Benzocoumarin Hydrazine: A Large Stokes Shift Fluorogenic Sensor for Detecting Carbonyls in Isolated Biomolecules and in Live Cells.
Detection and quantification of biomolecule carbonylation, a critical manifestation of oxidative stress, allows better understanding of associated disease states. Existing approaches for such analyses require further processing of cells and tissues, which leads to loss of both spatial and temporal information about carbonylated biomolecules in cells. Live cell detection of these species requires sensors that are nontoxic, sufficiently reactive with the biocarbonyl in the intracellular milieu, and detectable with commonly available instrumentation. Presented here is a new fluorescent sensor for biomolecule carbonyl detection: a hydrazine derivative of a benzocoumarin, 7-hydrazinyl-4-methyl-2H-benzo[h]chromen-2-one (BzCH), which meets these requirements. This probe is especially well suited for live cell studies. It can be excited by a laser line common to many fluorescence microscopes. The emission maximum of BzCH undergoes a substantial red shift upon hydrazone formation (from ∼430 to ∼550 nm), which is the result of fluorophore disaggregation. Additionally, the hydrazone exhibits an exceptionally large Stokes shift (∼195 nm). The latter properties eliminate self-quenching of the probe and the need to remove unreacted fluorophore for reliable carbonyl detection. Thus, biomolecule carbonylation can be detected and quantified in cells and in cell extracts in a one-step procedure using this probe.


MicroRNA-134 suppresses cell proliferation in gastric cancer cells via targeting of GOLPH3.
Emerging evidence has shown that microRNAs (miRNAs) play critical roles in tumor development and progression. miR-134 has been found to act as a tumor-suppressor in numerous types of cancers. However, little is known concerning the potential role of miR-134 in gastric carcinogenesis. In the present study, we found that miR-134 was highly downregulated in gastric cancer tissues and cell lines when compared with levels in their adjacent non-tumor tissues and the normal human gastric epithelial cell line GES-1. Additionally, overexpression of miR-134 was accompanied by reduced cell proliferation in vitro and decreased tumor size in vivo. Further investigation by luciferase reporter assay indicated that Golgi phosphoprotein 3 (GOLPH3), a potent oncogene, was a direct target of miR-134. The activity of a luciferase reporter carrying the miR-134 binding site in the 3'-untranslated region (3'-UTR) of GOLPH3 was repressed by overexpression of miR-134, while a mutation in the 3'-UTR of GOLPH3 abrogated this effect, indicating that GOLPH3 is a target gene of miR-134. Overexpression of GOLPH3 blocked the antiproliferative effect of pre-miR-134 in gastric carcinoma cells. Furthermore, overexpression of miR-134 was associated with decreased phosphorylation of AKT, mTOR and S6K. Taken together, these data suggest that miR-134 regulates gastric cancer cell proliferation, at least potentially, through downregulation of the GOLPH3 gene, implicating a candidate tumor-suppressor miRNA in the pathogenesis of gastric cancer.


Insomnia in children: when are hypnotics indicated?
Insomnia in children is a nonspecific impairing symptom that may be the result of normal developmental changes, psychosocial duress, a sleep disorder, a psychiatric disorder, other medical disorders, substance misuse, or an adverse effect of medication. Careful clinical assessment of insomnia in children may include the use of symptom rating scales, laboratory testing, or other medical assessment. Short- and long-term treatment of insomnia in children involves management of etiological factors and associated syndromes. Controlled treatment studies of pediatric insomnia are limited to <10 published studies of psychosocial and/or psychopharmacological treatment in young children. Directive parent education and behavior modification techniques have been effective in short-term treatment of insomnia in young children, and may be the preferred treatment of extrinsic insomnia, as well as an important adjunctive treatment of any insomnia symptoms. Two benzodiazepines [flurazepam and delorazepam (chlordesmethyldiazepam)], one antihistamine (niaprazine) and one phenothiazine [alimemazine (trimeprazine)] have been shown to be effective in the short-term treatment of insomnia in young children, although none of these agents have US Food and Drug Administration approval for pediatric insomnia. Short-acting benzodiazepines may have a role in the brief treatment of pediatric insomnia associated with an anxiety or mood disorder, psychosis, aggression, medication- induced activation, or anticipatory anxiety associated with a medical procedure. However, tachyphylaxis and risk of misuse preclude the long-term use of benzodiazepines for the treatment of insomnia in children. Newer hypnotics, which appear better tolerated than the benzodiazepines in studies of adults, may have a role when combined with psychosocial treatments of pediatric insomnia. Treatment of intrinsic pediatric insomnia may additionally involve chronotherapy or medical management.


Complications of Colles' fractures.
Patients with Colles' fractures have serious complications more frequently than is generally appreciated. A study of 565 fractures revealed 177 (31 per cent) with such complications as persistent neuropathies of the median, ulnar, or radial nerves (forty-five cases), radiocarpal or radio-ulnar arthrosis (thirty-seven cases), and malposition-malunion (thirty cases). Other complications included tendon ruptures (seven), unrecognized associated injuries (twelve), Volkmann's ischemia (four cases), finger stiffness (nine cases), and shoulder-hand syndrome (twenty cases). In many patients, incomplete restoration of radial length or secondary loss of the reduction position caused the complications.


Comparative analysis of the Monochamus alternatus immune system.
The pine sawyer beetle, Monochamus alternatus, is regarded as a notorious forest pest in Asia, vectoring an invasive pathogenic nematode, Bursaphelenchus xylophilus, which is known to cause pine wilt disease. However, little sequence information is available for this vector beetle. This hampered the research on its immune system. Based on the transcriptome of M. alternatus, we have identified and characterized 194 immunity-related genes in M. alternatus, and compared them with homologues molecules from other species known to exhibit immune responses against invading microbes. The lower number of putative immunity-related genes in M. alternatus were attributed to fewer C-type lectin, serine protease (SP) and anti-microbial peptide (AMP) genes. Phylogenetic analysis revealed that M. alternatus had a unique recognition gene, galectin3, orthologues of which were not identified in Tribolium castaneum, Drosophila melanogastor, Anopheles gambiae and Apis mellifera. This suggested a lineage-specific gene evolution for coleopteran insects. Our study provides the comprehensive sequence resources of the immunity-related genes of M. alternatus, presenting valuable information for better understanding of the molecular mechanism of innate immunity processes in M. alternatus against B. xylophilus.


