Time in therapeutic range values of patients using warfarin and factors that influence time in therapeutic range.
The time in therapeutic range (TTR) of international normalized ratio (INR) is essential for the safety and efficacy of warfarin treatment. In this study, we aimed to determine TTR and the factors that affect TTR in patients using warfarin. Patients taking warfarin for valvular and nonvalvular atrial fibrillation (AF) or prosthetic heart valves who were admitted to our cardiology outpatient clinic were enrolled. TTR was calculated using the linear interpolation method. The patients were analyzed according to warfarin indications and TTR efficiency (TTR ≥60%). Weekly warfarin dose, the duration of warfarin use, the frequency of INR visits per year, and the awareness of patients regarding target INR were noted. The TTR of 248 patients (aged 57.21±12.45 years, 33.1% male) was 55.92±27.84%, and 48.0% patients exhibited efficient TTR. Clinical and demographic characteristics (age, sex, socioeconomic status, and comorbidities) exerted no effect on TTR and TTR efficiency. The frequency of INR visits per year was 10.02±3.80. TTR was related to the frequency of annual INR visits (r=0.131, p=0.039). Only one-third (30.2%) of patients were aware of their target INR. The literacy of the patients and duration of warfarin use exerted a positive effect on awareness (p=0.011 and p=0.024, respectively). The findings of our study demonstrated that TTR and TTR efficiency were low and not associated with the characteristics of patients or indications. Unfortunately, in patients with valvular AF and prosthetic valves, warfarin is the sole drug that can be used. Thus, awareness and knowledge regarding target INR are essential to overcome poor anticoagulation monitoring with frequent INR visits.


Combination of Osimertinib and Anlotinib May Overcome the Resistance Mediated by in cis EGFR T790M-C797S in NSCLC: A Case Report.
The emergence of epidermal growth factor receptor (EGFR) exon 20 p.C797S is one of the major resistance mechanisms for osimertinib. However, there are no standard of care for non-small cell lung cancer (NSCLC) patients after acquiring EGFR C797S currently, which brings significant challenges to post-osimertinib clinical management. In the present study, we described a 52-year-old female patient with EGFR-mutated stage IV lung adenocarcinoma, who achieved a partial response (PR) to the treatment of gefitinib and osimertinib after acquiring EGFR exon 20 p.T790M-trans-C797S at osimertinib failure. After progression on the combinatorial treatment, allelic configuration shifted to T790M-cis-C797S. The patient subsequently received a regimen of osimertinib and anlotinib combined with chemotherapy, followed by osimertinib and anlotinib maintenance treatment, and achieved a PR lasting for 9 months. At disease progression, concomitant T790M-C797S mutations both in trans and cis were identified. A combination of chemo- and anti-angiogenic therapies was administrated for two cycles and then discontinued because of the poor physical condition of the patient. She passed away soon with an overall survival of 39 months and a post-osimertinib progression survival of 20 months. Our study provides the first clinical evidence that the osimertinib and anlotinib-based regimen may be an effective therapy in overcoming resistance mediated by T790M-cis-C797S. Our case also highlights the importance of dynamically monitoring the mutation status after osimertinib failure, which may provide patients with increased opportunities for targeted therapy and improve post-osimertinib progression survivals.


Evaluation of nonunion fractures in dogs by use of B-mode ultrasonography, power Doppler ultrasonography, radiography, and histologic examination.
To investigate the use of ultrasonography to assess nonunion of fractures in dogs and to compare results of ultrasonography, radiography, and histologic examination. 8 nonunion fractures in 6 dogs (1 each in 5 dogs and 3 in 1 dog); dogs ranged from 7 to 94 months of age and weighed 6 to 30 kg. Diagnostic assessment consisted of complete clinical and orthopedic examinations, radiography, B-mode (brightness mode) ultrasonography, and power Doppler ultrasonography. Biopsy samples were obtained during surgery for histologic examination. They were stained with H&E and immunolabeled by use of anti-CD31 antibodies. Correlations of power Doppler score, power Doppler count, vessel area, and radiographic prediction with the mean number of vessels counted per hpf were derived. Radiographically, 7 of 8 nonunion fractures were diagnosed as atrophic and were therefore estimated to be nonviable. Vascularity of nonunion fractures during power Doppler ultrasonography ranged from nonvascularized to highly vascularized. Absolute vessel count during histologic examination ranged from 0 to 63 vessels/hpf; 5 nonunion sites had a mean count of > 10 vessels/hpf. Vascularity during power Doppler ultrasonography was highly correlated with the number of vessels per hpf, whereas the correlation between the radiographic assessment and histologic evaluation was low. Radiographic prediction of the viability of nonunion fractures underestimated the histologically assessed vascularity of the tissue. Power Doppler ultrasonography provided a more accurate estimation of the viability of the tissue and therefore the necessity for debridement and autografts during revision surgery.


Stress hormones and AMPA receptor trafficking in synaptic plasticity and memory.
The acquisition and consolidation of memories of stressful events is modulated by glucocorticoids, a type of corticosteroid hormone that is released in high levels from the adrenal glands after exposure to a stressful event. These effects occur through activation of mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs). The molecular mechanisms that underlie the effects of glucocorticoids on synaptic transmission, synaptic plasticity, learning and memory have recently begun to be identified. Glucocorticoids regulate AMPA (α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate) receptor trafficking--which is crucially involved in synaptic transmission and plasticity--both rapidly and persistently. Stress hormones may, through modulation of AMPA receptor function, promote the consolidation of behaviourally relevant information.


Nonunion of the humerus.
Under certain circumstances, fractures of the humerus may not heal. Some fractures experience delayed union and some develop nonunion despite improved methods of treatment. This chapter discussed nonunion and fracture fixation methods in the proximal, middle, and distal thirds of the humerus. Special circumstances were discussed, such as infection, nerve palsy, comminution, and electrical stimulation.


Survival among the older adults with clinical signs of Lewy body dementia in 40 Swedish nursing homes: a 6-year follow-up study.
To investigate survival among elderly residents of Swedish nursing homes (NHs), with specific focus on those with two or more signs of Lewy body dementia (LBD). Prospective observational study. NHs in Malmö, the third largest city in Sweden. The study population was older adults (aged ≥65 years) living in the 40 NHs in Malmö. Clinical data were collected with a customised questionnaire assessing core clinical LBD signs. Patients were categorised based on 0-1 or 2-4 LBD signs. The head nurse at each NH collected the study data: LBD questionnaires, electronic medication lists and electronic medical records from 2012 to 2013. 80-month mortality. Five hundred and fifty-eight (96%) of the residents were deceased at follow-up; among these, mean (95% CI) overall survival time was 29 (28-31) months. Mean survival differed between the LBD groups; those with 0-1 LBD signs lived 8 months longer than those with 2-4 LBD signs. Mortality risk for residents in the LBD 2-4 group was also significantly higher. HR adjusted for age and sex was HR (95% CI) 1.60 (1.30 to 1.97). Mortality risk was also significantly higher in residents with signs of fluctuating cognition 1.36 (1.15 to 1.62), rapid eye movement sleep behaviour disorder 1.49 (1.11 to 1.98), balance problems 1.36 (1.14 to 1.61) or rigidity 1.41 (1.18 to 1.68). This large, longitudinal study shows the important survival effects of identifying and diagnosing older adults NH residents who have two or more LBD signs.


HDAC4/5-HMGB1 signalling mediated by NADPH oxidase activity contributes to cerebral ischaemia/reperfusion injury.
Histone deacetylases (HDACs)-mediated epigenetic mechanisms play critical roles in the homeostasis of histone acetylation and gene transcription. HDAC inhibitors have displayed neuroprotective properties in animal models for various neurological diseases including Alzheimer's disease and ischaemic stroke. However, some studies have also reported that HDAC enzymes exert protective effects in several pathological conditions including ischaemic stress. The mixed results indicate the specific roles of each HDAC protein in different diseased states. However, the subtypes of HDACs associated with ischaemic stroke keep unclear. Therefore, in this study, we used an in vivo middle cerebral artery occlusion (MCAO) model and in vitro cell cultures by the model of oxygen glucose deprivation to investigate the expression patterns of HDACs and explore the roles of individual HDACs in ischaemic stroke. Our results showed that inhibition of NADPH oxidase activity ameliorated cerebral ischaemia/reperfusion (I/R) injury and among Zn(2+) -dependent HDACs, HDAC4 and HDAC5 were significantly decreased both in vivo and in vitro, which can be reversed by NADPH oxidase inhibitor apocynin. We further found that both HDAC4 and HDAC5 increased cell viability through inhibition of HMGB1, a central mediator of tissue damage following acute injury, expression and release in PC12 cells. Our results for the first time provide evidence that NADPH oxidase-mediated HDAC4 and HDAC5 expression contributes to cerebral ischaemia injury via HMGB1 signalling pathway, suggesting that it is important to elucidate the role of individual HDACs within the brain, and the development of HDAC inhibitors with improved specificity is required to develop effective therapeutic strategies to treat stroke.


Friedelin: Structure, Biosynthesis, Extraction, and Its Potential Health Impact.
Pharmaceutical companies are investigating more source matrices for natural bioactive chemicals. Friedelin (friedelan-3-one) is a pentacyclic triterpene isolated from various plant species from different families as well as mosses and lichen. The fundamental compounds of these friedelane triterpenoids are abundantly found in cork tissues and leaf materials of diverse plant genera such as Celastraceae, Asteraceae, Fabaceae, and Myrtaceae. They possess many pharmacological effects, including anti-inflammatory, antioxidant, anticancer, and antimicrobial activities. Friedelin also has an anti-insect effect and the ability to alter the soil microbial ecology, making it vital to agriculture. Ultrasound, microwave, supercritical fluid, ionic liquid, and acid hydrolysis extract friedelin with reduced environmental impact. Recently, the high demand for friedelin has led to the development of CRISPR/Cas9 technology and gene overexpression plasmids to produce friedelin using genetically engineered yeast. Friedelin with low cytotoxicity to normal cells can be the best phytochemical for the drug of choice. The review summarizes the structural interpretation, biosynthesis, physicochemical properties, quantification, and various forms of pharmacological significance.


