicle, plau1 mRNA was detected in association with follicle cells, while Plau1 protein was localized in the oocyte egg membrane. Both an inactive precursor and an active form of Plau1 were present at constant levels in the membrane fraction via the latter half of the 24-h spawning cycle. Plasminogen activator inhibitor-1 (Pai1) was detected in the follicle layer of the preovulatory follicle, but the protein level was low at approximately 7 h prior to ovulation. We showed that plasmin hydrolyzed laminin, which is a major component of the basement membrane and is situated between the granulosa and theca cells of the follicle. In vitro ovulation of large follicles was significantly inhibited by anti-Plau1 antibodies and active recombinant Pai1. Levels of Pai1 expression were increased in vivo at approximately 7 h prior to ovulation. Expression of Pai1 was also induced in vitro in the follicle with recombinant medaka luteinizing hormone (Lh). Lh-induced expression of pail mRNA was significantly suppressed by the presence of MDL (an adenylyl cyclase inhibitor), trilostane (a 3beta-hydroxysteroid dehydrogenase inhibitor), and RU486 (a nuclear progestin receptor antagonist). These results support our recent proposal of a sequential two-step ECM protein hydrolysis model for follicle rupture for medaka ovulation.


HIV-induced syncytium formation requires the formation of conjugates between virus-infected and uninfected T-cells in vitro.
The transmission of HIV requires the interaction of the cell-surface CD4 receptor and the viral envelope glycoprotein. Experiments were performed to determine the role of other cell-surface molecules in the development of HIV-induced syncytia. Although CEM and MT-2 cells had similar cell-surface CD4 receptor densities, less than 1% of CEM cells and greater than 95% of MT-2 cells formed syncytia with H9 cells chronically infected with HIV-1 (H9-IIIB). When compared with CEM cells, MT-2 cells exhibited a 10-fold and threefold greater capacity to form homotypic and heterotypic conjugates with H9 cells, respectively. Increasing the conjugate formation capacity of CEM cells with the lectin wheat germ agglutinin led to a greater than 30-fold increase in the formation of syncytia with H9/IIIB cells. The formation of syncytia between MT-2 and H9/IIIB cells was magnesium-, energy-, temperature-, and actin-cytoskeleton-dependent, and could be inhibited (65%) by an anti-LFA-1 monoclonal antibody. The combination of anti-leukocyte function-associated antigen-1 (LFA-1) and anti-CD2 monoclonal antibodies resulted in a synergistic inhibition (89%) of syncytium formation. These results indicate that integrins and other cell-surface adhesion molecules regulate HIV-induced syncytium formation.


Quantitative phosphoproteomic analysis reveals unique cAMP signaling pools emanating from AC2 and AC6 in human airway smooth muscle cells.
Human airway smooth muscle (HASM) is the primary target of ßAR agonists used to control airway hypercontractility in asthma and chronic obstructive pulmonary disease (COPD). ßAR agonists induce the production of cAMP by adenylyl cyclases (ACs), activate PKA and cause bronchodilation. Several other G-protein coupled receptors (GPCR) expressed in human airway smooth muscle cells transduce extracellular signals through cAMP but these receptors elicit different cellular responses. Some G-protein coupled receptors couple to distinct adenylyl cyclases isoforms with different localization, partly explaining this compartmentation, but little is known about the downstream networks that result. We used quantitative phosphoproteomics to define the downstream signaling networks emanating from cAMP produced by two adenylyl cyclases isoforms with contrasting localization in uman airway smooth muscle. After a short stimulus of adenylyl cyclases activity using forskolin, phosphopeptides were analyzed by LC-MS/MS and differences between cells overexpressing AC2 (localized in non-raft membranes) or AC6 (localized in lipid raft membranes) were compared to control human airway smooth muscle. The degree of AC2 and AC6 overexpression was titrated to generate roughly equal forskolin-stimulated cAMP production. 14 Differentially phosphorylated proteins (DPPs) resulted from AC2 activity and 34 differentially phosphorylated proteins resulted from AC6 activity. Analysis of these hits with the STRING protein interaction tool showed that AC2 signaling is more associated with modifications in RNA/DNA binding proteins and microtubule/spindle body proteins while AC6 signaling is associated with proteins regulating autophagy, calcium-calmodulin (Ca2+/CaM) signaling, Rho GTPases and cytoskeletal regulation. One protein, OFD1, was regulated in opposite directions, with serine 899 phosphorylation increased in the AC6 condition 1.5-fold but decreased to 0.46-fold by AC2. In conclusion, quantitative phosphoproteomics is a powerful tool for deciphering the complex signaling networks resulting from discreet signaling events that occur in cAMP compartments. Our data show key differences in the cAMP pools generated from AC2 and AC6 activity and imply that distinct cellular responses are regulated by these two compartments.


Effect of cation alkyl chain length on 3-sulfopropylmethacrylate-based draw solutes having lower critical solution temperature.
We investigated the effect of change in alkyl chain length of cation in tributylalkylphosphonium 3-sulfopropyl methacrylate ([P444#][C3S], # = 4, 6, and 8) ionic liquids (ILs) on their osmolality and recovery properties as the draw solute in the forward osmosis (FO) process. The ILs aqueous solutions exhibited a characteristic of the lower critical solution temperature (LCST)-type phase separation, which allowed for the easy recovery of the draw solute or clean water from the diluted draw solution. The LCSTs of 31, 26, 22, and 18 °C were obtained from 2.5, 5.0, 7.5, and 10.0 wt% aqueous solutions of [P4446][C3S]. When deionized water, 2000 ppm NaCl solution, and 10.0 wt% orange juice aqueous solution were used as feed solution, the water fluxes of the aqueous [P4446][C3S] solutions were approximately 4.49, 3.87, and 1.55 LMH, respectively, in the active layer facing the draw solution mode at 7.5 wt% of draw solution. This study demonstrates the applicability of a thermoresponsive ionic structure material as a draw solute for the FO process.