Mycoplasmas under experimental antimicrobial selection: The unpredicted contribution of horizontal chromosomal transfer.
Horizontal Gene Transfer was long thought to be marginal in Mycoplasma a large group of wall-less bacteria often portrayed as minimal cells because of their reduced genomes (ca. 0.5 to 2.0 Mb) and their limited metabolic pathways. This view was recently challenged by the discovery of conjugative exchanges of large chromosomal fragments that equally affected all parts of the chromosome via an unconventional mechanism, so that the whole mycoplasma genome is potentially mobile. By combining next generation sequencing to classical mating and evolutionary experiments, the current study further explored the contribution and impact of this phenomenon on mycoplasma evolution and adaptation using the fluoroquinolone enrofloxacin (Enro), for selective pressure and the ruminant pathogen Mycoplasma agalactiae, as a model organism. For this purpose, we generated isogenic lineages that displayed different combination of spontaneous mutations in Enro target genes (gyrA, gyrB, parC and parE) in association to gradual level of resistance to Enro. We then tested whether these mutations can be acquired by a susceptible population via conjugative chromosomal transfer knowing that, in our model organism, the 4 target genes are scattered in three distinct and distant loci. Our data show that under antibiotic selective pressure, the time scale of the mutational pathway leading to high-level of Enro resistance can be readily compressed into a single conjugative step, in which several EnroR alleles were transferred from resistant to susceptible mycoplasma cells. In addition to acting as an accelerator for antimicrobial dissemination, mycoplasma chromosomal transfer reshuffled genomes beyond expectations and created a mosaic of resistant sub-populations with unpredicted and unrelated features. Our findings provide insights into the process that may drive evolution and adaptability of several pathogenic Mycoplasma spp. via an unconventional conjugative mechanism.


Spatiotemporal Landscape for the Sophisticated Transformation of Protein Assemblies Defined by Multiple Supramolecular Interactions.
Precise protein assemblies not only constitute a series of living machineries but also provide an advanced class of biomaterials. Previously, we developed the inducing ligand strategy to generate various fixed protein assemblies, without the formation of noncovalent interactions between proteins. Here, we demonstrated that controlling the symmetry and number of supramolecular interactions introduced on protein surfaces could direct the formation of unspecific interactions between proteins and induce various nanoscale assemblies, including coiling nanowires, nanotubes, and nanosheets, without manipulation of the protein's native surfaces. More importantly, these nanoscale assemblies could spontaneously evolve into more ordered architectures, crystals. We further showed that the transformation from the introduced supramolecular interactions to the interactions formed between proteins was crucial for pathway selection and outcomes of evolution. These findings reveal a transformation mechanism of protein self-assembly that has not been exploited before and may provide an approach to generate complex and transformable biomacromolecular self-assemblies.


Preparation of intravenous cholesterol tracer using current good manufacturing practices.
Studies of human reverse cholesterol transport require intravenous infusion of cholesterol tracers. Because insoluble lipids may pose risk and because it is desirable to have consistent doses of defined composition available over many months, we investigated the manufacture of cholesterol tracer under current good manufacturing practice (CGMP) conditions appropriate for phase 1 investigation. Cholesterol tracer was prepared by sterile admixture of unlabeled cholesterol or cholesterol-d7 in ethanol with 20% Intralipid(®). The resulting material was filtered through a 1.2 micron particulate filter, stored at 4°C, and tested at time 0, 1.5, 3, 6, and 9 months for sterility, pyrogenicity, autoxidation, and particle size and aggregation. The limiting factor for stability was a rise in thiobarbituric acid-reacting substances of 9.6-fold over 9 months (P < 0.01). The emulsion was stable with the Z-average intensity-weighted mean droplet diameter remaining at 60 nm over 23 months. The zeta potential (a measure of negative surface charge protecting from aggregation) was unchanged at -36.2. Rapid cholesterol pool size was 25.3 ± 1.3 g. Intravenous cholesterol tracer was stable at 4°C for 9 months postproduction. CGMP manufacturing methods can be achieved in the academic setting and need to be considered for critical components of future metabolic studies.


Adeno-Associated Virus-Based Gene Therapy for CNS Diseases.
Gene therapy is at the cusp of a revolution for treating a large spectrum of CNS disorders by providing a durable therapeutic protein via a single administration. Adeno-associated virus (AAV)-mediated gene transfer is of particular interest as a therapeutic tool because of its safety profile and efficiency in transducing a wide range of cell types. The purpose of this review is to describe the most notable advancements in preclinical and clinical research on AAV-based CNS gene therapy and to discuss prospects for future development based on a new generation of vectors and delivery.


Factors in stress and burnout among paediatric nurses in a general hospital.
High stress and staff turnover in a multispecialty paediatric area prompted this study that aimed to: 1) measure the burnout level of nurses in a multi-specialty paediatric area 2) identify and validate causes of stress 3) identify new ways of preventing stress on the ward. Fifty-four percent (n = 14) of the paediatric nurses completed a questionnaire booklet that included demographic data, the Maslach Burnout Inventory, the Nursing Situations Questionnaire, the Hopkins Symptom Checklist-21, the Ways of Coping Checklist and open-ended questions about sources of stress and satisfaction at work. Results indicated levels of burnout and distress comparable with larger studies. Conflict with doctors was the major source of stress, followed by workload, inadequate preparation in dealing with the emotional needs of patients and their families and death and dying. Conflict with doctors has not previously been identified as the major source of stress. However, workload and death and dying are commonly identified as sources in the literature. Suggestions for further research and the low response rate are discussed.


Use of gentamicin-collagen sponge (Collatamp® G) in minimally invasive colorectal cancer surgery: A propensity score-matched study.
Minimally invasive surgery is commonly used to treat patients with colorectal cancer, although it can cause surgical site infections (SSIs) that can affect the oncologic outcome. Use of a gentamicin-collagen sponge may help reduce the occurrence of SSIs. We aimed to determine the effectiveness of a gentamicin-collagen sponge in reducing SSIs in minimally invasive surgery for colorectal cancer. We retrospectively reviewed the records of 310 patients who were diagnosed with colorectal cancer at our hospital and underwent minimally invasive surgery between December 1, 2018, and February 28, 2021. Propensity score matching was conducted with a 1:1 ratio using logistic regression. The primary outcome was the incidence of SSIs in the mini-laparotomy wound. The secondary endpoints were factors affecting the incidence of SSIs. After propensity score matching, 130 patients were assigned to each group. There were no differences in clinical characteristics between the two groups. SSIs occurred in 2 (1.5%) and 3 (2.3%) patients in the gentamicin-collagen sponge and control groups, respectively (p<0.999). The following factors showed a statistically significant association with SSIs: body mass index >25 kg/m2 (odds ratio, 39.0; 95% confidence interval, 1.90-802.21; p = 0.018), liver disease (odds ratio, 254.8; 95% confidence interval, 10.43-6222.61; p = 0.001), and right hemicolectomy (odds ratio, 36.22; 95% confidence interval, 2.37-554.63; p = 0.010). Applying a gentamicin-collagen sponge to the mini-laparotomy wound did not reduce the frequency of SSIs. Further studies should be conducted on whether the selective use of gentamicin-collagen sponges may help reduce SSIs in high-risk patients.


