Comparison of supraspinatus cross-sectional areas according to shoulder abduction angles.
[Purpose] The purpose of this study was to determine the changes in the supraspinatus cross-sectional areas according to shoulder abduction angles, using ultrasonography. [Subjects and Methods] The subjects consisted of 40 individuals (20 males and 20 females). The cross-sectional areas of the supraspinatus of all subjects were measured with ultrasonography at abduction angle of 0°, 30°, 60°, 90°, and 120°. We set four abduction angle levels (I, II, III, and IV), 0° to 30°, 30° to 60°, 60° to 90°, and 90° to 120°, respectively, when determining the largest change in cross-sectional area. [Results] The results revealed that cross-sectional areas of the supraspinatus increased at all levels, but the abduction angle level with the largest increase in cross-sectional area of the supraspinatus was Level III. [Conclusion] The above results indicate that performing exercises at an abduction angle between 60° and 90° will be the most effective for supraspinatus strengthening in clinical practice.


Avoidance versus detection and recovery problem in buffer-space allocation of flexibly automated production systems.
Motivated by recent developments in the semiconductor manufacturing industry, this paper undertakes an analytical investigation of the problem of selecting optimally the deadlock resolution strategy for buffer space allocation in flexibly automated production systems. In the process, it extends the behavioral models for the aforementioned systems currently considered in the literature, to account for probabilistic uncontrollable effects like the requirement for extra finishing steps and/or rework, and it introduces a new deadlock resolution scheme, characterized as randomized deadlock avoidance. The combination of these two extensions brings the considered system behavior(s) to the realm of probabilistic automata, an area of increasing academic interest. For the resulting model, and under the assumption of Markovian timings, it develops an analytical methodology for selecting the optimal deadlock resolution strategy that maximizes the steady-state system throughput, and it demonstrates its effectiveness through application to a "prototype" system configuration. The obtained results provide an interesting analytical expression of the need to assess the gains obtained by the increased concurrency supported by the deadlock detection and recovery strategy versus the productivity losses experienced under this approach due to increased system blocking, and/or additional material handling overheads. It turns out that, for the considered system configuration, the optimal selection scheme switches between detection and recovery and pure deadlock avoidance, every time that the time cost of deadlock recovery, tau(d), crosses a threshold Theta, which is a function of the remaining system behavioral and timing parameters. Beyond its own theoretical merit, this last result raises also the question of whether the policy randomization introduced in this work will ever enhance the performance of any configuration in the considered class of Resource Allocation Systems (RAS); this issue will be investigated in a sequel paper.


Neural alpha dynamics in younger and older listeners reflect acoustic challenges and predictive benefits.
Speech comprehension in multitalker situations is a notorious real-life challenge, particularly for older listeners. Younger listeners exploit stimulus-inherent acoustic detail, but are they also actively predicting upcoming information? And further, how do older listeners deal with acoustic and predictive information? To understand the neural dynamics of listening difficulties and according listening strategies, we contrasted neural responses in the alpha-band (∼10 Hz) in younger (20-30 years, n = 18) and healthy older (60-70 years, n = 20) participants under changing task demands in a two-talker paradigm. Electroencephalograms were recorded while humans listened to two spoken digits against a distracting talker and decided whether the second digit was smaller or larger. Acoustic detail (temporal fine structure) and predictiveness (the degree to which the first digit predicted the second) varied orthogonally. Alpha power at widespread scalp sites decreased with increasing acoustic detail (during target digit presentation) but also with increasing predictiveness (in-between target digits). For older compared with younger listeners, acoustic detail had a stronger impact on task performance and alpha power modulation. This suggests that alpha dynamics plays an important role in the changes in listening behavior that occur with age. Last, alpha power variations resulting from stimulus manipulations (of acoustic detail and predictiveness) as well as task-independent overall alpha power were related to subjective listening effort. The present data show that alpha dynamics is a promising neural marker of individual difficulties as well as age-related changes in sensation, perception, and comprehension in complex communication situations.


Differential response of basal and tetrahydrobiopterin-stimulated activities of placental type III nitric oxide synthase to sodium dodecyl sulphate: relation to dimeric structure.
The major enzyme isoform that synthesizes nitric oxide (NO) in first trimester human placentae is endothelial or type III NO-synthase (NOS III) which exhibits high specific activity in the microsomal fraction. In the present study, we investigated the possible protective and enzyme-stabilizing role of tetrahydropterin (BH4). The anionic detergent, sodium dodecyl sulphate (SDS) and thermal stress (freeze-thaw) were used as non-specific 'subunit-dissociating' agents, and alterations in enzyme activity and subunit structure were investigated. SDS (> or =0.05% w/v) resulted in significant inhibition both of basal and BH4-stimulated activities of NOS III, but the latter responded more sensitively. Preincubation of microsomes with SDS (> or =0.1%, w/v), followed by incubation in an SDS-depleted reaction mixture led to an inhibition of BH4-stimulated enzyme activity, while no change in the basal activity was noted. This indicated that the SDS effect is only fully reversible in the case of basal activity. Considering that basal activity is due to the presence of endogenous BH4 tightly bound to the enzyme, this differential sensitivity of basal and BH4-stimulated enzyme activities to SDS may be related to a putative differential protective effect of BH4 on the two subunits of the NOS III dimer. Western blot analysis revealed that the SDS-induced inhibition of enzyme activity could not be ascribed to disruption of the dimeric structure. This finding confirms the view that SDS may affect NOS III activity without necessarily deteriorating quaternary protein structure. Nevertheless, BH4 is essential in maintaining dimeric structure under denaturing conditions, e.g. SDS treatment and freezing/thawing; it is even able to reverse the dissociation caused by SDS. A model describing the interaction between BH4 and NOS III, and its implications on the physiology and pathology of the human placenta, is discussed.


Methylmercury Causes Blood-Brain Barrier Damage in Rats via Upregulation of Vascular Endothelial Growth Factor Expression.
Clinical manifestations of methylmercury (MeHg) intoxication include cerebellar ataxia, concentric constriction of visual fields, and sensory and auditory disturbances. The symptoms depend on the site of MeHg damage, such as the cerebellum and occipital lobes. However, the underlying mechanism of MeHg-induced tissue vulnerability remains to be elucidated. In the present study, we used a rat model of subacute MeHg intoxication to investigate possible MeHg-induced blood-brain barrier (BBB) damage. The model was established by exposing the rats to 20-ppm MeHg for up to 4 weeks; the rats exhibited severe cerebellar pathological changes, although there were no significant differences in mercury content among the different brain regions. BBB damage in the cerebellum after MeHg exposure was confirmed based on extravasation of endogenous immunoglobulin G (IgG) and decreased expression of rat endothelial cell antigen-1. Furthermore, expression of vascular endothelial growth factor (VEGF), a potent angiogenic growth factor, increased markedly in the cerebellum and mildly in the occipital lobe following MeHg exposure. VEGF expression was detected mainly in astrocytes of the BBB. Intravenous administration of anti-VEGF neutralizing antibody mildly reduced the rate of hind-limb crossing signs observed in MeHg-exposed rats. In conclusion, we demonstrated for the first time that MeHg induces BBB damage via upregulation of VEGF expression at the BBB in vivo. Further studies are required in order to determine whether treatment targeted at VEGF can ameliorate MeHg-induced toxicity.


Medical support for law enforcement-extended operations incidents.
As the complexity and frequency of law enforcement-extended operations incidents continue to increase, so do the opportunities for adverse health and well-being impacts on the responding officers. These types of clinical encounters have not been well characterized nor have the medical response strategies which have been developed to effectively manage these encounters been well described. The purpose of this article is to provide a descriptive epidemiology of the clinical encounters reported during extended law enforcement operations, as well as to describe a best practices approach for their effective management. This study retrospectively examined the clinical encounters of the Maryland State Police (MSP) Tactical Medical Unit (TMU) during law enforcement extended operations incidents lasting 8 or more hours. In addition, a qualitative analysis was performed on clinical data collected by federal law enforcement agencies during their extended operations. Forty-four percent of missions (455/1,047) supported by the MSP TMU lasted 8 or more hours. Twenty-six percent of these missions (117/455) resulted in at least one patient encounter. Nineteen percent of patient chief complaints (45/238) were related to heat illness/ dehydration. Fifteen percent of encounters (36/238) were for musculoskeletal injury/pain. Eight percent of patients (19/238) had nonspecific sick call (minor illness) complaints. The next most common occurring complaints were cold-related injuries, headache, sinus congestion, and wound/laceration, each of which accounted for 7 percent of patients (16/238), respectively. Analysis of federal law enforcement agencies' response to such events yielded similar clinical encounters. A wide range of health problems are reported by extended law enforcement operations personnel. Timely and effective treatment of these problems can help ensure that the broader operations mission is not compromised. An appropriate operational strategy for managing health complaints reported during extended operations involves the deployment of a well-trained medical support team using the core concepts of tactical emergency medical support.


Atypical sensory profiles as core features of adult ADHD, irrespective of autistic symptoms.
Abnormal sensory sensitivity is a feature of autism-spectrum disorder (ASD), but is also reported in attention-deficit/hyperactivity disorder (ADHD). In many cases, ADHD and ASD are comorbid. This study investigated the prevalence of sensory hyper- and hyposensitivity among adults with ADHD, controlling for autistic symptoms. One hundred and sixteen adults diagnosed with ADHD completed the Adolescent/Adult Sensory Profile-NL (AASP-NL) and the Autism-spectrum Quotient (AQ) questionnaires. Prevalences of hyper- and hyposensitivity and autism-spectrum symptoms were compared to norm values. Multivariate binary logistic regressions were used to determine the association of autistic symptoms, age, gender, ADHD subtype, self-reported severity of ADHD symptoms, comorbid disorders, and use of medication on the sensory hypo- and hypersensitivity in adults with ADHD. Adults with ADHD had more autistic symptoms, and they had both more hyper- and hyposensitivity compared to norm groups. This was especially apparent in the Activity level and Auditory sensory modalities. Sensory hypo- and hypersensitivity were both related to an increased ADHD score, even showing a dose-response relationship, but not to any autistic symptom or comorbid disorder. As much as 43% of the females with ADHD reported sensory hypo- and/or hypersensitivity, compared to 22% of the men. Sensory hypo- and hypersensitivity may be viewed as key features of adult ADHD, especially in females, regardless of any autistic symptoms. Future research should be directed at the implications of this sensory dysregulation for the understanding of the pathophysiology of (female) ADHD, and on the usefulness of assessment of atypical sensory profiles in the diagnostic procedure of ADHD in adults.


