Noninvasive fractional flow reserve derived from coronary computed tomography angiography: integrated anatomical and functional assessment.
Coronary computed tomographic angiography (CCTA) provides anatomic detail of lumen stenosis and information on plaque burden, plaque extent and plaque characteristics. CCTA does not, however, provide insight into the hemodynamic significance of a stenosis, which is essential to allow appropriate revascularization decision-making. This could reduce downstream invasive coronary angiography and nonbeneficial coronary revascularization, particularly with intermediate coronary stenosis. Invasive fractional flow reserve (FFR) is the gold standard for the determination of lesion-specific ischemia and the need for revascularization. Advances in computational technology now permit calculation of FFR using resting CCTA image data, without the need for additional radiation or medication. Early data demonstrate improved accuracy and a discriminatory ability of FFR computed tomography to identify ischemia-producing lesions compared with CCTA alone. This new, combined anatomic-functional assessment has the potential to simplify the noninvasive diagnosis of coronary artery disease with a single study to identify patients with ischemia-causing stenosis who may benefit from revascularization.


Association between Nonmedical Marijuana and Pain Reliever Uses among Individuals Aged 50.
Marijuana and pain reliever use for medical and nonmedical purposes has been increasing among older adults. Using the 2012-2013 U.S. National Survey on Alcohol and Related Conditions (NESARC-III), this study examined: (1) the association between past-year nonmedical marijuana and pain reliever use among adults aged 50+ years (N = 14,715); and (2) sociodemographic, health, and pain-related correlates of nonmedical marijuana and/or pain reliever use. The findings show that 3.87% and 3.12%, respectively, used marijuana and pain relievers nonmedically and 14.40% of marijuana users, compared to 2.67% of nonusers, used pain relievers nonmedically. Controlling for sociodemographics, health status, pain interference, and mental and other substance use disorders, marijuana use anduse disorder were significantly associated with nonmedical pain reliever use and opioid use disorder, respectively. Compared to marijuana users (with or without nonmedical use of pain relievers), nonmedical pain reliever users (without marijuana) are older, married, and women. Users of both substances nonmedically are a small group (0.56% of the 50+ age group), but they are at greatest risk of lifetime opioid, alcohol, and nicotine use disorders. Pain interference is a significant correlate of nonmedical pain reliever use. Healthcare providers should assess for the nonmedical use of these medicines/drugs and help older adults receive effective pain treatment.


Gold Nanoclusters: Bridging Gold Complexes and Plasmonic Nanoparticles in Photophysical Properties.
Recent advances in the determination of crystal structures and studies of optical properties of gold nanoclusters in the size range from tens to hundreds of gold atoms have started to reveal the grand evolution from gold complexes to nanoclusters and further to plasmonic nanoparticles. However, a detailed comparison of their photophysical properties is still lacking. Here, we compared the excited state behaviors of gold complexes, nanolcusters, and plasmonic nanoparticles, as well as small organic molecules by choosing four typical examples including the Au10 complex, Au25 nanocluster (1 nm metal core), 13 diameter Au nanoparticles, and Rhodamine B. To compare their photophysical behaviors, we performed steady-state absorption, photoluminescence, and femtosecond transient absorption spectroscopic measurements. It was found that gold nanoclusters behave somewhat like small molecules, showing both rapid internal conversion (<1 ps) and long-lived excited state lifetime (about 100 ns). Unlike the nanocluster form in which metal-metal transitions dominate, gold complexes showed significant charge transfer between metal atoms and surface ligands. Plasmonic gold nanoparticles, on the other hand, had electrons being heated and cooled (~100 ps time scale) after photo-excitation, and the relaxation was dominated by electron-electron scattering, electron-phonon coupling, and energy dissipation. In both nanoclusters and plasmonic nanoparticles, one can observe coherent oscillations of the metal core, but with different fundamental origins. Overall, this work provides some benchmarking features for organic dye molecules, organometallic complexes, metal nanoclusters, and plasmonic nanoparticles.


Aperiodic neural activity reflects metacontrol.
Higher-level cognitive functions are mediated via complex oscillatory activity patterns and its analysis is dominating cognitive neuroscience research. However, besides oscillatory (period) activity, also aperiodic activity constitutes neural dynamics, but its relevance for higher-level cognitive functions is only beginning to be understood. The present study examined whether the broadband EEG aperiodic activity reflects principles of metacontrol. Metacontrol conceptualizes whether it is more useful to engage in more flexible processing of incoming information or to shield cognitive processes from incoming information (persistence-heavy processing). We examined EEG and behavioral data from a sample of n = 191 healthy participants performing a Simon Go/NoGo task that can be assumed to induce different metacontrol states (persistence-biased vs. flexibility-biased). Aperiodic activity was estimated using the FOOOF toolbox in the EEG power spectrum. There was a higher aperiodic exponent and offset in NoGo trials compared with Go trials, in incongruent (Go) trials compared with congruent (Go) trials. Thus, aperiodic activity increases during persistence-heavy processing, but decreases during flexibility-heavy processing. These findings link aperiodic features of the EEG signal and concepts describing the dynamics of how cognitive control modes are applied. Therefore, the study substantially extends the importance of aperiodic activity in understanding cognitive functions.


Fruit pit obstruction. "The propitious pit.".
Ingestion of fruit pit must be a frequent and innocuous phenomenon, judging from the expected frequency of such occurrences and the relative dearth of medical reports to the contrary. Reported here are four cases in which fruit pits of varied nature completed an otherwise incomplete intestinal obstruction. On of these was in the terminal ileum, with incomplete obstruction due to regional ileitis, in which the offending pit was seen radiologically but was not recognized as such. The other three were in the transverse colon, at the site of annular carcinomatous lesions. The completion of the obstruction by the fruit pits eventuated in earlier symptoms, diagnosis, and treatment. In one case, the fruit pits were multiple; in the remainder, they were single.


[CHOICE OF SANITARY-INDICATIVE MICROORGANISMS FOR THE ASSESSMENT OF THE SAFETY OF SPLIT-SYSTEMS].
Purpose of work is a compilation of data about the microflora which colonizes a split-system, with the aim of selection of sanitary-indicative microorganisms, whose presence in the sample would indicate to the need for cleaning and disinfection of split-systems. In the article there were used data of five years author's scientific inquiry, related to the prevention of respiratory diseases, associated with the usage of a local air conditioning systems. We also use the data from the literature. For selection of "indicative" microorganisms, we proposed the usage of nine criteria, each of them have numeric value from 0 to 3 points (risk for health, prevalence rate of the disease, epidemiological link, speed of split system's colonization, difficulty of cultivation, resistance in the environment, resistance to disinfectants, frequency of detection in home air conditioning systems, frequency of detection in air conditioning systems of public buildings). After the calculation Pseudomonas aeruginosa and Staphylococcus aureus received maximal score (20 points). Therefore, these two types of bacteria are indicative microorganisms. The detection of these microorganisms in split systems will indicate to the contamination of air-conditioning system. This microflora also is a criterion of cleaning and disinfection quality--presence of these microorganisms in the samples after this process will mean that the processing of air conditioning systems was performed poorly. Split systems are very faster colonized by conditionally pathogenic and pathogenic microflora. To prevent the possible hazard for population's health it is necessary to develop the normative base, according to which sanitary-and-hygienic control over the split-systems working must be carried out. Proposed criteria suggest that Pseudomonas aeruginosa and Staphylococcus aureus are indicative microorganisms, and it's identification in the air-conditioning system would mean risk for health and necessity for cleaning and disinfection.


(1,4,7-trimethyl-1,4,7-triazacyclononane)iron (III)-mediated cleavage of DNA: detection of selected protein-DNA interactions.
A new reagent for the oxidative cleavage of DNA, (1,4,7-trimethyl-1, 4,7-triazacyclononane)iron(III) chloride was recently introduced. We have determined the utility of this reagent for detecting protein-DNA interactions within two types of complexes. Interestingly, we find that the rates of DNA cleavage by this reagent are differentially affected by the two classes of protein-DNA interactons studied. We find that the rate of DNA cleavage by this reagent is relatively unaffected by the non-sequence-specific histone-DNA interactions within a nucleosome complex. Conversely, a clear footprint pattern is obtained with two different DNA sequence-specific protein-DNA complexes. The results suggest that (1,4,7-trimethyl-1,4,7-triazacyclononane)iron(III) chloride will be a useful reagent to probe trans -acting-factor-DNA interactions within a chromatin environment. Differences between these two types of protein-DNA interactions, which might account for this observation, are discussed.


SYNTAX Score and 1-Year Outcomes in the OPTIVUS-Complex PCI Study Multivessel Cohort.
The optimal revascularization strategy in patients with multivessel disease and intermediate SYNTAX score (SS) has not been fully elucidated. This study aimed to investigate the clinical outcomes of optimal intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) stratified by SS. This was a substudy of the OPTIVUS-Complex PCI study Multivessel Cohort, which aimed to meet the prespecified criteria for optimal stent expansion after IVUS-guided PCI. A total of 1,005 patients were divided into 3 groups according to SS: low, ≤22; intermediate, 23 to 32; and high, ≥33. The primary end points were major adverse cardiac and cerebrovascular events (MACCE) defined as a composite of death, myocardial infarction, stroke, or coronary revascularization. The cumulative 1-year incidence of the primary end point was significantly higher in patients with high SS than in those with intermediate or low SS (25.0%, 10.9%, and 9.5%, respectively; p = 0.003). This difference was mainly caused by the incidence of coronary revascularization. In the multivariable Cox proportional hazards models, the excess risk of patients with high versus low SS remained significant for the primary end point (hazard ratio 3.19, 95% confidence interval 1.65 to 6.16, p <0.001), whereas the excess risk of patients with intermediate versus low SS was no longer significant (hazard ratio 1.20, 95% confidence interval 0.72 to 2.01, p = 0.46). After IVUS-guided multivessel PCI, patients with intermediate SS had a similar 1-year risk of MACCE to that of patients with low SS, whereas patients with high SS had a higher 1-year risk of MACCE than those with low SS.


