An Exploration of Lung Volume Effects on Swallowing in Chronic Obstructive Pulmonary Disease.
Purpose Chronic obstructive pulmonary disease (COPD) limits respiration, which may negatively impact airway safety during swallowing. It is unknown how differences in lung volume in COPD may alter swallowing physiology. This exploratory study aimed to determine how changes in lung volume impact swallow duration and coordination in persons with stable state COPD compared with older healthy volunteers (OHVs). Method Volunteers ≥ 45 years with COPD (VwCOPDs; n = 9) and OHVs (n = 10) were prospectively recruited. Group and within-participant differences were examined when swallowing at different respiratory volumes: resting expiratory level (REL), tidal volume (TV), and total lung capacity (TLC). Participants swallowed self-administered 20-ml water boluses by medicine cup. Noncued (NC) water swallows were followed by randomly ordered block swallowing trials at three lung volumes. Estimated lung volume (ELV) and respiratory-swallow patterning were quantified using spirometry and respiratory inductive plethysmography. Manometry measured pharyngeal swallow duration from onset of base of tongue pressure increase to offset of negative pressure in the pharyngoesophageal segment. Results During NC swallows, the VwCOPDs swallowed at lower lung volumes than OHVs (p = .011) and VwCOPDs tended to inspire after swallows more often than OHVs. Pharyngeal swallow duration did not differ between groups; however, swallow duration significantly decreased as the ELV increased in VwCOPDs (p = .003). During ELV manipulation, the COPD group inspired after swallowing more frequently at REL than at TLC (p = .001) and at TV (p = .002). In conclusion, increasing respiratory lung volume in COPD should improve safety by reducing the frequency of inspiration after a swallow.


Bayesian meta-analysis of fMRI image data.
We composed an R-based script for Image-based Bayesian random-effect meta-analysis of previous fMRI studies. It meta-analyzes second-level test results of the studies and calculates Bayes Factors indicating whether the effect in each voxel is significantly different from zero. We compared results from Bayesian and classical meta-analyses by examining the overlap between the result from each method and that created by NeuroSynth as the target. As an example, we analyzed previous fMRI studies focusing on working memory extracted from NeuroSynth. The result from our Bayesian method showed a greater overlap than the classical method. In addition, Bayes Factors proved a better way to examine whether the evidence supported hypotheses than p-values. Given these, Bayesian meta-analysis provides neuroscientists with an alternative meta-analysis method for fMRI studies given the improved overlap with the NeuroSynth result and the practical and epistemological value of Bayes Factors that can directly test the presence of an effect.


Intestinal Obstruction for Anisakiasis: Surgical and Physical Therapy Treatment.
Anisakiasis, a zoonotic disease that can lead to small intestine obstruction, has seen a significant rise in Spain. The country has become the first in Europe with an annual incidence of 8000 cases, primarily due to the popularity of consuming exotic dishes of undercooked or raw fish and the impact of climate change. The clinical presentation of anisakiasis can mimic symptoms of acute appendicitis or intestinal obstruction, leading to potential misdiagnosis. This case report describes a 37-year-old patient with no significant medical history who presented abdominal distension and intense pain in the right lower quadrant. The patient underwent surgery and received physiotherapy treatment, including therapeutic exercises and pulsed-pressure myofascial vacuum therapy, to facilitate functional recovery. The increasing incidence of anisakiasis in Spain underscores the need to consider it in the differential diagnosis of digestive diseases, given the high consumption of poorly prepared or raw fish in the region.


Self-assembled hierarchical nanostructures for high-efficiency porous photonic crystals.
The nanoscale modulation of material properties such as porosity and morphology is used in the natural world to mold the flow of light and to obtain structural colors. The ability to mimic these strategies while adding technological functionality has the potential to open up a broad array of applications. Porous photonic crystals are one such technological candidate, but have typically underachieved in terms of available materials, structural and optical quality, compatibility with different substrates (e.g., silicon, flexible organics), and scalability. We report here an alternative fabrication method based on the bottom-up self-assembly of elementary building blocks from the gas phase into high surface area photonic hierarchical nanostructures at room temperature. Periodic refractive index modulation is achieved by stacking layers with different nanoarchitectures. High-efficiency porous Bragg reflectors are successfully fabricated with sub-micrometer thick films on glass, silicon, and flexible substrates. High diffraction efficiency broadband mirrors (R≈1), opto-fluidic switches, and arrays of photonic crystal pixels with size<10 μm are demonstrated. Possible applications in filtering, sensing, electro-optical modulation, solar cells, and photocatalysis are envisioned.


Blunted aldosterone and ACTH release after human CRH administration in depressed patients.
The authors measured pituitary adrenocortical responses to human corticotropin-releasing hormone (CRH) in 10 patients with a major depressive episode and 10 matched control subjects. Depressed patients had a significantly lower aldosterone and ACTH release, but cortisol and corticosterone responses were not different between groups.


Metabolic regulation at the tricarboxylic acid and glyoxylate cycles of the lignin-degrading basidiomycete Phanerochaete chrysosporium against exogenous addition of vanillin.
A proteomic differential display technique was utilized to study cellular responses of Phanerochaete chrysosporium exposed to vanillin, one of the key intermediates found during lignin biodegradation. Intracellular proteins were resolved by 2-DE and target protein spots were identified using MALDI-MS after in-gel tryptic digestions. Upon addition of vanillin to P. chrysosporium, up-regulation of homogentisate 1,2-dioxygenase, 1,4-benzoquinone reductases, aldehyde dehydrogenase, and aryl-alcohol dehydrogenase, which seem to play roles in vanillin metabolism, was observed. Furthermore, enzymes involved in glycolysis, the tricarboxylic acid cycle, the pentose-phosphate cycle, and heme biosynthesis were also activated. Up-regulation of extracellular peroxidase was also observed. One of the most unique phenomena against exogenous vanillin was a switch from the glyoxylate cycle to the tricarboxylic acid cycle, where a drastic increase in isocitrate dehydrogenase activity was observed. The exogenous addition of other aromatic compounds also caused an increase in its activity, which in turn triggered NAD(P)H production via the action of dehydrogenases in the tricarboxylic acid cycle, heme biosynthesis via the action of aminolevulinic acid synthase on succinyl-CoA, and energy production via activation of the mitochondrial electron transfer system. These metabolic shifts seem to be required for activating a metabolic system for aromatic compounds.


[Questions of epileptogenesis and prevention in symptomatic epilepsies].
Symptomatic epilepsies usually report themselves after a longer period of time after brain injury, after the so-called latent period. During this period progressive functional and structural changes occur which finally cause an increased excitatory condition. The process of epileptogenesis may be examined in animal models, such as in the kindling, status epilepticus, hypoxicischaemic models. Data gained from such sources support the hypothesis that the first injury results in a lower seizure threshold, but genetical and environmental factors also contribute to the development of epilepsy and most probably further insults may be needed. The development of epilepsy can be traced back to several reasons. In spite of this, the latent period provides opportunity for the prevention of epilepsy or for the influence of epileptogenesis in such a manner that later treatment can become more successful. Prevention should be an aim in clinical practice, as well. Medication used presently are more like to have anticonvulsive properties and their antiepileptogenic effect is questionable. Due to this fact, development of new drugs is necessary with new theoretical background. The most important influence on the incidence of epilepsy in recent years has been provided by the improvement in neonatal care. This highlights the fact that such optimal medical care should be provided in the acute period of brain injury which can terminate or lessen the risk of epilepsy.


Brainstem seizure severity regulates forebrain seizure expression in the audiogenic kindling model.
Although sound-induced (audiogenic) seizures in the genetically epilepsy-prone rat (GEPR) initially occur independent of the forebrain, repeated audiogenic seizures recruit forebrain seizure circuits in a process referred to as audiogenic kindling. In GEPR-3s, audiogenic kindling results in facial and forelimb (F&F) clonic seizures that are typical of forebrain seizures. However, in GEPR-9s, audiogenic kindling produces posttonic all-limb clonus not usually observed during forebrain seizures. We hypothesized that the more severe brainstem seizures of the GEPR-9 prevent the expression of F&F clonic seizures during audiogenic kindling. Therefore attenuation of audiogenic seizures during audiogenic kindling in GEPR-9s should allow F&F clonic seizures to be expressed. Likewise, intensifying audiogenic seizure severity in GEPR-3s should inhibit audiogenically kindled F&F clonic seizures. We have tested this hypothesis in the present study. Lesions of the superior colliculus or treatment with low-dose phenytoin were used to suppress audiogenic seizure severity in GEPR-9s. Depletion of brain serotonin was used to increase the seizure severity in GEPR-3s. All GEPRs were then subjected to audiogenic kindling. Behavioral and electrographic seizures were assessed. Suppression of audiogenic seizure severity during audiogenic kindling in GEPR-9s increased the incidence forebrain seizure behavior. Kindled GEPR-9s that continued to display full tonic seizures did not exhibit forebrain convulsions, but did show posttonic clonus and forebrain seizure activity in the EEG. GEPR-3s chronically depleted of brain serotonin, along with displaying tonic brainstem seizures, tended to display less severe forebrain seizures during audiogenic kindling. These findings support the concept that severe brainstem seizures prevent the behavioral expression of forebrain seizures in audiogenically kindled GEPR-9s. It appears that the severe brainstem seizure of the GEPR-9 does not allow the forebrain seizure to manifest its typical behavioral concomitants despite electrographic evidence that spike-wave discharge is occurring in the forebrain.


Prognostic evaluation of estrogen receptors and urinary androgens in ovariectomy for advanced breast cancer.
Eighty patients with advanced breast cancer were characterized by estrogen receptor (ER) status and by urine androgen (A) metabolites. After ovariectomy, patients with positive hormonal parameters were treated with hormonal therapy and patients with negative parameters were treated with chemotherapy. The results of the follow-up confirm that the survival is higher in patients with positive hormonal parameters (ER+, A+). In this group, the patients with increased urine androgen excretion (i.e. A+) apparently had a better long-term survival than ER+ cases.