Exposure to PM2.5 is associated with malignant pleural effusion in lung cancer patients.
Air pollution has been recognized to be a risk factor for lung cancer. The objective of this study was to investigate the effects of air pollution on heavy metal alterations in the pleural effusion of lung cancer patients. Pleural effusion was collected from patients with lung cancer and congestive heart failure (CHF). One-year average levels of particulate matter with an aerodynamic diameter of < 10 µm (PM10), PM2.5, NO2, and SO2 were linked to the exposure of these subjects. Traffic-related metals, included Al, Fe, Cu, Zn, and Pb, were determined in the pleural effusion. Logistic regression models were used to examine their associations. There were 63 lung cancer patients and 31 CHF patients enrolled in the current study. We found that PM10, PM2.5, and NO2 were negatively correlated with Al in the pleural effusion, whereas PM2.5 was positively correlated with Zn in the pleural effusion. Increases in 1 μg/m3 of PM2.5 and 1 ng/mL of Zn were associated with lung cancer (adjusted OR=2.394, 95% CI= 1.446-3.964 for PM2.5; adjusted OR=1.003, 95% CI=1.000-1.005 for Zn). Increases in PM2.5 and Zn in the pleural effusion increased the risk of malignant pleural effusion in lung cancer patients (adjusted OR=1.517; 95% CI=1.082-2.127 for PM2.5; adjusted OR=1.002, 95% CI=1.000-1.005 for Zn). Furthermore, we observed that adenocarcinomas increased in association with a 1-μg/m3 increase in PM2.5 (crude OR=1.683; 95% CI=1.006-2.817) in lung cancer patients. In conclusion, PM2.5 exposure and the possible resultant Zn in the pleural effusion associated with the development of malignant pleural effusion in lung cancer.


Elevated Neuroglobin Lessens Neuroinflammation and Alleviates Neurobehavioral Deficits Induced by Acute Inhalation of Combustion Smoke in the Mouse.
Acute inhalation of combustion smoke produces long-term neurologic deficits in survivors. To study the mechanisms that contribute to the development of neurologic deficits and identify targets for prevention, we developed a mouse model of acute inhalation of combustion smoke, which supports longitudinal investigation of mechanisms that underlie the smoke induced inimical sequelae in the brain. Using a transgenic mouse engineered to overexpress neuroglobin, a neuroprotective oxygen-binding globin protein, we previously demonstrated that elevated neuroglobin preserves mitochondrial respiration and attenuates formation of oxidative DNA damage in the mouse brain after smoke exposure. In the current study, we show that elevated neuronal neuroglobin attenuates the persistent inflammatory changes induced by smoke exposure in the mouse brain and mitigates concordant smoke-induced long-term neurobehavioral deficits. Specifically, we found that increases in hippocampal density of GFAP and Iba-1 positive cells that are detected post-smoke in wild-type mice are absent in the neuroglobin overexpressing transgenic (Ngb-tg) mice. Similarly, the smoke induced hippocampal myelin depletion is not observed in the Ngb-tg mice. Importantly, elevated neuroglobin alleviates behavioral and memory deficits that develop after acute smoke inhalation in the wild-type mice. Taken together, our findings suggest that the protective effects exerted by neuroglobin in the brains of smoke exposed mice afford protection from long-term neurologic sequelae of acute inhalation of combustion smoke. Our transgenic mouse provides a tool for assessing the potential of elevated neuroglobin as possible strategy for management of smoke inhalation injury.


Inhibition of NLRP3 inflammasome in tumor microenvironment leads to suppression of metastatic potential of cancer cells.
Tumor microenvironment favors tumor cells to promote their growth and metastasis such as migration, invasion, and angiogenesis. IL-1β, one of the inflammatory cytokines released from myeloid cells in tumor microenvironment, plays an important role in development and progress of tumor. The activation of inflammasome is a critical step to secrete mature IL-1β through stepwise reactions to activate capspase-1. Therefore, we investigated whether the inhibition of NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome in macrophages regulated the metastatic potential of tumor cells. NLRP3 inflammasome was activated by ATP in bone marrow-derived primary mouse macrophages. The metastatic potential of mouse melanoma cell line (B16F10) was determined by migration and invasion assays with transwell system. ATP-treated wild-type macrophages increased the migration and invasion of melanoma cells. However, NLRP3- or caspase-1-knockout macrophages exhibited greatly diminished ability to promote the migration and invasion of melanoma cells. In addition, treatment with celastrol, an inhibitor of NLRP3 inflammasome, reduced the potency of macrophages to stimulate migration and invasion of melanoma cells. The results demonstrate that inhibition of the NLRP3 inflammasome in macrophages by genetic deficiency or a pharmacological inhibitor is linked to suppression of the metastatic potential of tumor cells. The results would provide a novel anti-cancer strategy to modulate tumor microenvironment by suppressing NLRP3 inflammasome and consequently reducing IL-1β production.


Cedrol, a malaria mosquito oviposition attractant is produced by fungi isolated from rhizomes of the grass Cyperus rotundus.
Cedrol, a sesquiterpene alcohol, is the first identified oviposition attractant for African malaria vectors. Finding the natural source of this compound might help to elucidate why Anopheles gambiae and Anopheles arabiensis prefer to lay eggs in habitats containing it. Previous studies suggest that cedrol may be a fungal metabolite and the essential oil of grass rhizomes have been described to contain a high amount of different sesquiterpenes. Rhizomes of the grass Cyperus rotundus were collected in a natural malaria mosquito breeding site. Two fungi were isolated from an aqueous infusion with these rhizomes. They were identified as Fusarium falciforme and a species in the Fusarium fujikuroi species complex. Volatile compounds were collected from the headspace above fungal cultures on Tenax traps which were analysed by gas chromatography-mass spectrometry (GCMS). Cedrol and a cedrol isomer were detected in the headspace above the F. fujikuroi culture, while only cedrol was detected above the F. falciforme culture. Cedrol an oviposition attractant for African malaria vectors is produced by two fungi species isolated from grass rhizomes collected from a natural mosquito breeding site.


Palladium(0)-catalyzed highly regio- and stereoselective addition of organoboronic acids with 1,2-allenylphosphonates forming tri- or tetrasubstituted 1(E)-alkenylphosphonates.
A highly regio- and stereoselective palladium(0)-catalyzed addition of organoboronic acids with 1,2-allenylphosphonates in the presence of HOAc forming tri- or tetrasubstituted 1(E)-alkenylphosphonates is reported in this paper. The stereoselectivity is much higher than the reported cases. The effects of different R(1), R(2), and R(3) were studied. A mechanism of this reaction is proposed on the basis of our previous study.


Effect of laboratory acclimation on the variation of reproduction-related characters in Drosophila melanogaster.
The natural variation of sex-specific characters between populations can favor their behavioral isolation, eventually leading to the formation of new species. Marked variations for male courtship, mating and the production of sex pheromones - three complex characters potentially inducing sexual isolation - were found between Drosophila melanogaster populations of various origins acclimated for many generations in research laboratories. However, the natural variation of these three characters between natural populations and their evolution after long-term acclimation in the laboratory remains unknown. We measured many traits involved in these characters in six stocks initiated with distinct populations sampled in a restricted geographic area. Several sex-specific traits varied between stocks freshly brought back to the laboratory. After 100 generations spent in the laboratory without any experimental selection, traits varied in a strain-dependent manner. This variation was not related to a reduction of their variance except for copulation duration. This indicates that reproduction-related characters can diverge between neighboring D. melanogaster populations, and differently adapt to stable laboratory conditions.


The neural mechanisms underlying levodopa-induced dyskinesia in Parkinson's disease.
Treatment-related dyskinesias are the major limitation of dopamine replacement therapies such as levodopa in Parkinson's disease (PD). Recent studies in parkinsonian, nonhuman primates have highlighted abnormalities in neural functioning that might underlie the generation of dyskinetic symptoms in patients with PD who have received prolonged dopaminergic therapy. This article reviews studies on metabolic activity in subregions of the basal ganglia which suggest that profound abnormalities in basal ganglia output may underlie levodopa-induced dyskinesia. Such abnormalities may result from changes within basal ganglia circuitry and may include either overt changes in average firing rate or modulation of the pattern of cell-cell communication within subregions of the basal ganglia circuitry. An appreciation of abnormalities in the mechanisms responsible for modulating synaptic transmission in the basal ganglia may suggest novel therapeutic approaches to the problem of dyskinesia.


Evidence for partial dynamical symmetries in atomic nuclei.
Symmetries in nature offer very simple descriptions of complex systems. Partial Dynamical Symmetries (PDS) can considerably broaden their relevance. To present the first extensive test of a PDS for nuclei, we compare an SU(3) PDS to gamma to ground band B(E2) values for 47 deformed nuclei. The parameter-free PDS is found to be quite successful, but with characteristic discrepancies, suggesting that symmetry remnants are more pervasive than heretofore realized. Furthermore, the SU(3) PDS gives new insights into collective models (e.g., interacting boson approximation). If these reproduce the PDS, they reflect finite size effects, while differences from the PDS point to SU(3) configuration mixing.


Optogenerapy: When bio-electronic implant enters the modern syringe era.
Resort to medications dates back million years ago with the use of medicinal plants. In the nineteenth century, significant contributions in medicine appeared in different domains, among which the invention of a specific drug delivery device; the syringe. Nowadays, injection therapy of bio-manufactured drugs is routine practice for chronic diseases but remains constraining and painful. New emerging advanced therapies invest in genetic, electronics and cell-based therapy for addressing unmet needs for the caregivers and the patient. As digital process in health (eHealth) gains momentum, connected advanced bio-electronic devices now offer new strategies for personalized injection therapies. In this review, we take a journey along the genesis path of a new drug delivery system: the Optogenerapy, a synergy between optogenetic and gene therapy. Inside a bio-electronic implant, electronics and optogenetics are interfaced by light as a traceless inducer signal. By controlling a synthetic optogenetic pathway in the cell, therapeutics delivery can be fine-tuned with a precise spatiotemporal control. The technology holds promise of a new modern syringe era capable of producing a drug of interest at will directly inside the patient.