[Biopathology of craniocerebral injuries: experimental models].
In traumatic brain injury the secondary damage is responsible for the majority of the clinical and pathological sequels. This circumstance together with the difficulties of acquiring well preserved brain material for specialized neuropathological study impair the understanding of processes implied in their pathophysiology. The development of experimental models has played an outstanding role for the better knowledge of these processes. For the development of standardized experimental models the biophysical and anatomical characteristics of brain and skull of the various utilized species have to be considered, but the physiological, neurochemical and molecular peculiarities must also be taken into account. Various in vivo models have been developed, inducing direct impact to the skull or to the brain, or mimicking lesions subsequent to craniocerebral trauma, such as subarachnoid hemorrhage, hematoma or necrosis. To analyze the molecular mechanisms of cellular response in vitro models have been developed. A great amount of cells in the contusional area die immediately following traumatic brain injury, but a still higher number of cells will undergo in the following hours. This second wave of neuronal death is induced by phenomena such as secondary axotomy and brain edema. In the pathogenesis of both the damage of cytoplasmic membrane is involved.


Highly Basic Clusters in the Herpes Simplex Virus 1 Nuclear Egress Complex Drive Membrane Budding by Inducing Lipid Ordering.
During replication of herpesviruses, capsids escape from the nucleus into the cytoplasm by budding at the inner nuclear membrane. This unusual process is mediated by the viral nuclear egress complex (NEC) that deforms the membrane around the capsid by oligomerizing into a hexagonal, membrane-bound scaffold. Here, we found that highly basic membrane-proximal regions (MPRs) of the NEC alter lipid order by inserting into the lipid headgroups and promote negative Gaussian curvature. We also find that the electrostatic interactions between the MPRs and the membranes are essential for membrane deformation. One of the MPRs is phosphorylated by a viral kinase during infection, and the corresponding phosphomimicking mutations block capsid nuclear egress. We show that the same phosphomimicking mutations disrupt the NEC-membrane interactions and inhibit NEC-mediated budding in vitro, providing a biophysical explanation for the in vivo phenomenon. Our data suggest that the NEC generates negative membrane curvature by both lipid ordering and protein scaffolding and that phosphorylation acts as an off switch that inhibits the membrane-budding activity of the NEC to prevent capsid-less budding. IMPORTANCE Herpesviruses are large viruses that infect nearly all vertebrates and some invertebrates and cause lifelong infections in most of the world's population. During replication, herpesviruses export their capsids from the nucleus into the cytoplasm by an unusual mechanism in which the viral nuclear egress complex (NEC) deforms the nuclear membrane around the capsid. However, how membrane deformation is achieved is unclear. Here, we show that the NEC from herpes simplex virus 1, a prototypical herpesvirus, uses clusters of positive charges to bind membranes and order membrane lipids. Reducing the positive charge or introducing negative charges weakens the membrane deforming ability of the NEC. We propose that the virus employs electrostatics to deform nuclear membrane around the capsid and can control this process by changing the NEC charge through phosphorylation. Blocking NEC-membrane interactions could be exploited as a therapeutic strategy.


Sexually dimorphic swallows have higher extinction risk.
The effect of sexual selection on extinction risk remains unclear. In theory, sexual selection can lead to both increase and decrease extinction probability depending on the ecology of the study system. Thus, combining different groups might obscure patterns that can be found in groups that share similar ecological features. Using phylogenetic comparative analysis, we studied sexual plumage dimorphism in relation to the perceived risk of extinction in hirundines (subfamily: Hirundininae), in which all species are socially monogamous aerial foragers. Among the 72 species studied, five species are facing a perceived threat of extinction. Species with sexually dimorphic plumage had a higher risk of extinction than did species with sexually monomorphic plumage. Likewise, when focusing solely on tail ornamentation, species that exhibit a sexual dimorphism in tail length had a higher risk of extinction than did other species. In Hirundininae, which are affected a great deal by severe weather, sexual selection and the resultant sexual dimorphism would increase extinction risk.


Identification of Rare Variants in Metabolites of the Carnitine Pathway by Whole Genome Sequencing Analysis.
We use whole genome sequence data and rare variant analysis methods to investigate a subset of the human serum metabolome, including 16 carnitine-related metabolites that are important components of mammalian energy metabolism. Medium pass sequence data consisting of 12,820,347 rare variants and serum metabolomics data were available on 1,456 individuals. By applying a penalization method, we identified two genes FGF8 and MDGA2 with significant effects on lysine and cis-4-decenoylcarnitine, respectively, using Δ-AIC and likelihood ratio test statistics. Single variant analyses in these regions did not identify a single low-frequency variant (minor allele count > 3) responsible for the underlying signal. The results demonstrate the utility of whole genome sequence and innovative analyses for identifying candidate regions influencing complex phenotypes.


Venom and viral expression products of the endoparasitic wasp Campoletis sonorensis share epitopes and related sequences.
Endoparasitic wasps of lepidopteran insects must induce changes in host immunity and development to survive. Depending on the species, this may require wasp venom proteins and/or a polydnavirus. We describe an immunological and genetic relationship between the Campoletis sonorensis polydnavirus and the wasp's venom gland. Monoclonal antibodies raised against venom glands recognized epitopes conserved on several polydnavirus proteins and on multiple wasp oviduct and venom proteins. The viral envelope proteins had molecular masses of 16, 20, 45, and 50 kDa, while a complex of at least five immunoreactive venom-gland and soluble oviduct proteins ranged in size from 24 to 36 kDa. Since the conserved epitopes were present on the viral envelope, neutralization assays were performed. Monoclonal antibodies added to purified virus blocked the normal viral inhibition of host growth and development. To determine whether venom mRNA and viral genes were also related, venom-related cDNA clones were isolated from the wasp oviduct with a venom-gland cDNA probe. Venom-related viral clones were then identified and selected from a viral genomic library and from a parasitized Heliothis virescens cDNA library. Venom-related mRNAs were expressed in the venom gland, the oviduct, and the parasitized host. We propose that the immunological relationship between venom and viral proteins, and the hybridization of venom and viral genes, may reflect an evolutionary relationship in which venom gene homologs were incorporated into the viral genome, thereby allowing viral expression of venom-related genes and enhancing parasite survival.


[Pepsinogen I and duodenal ulcer].
In this revision article it was tried to focus on the role played by pepsinogen/pepsin since its discovery until its practical use. Pepsinogen determination as the gastric acid secretion has different basal or stimulated secretion levels in the peptic ulcer, gastritis, etc. The methods for pepsinogen determination are evaluated, verifying that, in spite of radioimmunoassay utilization another methods less sophisticated have been used successfully. The pepsinogen seric levels (PSL) after stimulation with Histalog, discriminate the patients suffering from duodenal ulcer from normal individuals, and they are higher among men than women. A parallelism is made between pepsinogen-I and II finding out pepsinogen-I higher level in smoking individuals. The pepsinogen-I is increased in the duodenal ulcer and II in the gastric ulcer and both of them bent to be characterized as a genetic marker for peptic ulcer. Finally, the main clinical applicability for PSL group I determination is the detection of atrophic gastritis considering its potential for gastric malignancy.


Precipitation of Pt, Pd, Rh, and Ru Nanoparticles with Non-Precious Metals from Model and Real Multicomponent Solutions.
This article presents studies on the precipitation of Pt, Pd, Rh, and Ru nanoparticles (NPs) from model and real multicomponent solutions using sodium borohydride, ascorbic acid, sodium formate, and formic acid as reducing agents and polyvinylpyrrolidone as a stabilizing agent. As was expected, apart from PGMs, non-precious metals were coprecipitated. The influence of the addition of non-precious metal ions into the feed solution on the precipitation yield and catalytic properties of the obtained precipitates was studied. A strong reducing agent, NaBH4 precipitates Pt, Pd, Rh, Fe and Cu NPs in most cases with an efficiency greater than 80% from three- and four-component model solutions. The morphology of the PGMs nanoparticles was analyzed via SEM-EDS and TEM. The size of a single nanoparticle of each precipitated metal was not larger than 5 nm. The catalytic properties of the obtained nanomaterials were confirmed via the reaction of the reduction of 4-nitrophenol (NPh) to 4-aminophenol (NAf). Nanocatalysts containing Pt/Pd/Fe NPs obtained from a real solution (produced as a result of the leaching of spent automotive catalysts) showed high catalytic activity (86% NPh conversion after 30 min of reaction at pH 11 with 3 mg of the nanocatalyst).


Histological and mutational profile of diffuse gastric cancer: current knowledge and future challenges.
Gastric cancer (GC) pathogenesis is complex and heterogeneous, reflecting morphological, molecular and genetic diversity. Diffuse gastric cancer (DGC) and intestinal gastric cancer (IGC) are the major histological types. GC may be sporadic or hereditary; sporadic GC is related to environmental and genetic low-risk factors and hereditary GC is caused by inherited high-risk mutations, so far identified only for the diffuse histotype. DGC phenotypic heterogeneity challenges the current understanding of molecular mechanisms underlying carcinogenesis. The definition of a DGC-specific mutational profile remains controversial, possibly reflecting the heterogeneity of DGC-related histological subtypes [signet-ring cell carcinoma (SRCC) and poorly cohesive carcinoma not otherwise specified (PCC-NOS)]. Indeed, DGC and DGC-related subtypes may present specific mutational profiles underlying the particularly aggressive behaviour and dismal prognosis of DGC vs IGC and PCC-NOS vs SRCC. In this systematic review, we revised the histological presentations, molecular classifications and approved therapies for gastric cancer, with a focus on DGC. We then analysed results from the most relevant studies, reporting mutational analysis data specifying mutational frequencies, and their relationship with DGC and IGC histological types, and with specific DGC subtypes (SRCC and PCC-NOS). We aimed at identifying histology-associated mutational profiles with an emphasis in DGC and its subtypes (DGC vs IGC; sporadic vs hereditary DGC; and SRCC vs PCC-NOS). We further used these mutational profiles to identify the most commonly affected molecular pathways and biological functions, and explored the clinical trials directed specifically to patients with DGC. This systematic analysis is expected to expose a DGC-specific molecular profile and shed light into potential targets for therapeutic intervention, which are currently missing.