Nonlinear decision-making with enzymatic neural networks.
Artificial neural networks have revolutionized electronic computing. Similarly, molecular networks with neuromorphic architectures may enable molecular decision-making on a level comparable to gene regulatory networks1,2. Non-enzymatic networks could in principle support neuromorphic architectures, and seminal proofs-of-principle have been reported3,4. However, leakages (that is, the unwanted release of species), as well as issues with sensitivity, speed, preparation and the lack of strong nonlinear responses, make the composition of layers delicate, and molecular classifications equivalent to a multilayer neural network remain elusive (for example, the partitioning of a concentration space into regions that cannot be linearly separated). Here we introduce DNA-encoded enzymatic neurons with tuneable weights and biases, and which are assembled in multilayer architectures to classify nonlinearly separable regions. We first leverage the sharp decision margin of a neuron to compute various majority functions on 10 bits. We then compose neurons into a two-layer network and synthetize a parametric family of rectangular functions on a microRNA input. Finally, we connect neural and logical computations into a hybrid circuit that recursively partitions a concentration plane according to a decision tree in cell-sized droplets. This computational power and extreme miniaturization open avenues to query and manage molecular systems with complex contents, such as liquid biopsies or DNA databases.


Bending deformation studies of orthodontic wires.
Bending deformation has been measured for orthodontic wires ranging in diameter from .010 to .051 inch. Results establish a revised expression for Young's modulus and show that either the stiffness tester or the torque meter will yield essentially the same measured values of bending properties. The dependence of test span length in determining Young's modulus and flexural yield strength is discussed.


The Predictive Value of the Maximal Liver Function Capacity Test for the Isolation of Primary Human Hepatocytes.
The need for primary human hepatocytes is constantly growing for basic research, as well as for therapeutic applications. However, the isolation outcome strongly depends on the quality of liver tissue, and we are still lacking a preoperative test that allows the prediction of the hepatocyte isolation outcome. In this study, we evaluated the "maximal liver function capacity test" (LiMAx) as predictive test for the quantitative and qualitative outcome of hepatocyte isolation. This test is already used in clinical routine to measure preoperative and to predict postoperative liver function. The patient's preoperative mean LiMAx was obtained from the patient records, and preoperative computed tomography and magnetic resonance images were used to calculate the whole liver volume to adjust the mean LiMAx. The outcome parameters of the hepatocyte isolation procedures were analyzed in correlation with the adjusted mean LiMAx. Primary human hepatocytes were isolated from partial hepatectomies (n = 64). From these 64 hepatectomies we included 48 to our study and correlated their isolation outcome parameters with volume corrected LiMAx values. From a total of 11 hepatocyte isolation procedures, metabolic parameters (albumin, urea, and aspartate aminotransferase or AST) were assessed during the hepatocyte cultivation period of 5 days. The volume adjusted mean LiMAx showed a significant positive correlation with the total cell yield (p = 0.049; r = 0.242; n = 48). The correlations of volume adjusted LiMAx values with viable cell yield and cell viability did not reach statistical significance. To create a more homogenous study group regarding tumor entities, subgroup analyses were performed. A subgroup analysis of isolations from patients with colorectal metastasis revealed a significant correlation between volume adjusted mean LiMAx and total cell yield (p = 0.012; r = 0.488; n = 21) and viable cell yield (p = 0.034; r = 0.405; n = 21), whereas a subgroup analysis of isolations of patients with carcinoma of the biliary tree showed significant correlations of volume adjusted mean LiMAx with cell viability (r = 0.387; p = 0.046; n = 20) and lacked significant correlations with total cell yield (r = -0.060; p = 0.401; n = 20) and viable cell yield (r = 0.012; p = 0.480; n = 20). The volume-adjusted mean LiMAx did not show a significant correlation with any of the metabolic parameters. In conclusion, the LiMAx test might be a useful tool to predict the quantitative outcome of hepatocyte isolation, as long as underlying liver disease is taken into consideration.


Effect of oxidation on the wettability of poly(dimethylsiloxane) surfaces.
The wetting of amorphous poly(dimethylsiloxane) (PDMS) surfaces by water has been studied using molecular dynamics simulations. PDMS surfaces were generated by compressing a long PDMS chain between two elastic boundaries at atmospheric pressure. Oxidation of the PDMS surface, achieved in real systems by exposure to air plasma or corona discharge, was modeled by replacing methyl groups on the PDMS chain with hydroxyl groups. Three surfaces of varying degrees of oxidation were characterized by measuring the water contact angle and the roughness. The dependence of the microscopic contact angle on drop size was measured from time averaged density profiles. The macroscopic contact angle was measured directly using a cylindrical drop of infinite length with zero contact line curvature. The measured macroscopic contact angle ranged from approximately 125 degrees on the untreated surface to 75 degrees on the most oxidized surface studied. The line tension was found to increase with increasing degree of oxidation, from a negligible value on the untreated surface to approximately 5x10(-11) J m(-1) on the most heavily oxidized surface.


Warming decreased and grazing increased plant uptake of amino acids in an alpine meadow.
Organic nitrogen (N) uptake by plants has been recognized as a significant component of terrestrial N cycle. Several studies indicated that plants have the ability to switch their preference between inorganic and organic forms of N in diverse environments; however, research on plant community response in organic nitrogen uptake to warming and grazing is scarce. Here, we demonstrated that organic N uptake by an alpine plant community decreased under warming with (13)C-(15)N-enriched glycine addition method. After 6 years of treatment, warming decreased plant organic N uptake by 37% as compared to control treatment. Under the condition of grazing, warming reduced plant organic N uptake by 44%. Grazing alone significantly increased organic N absorption by 15%, whereas under warming condition grazing did not affect organic N uptake by the Kobresia humilis community on Tibetan Plateau. Besides, soil NO 3-N content explained more than 70% of the variability observed in glycine uptake, and C:N ratio in soil dissolved organic matter remarkably increased under warming treatment. These results suggested warming promoted soil microbial activity and dissolved organic N mineralization. Grazing stimulated organic N uptake by plants, which counteracted the effect of warming.