Non-invasive imaging of stem cells by scanning ion conductance microscopy: future perspective.
The most valuable property of stem cells (SCs) is their potential to differentiate into many or all cell types of the body. So far, monitoring SC differentiation has only been possible after cells were fixed or destroyed during sample preparation. It is, however, important to develop nondestructive methods of monitoring SCs. Scanning ion conductance microscopy (SICM) is a unique imaging technique that uses similar principles to the atomic force microscope, but with a pipette for the probe. This allows scanning of the surface of living cells noninvasively and enables measurement of cellular activities under more physiological conditions than is possible with other high-resolution microscopy techniques. We report here the novel use of the SICM for studying SCs to assess and monitor the status of SCs and various cell types differentiated from SCs.


QSAR Modelling of CYP3A4 Inhibition as a Screening Tool in the Context of DrugDrug Interaction Studies.
Drugdrug interaction potential (DDI), especially cytochrome P450 (CYP) 3A4 inhibition potential, is one of the most important parameters to be optimized before preclinical and clinical pharmaceutical development as regard to the number of marketed drug metabolized mainly by this CYP and potentially co-administered with the future drug. The present study aims to develop in silico models for CYP3A4 inhibition prediction to help medicinal chemists during the discovery phase and even before the synthesis of new chemical entities (NCEs), focusing on NCEs devoid of any inhibitory potential toward this CYP. In order to find a relevant relationship between CYP3A4 inhibition and chemical features of the screened compounds, we applied a genetic-algorithm-based QSAR exploratory tool SQS (Stochastic QSAR Sampler) in combination with different description approaches comprising alignment-independent Volsurf descriptors, ISIDA fragments and Topological Fuzzy Pharmacophore Triplets. The experimental data used to build models were extracted from an in-house database. We derived a model with good prediction ability that was confirmed on both newly synthesized compound and public dataset retrieved from Pubchem database. This model is a promising efficient tool for filtering out potentially problematic compounds.


Intimatan prevents arterial and venous thrombosis in a canine model of deep vessel wall injury.
Resistance of fibrin-bound thrombin to inactivation by the heparin/antithrombin III complex is considered a limitation in the use of heparin as an antithrombotic agent. Intimatan (dermatan 4,6-di-O-sulfate) is a heparin cofactor II agonist that inhibits both free and bound forms of thrombin. The present study examines the hypothesis that Intimatan prevents thrombotic occlusion in response to vascular wall injury in a canine model of carotid artery/jugular vein thrombosis. The left carotid artery and right jugular vein served as vehicle-treated control vessels, whereas the right carotid artery and left jugular vein were subjected to electrolytic injury after administration of Intimatan (9 mg/kg bolus + 300 microg/kg/min infusion, i.v.) or dalteparin (Fragmin) (400 IU/kg, s.c.). Intimatan significantly increased time to carotid artery (226.0 +/- 14.0 min) and jugular vein (240.0 +/- 0.0 min) thrombosis, compared with control vessels (carotid artery, 87.1 +/- 7.9 min; jugular vein, 60.6 +/- 7.4 min). Vessel patency was maintained in eight of eight jugular veins and seven of eight carotid arteries during treatment with Intimatan. Dalteparin significantly increased time to carotid artery thrombosis (122.1 +/- 17.5 min) compared with control (64.3 +/- 8.2 min), but did not change the time to thrombosis in the jugular vein. Only one carotid artery remained patent at the end of the dalteparin protocol. The two drugs produced minimal increases in bleeding times, and Intimatan increased the activated partial thromboplastin time above that observed with dalteparin. The results demonstrate that Intimatan is effective in preventing occlusive arterial and venous thrombosis in an experimental model of deep vascular wall injury.


Are pumas subordinate carnivores, and does it matter?
Interspecific competition affects species fitness, community assemblages and structure, and the geographic distributions of species. Established dominance hierarchies among species mitigate the need for fighting and contribute to the realized niche for subordinate species. This is especially important for apex predators, many of which simultaneous contend with the costs of competition with more dominant species and the costs associated with human hunting and lethal management. Pumas are a widespread solitary felid heavily regulated through hunting to reduce conflicts with livestock and people. Across their range, pumas overlap with six apex predators (gray wolf, grizzly bear, American black bear, jaguar, coyote, maned wolf), two of which (gray wolf, grizzly bear) are currently expanding in North America following recovery efforts. We conducted a literature search to assess whether pumas were subordinate or dominant with sympatric apex predators, as well as with three felid mesocarnivores with similar ecology (ocelot, bobcat, Canada lynx). We also conducted an analysis of the spatial distributions of pumas and their dominant sympatric competitors to estimate in what part of their range, pumas are dominant versus subordinate. We used 64 sources to assess dominance among pumas and other apex predators, and 13 sources to assess their relationships with felid mesocarnivores. Evidence suggested that wolves, grizzly bears, black bears, and jaguars are dominant over pumas, but that pumas are dominant over coyotes and maned wolves. Evidence suggested that pumas are also dominant over all three felid mesocarnivores with which they share range. More broadly, pumas are subordinate to at least one other apex carnivore in 10,799,252 (47.5%) of their 22,735,268 km2 range across North and South America. Subordinate pumas change their habitat use, suffer displacement at food sources, likely experience increased energetic demands from harassment, exhibit increased starvation, and are sometimes directly killed in competitive interactions with dominant competitors. Nevertheless, we lack research clearly linking the costs of competition to puma fitness. Further, we lack research that assesses the influence of human effects simultaneous with the negative effects of competition with other sympatric carnivores. Until the time that we understand whether competitive effects are additive with human management, or even potentially synergistic, we encourage caution among managers responsible for determining harvest limits for pumas and other subordinate, apex carnivores in areas where they are sympatric with dominant species. This may be especially important information for managers working in regions where wolves and brown bears are recolonizing and recovering, and historic competition scenarios among multiple apex predators are being realized.


A Unique Case of Cutaneous Larva Migrans Acquired Within the Province of Quebec and Successfully Treated With Topical Ivermectin.
Cutaneous larva migrans (CLM) is a zoonotic helminthiasis frequently imported to Canada by travellers to beach destinations in the tropics. The preferred treatment is oral ivermectin. We present a case of CLM acquired within the province of Quebec, a first in our provincial health records. Our case also puts forward the use of topical ivermectin as a possibly effective CLM treatment approach as our patient was successfully treated with 1 month of an ivermectin 1% cream applied locally twice daily.