Predicting co-complexed protein pairs using genomic and proteomic data integration.
Identifying all protein-protein interactions in an organism is a major objective of proteomics. A related goal is to know which protein pairs are present in the same protein complex. High-throughput methods such as yeast two-hybrid (Y2H) and affinity purification coupled with mass spectrometry (APMS) have been used to detect interacting proteins on a genomic scale. However, both Y2H and APMS methods have substantial false-positive rates. Aside from high-throughput interaction screens, other gene- or protein-pair characteristics may also be informative of physical interaction. Therefore it is desirable to integrate multiple datasets and utilize their different predictive value for more accurate prediction of co-complexed relationship. Using a supervised machine learning approach--probabilistic decision tree, we integrated high-throughput protein interaction datasets and other gene- and protein-pair characteristics to predict co-complexed pairs (CCP) of proteins. Our predictions proved more sensitive and specific than predictions based on Y2H or APMS methods alone or in combination. Among the top predictions not annotated as CCPs in our reference set (obtained from the MIPS complex catalogue), a significant fraction was found to physically interact according to a separate database (YPD, Yeast Proteome Database), and the remaining predictions may potentially represent unknown CCPs. We demonstrated that the probabilistic decision tree approach can be successfully used to predict co-complexed protein (CCP) pairs from other characteristics. Our top-scoring CCP predictions provide testable hypotheses for experimental validation.


The value of the study of the psychopathology of expression.
The study of the psychopathology of expression deals with abnormal tendencies and themes in paintings and creative products of mental and other patients, and the same kinds of themes in the work of normal artists. Its values are as follows: for diagnosis in revealing patients' problems through observation of deviations from normal tendencies and themes in their art; for treatment in giving insight and understanding to the patient; in relation to modern art because it makes clear what is often confused and bizarre; in relation to classical art because some of the same themes and tendencies are often present and it helps us to understand them; in relation to the study of creativity because sources of inspiration become apparent when underlying themes and tendencies are revealed. It cannot, however, explain fully the real nature of art.


[Proteolytic enzymes of the lacrimal fluid as pathogenesis factors of chronic corneal ulcer].
Proteolytic enzymes, particularly collagenase, are involved in development of eye cornea chronic ulcers. Analysis of lacrimal fluid obtained from the patients enabled to find not only the collagenase activity but and serine enzymes exhibiting BAEE esterase activity. Plasmin, blood plasma and tissue kallikreins regulated permeability of capillaries in conjunctiva and lacrimal gland as well as they activated latent collagenase. Studies of BAEE esterase activity in lacrimal fluid of the patients are required for prescription of adequate pathogenetic treatment.


Macrophage heterogeneity in man. A subpopulation of HLA-DR-bearing macrophages required for antigen-induced T cell activation also contains stimulators for autologous-reactive T cells.
Utilizing somatic cell hybridization, we have developed a monoclonal antibody that interacts only with cells of the monocyte/macrophage (M phi) line and not with other myeloid or lymphoid cells. This antibody detects a 120,000-dalton determinant present on 37 +/- 2.8% of the peripheral blood M phi from several (HLA-DR)-disparate individuals and only depicts a subpopulation (approximately 30%) of HLA-DR-bearing M phi from any single subject. Cytolytic removal of this subpopulation of HLA-DR-bearing cells markedly diminished antigen-induced T cell reactivity, a deficiency that can be reconstituted with autologous M phi but not with either their soluble products containing lymphocyte-activating factor or with intact HLA-DR-disparate M phi. Whereas M phi bearing both the 120,000-dalton determinant and HLA-DR serve as effective stimulators for autologous mixed lymphocyte reactions. M phi bearing only HLA-DR determinants do not. However, this latter population of M phi can stimulate proliferation among alloreactive T cells. These studies indicate that the Mac-120 monoclonal antibody detects a subpopulation of HLA-DR-bearing M phi that is required for the genetically restricted presentation of conventional antigen to reactive T cells. Within the M phi population, these Mac-120+ cells constitute the most effective stimulators for autologous mixed lymphocyte reactions.


Protection against infection with Giardia muris by milk containing antibody to Giardia.
Mice ingesting milk from immune mothers are protected against infection with Giardia muris. In order to be protected, the infant mice must be suckling immune milk at the time of challenge with the parasite and must continue to do so for at least three to five days thereafter. Suckling immune milk does not induce sustained immunity; infants become susceptible to infection after weaning begins at 14 days of age. Immune milk contains specific IgA and IgG antibody to Giardia, which may be the mediators of the demonstrated protection. The properties of this protection are similar to those described for protection against other enteric infections by milk.


Systematic review of guidelines to identify recommendations for upper limb robotic rehabilitation after stroke.
Upper limb motor impairment is one of the most frequent stroke consequences. Robot therapy may represent a valid option for upper limb stroke rehabilitation, but there are still gaps between research evidence and their use in clinical practice. The aim of this study was to determine the quality, scope, and consistency of guidelines clinical practice recommendations for upper limb robotic rehabilitation in stroke populations. We searched for guideline recommendations on stroke published between January 1st, 2010 and January 1st, 2020. Only the most recent guidelines for writing group were selected. Electronic databases (N.=4), guideline repertories and professional rehabilitation networks (N.=12) were searched. We systematically reviewed and assessed guidelines containing recommendation statements about upper limb robotic rehabilitation for adults with stroke (PROSPERO registration number: CRD42020173386). Four independent reviewers used the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument, and textual syntheses were used to appraise and compare recommendations. From 1324 papers that were screened, eight eligible guidelines were identified from six different regions/countries. Half of the included guidelines focused on stroke management, the other half on stroke rehabilitation. Rehabilitation assisted by robotic devices is generally recommended to improve upper limb motor function and strength. The exact characteristics of patients who could benefit from this treatment as well as the correct timing to use it are not known. This systematic review has identified many opportunities to modernize and otherwise improve stroke patients' upper limb robotic therapy. Rehabilitation assisted by robot or electromechanical devices for stroke needs to be improved in clinical practice guidelines in particular in terms of applicability.


Single Cell RNA Sequencing Reveals Emergent Notochord-Derived Cell Subpopulations in the Postnatal Nucleus Pulposus.
Intervertebral disc degeneration is a leading cause of chronic low back pain. Cell-based strategies that seek to treat disc degeneration by regenerating the central nucleus pulposus hold significant promise, but key challenges remain. One of these is the inability of therapeutic cells to effectively mimic the performance of native nucleus pulposus cells, which are unique amongst skeletal cell types in that they arise from the embryonic notochord. In this study we use single cell RNA sequencing to demonstrate emergent heterogeneity amongst notochord-derived nucleus pulposus cells in the postnatal mouse disc. Specifically, we established the existence of early and late stage nucleus pulposus cells, corresponding to notochordal progenitor and mature cells, respectively. Late stage cells exhibited significantly higher expression levels of extracellular matrix genes including aggrecan, and collagens II and VI, along with elevated TGF-β and PI3K-Akt signaling. Additionally, we identified Cd9 as a novel surface marker of late stage nucleus pulposus cells, and demonstrated that these cells were localized to the nucleus pulposus periphery, increased in numbers with increasing postnatal age, and co-localized with emerging glycosaminoglycan-rich matrix. Finally, we used a goat model to show the Cd9+ nucleus pulposus cell numbers decrease with moderate severity disc degeneration, suggesting that these cells are associated with maintenance of the healthy nucleus pulposus extracellular matrix. Improved understanding of the developmental mechanisms underlying regulation of ECM deposition in the postnatal NP may inform improved regenerative strategies for disc degeneration and associated low back pain.


A unique strain of community-acquired Clostridium difficile in severe complicated infection and death of a young adult.
Clostridium difficile is the major cause of nosocomial antibiotic-associated diarrhoea with the potential risk of progressing to severe clinical outcomes including death. It is not unusual for Clostridium difficile infection to progress to complications of toxic megacolon, bowel perforation and even Gram-negative sepsis following pathological changes in the intestinal mucosa. These complications are however less commonly seen in community-acquired Clostridium difficile infection than in hospital-acquired Clostridium difficile infection. To the best of our knowledge, this was the first case of community-acquired Clostridium difficile infection of its type seen in Jamaica. We report a case of a 22-year-old female university student who was admitted to the University Hospital of the West Indies, Jamaica with a presumptive diagnosis of pseudomembranous colitis PMC. She presented with a 5-day history of diarrhoea following clindamycin treatment for coverage of a tooth extraction due to a dental abscess. Her clinical condition deteriorated and progressed from diarrhoea to toxic megacolon, bowel perforation and Gram-negative sepsis. Clostridium difficile NAP12/ribotype 087 was isolated from her stool while blood cultures grew Klebsiella pneumoniae. Despite initial treatment intervention with empiric therapy of metronidazole and antibiotic clearance of Klebsiella pneumoniae from the blood, the patient died within 10 days of hospital admission. We believe that clindamycin used for coverage of a dental abscess was an independent risk factor that initiated the disruption of the bowel micro-flora, resulting in overgrowth of Clostridium difficile NAP12/ribotype 087. This uncommon strain, which is the same ribotype (087) as ATCC 43255, was apparently responsible for the increased severity of the infection and death following toxic megacolon, bowel perforation and pseudomembranous colitis involving the entire large bowel. K. pneumoniae sepsis, resolved by antibiotic therapy was secondary to Clostridium difficile infection. The case registers community-acquired Clostridium difficile infection as producing serious complications similar to hospital-acquired Clostridium difficile infection and should be treated with the requisite importance.


Modeling interdependent risks.
In an interdependent world the risks faced by any one agent depend not only on its choices but also on those of all others. Expectations about others' choices will influence investments in risk management and the outcome can be suboptimal for everyone. We model this as the Nash equilibrium of a game and give conditions for such a suboptimal equilibrium to be tipped to an optimal one. We also characterize the smallest coalition to tip an equilibrium, the minimum critical coalition, and show that this is also the cheapest critical coalition, so that there is no less expensive way to move the system from the suboptimal to the optimal equilibrium. We illustrate these results by reference to airline security and the control of infectious diseases via vaccination.