Resistance to cyclic fatigue of PathFile, ScoutRaCe and ProGlider glide path files in an S-shaped canal.
To compare the cyclic fatigue resistance (CFR) of PathFile, ProGlider and ScoutRaCe nickel-titanium (NiTi) rotary instruments used in an S-shaped artificial canal. A total of 90 instruments were tested in an S-shaped artificial canal (n = 30 for each group: PathFile (size 16, 2% constant taper), ProGlider (size 16, variable taper between 2% and 8% along the shaft) and ScoutRaCe (size 15, 2% constant taper). All files were rotated until fracture. The number of cycles to failure was counted to determine CFR. The length of each fractured fragment was measured in millimetres. The CFR was analysed statistically with the Kruskal-Wallis test. The fragment length was analysed using one-way analysis of variance and Tukey's post hoc tests. The ProGlider instruments were associated with significantly greater CFR than the PathFile and ScoutRaCe files in the apical curvature (P < 0.05). There was no significant difference between the CFR of the PathFile and ScoutRaCe files in the apical curvature (P > 0.05). ProGlider, PathFile and ScoutRaCe instruments exhibited similar CFR in the coronal curvature (P > 0.05). The ProGlider files had greater cyclic fatigue resistance than the PathFile and ScoutRaCe files in the apical curvature of an artificial S-shaped canal.


Extra spinal osteoarticular tuberculosis: a case series of 66 patients from a tertiary care hospital in Karachi.
The demographic, clinical and laboratory data of patients diagnosed as extra-spinal osteoarticular tuberculosis, presenting at Department of Orthopaedic Surgery, Abbasi Shaheed Hospital, Karachi Medical and Dental College, Karachi, between December 2006 and January 2009 were analysed. There were 66 patients registered for the study. Forty four (66.66%) patients were females. The mean age was 26.5 +/- 13.5 years. Swelling and pain were the commonest symptoms. Knee and hip were the most frequent sites involved. The mean time to diagnosis was 12.32 +/- 18 months (range = 2- 96 months). Six (09.09%) patients had history of previous pulmonary kochs. Nine (13.63%) had concurrent pulmonary and 1(01.51%) had concurrent intestinal kochs. The average first hour ESR was 48 mm/h (16-102). Manteoux test was positive in 26/42 patients. Acid Fast Bacilli (AFB) stain was positive in 1/25 while culture was positive in 7/25 specimens. There was 1(14.28%) case of MDR tuberculosis. Most of the patients (95.45%), were diagnosed on positive histopathology report of involved tissues showing chronic granulomatous reaction with caseous necrosis.


[Relation of neopterin and beta 2 microglobulin to disease activity in chronic polyarthritis].
The correlations of the serum levels of neopterin and beta-2-microglobulin with the disease activity-measured by a clinical index-were investigated in 41 patients suffering from rheumatoid arthritis. Both parameters correlated significantly with the sum of the used disease activity index. There was a closer correlation between the serum levels of beta-2-microglobulin and the sum of the index and most of the particular parameters of the index than it was seen for the neopterin serum levels.


Study on the Mechanism of Ru-Catalyzed Cyclization of Aromatic Amides with Allylphosphine Oxides.
The mechanism of Ru-catalyzed cyclization of aromatic amides with allylphosphine oxides is studied by density functional theory calculation (DFT). The results show that, first, a 5-membered Ru ring intermediate is formed by N-H and C-H diprotons via the concerted metalation-deprotonation mechanism (CMD) and then the allylphosphine oxide is inserted through the ring-extending reaction to form a 7-membered ring intermediate. Next, reduction elimination is followed via intramolecular hydrogen transfer isomerization. At last, with the assistance of acetic acid, Ru (II) → Ru (IV) → Ru (II) complexes occur from the 7-membered Ru ring intermediate, and the final product is formed by reduction elimination and protonation reaction, while the catalyst is released to participate in the next cycle.


Modified Blalock-Taussig shunt patency for pulmonary atresia: assessment with electron beam CT.
The purpose of this work was to evaluate electron beam CT (EBCT) for the noninvasive assessment of modified Blalock-Taussig (BT) shunt patency in patients with pulmonary atresia. Five infants and children with pulmonary atresia and modified BT shunts underwent contrast-enhanced EBCT. Modified BT shunts from the subclavian artery to the pulmonary artery were performed to improve the pulmonary blood flow. Electrocardiogram (ECG)-triggered EBCT was obtained with a 100 ms exposure, 3 mm section thickness, and 2 mm table feed after intravenous administration of contrast material. Three-dimensional (3D) or maximum intensity projection (MIP) EBCT images were compared with conventional angiography. The visibility of modified BT shunts was graded and recorded with use of a four-point scale. Satisfactory visualization was achieved in both 3D and MIP EBCT images to evaluate modified BT shunt patency. Contrast-enhanced 3D or MIP EBCT imaging with ECG trigger may be used as an effective substitute to evaluate modified BT shunts with low radiation dose exposure.


Studies on the adjuvant action of bacterial endotoxins on antibody formation. III. Histologic response of the rabbit spleen to a single injection of a purified protein antigen.
Histologic changes occurring in the rabbit spleen during the primary response to intravenous injection of bovine gamma globulin alone and in combination with bacterial endotoxin have been described. The predominant morphologic changes associated with antibody formation in animals that received antigen alone were confined to the follicular areas of the spleen. Only minimal changes were seen in the red pulp. No new cellular types appeared following endotoxin stimulus. Rather, a profound augmentation of events observed following a single injection of bovine gamma globulin alone appears to account for the higher levels of antibody incited by this adjuvant. The cell type important in antibody formation under these conditions appeared to be a modified reticular cell. Plasma cells were not part of the cellular reaction. A hypothesis describing the primary antibody response is presented.