Altered Plasma Levels of Glial Cell Line-Derived Neurotrophic Factor in Patients with Internet Gaming Disorder: A Case-Control, Pilot Study.
Glial cell line-derived neurotrophic factor (GDNF) has been reported to be involved in negatively regulating the effects of addictive disorders. The objective of this study was to investigate alterations in the levels of GDNF in patients with Internet gaming disorder (IGD) and to assess the relationship between GDNF levels and the severity of IGD indices. Nineteen male patients with IGD and 19 sexmatched control subjects were evaluated for alteration of plasma GDNF levels and for relationship between GDNF levels and clinical characteristics of Internet gaming, including the Young's Internet Addiction Test (Y-IAT). The GDNF levels were found to be significantly low in patients with IGD (103.2±62.0 pg/mL) compared with the levels of controls (245.2±101.6 pg/mL, p<0.001). GDNF levels were negatively correlated with Y-IAT scores (Spearman's rho=-0.645, p=<0.001) and this negative correlation remained even after controlling for multiple variables (r=-0.370, p=0.048). These findings support the assumed role of GDNF in the regulation of IGD.


Design and Synthesis of Novel Schiff Base-Benzothiazole Hybrids as Potential Epidermal Growth Factor Receptor (EGFR) Inhibitors.
A series of novel Schiff bases -benzothiazole hybrids was designed, synthesized and evaluated for their anticancer activity by MTT assay and western blot method. Antiproliferative screening indicated that compound containing dihydroxy substituents had potent inhibitory activity with IC50 value 34µg/ml against SKOV3, A2780-S and A2780-CR cell lines. It showed more potent cytotoxicity in combination with cisplatin and paclitaxel than alone in the selected cell lines (SKOV3, A2780 and A2780-CR models). The in vitro cytotoxicity of the compounds on IOSE 364 cell line was evaluated to establish the selectivity. Molecular docking study exhibited good binding against epidermal growth factor receptor, which was further ascertained by immunoblot assay using specific antibody against phosphorylated EGFR, and thus unravelling the targeted anticancer mechanism.


Methicillin-resistant Staphylococcus aureus in Dutch soccer team.
An outbreak of community-acquired methicillin-resistant Staphylococcus aureus occurred among members and close contacts of a soccer team. Typing of the isolates showed the outbreak was caused by the well-known European ST80-IV strain. To our knowledge, this is the first report of an outbreak of this strain among members of a sports team.


Distribution and specific identification of papillomavirus major capsid protein epitopes by immunocytochemistry and epitope scanning of synthetic peptides.
Monoclonal (MAbs) and polyclonal antibodies were produced against the major capsid protein of detergent-disrupted, purified bovine papillomavirus type 1 (BPV-1). The precise locations of the corresponding epitopes were identified by the reactivity of MAbs and selected polyclonal antibodies with synthetic, overlapping, hexameric peptides corresponding with 95% of the BPV-1 major capsid protein. The topography of these epitopes was determined by reactivity of antibodies with intact (conformational and nonconformational surface epitopes) and disrupted (external or internal nonconformational epitopes) BPV-1 virions. The distribution of epitopes in various papillomaviruses of 13 different species was determined by reactivity of the MAbs and polyclonal sera with productively infected, formalin-fixed papillomas, fibropapillomas, and fibromas. Epitope scanning, using MAbs and polyclonal antisera, resulted in the precise location of BPV-1 hexameric epitopes that could be correlated with their topography on the capsid and distribution in papillomatous lesions of various species.


Cancer survival: an overview of measures, uses, and interpretation.
Survival statistics are of great interest to patients, clinicians, researchers, and policy makers. Although seemingly simple, survival can be confusing: there are many different survival measures with a plethora of names and statistical methods developed to answer different questions. This paper aims to describe and disseminate different survival measures and their interpretation in less technical language. In addition, we introduce templates to summarize cancer survival statistic organized by their specific purpose: research and policy versus prognosis and clinical decision making.


Comparative proteomic profiling of culture filtrate proteins of less and highly virulent Francisella tularensis strains.
The facultative intracellular bacterium Francisella tularensis is the causal agent of the serious infectious disease tularemia. Despite the dynamic progress, which has been made in last few years, important questions regarding Francisella pathogenicity still remain to be answered. Generally, secreted proteins play an important role in pathogenicity of intracellular microbes. In this study, we investigated the protein composition of the culture filtrate proteins of highly virulent F. tularensis subsp. tularensis, strain SCHU S4 and attenuated F. tularensis subsp. holarctica, live vaccine strain using a comparative proteomic analysis. The majority of proteins identified in this study have been implicated in virulence mechanisms of other pathogens, and several have been categorized as having moonlighting properties; those that have more than one unrelated function. This profiling study of secreted proteins resulted in the unique detection of acid phosphatase (precursor) A (AcpA), β-lactamase, and hypothetical protein FTT0484 in the highly virulent strain SCHU S4 secretome. The release of AcpA may be of importance for F. tularensis subsp. tularensis virulence due to the recently described AcpA role in the F. tularensis escape from phagosomes.


Effect of a pressure barrier on retrograde axoplasmic transport in vitro. A study in the motor neurons of the rabbit vagus.
Retrograde axoplasmic transport, demonstrated by the "double ligature method" was studied in vitro in the motor neurons of rabbit vagus nerve, labelled with 3H-leucine. When a pressure barrier with a maximal pressure of 30 mmHg, induced by a fluid jet, was applied to a small section of the nerve at 38 degrees C, retrograde flow was partially inhibited. More radioactivity was found in front of the barrier (with respect to direction of flow) than immediately behind it. This observation differs from findings in anterograde transport at the same pressure and tested with a similar technique, where most radioactivity was detected immediately behind the barrier (Hahnenberger 1978).


Impairment due to combined sleep restriction and alcohol is not mitigated by decaying breath alcohol concentration or rest breaks.
Epidemiological and laboratory-based driving simulator studies have shown the detrimental impact of moderate, legal levels of alcohol consumption on driving performance in sleepy drivers. As less is known about the time course of decaying alcohol alongside performance impairment, our study examined impairment and recovery of performance alongside decaying levels of alcohol, with and without sleep restriction. Sixteen healthy young males (18-27 years) underwent 4 counterbalanced conditions: Baseline, Alcohol (breath alcohol concentration [BrAC] < 0.05%), Sleep Restriction (5 hr time in bed), and Combined. Participants consumed alcohol (or control drink) ~4.5 hr post wake (12:30 p.m.). To test on the descending limb of alcohol, attention and vigilance test batteries commenced 1 hr after consumption and were completed every 30 min for 2 hr (1:30 p.m.-3:30 p.m.). The Combined condition impaired subjective and objective sleepiness. Here, performance deficits peaked 90 min after alcohol consumption or 30 min after the BrAC peak. Performance did not return to baseline levels until 2.5 hr following consumption, despite receiving rest breaks in between testing. These findings suggest that (a) falling BrACs are an inadequate guide for performance/safety and (b) rest breaks without sleep are not a safety measure for mitigating performance impairment when consuming alcohol following restricted sleep.


Sub-6 nm Palladium Nanoparticles for Faster, More Sensitive H2 Detection Using Carbon Nanotube Ropes.
Palladium (Pd) nanoparticle (NP)-decorated carbon nanotube (CNT) ropes (or CNT@PdNP) are used as the sensing element for hydrogen gas (H2) chemiresistors. In spite of the fact that Pd NPs have a mean diameter below 6 nm and are highly dispersed on the CNT surfaces, CNT@PdNP ropes produce a relative resistance change 20-30 times larger than is observed at single, pure Pd nanowires. Thus, CNT@PdNP rope sensors improve upon all H2 sensing metrics (speed, dynamic range, and limit-of-detection), relative to single Pd nanowires which heretofore have defined the state-of-the-art in H2 sensing performance. Specifically, response and recovery times in air at [H2] ≈ 50 ppm are one-sixth of those produced by single Pd nanowires with cross-sectional dimensions of 40 × 100 nm Pd. The LODH2 is <10 ppm versus 300 ppm, and the dynamic range (10 ppm -4%) is nearly twice that afforded by the Pd nanowire. CNT@PdNP rope sensors are prepared by the dielectrophoretic deposition of a single semiconducting CNT rope followed by the electrodeposition of Pd nanoparticles with mean diameters ranging from 4.5 (±1) nm to 5.8 (±3) nm. The diminutive mean diameter and the high degree of diameter monodispersity for the deposited Pd nanoparticles are distinguishing features of the CNT@PdNP rope sensors described here, relative to prior work on similar systems.


Analytic solutions for some reaction-diffusion scenarios.
Motivated currently by the problem of coalescence of receptor clusters in mast cells in the general subject of immune reactions, and formerly by the investigation of exciton trapping and sensitized luminescence in molecular systems and aggregates, we present analytic expressions for survival probabilities of moving entities undergoing diffusion and reaction on encounter. Results we provide cover several novel situations in simple 1-d systems as well as higher-dimensional counterparts along with a useful compendium of such expressions in chemical physics and allied fields. We also emphasize the importance of the relationship of discrete sink term analysis to continuum boundary condition studies.


Pomalidomide, dexamethasone, and daratumumab in relapsed refractory multiple myeloma after lenalidomide treatment.
Patients with multiple myeloma who have relapsed after or become refractory to lenalidomide in early treatment lines represent a clinically important population in need of effective therapies. The safety and efficacy of pomalidomide, low-dose dexamethasone, and daratumumab was evaluated in lenalidomide-pretreated patients with relapsed or refractory multiple myeloma (RRMM) after one to two prior treatment lines in the phase 2 MM-014 study. Patients received pomalidomide 4 mg daily from days 1-21 and dexamethasone 40 mg weekly (28-day cycles). Daratumumab 16 mg/kg was administered per label. Primary endpoint was overall response rate (ORR); secondary endpoints included progression-free survival (PFS) and safety. Per protocol, all patients (N = 112) had received lenalidomide in their most recent prior regimen (75.0% lenalidomide refractory). ORR was 77.7% (76.2% in lenalidomide-refractory patients); median follow-up was 17.2 months. Median PFS was not reached (1-year PFS rate 75.1%). The most common hematologic grade 3/4 treatment-emergent adverse event was neutropenia (62.5%). Grade 3/4 infections were reported in 31.3% of patients, including 13.4% with grade 3/4 pneumonia. These results demonstrate the safety and efficacy of pomalidomide-based therapy as early as second line in patients with RRMM, even immediately after lenalidomide failure, indicating that switching from the immunomodulatory agent class is not necessary.