Correlation between IPSET-t risk at diagnosis and subsequent hemorrhage in patients with essential thrombocythemia; a single institution experience.
Essential thrombocythemia (ET) is a myeloproliferative neoplasm characterized by an increased risk of thrombotic and hemorrhagic events, that represent the leading causes of mortality and morbidity. Currently, while thrombotic risk is assessed through the IPSET-t and r-IPSET scores, there is no specific prognostic tool used to predict hemorrhagic risk in ET. The aim of the study was to define incidence and risk factors connected to hemorrhagic events by retrospectively analyzing 308 ET patients diagnosed between 1996 and 2022 at the Division of Hematology of Udine and treated according to the current international guidelines. According to molecular status, 193 patients (62.7%) were JAK2 mutated, 66 (21.4%) had a CALR mutation, 14 (4.5%) had a MPL mutation, 21 patients (6.8%) were "triple negative," and 14 patients (4.5%) were not evaluable. According to IPSET-t score, 49.7% patients were at high, 24.3% at intermediate, and 26.0% at low-risk, respectively. Twelve (3.9%) patients experienced bleeding at ET diagnosis, while 24 (7.8%) had at least one hemorrhagic event during follow-up at a median time of 103 months (range: 1-309). Forty hemorrhagic events were totally recorded and defined as minor in 22 cases, moderate in 11 cases, and severe in 7 cases. Cumulative incidence (CI) of hemorrhage at 10 and 20 years was 6.0% and 12.0%, respectively. A statistically significant correlation between hemorrhagic risk and IPSET-t score emerged: 10 years hemorrhage CI was 3.2% for low-risk, 2.9% for intermediate-risk, and 9.8% for high-risk patients, respectively (p=0.002). We found no correlation between hemorrhagic risk and gender or mutational status. Results of our study highlight the validity of IPSET-t score in predicting individual hemorrhagic risk among ET patients, suggesting a possible role of IPSET-t scoring system as a global evaluator for vascular events in ET patients.


Mechanical defenses in leaves eaten by Costa Rican howling monkeys (Alouatta palliata).
Primate species often eat foods of different physical properties. This may have implications for tooth structure and wear in those species. The purpose of this study was to examine the mechanical defenses of leaves eaten by Alouatta palliata from different social groups at Hacienda La Pacifica in Costa Rica. Leaves were sampled from the home-ranges of groups living in different microhabitats. Specimens were collected during the wet and dry seasons from the same tree, same plant part, and same degree of development as those eaten by the monkeys. The toughness of over 300 leaves was estimated using a scissors test on a Darvell mechanical tester. Toughness values were compared between social groups, seasons, and locations on the leaves using ANOVA. Representative samples of leaves were also sun-dried for subsequent scanning electron microscopy and energy dispersive x-ray (EDX) analyses in an attempt to locate silica on the leaves. Both forms of mechanical defense (toughness and silica) were found to be at work in the plants at La Pacifica. Fracture toughness varied significantly by location within single leaves, indicating that measures of fracture toughness must be standardized by location on food items. Monkeys made some food choices based on fracture toughness by avoiding the toughest parts of leaves and consuming the least tough portions. Intergroup and seasonal differences in the toughness of foods suggest that subtle differences in resource availability can have a significant impact on diet and feeding in Alouatta palliata. Intergroup differences in the incidence of silica on leaves raise the possibility of matching differences in the rates and patterns of tooth wear.


The Good Food Junction: a Community-Based Food Store Intervention to Address Nutritional Health Inequities.
This is a 2-year study to assess the early impacts of a new grocery store intervention in a former food desert. The purpose of the study is to understand the early health effects of the introduction of a large-scale food and nutrition-focused community-based population health intervention, the Good Food Junction (GFJ) Cooperative Store, in a geographically bounded group of socially disadvantaged neighborhoods (the "core neighborhoods") in a midsized Canadian city. The GFJ grocery store was tasked with improving the access of residents to healthy, affordable food. The 5 research questions are: (1) What is the awareness and perception of the GFJ store among residents of the core neighborhoods? (2) Are there differences in awareness and perception among those who do and do not shop at the GFJ? (3) Will healthy food purchasing at the GFJ by residents of the core neighborhoods change over time, and what purchases are these individuals making at this store? (4) What early impact(s) will the GFJ have on key health-related outcomes (such as household food security status, vegetable and fruit intake, key aspects of self-reported mental health, self-reported health)? and (5) Are the effects of the intervention seen for specific vulnerable population groups, such as Aboriginal people, seniors (65 years old or older) and new immigrants (settled in Saskatoon for less than 5 years)? The research project examined initial impacts of the GFJ on the health of the residents in surrounding neighborhoods through a door-to-door cross-sectional survey of food access and household demographics; an examination of GFJ sales data by location of shoppers' residences; and a 1-year, 3-time-point longitudinal study of self-reported health of GFJ shoppers. Analyses are on-going, but preliminary results show that shoppers are using the store for its intended purpose, which is to improve access to healthy food in a former food desert. To our knowledge this is the first large-scale study of a full-service grocery store intervention in a former food desert in Canada that has used multiple data sources, as well as longitudinal analyses, to examine its effects. Its findings will contribute significantly to the knowledge base on food environment interventions.


Absorption and Metabolic Behavior of Hesperidin (Rutinosylated Hesperetin) after Single Oral Administration to Sprague-Dawley Rats.
We investigated the absorption and metabolic behavior of hesperidin (hesperetin-7-O-rutinoside) in the blood system of Sprague-Dawley rats by liquid chromatography- and matrix-assisted laser desorption ionization mass spectrometries (LC-MS and MALDI-MS). After a single oral administration of hesperidin (10 mg/kg), which was expected to be absorbed in its degraded hesperetin form, we detected intact hesperidin in the portal vein blood (tmax, 2 h) for the first time. We successfully detected glucuronized hesperidin in the circulating bloodstream, while intact hesperidin had disappeared. Further MS analyses revealed that homoeriodictyol and eriodictyol conjugates were detected in both portal and circulating blood systems. This indicated that hesperidin and/or hesperetin are susceptible to methylation and demethylation during the intestinal membrane transport process. Sulfated and glucuronized metabolites were also detected in both blood systems. In conclusion, hesperidin can enter into the circulating bloodstream in its conjugated forms, together with the conjugated forms of hesperetin, homoeriodictyol, and/or eriodictyol.


Electrochemical impedance spectroscopy in label-free biosensor applications: multivariate data analysis for an objective interpretation.
Electrochemical impedance spectroscopy plays an important role in biosensor science thanks to the possibility of finding specific information from processes with different kinetics at a chosen electrode potential in one experiment. In this paper we briefly discuss label-free impedimetric biosensors described in the literature. A novel method for neutral interpretation of impedance data is presented that includes complex number chemometrics. Three examples are given based on impedance measurements on synthetic biomembranes, in this case a lipid monolayer deposited on a mercury electrode. The interaction of various compounds with the monomolecular lipid layer is illustrated with the following: (1) different concentrations of magainin (Geladi et al. in Proc. Int. Fed. Med. Biomed. Eng. 9:219-220, 2005); (2) different derivatives of gramicidin A (Lindholm-Sethson et al. in Langmuir 24:5029-5032, 2007), and (3) an antimicrobial peptide (Ringstad et al. in Langmuir 24:208-216, 2008).


Consistent Condom Use with Paying and Nonpaying Partners among Female Sex Workers in Iran: Findings of a National Biobehavioral Survey.
Little is known about the dynamics of condom use among female sex workers (FSWs) in Iran. We investigated the correlates of consistent condom use (CCU) among FSWs, using data from a national biobehavioral surveillance survey in 2010. A total of 872 FSWs were recruited using a facility-based sampling strategy from 21 sites in 13 cities in Iran. Data were collected through face-to-face interviews using a standardized questionnaire. Overall, 33.6% and 17.3% of FSWs reported CCU with paying and nonpaying sex partners, respectively. Consistent condom use with paying partners was significantly associated with temporary marriage, accessing family planning services and history of working in brothels. Conversely, temporary marriage or married status, condom rupture/slippage, and HIV seropositivity remained independently significantly associated with CCU with nonpaying sex partners. Our findings indicated the urgent need for scaling up condom promotion interventions catered toward FSWs and their sex partners to practice safe sex consistently.


Seasonal abundance and diversity of culturable heterotrophic bacteria in relation to environmental factors in the Gulf of Antalya, Eastern Mediterranean, Turkey.
The abundance of culturable heterotropic bacteria studied on and according to depth levels and seasons in the Gulf of Antalya. Environmental factors were compared regarding culturable heterotrophic bacteria abundance and diversities of bacteria. During the study period (between August 2009 and April 2010, seasonally in the Gulf of Antalya, at six stations and six depth levels (0-20 cm, 10, 25, 50, 100, 200 m). The bacterial isolates were identified in the automated micro identification system VITEK 2 Compact 30 (Biomereux, France). The mean abundance was higher in Sts. D, E and F than Sts. A, B and C, located in the eastern part of the gulf. The mean abundance decreased as the depth level increased. The mean abundance of CHB ranged between 8.15 × 10(6) and 2.54 × 10(8) CFU ml(-1) throughout the year. Abundance of CHB differed according to the variations of biotic and abiotic factors. A total of 27 taxa of bacteria including six bacterial classes were reported in this study as the first records for the Gulf of Antalya. Six bacterial classes: Gamma Proteobacteria (46.81 %), Bacilli (27.66 %), Beta Proteobacteria (12.77 %), Alfa Proteobacteria (6.38 %), Actinobacteria (4.26 %) and Flavobacteria (2.13 %) were determined. The study resulted in increased knowledge on the composition and biochemical response of bacteria isolated from eutrophic and oligotrophic areas. 23 bacteria species belonging to 16 families were reported.


Semiquantitative acid-base analysis in dogs with typical hypoadrenocorticism.
To describe the semiquantitative acid-base status of dogs with untreated naturally occurring typical hypoadrenocorticism and to compare this to the status determined by traditional acid-base analysis. Retrospective study. University teaching hospital. Thirty-three dogs with newly diagnosed typical hypoadrenocorticism between 2000 and 2017. None. Dogs were included if they had newly diagnosed hypoadrenocorticism, post-ACTH stimulation serum cortisol concentration <2 μg/dL, and blood collected within 6 hours of presentation for acid-base, electrolyte, and serum biochemical assays. Dogs were excluded if the Na+ :K+ ratio was ≥28 or the dog had received a mineralocorticoid-containing corticosteroid medication within the preceding month. Traditional acid-base analysis identified normal acid-base status in 1 dog, simple respiratory acid-base abnormalities in 2 of 33 dogs, and simple metabolic acidosis in 14 of 33 dogs. A mixed disorder was most common, noted in 16 of 33 dogs. The semiquantitative approach identified metabolic abnormalities in all cases. All dogs had ≥1 acidifying process, and 29 of 33 had both acidifying and alkalinizing processes. Acidosis attributable to excess free water was present in all dogs, and an acidifying phosphate effect was present in 27 of 33. Hyperlactatemia contributed to the acidosis in 8 of 33 dogs, with a median (range) lactate concentration of 1.5 mmol/L (13.5 mg/dL) (0.3-4.2 mmol/L [2.7-37.8 mg/dL]). Dogs with untreated Addison's disease have complex acid-base derangements. The semiquantitative approach to acid-base analysis provides greater insight into the underlying mechanisms of metabolic acid-base abnormalities in these dogs, particularly because lactic acidosis appears to be a minor influence in most cases.


