Signal-inducing bone cements for MRI-guided spinal cementoplasty: evaluation of contrast-agent-based polymethylmethacrylate cements.
The purpose of this work is to evaluate two signal-inducing bone cements for MRI-guided spinal cementoplasty. The bone cements were made of polymethylmethacrylate (PMMA, 5 ml monomeric, 12 g polymeric) and gadoterate meglumine as a contrast agent (CA, 0-40 μl) with either saline solution (NaCl, 2-4 ml) or hydroxyapatite bone substitute (HA, 2-4 ml). The cement's signal was assessed in an open 1-Tesla MR scanner, with T1W TSE and fast interventional T1W TSE pulse sequences, and the ideal amount of each component was determined. The compressive and bending strength for different amounts of NaCl and HA were evaluated. The cement's MRI signal depended on the concentration of CA, the amount of NaCl or HA, and the pulse sequence. The signal peaks were recorded between 1 and 10 μl CA per ml NaCl or HA, and were higher in fast T1W TSE than in T1W TSE images. The NaCl-PMMA-CA cements had a greater MRI signal intensity and compressive strength; the HA-PMMA-CA cements had a superior bending strength. Concerning the MR signal and biomechanical properties, these cements would permit MRI-guided cementoplasty. Due to its higher signal and greater compressive strength, the NaCl-PMMA-CA compound appears to be superior to the HA-PMMA-CA compound.


Hotspots and development frontiers of circRNA based on bibliometric analysis.
Circular RNAs (circRNAs) are a big group of members of the noncoding RNA family following long non-coding RNA and microRNA. They play a regulatory role in many biological processes. Analyzing their current research status and future development trends is conducive to a more comprehensive understanding of circRNAs and contributes to the dedication to the biological field. The literature on circRNA from 2000 to 2021 in the Web of Science Core Collection of the Web of Science database with "circular RNA" as the subject was searched. R Studio's Bibliometrix package and biblioshiny software were used for publication trend analysis, citation analysis, keyword analysis, author analysis, research institution analysis, source analysis, country analysis, and collaboration analysis for all documents and highly cited documents. From 2000 to 2021, 3,186 circRNA-related articles were published worldwide, of which 193 were highly cited. The number of published articles had shown an explosive increase after 2013. These articles were mainly from Chinese research institutions and authors, but the country with the highest average number of citations per year in highly cited documents was Germany. Scientific research institutions came from countries represented by Germany, USA, China, Australia and Canada all had different degrees of cooperation. The theme and key points of the research had evolved over time from expression to the role and mechanism of circRNA in diseases, especially in cancer. CDR1as, circFOXO3, circHIPK3, circITCH, circMTO1, circSMARCA5 and circZNF609 are circRNAs that are mainly studied currently, their studies mainly involve cell biology, biological functions and cancer. The future research direction and trend would still be the application of circRNA in diseases. The basic situation and development trend of circRNA related research we described provide a direction for future research.


Conjugation of drug to poly(D,L-lactic-co-glycolic acid) for controlled release from biodegradable microspheres.
Poly(d,l-lactic-co-glycolic acid) (PLGA) was chemically conjugated to a model drug, N-(9-fluorenylmethoxycarbonyl-N-tert-butoxycarbonyl-l-tryptophan (Fmoc-Trp(Boc)) via an ester linkage. Various coupling reaction conditions were tested to optimize the conjugation process between a hydroxyl terminal group of PLGA and a carboxylic acid group of Fmoc-Trp(Boc). Two different lactic/glycolic acid compositions of PLGA (50/50 and 75/25) were used for the conjugation. The Fmoc-Trp(Boc)-PLGA conjugates were formulated into microspheres by a solvent evaporation technique for controlled release of Fmoc-Trp(Boc) over an one month period. A linear constant release of Fmoc-Trp(Boc) and its water-soluble PLGA oligomer conjugates was observed over an extended period without any initial burst effect, while unconjugated Fmoc-Trp(Boc) encapsulated within microspheres exhibited a rapid release profile. In addition, Fmoc-Trp(Boc) release rate solely depended on the PLGA composition that affected polymer degradation rate. The release rate of Fmoc-Trp(Boc) conjugated with fast degrading 50/50 PLGA was more rapid than that conjugated with relatively slow degrading 75/25 PLGA. This study demonstrates that PLGA-drug conjugation approach is a new and novel strategy to control the drug release rate from PLGA microspheres by utilizing the chemical degradation rate of PLGA backbone.


Improved methanogenesis in anaerobic wastewater treatment by magnetite@polyaniline (Fe3O4@PANI) composites.
The magnetite@polyaniline (Fe3O4@PANI) composites with different Fe3O4 loadings were prepared, and their effect on methane production in anaerobic systems was investigated. The Fe3O4@PANI composite with a 40% loading of Fe3O4 showed a better performance on accelerating methane production rate than other composites. The methane production rate was increased by 26.98% at the Fe3O4@PANI dosage of 0.6 g L-1. The results of the contact angle and CLSM revealed that Fe3O4@PANI had a good bio-affinity and contact directly with bacteria and archaea. Then the mechanisms related to the enhancement of methane production by the composites were explored by the species annotation and enzyme activity. It showed that Fe3O4@PANI promoted the enrichment of DIET-related functional bacteria and archaea and improved the enzyme activity related to the acetoclastic methanogenic pathway.


Intravascular lymphomatosis: a clinicopathological study of three cases.
In patients with intravascular lymphomatosis (IL) a broad spectrum of neuro-psychiatric disorders including dementia, focal neurological signs and seizures has been reported. Clinical diagnosis is difficult since neuroimaging findings are nonspecific. The clinical histories, biopsy and autopsy findings of three patients with IL, one with brain biopsy, are described. Two of them presented with rapidly progressive, fluctuating dementia. The third patient suffered from seizures followed by aphasia. Histology revealed large-cell lymphoma of the B cell type. The prognosis of IL, in general, is poor.


Geriatric care in European countries where geriatric medicine is still emerging.
Practicing geriatric medicine is a challenging task since it involves working together with other medical doctors while coordinating a multidisciplinary team. Global Europe Initiative (GEI) group within the European Geriatric Medicine Society gathers geriatricians from different regions where geriatrics is underrepresented or still developing to promote initiatives for the advancement of geriatric medicine within these countries. Here we present a first effort to describe several aspects that affect practicing geriatric medicine in five different countries: Greece, Portugal, Russia, Turkey, and Tunisia. We can notice discrepancies between countries concerning all dimensions of geriatrics (recognition, training, educational and professional standards, academic representation, working context). These differences correspond to the specificities of each country and set the frame where geriatric medicine is going to be developed across Europe. EuGMS with GEI group can provide useful support.


Effects of phenytoin, carbamazepine, and clonazepam on cortex- and amygdala-evoked potentials.
Multiple doses of phenytoin, carbamazepine, and clonazepam were tested against single- and double-pulse evoked potentials. Evoked responses were triggered from either the amygdala or the cortex and were recorded in both monosynaptic sites and the mesencephalic reticular formation (MRF). In accordance with previous studies of spinal potentials, it was expected that all three drugs would display a depressant action. Contrary to expectation, only clonazepam had any significant effect, and this drug was effective only against potentials triggered in the amygdala and recorded in the MRF. These data appear inconsistent with the traditional belief that anticonvulsants block seizure spread by antagonizing transmission in neural pathways.


Anthelminthic effect of oxantel and oxantel-pyrantel in intestinal nematode infections.
704 patients with intestinal nematode infestation were treated with oxantel and oxantel-pyrantel in either liquid or tablet form, at doses from 10 to 25mg/kg. All were given the drug or drugs as a single dose. In 699 patients with trichuriasis cure rates between 64 and 93% were obtained and there were egg reduction rates of between 90 and 100%. The best results were obtained using oxantel, either alone or in combination with pyrantel, at 15 to 20mg/kg. Only 2 of 152 patients with ascariasis were not cured after a single dose of pyrantel (given as oxantel-pyrantel) of 10, 15 or 20mg/kg, and both these patients were from the group given the lowest dose. Only mild side-effects were noted. The combination, oxantel-pyrantel is a safe and effective treatment for multiple intestinal nematode infection.


Influence of risperidone on balance control in young healthy individuals.
It has previously been shown that impairment of postural stability is a side effect of typical antipsychotic drugs, which are largely administered to control psychosis and behavioral symptoms in elderly patients. Surprisingly, no study has yet addressed this problem with second-generation antipsychotics. The objective of this study was to determine the extent to which risperidone at low doses altered balance control in healthy participants. Twelve healthy young adults received, following a randomized double-blind crossover design, a single oral dose of placebo, 1 and 3 mg of risperidone on separate days at least 14 days apart. Evaluation of extrapyramidal symptoms using the Extrapyramidal Symptom Rating Scale-abbreviated scoring form (ESRS-A) and measures of postural sway using a force platform were assessed over 9 h following drug ingestion. There is a significant increase in the postural stability item of the ESRS-A parkinsonism subscale at 3 and 6 h following 3 mg of risperidone only when compared to placebo. With regard to balance control, body sway measures were increased at 1 mg of risperidone but more pronounced at 3 mg. The peak effects were observed at 3 h after administration of the drug and had not completely returned to baseline after 9 h. Risperidone administered at low doses did not elicit clinically detectable EPS but had significant effects on balance control. A dose-response effect on impairment of balance was observed that followed the expected time course of the drug pharmacokinetics. These results are likely to apply to older or demented individuals who have pre-existing balance control deficit.


Students and simulation facilitators' experiences and perceptions of a distraction and interruption simulation: a mixed-methods study.
While distractions and interruptions are leading causes of errors during medication preparation, most nursing students are not taught how to manage distractions in a highly-interruptive environment. To help prepare nursing students to manage distractions and interruptions in clinical practice, we developed, implemented, and evaluated a medication preparation distraction and interruption simulation. To explore student and simulation facilitators experiences and perceptions of a distraction and interruption simulation. A sequential explanatory mixed-methods design was adopted including surveys, interviews, and focus groups. A mid-sized research intensive western Canadian university. A total of 112 third year nursing students who engaged in the distraction and interruption simulation, and five simulation facilitators who facilitated the distraction and interruption simulation, participated in this study. Students were invited to complete a cross sectional survey following the distraction and interruption simulation and were then invited to participate in focus groups. Simulation facilitators were invited to participate in one-on-one interviews following facilitating the distraction and interruption simulation. All data were collected between June and December 2020. Data from surveys, interviews, and focus groups were delineated into 4 themes related to the phases of the simulation. The prebriefing provided an overview of the simulation and helped create psychological safety that was imperative for learning about potential medication errors when being distracted and interrupted. The simulation scenario had a high degree of fidelity and helped students implement strategies to manage distractions and interruptions. The structured debrief provided an opportunity for meaningful reflection. The impact of the simulation was apparent as students articulated the balance between speed versus safety and new strategies developed to manage distractions and interruptions in clinical practice. This study supports the use of simulation to develop key skills for managing distractions and interruptions during medication preparation in clinical practice.