Sub-epithelial connective tissue graft for root coverage in nonsmokers and smokers: A pilot comparative clinical study.
Gingival recession is a common condition and is more prevalent in smokers. It is widely believed that root coverage procedures in smokers result in less desirable outcome compared to nonsmokers', and there are few controlled studies in literature to support this finding. Therefore, the purpose of this study was to evaluate and compare the outcome of root coverage with sub-epithelial connective tissue graft (SCTG) in nonsmokers and smokers. A sample of twenty subjects, 10 nonsmokers and 10 smokers were selected each with at least 1 Miller's Class I or II recession on a single rooted tooth. Clinical measurements of probing depth, clinical attachment level (CAL), gingival recession total surface area (GRTSA), depth of recession (RD), width of recession (RW), and width of keratinized tissue were determined at baseline, 3, and 6 months after surgery. The treatment of gingival recession with SCTG and coronally advanced flap showed a decrease in the GRTSA, RD, RW, and an increase in CAL and width of keratinized gingiva in both the groups. However, the intergroup comparison of the clinical parameters showed no statistical significance. About 6 out of 10 nonsmokers (60%) and 3 smokers (30%) showed complete root coverage. The mean percentage of root coverage of 71.2% in nonsmokers and 38% in smokers was observed. The results of the present study suggest that smoking may negatively influence gingival recession reduction and CAL gain. In addition, smokers may exhibit fewer chances of complete root coverage. Overall, nonsmokers showed better improvements in all the parameters compared to smokers at the end of 6 months.


Central and peripheral inhibition of angiotensin converting enzyme (ACE) in the SHR: correlation with the antihypertensive activity of ACE inhibitors.
A series of five structurally distinct ACE inhibitors were evaluated for their ability to inhibit tissue ACE activity in the SHR after oral administration. In the first series of experiments, the ACE inhibitors captopril, enalapril, pentopril, CGS 14824A and CGS 16617 were given to groups of SHR at doses that produced a 15 to 20 mm Hg reduction in blood pressure within 1 hour. Under these conditions of dose and time, only captopril significantly inhibited brain ACE activity (43%), whereas inhibition of serum ACE activity ranged from 72% to 99% with these agents. Inhibition of aortic ACE activity ranged from 54% to 87%, and lung ACE inhibition varied from 50% to 83%. In the second series of experiments, SHR were administered higher doses of each ACE inhibitor such that these compounds produced peak reductions in blood pressure (-25 mm Hg to -33 mm Hg) within a range of 2 to 6 hours. When tissue ACE activity was measured at the time corresponding to peak reduction in blood pressure, all five ACE inhibitors produced a significant inhibition of brain ACE activity ranging from 21% to 76%. Serum ACE activity was almost completely inhibited by these agents, with the exception of captopril (62% inhibition). The inhibition of aortic ACE activity ranged from 79% to 99%, while the inhibition of lung ACE activity did not increase under these conditions. These data suggest that ACE inhibitors may exert their maximal antihypertensive effects by inhibiting ACE in vascular tissues and brain.


An Inverse Neural Controller Based on the Applicability Domain of RBF Network Models.
This paper presents a novel methodology of generic nature for controlling nonlinear systems, using inverse radial basis function neural network models, which may combine diverse data originating from various sources. The algorithm starts by applying the particle swarm optimization-based non-symmetric variant of the fuzzy means (PSO-NSFM) algorithm so that an approximation of the inverse system dynamics is obtained. PSO-NSFM offers models of high accuracy combined with small network structures. Next, the applicability domain concept is suitably tailored and embedded into the proposed control structure in order to ensure that extrapolation is avoided in the controller predictions. Finally, an error correction term, estimating the error produced by the unmodeled dynamics and/or unmeasured external disturbances, is included to the control scheme to increase robustness. The resulting controller guarantees bounded input-bounded state (BIBS) stability for the closed loop system when the open loop system is BIBS stable. The proposed methodology is evaluated on two different control problems, namely, the control of an experimental armature-controlled direct current (DC) motor and the stabilization of a highly nonlinear simulated inverted pendulum. For each one of these problems, appropriate case studies are tested, in which a conventional neural controller employing inverse models and a PID controller are also applied. The results reveal the ability of the proposed control scheme to handle and manipulate diverse data through a data fusion approach and illustrate the superiority of the method in terms of faster and less oscillatory responses.


Modulation of the default-mode network between rest and task in Alzheimer's Disease.
Default-mode network (DMN) connectivity at rest is disrupted in Alzheimer's Disease (AD), but it is unknown whether this abnormality is a static feature, or if it varies across cognitive states. We measured DMN integrity in 16 patients with mild AD and 18 controls during resting state and a simple visual task. Patients showed resting-state deficits in the parahippocampal gyrus and posterior cingulate. No group differences were found during the task. Controls exhibited higher DMN connectivity of multiple regions during rest than task, while the patient group showed no modulation of the DMN between states. However, the relative degree of increased resting- versus task-state co-activation in the posterior cingulate and precuneus was predictive of mini-mental status exam (MMSE) scores in AD patients, while measures at rest or task alone were not associated with MMSE. These findings suggest that a resting state may be more suited to detecting DMN abnormalities in AD than a simple task. However, the degree of state-dependent modulation in the DMN may be a better predictor of the individual cognitive status than a single-state acquisition. This study demonstrates an apparent reduction in the capacity for DMN modulation in individuals with mild AD, the degree of which uniquely predicted cognitive status.


COVID19 Diagnosis Using Chest X-rays and Transfer Learning.
A pandemic of respiratory illnesses from a novel coronavirus known as Sars-CoV-2 has swept across the globe since December of 2019. This is calling upon the research community including medical imaging to provide effective tools for use in combating this virus. Research in biomedical imaging of viral patients is already very active with machine learning models being created for diagnosing Sars-CoV-2 infections in patients using CT scans and chest x-rays. We aim to build upon this research. Here we used a transfer-learning approach to develop models capable of diagnosing COVID19 from chest x-ray. For this work we compiled a dataset of 112120 negative images from the Chest X-Ray 14 and 2725 positive images from public repositories. We tested multiple models, including logistic regression and random forest and XGBoost with and without principal components analysis, using five-fold cross-validation to evaluate recall, precision, and f1-score. These models were compared to a pre-trained deep-learning model for evaluating chest x-rays called COVID-Net. Our best model was XGBoost with principal components with a recall, precision, and f1-score of 0.692, 0.960, 0.804 respectively. This model greatly outperformed COVID-Net which scored 0.987, 0.025, 0.048. This model, with its high precision and reasonable sensitivity, would be most useful as "rule-in" test for COVID19. Though it outperforms some chemical assays in sensitivity, this model should be studied in patients who would not ordinarily receive a chest x-ray before being used for screening.


Kidney allograft biopsy findings after COVID-19.
COVID-19 has been associated with acute kidney injury and published reports of native kidney biopsies have reported diverse pathologies. Case series directed specifically to kidney allograft biopsy findings in the setting of COVID-19 are lacking. We evaluated 18 kidney transplant recipients who were infected with SARS-CoV-2 and underwent allograft biopsy. Patients had a median age of 55 years, six were female, and five were Black. Fifteen patients developed COVID-19 pneumonia, of which five required mechanical ventilation. Notably, five of 11 (45%) biopsies obtained within 1 month of positive SARS-CoV-2 PCR showed acute rejection (four with arteritis, three of which were not associated with reduced immunosuppression). The remaining six biopsies revealed podocytopathy (n = 2, collapsing glomerulopathy and lupus podocytopathy), acute tubular injury (n = 2), infarction (n = 1), and transplant glomerulopathy (n = 1). Biopsies performed >1 month after positive SARS-CoV-2 PCR revealed collapsing glomerulopathy (n = 1), acute tubular injury (n = 1), and nonspecific histologic findings (n = 5). No direct viral infection of the kidney allograft was detected by immunohistochemistry, in situ hybridization, or electron microscopy. On follow-up, two patients died and most patients showed persistent allograft dysfunction. In conclusion, we demonstrate diverse causes of kidney allograft dysfunction after COVID-19, the most common being acute rejection with arteritis.


What safety net for children?
As our nation attempts to address the multiple health and social needs of children, it is obvious that the so-called safety net of services for children and families is currently not meeting their needs. Within the current dialogue over health care reform, the special needs of children and pregnant women must not be lost. This paper discusses basic components which should be included in any discussion of health care reform. Individualized personal involvement in the solution to the health and social problems of today's underserved children and families is crucial.


Action Unit Models of Facial Expression of Emotion in the Presence of Speech.
Automatic recognition of emotion using facial expressions in the presence of speech poses a unique challenge because talking reveals clues for the affective state of the speaker but distorts the canonical expression of emotion on the face. We introduce a corpus of acted emotion expression where speech is either present (talking) or absent (silent). The corpus is uniquely suited for analysis of the interplay between the two conditions. We use a multimodal decision level fusion classifier to combine models of emotion from talking and silent faces as well as from audio to recognize five basic emotions: anger, disgust, fear, happy and sad. Our results strongly indicate that emotion prediction in the presence of speech from action unit facial features is less accurate when the person is talking. Modeling talking and silent expressions separately and fusing the two models greatly improves accuracy of prediction in the talking setting. The advantages are most pronounced when silent and talking face models are fused with predictions from audio features. In this multi-modal prediction both the combination of modalities and the separate models of talking and silent facial expression of emotion contribute to the improvement.


Genetic predisposition to bronchopulmonary dysplasia.
The objective of this study is to review the candidate gene and genome-wide association studies relevant to bronchopulmonary dysplasia, and to discuss the emerging understanding of the complexities involved in genetic predisposition to bronchopulmonary dysplasia and its outcomes. Genetic factors contribute much of the variance in risk for BPD. Studies to date evaluating single or a few candidate genes have not been successful in yielding results that are replicated in GWAS, perhaps due to more stringent p-value thresholds. GWAS studies have identified only a single gene (SPOCK2) at genome-wide significance in a European White and African cohort, which was not replicated in two North American studies. Pathway gene-set analysis in a North American cohort confirmed involvement of known pathways of lung development and repair (e.g., CD44 and phosphorus oxygen lyase activity) and indicated novel molecules and pathways (e.g., adenosine deaminase and targets of miR-219) involved in genetic predisposition to BPD. The genetic basis of severe BPD is different from that of mild/moderate BPD, and the variants/pathways associated with BPD vary by race/ethnicity. A pilot study of whole exome sequencing identified hundreds of genes of interest, and indicated the overall feasibility as well as complexity of this approach. Better phenotyping of BPD by severity and pathophysiology, and careful analysis of race/ethnicity is required to gain a better understanding of the genetic basis of BPD. Future translational studies are required for the identification of potential genetic predispositions (rare variants and dysregulated pathways) by next-generation sequencing methods in individual infants (personalized genomics).