Cry1-/- circadian rhythmicity depends on SCN intercellular coupling.
In mammals, the suprachiasmatic nucleus (SCN) is the central pacemaker organizing circadian rhythms of behavior and physiology. At the cellular level, the mammalian clock consists of autoregulatory feedback loops involving a set of "clock genes," including the Cryptochrome (Cry) genes, Cry1 and Cry2. Experimental evidence suggests that Cry1 and Cry2 play distinct roles in circadian clock function. In mice, Cry1 is required for sustained circadian rhythms in dissociated SCN neurons or fibroblasts but not in organotypic SCN slices or at the behavioral level, whereas Cry2 is not required at any of these levels. It has been argued that coupling among SCN cellular oscillators compensates for clock gene defects to preserve oscillatory function. Here we test this hypothesis in Cry1(-/-) mice by first disrupting intercellular coupling in vivo using constant light (resulting in behavioral arrhythmicity) and then examining circadian clock gene expression in SCN slices at the single cell level. In this manner, we were able to test the role of intercellular coupling without drugs and while preserving tissue organization, avoiding the confounding influences of more invasive manipulations. Cry1(-/-) mice (as well as control Cry2(-/-) mice) bearing the PER2::LUC knock-in reporter were transferred from a standard light:dark cycle to constant bright light (~650 lux) to induce arrhythmic locomotor patterns. In SCN slices from these animals, we used bioluminescence imaging to monitor PER2::LUC expression in single cells. We show that SCN slices from rhythmic Cry1(-/-) and Cry2(-/-) mice had similarly high percentages of functional single-cell oscillators. In contrast, SCN slices from arrhythmic Cry1(-/-) mice had significantly fewer rhythmic cells than SCN slices from arrhythmic Cry2(-/-) mice. Thus, constant light in vivo disrupted intercellular SCN coupling to reveal a cell-autonomous circadian defect in Cry1(-/-) cells that is normally compensated by intercellular coupling in vivo.


Effects of Simulated High Altitude on Blood Glucose Levels During Exercise in Individuals With Type 1 Diabetes.
Current exercise guidelines for individuals with type 1 diabetes (T1D) do not consider the impact that high altitude may have on blood glucose levels (BGL) during exercise. To investigate the effect of acute hypoxia (simulated high altitude) on BGL and carbohydrate oxidation rates during moderate intensity exercise in individuals with T1D. Using a counterbalanced, repeated measures study design, 7 individuals with T1D completed 2 exercise sessions; normoxia and hypoxia (~4200 m simulated altitude). Participants cycled for 60 min on an ergometer at 45% of their sea-level V̇O2peak, and then recovered for 60 min. Before, during, and after exercise, blood samples were taken to measure glucose, lactate, and insulin levels. Respiratory gases were collected to measure carbohydrate oxidation rates. Early during exercise (<30 min), there was no fall in BGL in either condition. After 1 h of exercise and during recovery, BGL were significantly lower under the hypoxic condition compared to both pre-exercise levels (P = 0.008) and the normoxic condition (P = 0.027). Exercise in both conditions resulted in a significant rise in carbohydrate oxidation rates, which returned to baseline levels postexercise. Before, during, and after exercise, carbohydrate oxidation rates were higher under the hypoxic compared with the normoxic condition (P < 0.001). The greater decline in BGL during and after exercise performed under acute hypoxia suggests that exercise during acute exposure to high altitude may increase the risk of hypoglycemia in individuals with T1D. Future guidelines may have to consider the impact altitude has on exercise-mediated hypoglycemia.


Protein phosphatase with EF-hand domains 2 (PPEF2) is a potent negative regulator of apoptosis signal regulating kinase-1 (ASK1).
The function of protein phosphatases with EF-hand domains (PPEF) in mammals is not known. Large-scale expression profiling experiments suggest that PPEF expression may correlate with stress protective responses, cell survival, growth, proliferation, or neoplastic transformation. Apoptosis signal regulating kinase-1 (ASK1) is a MAP kinase kinase kinase implicated in cancer, cardiovascular and neurodegenerative diseases. ASK1 is activated by oxidative stress and induces pro-apoptotic or inflammatory signalling, largely via sustained activation of MAP kinases p38 and/or JNK. We identify human PPEF2 as a novel interacting partner and a negative regulator of ASK1. In COS-7 or HEK 293A cells treated with H(2)O(2), expression of PPEF2 abrogated sustained activation of p38 and one of the JNK p46 isoforms, and prevented ASK1-dependent caspase-3 cleavage and activation. PPEF2 efficiently suppressed H(2)O(2)-induced activation of ASK1. Overexpessed as well as endogenous ASK1 co-immunoprecipitated with PPEF2. PPEF2 was considerably more potent both as a suppressor of ASK1 activation and as its interacting partner as compared to protein phosphatase 5 (PP5), a well-known negative regulator of ASK1. PPEF2 was found to form complexes with endogenous Hsp70 and to a lesser extent Hsp90, which are also known interacting partners of PP5. These data identify, for the first time, a possible downstream signalling partner of a mammalian PPEF phosphatase, and suggest that, despite structural divergence, PPEF and PP5 phosphatases may share common interacting partners and functions.


Formate protects stationary-phase Escherichia coli and Salmonella cells from killing by a cationic antimicrobial peptide.
For a sustained infection, enteric bacterial pathogens must evade, resist or tolerate a variety of antimicrobial host defence peptides and proteins. We report here that specific organic acids protect stationary-phase Escherichia coli and Salmonella cells from killing by a potent antimicrobial peptide derived from the human bactericidal/permeability-increasing protein (BPI). BPI-derived peptide P2 rapidly halted oxygen consumption by stationary-phase cells preincubated with glucose, pyruvate or malate and caused a 109-fold drop in cell viability within 90 min of addition. In marked contrast, O2 consumption and viability were not significantly affected in stationary-phase cells preincubated with formate or succinate. Experiments with fdhH, fdoG, fdnG, selC and sdhO mutants indicate that protection by formate and succinate requires their oxidation by the Fdh-N formate dehydrogenase and succinate dehydrogenase respectively. Protection was also dependent on the BipA GTPase but did not require the RpoS sigma factor. We conclude that the primary lesion caused by this cationic peptide is not gross permeabilization of the bacterial cytoplasmic membrane but may involve specific disruption of the respiratory chain. Because P2 shares sequence similarity with a range of other antimicrobial peptides, its cytotoxic mechanism has broader significance. Additionally, protective quantities of formate are secreted by E. coli and Salmonella during growth suggesting that such compounds are important determinants of bacterial survival in the host.


Modelling pathways of alpha-chymotrypsin activation and deactivation.
The conformational change of alpha-chymotrypsin from an inactive, chymotrypsinogen like structure at high pH to an active conformation around pH 8.5 is used here as a model system to generate possible pathways for the transition by use of two different theoretical methods. One method, the 'targeted molecular dynamics' algorithm (TMD) adds a constraint in the direction of the target to a molecular dynamics force field and gives two different paths, one for every direction of the reaction (Schlitter,J., Engels,M., Krüger,P.J., Mol. Graphics (1994) 12, 84-89). The second method, the 'self penalty walk' algorithm (SPW), refines an initially guessed path by minimizing the sum of the energies of its structures (Elber,R. and Karplus,M., Chem. Phys. Lett. (1987) 139, 375-380). Thus, starting from a linear path as a first approximation, it produces a reaction coordinate of the transition. The structures of the TMD and SPW paths are similar only in the beginning while the middle part of the SPW path links the two TMD branches. The activation of alpha-chymotrypsin in the TMD path starts with a movement of loop VII (residues 215-225), pulling on loop VI (residues 186-194). Then the side chain of Met192 turns to the surface and Ile16 approaches Asp194 to form a salt bridge. In the TMD deactivation path, loop VII also moves and pushes loop VI to the protein core. The Met192 side chain adopts three intermediate conformations, till the salt bridge Ile16-Asp194 is broken and loop VI rearranges to its final conformation. In the SPW pathway both the formation of the salt bridge and the movement of Met192 happen simultaneously between two consecutive steps.


Influenza-like viral illnesses and flare-ups of fibrodysplasia ossificans progressiva.
Flare-ups of fibrodysplasia ossificans progressiva are most commonly triggered by soft tissue trauma. After observing severe flare-ups of fibrodysplasia ossificans progressiva in two half-sisters with culture-confirmed influenza B infections, we hypothesized that influenza-like viral illnesses also can trigger fibrodysplasia ossificans progressiva flare-ups. To address this hypothesis, we designed a questionnaire to assess whether patients with fibrodysplasia ossificans progressiva experienced influenza symptoms during the 2000 to 2001 influenza season, and whether these symptoms were correlated with flare-ups of the condition. The questionnaire was sent to patients with fibrodysplasia ossificans progressiva worldwide. Of the 264 patients surveyed, 123 (47%) responded. The survey revealed that the risk of a disease flare-up of fibrodysplasia ossificans progressiva during an influenza-like viral illness was increased at least threefold and possibly much more. The survey data strongly supported the hypothesis that influenza-like viral illnesses are associated with disease flare-ups in patients who have fibrodysplasia ossificans progressiva. Influenza-like viral illnesses may be a source of previously unrecognized muscle injury leading to heterotopic ossification and permanent loss of mobility in these patients. These findings have important implications for understanding and preventing environmental triggers of disease activity in this population of patients genetically susceptible to progressive heterotopic ossification.