Preparation, properties and metabolism of 5,6-monoepoxyretinoic acid.
1. Methyl retinoate has been converted into methyl 5,6-monoepoxyretinoate by reaction with monoperphthalic acid. The epoxy acid ester on alkaline hydrolysis gave 5,6-monoepoxyretinoic acid. 2. Treatment of the 5,6-monoepoxy compounds with ethanolic hydrochloric acid gave the corresponding 5,8-epoxy (furanoid) compounds. 3. With lithium aluminium hydride, the acid and the ester groups were selectively reduced to primary alcohols. 4. Administration of methyl 5,6-monoepoxyretinoate intraperitoneally and subcutaneously had good growth response in vitamin A-deficient rats. 5. 5,6-Monoepoxyretinoic acid, when given intraperitoneally as the sodium salt, was 157% as active as all-trans-retinyl acetate. 6. Methyl 5,6-monoepoxyretinoate was hydrolysed to the epoxy acid by rat-liver homogenate. It had 35% of the biological activity of all-trans-retinyl acetate in the rat when given orally.


Enhancing research with migrant women through focus groups.
Recent systematic reviews of measurement strategies have identified a striking lack of data to support the validity of most questionnaires used with multiethnic, migrant populations. In the context of two ongoing research studies examining the reproductive health needs of migrant women in Canada, cultural validation was required for proposed study questionnaires and protocols in a total of 13 languages. Multilingual, multiethnic women with various migrant profiles were recruited from the community to review research materials in a series of focus groups. Recommendations by these women were made in relation to consent and interpretation procedures, development of trust in research, home visits after birth, approaches to sensitive topics, inclusion of discrimination as a research variable, and reimbursement of participants. Preliminary work applying focus-group methods to mixed ethno-cultural groups yielded valuable information on appropriateness of planned research.


Circadian rhythms in the thermophilic cyanobacterium Thermosynechococcus elongatus: compensation of period length over a wide temperature range.
Proteins derived from the thermophilic cyanobacterium Thermosynechococcus elongatus BP-1, which performs plant-type oxygenic photosynthesis, are suitable for biochemical, biophysical, and X-ray crystallographic studies. We developed an automated bioluminescence real-time monitoring system for the circadian clock in the thermophilic cyanobacterium T. elongatus BP-1 that uses a bacterial luciferase gene set (Xl luxAB) derived from Xenorhabdus luminescens as a bioluminescence reporter gene. A promoter region of the psbA1 gene of T. elongatus was fused to the Xl luxAB gene set and inserted into a specific targeting site in the genome of T. elongatus. The bioluminescence from the cells of the psbA1-reporting strain was measured by an automated monitoring apparatus with photomultiplier tubes. The strain exhibited the circadian rhythms of bioluminescence with a 25-h period length for at least 10 days in constant light and temperature. The rhythms were reset by light-dark cycle, and their period length was almost constant over a wide range of temperatures (30 to 60 degrees C). Theses results indicate that T. elongatus has the circadian clock that is widely temperature compensated.


The neural processing of moral sensitivity to issues of justice and care.
The empirical and theoretical consideration of ethical decision making has focused on the process of moral judgment; however, a precondition to judgment is moral sensitivity, the ability to detect and evaluate moral issues [Rest, J. R. (1984). The major components of morality. In W. Kurtines & J. Gewirtz (Eds.), Morality, moral behaviour, and moral development (pp. 24-38). New York, NY: Wiley]. Using functional magnetic resonance imaging (fMRI) and contextually standardized, real life moral issues, we demonstrate that sensitivity to moral issues is associated with activation of the polar medial prefrontal cortex, dorsal posterior cingulate cortex, and posterior superior temporal sulcus (STS). These activations suggest that moral sensitivity is related to access to knowledge unique to one's self, supported by autobiographical memory retrieval and social perspective taking. We also assessed whether sensitivity to rule-based or "justice" moral issues versus social situational or "care" moral issues is associated with dissociable neural processing events. Sensitivity to justice issues was associated with greater activation of the left intraparietal sulcus, whereas sensitivity to care issues was associated with greater activation of the ventral posterior cingulate cortex, ventromedial and dorsolateral prefrontal cortex, and thalamus. These results suggest a role for access to self histories and identities and social perspectives in sensitivity to moral issues, provide neural representations of the subcomponent process of moral sensitivity originally proposed by Rest, and support differing neural information processing for the interpretive recognition of justice and care moral issues.


Comparison of self-reported and measured range of motion in total knee arthroplasty patients.
Total knee arthroplasty (TKA) is an established method used in the treatment of end-stage knee osteoarthritis. Range of motion (ROM) and relief from pain show success of TKA. One of the most important aims of this treatment is to achieve an adequate ROM. Numerous outcome instruments and patient-reported questionnaires are in use to evaluate of TKA patients. For this purpose, disease-specific questionnaires and self-reported ROM and function evaluation tools are also being developed. The most important criteria in musculoskeletal care is assessing the joint mobility of the patient's. Joint mobility can be measured with visual estimates, universal goniometer, X-ray radiography, digital gravity goniometers and applications found in smart phones. Apart from the reliability and validity of the method, obtaining the same results from different examiners is very important. The clinical follow-up of patients is an important part of postoperative care after TKA. The follow-up interval and duration remain dependent on the physician's anticipation of the clinical progress of the individual patient. Long-term surveillance of joint arthroplasty is necessary, but it has also become increasingly burdensome as greater numbers of TKAs are performed, and in younger populations. Patient self-reported questionnaires and self-goniometric measurement are used by many investigators to decrease this burden on the surgeon or staff, and in combination with telemedicine radiographs might be a reasonable option to routine clinic visits. They could reasonably be expected to lower the burden on both the patient and the clinician without eliminating contact and thus sacrificing quality of care. At the same time, it would reduce the financial burden too. Self-reported measured ROM can use in the routine follow-ups to reduce surgeons, physiotherapist and other staff.


Extinction and survival in two-species annihilation.
We study diffusion-controlled two-species annihilation with a finite number of particles. In this stochastic process, particles move diffusively, and when two particles of opposite type come into contact, the two annihilate. We focus on the behavior in three spatial dimensions and for initial conditions where particles are confined to a compact domain. Generally, one species outnumbers the other, and we find that the difference between the number of majority and minority species, which is a conserved quantity, controls the behavior. When the number difference exceeds a critical value, the minority becomes extinct and a finite number of majority particles survive, while below this critical difference, a finite number of particles of both species survive. The critical difference Δ_{c} grows algebraically with the total initial number of particles N, and when N≫1, the critical difference scales as Δ_{c}∼N^{1/3}. Furthermore, when the initial concentrations of the two species are equal, the average number of surviving majority and minority particles, M_{+} and M_{-}, exhibit two distinct scaling behaviors, M_{+}∼N^{1/2} and M_{-}∼N^{1/6}. In contrast, when the initial populations are equal, these two quantities are comparable M_{+}∼M_{-}∼N^{1/3}.


Comparison of muscle activity during sit-to-stand movement at different chair heights between obese and normal-weight subjects.
The purpose of present study was to compare the tibialis anterior (TA), rectus femoris (RF), and erector spinae (ES) muscle activities at variety chair height during sit-to-stand (STS) on normal weight and obese subjects. Also, we compared the muscle activity difference between the normal weight and obese subjects. The study included 26 subjects (normal weight 13 and obese 13). Each subject performed STS at three chair heights (40 cm, 50 cm, 60 cm) and TA, RF, and ES muscle activities measured. According to the results of the measurement, muscle activation of TA showed significantly higher than RF and ES muscle activation during STS at all chair heights on obese subjects. The muscle activation of TA showed significantly higher than RF muscle activation during STS at all chair heights on normal weight subjects. The muscle activation of RF and ES showed significantly higher in normal weight subjects than obese subjects at 40 cm and 50 cm of chair heights. However, the TA muscle activation showed no significant difference between normal weight subjects and obese subjects. This study's results suggested that obese subjects should practice the use of RF and ES muscles in a low-height chair during STS.


Carboxypeptidase N and creatine kinase-MB isoforms in acute myocardial infarction.
The aims of our study were to evaluate the plasma carboxypeptidase N activity in normal subjects and in patients with acute myocardial infarction and to delineate its relationship with creatine kinase-MB isoforms in monitoring of acute myocardial infarction, carboxypeptidase N being the major determinant of creatine kinase isoform conversion in plasma. The study was carried out in 34 healthy subjects and 19 patients with acute myocardial infarction diagnosed according to the World Health Organization (WHO) criteria in which the blood samples were collected immediately upon admission to the coronary care unit (median time 3.5 hours), every 4 to 6 hours for 24 hours, and every 12 hours until the third day post admission. Carboxypeptidase N activity, total creatine kinase, creatine kinase-MB mass concentration and creatine kinase-MB isoforms were determined in each sample from acute myocardial infarction patients, whereas only carboxypeptidase N and total creatine kinase activities were assayed in samples from healthy subjects. The results showed a high variability in carboxypeptidase N values among healthy subjects (median = 200 U/l; interquartile range = 190-247 U/l) and in the first available samples from acute myocardial infarction patients (median = 213 U/l; interquartile range = 234 U/l) without significant differences between groups and without a correlation between carboxypeptidase N and creatine activities either in healthy subjects or in acute myocardial infarction patients; in the latter group, however, a significant correlation (p < 0.01) with creatine kinase-MB calculated on all samples, was observed. In acute myocardial infarction patients carboxypeptidase N showed time-related variations, reaching the highest levels about 48 h after onset of chest pain. A statistically significant difference in carboxypeptidase N values (p = 0.0001) was found before and after creatine kinase-MB peak values as well as before and after MB2/MB1 normalization. Worthy of note is the finding that in two acute myocardial infarction patients presenting MB2/MB1 ratios lower than the cutoff value (1.5) throughout the period of observation, the baseline values for carboxypeptidase N were higher than in other patients studied. Our results suggest that the increase of carboxypeptidase N activity after infarction could be induced by an increase in endogenous substrate concentrations, in particular creatine kinase-MB released from damaged myocardium. Furthermore, high baseline levels of carboxypeptidase N will reduce the diagnosis efficiency of creatine kinase-MB isoforms in the diagnosis of acute myocardial infarction.


Palm olein oil produces less lipid peroxidation products than soya bean oil.
The soleus muscles of hyperthyroid rats were used to investigate the effect of palm olein oil and soya bean oil on the production of lipid peroxidation products. It was found that palm olein oil but not soya bean oil significantly decreased malonaldehyde and conjugated diene levels of the soleus muscles of hyperthyroid rats. These findings suggest that palm olein per se produces less lipid peroxidation products than soya bean oil. Such an assay method gives a composite net picture of the propensity of an oil to produce lipid peroxidation products.