Piglet birth weight and litter uniformity: effects of weaning-to-pregnancy interval and body condition changes in sows of different parities and crossbred lines.
Piglet birth weight and litter uniformity were studied in sows of different parities and crossbred lines in relation to: 1) weaning-to-pregnancy interval (WPI) and 2) sow body condition changes (in BW and backfat thickness) during lactation and gestation in sows with a short WPI (≤7d). At the Institute for Pig Genetics (IPG) research farm, individual piglet birth weights and sow body condition (BW and backfat thickness at farrowing and weaning) were measured for 949 TOPIGS20 and 889 TOPIGS40 sows with >4 total born piglets, inseminated between 2003 and 2011. In all analyses, mean piglet birth weight and birth weight SD and CV were corrected for total number born. Total number born was greater in sows with a WPI of 8 to 21 d (+1.2 piglets; n = 72) and >21 d (+0.7 piglets; n = 182), compared with sows with a WPI ≤7 d (P < 0.01; n = 1,584). Mean piglet birth weight was not affected by WPI. Birth weight SD (-23 g) and CV (-1.7%) were lower in sows with a WPI >21 d, compared with sows with a WPI ≤7 d (P < 0.01). Effects of WPI were independent of sow parity. Effects of body condition changes in sows with a WPI ≤7 d were studied separately in TOPIGS20 sows inseminated between 2006 and 2011 (n = 808), and in TOPIGS40 sows inseminated between 2003 and 2008 (n = 747). Sow body condition loss during lactation was not related with subsequent total number born or mean piglet birth weight. Only in TOPIGS20 sows, more BW loss during lactation was related with greater subsequent birth weight SD (β = 0.83 g/kg, P < 0.01; β = 1.62 g/%, P < 0.01). Additionally, more backfat loss during lactation was related with greater subsequent birth weight SD (β = 5.11 g/mm, P < 0.01) and CV (β = 0.36%/mm, P < 0.01), independent of sow parity. Sow BW increase during gestation was negatively related with total number born [TOPIGS20: β = -0.06 and -0.05 piglet/kg BW increase for parity 2 (P < 0.01), and 3 and 4 (P < 0.01), respectively; TOPIGS40: β = -0.04 piglet/kg BW increase (P < 0.01), independent of sow parity]. Sow BW increase during gestation was positively related with birth weight SD [TOPIGS20: β = 0.63 g/kg BW increase (P = 0.01), independent of sow parity]. Sow body condition increase during gestation was not related with mean piglet birth weight. To conclude, this study shows that litter uniformity is compromised by severe sow body condition loss during lactation and improved in sows with a prolonged WPI. These effects are likely related with (insufficient) restoration of follicle development.


Review of Randomized Controlled Trials of Massage in Preterm Infants.
Preterm birth affects about 10% of infants born in the United States. Massage therapy is being used in some neonatal intensive care units for its potential beneficial effects on preterm infants. This article reviews published randomized controlled trials on the effects of massage in preterm infants. Most studies evaluating the effect of massage in weight gain in premature infants suggest a positive effect on weight gain. Increase in vagal tone has been reported in infants who receive massage and has been suggested as a possible mechanism for improved weight gain. More studies are needed on the underlying mechanisms of the effects of massage therapy on weight gain in preterm infants. While some trials suggest improvements in developmental scores, decreased stress behavior, positive effects on immune system, improved pain tolerance and earlier discharge from the hospital, the number of such studies is small and further evidence is needed. Further studies, including randomized controlled trials, are needed on the effects of massage in preterm infants.


Persistent and selective upregulation of renin-angiotensin system in circulating T lymphocytes in unstable angina.
Unstable angina is associated with an acute systemic inflammatory reaction and circulating T lymphocytes are activated. We investigated whether in unstable angina with marked immune system activation a selective upregulation of the circulating T-cell renin-angiotensin system, modulated by angiotensin II, could occur. We studied 13 unstable angina patients, 10 patients with stable angina and 10 healthy subjects. After T-lymphocyte isolation, mRNAs for angiotensin-converting enzyme (ACE) and angiotensin type 1 receptor (AT1-R) were quantified at baseline and after angiotensin II stimulation. ACE activity in cell pellet and supernatant and angiotensin II cell content were measured. Plasma renin activity was similar in controls, stable and unstable angina patients. At baseline ACE and AT1-R mRNA levels were higher ( P<0.05) in T cells from unstable angina patients than in T cells from stable angina patients and controls, and further increased after angiotensin II addition to cultured T cells. ACE activity of unstable angina T cells was significantly higher than that of T cells from controls and stable angina patients. Only in T cells from unstable angina patients did angiotensin II stimulation cause the almost complete release of ACE activity in the supernatant. The circulating T-cell-based renin-angiotensin system from unstable angina patients was selectively upregulated. In vivo unstable angina T cells could locally increase angiotensin II concentration in tissues where they migrate independently of the circulating renin-angiotensin system.


Diet and body fat in adolescence and early adulthood: a systematic review of longitudinal studies.
Adipose tissue is a vital component of the human body, but in excess, it represents a risk to health. According to the World Health Organization, one of the main factors determining excessive body adiposity is the dietary habit. This systematic review investigated longitudinal studies that assessed the association between diet and body fat in adolescents and young adults. Twenty-one relevant papers published between 2001 and 2015 were selected. The most used method for estimating body fat was the body mass index (15 studies). Diet was most commonly assessed by estimating the consumption of food groups (cereals, milk and dairy products) and specific foods (sugar-sweetened beverages, soft drinks, fast foods, milk, etc.). Ten studies found a direct association between diet and quantity of body fat. During adolescence, adhering to a dietary pattern characterized by high consumption of energy-dense food, fast foods, sugar-sweetened beverages and soft drinks, as well as low fiber intake, appears to contribute to an increase in body fat in early adulthood. The findings of the present study suggest that the frequent consumption of unhealthy foods and food groups (higher energy density and lower nutrient content) in adolescence is associated with higher quantity of body fat in early adulthood.


The Efficacy of a Web-Based Stress Management Intervention for Employees Experiencing Adverse Working Conditions and Occupational Self-efficacy as a Mediator: Randomized Controlled Trial.
Work stress is highly prevalent and puts employees at risk for adverse health consequences. Web-based stress management interventions (SMIs) promoting occupational self-efficacy might be a feasible approach to aid employees to alleviate this burden and to enable them to improve an unbalanced situation between efforts and rewards at work. The first aim of this randomized controlled trial was to investigate the efficacy of a web-based SMI for employees perceiving elevated stress levels and an effort-reward imbalance in comparison to a waitlist control (WLC) group. Second, we investigated whether the efficacy of an SMI could be explained by an increase in occupational self-efficacy and whether this personal resource enables employees to change adverse working conditions. A total of 262 employees reporting effort-reward imbalance scores over 0.715 and elevated stress levels (10-item Perceived Stress Scale [PSS-10] score ≥22) were randomly assigned to either the intervention group (IG; SMI) or the WLC group. The primary outcome was perceived stress measured using the PSS-10. The secondary outcomes included mental and work-related health measures. Four different mediation analyses were conducted with occupational self-efficacy, efforts, and rewards as mediators. After eligibility screening, data were collected web based at baseline (T1), 7 weeks (T2) and 6 months (T3). Study participation was completed by 80% (105/130, 80.8%) in the IG and 90% (119/132, 90.2%) in the WLC group. Analyses of covariance revealed that stress reduction was significantly higher for the SMI group compared with the WLC group at T2 (d=0.87, 95% CI 0.61-1.12, P<.001) and T3 (d=0.65, 95% CI 0.41-0.90, P<.001). Mediation analyses indicated that occupational self-efficacy mediated the beneficial effect of the SMI on stress directly. Furthermore, the analyses revealed a significant indirect effect of occupational self-efficacy via rewards (b=0.18, t259=4.52, P<.001), but not via efforts (b=0.01, t259=0.27, P>.05) while efforts still had a negative impact on stress (b=0.46, t257=2.32, P<.05). The SMI was effective in reducing stress and improving occupational self-efficacy in employees despite them experiencing an effort-reward imbalance at work. Results from mediation analyses suggest that fostering personal resources such as occupational self-efficacy contributes to the efficacy of the SMI and enables employees to achieve positive changes regarding the rewarding aspects of the workplace. However, the SMI seemed to neither directly nor indirectly impact efforts, suggesting that person-focused interventions might not be sufficient and need to be complemented by organizational-focused interventions to comprehensively improve mental health in employees facing adverse working conditions. German Clinical Trials Register DRKS00005990; https://tinyurl.com/23fmzfu3.


4D flow cardiovascular magnetic resonance derived energetics in the Fontan circulation correlate with exercise capacity and CMR-derived liver fibrosis/congestion.
This study explores the relationship between in vivo 4D flow cardiovascular magnetic resonance (CMR) derived blood flow energetics in the total cavopulmonary connection (TCPC), exercise capacity and CMR-derived liver fibrosis/congestion. The Fontan circulation, in which both caval veins are directly connected with the pulmonary arteries (i.e. the TCPC) is the palliative approach for single ventricle patients. Blood flow efficiency in the TCPC has been associated with exercise capacity and liver fibrosis using computational fluid dynamic modelling. 4D flow CMR allows for assessment of in vivo blood flow energetics, including kinetic energy (KE) and viscous energy loss rate (EL). Fontan patients were prospectively evaluated between 2018 and 2021 using a comprehensive cardiovascular and liver CMR protocol, including 4D flow imaging of the TCPC. Peak oxygen consumption (VO2) was determined using cardiopulmonary exercise testing (CPET). Iron-corrected whole liver T1 (cT1) mapping was performed as a marker of liver fibrosis/congestion. KE and EL in the TCPC were computed from 4D flow CMR and normalized for inflow. Furthermore, blood flow energetics were compared between standardized segments of the TCPC. Sixty-two Fontan patients were included (53% male, 17.3 ± 5.1 years). Maximal effort CPET was obtained in 50 patients (peak VO2 27.1 ± 6.2 ml/kg/min, 56 ± 12% of predicted). Both KE and EL in the entire TCPC (n = 28) were significantly correlated with cT1 (r = 0.50, p = 0.006 and r = 0.39, p = 0.04, respectively), peak VO2 (r = - 0.61, p = 0.003 and r = - 0.54, p = 0.009, respectively) and % predicted peak VO2 (r = - 0.44, p = 0.04 and r = - 0.46, p = 0.03, respectively). Segmental analysis indicated that the most adverse flow energetics were found in the Fontan tunnel and left pulmonary artery. Adverse 4D flow CMR derived KE and EL in the TCPC correlate with decreased exercise capacity and increased levels of liver fibrosis/congestion. 4D flow CMR is promising as a non-invasive screening tool for identification of patients with adverse TCPC flow efficiency.