Motivators and barriers to engagement with evidence-based practice among medical and dental trainees from the UK and Republic of Ireland: a national survey.
To explore the extent to which doctors and dentists in training within the UK and Republic of Ireland (RoI) engage in and with evidence-based practice (EBP), and to identify motivators and barriers to them doing so. An observational, prepiloted web-based survey developed by a trainee-led focus group. The survey instrument was disseminated to doctors and dentists in training within the UK and RoI during June 2017 via social media and through deaneries, Royal Colleges and specialty-specific mailing lists. Data from 243 trainees were analysed; 188 doctors from 31 specialties and 55 dentists from 9 specialties. Responses were received from trainees at all stages of postgraduate training though the overall response rate was low. The motivators and barriers to, and the extent of, trainee engagement with EBP. Cronbach's α was 0.83. Most trainees (87.6% (n=148) of doctors and 75.1% (n=39) of dentists) consulted the evidence base at least monthly, while 23.1% [n=39 doctors, 12 dentists] of both specialties did so daily. The two most commonly cited barriers to engagement with EBP for both doctors and dentists, respectively, were insufficient time (57.6% (n=95) and 45.1% (n=23)) and a tendency to follow departmental practice (40.6% (n=67) and 45.1% (n=23)). Key motivators for EBP included curiosity, following the example set by senior colleagues and a desire to avoid harm. Most trainees reported high levels of confidence interpreting evidence yet for 26.8% (n=45) of doctors and 36.5% (n=19) of dentists, medical hierarchy would impede them querying a colleague's management plan based on their own reading of the evidence. Time, accepted departmental practice and the behaviour of senior clinicians all highly impact on trainee engagement with EBP. Given the low response rate, the extent to which these data represent the overall population is unclear.


Cell cycle changes in the adenylate cyclase of C6 glioma cells.
The adenylate cyclase of C6 glioma cell cultures was characterized for sensitivity to the beta-adrenergic agonist isoproterenol, as well as fluoride, and GTP as a function of the cell cycle. The mitotic phase of the cell cycle was emphasized because both the basal cellular cyclic AMP level and the intact C6 cell's capacity to accumulate cyclic AMP in response to isoproterenol decreased during mitosis. Basal and stimulated adenylate cyclase activities in mitotic cells were decreased relative to the enzyme activities in the G1, S, and G2 phases of the cell cycle. Analysis of the beta-adrenergic receptor using the radioligand(-)[3H]dihydroalprenolol showed that neither ligand affinity nor receptor density changed during the cell cycle, indicating that the reduced adenylate cyclase activity of the mitotic C6 cell was not caused by alterations in this hormone receptor. The reduction in the mitotic cell's basal adenylate cyclase activity was more prominent than the decrease in isoproterenol-, fluoride, or GTP-stimulated activities suggesting that the effectiveness of these enzymes activators (i.e., the efficiency of the coupling mechanism) was not attenuated during mitosis. These studies indicate that the intrinsic catalytic capacity (not the beta-adrenergic receptor or the coupling mechanism) of the C6 adenylate cyclase complex is reduced during mitosis and contributes to the mitotic cell's inability to accumulate and maintain the cyclic AMP concentration at the interphase level.


Anatomy of culturally sensitive interventions promoting nutrition and exercise in hispanics: a critical examination of existing literature.
Compared with non-Hispanic Whites, Hispanics experience a disproportionate burden of chronic diseases. Understanding the factors influencing the success of health programs in Hispanics requires a clearer examination of the principles and components of tailored interventions. This research comprises a comprehensive literature review of randomized controlled trials testing nutrition and exercise interventions tailored for Hispanics and an examination of how these interventions were constructed. The review of 18 interventions meeting study criteria suggests that most tailored programs promoting nutrition and exercise in Hispanics are theory driven and are informed by formative research. Also, the findings indicate that salient culturally sensitive intervention components are (a) bilingual and bicultural facilitators and materials, (b) family-based activities, (c) literacy-appropriate materials, and (d) social support. A clear understanding of Hispanic cultural values is also required. Further empirical examination is warranted to determine the factors mediating or predicting the efficacy of culturally sensitive health programs for Hispanics.


Recent Developments in Organophosphorus Flame Retardants Containing P-C Bond and Their Applications.
Organophosphorus compounds containing P-C bonds are increasingly developed as flame retardant additives due to their excellent thermal and hydrolytic stability and ease of synthesis. The latest development (since 2010) in organophosphorus flame retardants containing P-C bonds summarized in this review. In this review, we have broadly classified such phosphorus compounds based on the carbon unit linked to the phosphorus atom i.e., could be a part of either an aliphatic or an aromatic unit. We have only considered those published literature where a P-C bond was created as a part of synthetic strategy to make either an intermediate or a final organophosphorus compound with an aim to use it as a flame retardant. General synthetic strategies to create P-C bonds are briefly discussed. Most popular synthetic strategies used for developing P-C containing phosphorus based flame retardants include Michael addition, Michaelis-Arbuzov, Friedels-Crafts and Grignard reactions. In general, most flame retardant derivatives discussed in this review have been prepared via a one- to two-step synthetic strategy with relatively high yields greater than 80%. Specific examples of P-C containing flame retardants synthesized via suitable synthetic strategy and their applications on various polymer systems are described in detail. Aliphatic phosphorus compounds being liquids or low melting solids are generally applied in polymers via coatings (cellulose) or are incorporated in the bulk of the polymers (epoxy, polyurethanes) during their polymerization as reactive or non-reactive additives. Substituents on the P atoms and the chemistry of the polymer matrix greatly influence the flame retardant behavior of these compounds (condensed phase vs. the gas phase). Recently, aromatic DOPO based phosphinate flame retardants have been developed with relatively higher thermal stabilities (>250 °C). Such compounds have potential as flame retardants for high temperature processable polymers such as polyesters and polyamides. A vast variety of P-C bond containing efficient flame retardants are being developed; however, further work in terms of their economical synthetic methods, detailed impact on mechanical properties and processability, long term durability and their toxicity and environmental impact is much needed for their potential commercial exploitations.


In situ formation of Au-Pd bimetallic active sites promoting the physically mixed monometallic catalysts in the liquid-phase oxidation of alcohols.
The catalytic oxidation of alcohols with molecular oxygen on supported nanometallic catalysts represents one of the green methods in a crucial process for the synthesis of fine chemicals. We have designed an experiment using physically mixed Au/AC and Pd/AC (AC=activated carbon) as the catalyst in the liquid-phase oxidation of benzyl alcohol by aerobic oxygen. The evolution of the physically mixed catalyst structures at different stages in the catalytic reaction was investigated by aberration-corrected high-resolution transmission electron microscopy and spatially resolved element mapping techniques at the nanometre scale, and they were also compared with the structure of the bimetallic alloy. For the first time we show the formation of surface Au-Pd bimetallic sites by reprecipitation of Pd onto Au nanoparticles. Negligible Au leaching was observed. The in situ structural evolution can be directly correlated to the great enhancement of the catalyst activity. Moreover, we distinguish the different behaviours of Au and Pd, thus suggesting an oxygen differentiating mechanism for Au and Pd sites. The findings are of great importance to both the understanding of the structure-activity correlation and the design of highly active catalysts in green chemistry.


Wavelength effect on visual latency.
Chromatic stimuli were matched in luminance to a homogeneous white background field. The relative visual latency, as measured by subjective simultaneity, of 621-nanometer (red) light was 20 to 25 milliseconds less than that for 549-nanometer (green) light. When the chromatic stimuli were different in luminance fronm the background field, no differences in visual latency related to the wavelength of light were observed. The procedure of matching the luminance of test fields to that of a background field appears to be crucial for observing a visual latency difference related to wavelength.


Analysis of both NM23-h1 and NM23-H2 expression identifies "at-risk" patients with colorectal cancer.
Metastasis is the manifestation most directly affecting survival for patients with colorectal carcinoma. Identification of high-risk markers for metastases would allow focused selection of patients for adjuvant chemotherapy. Reports of the relationship between the putative metastasis suppressor NM23 and metastasis and/or survival in colorectal cancer patients are conflicting. The purpose of this study was to separately assess expression of NM23-H1 and NM23-H2 in primary colon cancers and determine whether expression was associated with regional nodal disease and/or liver metastases. Four patient cohorts were selected on the basis of histopathological staging at primary surgery (lymph node status/liver metastasis): -/- (n = 46), +/- (n = 47), -/+ (n = 43), and +/+ (n = 46). Primary tumors were evaluated by semiquantitative immunohistochemical analysis of NM23-H1 and NM23-H2. NM23-H2 expression was not related to survival; however, there was a modest survival advantage with low expression of NM23-H1 (P = 0.027). NM23-H1 expression in the +/+ group was increased compared with the other groups (P < 0.001). The -/+ group had the lowest expression of NM23-H2 (P < 0.001). This analysis distinguishes two high-risk groups of colorectal cancer patients. Prior discrepancies regarding the usefulness of NM23 staining may be explained by the need to evaluate both serotypes in addition to standard histopathological analysis to identify specific "at-risk" groups.


Testing feasibility of an accurate microscopic assessment of macrovesicular steatosis in liver allograft biopsies by smartphone add-on lenses.
Light microscopy is an essential tool in histological examination of tissue samples. However, the required equipment for a correct and rapid diagnosis is sometimes unavailable. Smartphones and mobile phone networks are widespread, and could be used for diagnostic imaging and telemedicine. Macrovesicular steatosis (MS) is a major risk factor for liver graft failure, and is only assessable by microscopic examination of a frozen tissue section. The aim of this study was to compare the microscopic assessment of MS in liver allograft biopsies by a smartphone with eyepiece adaptor (BLIPS device) to standard light microscopy. Forty liver graft biopsies were evaluated in transmitted light, using an Iphone 5s and 4 different mini-objective, add-on lenses. A significant correlation was reported between the two different approaches for graft MS assessment (Spearman's correlation coefficient: rs = 0.946; p < .001). Smartphone with eyepiece adaptor had similar discriminatory power to identify MS in liver grafts than standard light microscopy. Based on these findings, a smartphone integrated with a low-cost eyepiece adaptor can achieve adequate accuracy in the assessment of MS in liver graft, and could be used as an alternative to standard light microscope when unavailable.


[Intercultural nursing: analysis of changes in the perception of relational problems with foreign patients].
Today's society is highly impacted by immigration, as well as healthcare system. It is becoming increasingly common and frequent to establish relationships with patients with different cultural backgrounds. The aim of this study is analyzing Italian nurses' perception of the relational dynamics with foreign patients, to determine its evolution, and to identify the variables which can affect the quality of care. The study is both qualitative and quantitative with descriptive aim, using a questionnaire that assesses the theoretical-practical level of preparation, both perceptive and effective, of nurses when assisting foreign patients. To evaluate the emotional and experiential impact of the relationship with foreign patients, the difficulties encountered while establishing such relationship, and the resolution strategies - both effective and potential. The sample, composed of 101 Italian nurses employed at SanRaffaele Hospital in 6 specific Operational Units, resulted in a total of 91 returned questionnaires during the period May-June 2011. The data was analyzed through statistical instruments and compared to the results of a similar study done in 2004. The experience of intercultural nursing is seen by the sample as interesting and rewarding. The vast majority of nurses have positive responses. The more frequent issues are those connected with communication with foreign patients, and those connected with the increase workload due the presence of foreign patients. Nurses responded to difficulties more with human skills than with specific abilities, and tend to delegate the problem to the Cultural Mediation service. This new issue has a very high impact on nurses. The emerged difficulties have not decreased over time, this due to the lack of a proper policy within health care facilities in recent years, with the exception of a little improvement on the academic education. However the current academic education does not provide solutions useful in the everyday routing. This study, despite the small sample and a rather narrow degree of analysis, likes to draw attention on the topic both of nurses and on health care facilities managerial team in order to develop a effective startegie to deal with the emerged issues.