Narrative impairment, white matter damage and CSF biomarkers in the Alzheimer's disease spectrum.
Narrative discourse (ND) refers to one's ability to verbally reproduce a sequence of temporally and logically-linked events. Impairments in ND may occur in subjects with Amnestic Mild Cognitive Impairment (aMCI) and Alzheimer's Disease (AD), but correlates across this function, neuroimaging and cerebrospinal fluid (CSF) AD biomarkers remain understudied. We sought to measure correlates among ND, Diffusion Tensor Imaging (DTI) indexes and AD CSF biomarkers in patients within the AD spectrum. Groups differed in narrative production (NProd) and comprehension. aMCI and AD presented poorer inference abilities than controls. AD subjects were more impaired than controls and aMCI regarding WB (p<0.01). ROIs DTI assessment distinguished the three groups. Mean Diffusivity (MD) in the uncinate, bilateral parahippocampal cingulate and left inferior occipitofrontal fasciculi negatively correlated with NProd. Changes in specific tracts correlated with T-tau/Aβ1-42 ratio in CSF. AD and aMCI patients presented more ND impairments than controls. Those findings were associated with changes in ventral language-associated and in the inferior parahippocampal pathways. The latest were correlated with biomarkers' levels in the CSF. AD (N=14), aMCI (N=31) and Control (N=39) groups were compared for whole brain (WB) and regions of interest (ROI) DTI parameters, ND and AD CSF biomarkers.


Zinc sulfate supplementation for treatment of recurring oral ulcers.
Use of zinc sulfate in promotion of wound healing and in maintenance of epithelial integrity suggested its possible use in the treatment or prevention of recurrent oral ulcers. In a series of 32 patients with recurrent aphthous ulcers (RAU), serum zinc levels were observed. Seventeen patients, eight with initial serum zinc levels above 110microng/dl and nine with serum zinc levels below 110microng/dl, were provided zinc sulfate supplementation up to a total of 660 mg/day. All patients with initial serum zinc levels less than or equal to 110 microng/dl showed improvement; three of the eight patients with initial serum zinc levels above 110 microng/dl improved, five did not. Improvement consisted of 50% to 100% reduction in frequency of episodes. This suggests a combination of causes of RAU, one of which may be a local or general deficiency of zinc or a defect in metabolism, perhaps at the cellular level, related to zinc.


Combined lentiviral and RNAi technologies for the delivery and permanent silencing of the hsp25 gene.
Elevated heat shock protein 27 (Hsp27) expression has been found in a number of tumors, including breast, prostate, gastric, uterine, ovarian, head and neck, and tumor arising from the nervous system and urinary system, and determined to be a predictor of poor clinical outcome. Although the mechanism of action of Hsp27 has been well documented, there are currently no available inhibitors of Hsp27 in clinical trials. RNA interference (RNAi) has the potential to offer more specificity and flexibility than traditional drugs to silence gene expression. Not surprisingly, RNAi has become a major focus for biotechnology and pharmaceutical companies, which are now in the early stages of developing RNAi therapeutics, mostly based on short interfering RNA (siRNAs), to target viral infection, cancer, hypercholesterolemia, cardiovascular disease, macular degeneration, and neurodegenerative diseases. However, the critical issues associated with RNAi as a therapeutic are delivery, specificity, and stability of the RNAi reagents. To date, the delivery is currently considered the biggest hurdle, as the introduction of siRNAs systemically into body fluids can result in their degradation, off-target effects, and immune detection. In this chapter, we discuss a method of combined lentiviral and RNAi-based technology for the delivery and permanent silencing of the hsp25 gene.


Dynamics model for analyzing reaching movements during active and passive torso rotation.
We have developed an inverse dynamics model of unrestrained natural reaching movements. Such movements are usually not planar and often involve complex deformation of the shoulder girdle as well as rotary and linear torso motion. Our model takes as its input kinematic data about the positions of the finger, wrist, elbow, left and right acromion processes, and the sternum and produces the torques and forces developed at the shoulder, elbow, and wrist joints. The model can also be used to simulate the consequences of introducing passive torso rotation or linear acceleration on arm movements and to simulate the consequences of applying mechanical perturbations to the reaching limb. It separately quantifies the contributions of inertial forces resulting from torso rotation and translation. In experimental paradigms involving arm movements, different dynamic components can be present such as active or passive torso rotation and translation, external forces and Coriolis forces. Our model provides a means of evaluating the different sources of force and the total muscle force needed to control the trajectory of the arm in their presence.


Osteocutaneous defects of the clavicle: two case reports, analysis of the literature, and a novel management algorithm.
Osteocutaneous defects of the clavicle follow surgical management of chronic infections, tumors, and trauma. There are several reconstructive options, but it is unknown whether the bone needs to be reconstructed, which flaps are the best for reconstruction, nor why certain flaps favored over other options for a given scenario. Factors such as wound etiology, defect size, patient demographics, and co-morbidities guide therapy. The management of osteocutaneous defects of the clavicle is herein reviewed. Two clinical cases are presented, literature discussing clavicle form and function, disease pathogenesis, and reconstructive approaches are analyzed, and a resultant algorithm proposed.


Emerging chemotherapeutic strategies and the role of treatment stratification in Ewing sarcoma.
The Ewing sarcoma family of tumors (ESFT) is one of the most common groups of malignancies arising in children, adolescents, and young adults up to approximately 25 years of age. It comprises Ewing sarcoma arising from bone and extraosseous Ewing sarcoma arising from soft tissues (which includes peripheral neuroectodermal tumors and Askin tumor arising from the chest wall). Ewing sarcoma is treated successfully in many cases by a combination of chemotherapy, surgery, and radiotherapy. A number of prognostic factors have been identified that can be used to stratify patients according to the risk of relapse, allowing optimization of treatment. These can be categorized as tumor-related factors (presence of metastases, tumor site, volume, lactic dehydrogenase level, chromosomal translocation type, presence of fusion transcripts in blood and bone marrow), treatment-related factors (local therapy, histologic response to chemotherapy, radiologic response to chemotherapy, chemotherapy regimen), and patient-related factors (gender, age). Newer chemotherapeutic agents are currently being investigated, and there is now increasing interest in the identification of molecular targets in ESFT that could be exploited therapeutically, which include the mammalian target of rapamycin (mTOR) and insulin growth factor-1 (IGF-1) receptor pathways.


Human Papillomavirus Vaccination Uptake in Canada: A Systematic Review and Meta-analysis.
Human papillomavirus (HPV) is the most commonly sexually transmitted infection in the world and the primary cause of cervical cancer. Canada introduced publicly funded HPV vaccination programs in 2006. The objectives of this study are twofold and aim to (1) determine the levels and (2) examine the various factors influencing vaccine uptake among the general Canadian population. A literature search was conducted on seven databases, followed by screening, methodological quality review (using modified Newcastle-Ottawa Scale), and data extraction. Pooled meta-analysis and a subgroup analysis were conducted stratifying by a number of variables (age, sex, type of program, and method of payment) determined apriori. A total of 718 peer-reviewed articles were initially identified with 12 remaining after screening and underwent methodological quality review. HPV vaccination uptake in Canada varied from 12.40% (95% confidence interval [CI] 6.77-20.26) to 88.20% (95% CI 85.72-90.39). The pooled random effects model showed the HPV vaccination uptake to be 55.92% (95% CI 44.87-66.65). The subgroup analysis showed that vaccination uptake was 66.95% (95% CI 55.00-77.89) in participants ≤ 18 years as compared to 13.58% (95% CI 10.93-16.46) in participants > 18 years. Uptake for females was higher 57.23% (95% CI: 45.40-68.66) when compared to that of 47.01% (95% CI: 0.82-97.75) in males. HPV vaccine uptake among school-based programs was 69.62% (95% CI 57.27-80.68) as compared to 18.66% (95% CI 6.66-34.92) for community-based programs. Vaccination uptake for publicly funded programs was significantly higher 66.95% (95% CI 55.00-77.89) when compared to 13.58% (95% CI 10.92-16.46) for programs where participants had to pay out of pocket. To prevent infections and reduce the burden of HPV-related diseases (including cervical cancer), communities should be made aware and encouraged to vaccinate their children. There is a documented need to direct effort and focus interventions toward improving HPV vaccination uptake in Canada.


P value-driven methods were underpowered to detect publication bias: analysis of Cochrane review meta-analyses.
The aim of the study was to investigate the effect of number of studies in a meta-analysis on the detection of publication bias using P value-driven methods. The proportion of meta-analyses detected by Egger's, Harbord's, Peters', and Begg's tests to have asymmetry suggestive of publication bias were examined in 5,014 meta-analyses from Cochrane reviews. P values were also assessed in meta-analyses with varying number of studies, whereas symmetry was held constant. A simulation study was conducted to investigate if the above tests underestimate or overestimate the presence of publication bias. The proportion of meta-analyses detected as asymmetrical via Egger's, Harbord's, Peters', and Begg's tests decreased by 42.6%, 41.1%, 29.3%, and 28.3%, respectively, when the median number of studies in the meta-analysis decreased from 87 to 14. P values decreased as the number of studies increased in the meta-analysis, despite the level of symmetry remaining constant. The simulation study confirmed that when publication bias is present, P value tests underestimate the presence of publication bias, particularly when study numbers are small. P value-based tests used for the detection of publication bias-related asymmetry in meta-analysis require careful examination, as they underestimate asymmetry. Alternative methods not dependent on the number of studies are preferable.