Patient experience of implant loss after immediate breast reconstruction: An interpretative phenomenological analysis.
Immediate breast reconstruction (IBR) is an integral part of modern breast cancer treatment. Our aim was to investigate patient experience with implant loss after IBR by using interpretative phenomenological analysis (IPA). We conducted semi-structured interviews with eight informants. We analyzed data according to the IPA flexible seven-stage process and four main themes were developed: immediate breast reconstruction as the indisputable choice, a difficult experience, an altered body: redefining normality, and trying to cope. The experience of implant loss appears to affect women for many years and might overshadow some of the benefits of IBR.


The immunologically reactive O-linked polysaccharide chains derived from circulating cathodic antigen isolated from the human blood fluke Schistosoma mansoni have Lewis x as repeating unit.
The gut-associated excretory antigen circulating cathodic antigen (CCA) was isolated by immunoaffinity chromatography from adult Schistosoma mansoni worms, which were collected from infected golden hamsters. This antigen is probably involved in protection of the schistosome gut and is increasingly used in highly sensitive and specific immunodiagnostic assays. Amino acid analysis before and after alkaline borohydride treatment of CCA and monosaccharide analysis indicated that CCA is O-glycosylated mostly via GalNAc-Thr. After reductive alkaline treatment, the O-linked carbohydrate chains were fractionated by gel-permeation chromatography, followed by normal-phase HPLC on LiChrosorb-NH2. Carbohydrate-positive fractions were investigated by one-dimensional and two-dimensional 1H-NMR spectroscopy, fast atom bombardment mass spectrometry and collision-induced-dissociation tandem mass spectrometry. The analyses showed that the low-molecular-mass O-linked oligosaccharide alditols (the minor fraction) consist of disaccharides to hexasaccharides having the Gal beta (1-3)GalNAc-OL core in common. The major carbohydrate fraction comprises a population of polysaccharides, containing Lewis x repeating units (-3)Gal beta (1-4)[Fuc alpha (1-3)]GlcNAc beta (1-). CCA-specific monoclonal antibodies and IgM antibodies in patient sera recognized the fucosylated O-linked carbohydrate antigenic structures. Since CCA evokes a strong IgM antibody response and carbohydrate structures containing repeating Lewis x units are found on circulating neutrophils, it is proposed that the antigenic poly-Lewis x polysaccharide of CCA is involved in the induction of auto-immunity against granulocytes, resulting in the mild to moderate neutropenia observed during schistosome infection.


Extremely high levels of C-reactive protein in patients with acute lupus serositis.
Abstract We present the cases of two patients (19- and 40-year-old women) with systemic lupus erythematosus (SLE) who showed marked elevation of C-reactive protein (CRP). In both patients, pleural and/or peritoneal effusions were caused by lupus serositis. Methylprednisolone pulse therapy was effective in improving the serositis and normalizing CRP. Although it is generally considered that the CRP response is relatively weak in lupus patients, these cases suggest that a strong CRP response can occur in a subset of SLE.


Survivors and scientists: Hiroshima, Fukushima, and the Radiation Effects Research Foundation, 1975-2014.
In this article, I reflect on the Radiation Effects Research Foundation and its ongoing studies of long-term radiation risk. Originally called the Atomic Bomb Casualty Commission (1947-1975), the Radiation Effects Research Foundation has carried out epidemiological research tracking the biomedical effects of radiation at Hiroshima and Nagasaki for almost 70 years. Radiation Effects Research Foundation scientists also played a key role in the assessment of populations exposed at Chernobyl and are now embarking on studies of workers at the Fukushima Daiichi Nuclear Power Plant. I examine the role of estimating dosimetry in post-disaster epidemiology, highlight how national identity and citizenship have mattered in radiation risk networks, and track how participants interpreted the relationships between nuclear weapons and nuclear energy. Industrial interests in Japan and the United States sought to draw a sharp line between the risks of nuclear war and the risks of nuclear power, but the work of the Radiation Effects Research Foundation (which became the basis of worker protection standards for the industry) and the activism of atomic bomb survivors have drawn these two nuclear domains together. This is so particularly in the wake of the Fukushima disaster, Japan's 'third atomic bombing'. The Radiation Effects Research Foundation is therefore a critical node in a complex global network of scientific institutions that adjudicate radiation risk and proclaim when it is present and when absent. Its history, I suggest, can illuminate some properties of modern disasters and the many sciences that engage with them.


Diffusion in Al-Cu melts studied by time-resolved X-ray radiography.
We use time-resolved x-ray radiography in order to monitor interdiffusion processes in situ in liquid alloys. We measure temperature and composition dependent interdiffusion coefficients (D{AlCu}) in Al-rich Al-Cu melts. At constant temperature, D{AlCu} only exhibits a weak dependence of the alloy composition. As compared to self-diffusion, interdiffusion is enhanced by a factor of about 3. Our results demonstrate that it is not possible to express interdiffusion in terms of self-diffusion and thermodynamic driving forces.


Melatonin enhances KCl salinity tolerance by maintaining K+ homeostasis in Malus hupehensis.
Large amounts of potash fertilizer are often applied to apple (Malus domestica) orchards to enhance fruit quality and yields, but this treatment aggravates KCl-based salinity stress. Melatonin (MT) is involved in a variety of abiotic stress responses in plants. However, its role in KCl stress tolerance is still unknown. In the present study, we determined that an appropriate concentration (100 μm) of MT significantly alleviated KCl stress in Malus hupehensis by enhancing K+ efflux out of cells and compartmentalizing K+ in vacuoles. Transcriptome deep-sequencing analysis identified the core transcription factor gene MdWRKY53, whose expression responded to both KCl and MT treatment. Overexpressing MdWRKY53 enhanced KCl tolerance in transgenic apple plants by increasing K+ efflux and K+ compartmentalization. Subsequently, we characterized the transporter genes MdGORK1 and MdNHX2 as downstream targets of MdWRKY53 by ChIP-seq. MdGORK1 localized to the plasma membrane and enhanced K+ efflux to increase KCl tolerance in transgenic apple plants. Moreover, overexpressing MdNHX2 enhanced the KCl tolerance of transgenic apple plants/callus by compartmentalizing K+ into the vacuole. RT-qPCR and LUC activity analyses indicated that MdWRKY53 binds to the promoters of MdGORK1 and MdNHX2 and induces their transcription. Taken together, our findings reveal that the MT-WRKY53-GORK1/NHX2-K+ module regulates K+ homeostasis to enhance KCl stress tolerance in apple. These findings shed light on the molecular mechanism of apple response to KCl-based salinity stress and lay the foundation for the practical application of MT in salt stress.


Acne: treatment of scars.
Acne is a common disease affecting a significant proportion of the population.(1-3) It causes considerable morbidity through soreness, disfigurement, and social handicap due to inflammatory lesions.(4,5) Modern therapy ensures that a considerable proportion of all patients can be offered effective treatment of their disease, but the morbidity is not restricted solely to the inflammatory lesions of acne.(6,7) Despite appropriate and effective primary prevention of scarring, scarring occurs in some degree in 95% of all patients irrespective of the severity of inflammatory acne (although severe acne causes more scarring than the milder forms). The scarring causes long-term morbidity that requires specific therapy.(7)


Trends of Youth Marijuana Treatment Admissions: Increasing Admissions Contrasted with Decreasing Drug Involvement.
Recent changes in marijuana policies and their potential negative effects on youth development are a public health concern. Identifying the most appropriate treatment approaches for problematic marijuana use is important. The aim of this study was to track marijuana use among young people by examining national changes from 1995 to 2012 in the demographics, referral sources, and the substance use patterns related to youth admissions to substance abuse treatment programs. We examined first-time substance abuse treatment admissions among youth, utilizing the Treatment Episode Data Set - Admissions (TEDS-A) of the Substance Abuse Mental Health Services Administration (N = 12,025,787). Chi-squared analysis was used to examine differences between admission years and binomial logistic regression was used to examine trends over the 18 years. We found increasing numbers of youth in dependent living situations (e.g. with parents) admitted to substance use disorder treatment for marijuana. We also found a dramatic drop in the degree of drug involvement for those admissions over nearly two decades of data. Conclusions/Importance: While availability and changing perceptions of marijuana might have caused an increase in admissions to substance abuse treatment, our findings indicate that the severity of drug use involved in those admissions has decreased. This study highlights the importance of identifying youth in actual need of treatment services and not overlooking tools such as screening, brief intervention, and motivational interviewing as effective for varying levels of marijuana use by youth.


A situational analysis methodology to inform comprehensive HIV prevention and treatment programming, applied in rural South Africa.
Successful HIV prevention programming requires engaging communities in the planning process and responding to the social environmental factors that shape health and behaviour in a specific local context. We conducted two community-based situational analyses to inform a large, comprehensive HIV prevention programme in two rural districts of North West Province South Africa in 2012. The methodology includes: initial partnership building, goal setting and background research; 1 week of field work; in-field and subsequent data analysis; and community dissemination and programmatic incorporation of results. We describe the methodology and a case study of the approach in rural South Africa; assess if the methodology generated data with sufficient saturation, breadth and utility for programming purposes; and evaluate if this process successfully engaged the community. Between the two sites, 87 men and 105 women consented to in-depth interviews; 17 focus groups were conducted; and 13 health facilities and 7 NGOs were assessed. The methodology succeeded in quickly collecting high-quality data relevant to tailoring a comprehensive HIV programme and created a strong foundation for community engagement and integration with local health services. This methodology can be an accessible tool in guiding community engagement and tailoring future combination HIV prevention and care programmes.