Validity and reliability of the Neonatal Discharge Assessment Tool.
To investigate the reliability and validity of the Neonatal Discharge Assessment Tool (N-DAT) designed to assess risk factors related to infants' and parents' readiness for discharge to home. The sample was composed of 238 high-risk preterm infants, born at gestational age of 24 to 37 weeks, and their parents. High scores on the N-DAT indicated higher risk for discharge of preterm infants and their parents. Psychometric analyses of the N-DAT included content validity, internal consistency reliability, and construct validity. Content validity of the N-DAT items was supported by experts (content validity index = .98). Internal consistency reliability was supported by a Cronbach's alpha for the total instrument of .94. N-DAT total and subscale score correlations ranged from .42 to .89. Known-groups analysis indicated that infants born at <31 weeks' gestation and infants who were rehospitalized during 8 weeks after discharge had significantly higher N-DAT total and subscale scores than infants born at ≥31 weeks or not rehospitalized. Also, mothers who reported experiencing problems with infant care at home had significantly higher N-DAT Competencies subscale scores than mothers who did not report problems. The N-DAT is a reliable and valid instrument to evaluate the risks related to discharge of preterm infants so that nurses can provide parents with the necessary knowledge, skills, and resources they need prior to discharge.


Zero-energy resonances of hydrogen diatom isotopologs: tuning quasiresonant transitions in vibration space.
Highly efficient and specific energy transfer mechanisms that involve rotation-rotation, vibration-vibration, and vibration-rotation exchange in diatomic molecules are examined theoretically in ultracold H(2), D(2), and HD self-collisions as a function of initial vibrational level v. The three quasiresonant mechanisms are found to operate for all vibrational levels and yield complex scattering lengths which vary smoothly with v. Exceptions to this trend occur at select high values of v where the scattering lengths are modulated by orders of magnitude corresponding to the location of an s-wave zero-energy resonance in "vibration space." The quasiresonant mechanisms, which are not very sensitive to the details of the interaction potential, generally control the final distribution of molecular states for any given initial distribution. The zero-energy resonances are more sensitive to the potential and may be used to vibrationally "tune" the interaction strength, similar to methods which vary applied external fields.


Energy dispersive X-ray microanalysis, fluoride release, and antimicrobial properties of glass ionomer cements indicated for atraumatic restorative treatment.
The aim of this study was to compare constituents of glass powder, fluoride release, and antimicrobial properties of new atraumatic restorative treatment material with zirconia fillers and conventional glass ionomer cement (GIC) type IX. Thisin vitro study comparing Zirconomer and Fuji IX was executed in three parts: (1) energy dispersive X-ray microanalysis of glass powders (2) analysis of fluoride release at 1(st), 3(rd), 7(th), 15(th), and 30(th) day, and (3) antimicrobial activity against Streptococcus mutans, Lactobacillus casei, and Candida albicans at 48 hours. Data was analyzed using unpaired t-test and two way analysis of variance followed by least significant difference post hoc test. A P value of < 0.05 was considered statistically significant. Energy dispersive X-ray microanalysis revealed that, in both Zirconomer and Fuji IX glass powders, mean atomic percentage of oxygen was more than 50%. According to the weight percentage, zirconium in Zirconomer and silica in Fuji IX were the second main elements. Calcium, zinc, and zirconium were observed only in Zirconomer. At all the time intervals, statistically significant higher amount of fluoride release was observed with Zirconomer than Fuji IX. At 48 hours, mean ± standard deviation (SD) of zone of inhibition against Streptococcus mutans was 11.14 ± 0.77 mm and 8.51 ± 0.43 mm for Zirconomer and Fuji IX, respectively. Against Lactobacillus casei, it was 14.06 ± 0.71 mm for Zirconomer and 11.70 ± 0.39 mm for Fuji IX. No antifungal activity was observed against Candida albicans by Zirconomer and Fuji IX. Zirconomer had higher antibacterial activity against Streptococcus mutans and Lactobacillus casei, which may be attributed to its composition and higher fluoride release. However, it failed to show antifungal effect againstCandida albicans.


Hospitalization for physical illness and risk of subsequent suicide: a population study.
To examine suicide risk in relation to physical illness across a broad range of illnesses, including hospitalization history, specific organ or system illness and comorbidity. A nested case-control study. Data were retrieved from five Danish national registers. On the basis of the entire population of Denmark, this study included 27 262 suicide cases, and 468 007 live controls matched for sex and date of birth. Risk of suicide was assessed using conditional logistic regression. In the study population, 63.5% of suicide cases and 44.5% of comparison controls had a history of hospitalization for physical illness. A physical illness significantly increased the risk of subsequent suicide (incidence rate ratios 2.13, 95% CI 2.07-2.18) with a substantially greater effect in women than in men (P < 0.01). The elevated risk increased progressively with frequency and recency of hospitalization and was significant for diseases occurring in all organs or systems of the body. Comorbidity involving several organs or systems increased the risk substantially. The associated estimates were to some extent reduced but remained highly significant after adjustment for psychiatric history and socio-economic status. Taking into account both prevalence and adjusted effect size, physical illness accounted for 24.4%, 21.0% and 32.3% of population attributable risk for suicide in total, male and female populations, respectively. Physical illness constitutes a significant risk factor for suicide independent of psychiatric and socio-economic factors. Clinicians treating physically ill patients should be aware of the risk, especially amongst those with multiple or recent hospitalizations, or multiple comorbidities.


Heterologous production of ribostamycin derivatives in engineered Escherichia coli.
Aminoglycosides are a class of important antibiotic compounds used for various therapeutic indications. In recent times, their efficacy has been curtailed due to the rapid development of bacterial resistance. There is a need to develop novel derivatives with an improved spectrum of activity and higher sensitivity against pathogenic bacteria. Although efforts have been focused on the development of newer therapeutic agents by chemical synthesis, to our knowledge, there has been no attempt to harness the potential of microorganisms for this purpose. Escherichia coli affords a widely studied cellular system that could be utilized not only for understanding but also for attempting to engineer the biosynthetic pathway of secondary metabolites. The primary metabolic pathway of E. coli can be engineered to divert the precursor pool required for the biosynthesis of secondary metabolites. Utilizing this approach previously, we engineered E. coli host and generated E. coli M1. Here, we produced a ribostamycin derivative in the engineered host by heterologous expression of the recombinants constructed from the genes encoding the biosynthetic pathway in aminoglycoside-producing strains. The products obtained from the transformants were isolated, analyzed and verified to be ribostamycin derivatives. The study further demonstrated the importance of E. coli as surrogate antibiotic producer and also offered future possibility for the production of other aminoglycoside derivatives through genetic engineering and expression in a heterologous background.


Indoor air quality (IAQ) assessment in a multistorey shopping mall by high-spatial-resolution monitoring of volatile organic compounds (VOC).
In order to assess indoor air quality (IAQ), two 1-week monitoring campaigns of volatile organic compounds (VOC) were performed in different areas of a multistorey shopping mall. High-spatial-resolution monitoring was conducted at 32 indoor sites located in two storehouses and in different departments of a supermarket. At the same time, VOC concentrations were monitored in the mall and parking lot area as well as outdoors. VOC were sampled at 48-h periods using diffusive samplers suitable for thermal desorption. The samples were then analyzed with gas chromatography-mass spectrometry (GC-MS). The data analysis and chromatic maps indicated that the two storehouses had the highest VOC concentrations consisting principally of terpenes. These higher TVOC concentrations could be a result of the low efficiency of the air exchange and intake systems, as well as the large quantity of articles stored in these small spaces. Instead, inside the supermarket, the food department was the most critical area for VOC concentrations. To identify potential emission sources in this department, a continuous VOC analyzer was used. The findings indicated that the highest total VOC concentrations were present during cleaning activities and that these activities were carried out frequently in the food department. The study highlights the importance of conducting both high-spatial-resolution monitoring and high-temporal-resolution monitoring. The former was able to identify critical issues in environments with a complex emission scenario while the latter was useful in interpreting the dynamics of each emission source.


Standardized in vitro analysis of the degradability of hyaluronic acid fillers by hyaluronidase.
Hyaluronidase is a hyaluronic acid (HA) metabolizing enzyme, which is approved as an adjuvant for infiltration anesthesia. The "off-label" use of hyaluronidase is regarded as gold standard for the management of HA-filler-associated complications. Yet, up to date there are only few studies that have systematically assessed the degradability of different HA-fillers by hyaluronidase. To analyze the interactions of HA-fillers and hyaluronidase in a time-dependent manner using a novel standardized in vitro approach. Comparable HA-fillers, Belotero Balance Lidocaine (BEL; Merz), Emervel classic (EMV; Galderma) and Juvederm Ultra 3 (JUV; Allergan), were incubated with a fluorescent dye and bovine hyaluronidase (HYAL; Hylase "Dessau", Riemser) or control (NaCl) and monitored by time-lapse videomicroscopy. The degradation of HA-fillers was assessed as decrease in fluorescence intensity of HA-filler plus hyaluronidase vs. HA-filler plus control, quantified by computer-assisted image analysis (ImageJ). Hyaluronidase showed a significant degradation of the HA-fillers BEL and EMV. Degradation was measurable at 5 h (BEL) and 7 h (EMV), respectively; significance was reached at 14 h (BEL) and 13 h (EMV). No effect of hyaluronidase was observed for JUV. Time-lapse microscopy enables systematically, standardized, comparative in vitro analyses of the interactions of hyaluronidase and HA-fillers.