Lipophagy: A New Perspective of Natural Products in Type 2 Diabetes Mellitus Treatment.
Autophagy has been reported to involve in the pathogenesis of type 2 diabetes mellitus (T2DM), which protects the insulin target tissues and pancreatic β-cells. However, autophagy is inhibited when the cells are lipid overload. That, in turn, increases the accumulation of fat. Lipotoxicity caused by excessive lipid accumulation contributes to pathogenesis of T2DM. Therefore, it is undeniable to break the vicious circles between lipid excess and autophagy deficiency. Lipophagy, a selective form of autophagy, is characterized by selective breakdown of lipid droplets (LDs). The nutritional status of cells contributes to the way of autophagy (selective or non-selective), while selective autophagy helps to accurately remove excess substances. It seems that lipophagy could be an effective means to decrease abnormal lipid accumulation that leads to insulin resistance and β-cell impairment by removing ectopic LDs. Based on this process, many natural compounds have been reported to decrease lipid accumulation in tissues through autophagy-lysosomal pathway, which gradually highlights the significance of lipophagy. In this review, we focus on the mechanisms that lipophagy improves T2DM and natural products that are applied to induce lipophagy. It is also suggested that natural herbs with rich contents of natural products inducing lipophagy would be potential candidates for alleviating T2DM.


Culture and formulations of homicide: two case studies.
The killing of another human being is an execrable act and universally condemned. Simpler societies have informal ways of seeking retribution (Bohannan 1960; Hoebel 1954). Ancient states and civilizations evolved formal procedures and complex institutions for evaluating culpability, apportioning blame, and authorizing appropriate sanctions (Ng 1990; Robinson 1996). The evolution of the insanity defense in Anglo-American society has culminated in assigning to psychiatry and psychology the important task of determining whether the mental state of a person who perpetuates homicide meets criteria for legal sanction. Differences involving the traditional model of reasoning about human action that is standard in psychiatry compared to law have been discussed. A common basis of understanding and procedure for assessing responsibility has evolved (Moore 1984). However, usually neglected is the influence that culture has in shaping behavior of homicide and its forensic psychiatric assessment. Two cases are presented to examine why and how culture is influential in matters of homicide.


Combined argon laser peripheral iridoplasty and Nd: YAG laser shock wave therapy for recurrent XEN gel stent obstruction due to iris incarceration: A case report.
Despite its proven effectiveness and safety profile, the XEN Gel Stent (Allergan Inc., CA, USA) has a small lumen and is therefore likely to become occluded by fibrin, a blood clot, or even the iris. However, few studies have investigated XEN-iris occlusion and how to manage this condition. We describe the first case report of recurrent XEN gel stent obstruction by iris incarceration, which was resolved following a combined treatment with argon laser peripheral iridoplasty (ALPI) and low-energy neodymium-doped yttrium aluminum garnet (Nd: YAG) laser shock wave treatment. A 74-year-old Korean male underwent uncomplicated XEN gel stent implantation and presented with low intraocular pressure (IOP) with a well-functioning filtering bleb during the first postoperative week. On postoperative day 10, the XEN lumen was occluded by the iris and demonstrated an IOP spike of 33 mmHg. Despite the use of pilocarpine, the iris incarceration persisted. Therefore, surgery to reposition the XEN stent was attempted using a gonio-prism and intraocular forceps. After the first revision surgery, the IOP and stent position were stable for 2 weeks. However, recurrent partial obstruction of the stent by the iris, pigment dispersion into the intraluminal space, and an elevated IOP of 24 mmHg were observed later. Recurrent XEN gel stent occlusion by the iris and intraluminal pigment dispersion. Combined ALPI and low energy Nd: YAG laser shock wave therapy. IOP dropped from 24 mmHg to 10 mmHg immediately and continued to be well-controlled until 3 months later (range: 8-12 mmHg). To the best of our knowledge, this is the first case report of the efficacy of combined laser treatment for relieving recurrent XEN implant occlusion by the iris. This combination laser treatment might be a relatively safe rescue treatment to restore the patency of a XEN gel stent occluded by the iris, even in cases with recurrent XEN stent obstruction after surgical repositioning.


Development and Characterization of a Novel Monoclonal Antibody Against Chitinase-like Protein CHID1 Applicable for Immunohistochemistry on Formalin Fixed Paraffin-Embedded Sections.
CHID1 has been recently described as a predictive marker of different malignant tumors. Thus, monoclonal antibodies (mAbs) for CHID1 detection in different human liquids and in tissues are an important tool for the diagnosis of CHID1-positive cancers. However, only few mAbs have been established to date. In this study we describe the generation of a new hybridoma clone 3D4 producing anti-CHID1 antibodies. 3D4 mAb specifically binds human CHID1 and was successfully used in enzyme-linked immunosorbent assay, immunoblotting, immunofluorescence on paraformaldehyde-fixed cells, and in immunohistochemistry of paraffin-embedded tissue specimens. These results indicate that this new anti-CHID1 mAb 3D4 will be useful in the diagnosis of CHID1-related cancers and is a strong tool for both basic and clinical research on chitinase-like proteins.


Effects of antimicrobial treatment on selection of resistant Escherichia coli in broiler fecal flora.
Under field conditions, three commercial antimicrobials were sequentially prescribed to 16,000 broiler chickens during their rearing period, via drinking water using subtherapeutic levels for 3 days. A control group of 16,000 broilers was placed in the same controlled environment poultry house. Feed diet and fecal samples from both groups were collected periodically. One sample of the drinking water along with samples from the broiler house environment was also collected 1 day before bird placement. Samples were plated onto Tergitol BCIG Agar media; a maximum of 26 Escherichia coli were isolated per sample, and their susceptibility was tested to 12 antimicrobials by disk diffusion agar method. We have observed that day-old chicks were rapidly colonized by new antibiotic-resistant patterns shortly after treatment with lincomycin associated with spectinomycin. After medication with the second (sulfadiazine with trimethoprim) and third (tylosin) antimicrobials, a more radical displacement was observed, and, concurrently, antimicrobial resistance phenotypes have become more complex. In contrast, more than 70% of the strains isolated in control group during the experiment displayed exactly the same resistance pattern found in the day-old chicks. This study provides clear evidence that a sequential medication of a broiler flock, with different antimicrobial classes during short periods of time for prophylactic objectives, was accompanied by a dramatic increase in both antimicrobial resistance rates and phenotype diversity of E. coli strains.