Possible antiretroviral therapy-warfarin drug interaction.
Highly active antiretroviral therapy (HAART) for human immunodeficiency virus (HIV) has resulted in significant morbidity and mortality reductions. Lifelong antiretroviral therapy must be incorporated into each patient's medical regimen. Patients with HIV may also have simultaneous chronic medical conditions, resulting in the possibility of complex drug-drug interactions. We report a possible drug-drug interaction between HAART and warfarin in two patients, as assessed by the Naranjo adverse drug reaction probability scale and the Drug Interaction probability scale. Both patients' pharmacotherapy regimens included a nonnucleoside reverse transcriptase inhibitor (NNRTI), nevirapine, or a protease inhibitor, nelfinavir or lopinavir-ritonavir, and two nucleoside analogs. In both patients, high warfarin doses were required to maintain therapeutic international normalized ratios (INRs). Warfarin has two enantiomers, R-and S-warfarin, which are substrates primarily of cytochrome P450 (CYP) 3A4 (R-warfarin), CYP1A2 (R-warfarin), and CYP2C9 (S-warfarin). Protease inhibitors and NNRTIs have variable effects on CYP: induction, inhibition, or mixed. The increased warfarin doses required in these two patients may have been caused by induction of CYP3A4 by nevirapine, CYP2C9 by nelfinavir, or CYP2C9 by lopinavir-ritonavir. Thus, practitioners should prudently monitor INRs in patients receiving warfarin with concomitant HAART that includes either a protease inhibitor or an NNRTI.


Static and elevated pollen traps do not provide an accurate assessment of personal pollen exposure.
Background. Volumetric pollen traps are commonly used to assess pollen exposure. These traps are well suited for estimating the regional mean airborne pollen concentration but are likely not to provide an accurate index of personal exposure. In this study, we tested the hypothesis that hair sampling may provide different pollen counts from those from pollen traps, especially when the pollen exposure is diverse. Methods. We compared pollen counts in hair washes to counts provided by stationary volumetric and gravimetric pollen traps in 2 different settings: urban with volunteers living in short distance from one another and from the static trap and suburban in which volunteers live in a scattered environment, quite far from the static trap. Results. Pollen counts in hair washes are in full agreement with trap counts for uniform pollen exposure. In contrast, for diverse pollen exposure, .individual pollen counts in hair washes vary strongly in quantity and taxa composition between individuals and dates. These results demonstrate that the pollen counts method (hair washes vs. stationary pollen traps) may lead to different absolute and relative contributions of taxa to the total pollen count. Conclusions. In a geographic area with a high diversity of environmental exposure to pollen, static pollen traps, in contrast to hair washes, do not provide a reliable estimate of this higher diversity.


Environment-Dependent Stability and Mechanical Properties of DNA Origami Six-Helix Bundles with Different Crossover Spacings.
The internal design of DNA nanostructures defines how they behave in different environmental conditions, such as endonuclease-rich or low-Mg2+ solutions. Notably, the inter-helical crossovers that form the core of such DNA objects have a major impact on their mechanical properties and stability. Importantly, crossover design can be used to optimize DNA nanostructures for target applications, especially when developing them for biomedical environments. To elucidate this, two otherwise identical DNA origami designs are presented that have a different number of staple crossovers between neighboring helices, spaced at 42- and 21- basepair (bp) intervals, respectively. The behavior of these structures is then compared in various buffer conditions, as well as when they are exposed to enzymatic digestion by DNase I. The results show that an increased number of crossovers significantly improves the nuclease resistance of the DNA origami by making it less accessible to digestion enzymes but simultaneously lowers its stability under Mg2+ -free conditions by reducing the malleability of the structures. Therefore, these results represent an important step toward rational, application-specific DNA nanostructure design.


An interaction between {alpha}v{beta}8 integrin and Band 4.1B via a highly conserved region of the Band 4.1 C-terminal domain.
alphavbeta8 Integrin is highly expressed in the vertebrate CNS, and mice lacking the alphav or beta8 genes develop cerebral hemorrhage due to defective interactions between blood vessels and alphavbeta8-expressing neural cells. Although alphavbeta8 binds many of the same extracellular matrix protein ligands as other integrins, very little is known about the intracellular signal transduction events used by alphavbeta8 to regulate CNS development. Here we identify Band 4.1B as an intracellular factor that interacts selectively with the beta8 cytoplasmic tail. The association with alphavbeta8 occurs via the band 4.1B C-terminal domain, a region highly conserved among the various Band 4.1 family members. Indeed, we show that beta8 integrin interacts directly with the C-terminal domains of several Band 4.1 proteins and colocalizes with them in cultured astrocytes and in the brain. These data identify a previously uncharacterized interaction between an integrin and Band 4.1 family members and suggest an important functional role for alphavbeta8-Band 4.1 interactions in the development and maintenance of the CNS.


Factors Controlling Floc Formation and Structure in the Cyanobacterium Synechocystis sp. Strain PCC 6803.
Motile strains of the unicellular cyanobacterium Synechocystis sp. strain PCC 6803 readily aggregate into flocs, or floating multicellular assemblages, when grown in liquid culture. As described here, we used confocal imaging to probe the structure of these flocs, and we developed a quantitative assay for floc formation based on fluorescence imaging of 6-well plates. The flocs are formed from strands of linked cells, sometimes packed into dense clusters but also containing voids with very few cells. Cells within the dense clusters show signs of nutrient stress, as judged by the subcellular distribution of green fluorescent protein (GFP)-tagged Vipp1 protein. We analyzed the effects on flocculation of a series of mutations that alter piliation and motility, including Δhfq, ΔpilB1, ΔpilT1, and ΔushA mutations and deletion mutations affecting major and minor pilins. The extent of flocculation is increased in the hyperpiliated ΔpilT1 mutant, but active cycles of pilus extension and retraction are not required for flocculation. Deletion of PilA1, the major subunit of type IV pili, has no effect on flocculation; however, flocculation is lost in mutants lacking an operon coding for the minor pilins PilA9 to -11. Therefore, minor pilins appear crucial for flocculation. We show that flocculation is a tightly regulated process that is promoted by blue light perception by the cyanobacteriochrome Cph2. Floc formation also seems to be a highly cooperative process. A proportion of nonflocculating Δhfq cells can be incorporated into wild-type flocs, but the presence of a high proportion of Δhfq cells disrupts the large-scale architecture of the floc.IMPORTANCE Some bacteria form flocs, which are multicellular floating assemblages of many thousands of cells. Flocs have been relatively little studied compared to surface-adherent biofilms, but flocculation could play many physiological roles, be a crucial factor in marine carbon burial, and enable more efficient biotechnological cell harvesting. We studied floc formation and architecture in the model cyanobacterium Synechocystis sp. strain PCC 6803, using mutants to identify specific cell surface structures required for floc formation. We show that floc formation is regulated by blue and green light perceived by the photoreceptor Cph2. The flocs have a characteristic structure based on strands of linked cells aggregating into dense clusters. Cells within the dense clusters show signs of nutrient stress, pointing to a disadvantage of floc formation.


pH-induced vesicle-to-micelle transition in amphiphilic diblock copolymer: investigation by energy transfer between in situ formed polymer embedded gold nanoparticles and fluorescent dye.
The ability to regulate the formation of nanostructures through self-assembly of amphiphilic block copolymers is of immense significance in the field of biology and medicine. In this work, a new block copolymer synthesized by using reversible addition-fragmentation chain transfer (RAFT) polymerization technique from poly(ethylene glycol) monomethyl ether acrylate (PEGMA) and Boc-l-tryptophan acryloyloxyethyl ester (Boc-l-trp-HEA) was found to spontaneously form pH-responsive water-soluble nanostructures after removal of the Boc group. While polymer vesicles or polymerosomes were formed at physiological pH, the micelles were formed at acidic pH (< 5.2), and this facilitated a pH-induced reversible vesicle-to-micelle transition. Formation of these nanostructures was confirmed by different characterization techniques, viz. transmission electron microscopy, dynamic light scattering, and steady-state fluorescence measurements. Further, these vesicles were successfully utilized to reduce HAuCl4 and stabilize the resulting gold nanoparticles (AuNPs). These AuNPs, confined within the hydrophobic shell of the vesicles, could participate in energy transfer process with fluorescent dye molecules encapsulated in the core of the vesicles, thus forming a nanometal surface energy transfer (NSET) pair. Subsequently, following the efficiency of energy transfer between this pair, it was possible to monitor the process of transition from vesicles to micelles. Thus, in this work, we have successfully demonstrated that NSET can be used to follow the transition between nanostructures formed by amphiphilic block copolymers.


Chronic myelomonocytic leukemia with antecedent refractory anemia with excess blasts: further evidence for the arbitrary nature of current classification systems.
From a retrospective analysis of our series of myelodysplastic patients, we found 16 patients who were initially diagnosed as having a refractory anemia with excess of blasts (RAEB) according to FAB criteria, but later on (median time 4 months, range 2-8) developed a peripheral monocytosis >1 x 10(9)/L, leading to a disease re-classification into a dysplastic type of chronic myelomonocytic leukemia (MD-CMML). Analysis of clinical and prognostic aspects in this subgroup of patients as compared with those of primarily diagnosed MD-CMML patients, showed some significant differences in Hb level, platelet count, percentage of immature circulating precursor (IPC), bone marrow blastosis and trilineage dysplasia. Median survival for present group of patients was 33 months compared with 20 months for MD-CMML. Different prognostic scores were applied for evaluation of risk distribution and relative impact on survival prediction. We suggest on a possible atypical presentation of CMML and indicate a careful attention to be addressed to myelodysplastic patients who develop peripheral monocytosis, who might have a CMML variant, with more favourable prognosis and prolonged survival. Furthermore, we believe this is a further evidence for the arbitrary nature of current classification systems, which definitely exclude CMML from myelodysplastic syndromes.