Characterization of long cDNA clones from human adult spleen.
As an extension of our analysis of long cDNAs, we here report the characterization of cDNA clones from human adult spleen. From 2000 cDNA clones randomly sampled from a size-fractionated human spleen cDNA library (average size 4.5 kb), 97 clones were selected for sequencing according to their ability to code for protein at the 5'-end sequences and the novelty of their end sequences. The sequence data of these clones demonstrated that 87 out of 97 cDNA clones were derived from independent human genes. The average sizes of the inserts and corresponding open reading frames of these 87 cDNAs reached 4.5 kb and 1.4 kb (corresponding to 468 amino acid residues), respectively. In addition to these sequence analyses in silico, the expression profiles of the genes were also studied in ten human adult tissues by reverse transcription-coupled polymerase chain reaction, products of which were quantified by enzyme-linked immunosorbent assay. The results indicated that spleen could be used as an additional source of human long cDNAs to complement the list of human genes.


[Enterobius gregorii (Oxyuridae, Nematoda), a new human parasite].
A review of the Oxyurids parasites of Primates shows that most of the species described in the Malagasy Lemurs and in the Old World Monkeys are not single species, but couples of sister-species. The sister-species of each couple may be differentiated sometimes only by the characteristics of male spicule (less evoluated species), sometimes by other characteristics (cephalic structures, length of oesophagus, etc., in more evoluated species). In the first instance only males can be identified, in the second instance females may also be identified. In the Human parasites, which are very closely related to those of the Old World Monkeys, two types of spicules were described and we consider that each type belongs to a different species: Enterobius vermicularis (L., 1758) for the larger spicule (100 to 122 micrometers), and Enterobius gregorii n. sp. for the shorter spicule (70 to 80 micrometers).


High Concentrations of Angiopoietin-Like Protein 4 Detected in Serum from Patients with Rheumatoid Arthritis Can Be Explained by Non-Specific Antibody Reactivity.
Angiopoietin-like protein 4 (ANGPTL4) is suggested to be a master regulator of plasma triglyceride metabolism. Our aim was to study whether the previously reported high levels of ANGPTL4 detected in serum from patients with rheumatoid arthritis (RA) by ELISA was due to any specific molecular form of this protein (oligomers, monomers or fragments). ANGPTL4 levels were first determined in serum from 68 RA patients and 43 age and sex matched control subjects and the mean values differed by a factor of 5.0. Then, ANGPTL4 was analyzed after size exclusion chromatography (SEC) of serum samples. With serum from one of the RA patients with high levels of ANGPTL4, the dominant reactivity was found in fractions corresponding to high-molecular weight proteins. In addition, a minor peak of reactivity eluting late from the column was found both in the patient and in controls. By the use of HeteroBlock®, and by careful selection of antibodies, we documented non-specific reactions for ANGPTL4 in 39% of samples from the RA patients, most likely due to cross-reactivity of the antibodies with rheumatoid factor (RF). The corresponding figure for control subjects was 6.3%. After corrections for non-specific reactions, the mean level of ANGPTL4 in serum from RA patients was still significantly higher than in control individuals (mean levels were 101±62 and 67±39 ng/ml respectively, P = 0.02). We re-analyzed samples from our previously published studies on ANGPL4 levels in patients on hemodialysis and patients with diabetes type 2. These samples did not show false positive reactions. The levels of ANGPTL4 were comparable to those detected previously.


Rare emergency in children: Priapism and stepwise treatment approach.
Priapism is a rare condition in children and the treatment algorithm is controversial in this age group. Herein, we report eight cases with low-flow priapism and our stepwise treatment approach in light of literature. We present a simple stepwise treatment for low-flow priapism including five steps. Step 1: Cold compress and analgesia while evaluation the priapism and its etiology. Step 2: Corporal aspiration and adrenaline infusion in the ward. Step 3: Modified Winter shunt in the same place. Step 4: Ketamine application and caudal block in the operating room. Step 5: Sapheno-cavernous (Grayhack) shunt. Eight cases with low-flow priapism were reviewed retrospectively. Symptoms, duration of tumescence, the interventions, and step that provide detumescence were recorded. The mean age of patients was 8.5 years (1-17 y). The median time of the priapism before admission was 15 h (4-165 h). The etiological factors were sickle cell disease, hemodialysis due to chronic renal failure, and factor V Leiden mutation in three patients. Detumescence was achieved in one patient at Step 2, in two patients at Steps 3, 4, and 5, respectively. Rigidity of cavernous body was observed in one patient in long-term follow-up. Low-flow priapism is a urological emergency that may cause erectile dysfunction. Treatment options should be selected according to a protocol that prevents time loss and avoids more invasive treatment in unnecessary situations. Our algorithm with simple nature and its steps from less invasive to more invasive procedures may be an alternative for the treatment of low-flow priapism.


Compensatory Changes in Energy Balance Regulation over One Athletic Season.
Mechanisms in energy balance (EB) regulation may include compensatory changes in energy intake (EI) and metabolic adaption (MA), but information is unavailable in athletes who often change EB components. We aim to investigate EB regulation compensatory mechanisms over one athletic season. Fifty-seven athletes (39 males/18 females; handball, volleyball, basketball, triathlon, and swimming) were evaluated from the beginning to the competitive phase of the season. Resting and total energy expenditure (REE and TEE, respectively) were assessed by indirect calorimetry and doubly labeled water, respectively, and physical activity energy expenditure was determined as TEE - 0.1(TEE) - REE. Fat mass (FM) and fat-free mass (FFM) were evaluated by dual-energy x-ray absorptiometry and changed body energy stores was determined by 1.0(ΔFFM/Δtime) + 9.5(ΔFM/Δtime). EI was derived as TEE + EB. REE was predicted from baseline FFM, FM, sex, and sports. %MA was calculated as 100(measured REE/predicted REE-1) and MA (kcal) as %MA/100 multiplied by baseline measured REE. Average EI minus average physical activity energy expenditure was computed as a proxy of average energy availability, assuming that a constant nonexercise EE occurred over the season. Body mass increased by 0.8 ± 2.5 kg (P < 0.05), but a large individual variability was found ranging from -6.1 to 5.2 kg. The TEE raise (16.8% ± 11.7%) was compensated by an increase EI change (16.3% ± 12.0%) for the whole group (P < 0.05). MA was found in triathletes, sparing 128 ± 168 kcal·d, and basketball players, dissipating 168 ± 205 kcal·d (P < 0.05). MA was associated (P < 0.05) with EB and energy availability (r = 0.356 and r = 0.0644, respectively). TEE increased over the season without relevant mean changes in weight, suggesting that EI compensation likely occurred. The thrifty or spendthrift phenotypes observed among sports and the demanding workloads these athletes are exposed to highlight the need for sport-specific energy requirements.


Electromagnetic scattering from a spherical polydispersion of coated spheres.
The volume averaged cross sections for extinction, scattering, absorption, and radiation pressure along with the elements of the phase matrix were computed for a spherical polydispersion of water coated carbon particles. The wavelength used was 4910 A. Two cases were considered. For one we held the thickness of the water coating constant over the polydispersion, while the parameter q = r(0)/r, (the ratio of core radius to total radius) was varied. For the subsequent case we held q constant over the polydispersion, while the thickness of the coating varied. The results show that there are large differences in both the intensity and degree of polarization between dry and wet aerosols. Also interference phenomena can occur, which demonstrate that the assignment of an average refractive index to aerosols can be misleading and can lead to erroneous results.


Lactoperoxidase haem, an iron-porphyrin thiol.
The haem prosthetic group of lactoperoxidase can be prepared from the enzyme in high yield by reductive cleavage with mercaptoethanol in 8 M-urea under mild conditions. The product yields porphyrins, after removal of iron, which show visible spectroscopic properties similar to protoporphyrin but are considerably more polar. In the presence of iodoacetamide, a different product is obtained by reductive cleavage. The proton n.m.r. and mass spectra of this compound indicate that the prosthetic group of the enzyme is the iron complex of 18-mercaptomethyl-2,7,12-trimethyl-3,8-divinylporphyrin-13,17-d ipropionic acid. It is proposed that the unusual strength of binding of the prosthetic group to the apoprotein is due to formation of a disulphide bond from a cysteine residue to the porphyrin thiol.


Unveiling breast cancer risk profiles: a survival clustering analysis empowered by an online web application.
Aim: To develop a shiny app for doctors to investigate breast cancer treatments through a new approach by incorporating unsupervised clustering and survival information. Materials & methods: Analysis is based on the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset, which contains 1726 subjects and 22 variables. Cox regression was used to identify survival risk factors for K-means clustering. Logrank tests and C-statistics were compared across different cluster numbers and Kaplan-Meier plots were presented. Results & conclusion: Our study fills an existing void by introducing a unique combination of unsupervised learning techniques and survival information on the clinician side, demonstrating the potential of survival clustering as a valuable tool in uncovering hidden structures based on distinct risk profiles.


Short-term survival after acute myocardial infarction predicted by hemodynamic parameters.
In the acute phase of myocardial infarction, short-term prediction of the likelihood of survival helps the physician choose the appropriate therapy for individual patients. Of 122 patients admitted to the coronary care unit of the Thoraxcenter, University Hospital, Rotterdam, with an acute myocardial infarction, 16 died from pump failure. In these and the 106 survivors, the predictive value of peripheral systolic (SP) and diastolic (DP) blood pressure, pulmonary capillary wedge pressure (PCW), mixed venous oxygen saturation (MVO2sat) in the pulmonary artery and heart rate (HR), both alone and in combination, was evaluated at the time of admission and 24 hours later. When, at admission, (DP X MVO2sat)/PCW exceeded 250%, 97/99 patients survived, whereas values below 250% were associated with death in 14/23. All other papameters, taken alone or in other combinations, showed less discriminatory power. Thb mean value of this index in survivors (549%) was statistically different (P less than 0.001) from the mean value in nonsurvivors (183%). Twenty-four hours later all survivors with admission values lower than 250% had an improved index. Of the 14 nonsurvivors with admission values lower than 250%, seven had already died, and in seven others the index had decreased still further; Linear discriminant analysis showed that (0.024 SP -- 0.217 PCW + 0.234 MVO2sat) was the most powerful prognostic index at the time of admission; its time course did not provide a more effective prediction of ultimate fatality than (DP XMVO2sat)/PCW. Determination of (DP X MVO2sat)/PCW in patients hospitalized for acute myocardial infarction provides a reliable prognosis for short-term patient survival. Its practical value in guiding patient management, more particularly for initiating mechanical circulatory assistance or for emergency surgery, must be further assessed.