Relaxin reverses airway remodeling and airway dysfunction in allergic airways disease.
Mice deficient in the antifibrotic hormone relaxin develop structural changes in the airway that resemble airway remodeling, and demonstrate exaggerated remodeling changes in models of allergic airways disease (AAD). Relaxin expression in asthma has not been previously studied. We evaluated the efficacy of relaxin in the treatment of established airway remodeling in a mouse model of AAD. Relaxin expression in mouse AAD was also examined by immunohistochemistry and real-time PCR. BALB/c mice with established AAD were treated with relaxin or vehicle control (sc for 14 d), and effects on airway remodeling, airway inflammation, and airway hyperresponsiveness (AHR) were assessed. Relaxin expression was significantly reduced in the airways of mice with AAD compared with controls. Recombinant relaxin treatment in a mouse model of AAD reversed collagen deposition and epithelial thickening, and significantly improved AHR (all P < 0.05 vs. vehicle control), but did not influence airway inflammation or goblet cell hyperplasia. Relaxin treatment was associated with increased matrix metalloproteinase-2 levels, suggesting a possible mechanism for its antifibrotic effects. Endogenous relaxin expression is decreased in murine AAD, whereas exogenous relaxin represents a novel treatment capable of reversing established airway remodeling and AHR.


Spinal reflexes in chinoform-administered rats.
We examined the effects of chinoform (CF) on the spinal reflexes and the descending influences on the spinal reflexes from the locus coeruleus (LC) and the nucleus raphe magnus (NRM) in rats. The spinal reflex potential was recorded from the L5 ventral root following stimulation of the L5 dorsal root, and the effects of electrical stimulation of the LC and the NRM were tested in anesthetized rats. CF was suspended in Tween 80 and administered for two days (400 mg/kg, i. p./day) before the measurement of the spinal reflexes. In all rats treated with CF, death or motor incoordinations such as abnormal gait and hindlimb ataxia were observed. However, the control and CF-treated groups are not different in the amplitude and shape of the reflexes and in the influences of the LC and the NRM on the reflexes from the LC and the NRM. These results suggest that segmental spinal reflexes and descending influences from the LC and the NRM are not affected in rats suffered from motor incoordination by acute CF.


Methylphenidate-induced dendritic spine formation and DeltaFosB expression in nucleus accumbens.
Methylphenidate is the psychostimulant medication most commonly prescribed to treat attention deficit hyperactivity disorder (ADHD). Recent trends in the high usage of methylphenidate for both therapeutic and nontherapeutic purposes prompted us to investigate the long-term effects of exposure to the drug on neuronal adaptation. We compared the effects of chronic methylphenidate or cocaine (15 mg/kg, 14 days for both) exposure in mice on dendritic spine morphology and DeltaFosB expression in medium-sized spiny neurons (MSN) from ventral and dorsal striatum. Chronic methylphenidate increased the density of dendritic spines in MSN-D1 (MSN-expressing dopamine D1 receptors) from the core and shell of nucleus accumbens (NAcc) as well as MSN-D2 (MSN-expressing dopamine D2 receptors) from the shell of NAcc. In contrast, cocaine increased the density of spines in both populations of MSN from all regions of striatum. In general, the effect of methylphenidate on the increase of shorter spines (class 2) was less than that of cocaine. Interestingly, the methylphenidate-induced increase in the density of relatively longer spines (class 3) in the shell of NAcc was bigger than that induced by cocaine. Furthermore, methylphenidate exposure increased expression of DeltaFosB only in MSN-D1 from all areas of striatum, and surprisingly, the increase was greater than that induced by cocaine. Thus, our results show differential effects of methylphenidate and cocaine on neuronal adaptation in specific types of MSN in reward-related brain regions.


Draft genome sequences of the strains isolated from estuary sediments.
Draft genome sequences of four strains of the Bacillaceae were generated using nanopore technology. The size of the genome ranges from 4.2 to 4.4 Mb. This study aims to enhance our understanding of the diversity of probable probiotic strains, their metabolic activities, and their safety in real-world applications.


The homeostatic psyche: Freudian theory and somatic markers.
After years of reciprocal lack of interest, if not opposition, neuroscience and psychoanalysis are poised for a renewed dialogue. This article discusses some aspects of the Freudian metapsychology and its link with specific biological mechanisms. It highlights in particular how the physiological concept of homeostasis resonates with certain fundamental concepts of psychoanalysis. Similarly, the authors underline how the Freud and Damasio theories of brain functioning display remarkable complementarities, especially through their common reference to Meynert and James. Furthermore, the Freudian theory of drives is discussed in the light of current neurobiological evidences of neural plasticity and trace formation and of their relationships with the processes of homeostasis. The ensuing dynamics between traces and homeostasis opens novel avenues to consider inner life in reference to the establishment of fantasies unique to each subject. The lack of determinism, within a context of determinism, implied by plasticity and reconsolidation participates in the emergence of singularity, the creation of uniqueness and the unpredictable future of the subject. There is a gap in determinism inherent to biology itself. Uniqueness and discontinuity: this should today be the focus of the questions raised in neuroscience. Neuroscience needs to establish the new bases of a "discontinuous" biology. Psychoanalysis can offer to neuroscience the possibility to think of discontinuity. Neuroscience and psychoanalysis meet thus in an unexpected way with regard to discontinuity and this is a new point of convergence between them.


Collision induced dissociation products of disulfide-bonded peptides: ions result from the cleavage of more than one bond.
Disulfide bonds are a post-translational modification (PTM) that can be scrambled or shuffled to non-native bonds during recombinant expression, sample handling, or sample purification. Currently, mapping of disulfide bonds is not easy because of various sample requirements and data analysis difficulties. One step towards facilitating this difficult work is developing a better understanding of how disulfide-bonded peptides fragment during collision induced dissociation (CID). Most automated analysis algorithms function based on the assumption that the preponderance of product ions observed during the dissociation of disulfide-bonded peptides result from the cleavage of just one peptide bond, and in this report we tested that assumption by extensively analyzing the product ions generated when several disulfide-bonded peptides are subjected to CID on a quadrupole time of flight (QTOF) instrument. We found that one of the most common types of product ions generated resulted from two peptide bond cleavages, or a double cleavage. We found that for several of the disulfide-bonded peptides analyzed, the number of double cleavage product ions outnumbered those of single cleavages. The influence of charge state and precursor ion size was investigated, to determine if those parameters dictated the amount of double cleavage product ions formed. It was found in this sample set that no strong correlation existed between the charge state or peptide size and the portion of product ions assigned as double cleavages. These data show that these ions could account for many of the product ions detected in CID data of disulfide bonded peptides. We also showed the utility of double cleavage product ions on a peptide with multiple cysteines present. Double cleavage products were able to fully characterize the bonding pattern of each cysteine where typical single b/y cleavage products could not.


Predicting response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer with serum biomarkers.
Introduction The aim of this study was to identify patient factors including serum biomarkers that may predict response to neoadjuvant chemoradiotherapy (CRT) in patients with locally advanced rectal cancer staged on magnetic resonance imaging. Prediction of response may be helpful when selecting patients for a non-operative programme. Methods A retrospective review was carried out of patients undergoing neoadjuvant CRT for rectal cancer, conducted at the Royal Devon and Exeter Hospital. All patients were managed through the multidisciplinary team. Receiver operating characteristic (ROC) curve analysis was undertaken to assess the ability of biomarkers to predict response to neoadjuvant CRT. The biomarkers assessed included neutrophils, lymphocytes, monocytes, haemoglobin, platelets, C-reactive protein and carcinoembryonic antigen. Results Seventy-three patients underwent neoadjuvant CRT between January 2006 and December 2011. Nine (12.3%) of these experienced a clinical complete response and were managed with a 'watch and wait' approach. An additional ten patients (13.7%) had a pathological complete response following surgery. Using ROC curve analysis, the biomarkers with the largest area under the curve (AUC) were pre-CRT haemoglobin and post-CRT lymphocyte concentrations, producing AUC values of 0.673 and 0.618 respectively for clinical complete response. Pre-CRT haemoglobin and neutrophil concentrations produced the highest AUC values for pathological complete response at 0.591 and 0.614 respectively. Conclusions None of the assessed biomarkers offer the ability to predict response to neoadjuvant CRT in patients with rectal cancer. They cannot therefore assist in identifying complete clinical or pathological responders who could be considered for a non-operative, observational approach.


Communication is key: at-risk families' perspectives on follow-up in New Jersey's early hearing detection and intervention program.
Babies whose families possess multiple marginalized identities are at-risk for being late or lost to follow-up although there is a universal effort to screen and treat hearing loss in babies as part of state Early Hearing Detection and Intervention (EHDI) programs. Lack of timely follow-up puts young children at risk for delays in language acquisition, social skills, cognitive development, and school success. This qualitative study explored barriers to follow-up audiological care in at-risk families in New Jersey. Using thematic analysis, this research uncovered two major findings: 1) communication normalizes failed screenings, and 2) parents need clearer and more in-depth information. Health care social workers are well-suited to address these challenges due to their training in integrated social work practice, which can help them understand the complex interplay between individuals and their environments. In doing so social workers can improve access to needed services and promote health equity.