Hyperoxia-induced bronchopulmonary dysplasia: better models for better therapies.
Bronchopulmonary dysplasia (BPD) is a chronic lung disease caused by exposure to high levels of oxygen (hyperoxia) and is the most common complication that affects preterm newborns. At present, there is no cure for BPD. Infants can recover from BPD; however, they will suffer from significant morbidity into adulthood in the form of neurodevelopmental impairment, asthma and emphysematous changes of the lung. The development of hyperoxia-induced lung injury models in small and large animals to test potential treatments for BPD has shown some success, yet a lack of standardization in approaches and methods makes clinical translation difficult. In vitro models have also been developed to investigate the molecular pathways altered during BPD and to address the pitfalls associated with animal models. Preclinical studies have investigated the efficacy of stem cell-based therapies to improve lung morphology after damage. However, variability regarding the type of animal model and duration of hyperoxia to elicit damage exists in the literature. These models should be further developed and standardized, to cover the degree and duration of hyperoxia, type of animal model, and lung injury endpoint, to improve their translational relevance. The purpose of this Review is to highlight concerns associated with current animal models of hyperoxia-induced BPD and to show the potential of in vitro models to complement in vivo studies in the significant improvement to our understanding of BPD pathogenesis and treatment. The status of current stem cell therapies for treatment of BPD is also discussed. We offer suggestions to optimize models and therapeutic modalities for treatment of hyperoxia-induced lung damage in order to advance the standardization of procedures for clinical translation.


New insights into the generation of Th2 immunity and potential therapeutic targets for the treatment of asthma.
Asthma is a heterogeneous disease with unknown cause; however, allergic asthma is driven largely by Th2-type immune responses. The pathways that interact to induce Th1 and Th17-type immune responses are well understood; however, until recently the innate immune pathways involved in the induction of Th2-type immunity were unknown. In this review we sought to outline many of the recent advances in uncovering the cell and molecular mechanisms that generate Th2 responses. It is clear that the Th2 pathway can no longer be considered a 'default pathway' of the lung immune system as multiple cells and cytokines have now been identified that work to actively instruct Th2 differentiation. Basophils and dendritic cells have been investigated for their critical role in Th2 induction, and newly identified cell subsets have also been shown to play an important function in Th2 responses. The identification of the Th2-inducing cytokines IL-25, IL-33 and thymic stromal lymphopoietin has also accelerated studies examining the development of Th2 responses in asthma. Studies of the role played by the innate immune system in the induction of Th2 responses have begun to unravel the cellular and molecular mechanisms potentially underlying the pathogenesis of allergic asthma. Further study in this area may lead to the discovery of new therapeutics for the treatment of allergic disease.


Modeling single ventricle physiology: review of engineering tools to study first stage palliation of hypoplastic left heart syndrome.
First stage palliation of hypoplastic left heart syndrome, i.e., the Norwood operation, results in a complex physiological arrangement, involving different shunting options (modified Blalock-Taussig, RV-PA conduit, central shunt from the ascending aorta) and enlargement of the hypoplastic ascending aorta. Engineering techniques, both computational and experimental, can aid in the understanding of the Norwood physiology and their correct implementation can potentially lead to refinement of the decision-making process, by means of patient-specific simulations. This paper presents some of the available tools that can corroborate clinical evidence by providing detailed insight into the fluid dynamics of the Norwood circulation as well as alternative surgical scenarios (i.e., virtual surgery). Patient-specific anatomies can be manufactured by means of rapid prototyping and such models can be inserted in experimental set-ups (mock circulatory loops) that can provide a valuable source of validation data as well as hydrodynamic information. Such models can be tuned to respond to differing the patient physiologies. Experimental set-ups can also be compatible with visualization techniques, like particle image velocimetry and cardiovascular magnetic resonance, further adding to the knowledge of the local fluid dynamics. Multi-scale computational models include detailed three-dimensional (3D) anatomical information coupled to a lumped parameter network representing the remainder of the circulation. These models output both overall hemodynamic parameters while also enabling to investigate the local fluid dynamics of the aortic arch or the shunt. As an alternative, pure lumped parameter models can also be employed to model Stage 1 palliation, taking advantage of a much lower computational cost, albeit missing the 3D anatomical component. Finally, analytical techniques, such as wave intensity analysis, can be employed to study the Norwood physiology, providing a mechanistic perspective on the ventriculo-arterial coupling for this specific surgical scenario.


Gingival crevicular fluid levels of cytokine, chemokine, and growth factors in patients with periodontitis or gingivitis and periodontally healthy subjects: a cross-sectional multiplex study.
Gingival crevicular fluid (GCF) is an important resource for detecting inflammatory biomarkers related to periodontal disease. The purpose of this research was to identify the possible relation between cytokine levels and periodontal status. GCF samples collected from 25 periodontally healthy individuals, 24 with gingivitis, and 24 with periodontitis were analyzed using the MAGPIX system with a Bio-Plex Pro Human Cytokine 27-plex kit. Gingival index (GI), periodontal pocket depth (PPD), plaque index (PI), and clinical attachment level (CAL) were measured from each tooth to determine each patient's periodontal status. All clinical parameters showed statistically significant differences between groups. While interleukin (IL)-1β, IL-6, macrophage chemotactic protein 1 (MCP-1), interferon γ-induced protein 10 (IP-10) and vascular endothelial growth factor (VEGF) levels were statistically significantly higher in patients with periodontitis compared to periodontally healthy subjects, IL-15 levels were found to be statistically significantly higher in periodontally healthy individuals compared to periodontitis (p < 0.05). Also, IL-1β and IP-10 showed positive correlations with PPD, CAL, GI and bleeding on probing (BOP). It is considered that IL-1β, IL-6, IL-15, MCP-1, VEGF and IP-10 could be related to periodontal disease and health and can be used as an adjunct to clinical examination in future research design. Scanning cytokines in GCF with a multiplex immunoassay technique is consequential, especially because many cytokine types are found in one sample.