Interreader reproducibility of the Neck Imaging Reporting and Data system (NI-RADS) lexicon for the detection of residual/recurrent disease in treated head and neck squamous cell carcinoma (HNSCC).
To evaluate the inter- and intrareader agreement and reproducibility of the NI-RADS scoring system and lexicon with contrast-enhanced computed tomography (CECT) and contrast-enhanced magnetic resonance imaging (CEMRI). This retrospective study included 97 CECT and CEMRI scans from 58 treated cases of head and neck squamous cell carcinoma (HNSCC) after the exclusion of head and neck cancers (HNCs) other than SCC and noncontrast and poor quality CT and MRI scans, with a total of 111 primary targets and 124 lymph node (LN) targets. Two experienced readers independently scored the likelihood of residual/recurrence for these targets based on the NI-RADS criteria and filled in report templates for NI-RADS lexicon diagnostic features. Inter- and intraobserver reproducibility was assessed with Cohen's kappa, and the percent agreement was calculated. Almost perfect interreader agreement was found for the final NI-RADS category of the primary lesions and LNs, with K = 0.808 and 0.806, respectively. Better agreement was found for CT than for MRI (K = 0.843 and 0.77, respectively, P value 0.001). There was almost perfect agreement for excluding tissue enhancement (K = 0.826, 95% CI = 0.658-0.993, P value 0.001), with a percent agreement of 96.4%, and substantial agreement for discrete nodular and diffuse mucosal enhancement (K = 0.826, 95% CI = 0.658-0.993, P value 0.001), with a percent agreement of 96.4%. There was fair agreement for focal mucosal nonmass and deep ill-defined enhancement. The intrareader agreement was almost perfect for most of the rated features (K ranging from 0.802 to 1), with the exception of enlarging discrete nodule/mass and focal mucosal nonmass-like enhancement, which had substantial intraobserver agreement (K ranging from 0.768 to 0.786). The individual features of NI-RADS show variable degrees of confidence; however, the overall NI-RADS category was not significantly affected.


Developing a peer-mentor program for medical students.
Doctoring is a 2-year preclinical course designed to teach medical students fundamental clinical skills. We designed, implemented, and evaluated an innovative and cost-effective peer-mentoring program embedded within Doctoring. Our Teaching Academy (TA) included a formal orientation for teaching "Fellows." During academic years 2008-09 and 2009-10, 2nd-year students were systematically selected by course faculty and then trained as TA Fellows to peer-mentor 1st-year students. Both TA Fellows and 1st-year medical students completed anonymous written surveys. Peer-mentors reported a significant increase of confidence in their ability to provide feedback (p < .001). First-year students reported a significant increase of confidence in their ability to conduct a medical interview and perform a physical exam (p < .001 for each). Student participation in a formal peer-mentor program embedded within a clinical skills course significantly increased, for both teachers and learners, confidence in their skills. Our program is easily transferrable to other courses and institutions.


The Cryptic dsdA Gene Encodes a Functional D-Serine Dehydratase in Pseudomonas aeruginosa PAO1.
D-Serine, an important neurotransmitter, also contributes to bacterial adaptation and virulence in humans. It was reported that Pseudomonas aeruginosa PAO1 can grow on D-serine as the sole nitrogen source, and growth was severely reduced in the dadA mutant devoid of the D-alanine dehydrogenase with broad substrate specificity. In this study, the dsdA gene (PA3357) encoding a putative D-serine dehydratase was subjected to further characterization. Growth on D-serine as the sole source of nitrogen was retained in the ∆dsdA mutant and was abolished completely in the ∆dadA and ∆dadA-∆dsdA mutants. However, when complemented by dsdA on a plasmid, the double mutant was able to grow on D-serine as the sole source of carbon and nitrogen, supporting the proposed biochemical function of DsdA in the conversion of D-serine into pyruvate and ammonia. Among D- and L-amino acids tested, only D-serine and D-threonine could serve as the substrates of DsdA, and the Km of DsdA with D-serine was calculated to be 330 μM. Comparative genomics revealed that this cryptic dsdA gene was highly conserved in strains of P. aeruginosa, and that most strains of Pseudomonas putida possess putative dsdCAX genes encoding a transcriptional regulator DsdC and a D-serine transporter DsdX as in enteric bacteria. In conclusion, this study supports the presence of a cryptic dsdA gene encoding a functional D-serine dehydratase in P. aeruginosa, and the absence of dsdA expression in response to exogenous D-serine might be due to the loss of regulatory elements for gene activation during evolution.


Amphetamine-induced taste aversion demonstrated with operant behaviour.
Amphetamine can be used to condition strong taste aversions, but little is known about the possible effects of flavour-amphetamine pairings on operant behaviour. Rats were trained to press bars for water reinforcers delivered after every 40 responses (FR 40). Flavoured reinforcers were then substituted for the water and post-session injections of amphetamine (1 mg/kg) were given. Even a single flavour-amphetamine pairing produced some decrement in responding for that flavour, whereas three flavour-amphetamine pairings almost completely suppressed responding. In the same rats, a flavour which was paired with saline injections did not suppress responding. Flavour-amphetamine pairings can therefore have a powerful influence on operant behaviour and the different outcomes of flavour-conditioning and self-administration procedures cannot be attributed simply to the type of response required from the rat.


Hemodynamic Effect of Resuscitative Endovascular Balloon Occlusion of the Aorta in Hemodynamic Instability Secondary to Acute Cardiac Tamponade in a Porcine Model.
The pre-hospital use of Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) is increasing, although it remains controversial, in part because of suggested contraindications such as acute cardiac tamponade (ACT). As both the pre-hospital and in-hospital use of REBOA might potentially occur with concurrent ACT, knowledge of the hemodynamic effect of REBOA in this setting is crucial. This study, therefore, aimed at investigating the physiological effects of REBOA in hemodynamic instability secondary to ACT in a porcine model. We hypothesize that REBOA can temporarily increase systemic blood pressure and carotid blood flow, and prolong survival, in hemodynamic shock caused by ACT. Fourteen pigs (24-38 kg) underwent ACT, through true cardiac injury and hemorrhage into the pericardial space, and were allowed to hemodynamically deteriorate. At a systolic blood pressure (SBP) of 50 mm Hg (SBP50) they were randomized to total occlusion REBOA in zone 1 or to a control group. Survival, hemodynamic parameters, carotid blood flow (CBF), femoral blood flow (FBF), cardiac output (CO), end-tidal CO2, and arterial blood gas parameters were analyzed. REBOA intervention was associated with a significant increase in SBP (50 mm Hg to 74 mm Hg, P = 0.016) and CBF (110 mL/min to 195 mL/min, P = 0.031), with no change in CO, compared to the control group. At 20 min after SBP50, the survival rate in the intervention group was 86% and in the control group 14%, with time to death being significantly longer in the intervention group. This randomized animal study demonstrates that REBOA can help provide hemodynamic stabilization and prolong survival in hemodynamic shock provoked by ACT. It is important to stress that our study does not change the fact that urgent pericardiocentesis or cardiac surgery is, and should remain, the standard optimal treatment for ACT.Level of evidence: Prospective, randomized, experimental animal study. Basic science study, therapeutic.


Bioleaching of the α-alumina layer of spent three-way catalysts as a pretreatment for the recovery of platinum group metals.
Acid bioleaching of Al by Acidithiobacillus thiooxidans has been explored as an environmentally friendly pretreatment to facilitate the extraction of platinum group metals from spent three-way catalysts (TWC). Biogenic sulfur obtained from desulfurization bioreactors improved the production of acid by A. thiooxidans compared to commercially available elemental sulfur. The lixiviation abilities of bacteria-free biogenic acid and biogenic acid with exponential or stationary phase bacteria were compared against a control batch produced by commercial H2SO4. The maximum Al leaching percentage (54.5%) was achieved using biogenic acids with stationary-phase bacteria at a TWC pulp density of 5% w/v whereas bacteria-free biogenic acid (23.4%), biogenic acid with exponential phase bacteria (21.7%) and commercial H2SO4 (24.7%) showed lower leaching abilities. The effect of different pulp densities of ground TWC (5, 30, and 60% w/v) on Al leaching and bacterial growth was determined. While greater Al leaching yields were obtained at lower TWC pulp density solutions (54.5% at 5% w/v and 2.5% at 60% w/v), higher pulp densities enhanced microbial growth (2.3 × 109 cells/mL at 5% w/v and 9.5 × 1010 cells/mL at 60% w/v). The dissolution of the metal from the solid into the liquid phase triggered the production of biological polymeric substances that were able to absorb traces of both Al (up to 24.80% at 5% w/v) and Pt (up to 0.40% at 60% w/v).


Retracted: Decision-Making Application of the Cloud-Fog Hybrid Model Based on the Improved Convolutional Neural Network in Financial Services in Smart Medical Care.
[This retracts the article DOI: 10.1155/2022/5732379.].


How predictive is body weight on fluid intake in rats? It depends on sex.
The assumption that body weight is a predictor of fluid intake is often used as rationale for normalizing intake to body weight when examining sex differences in drinking behavior. Nonuniform application of this body weight correction likely contributes to discrepancies in the literature. We, however, previously demonstrated sex differences in the relationship between body weight and angiotensin II (AngII)-stimulated water intake. Only after a pharmacological dose of AngII did water intake correlate with body weight, and only in males. Here we investigated whether body weight correlated with fluid intake stimulated by additional dipsogenic agents in male and female rats. We found that intake stimulated by either water deprivation or furosemide correlated with body weight in male rats. We found no relationship between intake and body weight after water deprivation, furosemide treatment, or isoproterenol treatment in females, nor did we find a relationship between intake and body weight after hypertonic saline treatment in either males or females. Finally, we report that daily water intake correlated with body weight in females. This effect, however, is likely the result of a relationship between body weight and food intake because when food was absent or reduced, the correlation between body weight and intake disappeared. These results demonstrate that multiple factors need to be considered when determining the best way to compare fluid intake between males and females and provides insight to help explain the discrepancies in the literature regarding sex differences in fluid intake.


Therapeutic targeting of Toll-like receptors for inflammatory and infectious diseases.
Roles for Toll-like receptors (TLRs) are emerging in conditions such as sepsis syndrome, systemic lupus erythromatosis, rheumatoid arthritis and asthma, suggesting that the selective targeting of TLRs might be useful therapeutically. TLRs are defined by the presence of extracellular leucine-rich repeats and an intracellular Toll/interleukin-1 receptor domain, and play a role in host defence and inflammation. Signalling pathways activated by TLRs show remarkable similarity to those activated by the pro-inflammatory cytokine interleukin-1 (the receptor for which also has a Toll/interleukin-1 receptor domain), although adaptor proteins specific for certain TLRs are starting to emerge (e.g. Mal and Trif). The common signalling pathways used by all members of the TLR superfamily are being targeted, with drugs that block nuclear factor-kappaB and p38 mitogen-activated protein kinase in clinical development for diseases such as rheumatoid arthritis and psoriasis. As we learn more about TLR signal transduction, more options are presenting themselves for pharmacological targeting.


One-way PCR-based mapping of a replication initiation point (RIP).
The lamin B2 locus is the only mammalian origin whose replication initiation points (RIPs) have been mapped. Although this paper was published 8 years ago, no further mammalian RIP-mapping studies have been reported, largely due to technical difficulties of ligation-mediated (LM)-PCR used by the authors. Here, we report the development of a simple, one-way PCR-based protocol that allows one to accurately determine RIPs at mammalian origins. The procedure can be completed within 48 h from the time of cell lysis in the agarose gel. Nascent DNA is then isolated from the same gel after DNA is separated by alkaline gel electrophoresis. Subsequently, RIPs are determined by one-way PCR-based primer extension using labeled primers. Using this protocol, we have successfully mapped RIPs in the human DBF4 locus. As one-way PCR is routinely used by many scientists, this protocol will provide a powerful new tool for studying DNA replication in many organisms including mammalian cells.