Risk factors associated with the occurrence of silent pulmonary embolism in patients with deep venous thrombosis of the lower limb.
The aim of our study is to investigate the prevalence of silent pulmonary embolism in patients with deep venous thrombosis in the lower limbs and to evaluate the associated risk factors. A total of 322 patients with acute deep venous thrombosis confirmed by CT venography or Doppler ultrasonography were studied. The diagnosis of silent pulmonary embolism was established by computed tomography pulmonary arteriography (CTPA). The association between covariates and the prevalence of silent pulmonary embolism in patients with deep venous thrombosis in lower limbs were assessed using chi-square test and multivariable regression. The incidence of silent pulmonary embolism was 33.5% (108 in 322 patients) in all patients with deep venous thrombosis in lower limbs. Chi-square test showed male gender, the right lower limb, proximal location of the thrombus, unprovoked venous thrombosis and coexisting heart diseases were related to a higher incidence of silent pulmonary embolism in patients with deep venous thrombosis in lower limbs. The multivariate regression analysis confirmed that the risk factors associated with silent pulmonary embolism in deep venous thrombosis patients included the right side and proximal location of the thrombus (odds ratio: 2.023, 95% CI: 1.215-3.368; odds ratio: 3.610, 95% CI: 1.772-7.354), unprovoked venous thrombosis (odds ratio: 2.037, 95% CI: 1.188-3.493), coexisting heart diseases (odds ratio: 4.507, 95% CI: 2.667-7.618). Silent pulmonary embolism occurred frequently in patients with deep venous thrombosis in lower limbs. The right side, the proximal location of the thrombus, unprovoked venous thrombosis and coexisting heart diseases increased the risk for the occurrence of silent pulmonary embolism.


Emergency hernia repair in cirrhotic patients with ascites.
The optimal treatment for abdominal wall hernias in the setting of ascites is not clear. We describe our experience with emergent surgery for hernias in patients with cirrhosis and ascites and assess variables associated with poor short- and long-term outcomes to inform decisions about aggressive early repair. We performed a retrospective review of all emergency abdominal wall hernia repairs admitted from the emergency department from January 2000 to December 2011 in all patients with ascites caused by liver cirrhosis. Demographic data, comorbidities, complications, operative details, hospital length of stay, and admission model of end-stage liver disease (MELD) score was determined. Follow-up was detailed via comprehensive liver service electronic records. There were 69 emergent hernia surgeries in 68 patients during the study period. There were two early deaths (both MELD score> 20). Multivariate analysis revealed MELD score (18% increase in risk with each point of MELD), preoperative anemia (sevenfold increase in risk), and preoperative small bowel obstruction (ninefold increase in risk) as predictive factors of major complication. In patients with MELD score greater than 10, morbidity was more than 50%, and major morbidity is greater than 12% when MELD score is greater than 20. Emergent hernia surgery in patients with ascites has low mortality but high morbidity and requires intense use of resources. To decrease the incidence of emergent hernia surgery, we recommend the aggressive use of elective repair. Emergent hernia repair, when necessary, should be performed at experienced centers and must include adequate ascites control with diuretic therapy and percutaneous paracentesis. Preoperative anemia and electrolyte abnormalities should be aggressively treated. Finally, while wound complications are common and frequently require reintervention, they are not associated with increased mortality. Prognostic and epidemiologic study, level V.


Edoxaban vs. warfarin in vitamin K antagonist experienced and naive patients with atrial fibrillation†.
Edoxaban is an oral, once-daily factor Xa inhibitor that is non-inferior to well-managed warfarin in patients with atrial fibrillation (AF) for the prevention of stroke and systemic embolic events (SEEs). We examined the efficacy and safety of edoxaban vs. warfarin in patients who were vitamin K antagonist (VKA) naive or experienced. ENGAGE AF-TIMI 48 randomized 21 105 patients with AF at moderate-to-high risk of stroke to once-daily edoxaban vs. warfarin. Subjects were followed for a median of 2.8 years. The primary efficacy endpoint was stroke or SEE. As a pre-specified subgroup, we analysed outcomes for those with or without prior VKA experience (>60 consecutive days). Higher-dose edoxaban significantly reduced the risk of stroke or SEE in patients who were VKA naive [hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.56-0.90] and was similar to warfarin in the VKA experienced (HR 1.01, 95% CI 0.82-1.24; P interaction = 0.028). Lower-dose edoxaban was similar to warfarin for stroke or SEE prevention in patients who were VKA naive (HR 0.92, 95% CI 0.73-1.15), but was inferior to warfarin in those who were VKA experienced (HR 1.31, 95% 1.08-1.60; P interaction = 0.019). Both higher-dose and lower-dose edoxaban regimens significantly reduced the risk of major bleeding regardless of prior VKA experience (P interaction = 0.90 and 0.71, respectively). In patients with AF, edoxaban appeared to demonstrate greater efficacy compared with warfarin in patients who were VKA naive than VKA experienced. Edoxaban significantly reduced major bleeding compared with warfarin regardless of prior VKA exposure.


Knowledge, attitudes and practices of prevention for cervical cancer and breast cancer among medical students.
Objective To assess the knowledge, attitudes and practices of medical students for health promotion, primary prevention and early detection of breast neoplasm and uterine cervical neoplasm, as well as to make recommendations for improving the Public Health curriculum at the Universidad de los Andes. Methodology This study utilized a survey of medical knowledge, attitudes and practices applied to fifth year Colombian medical students attending the Universidad de los Andes in the first semester of 2013. Results 64/76 students answered the surveys (response rate 84.2 % ): 62.5 % (40/64) and 37.5 % (24/64) response rates from students in their ninth and tenth semesters, respectively; and 64.1 % (41/64) and 35.9 % (23/64) response rates from female and male students, respectively. Knowledge: clinical breast exam (CBE), breast self-examination (BSE) and mammography were recommended by 95.3 % (61/64) of students, 96.9 % (62/64) of medical students and 90.7 % (58/64) of students, respectively. Attitude: the most effective tests to reduce mortality in women aged ≥ 50 years were the Papanicolaou test according to 90.6 % (58/64) of students and mammography according to 82.8 % (53/64) of students. Practice: 55.0 % (35/64) of students had received training in the guidelines and protocols for breast neoplasm and uterine cervical neoplasm screening. Discussion To promote early detection of cervical and breast cancer, knowledge, attitudes and practices must be improved to enhance clinical practices (e.g. Papanicolaou test) and medical student training guidelines or protocols for these two cancers. Overall, with induced demand and support from research communities and institutions seeking to make these improvements, we collaborate to decrease missed opportunities in medical research and Public Health.


Estrogen-dependent rapid activation of protein kinase C in estrogen receptor-positive MCF-7 breast cancer cells and estrogen receptor-negative HCC38 cells is membrane-mediated and inhibited by tamoxifen.
We examined protein kinase C (PKC) in the regulation of breast cancer cells by estrogen. Estrogen receptor (ER)- positive (+) MCF-7 and ER-negative (-) HCC38 cells were treated with 17 beta-estradiol (E(2)) or E(2)-BSA, which cannot enter the cell. E(2) and E(2)-BSA rapidly increased PKC-alpha in both cells via phosphatidylinositol-dependent phospholipase C and G protein, but not phospholipase A(2) or arachidonic acid. In MCF-7 cells, E(2) and E(2)-BSA had comparable effects, maximal at 90 min. In HCC38 cells, PKC was maximal at 9 min, with E(2)-BSA more than E(2). Tamoxifen blocked estrogen-dependent PKC in MCF-7 cells and reduced it in HCC38 cells. ER-antagonist ICI 182780, ER-agonist diethylstilbestrol, and antibodies to ER alpha and ER beta had no effect. E(2) stimulated [(3)H]thymidine incorporation in MCF-7 only; E(2)-BSA had no effect. Tamoxifen did not alter E(2)-dependent increases in MCF-7 cells, whereas ICI 182780 reduced DNA synthesis in control and E(2)-treated cultures. PKC activity was positively correlated with tumor severity in 133 breast cancer specimens and was greater in ER(-) tumors. Tamoxifen treatment reduced recurrence, and recurrent tumors had higher PKC activity. This indicates that E(2) rapidly increases PKC activity via membrane pathways not involving ER alpha or ER beta and suggests that tamoxifen works by reducing PKC activity through non-ER alpha/ER beta-dependent mechanisms.


[Diagnosis and staging of colorectal cancer].
Colorectal cancer is a frequent disease in Norway. New and improved surgical techniques and the implementation of adjuvant and neoadjuvant therapy have improved 5-year survival rates significantly. Accurate preoperative assessment of tumour extent is essential for choosing the appropriate therapeutic strategy, and thus for patient prognosis. Both established and recent imaging methods are presented and discussed. This review is based on a selection of articles from Pub-Med, with an emphasis on meta-analyses and prospective investigations, and on the clinical experiences of the authors. Recto-/colonoscopy with biopsy is still the most common approach for diagnosis. In Norway, magnetic resonance imaging (MRI) is the preferred imaging modality for rectal cancer. With optimal technique MRI provides a good visualisation of important local prognostic factors. Endoscopic ultrasound is the modality of choice for small, superficial tumours. The role of multidetector computer tomography (MDCT) in the local evaluation of rectal cancer is not entirely established. The evaluation of metastases of regional lymph nodes is a challenge with all the available imaging modalities. CT-colonography is a recent method for imaging of the colon. It provides an accurate evaluation of the bowel, of tumour invasion outside the bowel wall and of extracolonic (glandula- and liver-) metastases. Double-contrast barium enema, or abdominal and pelvic CT are alternative methods for evaluation of colon cancer. CT of the thorax and abdomen is recommended for screening of distant metastasis.


Modulation of melphalan resistance in glioma cells with a peripheral benzodiazepine receptor ligand-melphalan conjugate.
Peripheral benzodiazepine receptors (PBRs) are located on the outer membrane of mitochondria, and their density is increased in brain tumors. Thus, they may serve as a unique intracellular and selective target for antineoplastic agents. A PBR ligand-melphalan conjugate (PBR-MEL) was synthesized and evaluated for cytotoxicity and affinity for PBRs. PBR-MEL (9) (i.e., 670 amu) was synthesized by coupling of two key intermediates: 4-[bis(2-chloroethyl)-amino]-L-phenylalanine ethyl ester trifluoroacetate (6) and 1-(3'-carboxylpropyl)-7-chloro-1,3- dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one (8). On the basis of receptor-binding displacement assays in rat brain and glioma cells, 9 had appreciable binding affinity and displaced a prototypical PBR ligand, Ro 5-4864, with IC50 values between 289 and 390 nM. 9 displayed differential cytotoxicity to a variety of rat and human brain tumor cell lines. In some of the cell lines tested including rat and human melphalan-resistant cell lines, 9 demonstrated appreciable cytotoxicity with IC50 values in the micromolar range, lower than that of melphalan alone. The enhanced activity of 9 may reflect increased membrane permeability, increased intracellular retention, or modulation of melphalan's mechanisms of resistance. The combined data support additional studies to determine how 9 may modulate melphalan resistance, its mechanisms of action, and if target selectivity can be achieved in in vivo glioma models.