Augmentation of the exercise pressor reflex in prehypertension: roles of the muscle metaboreflex and mechanoreflex.
This study investigated the hemodynamic mechanisms underlying the exaggerated blood pressure response to muscle contraction in prehypertensive humans and the potential role of skeletal muscle metabo- and mechanoreceptors in this response. To accomplish this, changes in peak mean arterial blood pressure (ΔMAP), cardiac output, and total peripheral resistance (ΔTPR) were compared between prehypertensive (n = 23) and normotensive (n = 19) male subjects during 2 min of static contraction (at 50% of maximal tension), 2 min of postexercise muscle ischemia (metaboreflex), and 1 min of passive dorsiflexion of the foot (tendon stretch, mechanoreceptor reflex). These variables were assessed before and during the interventions. Percentage increases from baseline in MAP and TPR in response to the exercise pressor reflex were augmented in the prehypertensives, compared with the normotensives (44% ± 5% vs. 33% ± 4% and 34% ± 15% vs. 2% ± 8%, respectively) (p < 0.05). Metaboreflex-induced increases in MAP and TPR were also augmented in the prehypertensives (28% ± 5% vs. 14% ± 4% and 36% ± 12% vs. 14% ± 9%, respectively) (p < 0.05). In response to the mechanoreflex, no differences in the percentage increase in MAP or TPR were seen between groups. The results indicate that the reflex pressor response to static contraction is augmented in prehypertension and suggest that this phenomenon is due, at least in part, to enhanced activation of metaboreceptors.


Transcranial magnetic stimulation: Emerging biomarkers and novel therapeutics in Alzheimer's disease.
Alzheimer's disease (AD) is one of the most devastating conditions affecting elderly in Western World. Unfortunately, there are no effective treatments, and patients diagnosed with AD face an uncertain future, caused by the current inability to predict the course of the disease. This is mainly due to the poor comprehension of AD pathophysiology and of patients' clinical heterogeneity. In recent years, several evidences supported the concept that loss of synaptic density could be an early event and precede neuronal degeneration, suggesting that the impairment of synaptic transmission should play a key role in the pathogenesis of different forms of dementia, including AD, frontotemporal dementia and Lewy body dementia. Despite this emerging background it has not been possible to quantify synaptic functioning (or dysfunction) directly in vivo in AD patients. Transcranial magnetic stimulation (TMS) has been recently introduced as a novel approach able to identify the early signatures of synaptic dysfunction characterizing the different forms of AD. We review the novel emerging neurophysiological signatures of AD and how this information may be used as biomarkers for differential diagnosis, disease progression and response to therapy. Finally, we also consider novel therapeutic approaches based on the clinical use of repetitive TMS.


Catalytic Mechanism of the Hotdog-Fold Thioesterase PA1618 Revealed by X-ray Structure Determination of a Substrate-Bound Oxygen Ester Analogue Complex.
Thioesterase activity accounts for the majority of the activities in the hotdog-fold superfamily. The structures and mechanisms of catalysis for many hotdog enzymes have been elucidated by X-ray crystallography and kinetics to probe the specific substrate usage and cellular functions. However, structures of hotdog thioesterases in complexes with substrate analogues reported to date utilize ligands that either represent truncations of the substrate or include additional atoms to prevent hydrolysis. Here we present the synthesis of an isosteric and isoelectronic substrate analogue-benzoyl-OdCoA-and the X-ray crystal structure of a complex of the analogue with Pseudomonas aeruginosa hotdog thioesterase PA1618 (at 1.72 Å resolution). The complex is compared with that of the "imperfect" substrate analogue phenacyl-CoA, refined to a resolution of 1.62 Å. Kinetic and structural results are consistent with Glu64 as the catalytic residue and with the involvement of Gln49 in stabilization of the transition state. Structural comparison of the two ligand-bound structures revealed a crucial ordered water molecule coordinated in the active site of the benzoyl-OdCoA structure but not present in the phenacyl-CoA-bound structure. This suggests a general base mechanism of catalysis in which Glu64 activates the coordinated water nucleophile. Together, our findings reveal the importance of a closely similar substrate analogue to determine the true substrate binding and catalytic mechanism.


Catalytic removal of phenol from gas streams by perovskite-type catalysts.
Three perovskite-type catalysts prepared by citric acid method are applied to remove phenol from gas streams with the total flow rate of 300mL/min, corresponding to a GHSV of 10,000/hr. LaMnO3 catalyst is first prepared and further partially substituted with Sr and Cu to prepare La0.8Sr0.2MnO3 and La0.8Sr0.2Mn0.8Cu0.2O3, and catalytic activities and fundamental characteristics of these three catalysts are compared. The results show that phenol removal efficiency achieved with La0.8Sr0.2Mn0.8Cu0.2O3 reaches 100% with the operating temperature of 200°C and the rate of mineralization at 300°C is up to 100%, while the phenol removal efficiencies achieved with La0.8Sr0.2MnO3 and LaMnO3 are up to 100% with the operating temperature of 300°C and 400°C, respectively. X-ray photoelectron spectroscopy (XPS) analysis shows that the addition of Sr and Cu increases the lattice oxygen of La0.8Sr0.2Mn0.8Cu0.2O3, and further increases mobility or availability of lattice oxygen. The results indicate that La0.8Sr0.2Mn0.8Cu0.2O3 has the best activity for phenol removal among three catalysts prepared and the catalytic activity of phenol oxidation is enhanced by the introduction of Sr and Cu into LaMnO3. Apparent activation energy of 48kJ/mol is calculated by Mars-Van Krevelen Model for phenol oxidation with La0.8Sr0.2Mn0.8Cu0.2O3 as catalyst.


Posterior Reversible Encephalopathy Syndrome and Eclampsia in a Primigravid Woman: The First Reported Case from Sierra Leone.
Posterior Reversible Encephalopathy Syndrome (PRES) is a clinico-neuroradiological entity with neurological symptoms and characteristic radiologic findings. It may complicate eclampsia either during pregnancy or in the puerperal period and it is a very serious neurological condition manifesting as acute headache,impairment of consciousness, seizures, cortical blindness and occasionally, focal neurological signs accompanied by a typical CT or MR imaging pattern.A 30 years old right handed primigravida housewife was managed for PRES and this is the first reported case in Sierra Leone. Clinicians in Africa should consider this diagnosis in all cases of eclampsia in order to reduce the morbidity and mortality that may result from delayed diagnosis.


A bilateral advantage for maintaining objects in visual short term memory.
Research has shown that attentional pre-cues can subsequently influence the transfer of information into visual short term memory (VSTM) (Schmidt, B., Vogel, E., Woodman, G., & Luck, S. (2002). Voluntary and automatic attentional control of visual working memory. Perception & Psychophysics, 64(5), 754-763). However, studies also suggest that those effects are constrained by the hemifield alignment of the pre-cues (Holt, J. L., & Delvenne, J.-F. (2014). A bilateral advantage in controlling access to visual short-term memory. Experimental Psychology, 61(2), 127-133), revealing better recall when distributed across hemifields relative to within a single hemifield (otherwise known as a bilateral field advantage). By manipulating the duration of the retention interval in a colour change detection task (1s, 3s), we investigated whether selective pre-cues can also influence how information is later maintained in VSTM. The results revealed that the pre-cues influenced the maintenance of the colours in VSTM, promoting consistent performance across retention intervals (Experiments 1 & 4). However, those effects were only shown when the pre-cues were directed to stimuli displayed across hemifields relative to stimuli within a single hemifield. Importantly, the results were not replicated when participants were required to memorise colours (Experiment 2) or locations (Experiment 3) in the absence of spatial pre-cues. Those findings strongly suggest that attentional pre-cues have a strong influence on both the transfer of information in VSTM and its subsequent maintenance, allowing bilateral items to better survive decay.