Keys to successful implementation of routine symptom monitoring in head and neck oncology with "Healthcare Monitor" and patients' perspectives of quality of care.
Value-based health care is increasingly used to facilitate a systematic approach during follow-up of patients. We developed Healthcare Monitor (HM): a structure of electronic patient-reported outcome measures (ePROs) for the longitudinal follow-up of head and neck cancer (HNC) patients. This study shares key lessons from implementation and seeks to provide insight into how patients experience HM. We conducted a mixed-methods study using quantitative data from a nonrandomized retrospective survey of patients who received HM (n = 45) vs standard care (n = 46) and qualitative data from structured interviews (n = 15). Implementation of HM included significant challenges. Finding common ground among clinicians, administrators, and IT staff was most important. Qualitative findings suggest that patients experienced better doctor-patient communication and increased efficiency of the consultation using HM. Patients felt better prepared and experienced more focus on critical issues. Quantitative analysis did not show significant differences. Integration of HM into routine care for HNC patients may have increased patient-centered care and facilitated screening of symptoms. However, future research is needed to analyze the potential benefits more extensively.


Misplacement of LVAD inflow cannula leads to insufficient output and tissue hypoperfusion.
A 63-year-old man with a newly placed left ventricular assist device (LVAD) was emergently taken to the operating room for mediastinal exploration secondary to worsened LVAD output, hemodynamic instability, and organ hypoperfusion. Intraoperative transesophageal echocardiography showed the LVAD inflow cannula intermittently aspirating the atrial septal wall, resulting in occlusion of the inflow cannula. Upon gradual withdrawal of the inflow cannula by several centimeters, dramatic improvements in LVAD output, hemodynamics, and tissue perfusion occurred. Clinical implications of a patient who has a malfunctioning LVAD are discussed.


Ecological risk assessment of TBT in Ise Bay.
An ecological risk assessment of tributyltin (TBT) in Ise Bay was conducted using the margin of exposure (MOE) method. The assessment endpoint was defined to protect the survival, growth and reproduction of marine organisms. Sources of TBT in this study were assumed to be commercial vessels in harbors and navigation routes. Concentrations of TBT in Ise Bay were estimated using a three-dimensional hydrodynamic model, an ecosystem model and a chemical fate model. Estimated MOEs for marine organisms for 1990 and 2008 were approximately 0.1-2.0 and over 100 respectively, indicating a declining temporal trend in the probability of adverse effects. The chemical fate model predicts a much longer persistence of TBT in sediments than in the water column. Therefore, it is necessary to monitor the harmful effects of TBT on benthic organisms.


Comparison between cell motion analyser, autosperm, and conventional semen analysis.
With the aim of explaining some of the controversy on the value of computer-assisted methods of semen analysis, a study was conducted comparing the fully automated cell motion analyzer (CMA), the semi-computerized autosperm system (AS) and the conventional manual method. The CMA equipment gave higher values for sperm concentration than the mean of the three methods. Sperm concentration estimated with the conventional method was below the average of the three methods. The conventional method overestimated sperm motility, which was underestimated by CMA. The correlation between sperm velocity characteristics estimated by CMA and AS was significant, but only 18% of variability of one method could be explained by variability of the other. The reasons for the discrepancy between velocity measurements in the two methods are discussed in relation to possible shortcomings in sperm paths smoothing using the CMA method and the effect of technician training in the AS method. The AS method was found to provide more reproducible results which correlated better with those of the manual method as recommended by the World Health Organization.


A technique for knotting a suture around the loops of a dislocated intraocular lens, within the eye, for fixation in the ciliary sulcus.
I describe a new, simpler, technique for attaching a suture to the haptic of a dislocated posterior chamber lens implant. A 10-0 polypropylene suture is used, doubly armed with straight needles. This technique has been used successfully in five cases.


Frequency, predictors and outcome of stent fracture after sirolimus-eluting stent implantation.
Recently, stent fracture (SF) of sirolimus-eluting stents (SES) has been shown to be associated with an increased risk of in-stent restenosis. We sought to evaluate the incidence, predictors and clinical outcome of SF after SES implantation in comparable unselected lesions. A total of 430 lesions of 382 patients treated with SES were analyzed. SF was defined as single or multiple stent strut fracture as well as complete separation of stent segments. At follow-up, SF was identified in 33 of 430 lesions (7.7%). In lesions with SF, the in-stent restenosis was observed more frequently than non-SF lesions (15.2% vs. 4.0%, P=0.004). At 450 days, however, the cumulative rate of major cardiac events was not significantly different between lesions with and without SF (9.1% vs. 7.1%, P=0.722). The risk of SF was independently associated with total stent length (OR 2.22; 95% CI, 1.25 to 3.95; P=0.007), the change in the angulation of the lesion after stenting (OR 1.55; 95% CI, 1.07 to 2.25; P=0.020), and the right coronary artery lesions (OR 3.26; 95% CI, 1.18 to 8.96; P=0.022). The occurrence of SF after SES implantation, was found to be relatively common in the particular population, however, did not lead to an increased risk of adverse cardiac events at 450 days, despite a higher incidence of in-stent restenosis.


Evaluation of macular abnormalities in Stargardt's disease using optical coherence tomography and scanning laser ophthalmoscope microperimetry.
The purpose of this study is to evaluate the diagnostic value of optical coherence tomography (Stratus OCT) and scanning laser ophthalmoscope (SLO) microperimetry in patients with Stargardt's disease (STGD), and the correlation between macular morphology and visual function in these patients. Twenty-two patients with STGD (mean age 44 years, range 11 to 71 years) and 20 age-matched healthy control subjects were included in the study. OCT imaging was performed using six radial line scans manually centered on the fovea. SLO microperimetry was used to assess central scotoma and fixation behavior in patients with STGD. Mean best corrected Snellen visual acuity (BCVA) was 20/80, range 20/25 to 20/300 (log MAR 0.6, range 0.1 to 1.2) in the STGD group and 20/20 (log MAR 0.0) in the control group. Foveal thickness was significantly reduced in patients with STGD (119.0 +/- 19.6 microm) compared to controls (210.7 +/- 19.6 microm, P < 0.0001). A significant correlation between foveal thickness and BCVA was observed within the STGD group (R(2) = 0.62, P < 0.0001). Photoreceptor loss in the macular area and a corresponding central scotoma were observed in all STGD patients. OCT findings, particularly reduced foveomacular thickness and photoreceptor loss in the macular area may be useful in the diagnosis of STGD. Furthermore, a strong correlation between foveal thickness and visual function was observed in our patients. Assessment of central visual function using SLO microperimetry provides additional useful information, important in the management of STGD.


The role of metabolism in aging.
Metabolism appears to play a significant role in determining the rate of aging. Long-lived mutants and selected stocks of model experimental organisms exhibit characteristic changes in life history and physiological features consistent with altered metabolism. Specifically, these include the accumulation of metabolite pools of glycogen, lipid and polyhedric alcohols, suggesting that prolonged life is associated with restriction of the flow of carbon through glycolysis. Limiting carbon flow by reducing caloric intake is well known to extend life. Studies examining the mRNA expression pattern of functional gene groups generally indicate that nutrient restriction does affect metabolism. One study of Drosophila melanogaster has demonstrated that the flux of carbon through glycolysis is reduced in larvae of selected long-lived populations. Here we propose a new hypothesis describing the interaction between the glycation process, glucose level, damage by free oxygen radicals and chaperonin proteins. Intermediate steps of the Maillard Reaction produce free radicals, similar to those produced during respiration, that also damage lipids, proteins and DNA. Antioxidant enzymes themselves can be inactivated by glycation. This establishes a positive feed-back between the rate of metabolism, glucose availability and damage by free oxygen radicals. The high levels of available glucose in ad libitum feeding should add to production of radicals, reduce levels of protective antioxidants and proportionally increase damage by free radicals. Thus, caloric restriction should lower available glucose, increase the level of antioxidants and thereby slow the rate of aging. Chaperonins act to block glycation, reducing its negative effect on antioxidant enzymes release and contribution of free radicals.


Transcription-dependent structural changes in the C-terminal domain of mammalian RNA polymerase subunit IIa/o.
The C-terminal domain of mammalian RNA polymerase subunit IIa consists of 52-tandem repeats of the consensus sequence Tyr-Ser-Pro-Thr-Ser-Pro-Ser. This C-terminal domain is essentially unmodified in RNA polymerase IIA and extensively phosphorylated in RNA polymerase IIO. A monoclonal antibody directed against the C-terminal domain was shown by kinetic enzyme-linked immunosorbent assay to have a 10-fold higher reactivity with RNA polymerase IIA than with RNA polymerase IIO. The ability of increasing concentrations of this monoclonal antibody to inhibit the initiation and elongation phase of transcription was determined. Although both phases of the transcription reaction were inhibited, a 10-fold higher concentration of antibody was required to inhibit elongation than was required to inhibit initiation. These results support the hypothesis that RNA polymerase IIA, containing an unphosphorylated C-terminal domain, is involved in the formation of an initiated complex, whereas elongation is catalyzed by RNA polymerase IIO, containing a phosphorylated C-terminal domain. Further indication that the C-terminal domain undergoes a structural change during the transcription cycle results from the observation that this domain is 3-fold more sensitive to clostripain cleavage in the elongation enzyme than in the free enzyme.


Quadriparesis as an unusual manifestation of chronic subdural haematoma.
Chronic subdural haematomas are frequently seen in neurosurgical practice, but because of the multitude of their clinical presentations, appropriate diagnosis is often not made in the early stages. The cases reported concern a 62-year-old male and a 54-year-old woman, both presenting in an unusual manner, namely a progressive quadriparesis.