Stevia rebaudiana ethanolic extract exerts better antioxidant properties and antiproliferative effects in tumour cells than its diterpene glycoside stevioside.
Steviol glycosides are currently being used as natural sweeteners by the food industry and Stevia rebaudiana has long been used as a sweet plant in South America for patients suffering from diabetes. In this study, a Stevia rebaudiana ethanolic extract (SREE) was prepared, analysed and tested for antioxidant activity in terms of free radical scavenging properties and antiproliferative effects in cervix (HeLa), pancreatic (MiaPaCa-2) and colonic (HCT116) cancer cells. The antiproliferative mechanism was confirmed by testing the effects on cyclin D1-CDK4. Bioassays were also performed for the diterpene glycoside stevioside. Our results demonstrate that the extract acts as an antioxidant being able to scavenge free radicals, but this activity was not due to stevioside. The extract also induced cell death in the three cell lines, being more active against cervix cancer cells (HeLa); however, the concentration of stevioside needed to produce antiproliferative effects was higher than the amount of steviol glycosides found in a lower dose of extract inducing cell death. In addition, the extract clearly inhibited CDK4 whereas stevioside did not, concluding that the antiproliferative activity of stevia may be due to inhibition of cyclin-dependent kinases performed by other compounds of the extract.


Structural characterization and subcellular localization of Drosophila organic solute carrier partner 1.
Organic solute carrier partner 1 (OSCP1) is known to facilitate the transport of various organic solutes into cells and reported to play a role in cell growth and cell differentiation. Moreover, OSCP1 is known as a tumor suppressor gene that is frequently down-expressed in nasopharyngeal carcinomas and acute myeloid leukemia. However, the underlying mechanisms of action remain unclear and the subcellular localization of OSCP1 has yet to be determined in detail. Drosophila contains a single orthologue of OSCP1 (dOSCP1) that shares 58% homology with its human counterpart. To study the expression pattern and subcellular localization of dOSCP1, we prepared a specific antibody. Subcellular localization analyses of dOSCP1 with these revealed localization in the plasma membrane, endoplasmic reticulum, Golgi apparatus and mitochondria, but no detection in cytosol. dOSCP1 signals were also detected in the nucleus, although at weaker intensity than in plasma membranes and subcellular organelles. In addition, native polyacrylamide gel electrophoresis analysis with and without β-mercaptoethanol treatment revealed that recombinant dOSCP1 forms dimers and trimers in solution. The dimer form of dOSCP1 could also be detected by Western immunoblot analyses in third instar larval extracts. The data revealed that dOSCP1 localizes not only in the plasma membrane but also in the nucleus, ER, Golgi apparatus and mitochondria. It is therefore conceivable that this protein may interact with various partners or form multimeric complexes with other proteins to play multiple roles in cells, providing clues to understanding the functions of dOSCP1 during Drosophila development.


Bioassayed demineralized bone matrix and calcium sulfate: use in bone-grafting procedures.
A combination product of bioassayed, demineralized bone matrix (AlloGro, AlloSource, Denver CO) and calcium sulfate pellets (OsteoSet, Wright Medical Technology, Arlington TN) was utilized in a prospective clinical study in 50 patients in need of bone-grafting procedures. It was proposed that the osteoinductive activity of the demineralized bone matrix combined with the osteoconduction and rapid dissolution of the calcium sulfate pellets would complement each other in promoting bone formation. The patients were evaluated clinically and radiographically at regular intervals post-operatively by an independent clinician. A total 10-point healing score was used to determine healing characteristics and progress. Fifty patients (24 males and 26 females) were treated for benign bone lesions (35), nonunion (11), osteomyelitis (3), and acute fracture (1). The average age was 33 years (range, 3-64 years). Lesions were located in the femur (16), tibia (15), humerus (7), and other sites (12). The average length of follow-up was 14 months (range, 6-32 months). Forty-nine of 50 patients healed their lesions (98%), requiring an average time to heal of 11.8 weeks (range, 3-48 weeks). There were no graft-related complications. The results of this preliminary clinical study suggest that a combination of bioassayed demineralized bone matrix and calcium sulfate is very effective in treating benign lesions of bone, as well as nonhealing fractures, which is comparable to grafting with autograft. Future studies have been undertaken utilizing this combination in all acute operative settings and fracture management situations.


Characteristics of B cells and immunoglobulin profile in Takayasu's arteritis.
Disorders of humoral immunity in Takayasu's arteritis (TAK) have not been well explored. This study describes the characteristics of B cells and immunoglobulin (Ig) profile in patients with TAK. Peripheral B cell populations assessed using flow cytometry and serum Ig levels assessed using a biochemical analyser in 98 newly diagnosed patients with TAK were analysed and compared with those of 31 patients with systemic lupus erythematosus (SLE) and 60 healthy controls (HCs). CD19+ B cell and IgG infiltration to the aortic tissue was evaluated by immunohistochemical staining. The proportion of peripheral CD3-CD19+ B cells and levels of serum IgG in TAK were lower than those in SLE, but higher than those in HCs. CD3-CD19+ B cell counts were higher in TAK than in HCs. Serum IgG and IgG1 levels were higher in active TAK than in non-active TAK. In TAK, positive correlations of serum IgG levels with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, Kerr score, and Indian Takayasu Clinical Activity Score (ITAS2010, ITAS-A) were observed before immunotherapy. After 6 months of immunotherapy, serum Ig levels significantly decreased. Positive correlations between the changes in IgG levels and values of ESR, CRP, Kerr score, and ITAS-A were detected. Immunohistochemical staining confirmed CD19+ B cell and IgG infiltration to the aortic wall in patients with TAK. Enhanced B cells might contribute to the pathogenesis of TAK, and serum IgG levels could serve as a simple, useful biomarker to assess disease activity and monitor treatment response in TAK.


Tuning Chemistry and Topography of Nanoengineered Surfaces to Manipulate Immune Response for Bone Regeneration Applications.
Osteoimmunomodulation has informed the importance of modulating a favorable osteoimmune environment for successful materials-mediated bone regeneration. Nanotopography is regarded as a valuable strategy for developing advanced bone materials, due to its positive effects on enhancing osteogenic differentiation. In addition to this direct effect on osteoblastic lineage cells, nanotopography also plays a vital role in regulating immune responses, which makes it possible to utilize its immunomodulatory properties to create a favorable osteoimmune environment. Therefore, the aim of this study was to advance the applications of nanotopography with respect to its osteoimmunomodulatory properties, aiming to shed further light on this field. We found that tuning the surface chemistry (amine or acrylic acid) and scale of the nanotopography (16, 38, and 68 nm) significantly modulated the osteoimmune environment, including changes in the expression of inflammatory cytokines, osteoclastic activities, and osteogenic, angiogenic, and fibrogenic factors. The generated osteoimmune environment significantly affected the osteogenic differentiation of bone marrow stromal cells, with carboxyl acid-tailored 68 nm surface nanotopography offering the most promising outcome. This study demonstrated that the osteoimmunomodulation could be manipulated via tuning the chemistry and nanotopography, which implied a valuable strategy to apply a "nanoengineered surface" for the development of advanced bone biomaterials with favorable osteoimmunomodulatory properties.


CK2 is a novel negative regulator of NADPH oxidase and a neuroprotectant in mice after cerebral ischemia.
NADPH oxidase is a major complex that produces reactive oxygen species (ROSs) during the ischemic period and aggravates brain damage and cell death after ischemic injury. Although many approaches have been tested for preventing production of ROSs by NADPH oxidase in ischemic brain injury, the regulatory mechanisms of NADPH oxidase activity after cerebral ischemia are still unclear. In this study, we identified casein kinase 2 (CK2) as a critical modulator of NADPH oxidase and elucidated the role of CK2 as a neuroprotectant after oxidative insults to the brain. We found that the protein levels of the catalytic subunits CK2alpha and CK2alpha', as well as the total activity of CK2, are significantly reduced after transient focal cerebral ischemia (tFCI). We also found this deactivation of CK2 caused by ischemia/reperfusion increases expression of Nox2 and translocation of p67(phox) and Rac1 to the membrane after tFCI. Interestingly, we found that the inactive status of Rac1 was captured by the catalytic subunit CK2alpha under normal conditions. However, binding between CK2alpha and Rac1 was immediately diminished after tFCI, and Rac1 activity was markedly increased after CK2 inhibition. Moreover, we found that deactivation of CK2 in the mouse brain enhances production of ROSs and neuronal cell death via increased NADPH oxidase activity. The increased brain infarct volume caused by CK2 inhibition was restored by apocynin, a NADPH oxidase inhibitor. This study suggests that CK2 can be a direct molecular target for modulation of NADPH oxidase activity after ischemic brain injury.


Incomplete reporting of patient-reported outcomes in multiple sclerosis: A meta-epidemiological study of randomized controlled trials.
Multiple Sclerosis significantly affects quality of life, which is often measured by patient-reported outcomes. The incorporation of patient-reported outcomes within clinical trials supplements the efficacy of outcomes in order to provide a patient's perspective for clinicians. Our objective was to evaluate current literature for completeness of reporting of PROs in randomized controlled trials (RCTs) for the management of MS. We used MEDLINE, Embase, and Cochrane Central Register of Controlled Trials to search for RCT publications investigating the management of MS. After duplicate screening via Rayyan, RCTs fitting our inclusion criteria were abstracted employing the Consolidated Standards of Reporting Trials - Patient-Reported Outcome (CONSORT-PRO) adaptation and the Cochrane Collaboration Risk of Bias (RoB) 2.0 tool. Mean percent completion of an adaptation of CONSORT-PRO was calculated to address completeness of reporting. In addition, bivariate regression models were used to evaluate relationships between trial characteristics and completeness of reporting. Our search returned 3,966 results and 92 RCTs were included for data abstraction and analysis. We found an overall completion of 48.68% (SD=19.03). Sixty-five (of 92; 70.65%) of the RCTs were evaluated as having 'high' RoB. There were significant associations between completeness of reporting and the following: mention of CONSORT within published RCTs (t=2.55, p=.013), length of PRO follow-up (t=2.9, p=.005; t=2.14, p=.035), and sample size (t=3.12, p=.002). No other significant associations were found. Our study found incomplete adherence to the CONSORT-PRO adaptation among RCTs pertaining to MS. Of the most underreported items, the failure to report a hypothesis and define an approach to missing data threaten the validity of the evidence acquired from RCTs. Furthermore, PROs provide an opportunity to supplement trial outcomes with the patient's perspective. Thus, trialists of future RCTs may improve PRO reporting with increased adherence to the CONSORT-PRO adaptation.