Circulating progenitor cells and the expression of Cxcl12, Cxcr4 and angiopoietin-like 4 during wound healing in the murine ear.
Migration of cells from both local and systemic sources is essential for the inflammatory and regenerative processes that occur during normal wound healing. CXCL12 is considered a critical regulator of CXCR4-positive cell migration during tissue regeneration. In this study, we investigated the expression of Cxcl12 and Cxcr4 during healing of a murine full thickness ear wound. We also investigated the expression of angiopoietin-like 4, which has been shown to participate in wound angiogenesis and reepithelialization. At time points up to 48hrs, complete blood counts were performed using automated hematology analysis, and the numbers of circulating stem and progenitor cells quantified using flow cytometry. Expression of both Cxcr4 and Angptl4 was significantly elevated within 3 days of wounding, and both were strongly expressed in cells of the epidermis. ANGPTL4 protein expression remained elevated in the epithelium through day 14. Cxcl12 expression was increased significantly at day 3, and remained elevated through day 21. Faint Cxcl12 staining was detectable in the epithelium at day 1, and thereafter staining was faint and more generalized. There were significantly fewer circulating total white blood cells and lymphocytes 1hr following ear punching. Similarly, there was a significant early (1hr) reduction in the number of circulating endothelial progenitor cells. Further studies are warranted to investigate whether ANGPTL4 and CXCL12/CXCR4 interact or synergize to facilitate cell recruitment and migration, and to potentiate reepithelialization and wound healing.


Redundancy in periplasmic binding protein-dependent transport systems for trehalose, sucrose, and maltose in Sinorhizobium meliloti.
We have identified a cluster of six genes involved in trehalose transport and utilization (thu) in Sinorhizobium meliloti. Four of these genes, thuE, -F, -G, and -K, were found to encode components of a binding protein-dependent trehalose/maltose/sucrose ABC transporter. Their deduced gene products comprise a trehalose/maltose-binding protein (ThuE), two integral membrane proteins (ThuF and ThuG), and an ATP-binding protein (ThuK). In addition, a putative regulatory protein (ThuR) was found divergently transcribed from the thuEFGK operon. When the thuE locus was inactivated by gene replacement, the resulting S. meliloti strain was impaired in its ability to grow on trehalose, and a significant retardation in growth was seen on maltose as well. The wild type and the thuE mutant were indistinguishable for growth on glucose and sucrose. This suggested a possible overlap in function of the thuEFGK operon with the aglEFGAK operon, which was identified as a binding protein-dependent ATP-binding transport system for sucrose, maltose, and trehalose. The K(m)s for trehalose transport were 8 +/- 1 nM and 55 +/- 5 nM in the uninduced and induced cultures, respectively. Transport and growth experiments using mutants impaired in either or both of these transport systems show that these systems form the major transport systems for trehalose, maltose, and sucrose. By using a thuE'-lacZ fusion, we show that thuE is induced only by trehalose and not by cellobiose, glucose, maltopentaose, maltose, mannitol, or sucrose, suggesting that the thuEFGK system is primarily targeted toward trehalose. The aglEFGAK operon, on the other hand, is induced primarily by sucrose and to a lesser extent by trehalose. Tests for root colonization, nodulation, and nitrogen fixation suggest that uptake of disaccharides can be critical for colonization of alfalfa roots but is not important for nodulation and nitrogen fixation per se.


Stem maintenance and construction respiration in Pinus ponderosa grown in different concentrations of atmospheric CO(2).
To determine whether long-term growth in enriched CO(2) atmospheres changes the woody tissue respiration component of aboveground carbon budgets, we measured woody tissue respiration of stems of 3-year-old ponderosa pine (Pinus ponderosa Laws.) grown in ambient (350 ppm) or twice ambient (700 ppm) atmospheric CO(2) concentrations in open-top field chambers located in Placerville, CA. Total respiration rate was measured by gas exchange, and construction respiration was calculated from the construction cost, percent carbon of stem samples and relative growth rate. Maintenance respiration was determined as the difference between total and construction respiration. The Q(10) of respiration was greater in stems grown in elevated CO(2) than in stems grown in ambient CO(2) (2.20 versus 1.67). As a result, mean daily respiration per unit volume of wood modeled for the month of September was greater in trees growing in elevated CO(2) than in ambient CO(2) (46.75 versus 40.45 mol m(-3) day(-1)). These effects of atmospheric CO(2) concentration were not the result of differences in relative growth rate. Calorimetric analyses of woody tissue construction cost indicated no difference between treatments; however, trees in the elevated CO(2) treatment showed a 1% lower carbon concentration than trees in the ambient CO(2) treatment. Estimates of construction respiration did not differ between treatments, confirming that the treatment differences in mean daily respiration rate were attributable to the maintenance component. Under future predicted atmospheric conditions, changes in the maintenance respiration of woody tissue may lead to an increase in the respiration component of whole-plant carbon budgets of ponderosa pine. Our results suggest that potential increases in the maintenance component of stem respiration should be considered when modeling the response of forest stand growth to enriched CO(2) atmospheres.


Performance of the Cough and Sputum Assessment Questionnaire (CASA-Q) in COPD: Evidence from Clinical and Online Patient Interaction Studies.
Patient perception of the burden of chronic bronchitis symptoms in chronic obstructive pulmonary disease (COPD) can be assessed using patient-reported outcome measures (PROMs). The Cough and Sputum Assessment Questionnaire (CASA-Q) was developed and tested for this purpose. This study reviewed the performance of the CASA-Q in published online studies and tested a novel approach to complement traditional methods of qualitative content validation. A targeted literature search was performed to identify published clinical studies of COPD using the CASA-Q as an endpoint. The performance of the questionnaire was examined in relation to other study endpoints, including clinical and functional measurements and other PROMs. Assessment of the content validity of the CASA-Q was carried out by comparing the content and structure of the questionnaire with published qualitative patient data from previously conducted online social media listening (SML) and online bulletin board (OBB) studies. In the interventional clinical trials, CASA-Q change scores were consistent with study objectives and other endpoints, including FEV1 and other PROMs. Two observational studies showed cross-sectional correlations with other PROMs like the St.-George's Respiratory Questionnaire (SGRQ) and COPD assessment test (CAT) scores. Qualitative data from the SML and OBB patient studies were consistent with the content and structure of the CASA-Q, supporting the content validity of the measure. Results suggest that the CASA-Q is appropriately responsive to changes in cough and sputum symptoms and clinical impact in trials of COPD. The mapping of qualitative findings from online SML and OBB studies to CASA-Q domains and items confirm the content validity of the instrument. These results suggest the CASA-Q can be a valuable tool for evaluating treatment effect in COPD trials.


Diagnosis of Wuchereria bancrofti infection by the polymerase chain reaction using urine and day blood samples from amicrofilaraemic patients.
A sensitive and specific polymerase chain reaction (PCR) based on a highly repeated deoxyribonucleic acid (DNA) sequence (188 bp; SspI repeat) was tested for the detection of Wuchereria bancrofti DNA in blood and urine samples collected during the day from individuals in Coque, Recife, Brazil, an endemic area for W. bancrofti. All microfilaraemic individuals were also positive by PCR, irrespective of the samples used. The PCR system was capable of detecting W. bancrofti DNA in amicrofilaraemic individuals: c. 93% were positive by PCR when day blood samples were used and 59.7% when urine samples collected at 07:00 were used. Thus, nocturnally periodic W. bancrofti infection can be detected in blood samples collected during the day, which is convenient for large-scale screening. In addition, non-invasive urine collection provided suitable samples for PCR, which is clearly advantageous for preliminary mass diagnosis.


Gene expression profiling of cultured mouse testis fragments treated with ethinylestradiol.
The assessment of xenobiotic-induced testicular toxicity is important in drug development. Nonetheless, in vitro models to test drugs and chemicals that may cause testicular toxicity are lacking, requiring the continued use of animal models for those studies. We previously evaluated an in vitro mouse testis organ culture system using ethinylestradiol (EE), a well-studied testicular toxicant, and demonstrated a dose-dependent relationship between adverse effects to germ cell differentiation and increasing EE concentrations. However, we terminated that study after 20 days of culture due to oxygen deficiency during germ cell differentiation. Therefore, in the current study, we aimed to identify gene(s) with potential for supporting the histopathological evaluations of testicular toxicity using in vitro testis organ culture system. We cultured testis fragments obtained from mice at postnatal day (PND) 5 in α-Minimal Essential Medium containing 40 mg/mL AlbuMAX™ I and treated them with 0.01 or 1 nM EE on day 1 of culture. On day 20, we collected testis fragments for RNA sequencing analysis and quantitative polymerase chain reaction (qPCR). We found that phospholipase C, zeta 1 and testis-specific serine kinase 4 genes, that are involved in spermatogenesis and predominantly expressed in the testis, were significantly reduced in testis fragments treated with the highest concentration of EE. Also, cytochrome P450, family 26, subfamily b, polypeptide 1 (Cyp26b1) and interleukin 16 (Il16) were up-regulated in the highest EE-treated groups. Further studies are needed to confirm the variations of these gene expression using other testicular toxicants.