New regiospecific isothiazole C-C coupling chemistry.
Regioselective palladium catalysed coupling reactions are achieved in good to high yields, starting from either 3,5-dichloro- or 3,5-dibromoisothiazole-4-carbonitriles 1 and 2, providing 3-halo-5-(hetero/aryl, alkenyl and alkynyl)isothiazoles 3, 4, 6-9 from Stille couplings, 3-halo-5-(hetero/arylethynyl)isothiazoles 14-19 from Sonogashira and 5,5'-bi(3-chloroisothiazole-4-carbonitrile) (13) from an Ullmann type coupling. 3,5-Dibromoisothiazole-4-carbonitrile 2 is more reactive than the dichloroisothiazole-4-carbonitrile 1 and effective enough for Stille, Negishi and Sonogashira couplings. 5,5-Bi(3-chloroisothiazole-4-carbonitrile) (13) is prepared by a palladium catalysed Ullmann coupling from 3-chloro-5-iodoisothiazole-4-carbonitrile (11). A variety of 3-substituted isothiazoles (3-substituents = Cl, Br, OMs, OTs and OTf) are less reactive and fail to give successful Suzuki couplings at the isothiazole C-3 position. The 3-iodo-5-phenyl-isothiazole-4-carbonitrile (28), prepared via Sandmeyer iodination, participates successfully in Suzuki, Ullmann type, Stille, Negishi and Sonogashira coupling reactions. All products are fully characterized.


Resurrection of steroids for sepsis resuscitation.
Corticosteroids were proposed to treat patients with severe sepsis as early as 1940. A summary of all available randomized controlled trials performed between 1966 and 1993 was provided in two systematic review that recommended to abandon the use of high dose coricosteroids to treat patients with severe infection. Nonetheless, a doubt still persist regarding the efficacy of a strategy of replacement therapy in cathecolamines-dependent shock. This strategy relies mainly on the concept that septic shock may be complicated by 1) an occult adrenal insufficiency, 2) a glucocorticoid peripheral resistance syndrome. Some studies demonstrated the effect of replacement therapy with hydrocortisone on the sistemic inflammatory response and on the cardiovascular function during sepsis. The effect of this therapy on survival to septic shock is controversial both in recent and old studies. Finally a recently completed multicenter, placebo controlled, randomized, double-blind study has evaluated the efficacy and tolerance of a replacement therapy with a combination of hydrocortisone (50 mg intravenous bolus four times per day) and fludrocortisone (50 g orally once a day) given for 7 days. This study included 300 catecholamines- and ventilator-dependent septic shock. The authors found a significant reduction in 28-day mortality in patient with occult renal insufficiency. In sum, short course with high doses of corticosteroids should not be given in severe sepsis, except for specific entitles like severe typhoid fever, pneumocystis carinii pneumonia in AIDS or bacterial meningitis in children. The rational for a replacement therapy with hydrocortisone in catecholamines-dependent septic shock grows stronger.


Short- and long-term wildfire threat when adapting infrastructure for wildlife conservation in the boreal forest.
Managers designing infrastructure in fire-prone wildland areas require assessments of wildfire threat to quantify uncertainty due to future vegetation and climatic conditions. In this study, we combine wildfire simulation and forest landscape composition modeling to identify areas that would be highly susceptible to wildfire around a proposed conservation corridor in Québec, Canada. In this measure, managers have proposed raising the conductors of a new 735-kV hydroelectric powerline above the forest canopy within a wildlife connectivity corridor to mitigate the impacts to threatened boreal woodland caribou (Rangifer tarandus). Retention of coniferous vegetation, however, can increase the likelihood of an intense wildfire damaging powerline infrastructure. To assess the likelihood of high-intensity wildfires for the next 100 years, we evaluated three time periods (2020, 2070, 2120), three climate scenarios (observed, RCP 4.5, RCP 8.5), and four vegetation projections (static, no harvest, extensive harvesting, harvesting excluded in protected areas). Under present-day conditions, we found a lower probability of high-intensity wildfire within the corridor than in other parts of the study area, due to the protective influence of a nearby, poorly regenerated burned area. Wildfire probability will increase into the future, with strong, weather-induced inflation in the number of annual ignitions and wildfire spread potential. However, a conversion to less-flammable vegetation triggered by interactions between climate change and disturbance may attenuate this trend. By addressing the range of uncertainty of future conditions, we present a robust strategy to assist in decision-making about long-term risk management for both the proposed conservation measure and the powerline.


Unsupervised Monocular Depth Estimation from Light Field Image.
Learning based depth estimation from light field has made significant progresses in recent years. However, most existing approaches are under the supervised framework, which requires vast quantities of ground-truth depth data for training. Furthermore, accurate depth maps of light field are hardly available except for a few synthetic datasets. In this paper, we exploit the multi-orientation epipolar geometry of light field and propose an unsupervised monocular depth estimation network. It predicts depth from the central view of light field without any ground-truth information. Inspired by the inherent depth cues and geometry constraints of light field, we then introduce three novel unsupervised loss functions: photometric loss, defocus loss and symmetry loss. We have evaluated our method on a public 4D light field synthetic dataset. As the first unsupervised method published in the 4D Light Field Benchmark website, our method can achieve satisfactory performance in most error metrics. Comparison experiments with two state-of-the-art unsupervised methods demonstrate the superiority of our method. We also prove the effectiveness and generality of our method on real-world light-field images.


Randomized clinical trial comparing lumbar percutaneous hydrodiscectomy with lumbar open microdiscectomy for the treatment of lumbar disc protrusions and herniations.
Hydrodiscectomy is a new technique used for percutaneous spinal discectomy that employs a high-intensity stream of water for herniated disc ablation and tissue aspiration. No previous clinical study has examined the effects of percutaneous hydrodiscectomy. The aim of this study is to evaluate the outcomes of hydrodiscectomy compared to open microdiscectomy regarding pain, function, satisfaction, complications and recurrence rates. In this randomized clinical trial, patients referred to our tertiary hospital for lumbar back pain were recruited and included in the study if they had disc protrusion or small herniation in only one level, without neurological deficits and with no resolution after six weeks of conservative treatment. One group underwent open microdiscectomy, and the other group underwent percutaneous microdiscectomy via hydrosurgery. Function was evaluated using the Oswestry Disability Index and pain was assessed using a visual analog scale. Evaluations were performed preoperatively, and then during the first week and at one, three, six and twelve months postoperatively. Personal satisfaction was verified. Clinicaltrials.gov: NCT01367860. During the study period, 20 patients were included in each arm and 39 completed one-year of follow-up (one patient died of unrelated causes). Both groups exhibited equal improvement on the visual analog scale and Oswestry evaluations after treatment, without any significant differences. The improvement in the lumbar visual analog scale score was not significant in the hydrodiscectomy group (p=0.138). The rates of infection, pain, recurrence and satisfaction were similar between the two groups. Percutaneous hydrodiscectomy was demonstrated to be as effective as open microdiscectomy for reducing pain. The rates of complications and recurrence of herniation were similar between groups. Patient satisfaction with the treatment was also similar between groups.


Muscle infarction in diabetes: clinical manifestations and course.
To characterize the initial manifestations and course of muscle infarction in diabetes, a rarely diagnosed condition. We describe two patients with this disorder and review the clinical characteristics of previously reported cases. Usually, the initial complaint in patients with muscle infarction in diabetes is swelling of the thigh or calf that has evolved over days to months. Biopsy of the muscle is often necessary for diagnosis and reveals extensive muscle necrosis. Although the pathogenesis is unknown, hypercoagulability may have a role. Bilateral involvement and recurrent disease are common. Treatment is supportive; our patients required narcotics for alleviation of pain. Muscle infarction in diabetes may mimic thrombophlebitis, soft tissue infection, or a neoplasm. Medical evaluation may be directed toward these entities, and the diagnosis of a diabetes-associated disorder may be completely overlooked. The presence of atraumatic swelling of an extremity in a patient with diabetes should suggest diabetes-related muscle infarction.


Primary colorectal inflammatory myofibroblastic tumour: a clinicopathological and immunohistochemical study of seven cases.
Primary colorectal inflammatory myofibroblastic tumours are rare. Here we report seven such cases to demonstrate their clinicopathological features and prognosis. Clinical and pathological data of seven cases of colorectal inflammatory myofibroblastic tumour were reviewed. Immunohistochemical staining was also performed. The presenting symptoms included abdominal or pelvic mass (7 patients), abdominal pain (7 patients), and lower gastrointestinal haemorrhage (2 patients). The tumour size ranged from 3.8 cm to 6.3 cm in greatest dimension. Histologically these tumours showed three patterns: myxoid hypocellular, fascicular, and hyalinised pattern. A lymphoplasmacytic infiltrate was present in all seven tumours. Mitotic figures were 0 approximately 2 per 10 high power fields (HPF) in five cases and were focally up to 4 approximately 6 per 10 HPF in two tumours. Nuclear atypia was mild in five and moderate focally in two tumours. Necrosis was absent. Anaplastic lymphoma kinase (ALK), smooth muscle actin, and vimentin staining were present in all tumours. S100, CD21, CD34, CD35, desmin, CK, CD68, and CD117 were negative in all inflammatory myofibroblastic tumours. The patients were followed up for 3-8 years (mean 4.9 years). Five patients were alive without evidence of disease after tumour resection. Two patients had a tumour recurrence 14 and 18 months after the initial surgery, respectively. A second surgical resection was performed for the recurrent tumours and the patients have been free of disease since (now 22 and 35 months after the second surgery, respectively). Colorectal inflammatory myofibroblastic tumours are rare, benign or low malignant tumours and ALK positivity is helpful in pathological diagnosis.


Biosynthesis of silver and platinum nanoparticles using orange peel extract: characterisation and applications.
This study focuses on the green synthesis of noble metal nanoparticles (silver (Ag) and platinum (Pt)) and how the size and shape of the nanoparticles produced can be controlled through changes in the initial pH value of the precursor solution. The nanoparticles were characterised by ultra-violet-visible spectroscopy, transmission electron microscopy and X-ray diffraction. This simple and environmentally friendly method allows the synthesis of diverse nanostructures in the absence of a surfactant or polymer to direct nanoparticle growth, and without externally adding seed crystallites. The antibacterial effects of Ag nanoparticles and catalytic properties of Pt nanoparticles were explored for future promising biotechnological approaches in different fields.


Shedding Light on Bacterial Physiology with Click Chemistry.
Bacteria constitute a major lifeform on this planet and play numerous roles in ecology, physiology, and human disease. However, conventional methods to probe their activities are limited in their ability to visualize and identify their functions in these diverse settings. In the last two decades, the application of click chemistry to label these microbes has deepened our understanding of bacterial physiology. With the development of a plethora of chemical tools that target many biological molecules, it is possible to track these microorganisms in real-time and at unprecedented resolution. Here, we review click chemistry, including bioorthogonal reactions, and their applications in imaging bacterial glycans, lipids, proteins, and nucleic acids using chemical reporters. We also highlight significant advances that have enabled biological discoveries that have heretofore remained elusive.