Reported Alcohol and Tobacco Use and Screening Among College Women.
To describe the reports of young women in their senior college years related to alcohol and tobacco use and to describe their health screening experiences in college health centers. A secondary analysis of data collected as part of a cross-sectional study of college women. For the original study, women were recruited from two accredited 4-year universities in the Northeastern United States. The first was a private university, and the second was a public university; both had on-campus health centers. The participants were 615 female undergraduate students enrolled in their senior year of college. A Web-based survey was sent to approximately 1,200 women at each university. Women were asked about their alcohol and tobacco use and about screening experiences in college health centers. The mean response rate was 25.8%. Nearly 90% (n = 550) of the women reported drinking alcohol in the last 3 months, and of those, more than two thirds (n = 370) met the Centers for Disease Control and Prevention definition of hazardous drinking. However, only 21.5% (n = 56) reported being screened for alcohol use. Similarly, only 19.7% (n = 52) reported being screened for tobacco use. College health centers are ideally positioned to screen and provide interventions for young women who are at high risk for alcohol misuse and tobacco use. Despite prevalence of use and importance of screening, reported screening is low. Future research is needed to understand barriers to screening and implement recommendations for college health centers.


Metabolic engineering of Escherichia coli using synthetic small regulatory RNAs.
Small regulatory RNAs (sRNAs) regulate gene expression in bacteria. We designed synthetic sRNAs to identify and modulate the expression of target genes for metabolic engineering in Escherichia coli. Using synthetic sRNAs for the combinatorial knockdown of four candidate genes in 14 different strains, we isolated an engineered E. coli strain (tyrR- and csrA-repressed S17-1) capable of producing 2 g per liter of tyrosine. Using a library of 130 synthetic sRNAs, we also identified chromosomal gene targets that enabled substantial increases in cadaverine production. Repression of murE led to a 55% increase in cadaverine production compared to the reported engineered strain (XQ56 harboring the plasmid p15CadA). The design principles and the engineering strategy using synthetic sRNAs reported here are generalizable to other bacteria and applicable in developing superior producer strains. The ability to fine-tune target genes with designed sRNAs provides substantial advantages over gene-knockout strategies and other large-scale target identification strategies owing to its easy implementation, ability to modulate chromosomal gene expression without modifying those genes and because it does not require construction of strain libraries.


Medial collateral ligament of the knee on magnetic resonance imaging: does the site of the femoral origin change at different patient ages in children and young adults?
The medial patellofemoral ligament (MPFL), a chief medial restraint preventing lateral patellar dislocation, often is reconstructed in children with recurrent dislocation. The femoral MPFL attachment can be difficult to delineate at surgery. Therefore, the origin of the medial collateral ligament (MCL) frequently is used to approximate the reattachment site. The purpose of our study was to compile normative data from MR imaging examinations over different patient ages, to determine the effect of growth on the relationship of the MCL origin site to the distal femoral physis and medial femoral condyle (MFC). This HIPAA-compliant study was IRB approved. Informed consent requirement was waived. Three hundred knee MR imaging examinations (143 boys, 157 girls, 0-20 y) were evaluated. MCL origin to femoral physis distance, MFC height, and MCL origin-physis distance: MFC height ratio (MCL:MFC ratio) were calculated. Relationships between these values and age, gender, and physeal patency were assessed using linear regression models. With physeal patency, MCL origin-physis distance was significantly associated with increasing age in boys (P=0.0394), and trended toward significance in girls (P=0.0557). Distance increased 0.01 cm/y in both genders. MFC height increased 0.15 cm/y in boys and 0.13 cm/y in girls (P<0.0001). MCL:MFC ratio decreased 0.01/y (P<0.0001). With physeal closure, no significant change was measured for any variable. During growth, there are statistically significant, albeit minimal, changes of the MCL origin-physis distance and MFC height. As these changes are essentially negligible, no adjustment for age is needed during restorative MPFL surgery in growing children. As there is neglible change in location of the origin of the MCL relative to the distal femoral physis during skeletal growth in both boys and girls, no adjustment for patient age is necessary when using the origin of the MCL as a landmark to locate the site of femoral reattachment of a disrupted MPFL.


N-Acetylcysteine accelerates amputation stump healing in the setting of diabetes.
Over 60% of lower extremity amputations are performed in patients with diabetes and peripheral arterial disease, and at least 25% require subsequent reamputation due to poor surgical site healing. The mechanisms underlying poor amputation stump healing in the setting of diabetes are not understood. N-acetylcysteine (NAC) is known to promote endothelial cell function and angiogenesis and may have therapeutic benefits in the setting of diabetes. We tested the hypothesis that NAC alters the vascular milieu to improve healing of amputation stumps in diabetes using a novel in vivo murine hindlimb ischemia-amputation model. Amputation stump tissue perfusion and healing were evaluated in C57BL/6J adult mice with streptozotocin-induced diabetes. Compared with controls, mice treated with daily NAC demonstrated improved postamputation stump healing, perfusion, adductor muscle neovascularization, and decreased muscle fiber damage. Additionally, NAC stimulated HUVEC migration and proliferation in a phospholipase C β-dependent fashion and decreased Gαq palmitoylation. Similarly, NAC treatment also decreased Gαq palmitoylation in ischemic and nonischemic hindlimbs in vivo In summary, we demonstrate that NAC accelerates healing of amputation stumps in the setting of diabetes and ischemia. The underlying mechanism appears to involve a previously unrecognized effect of NAC on Gαq palmitoylation and phospholipase C β-mediated signaling in endothelial cells.-Zayed, M. A., Wei, X., Park, K., Belaygorod, L., Naim, U., Harvey, J., Yin, L., Blumer, K., Semenkovich, C. F. N-acetylcysteine accelerates amputation stump healing in the setting of diabetes.


Pharmacotherapy Prescription Trends for Cognitive-Behavioral Disorder in Patients With Brain Injury in Korea.
To investigate the current status of pharmacotherapy prescribed by physiatrists in Korea for cognitive-behavioral disorder. A cross-sectional study was performed by mailing questionnaires to 289 physiatrists working at teaching hospitals. Items on the questionnaire evaluated prescribing patterns of 16 drugs related to cognitive-behavioral therapy, the status of combination pharmacotherapy, and tools for assessing target symptoms. Fifty physiatrists (17.3%) including 24 (48%) specializing in neurorehabilitation completed the questionnaires. The most common target symptom was attention deficit (29.5%). Donepezil and methylphenidate (96.0%) were the most frequently prescribed drugs for cognitive-behavioral improvement. Mostly, a combination of two drugs was prescribed (38.0%), and the most common combination therapy included donepezil plus methylphenidate (19.1%). Pharmacotherapy for cognitive-behavioral disorder after brain injury was typically initiated within 2 months (69.5%). A follow-up assessment was usually performed at 1 month after treatment initiation (31.0%). The most common reason for treatment discontinuation was improvement of target symptoms (37.8%). The duration of pharmacotherapy was 3-12 months (57.7%), 1-2 years (17.9%), or 1-2 months (13.6%). According to the survey, combination pharmacotherapy is preferred to monotherapy for the treatment of cognitive-behavioral disorder in patients with brain injury. Physiatrists expressed diverse views on the definition of target symptoms, prescribing patterns, and the status of drug combination therapy. Guidelines are needed for cognitive-behavioral pharmacotherapy. Further research should investigate drug costs and aim to reduce polypharmacy and adverse drug reactions.