Pressure Injury Prevention: Knowledge and Attitudes of Iranian Intensive Care Nurses.
Pressure injuries are the third most expensive condition after cancer and cardiovascular disease. Nurses are responsible for the direct and continuous care, treatment, and prevention of pressure injuries. To achieve optimal quality care, nursing knowledge and attitudes must be based on the best scientific evidence. This study aimed to examine the knowledge and attitudes of nurses working in intensive care units of hospitals affiliated with Zahedan Medical Sciences University regarding the prevention of pressure injuries. This was a descriptive analytic study involving 89 critical care nurses. Data analysis was conducted using a 3-part questionnaire: demographic data, knowledge, and attitudes of intensive care nurses toward the prevention of pressure injuries. Collected data were analyzed with SPSS version 19 (IBM, Armonk, New York), using descriptive and inferential statistics (such as Pearson correlation coefficient, independent t test, and analysis of variance). The results showed that the mean ± SD score of pressure injury knowledge was 0.44 ± 0.12, and the attitude of participants toward pressure injury prevention was 2.69 ± 0.47. Scores varied widely; "nutrition" showed the highest mean score (0.71 ± 0.45), but "etiology and development" (0.42 ± 0.21) and "classification and observation" (0.42 ± 0.24) showed the lowest mean scores. Of the different aspects of attitudes toward pressure injury prevention, "the impact of pressure injuries" showed the highest mean score (2.95 ± 0.56), and "confidence in the effectiveness of prevention" showed the lowest mean score (2.56 ± 0.46). A statistically significant relationship was observed between pressure injury knowledge and attitudes toward pressure injury prevention (P < .001). Pressure injury prevention is one of many nursing care priorities and is a key indicator of the quality of nursing care. In order to achieve optimal quality care in this area, nurse managers and other administrators should make efforts to improve nursing knowledge and attitudes based on the latest scientific evidence for pressure injury prevention.


Induction chemotherapy with versus without hormonal synchronisation in locally advanced breast cancer.
Sixty-nine patients with locally advanced breast cancer were given induction chemotherapy with doxorubicin and cyclophosphamide (day 1) followed by methotrexate and 5-Fu (day 8). Thirty-two of these patients were also given tamoxifen (days 2-6) in an attempt to induce a G1 arrest in cancer cells, and oestrogen (days 7-8) to stimulate proliferation and thus induce a synchronized wave of proliferating cells. The induction therapy response rate was 61% in the series as a whole (n = 69), but was found to be significantly better in the group on the tamoxifen/oestrogen synchronization regimen than in the remainder on chemotherapy alone (82% vs. 43%). This difference was particularly marked in the respective receptor-positive subgroups [90% (9/10) vs. 30% (3/10); p < 0.001]. The findings suggest that, in combination with chemotherapy, tamoxifen/oestrogen therapy, given in the sequence outlined here, constitutes a promising regimen for the treatment of locally advanced receptor-positive breast cancer patients.


Stability of avian leukosis virus type-specific antigen in the cell after fixation in periodate-lysine-paraformaldehyde.
Stability of avian leukosis virus type-specific antigen in chicken embryo fibroblasts after fixation in periodate-lysine-paraformaldehyde was tested by the indirect immunoperoxidase method. Antigen that had been steeped in 0.015M Tris-HCl saline buffer solution containing 20% bovine serum and 30% glycerin was preserved at -20 degrees C, 4 degrees C and room temperature without loss of its antigenicity as long as 16 weeks. It was also stable against heat treatment at 56 degrees C, acid treatment and ethyl ether treatment.


Acetylenic spacers in phenylene end-substituted oligothiophene core for highly air-stable organic field-effect transistors.
Two thiophene-phenylene semiconductors, bis(2-phenylethynyl) end-substituted oligothiophenes (diPhAc-nTs, n = 2, 3), were synthesized and studied with respect to their optical, electrochemical, structural and electrical properties. The optical and electrochemical properties of the oligomers in solution were investigated by UV-vis absorption and photoluminescence spectroscopies, and cyclic voltammetry. High vacuum evaporated thin films were investigated by optical absorption, X-ray diffraction and AFM, and implemented as p-type semiconducting layers into organic thin-film transistors (OTFTs). A comparative study in solution and in the solid state with distyryl-oligothiophenes (DSnTs, n = 2, 3) reveals the great influence of acetylenic (-C[triple bond]C-) vs. olefinic (-C=C-) spacers in thiophene-phenylene derivatives on electronic structure, physical properties, and device efficiencies. Substituting olefinic for acetylenic pi-spacers in terthiophene-based conjugated semiconductors leads to one of incontrovertible attributes of OTFTs for low cost applications, a high mobility at low substrate temperature (T(sub)) i.e. typically 25 degrees C. Fine-tuning in the HOMO/LUMO levels by reducing the HOMO level introduces increased air-oxidation strength of thin films where OTFTs provide exactly the same hole mobility value after 100 days in air. All the results suggested that introduction of carbon-carbon triple bonds provided an efficient route to highly air-stable organic thin film transistors.


Detection of Cytoplasmic and Nuclear Circular RNA via RT-qPCR.
Circular RNA (circRNA) is an intriguing class of non-coding RNA that exists as a continuous closed loop. With the improvements in high throughput sequencing, biochemical analysis, and bioinformatic algorithms, studies on circRNA expression became abundant in recent years. However, functional studies of circRNA are still limited. Subcellular localization of circRNA may provide some clues in elucidating its biological functions by performing subcellular fractionation assay. Notably, circRNAs that are predominantly found in the cytoplasm are more likely to be involved in post-transcriptional gene regulation, e.g., acting as micoRNA sponge, whereas nuclear-retained circRNAs are predicted to play a role in transcriptional regulation. Subcellular fractionation could help researchers to narrow down and prioritize downstream experiments. The majority of the currently available protocols describe the steps for subcellular fractionation followed by western blot analysis for protein molecules. Here, we present a protocol for the subcellular fractionation of cells to detect circRNA via RT-qPCR with divergent primers. Moreover, detailed steps for the generation of specific circRNAs-enriched cDNA included in this protocol will enhance the amplification and detection of low-abundance circRNAs. This will be useful for researchers studying low-abundance circRNAs. Key features This protocol builds upon the method developed by Gagnon et al. (2014) and extends its application to circRNA study. Protocol for amplification of low levels of circRNA expression. Analysis takes into consideration the ratio of cytoplasmic RNA concentration to nuclear RNA concentration.


Medical expulsive therapy use in emergency department patients diagnosed with ureteral stones.
Recent studies have clarified the role of alpha-blockers, such as tamsulosin, for patients diagnosed with ureteral stones <10mm not requiring an urgent intervention. Prior studies have reported low rates of use of MET by emergency physicians. We sought to describe patterns of alpha-blocker use and to determine factors associated with utilization in patients diagnosed with ureterolithiasis in the ED. We used data from a randomized trial of CT scan vs. ultrasound in participants with suspected urolithiasis enrolled at 15 EDs between October 2011 and February 2013. The use of medical expulsive therapy was identified by the prescription of an alpha-blocker, calcium channel blocker, or steroid at the ED visit. The prevalence of alpha-blocker use in participants with ureteral stones on imaging was calculated, and multivariable models were used to examine risk factors for utilization. Of the 524 participants who were identified with a ureteral stone on CT scan and discharged from the ED, 375 (71.4%) received an alpha-blocker, and 2 (<1%) received a steroid. There was no significant difference in alpha-blocker use for participants based on stone size or location. However, there was a 3.6-fold difference in alpha-blocker use between the lowest and highest use ED sites. In the multivariable analysis, ED site was independently associated with utilization of alpha-blockers. Alpha-blockers were prescribed in more than two-thirds of patients with a distal ureteral stone on imaging, a much higher prevalence than previously reported. There was substantial variability in alpha-blocker use based on ED site.


Strangulated gallbladder caused by a tip of the omentum attached to the abdominal wall: a case report.
Strangulation of the gallbladder associated with the omentum is extremely rare and, to our knowledge, only two cases have been previously reported. The patient was a 91-year-old female who presented to our emergency room with a chief complaint of upper abdominal pain. Computed tomography imaging revealed a gourd-shaped gallbladder with biphasic appearance divided clearly at the body. In the fundus side, the wall of the gallbladder was oedematous and thickened, while the neck side was intact. On the second day after onset, a laparoscopic cholecystectomy was performed. A tip of the omentum encircling the gallbladder was adhered to the abdominal wall and was strangling the gallbladder. By cutting the omentum at the attachment site, the strangulation was released. Laparoscopic cholecystectomy was performed, and the patient was discharged with an uneventful course. We experienced an extremely rare case of strangulated gallbladder caused by a tip of the omentum attached to the abdominal wall.


[An electron microscopic study of Nocardia rubra growing in a medium containing phenol].
Changes in the cytoplasm were detected in the ultrastructure of Nocardia rubra 80 growing on a medium containing phenol: the cytoplasm aggregated to yield inclusions with different electron density, having round shape and granular structure. The inclusions are surrounded with bright zones. Cells were formed, which resembled bacterial endospores by their formation and structure; however, typical refractive spores with envelopes and cortex have not been detected.


Creation of synthetic homogeneous neighbourhoods using zone design algorithms to explore relationships between asthma and deprivation in Strasbourg, France.
The concept of 'neighbourhood' as a unit of analysis has received considerable research attention over the last decade. Many of these studies raise the question of the influence of local characteristics on variations in health and more recently, researchers have sought to understand how the neighbourhood can influence individual health through individual behaviour. Relatively few studies discuss the question of the borders and definition of a neighbourhood but we know that the results from health or population datasets are very sensitive to how zones are constructed - part of the Modifiable Areal Unit Problem (MAUP). In reality, we know that neighbourhoods are not constrained by artificial statistical boundaries, but rather exist as complex multi-dimensional living communities. This paper tries to better represent the reality on the ground of these communities to better inform studies of health. In this work, we have developed an experimental approach for the automated design of neighbourhoods using a small tessellated cell as a basic building block. Using the software AZTool, we considered population, shape and homogeneity constraints to develop a highly innovative approach to zone construction. The paper reports the challenges and compromises involved in building these new synthetic neighbourhoods. We provide a fully worked example of how our new synthetic homogeneous zones perform using data from Strasbourg, France. We examine data on Asthma reported through calls to the emergency services, and compare these rates with an index of multiple deprivation (NDI) which we have constructed and reported elsewhere. Higher correlations between Asthma and NDI were found using our newly constructed synthetic zones than using the existing French census areas of similar size. The significance of our work is that we show that careful construction of neighbourhoods - which we claim are more realistic than census areas - can greatly aid unpacking our understanding of neighbourhood relationships between health and the social and physical environments.


A Novel Utility of Bilobed Flap for Amputation Stump Coverage.
Preparing a good amputation stump with a well-padded, stable, sensate, and painless soft tissue coverage is of utmost importance to achieve early ambulation and return the patient to the daily activity level. When the primary closure is impossible or fails to achieve a good closure, secondary closure must be considered. To date, no literature reported the use of bilobed flaps for stump defect closure. We aimed to utilize this technically easy procedure for better management of defect closure on amputated limb stumps that often cause complex clinical problems. This is a retrospective observational study in limb amputation patients with various etiologies: crush injury, chronic limb necrosis, and amniotic band syndrome. All patients had stump defect closure with bilobed flap and were observed with a minimum of 6-months follow-up to evaluate the wound healing, the use of prosthesis, and the complications. A bilobed flap was performed in 11 amputation cases as the final closure (64% trans-femoral, 18% trans-tibial, 9% trans-humeral, and 9% trans-radial). The mean follow-up time was 8.5 ± 2.21 months. Most of the patients healed uneventfully with the optimal use of prosthesis in a mean healing time of 29.64 ± 7.49 days. The bilobed flap potentially provides a good amputation stump coverage that is ideal for prosthesis fitting. This simple procedure can be done without the necessity of special microsurgery settings. Thus, when the neighboring tissue is available and mobile enough to be transposed to the stump defect, a bilobed flap can be considered.