Partnerships and Collaborations: The Right Alliances for Clinical Trials in Africa.
Africa attracts < 1% of all trials conducted around the world. The implication is that proof of safety and efficacy in Africans is lacking for a lot of new therapies. The sizeable proportion of approximately 20% of the global population that Africa represents largely does not have empiric data to support use of new therapies in a population with a distinct genetic and racial profile. Beyond the imperative of evidence-based interventions, Africans carry a disproportionately heavy burden of certain diseases, including prostate cancer, sickle cell anemia, and malaria. It therefore provides opportunity for efficient recruitment of participants for trials for such diseases. However, this advantage has not convinced sponsors to carry out clinical trials in Africa. India and China each have roughly the same population size as Africa, but each presents just one regulatory jurisdiction for clinical trials. Africa has 54 countries, and a sponsor would theoretically need to file 54 different applications to cover the entire continent. Collaboration and partnership among all stakeholders in the clinical trial ecosystem will reduce the burden on sponsors and make Africa competitive as a destination for clinical trials. Collaboration among national regulatory agencies will enable Africa to be treated as one regulatory jurisdiction and reduce administrative burden. Sites and researchers can partner to improve quality, attain necessary certifications, and increase overall efficiency. Central to all of these are clinical research organizations that can coordinate and work across borders to make clinical trial projects seamless. Ultimately, patients will benefit as quality of clinical practice improves and access to new therapies is enhanced.


Trap-Filling Magnetoconductance as an Initialization and Readout Mechanism of Triplet Exciton Spins.
Photoexcited triplet states are promising candidates for hybrid qubit systems, as they can be used as a controlling gate for nuclear spins. But microwave readout schemes do not generally offer the sensitivity needed to approach the single-molecule limit or the scope to integrate such systems into devices. Here, we demonstrate the possibility of electrical readout of triplet spins at room temperature through a specific mechanism of magnetoconductance (MC) in polycrystalline pentacene. We show that hole-only pentacene devices exhibit a positive photoinduced MC response that is consistent with a trap-filling mechanism. Spin and magnetic-field-dependent quenching of photogenerated triplets by holes quantitatively explains the MC response we observe. These results are distinct in both sign and proposed mechanism compared to previous reports on polyacene materials and provide clear design rules for future spintronic devices based on this spin-sensing mechanism.


[Progress in the research of therapeutic enzyme].
With the development of the research on biotechnology and modern pharmacy, the application of enzyme drugs have grown rapidly and enzyme drugs have become an important branch of biopharmaceutics. In this article, some new varieties of therapeutic enzymes, enzyme targets, mechanisms and new technologies of application in therapeutic enzymes were reviewed, and the direction of development of therapeutic enzymes were discussed.


Quantifying Visible-Light-Induced Electron Transfer Properties of Single Dye-Sensitized ZnO Entity for Water Splitting.
Quantifying the photoinduced electron transfer properties of a single entity is of paramount importance for clarifying the link between the photoelectrochemical performance and the specific properties of an individual. Here, we successfully monitored the photoelectrochemical behavior of a single dye-sensitized ZnO entity on a Au ultramicroelectrode with different TiO2 film thicknesses. Due to a trap-limited electron diffusion in TiO2 film, a sub-millisecond photocurrent transient was observed for an individual N719@ZnO associated with single-particle photocatalytic water splitting. Furthermore, a Monte Carlo random walk numerical simulation model was developed to simulate the photoinjected electron transport dynamics and recombination in a nanoparticulate TiO2 film. Our approach allowed the photocatalytic properties of N719 at the single-molecule level to be quantified, and electron diffusivity and electron collection efficiency as a function of the film thickness were estimated by simulation analyses. Excellent agreement was obtained between the experimental results and theoretical simulations, indicating that the underlying photoinduced electron transfer processes can be reliably explored.


How Ethical Leadership Prompts Employees' Voice Behavior? The Roles of Employees' Affective Commitment and Moral Disengagement.
Previous literature has demonstrated that ethical leadership could predict employees' voice behavior. However, it's not clear how to heighten these positive effects of ethical leadership on employees' voice behavior. Building on the AET and moral disengagement studies, we developed an integrated model. A three-wave field study (N = 232) investigated the relationship between ethical leadership and voice behavior by focusing on the mediating role of employees' affective commitment and the moderating role of employees' moral disengagement. Our matched data analysis results indicated that: (1) employees' affective commitment partly mediated the relationship between ethical leadership and employees' voice behavior. In addition, employees' moral disengagement moderated (2) the effect of ethical leadership on employees' affective commitment and (3) the effect of employees' affective commitment on voice behavior, similarly, (4) the indirect effect of ethical leadership on employees' voice behavior via employees' affective commitment. Theoretical and practical implications of these results are discussed.


Pyrrolidine PNA-DNA chimeric oligonucleotides with extended backbone.
Cis-D-2-hydroxy-4-thymin-1-yl-pyrrolidine propionic acid unit is used to make PNA-DNA dimer block that is incorporated in DNA sequences at selected positions. Since the amide linkage is shorter than phosphodiester linkage, insertion of an extra atom in the backbone with amide linkage seems to be better accommodated for internucleotide distance-complementarity.


AICRG, Part IV: Patient satisfaction reported for Ankylos implant prostheses.
Although many maxillary dentures exhibit sufficient retention and stability for patients to adapt well to them, mandibular dentures present a major challenge. The introduction of the endosseous dental implant provided the opportunity for the patient to have esthetic replacements (implant prostheses) that were retentive and stable for all missing natural teeth. This paper reports on the satisfaction of over 470 patients with implant prostheses fabricated using a new and innovative implant design (Ankylos, Dentsply-Friadent, Mannheim, Germany). A total of 1500 Ankylos implants were placed, restored, and followed for 3 to 5 years. Patients were asked to respond to a series of questions related to their satisfaction with their new replacements for missing natural teeth. A total of 95.6% of the patients rated chewing ability with Ankylos prosthesis as excellent to good; 92.2% indicated a significant improvement in their ability to chew; 92.6% reported overall clinical function much better than conventional dentures; 99.1% indicated that speech had improved or was not changed; 96.3% indicated hot and cold foods tasted better; 98.8% indicated no pain or discomfort during clinical function; 99.4% liked their new implant prosthesis; 98.0% would seek implant-prostheses treatment again, if necessary; 99.1% would recommend implant prostheses to friends and relatives; and 98.8% indicated the advantages of Ankylos prostheses far exceeded any disadvantages that may exist. Patients indicated that they (1) were highly satisfied with the final results of the replacements for their natural teeth that were retained or supported by this new implant design, (2) would not hesitate to recommend this form of treatment to their friends and relatives, and (3) would not hesitate to seek the same treatment again if necessary in the future.


Understanding pain, part 2: pain management.
This article is the second in a two-part series which explores pain and its management from a physiological perspective. Nurses play an important role in assessing and managing pain. Effective pain management by nurses requires them to have an understanding of the biological basis of the pain interventions which may be used to control pain. This article emphasizes the importance of pain assessment as a precursor for effective pain management and explores the biological basis of pain interventions which contribute to pain control. The role of non-pharmacological approaches in alleviating pain and their actions which contribute to pain relief are explored. The three main types of pharmaceutical agents used, non-opioids, opioids and adjuvant drugs, are introduced and their mechanisms of actions discussed.


The histone gene transcription factor HiNF-P stabilizes its cell cycle regulatory co-activator p220NPAT.
Orderly progression through the cell cycle requires the transcriptional activation of histone genes to support packaging of newly replicated DNA. Induction of human histone gene expression is mediated by a co-activation complex containing transcription factor HiNF-P and its cofactor p220NPAT. Here, using cells synchronized in S-phase and in mitosis, as well as serum-stimulated cells, we have investigated how HiNF-P is regulated during the cell cycle and examined its stability relative to p220NPAT. We find that while HiNF-P is maintained at steady-state levels throughout the cell cycle, both HiNF-P and p220NPAT are actively degraded by the proteasome pathway. Importantly, elevation of HiNF-P levels enhances the stability of its co-activator p220NPAT. The HiNF-P-dependent stabilization of p220NPAT may reinforce signaling through the cyclin E/CDK2/p220NPAT pathway and contribute to coordinate control of histone gene expression.


GENETIC ORGANIZATION AND EVOLUTIONARY HISTORY IN TWO NORTH AMERICAN SPECIES OF CIRSIUM.
Relationships involving progenitor and derivative species pairs have been documented for a number of plant taxa. In this study, we used starch-gel electrophoresis to examine the probable relationship between Cirsium pitcheri, an endemic thistle restricted to the shorelines of the Great Lakes, and Cirsium canescens, a closely related species of the central Great Plains (U.S.A.). The species shared the same enzyme loci but differed greatly in levels of genetic diversity. C. pitcheri was genetically much less variable than its congener, with fewer polymorphic loci and significantly lower heterozygosity. The genetic variation in C. pitcheri represents a depauperate subset of the alleles present in C. canescens, consistent with the hypothesis that the two species represent a progenitor-derivative species pair. We suggest that C. pitcheri migrated into newly created dune habitats in the Great Lakes region near the end of the Wisconsin glaciation and that its low genetic variability results from repeated and probably prolonged population bottlenecks which accompanied its movement.


Simple model for drag reduction.
Direct numerical simulations established that the finite-extension nonlinear-elasticity-Peterlin (FENE-P) model of viscoelastic flows exhibits the phenomenon of turbulent drag reduction which is caused in experiments by dilute polymeric additives. To gain analytic understanding of the phenomenon, we introduce in this paper a simple one-dimensional model of the FENE-P equations. We demonstrate drag reduction in the simple model, and explain analytically the main observations which include (i) reduction of velocity gradients for fixed throughput and (ii) increase of throughput for fixed dissipation.