Efficacy and safety of 10% and 16% carbamide peroxide tooth-whitening gels: a randomized clinical trial.
This double-blind randomized clinical trial evaluated the efficacy and safety of two carbamide peroxide concentrations used in at-home vital bleaching. Ninety-two volunteers with a shade mean of C1 or darker for the six maxillary anterior teeth were randomized into two balanced groups (n=46) according to bleaching agent concentration: 10% (CP10) or 16% (CP16) carbamide peroxide. The patients were instructed to use the whitening agent in a tray for two hours once a day for three weeks. Shade evaluations were done with a value-oriented shade guide and a spectrophotometer at baseline and one week post-bleaching (four-week evaluation). Tooth sensitivity was measured daily using a scale ranging from 0 (no sensitivity) to 4 (severe sensitivity). At the end of the study, the volunteers filled out a questionnaire with seven questions aimed to give their opinion about the adopted treatment regimen. Both carbamide peroxide concentrations resulted in significantly lighter teeth at the four-week evaluation compared to the baseline for all color parameters (p < 0.0001) and shade median (p < 0.001). There was no significant difference between the two groups in terms of shade change difference with either the spectrophotometer (p = 0.1) or the shade guide (p = 0.7). Also, no statistically significant difference was found in relation to deltaL* (p = 0.7), delta a* and deltaE* (p = 0.5). A significant reduction in yellowness (delta b*) was observed for CP16 compared to CP10 (p = 0.05) in crude analysis, which disappeared after controlling for b* parameter at baseline. The group treated with CP16 experienced more tooth sensitivity during the first (p = 0.02) and third (p = 0.01) weeks of treatment compared to the CP10 group. However, no major difference was observed (p = 0.09) when the degree of tooth sensitivity between groups was compared. Both 10% and 16% carbamide peroxide concentrations were equally effective and safe for a three-week at-home tooth-bleaching treatment.


Efficacy and safety of lanreotide autogel compared with lanreotide 40 mg prolonged release in Chinese patients with active acromegaly: results from a phase 3, prospective, randomized, and open-label study (LANTERN).
Lanreotide autogel is a somatostatin analog (SSA) approved for the treatment of acromegaly in 73 countries worldwide; however, it is not yet approved in China. The aim of this study was to evaluate the efficacy and safety of lanreotide autogel compared with lanreotide 40 mg prolonged release (PR) in Chinese patients with active acromegaly. LANTERN was a phase 3, randomized, open-label, non-inferiority study. Patients with active acromegaly who had undergone surgery ≥3 months prior, or were unlikely or unable to undergo surgery, were treated with lanreotide autogel 60/90/120 mg (monthly deep subcutaneous injection) or lanreotide 40 mg PR (intramuscular injection every 7, 10, or 14 days) for 32 weeks. Primary endpoint was mean change-from-baseline in age-adjusted insulin-like growth factor-1 (IGF-1) standard deviation scores (SDS) at the end-of-study. Secondary endpoints included: growth hormone (GH) levels ≤2.5 μg/L or ≤ 1.0 μg/L, ≥20% reduction in tumor volume (TV) and safety. In total, 128 patients were randomized and received study treatment. Lanreotide autogel was non-inferior to lanreotide 40 mg PR: treatment difference (95% CI) for IGF-1 SDS between groups was - 0.32 (- 0.74, 0.11; per protocol population) and - 0.27 (- 0.63, 0.09; intention-to-treat [ITT] population), respectively. Reductions in IGF-1 (- 6.453 vs - 7.003) and GH levels (- 9.548 μg/L vs - 13.182 μg/L), and the proportion of patients with ≥1 acromegaly symptom (- 20.3% vs - 32.5%) were observed from baseline to end-of-study in lanreotide autogel and lanreotide 40 mg PR groups, respectively. In the lanreotide autogel group, 45.5% (25/55) patients achieved ≥20% reduction in TV compared with 50.9% (25/53) in lanreotide 40 mg PR group (ITT). Safety profiles were similar in both treatment groups. Lanreotide autogel was non-inferior to lanreotide 40 mg PR in Chinese patients with active acromegaly after 32 weeks of treatment. Retrospectively registered on ClinicalTrials.gov: NCT02493517 (9 July 2015); prospectively registered on chinadrugtrials.org.cn: CTR20140698 (24 October 2014).


Susceptibility of laboratory and wild rodents to Rattus or Apodemus-type hantaviruses.
Adult Wistar rats (Rattus norvegicus), Apodemus agrarius, Meriones unguiculatus, Clethrionomys rufocanus, and Apodemus argenteus were inoculated with Rattus-type (SR-11, KI-262, and TB-314) or Apodemus-type (Hantaan 76-118) hantaviruses. Production of serum antibody to the inoculated virus (IAHA titres of 1:32 to 1:4 096) was obsersved in all rodent species 10 weeks after virus inoculation. Rattus-type virus was detected in some organs of all the rodent species employed except of Apodemus agrarius. Apodemus-type virus was found only in some organs of Apodemus agrarius. Newborn Wistar rats induced antibody in high titres to both Rattus- and Apodemus-type hantaviruses. Rattus-type virus was detected in all the organs examined for up to 6 weeks after inoculation, whereas Apodemus-type virus disappeared from all organs except of brain and lung tissues. The virulence of the three Rattus-type viruses to newborn rats was different. These findings indicate that the susceptibility of rodents may vary depending on the combination of rodent species and virus strains; they also suggest that the various species of rodents may be the reservoir animals of hantavirus infection in nature.


Sustainability Indicators Concerning Waste Management for Implementation of the Circular Economy Model on the University of Lome (Togo) Campus.
The circular economy aims to reduce the volume of waste generated in the world, transforming it into resources. The concept of indicator of circular economy was introduced to evaluate the improvement obtained regarding efficiency in terms of reduction, reuse and recycling of waste generated on the campus of the University of Lome (Togo). These indicators showed that 59.5% of the waste generated on the campus in 2018 could be introduced into the circular economy paradigm through composting, and 27.0% of the energy consumed could be replaced by clean energy obtained from biogas. The entire plastic fraction can be introduced into the circular economy paradigm by reusing plastic bottles and selling the rest in the port of the city. Thus, the income obtained could range from €15.5/day in 2018 to €34.5/day in 2027. Concerning old tires, 1.5% of the rubber needed to pave the entire roadway of the campus could be replaced by the waste generated by the tires currently existing there. Consequently, waste management on the campus could be controlled thanks to these indicators, and this could serve as a model for the rest of the country.