Dual Inhibition of EGFR and c-Src by Cetuximab and Dasatinib Combined with FOLFOX Chemotherapy in Patients with Metastatic Colorectal Cancer.
Purpose: Aberrant activation of the intracellular tyrosine kinase Src has been implicated as a mechanism of acquired chemotherapy resistance in metastatic colorectal cancer (mCRC). Here, the oral tyrosine kinase Src inhibitor, dasatinib, was investigated in combination with FOLFOX and cetuximab.Experimental Design: We performed a phase IB/II study of 77 patients with previously treated mCRC. Primary objectives were to determine the maximum tolerated dose, dose-limiting toxicities (DLT), pharmacodynamics, and efficacy. Using a 3 + 3 design, patients received FOLFOX6 with cetuximab and escalating doses of dasatinib (100, 150, 200 mg daily), followed by a 12-patient expansion cohort at 150 mg. Phase II studies evaluated FOLFOX plus dasatinib 100 mg in KRAS c12/13mut patients or in combination with cetuximab if KRAS c12/13WT FAK and paxillin were utilized as surrogate blood biomarkers of Src inhibition, and paired biopsies of liver metastases were obtained in patients in the expansion cohort.Results: In phase IB, the DLTs were grade 3/4 fatigue (20%) and neutropenia (23%). In phase II, grade 3/4 fatigue (23%) and pleural effusions (11%) were present. Response rates were 20% (6 of 30) in the phase IB escalation and expansion cohort and 13% (3 of 24) and 0% (0 of 23) in the KRAS c12/13WT and mutant cohorts of phase II, respectively. Median progression-free survival was 4.6, 2.3, and 2.3 months, respectively. There was no evidence of Src inhibition based on surrogate blood biomarkers or paired tumor biopsies.Conclusions: The combination of dasatinib plus FOLFOX with or without cetuximab showed only modest clinical activity in refractory colorectal cancer. This appears to be primarily due to a failure to fully inhibit Src at the achievable doses of dasatinib. The combination of dasatinib plus FOLFOX with or without cetuximab did not show meaningful clinical activity in refractory colorectal cancer due to failure to fully inhibit Src. Clin Cancer Res; 23(15); 4146-54. ©2017 AACR.


Application of Roof-Shape Amines as Chiral Solvating Agents for Discrimination of Optically Active Acids by NMR Spectroscopy: Study of Match-Mismatch Effect and Crystal Structure of the Diastereomeric Salts.
Optically active roof-shape amines were prepared and scanned as chiral solvating agents to study molecular recognition of acids by NMR analysis. Three types of amines were studied to establish a match-mismatch effect for structurally diverse acid analytes. Single-crystal X-ray diffraction analysis was performed on the diastereomeric salts of roof-shape amines and both isomers of mandelic acid to establish molecular conformation and correlate the absolute configuration with the observed NMR shift. The present system also recognizes the two isomers of weakly acidic BINOL and its derivatives.


Pretreatment CT Texture Parameters as Predictive Biomarkers of Progression-Free Survival in Follicular Lymphoma Treated with Immunochemotherapy and Rituximab Maintenance.
The purpose of this study was to determine whether texture analysis features present on pretreatment unenhanced computed tomography (CT) images, derived from 18F-fluorodeoxyglucose positron emission/computed tomography (18-FDG PET/CT), can predict progression-free survival (PFS), progression-free survival at 24 months (PFS 24), time to next treatment (TTNT), and overall survival in patients with high-tumor-burden follicular lymphoma treated with immunochemotherapy and rituximab maintenance. Seventy-two patients with follicular lymphoma were retrospectively included. Texture analysis was performed on unenhanced CT images extracted from 18-FDG PET/CT examinations that were obtained within one month before treatment. Skewness at a fine texture scale (SSF = 2) was an independent predictor of PFS (hazard ratio = 3.72 (95% CI: 1.15, 12.11), p = 0.028), PFS 24 (hazard ratio = 13.38; 95% CI: 1.29, 138.13; p = 0.029), and TTNT (hazard ratio = 5.11; 95% CI: 1.18, 22.13; p = 0.029). Skewness values above -0.015 at SSF = 2 were significantly associated with lower PFS, PFS 24, and TTNT. Kurtosis without filtration was an independent predictor of PFS (SSF = 0; HR = 1.22 (95% CI: 1.04, 1.44), p = 0.013), and TTNT (SSF = 0; hazard ratio = 1.23; 95% CI: 1.04, 1.46; p = 0.013). This study shows that pretreatment unenhanced CT texture analysis-derived tumor skewness and kurtosis may be used as predictive biomarkers of PFS and TTNT in patients with high-tumor-burden follicular lymphoma treated with immunochemotherapy and rituximab maintenance.


Clinical evaluation of effects of prazosin in patients with benign prostatic obstruction. A double-blind, multi-institutional, Paraprost-controlled study.
Prazosin, a selective alpha 1-adrenoceptor blocker, was compared with Paraprost in a double-blind, multi-institutional study in patients with benign prostatic hyperplasia. The trial encompassed 77 evaluable patients in the prazosin group and 79 in the Paraprost group. Both drugs significantly improved obstructive and irritative symptoms. Residual urine (volume or percentage of total urine) was reduced by both prazosin and Paraprost. Average and maximum flow rates increased significantly in the prazosin group while those were unchanged in the Paraprost group. Side effects occurred in 1 patient treated with prazosin (1.1%) and 3 patients with Paraprost (3.3%). Thus, we confirm the clinical value and minimal side effects of prazosin in the treatment of bladder outflow obstruction resulting from benign prostatic hyperplasia.


Ridge preservation with the socket-shield technique and immediate provisionalization for delayed implant placement.
The present case report with medium-term follow-up aims to report on the successful outcomes of ridge preservation using anorganic bovine bone mineral (ABBM) combined with the socket-shield technique (SST) in conjunction with immediate ovate pontic provisionalization of the extraction site, followed by delayed flapless implant placement and immediate implant provisionalization in the rehabilitation of the maxillary anterior esthetic region. Clinical protocol: Three consecutive patients with failing maxillary anterior teeth were treated with this protocol. The alveolar ridge dimension was preserved utilizing ABBM, combined with the retention of a partial tooth root segment in the buccal portion of the extraction socket, to minimize ridge resorption following tooth extraction. An immediate fixed provisional restoration with an ovate base in direct contact with the extraction site was fabricated and delivered immediately to maintain the soft tissue contour. At 4 months postextraction, flapless implant placement was performed via a computer-generated surgical guide, along with immediate implant provisionalization. Definitive restorations were delivered 4 months following implant placement. At the 2-year follow-up after loading, prosthetic and implant success was demonstrated, with a favorable esthetic outcome and a high level of patient satisfaction. The immediate ovate pontic provisionalization in conjunction with ridge preservation combining ABBM and the SST, followed by flapless computer-guided implant placement with an immediate implant provisionalization protocol, as proposed in this article, offers a viable method to minimize alveolar ridge resorption as well as optimize esthetic outcomes.


PATTERNS OF MATING IN WILD SUNFLOWER HYBRID ZONES.
Theory predicts that homoploid hybrid speciation will be facilitated by selfing, yet most well-documented hybrid species are outcrossers. One possible explanation for this puzzle is that conditions in hybrid populations may favor selfing, even in otherwise outcrossing species. For example, in self-incompatible plants, mixtures of self and interspecific pollen often induce selfing. Here, we examine patterns of mating in three hybrid zones and four "pure" populations of Helianthus annuus and H. petiolaris, wild, self-incompatible sunflower species that are thought to have parented three homoploid hybrid species. Fourteen to 16 maternal families from each pure population and 44-46 maternal families from each hybrid zone were analyzed for seven polymorphic isozyme loci. Maximum-likelihood (ML) methods were used to estimate multilocus outcrossing rates (Tm ) and hybridization frequencies for each maternal family, each phenotypic group within each hybrid zone (annuus-like, hybrid, and petiolaris-like), and each population. As predicted for self-incompatible species, all four parental populations have outcrossing rate ML estimates of 1.0. Within the hybrid zones, outcrossing rates were lowest in the H. annuus-like fraction of the population (0.73, 0.72, and 0.74 in the three hybrid zones, respectively), largely intermediate in the H. petiolaris-like group (0.94, 0.90, and 0.94), and highest in the hybrid group (0.97, 0.93, and 0.97). Although outcrossing rates are lower in hybrid zones than in pure populations, it is unlikely that the observed decrease facilitates hybrid speciation because outcrossing rates in the critical hybrid fraction of the population do not differ significantly from 1.0. Dividing the outcrossed pollen pool into intraspecific and interspecific components revealed that maternal plants are largely fertilized by conspecific pollen, confirming an important role for pollen competition as a reproductive barrier. Highly sterile hybrid plants do not appear to discriminate between parental species pollen, but hybrids with higher fertility tend to be fertilized by pollen from the parental group they resemble genetically. Thus, gametic selection leads to substantial assortative mating in these hybrid zones.


Oxidative metabolism and glycolysis in benign brain tumors.
Glucose utilization in vivo and hexokinase activity and mitochondrial oxygen consumption in vitro were measured in a series of human brain tumors. Several relatively slow-growing tumors appeared to have depressed electron-transport activities coupled with a compensatory elevated glucose utilization. These data suggest that a decrease in oxidative metabolism and a corresponding increase in glycolysis are not necessarily correlated with malignancy in certain human brain tumors.