Phenotypic analysis of Arabidopsis mutants: germination rate under salt/hormone-induced stress.
Abiotic stress, such as high salt or low temperature, adversely affects plant growth and development. Salt stress inhibits seed germination, retards plant growth, and accelerates senescence. Freezing or drought stress can cause cell damage and plant death. The following parameters can be used to evaluate plant tolerance to salt, drought, or freezing stress: root elongation, fresh weight gain, seed germination (described here), electrolyte leakage, or water loss measurement. Several stress mutants have been characterized using these tests, including hos1 and hos2, which show higher expression of some stress-regulated genes when exposed to low-temperature stress; hos5, which shows higher expression of some stress-regulated genes under abscisic acid (ABA) and salt treatments; sfr mutants, which are deficient in freezing tolerance; and eskimo1, which is constitutively freezing-tolerant. This protocol describes a germination assay that can be carried out on seeds subjected to osmotic or hormone-induced stress. The seeds are plated on filter paper saturated with ABA (for hormonal stress) or with NaCl or mannitol (for osmotic stress). The germination rate can be scored on different days; germination is considered to have occurred when the radicles have penetrated the seed coats. The levels of stress suggested in this protocol may need to be adjusted, depending on the ecotype and growth conditions used.


Burden of community-acquired pneumonia in adults over 18 y of age.
This study aimed to determine the economic burden and affecting factors in adult community-acquired pneumonia (CAP) patients (≥ 18 years) by retrospectively evaluating the data of 2 centers in Istanbul province, Turkey. Data of outpatients and inpatients with CAP from January 2013 through June 2014 were evaluated. The numbers of laboratory analyses, imaging, hospitalization days, and specialist visits were multiplied by the relevant unit costs and the costs of the relevant items per patient were obtained. Total medication costs were calculated according to the duration of use and dosage. The mean age was 61.56 ± 17.87 y for the inpatients (n = 211; 48.6% female) and 53.78 ± 17.46 y for the outpatients (n = 208; 46.4% male). The total mean cost was €556.09 ± 1,004.77 for the inpatients and €51.16 ± 40.92 for the outpatients. In the inpatients, laboratory, medication, and hospitalization costs and total cost were significantly higher in those ≥ 65 y than in those <65 y. Besides the hospitalization duration, specialist visit, imaging, laboratory, medication, and hospitalization costs and total cost were significantly higher in those hospitalized more than once than in those hospitalized once. While the specialist visit cost was higher in the inpatients with comorbidities, the imaging cost was higher in the outpatients with comorbidities. CAP poses a higher cost in inpatients, elders, and individuals with comorbidities. Costs can be decreased by rational decisions about hospitalization and antibiotic use according to the recommendations of guidelines and authorities. Vaccination may decrease medical burden and contribute to economy by preventing the disease, especially in risk groups.


Rat pulmonary artery wall injury by chronic intermittent infusions of Escherichia coli endotoxin. Obliterative vasculitis and vascular occlusion.
To examine the effect of intermittent endotoxemia on rat pulmonary artery structure and hemodynamic function we infused purified Escherichia coli endotoxin on four occasions over 3 weeks (at 7-day intervals), through an indwelling catheter placed in the external jugular vein. The fourth infusion of endotoxin was associated with widespread but focal alveolar consolidation, reduced perfusion of small pulmonary arteries by lumen occlusion and obliteration, pulmonary vascular wall injury, and a peripheral leukocytosis (mean +/- SEM total leukocytes, endotoxin 133.5 +/- 23 X 10 mm3, control 12.2 +/- 1.2 X 10 mm3, p less than 0.001) in which polymorphonuclear (PMN) leukocytes predominated at the expense of lymphocytes (p2x less than 0.01). The alveolar wall was thickened and the alveolar space was consolidated by degenerating polymorphonuclear leukocytes, mononuclear cells, lipid laden alveolar macrophages, erythrocytes, fibrin, and cell debris. In regions of alveolar consolidation vessel lumens were either narrowed by subendothelial cell collections that consisted either of mononuclear cells or degenerating mural and inflammatory cells, or they were occluded by degenerating inflammatory cells and cell debris. The walls of occluded vessels were evident only by their residual elastic laminae: remnants of lysed endothelial cells lined the intima and the media consisted of degenerating mural and inflammatory cells. Capillary endothelial cells showed extensive hydropic degeneration and lysis of cell contents. Intimal precursor smooth muscle cells were hypertrophied but were not associated with the appearance of mature smooth muscle cells in the walls of small pulmonary arteries. In regions of less severe alveolar consolidation by inflammatory cells, vessel wall injury was still evident but less marked; precursor smooth muscle cells were hypertrophied; subepithelial and subendothelial collections of fluid and fibrin were present; and plasma membranes of endothelial cells were disrupted. Despite extensive pulmonary vascular injury, chronic intermittent endotoxemia did not produce the structural changes associated with pulmonary hypertension (medial thickening and appearance of medial muscle in previously nonmuscular arteries) nor a significant change in pulmonary artery pressure.


Robotic-assisted radical prostatectomy - the 5-year Romanian experience.
Radical prostatectomy is the standard therapeutic approach for localized prostate cancer. After the implementation of robotic surgery in Romania, the indication extended progressively to locally advanced prostate cancer. Our objective was to evaluate the oncological and functional outcomes in patients undergoing robotic-assisted radical prostatectomy (RARP), 5 years after the first intervention in Romania. Between November 2009 and July 2014, 207 RARPs were performed using the da Vinci SI Surgical System. Perioperative data were prospectively collected. The oncological and functional follow-up was up to 55 months (range 3-55). Patient stratification according to D'Amico risk categories was 16% low risk, 56.7% intermediate risk and 27.3% high risk. Median console time was 210 min (range 160-360). Median blood loss was 300 ml (range 50-1300), transfusion being required in 2.9% of the cases. Histopathological examinations showed pT3 in 40.8% of the cases, with a positive surgical margin rate of 21.1%, 13.6% for pT2, and 32.1% for pT3. Continence rate (0-1 daily safety pad) at 6, 12, 24 and 55 months was 88.3, 88.8, 90.1, and 93.7% respectively. Overall sexual function restoration rate at 6, 12, 24 and 55 months was 41.1, 44.4, 47.4 and 53%, respectively. Biochemical recurrence rate during follow-up was 6.9%. RARP is a minimally invasive therapeutic approach for prostate cancer, with acceptable outcomes, even in countries such as Romania, where the detection rate for localized prostate cancer is lower compared to other European countries due to lack of national screening programs.


Efficacy and safety of dacomitinib in treatment-naïve patients with advanced NSCLC harboring uncommon EGFR mutation: an ambispective cohort study.
About 10% of non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations are harbored as uncommon mutations. This study aimed to explore the efficacy and safety of dacomitinib, a second-generation EGFR tyrosine kinase inhibitor (EGFR-TKIs), in treating uncommon EGFR-mutated advanced NSCLC. Treatment-naïve advanced NSCLC patients treated with dacomitinib at Hunan Cancer Hospital with uncommon EGFR mutations were evaluated. The primary endpoint was progression-free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety. Between December 2019 and December 2021, a total of 16 patients was included. Median PFS was 14.0 (95% CI 4.32-23.7) months, and median OS was not reached. ORR was 68.8% (95% CI 41.3 to 89.0%) and DCR was 93.8% (95%CI 69.8 to 99.8%), including three achieving complete remission (CR) and eight achieving partial remission (PR). Median PFS for patients with brain metastasis was 9.0 (95%CI 6.9 to 11.1) months. Intracranial ORR was 100%, including 2 CR and 4 PR. Major treatment-related adverse events (TRAEs) included rash (87.5%), paronychia (62.5%), oral ulcers (50.0%), and diarrhea (50.0%), none of which were ≥ grade 3 TRAEs. Dacomitinib showed good activity and manageable toxicity in NSCLC patients with uncommon EGFR mutations.


Immature neurons and GABA networks may contribute to epileptogenesis in pediatric cortical dysplasia.
Cortical dysplasia (CD), a frequent pathological substrate of pediatric epilepsy surgery patients, has a number of similarities with immature cortex, such as reduced Mg2+ sensitivity of N-methyl-D-aspartate (NMDA) receptors and the persistence of subplate-like neurons and undifferentiated cells. Because gamma-aminobutyric acid (GABA) is the main neurotransmitter in early cortical development, we hypothesized increased GABA receptor-mediated synaptic function in CD tissue. Infrared videomicroscopy and whole-cell patch clamp recordings were used to characterize the morphology and electrophysiological properties of immature and normal-appearing neurons in slices from cortical tissue samples resected for the treatment of pharmacoresistant epilepsy in children (0.2-14 years). In addition, we examined spontaneous and evoked synaptic activity, as well as responses to exogenous GABA application. We demonstrate both the presence of immature pyramidal neurons and networks in young CD tissue and the predominance of GABA synaptic activity. In addition, spontaneous GABA depolarizations frequently induced action potentials, supporting a potential excitatory role of GABA in CD. Evoked synaptic responses mediated by GABA were also prominent, and bath application of 4-aminopyridine induced rhythmic depolarizations that were blocked by bicuculline. Finally, responses to exogenous application of GABA had depolarized reversal potentials in severe compared to mild and non-CD cases. The present data support the hypothesis that CD shares features of immature cortex, with predominant and potentially excitatory GABA(A) receptor-mediated neurotransmission. These results could partially explain the increased excitability of the cortical network in pediatric CD.


Identification of Patients with Brain Metastases with Favorable Prognosis After Local and Distant Recurrence Following Stereotactic Radiosurgery.
This retrospective study aimed to determine the prognostic factors associated with overall survival after intracranial local and distant recurrence in patients undergoing stereotactic radiosurgery (SRS) for brain metastases. Clinical characteristics and therapeutic parameters of 251 patients, who were treated with initial stereotactic radiosurgery for brain metastases and later experienced intracranial recurrence, were analyzed to identify prognostic factors of post-recurrence overall survival (PROS). A Cox proportional hazard model was applied for univariate and multivariate analyses. Among the 251 patients, the median post-recurrence overall survival was 8 months, and the six-month PROS rate was 60.2%. The interval from initial radiosurgery treatment to intracranial recurrence (hazard ratio [HR]:0.970), the number of brain recurrent tumors (HR:1.245), the number of extracranial metastatic organs (HR:1.183), recursive partition analysis (RPA) (HR:1.778), and Eastern Cooperative Oncology Group Performance Status (ECOG PS) (HR:2.442) were identified as independent prognostic factors. The patients who received local treatment for solitary brain recurrence achieved better survival (the median survival time after recurrence was 22 months). In patients without extracranial metastasis, the median post-recurrence overall survival of the local treatment group was longer than that in the whole brain radiation therapy (WBRT) group (P<0.001) and the systemic therapy group (P<0.001). A shorter interval from initial stereotactic radiosurgery to recurrence, an increasing number of brain recurrences and extracranial metastatic organs, and poor RPA and ECOG PS values are associated with poor post-recurrence prognosis. When the number of brain recurrent tumors and extracranial metastatic organs was limited, local treatment including stereotactic radiosurgery, surgery or intensity-modulated radiation therapy (IMRT) improved the post-recurrence overall survival.