Macrophage activation in response to shape memory polymer foam-coated aneurysm occlusion devices.
Brain aneurysms can be treated with embolic coils using minimally invasive approaches. It is advantageous to modulate the biologic response of platinum embolic coils. Our previous studies demonstrated that shape memory polymer (SMP) foam coated embolization coils (FCC) devices demonstrate enhanced healing responses in animal models compared with standard bare platinum coil (BPC) devices. Macrophages are the most prevalent immune cell type that coordinate the greater immune response to implanted materials. Hence, we hypothesized that the highly porous SMP foam coatings on embolic coils activate a pro-regenerative healing phenotype. To test this hypothesis, we analyzed the number and type of infiltrating macrophages in FCC or BPC devices implanted in a rabbit elastase aneurysm model. FCC devices elicited a great number of infiltration macrophages, skewed significantly to a pro-regenerative M2-like phenotype 90 days following implantation. We devised an in vitro assay, where monocyte-derived macrophages were placed in close association with FCC or BPC devices for 6-72 h. Macrophages encountering SMP FCC-devices demonstrated highly mixed activation phenotypes at 6 h, heavily skewing toward an M2-like phenotype by 72 h, compared with macrophages encountering BPC devices. Macrophage activation was evaluated using gene expression analysis, and secreted cytokine evaluation. Together, our results demonstrate that FCC devices promoted a pro-regenerative macrophage activation phenotype, compared with BPC devices. Our in vitro findings corroborate with in vivo observations that SMP-based modification of embolic coils can promote better healing of the aneurysm site, by sustaining a pro-healing macrophage phenotype.


Locating primary somatosensory cortex in human brain stimulation studies: experimental evidence.
Transcranial magnetic stimulation (TMS) over human primary somatosensory cortex (S1) does not produce immediate outputs. Researchers must therefore rely on indirect methods for TMS coil positioning. The "gold standard" is to use individual functional and structural magnetic resonance imaging (MRI) data, but the majority of studies don't do this. The most common method to locate the hand area of S1 (S1-hand) is to move the coil posteriorly from the hand area of primary motor cortex (M1-hand). Yet, S1-hand is not directly posterior to M1-hand. We localized the index finger area of S1-hand (S1-index) experimentally in four ways. First, we reanalyzed functional MRI data from 20 participants who received vibrotactile stimulation to their 10 digits. Second, to assist the localization of S1-hand without MRI data, we constructed a probabilistic atlas of the central sulcus from 100 healthy adult MRIs and measured the likely scalp location of S1-index. Third, we conducted two experiments mapping the effects of TMS across the scalp on tactile discrimination performance. Fourth, we examined all available neuronavigation data from our laboratory on the scalp location of S1-index. Contrary to the prevailing method, and consistent with systematic review evidence, S1-index is close to the C3/C4 electroencephalography (EEG) electrode locations on the scalp, ~7-8 cm lateral to the vertex, and ~2 cm lateral and 0.5 cm posterior to the M1-hand scalp location. These results suggest that an immediate revision to the most commonly used heuristic to locate S1-hand is required. The results of many TMS studies of S1-hand need reassessment. NEW & NOTEWORTHY Noninvasive human brain stimulation requires indirect methods to target particular brain areas. Magnetic stimulation studies of human primary somatosensory cortex have used scalp-based heuristics to find the target, typically locating it 2 cm posterior to the motor cortex. We measured the scalp location of the hand area of primary somatosensory cortex and found that it is ~2 cm lateral to motor cortex. Our results suggest an immediate revision of the prevailing method is required.


Exploring dementia family carers' self-initiated strategies in managing behavioural and psychological symptoms in dementia: a qualitative study.
Carer's self-initiated management strategies of behavioural and psychological symptoms of dementia (BPSD) can inform intervention development. These strategies are affected by cultural values. Little is known about non-Western dementia carers' BPSD management strategies. This study aimed to explore self-initiated strategies in managing BPSD adopted by Chinese carers. Qualitative study using thematic framework method. Community setting in Hong Kong. 16 dementia carers with purposive sampling to include carers of different relationships to the people living with dementia (PLwD), education level and living arrangement. Six overarching themes emerged from the data: (1) maintaining personhood in PLwD, (2) responding positively to BPSD, (3) explanation and bargaining, (4) responding negatively to BPSD, (5) controlling upsetting thoughts, and (6) getting respite care. Chinese carers treasured warm and supportive family relationships. They identified and minimised triggers to alleviate BPSD. Some carers struggled with care tasks and reacted with confrontation and avoidance. Changing attitudes and getting social and emotional support were described to manage carers' distress. Few self-care strategies including getting respite care were reported. Carers' self-initiated strategies largely aligned with existing theoretical frameworks in BPSD management, such as person-centred approach, and echoed Asian culture, which advocates filial piety and supportive family relationships. While these cultural values encourage the engagement of people living with dementia in the normal process of family life, they may also prevent carers from taking time away from care. Interventions could support carers by enhancing their knowledge and skills in managing BPSD, providing social and emotional support, and providing guidance in self-care. Future cross-cultural research could explore factors contributing to how carers manage BPSD and how interventions could be culturally adapted to facilitate carers to apply learnt skills in daily practice and hence benefit the people living with dementia and carer population.


Comparing the old to the new: A comparison of similarities and differences of the accreditation standards of the chiropractic council on education-international from 2010 to 2016.
Chiropractic programs are accredited and monitored by regional Councils on Chiropractic Education (CCE). The CCE-International has historically been a federation of regional CCEs charged with harmonising world standards to produce quality chiropractic educational programs. The standards for accreditation periodically undergo revision. We conducted a comparison of the CCE-International 2016 Accreditation Standards with the previous version, looking for similarities and differences, expecting to see some improvements. The CCE-International current (2016) and previous versions (2010) were located and downloaded. Word counts were conducted for words thought to reflect content and differences between standards. These were tabulated to identify similarities and differences. Interpretation was made independently followed by discussion between two researchers. The 2016 standards were nearly 3 times larger than the previous standards. The 2016 standards were created by mapping and selection of common themes from member CCEs' accreditation standards and not through an evidence-based approach to the development and trialling of accreditation standards before implementation. In 2010 chiropractors were expected to provide attention to the relationship between the structural and neurological aspects of the body in health and disease. In 2016 they should manage mechanical disorders of the musculoskeletal system. Many similarities between the old and the new standards were found. Additions in 2016 included a hybrid model of accreditation founded on outcomes-based assessment of education and quality improvement. Both include comprehensive competencies for a broader role in public health. Omissions included minimal faculty qualifications and the requirement that students should be able to critically appraise scientific and clinical knowledge. Another omission was the requirement for chiropractic programs to be part of a not-for-profit educational entity. There was no mention of evidence-based practice in either standards but the word 'evidence-informed' appeared once in the 2016 standards. Some positive changes have taken place, such as having bravely moved towards the musculoskeletal model, but on the negative side, the requirement to produce graduates skilled at dealing with scientific texts has been removed. A more robust development approach including better transparency is needed before implementation of CCE standards and evidence-based concepts should be integrated in the programs. The CCE-International should consider the creation of a recognition of excellence in educational programs and not merely propose minimal standards.


Global Health Security Demands a Strong International Health Regulations Treaty and Leadership From a Highly Resourced World Health Organization.
If the Ebola tragedy of West Africa has taught us anything, it should be that the 2005 International Health Regulations (IHR) Treaty, which gave unprecedented authority to the World Health Organization (WHO) to provide global public health security during public health emergencies of international concern, has fallen severely short of its original goal. After encouraging successes with the 2003 severe acute respiratory syndrome (SARS) pandemic, the intent of the legally binding Treaty to improve the capacity of all countries to detect, assess, notify, and respond to public health threats has shamefully lapsed. Despite the granting of 2-year extensions in 2012 to countries to meet core surveillance and response requirements, less than 20% of countries have complied. Today it is not realistic to expect that these gaps will be solved or narrowed in the foreseeable future by the IHR or the WHO alone under current provisions. The unfortunate failures that culminated in an inadequate response to the Ebola epidemic in West Africa are multifactorial, including funding, staffing, and poor leadership decisions, but all are reversible. A rush by the Global Health Security Agenda partners to fill critical gaps in administrative and operational areas has been crucial in the short term, but questions remain as to the real priorities of the G20 as time elapses and critical gaps in public health protections and infrastructure take precedence over the economic and security needs of the developed world. The response from the Global Outbreak Alert and Response Network and foreign medical teams to Ebola proved indispensable to global health security, but both deserve stronger strategic capacity support and institutional status under the WHO leadership granted by the IHR Treaty. Treaties are the most successful means the world has in preventing, preparing for, and controlling epidemics in an increasingly globalized world. Other options are not sustainable. Given the gravity of ongoing failed treaty management, the slow and incomplete process of reform, the magnitude and complexity of infectious disease outbreaks, and the rising severity of public health emergencies, a recommitment must be made to complete and restore the original mandates as a collaborative and coordinated global network responsibility, not one left to the actions of individual countries. The bottom line is that the global community can no longer tolerate an ineffectual and passive international response system. As such, this Treaty has the potential to become one of the most effective treaties for crisis response and risk reduction worldwide. Practitioners and health decision-makers worldwide must break their silence and advocate for a stronger Treaty and a return of WHO authority.


In Vitro Culture of Human Corneal Endothelium on Non-Mulberry Silk Fibroin Films for Tissue Regeneration.
The purpose of this study was to determine if non-mulberry varieties of silk are suitable for the culture of corneal endothelium (CE). Aqueous silk fibroin derived from Philosamia ricini (PR), Antheraea assamensis (AA), and Bombyx mori (BM) were cast as approximately 15 µm films with and without pores on which human CE cells were cultured. Tensile strength, elasticity, transmittance in visible range, and degradation properties of the films were characterised. Adhesion of CE to the silk films was quantified using MTT assay in addition to quantifying the number and area of focal adhesions using paxillin. Expression of CE markers was determined at the gene and protein levels using PCR and immunostaining, respectively. Barrier integrity of the cultured cells was measured as permeability to FITC dextran (10 kDa) in the presence or absence of thrombin. The films exhibited robust tensile strength, >95% transmittance and a refractive index comparable to the native cornea. BM degraded significantly faster when compared to PR and AA. A comparison between the three varieties of silk showed that significantly more cells were adhered to PR and AA than to BM. This was also reflected in the expression of stable focal adhesions on PR and AA, thus enabling the formation of intact monolayers of cells on these varieties unlike on BM. Treatment with thrombin significantly increased cellular permeability to dextran. Our data shows that PR and AA varieties sufficiently support the growth and function of CE cells. This could be attributed to the presence of natural cell binding motifs (RGD) in these varieties. Development of a suitable carrier for engineering the CE to address a major clinical requirement of healthy donor tissues for transplantation.