The efficacy of the ribonucleotide reductase inhibitor Didox in preclinical models of AML.
Acute Myeloid Leukemia (AML) is an aggressive malignancy which leads to marrow failure, and ultimately death. There is a desperate need for new therapeutics for these patients. Ribonucleotide reductase (RR) is the rate limiting enzyme in DNA synthesis. Didox (3,4-Dihydroxybenzohydroxamic acid) is a novel RR inhibitor noted to be more potent than hydroxyurea. In this report we detail the activity and toxicity of Didox in preclinical models of AML. RR was present in all AML cell lines and primary patient samples tested. Didox was active against all human and murine AML lines tested with IC50 values in the low micromolar range (mean IC50 37 µM [range 25.89-52.70 µM]). It was active against primary patient samples at concentrations that did not affect normal hematopoietic stem cells (HSCs). Didox exposure resulted in DNA damage and p53 induction culminating in apoptosis. In syngeneic, therapy-resistant AML models, single agent Didox treatment resulted in a significant reduction in leukemia burden and a survival benefit. Didox was well tolerated, as marrow from treated animals was morphologically indistinguishable from controls. Didox exposure at levels that impaired leukemia growth did not inhibit normal HSC engraftment. In summary, Didox was well tolerated and effective against preclinical models of AML.


Synthesis of 1-(4-thio-beta-D-ribofuranosyl)-1,2,4-triazole-3-carboxamide.
The synthesis of 1-(4-thio-beta-D-ribofuranosyl)-1,2,4-triazole-3-carboxamide (3) is described. The acid-catalyzed fusion procedure with 3-cyano-1,2,4-triazole and 1,2,3,5-tetra-O-acetyl-4-thio-D-ribofuranose provided 3-cyano-1-(2,3,5-tri-O-acetyl-4-thio-beta-D-ribofuranosyl-1,2,4-triazole (2) which was converted with NH4OH to 3. In contrast to 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (1), the 4'-thio nucleoside 3 did not exhibt significant antiviral activity in vitro.


Bounding the infectiousness effect in vaccine trials.
In vaccine trials, the vaccination of one person might prevent the infection of another; a distinction can be drawn between the ways such a protective effect might arise. Consider a setting with 2 persons per household in which one of the 2 is vaccinated. Vaccinating the first person may protect the second person by preventing the first from being infected and passing the infection on to the second. Alternatively, vaccinating the first person may protect the second by rendering the infection less contagious even if the first is infected. This latter mechanism is sometimes referred to as an "infectiousness effect" of the vaccine. Crude estimators for the infectiousness effect will be subject to selection bias due to stratification on a postvaccination event, namely the infection status of the first person. We use theory concerning causal inference under interference along with a principal-stratification framework to show that, although the crude estimator is biased, it is, under plausible assumptions, conservative for what one might define as a causal infectiousness effect. This applies to bias from selection due to the persons in the comparison, and also to selection due to pathogen virulence. We illustrate our results with an example from the literature.


Removing ECG Artifact from the Surface EMG Signal Using Adaptive Subtraction Technique.
The electrocardiogram artifact is a major contamination in the electromyogram signals when electromyogram signal is recorded from upper trunk muscles and because of that the contaminated electromyogram is not useful. Objective : Removing electrocardiogram contamination from electromyogram signals. In this paper, the clean electromyogram signal, electrocardiogram artifact and electrocardiogram signal were recorded from leg muscles, the pectoralis major muscle of the left side and V4, respectively. After the pre-processing, contaminated electromyogram signal is simulated with a combination of clean electromyogram and electrocardiogram artifact. Then, contaminated electromyogram is cleaned using adaptive subtraction method. This method contains some steps; (1) QRS detection, (2) formation of electrocardiogram template by averaging the electrocardiogram complexes, (3) using low pass filter to remove undesirable artifacts, (4) subtraction. Performance of our method is evaluated using qualitative criteria, power spectrum density and coherence and quantitative criteria signal to noise ratio, relative error and cross correlation. The result of signal to noise ratio, relative error and cross correlation is equal to 10.493, 0.04 and %97 respectively. Finally, there is a comparison between proposed method and some existing methods. The result indicates that adaptive subtraction method is somewhat effective to remove electrocardiogram artifact from contaminated electromyogram signal and has an acceptable result.


Effect of physical training on exercise capacity, gas exchange and N-terminal pro-brain natriuretic peptide levels in patients with chronic heart failure.
Decreased exercise capacity is the main factor restricting the daily life of patients with chronic heart failure. N-terminal pro-brain natriuretic peptide (NT pro-BNP) is strongly related to the severity of and is an independent predictor of outcome in chronic heart failure. The study aimed to evaluate the effect of exercise training on functional capacity and on changes in NT pro-BNP levels and to assess the effect of exercise training on quality of life. Sixty patients (45 men/15 women, mean age 52.7 years; +/-5.3 SD), with stable heart failure (45 ischaemic/hypertensive and 15 idiopathic patients), in New York Heart Association (NYHA) functional class II (n=35) to III (n=25), with an ejection fraction less than 40%, were randomly assigned to a training (n=30) and a control group (n=30). The training group (30 patients) performed 3 months of supervised physical training programme using a bicycle ergometer for 30 min three times a week at a load corresponding to 60-70% of their oxygen consumption (VO2) peak. The control group did not change their previous physical activity. A graded maximal exercise test with respiratory gas analysis and an endurance test with constant workload corresponding to 85% of the peak oxygen load at the baseline and after 3 months were performed, and at the same times NT pro-BNP levels were measured. The exercise capacity increased from 15.8 (+/-2.3 SD) to 29.9 (+/-2.1 SD) min (P<0.0001) and the peak VO2 tended to improve from 14.5 (+/-1.4 SD) to 17.7 (+/-2.6 SD) ml/kg per min (P<0.0001) during the supervised training period. VO2 at the anaerobic threshold increased from 12.9 (+/-1.0 SD) to 15.5 (+/-1.7 SD) ml/kg per min (P<0.0001). NT pro-BNP levels decreased from 3376 (+/-3133 SD) to 1434 (+/-1673 SD) pg/ml (P=0.043). The positive training effects were associated with an improvement in the NYHA functional class. Physical training of moderate intensity significantly improves the exercise capacity and neurohormonal modulation in patients with chronic heart failure. This is associated with an alleviation of symptoms and improvement in quality of life.