Acute exposure to traffic-related air pollution alters antioxidant status in healthy adults.
Exposure to traffic-related air pollution is associated with an increased risk of cardiovascular and respiratory disease. Evidence suggests that inhaled pollutants precipitate these effects via multiple pathways involving oxidative stress. Postulating that a decrease in circulating antioxidant levels reflect an oxidative response, we investigated the effect of inhaled diesel exhaust (DE) on the ratio of reduced to oxidized glutathione (GSH/GSSG) in healthy adults, and whether pre-exposure antioxidant supplementation blunted this response. We also examined exposure-related changes in antioxidant/stress response leukocyte gene expression (GCLc, HMOX-1, IL-6, TGFβ) and plasma IL-6 levels. Nineteen nonsmoking adults participated in a double-blind, randomized, four-way crossover study. Each subject completed 120-min exposures to filtered air and DE (200 μg/m3), with and without antioxidant pretreatment. Antioxidant comprised 1000 mg ascorbate for 7 days and 1200 mg N-acetylcysteine 1 day prior to exposure, with 1000 mg and 600 mg, respectively, administered 2 h prior to exposure. Whole blood glutathione was measured pre- and post-exposure; plasma IL-6 and mRNA expression were quantified pre, during and post exposure. Diesel exhaust exposure was associated with significantly decreased GSH/GSSG (p = 0.001) and a 4-fold increase in IL-6 mRNA (p = 0.01) post exposure. Antioxidant pretreatment did not significantly mediate the effect of DE exposure on GSH/GSSG, though appeared to decrease the effect of exposure on IL-6 mRNA expression. Acute DE inhalation induced detectable oxidative effects in healthy adults, which were not significantly attenuated by the selected antioxidant pre-treatment. This finding supports the premise that oxidative stress is one mechanism underlying the adverse effects of traffic-related air pollution.


Alternation of bottom-up and top-down regulation in a natural population of an agromyzid leafminer, Chromatomyia suikazurae.
The population dynamics and the relative importance of bottom-up and top-down effects in a plant-leafminer-multiparasitoid interaction was studied between 1981 and 1990 in a natural forest in Kyoto, Japan. The leafminer, Chromatomyia suikazurae (Agromyzidae, Diptera), passed two generations (G1 and G2) on Lonicera gracilipes (Caprifoliaceae). The G1 population in February was free from parasitoid attack, and the mortality in G1 was mainly caused by resource limitation. Intraspecific competition for resources occurred at the larval stage in G1, and the larval mortality was density-dependent. The G1 adult density was resource-limited (the number of newly opened leaves), and its variability was lower than that of G2. The G2 population in April was not resource-limited but subject to intense attack by a species-rich parasitoid complex, and thus total mortality was much larger than that in G1. Significant density dependence was detected not in larval but in pupal mortalities, which were mainly caused by parasitism by parasitoids that attacked the pupa. The host population alternately experienced "bottom-up" effects during the larval stage in G1 and "top-down" effects during the pupal stage in G2. Overall population fluctuation was non-cyclic and mainly due to climatically-induced fluctuation of available plant resources in G1.


Proteomics in rheumatology: a new direction for old diseases.
Completion of the human genome project has stimulated scientists to begin looking for the next step in unraveling normal and abnormal functions within biological systems. Consequently, there is new focus on the role of proteins in these processes. Proteomics is a rapidly growing field that may provide a valuable approach to evaluate the field of rheumatology. The objectives of this article is to provide an overview of biophysical techniques, as "re-invented" research tools, as applied to the investigation of rheumatoid arthritis and osteoarthritis. MEDLINE search of articles in English-language journals from 1966 to 2004. The index words "Rheumatoid/osteoarthritis/connective tissue disorders" and the following co-indexing terms were used: "mass spec," "NMR," "SPR" and "Proteomics." Papers identified were reviewed, abstracted, and summarized. The authors' own work in the field is also presented. As we move into the postgenomics era, new and exciting tools are being developed to study protein expression and protein interactions and identify new biomarkers for disease diagnosis and prognosis. Proteomics is an emerging field with widespread potential applications to rheumatic disease. In this review the biophysical techniques of nuclear magnetic resonance, mass spectroscopy, and surface plasmon resonance as proteomic tools in the study of rheumatoid and osteoarthritis were reviewed. What is emerging is the identification of new biomarkers with clinical and therapeutic relevance.


Identifying asymptomatic healthcare workers with COVID-19 in a community hospital: an institution's experience.
The outbreak related to SARS-CoV-2 or COVID-19 has been classified as a pandemic. Many healthcare institutions enacted policies to limit the spread within their facility. As hospitals begin to return to normal particularly with elective procedures, a common concern is how an organization should react in the event that healthcare workers test positive for COVID-19. When our organization had a cluster of positive inpatient healthcare workers, we elected to test all direct patient care healthcare workers. Through this process we learned two valuable lessons that have redefined our practice: 1) the recognition that aggressive contact tracing provides greater yield than testing everyone and 2) organizations must implement effective social distancing both within each department and how departments interact with each other to limit the scope of contract tracing.


Association between long-term occupational noise exposure and obesity.
Noise exposure has been linked to several health outcomes including obesity. This cross-sectional study examined the association between occupational noise exposure and body mass index as a measure of general obesity in 913 textile workers (totally from nine factories) in Yazd city, Iran, from winter to summer of 2018. The sound pressure level (dBA) at each working station was measured by a calibrated sound level meter. The long-term noise exposure score of each worker (as dBA.year) was calculated by multiplying the working history in each unit to its corresponding noise level. Models were adjusted for personal, behavioral, environmental, and family history factors. In total, 81.05% (n = 740) of the participants were exposed to noise levels higher than 85 dBA. The direct association was found for the fully adjusted model (β = 0.002; 95% CI: 0.001: 0.004). For the model with past year noise exposure, a 10.6% increase in odds was observed for each 5 dBA increase in noise exposure (95% CI: 1.005: 1.216). We found a 0.1% increase in the odds of being overweight in mixed-gender analysis (95% CI: 1.001:1.002) for each 5 dBA.year in the fully adjusted model. Occupational noise exposure should be regarded as a risk factor for cardiometabolic outcomes in industrial workers.


Identification of differentially expressed genes and signaling pathways using bioinformatics in interstitial lung disease due to tyrosine kinase inhibitors targeting the epidermal growth factor receptor.
Interstitial lung disease (ILD) is a rare but lethal adverse effect of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) treatment. The specific mechanism of this disease is not fully understood. To systematically analyze genes associated with EGFR-TKI induced ILD, gene data of EGFR-TKI induced ILD were extracted initially using text mining, and then the intersection between genes from text mining and Gene Expression Omnibus (GEO) dataset was taken for further protein-protein interaction (PPI) analysis using String-bd database. Go ontology (GO) and pathway enrichment analysis was also conducted based on Database of Annotation, Visualization and Integrated Discovery (DAVID) platform. The PPI network generated by STRING was visualized by Cytoscape, and the topology scores, functional regions and gene annotations were analyzed using plugins of CytoNCA, molecular complex detection (MCODE) and ClueGo. 37 genes were identified as EGFR-TKI induced ILD related. Gene enrichment analysis yield 18 enriched GO terms and 12 associated pathways. A PPI network that included 199 interactions for a total of 35 genes was constructed. Ten genes were selected as hub genes using CytoNCA plugin, and four highly connected clusters were identified using MCODE plugin. GO and pathway annotation analysis for the cluster one revealed that five genes were associated with either response to dexamethasone or with lung fibrosis, including CTGF, CCL2, IGF1, EGFR and ICAM1. Our data might be useful to reveal the pathological mechanisms of EGFR-TKI induced ILD and provide evidence for the diagnosis and treatment in the future.


Binding mode analysis of 3-(4-benzoyl-1-methyl-1H-2-pyrrolyl)-N-hydroxy-2-propenamide: a new synthetic histone deacetylase inhibitor inducing histone hyperacetylation, growth inhibition, and terminal cell differentiation.
The binding mode of 3-(4-aroyl-1H-2-pyrrolyl)-N-hydroxy-2-propenamides 1a-c, belonging to a recently reported class of synthetic histone deacetylase (HDAC) inhibitors (Massa, S.; et al. J. Med. Chem. 2001, 44, 2069-2072), into the new modeled HDAC1 catalytic core is presented, and enzyme/inhibitor interactions are discussed. HDAC1 X-ray coordinates were obtained by virtual "mutation" of those of histone deacetylase-like protein, a bacterial HDAC homologue. In in vitro antimaize HD2 as well as antimouse HDAC1 assay, compounds 1a-c showed inhibitory activities in the low micromolar range. Similarly, 1a-c are endowed with anti-HDAC activity in vivo: on mouse A20 cells, 1a-c induced histone hyperacetylation leading to a highly increased acetylation level of H4 as compared to control histones. Results obtained with acid-urea-triton polyacrylamide gel electrophoresis have been confirmed by Western Blot experiments. Finally, compound 1a, chosen as a representative member of this class of HDAC inhibitors, resulted endowed with antiproliferative (45 and 85% cell growth inhibition at 40 and 80 microM, respectively) and cellular differentiation (18 and 21% of benzidine positive cells at the same concentrations) activities in murine erythroleukemic cells.


Nutritional status of human T-lymphotropic virus 1 patients: A retrospective study.
The nutritional status of people with human T-lymphotropic virus (HTLV-1) infection has been poorly described because it involves a neglected disease. The few studies that have been conducted mostly involve people with neurologic consequences and the possible clinical evolutions of the disease. The aim of this study was to describe the nutritional status of patients with HTLV-1, including those with associated myelopathy/tropical spastic paraparesis, and to evaluate food security in these patients. A retrospective observational study was conducted in people with HTLV-1 admitted to a referral hospital. We collected data from 17 medical records, including anthropometric data (i.e., body mass index, mid-upper arm circumference, triceps skinfold, and mid-arm muscle circumference), laboratory test results (i.e., haemoglobin, haematocrit, albumin, globulin, iron fixation capacity, and iron), the Subjective Global Assessment (SGA) method, and food security (Brazilian Food Insecurity Scale) data. The data were analysed using the R-project software. To evaluate possible associations between the outcomes and predictors (age at hospitalisation, food security, presence of children <18 years of age living in the household, income, schooling, ANSG, BMI, difference between ideal weight and hospitalisation, TSF, MUAC ICU days, hospitalisation outcome, rehospitalisation in the first year after discharge, interval between readmissions, death, associated conditions, constipation upon admission), we used Kruskal-Wallis, Mann-Whitney, Fisher's exact, chi-square tests with continuity correction, and Spearman's correlation coefficient. Hypothesis tests were considered statistically significant when p ≤ 0.05. The mean age of the patients was 57 (52-60) years. The patients were predominantly women (59%) and had an income lower than the local minimum wage with at least 6 years of schooling (52.3%). Only 18.2% of patients were eutrophic according to their BMI and 23.5% of patients were malnourished based on the SGA method. Patients predominantly had food security (64.7%) and good intestinal functions (64.7%) during their hospital stay. Despite having a limited number of patients in this study, HTLV-1 patients admitted to hospital are at high risk of malnutrition based on the scores from the SGA method.