Promoting well-being: time for a paradigm shift in health and human services1.
The promotion of personal, relational, and collective well-being has evolved markedly in the last three decades. However positive and needed, recent developments in health promotion require further conceptual clarification and synergistic applications. To assist with conceptual clarification, this article proposes to distinguish among sites, signs, sources, and strategies of well-being. With respect to applications, progress is discussed along four domains: temporal, ecological, participation, and capabilities. The temporal domain refers to the timing of interventions and entails a continuum from reactive to proactive strategies. The ecological domain pertains to the site of interventions, ranging from person-centered to community-centered. The participation domain refers to voice and choice of citizens and consumers in delivery of services and access to resources. At one end of this continuum there is empowerment, while at the opposite end we see disempowerment and detachment. Finally, the capabilities domain refers to the concentration on either strengths or deficits. This article argues that a singular focus on strength, prevention, empowerment, or community conditions is insufficient. It presents a framework for the conceptual integration of these four approaches, while illustrating the benefits of their synergy and the risks of their fragmentation. It is high time for a paradigm shift in health and human services, and this article argues that only a new approach that focuses on strengths, prevention, empowerment, and community conditions can make considerable progress towards the achievement of well-being for all.


Maggot debridement therapy in chronic wound care.
To review the current evidence on the mechanism of actions and clinical applications of maggot debridement therapy. Literature search of PubMed and Medline was performed up to January 2007. Original and major review articles related to maggot debridement therapy were reviewed. Key words used in the literature search were 'maggot debridement therapy', 'wound healing', and 'chronic wound management'. All relevant English and Chinese articles. The mechanism of such maggot therapy was shown to be due to the debridement, disinfection, and wound healing enhancement actions of maggot excretions/secretions. The efficacy of maggot debridement therapy in chronic wound management has been demonstrated in chronic venous ulcers, pressure ulcers, and diabetic ulcers. There is also a new delivery system for the excretions/secretions, which has been shown to be as effective as using live maggots. Maggot debridement therapy has been shown to be a safe and effective means of chronic wound management. However, there are a number of limitations when considering its local applicability. Future development of the delivery system may help to overcome some of these limitations and improve its acceptability.


Assessment and prediction of joint algal toxicity of binary mixtures of graphene and ionic liquids.
Graphene and ionic liquids (ILs) released into the environment will interact with each other. So far however, the risks associated with the concurrent exposure of biota to graphene and ILs in the environment have received little attention. The research reported here focused on observing and predicting the joint toxicity effects in the green alga Scenedesmus obliquus exposed to binary mixtures of intrinsic graphene (iG)/graphene oxide (GO) and five ILs of varying anionic and cationic types. The isolated ILs in the binary mixtures were the main contributors to toxicity. The binary GO-IL mixtures resulted in more severe joint toxicity than the binary iG-IL mixtures, irrespective of mixture ratios. The mechanism of the joint toxicity may be associated with the adsorption capability of the graphenes for the ILs, the dispersion stability of the graphenes in aquatic media, and modulation of the binary mixtures-induced oxidative stress. A toxic unit assessment showed that the graphene and IL toxicities were additive at low concentration of the mixtures but antagonistic at high concentration of the mixtures. Predictions made using the concentration addition and independent action models were close to the observed joint toxicities regardless of mixture types and mixture ratios. These findings provide new insights that are of use in the risk assessment of mixtures of engineered nanoparticles and other environmentally relevant contaminants.


Search for methylation-sensitive amplification polymorphisms in mutant figs.
Fig (Ficus carica) breeding programs that use conventional approaches to develop new cultivars are rare, owing to limited genetic variability and the difficulty in obtaining plants via gamete fusion. Cytosine methylation in plants leads to gene repression, thereby affecting transcription without changing the DNA sequence. Previous studies using random amplification of polymorphic DNA and amplified fragment length polymorphism markers revealed no polymorphisms among select fig mutants that originated from gamma-irradiated buds. Therefore, we conducted methylation-sensitive amplified polymorphism analysis to verify the existence of variability due to epigenetic DNA methylation among these mutant selections compared to the main cultivar 'Roxo-de-Valinhos'. Samples of genomic DNA were double-digested with either HpaII (methylation sensitive) or MspI (methylation insensitive) and with EcoRI. Fourteen primer combinations were tested, and on an average, non-methylated CCGG, symmetrically methylated CmCGG, and hemimethylated hmCCGG sites accounted for 87.9, 10.1, and 2.0%, respectively. MSAP analysis was effective in detecting differentially methylated sites in the genomic DNA of fig mutants, and methylation may be responsible for the phenotypic variation between treatments. Further analyses such as polymorphic DNA sequencing are necessary to validate these differences, standardize the regions of methylation, and analyze reads using bioinformatic tools.


Malignancy in large colorectal lesions.
The size of colorectal lesions, besides a risk factor for malignancy, is a predictor for deeper invasion objectives: To evaluate the malignancy of colorectal lesions ≥20 mm. Between 2007 and 2011, 76 neoplasms ≥20 mm in 70 patients were analyzed. The mean age of the patients was 67.4 years, and 41 were women. Mean lesion size was 24.7 mm ± 6.2 mm (range: 20 to 50 mm). Half of the neoplasms were polypoid and the other half were non-polypoid. Forty-two (55.3%) lesions were located in the left colon, and 34 in the right colon. There was a high prevalence of III L (39.5%) and IV (53.9%) pit patterns. There were 72 adenomas and 4 adenocarcinomas. Malignancy was observed in 5.3% of the lesions. Thirty-three lesions presented advanced histology (adenomas with high-grade dysplasia or early adenocarcinoma), with no difference in morphology and site. Only one lesion (1.3%) invaded the submucosa. Lesions larger than 30 mm had advanced histology (P = 0.001). The primary treatment was endoscopic resection, and invasive carcinoma was referred to surgery. Recurrence rate was 10.6%. Large colorectal neoplasms showed a low rate of malignancy. Endoscopic treatment is an effective therapy for these lesions.


Enhanced regeneration of corneal tissue via a bioengineered collagen construct implanted by a nondisruptive surgical technique.
Severe shortage of donor corneas for transplantation, particularly in developing countries, has prompted the advancement of bioengineered tissue alternatives. Bioengineered corneas that can withstand transplantation while maintaining transparency and compatibility with host cells, and that are additionally amenable to standardized low-cost mass production are sought. In this study, a bioengineered porcine construct (BPC) was developed to function as a biodegradable scaffold to promote corneal stromal regeneration by host cells. Using high-purity medical-grade type I collagen, high 18% collagen content and optimized EDC-NHS cross-linker ratio, BPCs were fabricated into hydrogel corneal implants with over 90% transparency and four-fold increase in strength and stiffness compared with previous versions. Remarkably, optical transparency was achieved despite the absence of collagen fibril organization at the nanoscale. In vitro testing indicated that BPC supported confluent human epithelial and stromal-derived mesenchymal stem cell populations. With a novel femtosecond laser-assisted corneal surgical model in rabbits, cell-free BPCs were implanted in vivo in the corneal stroma of 10 rabbits over an 8-week period. In vivo, transparency of implanted corneas was maintained throughout the postoperative period, while healing occurred rapidly without inflammation and without the use of postoperative steroids. BPC implants had a 100% retention rate at 8 weeks, when host stromal cells began to migrate into implants. Direct histochemical evidence of stromal tissue regeneration was observed by means of migrated host cells producing new collagen from within the implants. This study indicates that a cost-effective BPC extracellular matrix equivalent can incorporate cells passively to initiate regenerative healing of the corneal stroma, and is compatible with human stem or organ-specific cells for future therapeutic applications as a stromal replacement for treating blinding disorders of the cornea.


Randomized Adjuvant Chemotherapy of EGFR-Mutated Non-Small Cell Lung Cancer Patients with or without Icotinib Consolidation Therapy.
Epidermal growth factor receptor (EGFR) mutations occur in up to 50% of Asian patients with non-small cell lung cancer (NSCLC). Treatment of advanced NSCLC patients with EGFR-tyrosine kinase inhibitor (EGFR-TKI) confers a significant survival benefit. This study assessed the efficacy and safety of chemotherapy with or without icotinib in patients undergoing resection of stage IB to ⅢA EGFR-mutated NSCLC. Patients with surgically resected stage IB (with high risk factors) to ⅢA EGFR-mutated NSCLC were randomly assigned (1:1) to one of two treatment plans. One group received four cycles of platinum-based doublet chemotherapy every three weeks, and the other group received platinum-based chemotherapy supplemented with consolidation therapy of orally administered icotinib (125 mg thrice daily) two weeks after chemotherapy. The icotinib treatment continued for four to eight months, or until the occurrence of disease relapse, metastasis or unacceptable icotinib or chemotherapy toxicity. The primary endpoint was disease-free survival (DFS). 41 patients were enrolled between Feb 9, 2011 and Dec 17, 2012. 21 patients were assigned to the combined chemotherapy plus icotinib treatment group, while 20 patients received chemotherapy only. DFS at 12 months was 100% for icotinib-treated patients and 88.9% for chemotherapy-only patients (p = 0. 122). At 18 months DFS for icotinib-treated vs. chemotherapy-only patients was 95.2% vs. 83.3% (p = 0. 225), respectively, and at 24 months DFS was 90.5% vs. 66.7% (p = 0. 066). The adverse chemotherapy effects predominantly presented as gastrointestinal reactions and marrow suppression, and there was no significant difference between the two treatment groups. Patients in the chemotherapy plus icotinib treatment group showed favorable tolerance to oral icotinib. The results suggest that chemotherapy plus orally icotinib displayed better DFS compared with chemotherapy only, yet the difference in DFS was not significant. We would think the preliminary result here was promising, and further trials with larger sample sizes might confirm the efficiency of adjuvant TKI in selected patients. ClinicalTrials.gov NCT02430974.


Helically Chiral Peptides That Contain Ferrocene-1,1'-diamine Scaffolds as a Turn Inducer.
A series of peptides that contain homo- and heterochiral Ala-Pro sequences attached to the turn-inducing ferrocene-1,1'-diamine scaffold were synthesized. The effects of the backbone chirality and the N-terminal group (Boc/Ac) on the conformational properties of the novel peptidomimetics were thoroughly explored by IR, NMR, and CD spectroscopy and the experimental observations were corroborated by DFT studies in solution. The most stable conformers of the homochiral peptides adopted the interstrand hydrogen-bond patterns, realized through ten- and thirteen-membered rings. The common feature of the most stable conformers of the heterochiral peptides was the adoption of the turn-like structures that feature the simultaneous intra- (seven-membered) and interstrand (sixteen-membered) hydrogen-bonded rings. An exchange of two N-terminal groups had a somewhat larger influence on the distribution of the hydrogen-bond patterns in homochiral than in heterochiral derivatives. The homochiral peptides that contain pyridine moieties as metal coordination sites formed 1:1 complexes with divalent metal ions, which included Zn2+ , Cd2+ , Cu2+ and Fe2+ .