Production and characterization of a PEGylated derivative of recombinant human deoxyribonuclease I for cystic fibrosis therapy.
Recombinant human deoxyribonuclease I (rhDNase) is the mucolytic agent most widely used for the treatment of respiratory disease in cystic fibrosis. However, rhDNase is rapidly cleared from the lungs which implies a high dosing frequency and limited patient adherence. The aim of this study was to produce a long-acting PEGylated derivative of rhDNase presenting a preserved enzymatic activity. Site-specific PEGylation on the N-terminal (N-ter) leucine residue of rhDNase was achieved by reductive alkylation at acidic pH using linear 20kDa, linear 30kDa or two-arm 40kDa polyethylene glycol (PEG) propionaldehydes. Yields of mono-PEGylated products ranged between 45% and 61%. Conjugation to PEG fully preserved the secondary structure and the in vitro enzymatic activity of the native protein. These properties offer interesting perspectives for in vivo inhalation studies of the PEGylated enzyme.


Kidney and adrenocortical hormones.
We have presented a review of the interrelationship between the kidney and the adrenocortical steroids, aldosterone and cortisol primarily in the regulation of water and electrolyte metabolism. The presentation is divided into three parts: (1) the influence of cortisol and aldosterone on renal structure and function; (2) the effect of kidney disease on secretion and metabolism of these steroids, and (3) the role of the kidneys in the plasma clearance of these steroids and their metabolites. There is no evidence that an excess or deficit of these steroids have a direct effect on renal structure, but both are necessary to maintain normal GFR and RPF. Glucocorticoids augment renal hemodynamics in pharmacologic doses. The phenomenon of 'escape' by the kidney from the sodium-retaining effect of adrenocortical steroids is discussed in detail, as well as the ability of glucocorticoid to antagonize the sodium retaining activity of any adrenal steroid of analogue with lesser glucocorticoid noperties. It is included that the impaired water dunesis of glycocorticoid deficiency is due to the absence of the permissive action of these steroids on the kidney, augmented at times by enhanced ADH secretion in response to sustained nonosmotic stimuli. The effect of gluco and mineralocorticoids on the renal excretion of divalentions and uric acid is also discussed. While progressive chronic renal failure (CRF) does not seem to significantly after the secretion or metabolism of cortisol it is possible that CRF causes a state of chronic hyperaldosteronism that is essential to maintain normal excretion (secretion) of potassium per nephron as renal mass progressively decreases. A direct or an indirect effect of potassium ion may be responsible for the hypersecretion or aldosterone rather than the renin-angiotensin system.


Genetics of coagulation: considerations for cardiac surgery.
Genetic variants in the coagulation system have been known since antiquity. Today, because of modern improvements in diagnosis and medical management, the clinician is likely to encounter a spectrum of coagulation factor deficiencies and identified polymorphic variants in the surgical population. Because perioperative hemorrhagic and thrombotic complications are potentially serious, it is important to understand the role that these defects and variants may play in predicting risk and optimizing patient management. The implications of coagulation genetics on the perioperative management of the cardiac surgery patient are reviewed.


Ubiquitous Creation of Bas-Relief Surfaces with Depth-of-Field Effects Using Smartphones.
This paper describes a new method to automatically generate digital bas-reliefs with depth-of-field effects from general scenes. Most previous methods for bas-relief generation take input in the form of 3D models. However, obtaining 3D models of real scenes or objects is often difficult, inaccurate, and time-consuming. From this motivation, we developed a method that takes as input a set of photographs that can be quickly and ubiquitously captured by ordinary smartphone cameras. A depth map is computed from the input photographs. The value range of the depth map is compressed and used as a base map representing the overall shape of the bas-relief. However, the resulting base map contains little information on details of the scene. Thus, we construct a detail map using pixel values of the input image to express the details. The base and detail maps are blended to generate a new depth map that reflects both overall depth and scene detail information. This map is selectively blurred to simulate the depth-of-field effects. The final depth map is converted to a bas-relief surface mesh. Experimental results show that our method generates a realistic bas-relief surface of general scenes with no expensive manual processing.


Spatiotemporal expression of repulsive guidance molecules (RGMs) and their receptor neogenin in the mouse brain.
Neogenin has been implicated in a variety of developmental processes such as neurogenesis, neuronal differentiation, apoptosis, migration and axon guidance. Binding of repulsive guidance molecules (RGMs) to Neogenin inhibits axon outgrowth of different neuronal populations. This effect requires Neogenin to interact with co-receptors of the uncoordinated locomotion-5 (Unc5) family to activate downstream Rho signaling. Although previous studies have reported RGM, Neogenin, and/or Unc5 expression, a systematic comparison of RGM and Neogenin expression in the developing nervous system is lacking, especially at later developmental stages. Furthermore, information on RGM and Neogenin expression at the protein level is limited. To fill this void and to gain further insight into the role of RGM-Neogenin signaling during mouse neural development, we studied the expression of RGMa, RGMb, Neogenin and Unc5A-D using in situ hybridization, immunohistochemistry and RGMa section binding. Expression patterns in the primary olfactory system, cortex, hippocampus, habenula, and cerebellum were studied in more detail. Characteristic cell layer-specific expression patterns were detected for RGMa, RGMb, Neogenin and Unc5A-D. Furthermore, strong expression of RGMa, RGMb and Neogenin protein was found on several major axon tracts such as the primary olfactory projections, anterior commissure and fasciculus retroflexus. These data not only hint at a role for RGM-Neogenin signaling during the development of different neuronal systems, but also suggest that Neogenin partners with different Unc5 family members in different systems. Overall, the results presented here will serve as a framework for further dissection of the role of RGM-Neogenin signaling during neural development.