Enterprise Microblogging to Augment the Subinternship Clinical Learning Experience: A Proof-of-Concept Quality Improvement Study.
Although the Clerkship Directors in Internal Medicine (CDIM) has created a core subinternship curriculum, the traditional experiential subinternship may not expose students to all topics. Furthermore, academic institutions often use multiple clinical training sites for the student clerkship experience. The objective of this study was to sustain a Web-based learning community across geographically disparate sites via enterprise microblogging to increase subintern exposure to the CDIM curriculum. Internal medicine subinterns used Yammer, a Health Insurance Portability and Accountability Act (HIPAA)-secure enterprise microblogging platform, to post questions, images, and index conversations for searching. The subinterns were asked to submit 4 posts and participate in 4 discussions during their rotation. Faculty reinforced key points, answered questions, and monitored HIPAA compliance. In total, 56 medical students rotated on an internal medicine subinternship from July 2014 to June 2016. Of them, 84% returned the postrotation survey. Over the first 3 months, 100% of CDIM curriculum topics were covered. Compared with the pilot year, the scale-up year demonstrated a significant increase in the number of students with >10 posts (scale-up year 49% vs pilot year 19%; P=.03) and perceived educational experience (58% scale-up year vs 14% pilot year; P=.006). Few students (6%) noted privacy concerns, but fewer students in the scale-up year found Yammer to be a safe learning environment. Supplementing the subinternship clinical experience with an enterprise microblogging platform increased subinternship exposure to required curricular topics and was well received. Future work should address concerns about safe learning environment.


A comparison between triplet and doublet chemotherapy in improving the survival of patients with advanced gastric cancer: a systematic review and meta-analysis.
Chemotherapy can improve the survival of patients with advanced gastric cancer. However, whether triplet chemotherapy can further improve the survival of patients with advanced gastric cancer compared with doublet chemotherapy remains controversial. This study reviewed and updated all published and eligible randomized controlled trials (RCTs) to compare the efficacy, prognosis, and toxicity of triplet chemotherapy with doublet chemotherapy in patients with advanced gastric cancer. RCTs on first-line chemotherapy in advanced gastric cancer on PubMed, Embase, and the Cochrane Register of Controlled Trials and all abstracts from the annual meetings of the European Society for Medical Oncology (ESMO) and the American Society of Clinical Oncology conferences up to October 2018 were searched. The primary outcome was overall survival, while the secondary outcomes were progression-free survival (PFS), time to progress (TTP), objective response rate (ORR), and toxicity. Our analysis included 23 RCTs involving 4540 patients and 8 types of triplet and doublet chemotherapy regimens, and systematic review and meta-analysis revealed that triplet chemotherapy was superior compared with doublet chemotherapy in terms of improving median OS (HR = 0.92; 95% CI, 0.86-0.98; P = 0.02) and PFS (HR = 0.82; 95% CI, 0.69-0.97; P = 0.02) and TTP (HR = 0.92; 95% CI, 0.86-0.98; P = 0.02) and ORR (OR = 1.21; 95% CI, 1.12-1.31; P < 0.0001) among overall populations. Compared with doublet chemotherapy, subgroup analysis indicated that OS improved with fluoropyrimidine-based (HR = 0.80; 95% CI, 0.66-0.96; P = 0.02), platinum-based (HR = 0.75; 95% CI, 0.57-0.99; P = 0.04), and other drug-based triplet (HR = 0.79; 95% CI, 0.69-0.90; P = 0.0006) chemotherapies while not with anthracycline-based (HR = 0.70; 95% CI, 0.42-1.15; P = 0.16), mitomycin-based (HR = 0.81; 95% CI, 0.47-1.39; P = 0.44), taxane-based (HR = 0.91; 95% CI, 0.81-1.01; P = 0.07), and irinotecan-based triplet (HR = 1.01; 95% CI, 0.82-1.24; P = 0.94) chemotherapies. For different patients, compared with doublet chemotherapy, triplet chemotherapy improved OS (HR = 0.89; 95% CI, 0.81-0.99; P = 0.03) among Western patients but did not improve (HR = 0.96; 95% CI, 0.86-1.07; P = 0.47) that among Asian patients. Compared with doublet chemotherapy, triplet chemotherapy improved OS, PFS, TTP, and ORR in patients with advanced gastric cancer in the population overall, and improved OS in Western but not in Asian patients.


Geometric conservation laws for cells or vesicles with membrane nanotubes or singular points.
On the basis of the integral theorems about the mean curvature and Gauss curvature, geometric conservation laws for cells or vesicles are proved. These conservation laws may depict various special bionano structures discovered in experiments, such as the membrane nanotubes and singular points grown from the surfaces of cells or vesicles. Potential applications of the conservation laws to lipid nanotube junctions that interconnect cells or vesicles are discussed.


Bile exosomal miR-182/183-5p increases cholangiocarcinoma stemness and progression by targeting HPGD and increasing PGE2 generation.
Cholangiocarcinoma (CCA) is a highly lethal malignancy originating from the biliary ducts. Current CCA diagnostic and prognostic assessments cannot satisfy the clinical requirement. Bile detection is rarely performed, and herein, we aim to estimate the clinical significance of bile liquid biopsy by assessing bile exosomal concentrations and components. Exosomes in bile and sera from CCA, pancreatic cancer, and common bile duct stone were identified and quantified by transmission electronmicroscopy, nanoparticle tracking analysis, and nanoFCM. Exosomal components were assessed by liquid chromatography with tandem mass spectrometry and microRNA sequencing (miRNA-seq). Bile exosomal concentration in different diseases had no significant difference, but miR-182-5p and miR-183-5p were ectopically upregulated in CCA bile exosomes. High miR-182/183-5p in both CCA tissues and bile indicates a poor prognosis. Bile exosomal miR-182/183-5p is secreted by CCA cells and can be absorbed by biliary epithelium or CCA cells. With xenografts in humanized mice, we showed that bile exosomal miR-182/183-5p promotes CCA proliferation, invasion, and epithelial-mesenchymal transition (EMT) by targeting hydroxyprostaglandin dehydrogenase in CCA cells and mast cells (MCs), and increasing prostaglandin E2 generation, which stimulates PTGER1 and increases CCA stemness. In single-cell mRNA-seq, hydroxyprostaglandin dehydrogenase is predominantly expressed in MCs. miR-182/183-5p prompts MC to release VEGF-A release from MC by increasing VEGF-A expression, which facilitates angiogenesis. CCA cells secret exosomal miR-182/183-5p into bile, which targets hydroxyprostaglandin dehydrogenase in CCA cells and MCs and increases prostaglandin E2 and VEGF-A release. Prostaglandin E2 promotes stemness by activating PTGER1. Our results reveal a type of CCA self-driven progression dependent on bile exosomal miR-182/183-5p and MCs, which is a new interplay pattern of CCA and bile.


Apicoplast translation, transcription and genome replication: targets for antimalarial antibiotics.
Several antibiotics possess antimalarial properties, although the mechanisms by which they kill malaria parasites have been poorly understood. Recent data suggest that the target for multiple antimalarial antibiotics is the apicoplast, a chloroplast-like organelle of uncertain function. Translation inhibitors (such as tetracyclines, clindamycin and macrolides) and gyrase inhibitors (such as ciprofloxacin) cause modest antimalarial effects initially but are much more potent against the progeny of treated parasites. These progeny inherit nonfunctional apicoplasts, suggesting that blocking production of apicoplast proteins causes the 'delayed-death effect'. Interestingly, the antibiotics thiostrepton and rifampin are fast acting and might target additional processes outside the apicoplast.


Pioglitazone + metformin: new drug. A combination product to avoid.
More serious adverse effects, and still no tangible proof of efficacy.


Optimizing Care of Patients With Right Bundle Branch Block Undergoing Transcatheter Aortic Valve Replacement.
To evaluate the use of temporary-permanent pacemaker (TPP) in patients with right bundle branch block (RBBB) undergoing transcatheter aortic valve replacement (TAVR). We also sought to identify key predictors of permanent pacemaker (PPM) within 30 days of TAVR in this population. RBBB is a well-recognized risk factor for PPM post TAVR. TPP provides stable transient pacing and reduces the need for critical care beds. This is a retrospective chart review of 371 patients who underwent TAVR at our institution. All patients with pre-existing RBBB had TPP placed prior to TAVR (n = 37). The primary outcome was the need for critical care beds. Multivariate logistic regression analysis was performed to identify predictors of PPM within 30 days of TAVR. 67 patients required PPM within 30 days of TAVR, and 56 implanted before discharge. 51% (19 out of 37) of TPP group required PPM before discharge compared to 11% (37 out of 334) of No TPP (p < 0.001), yet TPP group spent significantly fewer hours in a critical care bed (19 vs 28 h, p = 0.01). Length of membranous septum (LMS) <8.49 mm was the strongest independent predictor of PPM within 30 days of TAVR (RAUC of 0.80, Sensitivity 0.7 and Specificity 0.8) and 98% of patients with LMS < 7 mm required PPM within 30 days. TPP-TAVR is a well-defined multidisciplinary protocol that reduces the need for critical care beds in patients with pre-existing RBBB referred for TAVR. Additionally, LMS is the strongest predictor of PPM implantation in this population. CONDENSED ABSTRACT (100 WORDS): This study evaluated the use of temporary-permanent pacemakers (TPP) in patients with right bundle branch block (RBBB) undergoing transcatheter aortic valve replacement (TAVR). TPP-TAVR provided stable pacing allowing for early mobilization and reduced the need for critical care beds. Multivariate logistic regression analysis identified length of membranous septum (LMS) <8.49 mm in patients with RBBB as the strongest independent predictor of PPM need within 30 days of TAVR. 98% of patients with RBBB and LMS < 7 mm required PPM at 30 days regardless of other characteristics including valve type and size.


Differential expression levels of β-catenin are associated with invasive behavior of both functional and non-functional pituitary neuroendocrine tumor (PitNET).
Although research continues to elucidate the molecular mechanism underlying pituitary tumor pathogenesis, limited information is available on the potential role and expression profile of β-catenin in functional and non-functional pituitary neuroendocrine tumors (PitNETs). In the current study, 104 pituitary samples (tumors and cadaveric healthy pituitary tissues) were included and the gene and protein expression levels of β-catenin were assessed by Real-Time PCR and immunohistochemistry, respectively. The correlation between expression level of β-catenin and tumor invasive feature and size as well as patient age, gender, and hormonal level was measured. The data showed that PitNET samples expressed higher levels of the β-catenin gene and protein compared to healthy pituitary tissues. Although there was no difference in β-catenin expression level between non-functioning (NF-PitNETs) and growth hormone-producing tumors (GH-PitNETs), both tumor types showed significantly elevated β-catenin levels compared to healthy pituitary tissues. The high level of β-catenin in the invasive functional and non-functional tumors is indicative of the association of β-catenin with PitNETs invasion. The expression pattern of the β-catenin gene and protein was consistently and significantly associated with these tumor types. The correlation between β-catenin and insulin-like growth factor 1 (IGF-1) in GH-PitNETs indicates the potential relevance of β-catenin and IGF-1 for GH-PitNETs. The simultaneous increase in the expression of β-catenin gene and protein level in PitNET tissues and their relationship to the tumor severity indicates the possible contributing role of β-catenin and its underlying signaling mediators in PitNET pathogenesis.