Highly efficient dandelion-like near-infrared light photoinitiator for free radical and thiol-ene photopolymerizations.
Efficient photopolymerization activated by nonharmful near-infrared (NIR) light is important for various biological applications. Here we propose a NIR light free-radical photoinitiator (PI) fabricated by incorporating oxime-ester coumarin functionality on the surface of upconversion nanoparticles (UCNPs). The coumarin groups of PI absorb the light emitted from the UCNP core, whereas the oxime ester groups undergo cleavage to form radicals. Upon irradiation at 980 nm, the mobile radicals, formed in a manner similar to that of dandelion seed release, initiate both free-radical and thiol-ene photopolymerizations. The superior efficiency of dandelion-like PIs assisted photopolymerizations can be attributed to the reduction of energy loss and increased local PI concentration due to Förster resonance energy transfer process and confinement effect, respectively. Moreover, the proposed PI system can initiate polymerization under low-power NIR laser and reduces the thermal side effects. The possibility of its potential use in deep curing applications was also demonstrated.


An Automated Canine Line-Up for Detection Dog Research.
Currently, there is a need to develop technology that facilitates and improves detection dog research. The aim of this research was to develop an automated computer-driven olfactory line-up task. The apparatus consisted of three olfactometers. Each olfactometer was equipped with flow meters to regulate air flow and dilution and six solenoid valves connected to odor jars. Each olfactometer generated an odor which was carried to an odor port where the dogs sample it. The olfactometer's valves were activated by a microcontroller, and a Python program was built to control each olfactometer and randomize and balance the odor presentation. Dogs (N = 12) received one or two 40-trial training sessions in a day where they progressed through a series of training phases where they learned to detect and alert to double-base smokeless powder (SP). An "alert" consisted of a 4-s nose hold. This was measured by infrared sensors in the ports. For each trial, the apparatus recorded dogs' search latency, sniff time, port entries, and response. All this information was automatically recorded in a csv file. A photoionization detector (PID) and solid-phase microextraction followed by gas chromatography-mass spectrometry (SPME-GC/MS) were used to evaluate the odor dynamics and to instrumentally verify odor presence and clearance. A control test was conducted at the end of the training to ensure dogs were alerting exclusively to the odorant. All 12 dogs readily learned to operate the apparatus within 23 days, and all exceeded 85% accuracy. Control tests indicated dogs were leveraging only olfactory cues and not unintentional cues such as auditory cues from the apparatus. Analytical data showed that odor was detected in the port immediately after the activation of a valve and that odor clearance occurred immediately after the valve was closed. The apparatus developed was easy to operate by the dogs and allowed substantial data collection using double-blind testing procedures in a very short period at an affordable cost point for research equipment (~$5,000 USD). The apparatus may prove to be a useful research tool to provide optimal odor stimuli control, ensure double-blind conditions, reduce labor, and significantly increase the amount of data collected.


Survival effects of prenatal famine exposure.
Adverse intrauterine conditions are known to be associated with an increased risk of chronic diseases in adult life. Previously, we showed that prenatal famine exposure increased the incidence of cardiovascular and metabolic disease in adulthood. We examined the association between prenatal famine exposure and adult mortality. We studied adult mortality among 1991 term singletons from the Dutch Famine Birth Cohort. We compared overall and cause-specific adult mortality among people exposed to famine in late, mid, and early gestation with those unexposed to famine in utero by using Cox proportional hazard models. A total of 206 persons (10%) had died by the end of follow-up. Compared with unexposed women, women exposed to famine in early gestation had a significantly higher risk of overall adult mortality (HR: 1.9; 95% CI: 1.1, 3.4), cardiovascular mortality (HR: 4.6; 95% CI: 1.2, 17.7), cancer mortality (HR: 2.3; 95% CI: 1.1, 4.7), and breast cancer mortality (HR: 8.3; 95% CI: 1.1, 63.0). In men exposed to famine in early gestation, these associations were as follows compared with unexposed men: overall adult mortality (HR: 0.4; 95% CI: 0.2, 1.1), cardiovascular mortality (HR: 0.9; 95% CI: 0.3, 3.1), and cancer mortality (HR: 0.3; 95% CI: 0.0, 1.9). Women exposed to famine in early gestation had a higher overall adult, cardiovascular, cancer, and breast cancer mortality risk than did women not exposed to famine. No such effects were observed in men exposed to famine in early gestation.


Using a Rapid Knowledge Translation Approach for Better Sexual and Reproductive Health and Rights in Bangladesh, Burundi, Indonesia, and Jordan.
Translation of knowledge into policy and practice is important to prevent sexual reproductive health and rights (SRHR)-related morbidity and mortality and ensure access to rights. Existing approaches to knowledge translation are often relatively rigid and implicitly assume linear processes, leading to time-consuming processes that are not tailored to countries' needs. SRHR knowledge platforms designed and implemented a collaborative rapid improvement model for knowledge translation (CRIM-KT) in Burundi, Bangladesh, Indonesia, and Jordan. The approach consisted of learning sessions and action periods aimed at improving policies and practices addressing the prevention of child marriage and teenage pregnancies. To evaluate the approach, a participatory action learning process took place throughout the implementation (September 2017 and January 2019). An end evaluation was conducted using a desk review of project documentation, in-depth interviews, and a focus group discussion to document the process, outcomes, and lessons learned. In Indonesia, a local government policy was changed that aims to prevent child marriage by avoiding misinterpretation of a local cultural practice. In Jordan, the cabinet endorsed a national action plan to prevent child marriage and changes in practice took place. In Burundi, no tangible changes in policy and practice in SRHR were observed. In Bangladesh, practice changed by strengthening coordination for collaboration and exchange among stakeholders to prevent child marriage. In all countries, the approach considerably strengthened participants' knowledge translation capacities. The CRIM-KT led to improvements in policy and practice in a relatively short time frame and different contexts. This can be explained by the systematic, structured, and participatory approach, allowing for contextual adaptation and involvement of stakeholders, as well as the cross-learning on 2 levels (international and country collaboration teams). The principles of the CRIM-KT may be further developed and applied in other fields in global health to strengthen knowledge translation processes.


Intrauterine Device Insertion during Cesarean Section in Women without Prenatal Contraception Counseling: Lessons from a Country with High Cesarean Rates.
The moment of admission for delivery may be inappropriate for offering an intrauterine device (IUD) to women without prenatal contraception counseling. However, in countries with high cesarean rates and deficient prenatal contraception counseling, this strategy may reduce unexpected pregnancies and repeated cesarean sections. This was a prospective cohort study involving 100 women without prenatal contraception counseling. Postplacental IUD was offered after admission for delivery and placed during cesarean. The rates of IUD continuation, uterine perforation, and endometritis were assessed at 6 weeks and 6 months, and the proportion of women continuing with IUD at 6 months was assessed with respect to the number of previous cesareans. Ninety-seven women completed the follow-up. The rate of IUD continuation was 91% at 6 weeks and 83.5% at 6 months. The expulsion/removal rate in the first 6 weeks was not different from that between 6 weeks and 6 months (9 vs 9.1%, respectively). There were 2 cases of endometritis (2.1%), and no case of uterine perforation. Among 81 women continuing with intrauterine device after 6-months, 31% had undergone only the cesarean section in which the IUD was inserted, 44% had undergone 2 and 25% had undergone 3 or more cesarean sections. Two thirds of the women who continued with IUD at 6 months had undergone 2 or more cesarean sections. Since offering trial of labor is unusual after 2 or more previous cesareans, we believe that offering IUD after admission for delivery may reduce the risk of repeated cesarean sections and its inherent risks.


Use of electronic health records to support a public health response to the COVID-19 pandemic in the United States: a perspective from 15 academic medical centers.
Our goal is to summarize the collective experience of 15 organizations in dealing with uncoordinated efforts that result in unnecessary delays in understanding, predicting, preparing for, containing, and mitigating the COVID-19 pandemic in the US. Response efforts involve the collection and analysis of data corresponding to healthcare organizations, public health departments, socioeconomic indicators, as well as additional signals collected directly from individuals and communities. We focused on electronic health record (EHR) data, since EHRs can be leveraged and scaled to improve clinical care, research, and to inform public health decision-making. We outline the current challenges in the data ecosystem and the technology infrastructure that are relevant to COVID-19, as witnessed in our 15 institutions. The infrastructure includes registries and clinical data networks to support population-level analyses. We propose a specific set of strategic next steps to increase interoperability, overall organization, and efficiencies.


The history of tumor virology.
In the century since its inception, the field of tumor virology has provided groundbreaking insights into the causes of human cancer. Peyton Rous founded this scientific field in 1911 by discovering an avian virus that induced tumors in chickens; however, it took 40 years for the scientific community to comprehend the effect of this seminal finding. Later identification of mammalian tumor viruses in the 1930s by Richard Shope and John Bittner, and in the 1950s by Ludwik Gross, sparked the first intense interest in tumor virology by suggesting the possibility of a similar causal role for viruses in human cancers. This change in attitude opened the door in the 1960s and 1970s for the discovery of the first human tumor viruses--EBV, hepatitis B virus, and the papillomaviruses. Such knowledge proved instrumental to the development of the first cancer vaccines against cancers having an infectious etiology. Tumor virologists additionally recognized that viruses could serve as powerful discovery tools, leading to revolutionary breakthroughs in the 1970s and 1980s that included the concept of the oncogene, the identification of the p53 tumor suppressor, and the function of the retinoblastoma tumor suppressor. The subsequent availability of more advanced molecular technologies paved the way in the 1980s and 1990s for the identification of additional human tumor viruses--human T-cell leukemia virus type 1, hepatitis C virus, and Kaposi's sarcoma virus. In fact, current estimates suggest that viruses are involved in 15% to 20% of human cancers worldwide. Thus, viruses not only have been shown to represent etiologic agents for many human cancers but have also served as tools to reveal mechanisms that are involved in all human malignancies. This rich history promises that tumor virology will continue to contribute to our understanding of cancer and to the development of new therapeutic and preventive measures for this disease in the 21st century.