Pulse processing affects gas production by gut bacteria during in vitro fecal fermentation.
Flatulence is one barrier to pulse consumption for many people. Therefore, we examined how processing affects gas production by the microbiome in three classes of pulses. Processing did not affect gas production from Navy beans. However, in Pardina lentils and green peas, (-1.9 ± 0.3 mL/24 h, p < 0.001; -2.3 ± 0.3 mL/24 h, p < 0.001, respectively). In Pardina lentils and green peas, germination diminished carbohydrate utilization by the microbiome compared with unprocessed samples. In Pardina lentils germination reduced abundance germination resulted in the greatest reduction in gas production among six processing methods of amplicon sequence variants (ASVs) from Bacteroides and Lachnospiraceae and reduced propionate production compared with unprocessed samples. In green peas, germination reduced ASVs from Lachnospiraceae, including one from Roseburia, and reduced proportion of butyrate production during fermentation. Three ASVs from Clostridium sensu stricto (cluster 1), Megasphaera elsdenii, and unclassified Veillonellaceae, were strongly associated with increased gas production across all samples (ρ = 0.67-0.69, p < 0.001). This study showed that processing can reduce gas production by the microbiome in some pulses, but also reduces saccharolytic fermentation and production of beneficial microbial metabolites.


The optimization method for synthesis of technetium-99m-luteolin as radiotracer in the development of cancer drugs from flavonoid.
The aim of this study is to find the optimum conditions of labeling luteolin flavonoid compounds with technetium-99m (99mTc) to meet the purity requirements stated in the United States Pharmacopeia. This compound is expected to be a potential radiotracer compound for diagnosing cancer. The optimization method in labeling luteolin with technetium determines the parameters such as pH, SnCl2.2H2O, genistein concentration, and incubation time. Optimization results of Technetium-99m-luteolin labeling obtained optimum pH conditions 8, the amount of SnCl2.2H2O as a reducing agent 60 μL, the optimum amount of luteolin 6 mg/ml, and the optimum incubation time is 30 min. This optimum condition obtained a 99mTc-Luteolin radiochemical purity yield of 94.15%. The radiochemical purity percentage of the 99mTc-Luteolin compound has fulfilled the requirements listed at United States Pharmacopeia, which is ≥90%.


Differences in the antibody response to a mucosal bacterial antigen between allergic and non-allergic subjects.
The immune response to bacterial antigens on mucosal surfaces may be modified in individuals allergic to aeroallergens due to a maturational or genetic difference or from the interaction between inhaled allergens and bacteria at the mucosa. Plasma from children and adults allergic (n = 97) and non-allergic (n = 54) to aeroallergens were initially tested for IgG1 (Th1) and IgG4 (Th2) reactivity to P6, a conserved outer membrane protein of Haemophilus influenzae. IgE binding was measured for some allergic donors. The development of the antibody responses to P6 was subsequently examined in the plasma from 35 children aged 1, 2 and 5 years taken from a prospective birth cohort. IgG4 antibodies to P6 were more readily detected in allergic subjects than in non-allergic subjects (p<0.001), with a strong bias to the male gender. Some allergic subjects (35%) also had IgE antibody (1-10 ng/ml) that was not associated with IgG4 or gender. In the cohort study of infants, subjects who developed skin prick test positivity to mite allergens by 5 years of age had an 85% reduction in the IgG1 anti-P6 antibody at year 2 (p<0.05) and, unlike skin test negative infants, this group had IgG4 anti-P6 antibodies at 5 years of age. The antibodies of subjects allergic to a bacterial antigen included IgE and IgG4 (particularly for males) compared with the almost exclusive IgG1 response of non-allergic subjects. The IgG1 responses of 2-year-old children who became skin test positive was markedly reduced and P6-specific IgG4 became detectable at 5 years of age.


Unusual presentation of Kaposi sarcoma in an HIV-negative woman.
Kaposi sarcoma typically presents as violaceous macules and papules in immunocompromised, specifically HIV-positive, patients. Its distinct clinical features often facilitate rapid diagnosis. In this article, we report a case of Kaposi sarcoma presenting as a concerning yet nondescript lesion in an HIV-negative woman. Although Kaposi sarcoma is frequently part of the differential diagnosis for skin lesions affecting HIV-positive patients, it is less frequently considered in HIV-negative individuals. Additionally, this case differs from the classic clinical presentation of Kaposi sarcoma by resembling a squamous cell carcinoma or superficial basal cell carcinoma. Therefore, it illustrates the importance of suspicious lesion biopsies to ensure accurate diagnosis and appropriate treatment.


Correlation between Intrinsic Brain Activity and Thyroid-Stimulating Hormone Level in Unmedicated Bipolar II Depression.
Although abnormalities of amplitude of low-frequency fluctuations (ALFF) and hormone levels of hypothalamus-pituitary-thyroid axis have been reported in patients with bipolar disorder (BD), the association between abnormal ALFF and serum thyroid hormone levels remains unknown. A total of 90 patients with unmedicated BD II depression and 100 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging, and then routine band (0.01-0.1 Hz), slow-5 band (0.01-0.027 Hz), and slow-4 band (0.027-0.073 Hz) ALFF analysis were performed. Additionally, serum thyroid hormone levels including free tri-iodothyronine (FT3), total tri-iodothyronine (TT3), free thyroxin (FT4), total thyroxin (TT4), and thyroid-stimulating hormone (TSH) were detected. The correlation between abnormal serum thyroid hormone levels and ALFF values in patients with BD II depression was calculated. Compared with the HCs, patients with BD II depression showed decreased ALFF in bilateral precuneus (PCu)/posterior cingulate cortex (PCC) in routine and slow-4 frequency bands, decreased ALFF in the right PCu, and increased ALFF in the right middle occipital gyrus (MOG) in the slow-5 frequency band. Additionally, patients with BD II depression showed lower TSH level than HCs, and TSH level was positively correlated with ALFF values in the bilateral PCu/PCC in the routine frequency band. These findings suggest that patients with BD II depression display intrinsic activity abnormalities, mainly in the PCu/PCC and MOG, which are associated with specific frequency bands. Moreover, altered intrinsic activity in the PCu/PCC may be related to TSH levels in bipolar II depression.