A new method for determining dose rate distribution from radioimmuno-therapy using radiochromic media.
To describe and evaluate a new, simple, inexpensive method for directly measuring the radiation dose and its spatial distribution generated from explanted tissues of animals previously injected with radiolabeled immunoconjugates or other agents. This technique uses the newly developed radiochromic dye medium (Gafchromic) which responds reproducibly for therapeutic dose exposures, has high spatial resolution, does not require film processing, and is relatively insensitive to ambient light. We have evaluated the dose distribution from LS174T tumors and selected normal tissues in nude mice previously injected with 90Y labeled anti-carcinoembrionic antigen antibodies. Individual tissues from sacrificed animals are halved and the flat section of the tissue is placed onto the dosimetry media and then frozen. The dosimetry medium is exposed to beta and Bremsstrahlung radiation originating from the frozen tissues. The relative darkening of the dosimetry medium depends on the dose deposited in the film. The dosimetry medium is scanned with a commercial flatbed scanner and the image intensity is digitally stored and quantitatively analyzed. Isodose curves are generated and compared to the actual tissue outline. The absorbed dose distribution due to 90Y exposure show only slight gradients in the interior of the tissue, with a markedly decreasing dose near the edges of the tissue. In addition, the isodose curves follow the tissue outline except in regions having radii of curvature smaller than the range of the beta-particle (R90 = 5 mm). These results suggest that the shape of the tumor, and its curvature, are important in determining the minimum dose delivered to the tumor by radiation from 90Y monoclonal antibodies, and hence in evaluating the tumor response to the radiation. The dose and spatial dose distribution were calculated assuming that the total 90Y activity is distributed uniformly throughout a half ellipsoid. The calculated spatial dose distributions for the half ellipsoids were similar to those observed from the dosimetry media that had been exposed to radioactivity contained in the tumors. This method provides direct dose evaluation without elaborate summary calculations based on activity measurements from serial slices. The measured radiation dose actually indicates the dose rate at the time of animal sacrifice. Quantitative analysis of radiation emitted from the tissues is relatively fast, making it feasible to examine a number of tissues under a variety of conditions.


[Transcutaneous oxygen partial pressure and systolic malleolar artery pressure in patients with peripheral arterial occlusive disease. Longitudinal measurements over 14 days].
In 40 legs of 35 patients with Fontaine's stage I to IV peripheral arterial occlusive disease aged between 41 and 77 years, tcPO2 and malleolar artery systolic pressure were measured over a period of two weeks. It was found that the tcPO2 on the dorsum of the foot varied between 10.2 and 18.9 mm Hg, in the lower leg between 13.4 and 22.0 mm Hg, and in the thigh between 10.8 and 14.5 mm Hg as compared with the baseline value. In contrast, the dorsal pedis and anterior tibial arterial blood pressures showed no significant variation over time. The range of variation of tcPO2 in feet, lower legs and thighs must be taken into account in long-term measurements.


Distinct renin/aldosterone activity profiles correlate with renal function, natriuretic response, decongestive ability and prognosis in acute heart failure.
Although renin-angiotensin-aldosterone system (RAAS) activation is believed to be the major driver of acute heart failure (AHF) episodes our understanding of its prevalence and clinical relevance in contemporary settings is incomplete. Serum renin and aldosterone were measured at day-1 and at discharge in patients (n = 211) that were hospitalized between 2016 and 2017 for AHF in a single cardiology center. The population was profiled based on upper limits of normal (ULN) of both biomarkers assessed at day-1 and linked with the clinical course and outcomes. The study population constituted of three profiles: RAAS-/- (n = 121 [57%]); RAAS+/- (n = 60 [28%]); and RAAS+/+ (n = 30 [14%]). The RAAS+/+ profile had the lowest blood pressure and serum sodium at admission, day-2 and discharge compared to the other profiles (p < 0.001). The RAAS+/+ patients had significantly lower urine Na+ at admission (57.8 ± 36.7 vs 97.3 ± 31.3 and 86.4 ± 35.0), day-1 (52.7 ± 32.7 vs 85.3 ± 36.3 and 75.5 ± 33.9) mmol/l, vs RAAS-/- and RAAS+/- profiles, respectively, all p < 0.001. There was also a gradual decrease of renal function across increasing RAAS profiles. The RAAS+/+ profile received higher dose of furosemide at discharge 120 [80-160] vs the other profiles 80 [40-120] mg, p < 0.01. The risks of one year mortality or HF rehospitalization increased across the RAAS profiles (p < 0.001). The trajectory of renin or aldosterone change during hospitalization was not related to outcomes. The RAAS overactivity is not essential for development of AHF. However, elevated RAAS is a marker of more advanced stages of heart failure, is related to low natriuresis and adverse clinical outcomes.


Reproducibility and influence of hand rotation on computer-aided joint space analysis.
Computer-aided joint space analysis (CAJSA) is a recently developed, semi-automated tool to aid in the measurement of joint space margins based on hand radiographs. The objective of this study is to verify the potential effect of hand rotation during X-ray imaging on the measurement of joint space width using CAJSA and to evaluate the reproducibility of the CAJSA technique in healthy subjects and in patients with rheumatoid arthritis. All joint space distance (JSD) measurements were performed using CAJSA-technology at the metacarpophalangeal articulation based on conventional and digital hand radiographs. I. Hand rotation showed an effect on the reproducibility with CV ranging between 0.39% (angulation 1°) and 1.66% (angulation 19°). II. Regarding the overall reproducibility of the CAJSA method, the intra-radiograph reproducibility of JSD was calculated with CV=0.54% for conventional images and CV=0.38% for digital images. The inter-radiograph reproducibility error was observed with CV=0.66% (conventional images) and CV=0.63% (digital images). III. The study revealed a reproducibility for CAJSA measurements in RA ranging between 0.37% (JSD-MCP ring finger; van der Heijde-modification of the Sharp method score 1) to 1.37% (JSD-MCP index finger; van der Heijde-modification of the Sharp method score 3). CAJSA measures JSD at the metacarpophalangeal articulation with high reproducibility in healthy subjects and in patients with differing stages of rheumatoid arthritis. Additional findings show that hand rotation during X-ray imaging has an impact on the CAJSA measurements; thus avoiding acquisition of hand radiographs with a rotation error of more than 15 degrees can be recommended.


Patients with SARS-CoV-2 and HBV co-infection are at risk of greater liver injury.
To date, it remains unclear if severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) co-infection exacerbates liver injury in patients with chronic hepatitis B virus (HBV) infection. In this study, we present a retrospective study of 133 hospitalized confirmed mild coronavirus disease 2019 (COVID-19) cases, including 116 patients with COVID-19 with negative serum hepatitis B antigen and 17 HBV inactive carriers with COVID-19. We found that there were no significant differences for the discharge rate or duration of hospitalization between the two groups. However, inactive HBV carriers with SARS-CoV-2 co-infection are at a higher risk of abnormal liver function tests. The enhanced liver injury induced by SARS-CoV-2 and HBV co-infection was identified as the hepatocyte type rather than the cholangiocyte type. Moreover, the inflammatory response, including abnormal lactate dehydrogenase, D-dimer and interleukin-6 production, may contribute to this injury following SARS-CoV-2 co-infection. Collectively, SARS-CoV-2 and HBV co-infection exacerbates liver function of the patients with COVID-19.


TRPV1 modulation of contextual fear memory depends on stimulus intensity and endocannabinoid signalling in the dorsal hippocampus.
The transient receptor potential vanilloid type-1 (TRPV1) channels have been implicated in the modulation of aversive responses. The endocannabinoid anandamide acts as an endogenous TRPV1 agonist, exerting opposite functions at TRPV1 and type-1 cannabinoid receptors (CB1R). Here we tested the hypothesis that hippocampal TRPV1 modulates contextual fear memory retrieval and investigated the influence of the aversive stimulus intensity as well as the role of endocannabinoid signaling. Male C57BL/6J mice were tested for contextual fear memory after low-, moderate-, or high-intensity shock protocols. The selective TRPV1 blockers SB366791 (1-10 nmol) and 6-I-NC (2 nmol) were infused via intra-dorsal hippocampus before the retrieval test session. The local levels of endocannabinoids and Arc and Zif268 mRNAs, involved in synaptic plasticity and memory, were quantified. First, both TRPV1 blockers reduced memory retrieval in animals exposed to moderate or high (but not low) intensity training protocols. In the second series of results, the magnitude of the freezing responses positively correlated with the hippocampal anandamide levels; TRPV1 and CB1R were found co-localized in this brain region; and the CB1R antagonist, AM251, prevented the effects of SB366791. Thus, endocannabinoid signaling possibly mediates the effects of TRPV1 blockers. Finally, inhibition of memory retrieval by TRPV1 blockers increased Arc and Zif268 mRNAs and impaired fear memory reinstatement. In conclusion, the modulation of fear memories by dorsal hippocampal TRPV1 channels may depend on the aversive stimulus intensity and occur via anandamide/CB1 signaling. Moreover, TRPV1 blockers promote Arc and Zif268 transcription, with subsequent attenuation of aversive memory reinstatement.


Physiological integration in Cassia fasciculata Michx.: inflorescence removal and defoliation experiments.
In the annual herb Cassia fasciculata virtually every leaf subtends an axillary inflorescence. We examined the degree to which these leaf-inflorescence units (reproductive nodes) were physiologically independent of each other in the production of flowers, fruits, and seeds. Removal of up to 4 of every 5 inflorescences resulted in substantial increases in fruit and seed production by remaining, intact reproductive nodes. These increases nearly compensated for and manipulated reproductive nodes were associated with different vascular strands. When 2 of every 3 leaves were removed, fruit and seed production were reduced at both intact and defoliated reproductive nodes. Taken together, these results suggest that neighboring reproductive nodes in C. fasciculata are not physiologically independent of one another, and that competition among fruits and seeds for parental resources occurs over several reproductive nodes.