Hepatic Resection for Liver Metastases from Cervical Cancer Is Safe and May Have Survival Benefit.
The goal of this study was to evaluate the single-centre experience with hepatectomy for liver metastases from cervical cancer (CCLM). Fifteen patients who underwent such surgery at the Fundeni Clinical Hospital between January 2002 and April 2014 were retrospectively reviewed. Liver lesions diagnosed at more than 6 months from cervical cancer diagnosis were classified as metachronous lesions, while lesions occurring within the first 6 months were considered synchronous lesions. Two patients were diagnosed with synchronous CCLM, while the other 13 patients had metachronous. Early postoperative death occurred in a single patient with metachronous liver metastases and pelvic recurrence, but this was not related to liver surgery. The median overall survival for the entire cohort was 18 months from the time of liver resection; patients with metachronous lesions had an improved outcome when compared to those with synchronous lesions. In patients with metachronous liver metastases, prognostic factors associated with an improved outcome were the general biological status of the patient, grade of tumoural differentiation and absence of other abdomino-pelvic recurrences. In multivariate analysis, only the grade of differentiation was statistically significant. In conclusion, hepatic resection for liver metastases from cervical cancer can be performed safely, may prove effective, and should be part of the multimodal treatment.


Infrared spectra of the complexes of trifluoroethene with dimethyl ether, acetone, and oxirane: a cryosolution study.
Infrared spectra of solutions of trifluoroethene and dimethyl ether, acetone, or oxirane in liquid krypton and liquid argon have been studied. For each Lewis base the formation of a 1:1 complex with the Lewis acid was observed. The C-H stretching of trifluoroethene being perturbed by a strong Fermi resonance, the complexes with trifuloroethene-d were also investigated and showed that in each case the hydrogen bond between the acid and base is of the traditional, red-shifting type. The structures of the complexes were investigated using ab initio calculations. These indicate that with dimethyl ether and acetone two different isomeres can be formed, but with a single one detected in the solution in each case. The Fermi resonance in the complex with unlabeled trifluoroethene is discussed using data derived form ab initio potential and dipole hypersurface calculations. The complexation enthalpies of the complexes were obtained from temperature dependent studies of the solutions and are discussed in relation to the ab initio complexation energies and Monte Carlo free energy perturbation calculations of solvent effects.


Homophilic binding of mouse monoclonal antibodies against GD3 ganglioside.
R24, a mouse IgG3 mAb against GD3 ganglioside, was shown to bind to itself in a homophilic manner. This was demonstrated by augmented binding of 125I-labeled R24 to the cell surface of GD3+ cells by unlabeled R24 and by direct binding of biotinylated R24 to R24 adsorbed on solid phase. Although homophilic binding was evident when R24 was bound to solid phase, R24-R24 aggregates could not be detected in solution under otherwise identical conditions. R24 bound to four other mAb (two IgG3, one IgG2a, one IgM) directed against GD3 but did not bind to a panel of 21 other mAb including other IgG3 mAb and mAb directed against non-GD3 ganglioside. Evidence implicating the GD3-binding site of R24 in homophilic binding included the following observations: 1) F(ab')2 fragments of R24 could bind to R24, 2) an antiidiotypic mAb against the GD3-binding site of R24 inhibited R24 homophilic binding, 3) an IgM anti-GD3 mAb also demonstrated homophilic binding to R24, and 4) homophilic binding was a function of immunoreactivity and avidity for GD3. R24 variants with 40-fold lower avidity for GD3 demonstrated a similar decrease in homophilic binding. Inasmuch as R24 bound to R24 F(ab')2 fragments and specifically to anti-GD3 mAb, it appeared that the target for homophilic binding was an epitope within the V region of anti-GD3 mAb. It is likely that homophilic interactions result in increased affinity of R24 for GD3 through increased effective valency of antibody-Ag complexes.


Multifunctional Poly(ethylene glycol)s.
In the rapidly evolving multidisciplinary field of polymer therapeutics, tailored polymer structures represent the key constituent to explore and harvest the potential of bioactive macromolecular hybrid structures. In light of the recent developments for anticancer drug conjugates, multifunctional polymers are becoming ever more relevant as drug carriers. However, the potentially best suited polymer, poly(ethylene glycol) (PEG), is unfavorable owing to its limited functionality. Therefore, multifunctional linear copolymers (mf-PEGs) based on ethylene oxide (EO) and appropriate epoxide comonomers are attracting increased attention. Precisely engineered via living anionic polymerization and defined with state-of-the-art characterization techniques-for example real-time (1)H NMR spectroscopy monitoring of the EO polymerization kinetics-this emerging class of polymers embodies a powerful platform for bio- and drug conjugation.


[The practice guideline 'Otitis externa' (first revision) from the Dutch College of General Practitioners; a response from the perspective of general practice].
The first revision of the practice guideline 'Otitis externa' from the Dutch College of General Practitioners has been published. Data from a clinical trial in primary care clearly show that acid eardrops containing corticosteroids are superior to acid eardrops without corticosteroids. Other minor changes have been made. A KOH test is no longer necessary in general practice. Aluminium acetotartrate eardrops 1.2% are reserved for otitis externa with tympanic membrane perforation.