The impact of rotator cuff pathology on isometric and isokinetic strength, function, and quality of life.
The purposes of this study were to determine the reliability of strength and self-reporting measures, the relationship of different strength measures to function, and the impact of rotator cuff pathology on patients' quality of life. Patients with nonoperated rotator cuff pathology (n = 36) and unaffected control subjects (n = 48) were assessed by use of the LIDO dynamometer to determine isometric and isokinetic (concentric and eccentric) strength of the shoulder rotators. The Shoulder Pain and Disability Index and Short Form-36 were self-reported by patients. Intraclass correlation coefficients (ICCs) were used to assess reliability, and Pearson correlations and multiple linear regression were used to determine the relationship between strength and function. The findings of this study include the following: (1) measures of self-reported physical disability had high reliability (ICC = 0.89); (2) the LIDO dynamometer reliably measured internal and external shoulder rotation strength in both concentric and isometric modes of testing (ICC = 0.78-0.94), whereas eccentric muscle actions had lower reliability; (3) all shoulder rotation strength measures were predictive of disability, with isometric external rotation strength being the most predictive (r = 0.56); and (4) the presence of rotator cuff pathology was highly predictive of impaired physical health quality of life (R(2) = 0.71, P < .001).


Down-regulation of abaI, abaR, Bap and OmpA genes in Acinetobacter baumannii by ethanol extract of Glycyrrhiza glabra after toxicity assessment.
Acinetobacter baumannii is a pathogen that has caused rising concerns within healthcare facilities in recent years. As antibiotic overuse and resistance rise, natural remedies with the potential have received attention as antibiotics that might have fewer side effects and lower resistance. Glycyrrhiza glabra was used to investigate its effects on A. baumannii's quorum sensing and biofilm production abilities. In this study, the toxicity assessment of Glycyrrhiza glabra L. extract on rats, the phytochemical analysis and the quantitative measurement for the association of the biofilm reduction with the active components in the plant was determined. The results indicated ciprofloxacin and gentamicin were the most effective antibiotics and that various capabilities of biofilm-productions were demonstrated, only four percent of the samples established robust biofilm, while 40% to 56% demonstrated weak to moderate biofilm production, respectively. Phytochemical qualitative testing of ethanol leaf extracts from Glycyrrhiza glabra showed the existence of flavonoids, alkaloids, phenolic, tannic acid, and terpenoids, but no saponins. Assessment of toxicity revealed a low hazard, with an LD50 of 4.95 g/Kg. Our results showed that the extract's SICs elucidated a substantial quantitative decrease in biofilm production by the bacterial isolates, including the reference ATCC strain, which is known to be a potent biofilm producer. As a conclusion, biofilm creation in Acinetobacter baumannii has been shown to be greatly reduced by G. glabra extract.


Salivary phenytoin concentrations in geriatric patients.
The concentrations of phenytoin in saliva (Csal) and serum (C) in geriatric patients were compared. Salivary and venous blood samples were collected from 13 patients over 55 years old who were taking oral phenytoin for at least one week. The data of 10 patients were suitable for analysis. Phenytoin concentrations were determined with an immunoassay. Phenytoin Csal/C ratios were calculated. Based on previously reported Csal/C ratios of approximately 0.1 for general patient samples, an expected Csal for each patient was calculated as (C)(0.1). A Student's t test for paired data was used to test for differences between the expected and measured salivary concentrations. The mean Csal/C ratio was 0.098 (S.D. = 0.03, range 0.041-0.152). The correlation between the measured Csal and C was 0.96. There was no significant difference between the expected and measured salivary phenytoin concentrations (p greater than 0.6). This study suggests that age does not affect the ratio of salivary to serum phenytoin concentrations. The wide range of ratios observed, however, indicates that more research is needed before salivary phenytoin concentrations should be used clinically in geriatric patients.


Transformative optimisation of agricultural land use to meet future food demands.
The human population is expected to reach ∼9 billion by 2050. The ensuing demands for water, food and energy would intensify land-use conflicts and exacerbate environmental impacts. Therefore we urgently need to reconcile our growing consumptive needs with environmental protection. Here, we explore the potential of a land-use optimisation strategy to increase global agricultural production on two major groups of crops: cereals and oilseeds. We implemented a spatially-explicit computer simulation model across 173 countries based on the following algorithm: on any cropland, always produce the most productive crop given all other crops currently being produced locally and the site-specific biophysical, economic and technological constraints to production. Globally, this strategy resulted in net increases in annual production of cereal and oilseed crops from 1.9 billion to 2.9 billion tons (46%), and from 427 million to 481 million tons (13%), respectively, without any change in total land area harvested for cereals or oilseeds. This thought experiment demonstrates that, in theory, more optimal use of existing farmlands could help meet future crop demands. In practice there might be cultural, social and institutional barriers that limit the full realisation of this theoretical potential. Nevertheless, these constraints have to be weighed against the consequences of not producing enough food, particularly in regions already facing food shortages.


[Catabolism of threonine in the bacterium Clostridium sticklandii].
Catabolism of L-threonine in the anaerobic bacteria Cl. sticklandii has been studied. Degradation of this amino acid was shown to occur with participation of the following enzymes: NAD-dependent L-threonine-3-dehydrogenase (EC 126.96.36.199), glycine acetyltransferase (EC 220.127.116.11), phosphotransacetylase (EC 188.8.131.52) and acetate kinase (EC 22.214.171.124). The presence of the first two enzymes in Clostridia has been shown for the first time. A scheme of threonine oxidation down to acetic acid and glycine by Cl. sticklandii was proposed. The oxidation of one threonine molecule is coupled with phosphorylation of one ADP molecule and reduction of one NAD+ molecule.


The production effect in memory: multiple species of distinctiveness.
The production effect is the difference in memory favoring words read aloud relative to words read silently during study. According to a currently popular explanation, the distinctiveness of aloud words relative to silent words at the time of encoding underlies the better memory for the former. This distinctiveness is attributable to the additional dimension(s) of encoding for the aloud items that can be subsequently used during retrieval. In this study we argue that encoding distinctiveness is not the sole source of distinctiveness and that, in fact, there is an independent source of distinctiveness, statistical distinctiveness, which may or may not work in harmony with encoding distinctiveness in influencing memory. Statistical distinctiveness refers to the relative size of a subset of items marked by a(ny) unique property. Silently read words can carry statistical distinctiveness if they form a salient minority on the background of a majority of vocalized words. We show that, when the two sources are placed in opposition, statistical distinctiveness modifies the PE in a profound way.


Comparison of the efficacy of two different glucocorticoid regimens for treatment of active moderate-to-severe Graves' orbitopathy.
Intravenous glucocorticoids (GCs) are the mainstay of treatment for severe forms of Graves' orbitopathy (GO). Our aim was to assess the effectiveness and safety of a modified monthly regimen (mMR) and to compare them with those of the established weekly regimen (WR). This was a prospective non-randomized single-center study involving 62 patients, divided into two therapeutic groups depending on their referral time. Thirty-one subjects, admitted in the period 2017-2018, were treated with mMR, total dose-5.5 g, with intake of oral GCs after completion of intravenous infusions. Thirty subjects, who were referred in the period 2019-2020, were treated with WR, total dose-4.5 g One patient refused to be part of the WR group and was treated with mMR. Eye status and therapeutic response were evaluated on the 1st, 3rd and 6th months, quality of life-at 3rd and 6th month. At 1st month and 3rd month, there was no significant difference in the therapeutic response between the two groups. At 3rd month, the proportion of patients with improvement in soft tissue manifestations and subjective complaints was significantly higher in mMR group (65.6% vs. 40% and 81.3% vs. 46.7%, respectively) and the same manifestations were of significantly milder degree. At 3rd month, significant improvement in quality of life was found without significant difference between the two groups. At 6th month, worsening of GO occurred in 3 patients from WR group, while in 5 patients from mMR group further improvement was found. The two GC regimens have comparable efficacy with small differences in the time of onset of the effect and its duration, as well as in the effectiveness on some ocular manifestations. Trial registration number NCT05793359/29.03.2023, retrospectively registered..


Relationship between uric acid albumin ratio and peripheral artery disease complexity.
Uric acid to albumin ratio (UAR) reflects inflammatory activity and its predictive value has been shown in various diseases. In this study, we sought to evaluate the value of uric acid to albumin ratio in patients with peripheral arterial disease (PAD). Two hundred forty-three PAD patients were divided into TransAtlantic Inter-Society Consensus-II (TASC-II) A-B and TASC-II C-D groups, according to their TASC-II classification. Biochemical variables of the patients were recorded, and the UAR of each patient was calculated. Patients who had TASC-II A-B disease were younger than the patients who had TASC-II C-D disease (60.7±8.71 vs. 63.28±8.8 years, p=0.024). Quade ANCOVA results showed that patients with TASC-II C-D disease had higher values of UAR when age was used as a covariate (t=-5.045, p<0.001). Lymphocyte count was significantly lower, and UAR was significantly higher in patients with TASC-II C-D disease (p=0.035 and p<0.001, respectively). UAR and lymphocyte count showed a significant positive correlation and a negative correlation with the TASC-II class of the disease (r=0.403, and r=-0.299, p<0.001 for both). A UAR of 1.54 predicted TASC-II C-D disease with a sensitivity and specificity of 57.9% and 78.8%, respectively. UAR predicted severe PAD with an OR of 3.723. UAR was a better tool for predicting TASC-II C-D disease compared to uric acid and albumin levels. UAR is an easily calculable parameter that can be used in clinical practice.


Significant thermal rectification induced by phonon mismatch of functional groups in a single-molecule junction.
Single-molecule junctions may bring exotic physical effects. In this work, a significant thermal rectification effect is observed in a cross-dimensional system, comprising a diamond, a single-molecule junction, and a carbon nanotube (CNT). The molecular dynamics (MD) simulations indicate that the interfacial thermal resistance varies with the direction of heat flow, the orientation of the crystal planes of the diamond, and the length of the CNT. We find that the thermal rectification ratio escalates with the length of the CNT, achieving a peak value of 730 % with the CNT length of 200 nm. A detailed analysis of phonon vibrations suggests that the primary cause of thermal rectification is the mismatched vibrations between the biphenyl and carbonyl groups. This discovery may offer theoretical insights for both the experimental exploration and practical application of single-molecule junctions in efficient thermal management strategy for high power and highly integrated chips.&#xD.