Automatic detection of venous air embolism using transesophageal echocardiography in patients undergoing neurological surgery in the semi-sitting position: a pilot study.
Neurological surgery in the semi-sitting position is linked with a pronounced incidence of venous air embolism (VAE) which can be fatal and therefore requires continuous monitoring. Transesophageal echocardiography (TEE) provides a high sensitivity for the intraoperative detection of VAE; however, continuous monitoring with TEE requires constant vigilance by the anaesthesiologist, which cannot be ensured during the entire surgical procedure. We implemented a fully automatic VAE detection system for TEE based on a statistical model of the TEE images. In the sequence of images, the cyclic heart activity is regarded as a quasi-periodic process, and air bubbles are detected as statistical outliers. The VAE detection system was evaluated by means of receiver operating characteristic (ROC) curves using a data set consisting of 155.14 h of intraoperatively recorded TEE video and a manual classification of periods with visible VAE. Our automatic detection system accomplished an area under the curve (AUC) of 0.945 if all frames with visible VAE were considered as detection target, and an AUC of 0.990 if frames with the least severe optical grade of VAE were excluded from the analysis. Offline-review of the recorded TEE videos showed that short embolic events (≤ 2 min) may be overseen when monitoring TEE video manually. Automatic detection of VAE is feasible and could provide significant support to anaesthesiologists in clinical practice. Our proposed algorithm might possibly even offer a higher sensitivity compared to manual detection. The specificity, however, requires improvement to be acceptable for practical application. Trial Registration: German Clinical Trials Register (DRKS00011607).


Production of zearalenone-4-glucoside, a-zearalenol-4-glucoside and ß-zearalenol-4-glucoside.
The work at hand describes the production of the zearalenone (ZON) metabolites zearalenone-4-glucoside (ZON-4G), a-zearalenol-4-glucoside (oc-ZOL-4G) and ß-zearalenol-4-glucoside (ß-ZOL-4G). In a first step a genetically modified yeast strain, expressing theArabidopsis thaliana UDP-glu-cosyltransferase UGT73C6, was treated with ZON to produce ZON-4G. The substance was purified by solid phase extraction and subsequent reversed phase preparative HPLC prior to the reduction with sodium borohydride to yield 0C-ZOL-4G and ß-ZOL-4G. The identity and purity of the substances were confirmed by(13)C-and(1)H-NMR as well as by HPLC-UV. In total, 50 mg of ZON were used to produce 5 mg of a-ZOL-4G with a purity of 98%, 6 mg of ß-ZOL-4G with a purity of 99% and 5 mg of ZON-4G with a purity of 99%.


Polyglandular autoimmune syndrome type 2 presenting for the first time during pregnancy.
We report a case of polyglandular autoimmune deficiency presenting during pregnancy which was associated with a favourable outcome for both mother and fetus (apart from fetal growth retardation) with appropriate replacement therapy and adequate steroid cover at the time of delivery.


Associations of family feeding and mealtime practices with children's overall diet quality: Results from a prospective population-based cohort.
Food parenting practices are considered to have a key influence on children's dietary habits, with potential long term effects. In this study, we explored the associations of parental feeding practices and family mealtime practices in early childhood with children's overall diet quality at school age among 3626 parents and their children in a population-based cohort study in Rotterdam, the Netherlands. Parental feeding practices (monitoring, pressure to eat, and restriction) and family mealtime practices (meal skipping behaviors and family meal frequency) at age 4 years were assessed by parental questionnaires. Children's dietary intake was assessed at age 8 years using a food-frequency questionnaire, from which diet quality scores (range 0-10) were calculated, reflecting adherence to age-specific dietary guidelines. Using multivariable linear regression models, we found that monitoring was associated with higher diet quality of children (β = 0.12; 95%CI: 0.08, 0.16), whereas pressure to eat was associated with lower diet quality (β = -0.08; 95%CI: -0.12, -0.04)), both independent of child BMI. Restriction was associated with a higher child diet quality, but this association was explained by child BMI. As compared to children who did not skip meals, children who skipped meals had a lower diet quality (e.g. breakfast skipping: β = -0.32; 95%CI: -0.48, -0.17). Similarly, children who had less frequent family meals had a lower diet quality compared with those who had family meals every day (e.g. family dinner ≤2 days/week: β = -0.37; 95%CI: -0.60, -0.14). These associations were not driven by single food groups. In conclusion, parental monitoring and family mealtime routines in early childhood may provide a supportive food environment that promotes children's overall diet quality. Longitudinal studies with repeated measurements are needed to replicate our findings.


The Kaniadakis Distribution for the Analysis of Income and Wealth Data.
The paper reviews the "κ-generalized distribution", a statistical model for the analysis of income data. Basic analytical properties, interrelationships with other distributions, and standard measures of inequality such as the Gini index and the Lorenz curve are covered. An extension of the basic model that best fits wealth data is also discussed. The new and old empirical evidence presented in the article shows that the κ-generalized model of income/wealth is often in very good agreement with the observed data.


Emotional eating and cognitive restraint mediate the association between sleep quality and BMI in young adults.
This cross-sectional study was designed to investigate whether diet quality and eating behaviors could mediate the association between sleep quality and body mass index (BMI) in young adults. For all participants (n = 925; aged 21.4 ± 2.5 years; 77.8% women) we evaluated: BMI, sleep quality, diet quality, and eating behavior dimensions (emotional eating, cognitive restraint, and uncontrolled eating). Linear regression models were used to test associations between exposure and outcome variables. Path analysis was conducted with all potential mediators and covariates entered at the same time. Results showed that emotional eating (β = 0.04 [95% CI: 0.03; 0.06]), cognitive restraint (β = 0.03 [95% CI: 0.01; 0.04]), uncontrolled eating (β = 0.02 [95% CI: 0.01; 0.04]) and diet quality (β = -0.14 [95% CI: 0.19;-0.08]) were significantly associated with sleep quality. Additionally, BMI was significantly associated with PSQI score (β = 0.09 [95% CI: 0.01; 0.17]), emotional eating (β = 0.89 [95% CI: 0.60; 1.18]), and cognitive restraint (β = 1.37 [95% CI: 1.02; 1.71]). After testing for mediation, results revealed that emotional eating and cognitive restraint evidenced a significant mediating effect on the association between sleep quality and BMI. Additionally, diet quality was significantly associated with emotional eating (β = -0.35 [95% CI: 0.56;-0.13]), cognitive restraint (β = 0.53 [95% CI: 0.27; 0.79]), and uncontrolled eating (β = -0.49 [95% CI: 0.74;-0.25]). In conclusion, young adults with poor sleep quality are more likely to deal with negative emotions with food, which, in turn, could be associated with higher cognitive restraint, becoming a vicious cycle that has a negative impact on body weight. Our results also emphasize the role of eating behaviors as determinants of diet quality, highlighting the importance of considering sleep quality and eating behaviors when designing obesity prevention strategies in this population.


Selective vulnerability of neural cells and age-related susceptibility to OC43 virus in mice.
Suckling CD 1 mice infected intracerebrally or extraneurally with OC43 virus developed a lethal neurotropic infection with high titres of virus in the brain. Examination of infected brain by routine H & E staining revealed no necrosis even in extensively infected tissue. Resistance to infection developed with increasing age, and by 20 days of age mice were completely insusceptible to i.c. inoculation. Virus replication was also demonstrable by FA staining, in spinal cord, dorsal root ganglia and retina. All other tissues were insusceptible and in particular, macrophages from both susceptible and resistant mice were found to be resistant to infection both in vivo and in vitro. Immunosuppression rendered 15 day old mice more susceptible to infection but adult mice remained insusceptible. The transfer of immune or non immune spleen cells from resistant mice did not confer resistance to newborn mice. Treatment of resistant mice with anti interferon globulin (AIG) did not render them more susceptible. These results indicate that the immune response is partially responsible for the development of resistance to OC43 infection but that it is only partially protective and other factors must also be required. The basis for the unique susceptibility of neural tissues in suckling mice is being investigated.


Screening toll-like receptor markers to predict latent tuberculosis infection and subsequent tuberculosis disease in a Chinese population.
We investigated whether polymorphisms in the toll-like receptor genes or gene-gene interactions are associated with susceptibility to latent tuberculosis infection (LTBI) or subsequent pulmonary tuberculosis (PTB) in a Chinese population. Two matched case-control studies were undertaken. Previously reported polymorphisms in the toll-like receptors (TLRs) were compared between 422 healthy controls (HC) and 205 LTBI patients and between 205 LTBI patients and 109 PTB patients, to assess whether these polymorphisms and their interactions are associated with LTBI or PTB. A PCR-based restriction fragment length polymorphism analysis was used to detect genetic polymorphisms in the TLR genes. Nonparametric multifactor dimensionality reduction (MDR) was used to analyze the effects of interactions between complex disease genes and other genes or environmental factors. Sixteen markers in TLR1, TLR2, TLR4, TLR6, TLR8, TLR9, and TIRAP were detected. In TLR2, the frequencies of the CC genotype (OR = 2.262; 95% CI: 1.433-3.570) and C allele (OR = 1.566; 95% CI: 1.223-1.900) in single-nucleotide polymorphism (SNP) rs3804100 were significantly higher in the LTBI group than in the HC group, whereas the GA genotype of SNP rs5743708 was associated with PTB (OR = 6.087; 95% CI: 1.687-21.968). The frequencies of the GG genotype of SNP rs7873784 in TLR4 (OR = 2.136; 95% CI: 1.312-3.478) and the CC genotype of rs3764879 in TLR8 (OR = 1.982; 95% CI: 1.292-3.042) were also significantly higher in the PTB group than in the HC group. The TC genotype frequency of SNP rs5743836 in TLR9 was significantly higher in the LTBI group than in the HC group (OR = 1.664; 95% CI: 1.201-2.306). An MDR analysis of gene-gene and gene-environment interactions identified three SNPs (rs10759932, rs7873784, and rs10759931) that predicted LTBI with 84% accuracy (p = 0.0004) and three SNPs (rs3804100, rs1898830, and rs10759931) that predicted PTB with 80% accuracy (p = 0.0001). Our results suggest that genetic variation in TLR2, 4, 8 and 9, implicating TLR-related pathways affecting the innate immunity response, modulate LTBI and PTB susceptibility in Chinese.


Ocean in peril: reforming the management of global ocean living resources in areas beyond national jurisdiction.
This article presents the outcome of research aimed at assisting governments in meeting their commitments and legal obligations for sustainable fisheries, based on increasing evidence that global fisheries are in crisis. The article assesses the effectiveness of the existing legal and institutional framework for high seas living resources. It focuses on: (1) the role of regional fisheries management organizations (RFMOs); (2) tools for compliance and enforcement to stem illegal fishing; and (3) mechanisms for habitat protection. The article further highlights a variety of options for addressing key weaknesses and gaps in current ocean governance, including United Nations General Assembly (UNGA) resolutions, reforms at the regional level, as well as a possible new legal instrument, with a view to informing international discussions on ways to ensure the sustainable use of high seas resources without compromising the health of the marine environment.