Clinical application of epiderm growth factor in patients with most severe eye burns.
20 eyes of 11 patients suffering from most severe eye burns of grade 4 or worse were treated in addition to various other drugs with epiderm growth factor (EGF) or placebo in a double-blind test. Among 10 eyes treated with EGF, 6 achieved complete regeneration of the corneal epithelium, and 1 additional case, of the conjunctival epithelium. Among the eyes receiving placebo, only 3 out of 10 healed; all of them were also treated with fibronectin. Although in these very difficult cases EGF could not be investigated as a single therapy, and various other undefined factors may have been effective, in the extended course of the disease the period of EGF treatment was marked by a significant better regeneration of the epithelium.


In vivo targeting and multimodal imaging of cerebral amyloid-β aggregates using hybrid GdF3 nanoparticles.
Aim: To propose a new multimodal imaging agent targeting amyloid-β (Aβ) plaques in Alzheimer's disease. Materials & methods: A new generation of hybrid contrast agents, based on gadolinium fluoride nanoparticles grafted with a pentameric luminescent-conjugated polythiophene, was designed, extensively characterized and evaluated in animal models of Alzheimer's disease through MRI, two-photon microscopy and synchrotron x-ray phase-contrast imaging. Results & conclusion: Two different grafting densities of luminescent-conjugated polythiophene were achieved while preserving colloidal stability and fluorescent properties, and without affecting biodistribution. In vivo brain uptake was dependent on the blood-brain barrier status. Nevertheless, multimodal imaging showed successful Aβ targeting in both transgenic mice and Aβ fibril-injected rats.


Deaths in custody revisited.
This study has surveyed deaths that have occurred while in police custody in Metropolitan Dade County from 1956 to 1982. Cases were then subdivided by age, race, sex, cause, and manner of death as well as place of death or incident leading to the victim's demise. The results of this study indicate that natural disease--predominantly cardiocerebral vascular and alcohol-related--was most common followed by suicides and accidents. The natural deaths occurred in an older age group, whereas suicides occurred in a younger age group. Racially, most deaths in all categories involved white people. Accidents were given an historical perspective with an admonition to the reader to document all findings should a case be presented to them. Homicides and unclassified deaths were infrequent and axiomatically a function of the facilities studied.


[Characterization of eosinophils in soft tissue eosinophilic granuloma].
Soft tissue eosinophilic granuloma assumes the form of a poorly-demarcated painless mass, and is characterized by marked eosinophil infiltration. Although this tumor decreases in size in response to steroid therapy, it grows again after discontinuation of it, and ultimately proves intractable to treatment. We recently attempted to characterize electron-microscopically the eosinophils in the area affected by soft tissue eosinophilic granuloma. Needle biopsy of subauricular masses was carried out before and after steroid treatment. The collected tissue was observed under an electron microscope. Before treatment, more than 90% of the eosinophils constituting the granulation tissue had a broken cell membrane. A number of Charcot-Leyden crystals were noted in the intercellular spaces. Following steroid treatment, more than 90% of eosinophils were intact, and Charcot-Leyden crystals were no longer observed. These findings suggest that destruction of eosinophils within granulation tissue aggravates soft tissue eosinophilic granulom.


Accessory Ossicles of the Foot and Ankle: Disorders and a Review of the Literature.
Accessory ossicles of the foot and ankle are normal variants of bone development that usually remain asymptomatic. However, they may be involved in various disorders and become a source of pain such as in fractures, dislocations, degenerative changes, osteonecrosis, osteoarthritis, osteochondral lesions, avascular necrosis, and irritation or impingement of adjacent soft tissues. Hence, during the assessment of the situations above, knowledge about these little-known ossicles could be very important to reach the correct diagnosis. Recent studies in the literature have mostly focused on the most frequent 9-12 accessory bones. In this review, 24 types of accessory ossicle are described. These ossicles are accessory navicular bone, os peroneum, os trigonum, os intermetatarseum, os vesalianum. os subfibulare, os subtibiale, os calcaneus secundarius, os calcanei accessorium, os supratalare, os sustentaculi, os talotibiale, os tali accessorium, talus secundarius, os subcalcis, os cuboideum secundarium, os supranaviculare, os infranaviculare, os paracuneiforme, os intercuneiforme, os cuneometatarsale I tibiale, os cuneometatarsale plantare, os cuneo-I metatarsale-II dorsale, and os aponeurosis plantaris. The clinical importance of these bones should be known thoroughly to reduce unnecessary orthopedic consultations and misdiagnosis. This article describes the clinical importance of the accessory ossicles and their possible pathological conditions. Understanding the possible disorders of the accessory ossicles of the foot and ankle can provide a more accurate diagnostic process.


What is the ecotoxicity of a given chemical for a given aquatic species? Predicting interactions between species and chemicals using recommender system techniques.
Ecotoxicological safety assessment of chemicals requires toxicity data on multiple species, despite the general desire of minimizing animal testing. Predictive models, specifically machine learning (ML) methods, are one of the tools capable of solving this apparent contradiction as they allow to generalize toxicity patterns across chemicals and species. However, despite the availability of large public toxicity datasets, the data is highly sparse, complicating model development. The aim of this study is to provide insights into how ML can predict toxicity using a large but sparse dataset. We developed models to predict LC50-values, based on experimental LC50-data covering 2431 organic chemicals and 1506 aquatic species from the ECOTOX-database. Several well-known ML techniques were evaluated and a new ML model was developed, inspired by recommender systems. This new model involves a simple linear model that learns low-rank interactions between species and chemicals using factorization machines. We evaluated the predictive performances of the developed models based on two validation settings: 1) predicting unseen chemical-species pairs, and 2) predicting unseen chemicals. The results of this study show that ML models can accurately predict LC50-values in both validation settings. Moreover, we show that the novel factorization machine approach can match well-tuned, complex, ML approaches.


[Research advances of prostaglandin E2 synthases and receptors in cardiovascular diseases].
Prostaglandin E2 (PGE2) is an important lipid mediator derived from arachidonic acid. It is widely distributed in various tissues and involved in numerous physiological and pathophysiological processes. Based on the inhibition of inflammatory PGE2 production, non-steroidal anti-inflammatory drugs (NSAIDs) are considered as the most commonly used drugs to treat pain and inflammation. However, clinical trials have revealed that NSAIDs, especially cyclooxygenase-2 (COX-2) selective inhibitors, may predispose patients to a remarkably increased cardiovascular risk, including hypertension, myocardial infarction, and heart failure. This promotes scientists to develop new drugs to not only afford pain relief but also have cardiovascular efficacy. Microsomal prostaglandin E synthase-1 (mPGES-1), the key terminal enzyme catalyzing the synthesis of inflammatory PGE2, and the four PGE2 receptors (EP1-4) have gained more attention as the promising alternative drug targets for the development of novel NSAIDs. The role of mPGES-1 and EP receptors in cardiovascular diseases also has been widely studied. In this review, we highlight the most recent advances from our and other studies on the role of PGE2, particularly mPGES-1 and the four PGE2 receptors, in cardiovascular diseases.


Modeling the Conformational Preference of the Lignocellulose Interface and Its Interaction with Weak Acids.
We have examined the conformational space of model systems for the hydrogen-bonded and covalent linkages between the sugar and lignin components of lignocellulose. Specifically, glucose and paracoumaryl alcohol moieties are used in our models. Multistage screening protocols are used to identify and validate a set of lowest-energy isomers. We found a cost-effective screening process involving an initial screening with DFTB3/3ob using a 20 kJ mol-1 threshold, a refinement with the SCANh/6-31+G(2d,p) method with a 10 kJ mol-1 cutoff, a third step at the DSD-PBEP86/ma-def2-TZVP//MS1-D3/6-31+G(2d,p) level with the same 10 kJ mol-1 threshold, and a last step at the CCSD(T)/CBS//B3LYP/cc-pVTZ level with a tighter 5 kJ mol-1 threshold. The use of machine learning (with the London and Axilrod-Teller-Muto potential) can further accelerate the screening process. In general, all low-energy conformers are characterized by hydrogen bonding between the sugar and lignin moieties. We examined the interactions of covalently bonded sugar-lignin models with weak acids (HSO3-, H2PO3-, HSeO3-, H2citrate-, etc.) and found that they interacted strongly with the oxygen of the sugar-O-lignin linkage. Our results suggest that acids such as dihydrogen citrate may be attractive alternatives to the commonly used HSO3- for lignocellulose processing.


Self-expanding mesh stent for esophageal cancer stenosis.
The implantation of new self-expanding mesh stents (20 mm in diameter, when fully expanded) in a 67-year-old woman with extensive esophageal cancer stenosis is reported. Prosthesis insertion was easily accomplished without the need for general anesthesia. The patient has been doing well since. The potential advantages of the new stenting procedure suggest further investigation.


Evaluation of Bacterial Contamination as an Indicator of Viral Contamination in a Sedimentary Aquifer in Uruguay.
In Uruguay, groundwater is frequently used for agricultural activities, as well as for human consumption in urban and rural areas. As in many countries worldwide, drinking water microbiological quality is evaluated only according to bacteriological standards and virological analyses are not mentioned in the legislation. In this work, the incidence of human viral (Rotavirus A, Norovirus GII, and human Adenovirus) and bacterial (total and thermotolerant coliform and Pseudomonas aeruginosa) contamination in groundwater in the Salto district, Uruguay, as well as the possible correlation between these groups of microorganisms, was studied. From a total of 134 groundwater samples, 42 (32.1%) were positive for Rotavirus, only 1 (0.7%) for both Rotavirus and Adenovirus, and 96 (72.6%) samples were positive for bacterial indicators. Results also show that Rotavirus presence was not associated with changes in chemical composition of the aquifer water. Bacteriological indicators were not adequate to predict the presence of viruses in individual groundwater samples (well scale), but a deeper spatial-temporal analysis showed that they are promising candidates to assess the viral contamination degree at aquifer scale, since from the number of wells with bacterial contamination the number of wells with viral contamination could be estimated.