Hydroheteroarylation of Unactivated Alkenes Using N-Methoxyheteroarenium Salts.
We report the first reductive coupling of unactivated alkenes with N-methoxy pyridazinium, imidazolium, quinolinium, and isoquinolinium salts under hydrogen atom transfer (HAT) conditions, and an expanded scope for the coupling of alkenes with N-methoxy pyridinium salts. N-Methoxy pyridazinium, imidazolium, quinolinium, and isoquinolinium salts are accessible in 1-2 steps from the commercial arenes or arene N-oxides (25-99%). N-Methoxy imidazolium salts are accessible in three steps from commercial amines (50-85%). In total 36 discrete methoxyheteroarenium salts bearing electron-donating, electron-withdrawing, alkyl, aryl, halogen, and haloalkyl substituents were prepared (several in multigram quantities) and coupled with 38 different alkenes. The transformations proceed under neutral conditions at ambient temperature, provide monoalkylation products exclusively, and form a single alkene addition regioisomer. Preparatively useful and complementary site selectivities in the addition of secondary and tertiary radicals to pyidinium salts are documented: harder secondary radicals favor C-2 addition (2->10:1), while softer tertiary radicals favor bond formation to C-4 (4.7->29:1). A diene possessing a 1,2-disubstituted and 2,2-disubstituted alkene undergoes hydropyridylation at the latter exclusively (61%) suggesting useful site selectivities can be obtained in polyene substrates. The methoxypyridinium salts can also be employed in dehydrogenative arylation, borono-Minisci, and tandem arylation processes. Mechanistic studies support the involvement of a radical process.


Effects of woody forages on biodiversity and bioactivity of aerobic culturable gut bacteria of tilapia (Oreochromis niloticus).
The present study investigated the effects of four woody forages (Moringa oleifera Lam (MOL), fermented MOL, Folium mori (FM) and fermented FM) on biodiversity and bioactivity of aerobic culturable gut bacteria of tilapia (Oreochromis niloticus) by a traditional culture-dependent method. A total of 133 aerobic culturable isolates were recovered and identified from the gut of tilapia, belonging to 35 species of 12 genera in three bacterial phyla (Firmicutes, Actinobacteria and Proteobacteria). Among them, 6 bacterial isolates of Bacillus baekryungensis, Bacillus marisflavi, Bacillus pumilus, Bacillus methylotrophicus, Proteus mirabilis and Pseudomonas taiwanensis were isolated from all the five experimental groups. The Bray-Curtis analysis showed that the bacterial communities among the five groups displayed obvious differences. In addition, this result of bioactivity showed that approximate 43% of the aerobic culturable gut bacteria of tilapia displayed a distinct anti-bacterial activity against at least one of four fish pathogens Streptococcus agalactiae, Streptococcus iniae, Micrococcus luteus and Vibrio parahemolyticus. Furthermore, Bacillus amyloliquefaciens and Streptomyces rutgersensis displayed strong activity against all four indicator bacteria. These results contribute to our understanding of the intestinal bacterial diversity of tilapia when fed with woody forages and how certain antimicrobial bacteria flourished under such diets. This can aid in the further exploitation of new diets and probiotic sources in aquaculture.


Fibrositis: misnomer for a common rheumatic disorder.
Fibrositis is a misnomer for a very common form of nonarticular rheumatism. The name implies an inflammatory process in fibroconnective tissue which has never been verified. The symptoms of fibrositis are ill-defined musculoskeletal pain made worse by stress, cold, noise and unaccustomed exercise; there is usually a significant element of depression, nonrestorative sleep, chronic fatigue and early morning stiffness. Results of physical examination are strikingly normal, apart from painful tender spots which are remarkably consistent in location from patient to patient. It is important to realize that fibrositis can complicate diseases such as rheumatoid arthritis and systemic lupus erythematosus, where its prompt recognition is essential in averting inappropriate medication. Drug therapy alone is seldom effective in alleviating symptoms; a carefully planned education program is necessary to readjust both psyche and soma.


Proposed Geometrical Tool for Cases of Laterally Adapted Tibial Tubercle during Total Knee Replacement.
The alignment of tibial component in total knee replacement operation must be achieved in three planes to ensure optimum results. In coronal plane, the alignment depends on three anatomical landmarks. These landmarks are tibial tuberosity, leg shin, and midtalar point. In eastern community, people get used to sit cross-legged which causes additional tension in the quadriceps muscle which is attached distally to the tibial tuberosity. This tension causes adaptation of the tuberosity laterally. Tuberosity adaptation causes the three anatomical landmarks being not collinear. In this work, eight cases of lateral adapted tubercle were diagnosed of this condition before the surgery and their X-ray images after the surgery were checked regarding tibial alignment. Tibial alignment has been checked by measuring the medial proximal tibial angle (MPTA) which is the angle between the mechanical tibial axis and the tibial component plateau. MPTAs for the eight cases were (86.9°-93.6°). Three cases had MPTA less than 90° indicating varus alignment and five of them had MPTA more than 90° indicating valgus alignment. A geometrical tool was designed using the DesignSpark Mechanical software as a proposed solution to solve the adaptation problem. The tool can give a method for fixing the tibial component precisely without any varus\valgus malalignment.


Evenly transferred single-layered graphene membrane assisted by strong substrate adhesion.
We explored the transfer of a single-layered graphene membrane assisted by substrate adhesion. A relatively larger adhesion force was measured on the SiO2 substrate compared with its van der Waals contribution, which is expected to result from the additional contribution of the chemical bonding force. Density functional theory calculations verified that the strong adhesion force was indeed accompanied by chemical bonding. The transfer of single-layered graphene and subsequent deposition of the dielectric layer were best performed on the SiO2 substrate exhibiting a larger adhesion force. This study suggests the selection and/or modification of the underlying substrate for proper transfer of graphene as well as other 2D materials similar to graphene.


Comparative evaluation of a dentifrice containing calcium sodium phosphosilicate to a dentifrice containing potassium nitrate for dentinal hypersensitivity: A clinical study.
Calcium sodium phosphosilicate is a recently introduced desensitizing agent which acts by occluding the dentinal tubules and also resists acid decalcification. This study was designed to assess the efficacy of a new toothpaste containing 5% calcium sodium phosphosilicate for the treatment of dentinal hypersensitivity and also compare it with 5% potassium nitrate. Sixty patients with the chief complaint of dentinal hypersensitivity were enrolled and randomly divided into two groups. The visual analog scale (VAS) scores were taken for water and air stimuli at baseline, 3 weeks after usage of the respective toothpaste, and 3 weeks after discontinuation of the respective toothpaste. Both the groups showed reduction in hypersensitivity scores at 3 weeks and 6 weeks for air stimulus and cold water. The calcium sodium phosphosilicate group, however, showed significantly reduction in hypersensitivity compared to the potassium nitrate group at any time point for both measures of hypersensitivity. The 5% calcium sodium phosphosilicate group showed immense reduction in dentinal hypersensitivity symptoms. The 5% calcium sodium phosphosilicate showed prolonged effects even after discontinuation as compared to 5% potassium nitrate, due to its dentinal tubular occlusion property.


Dermoscopy Patterns and Histopathological Findings in Nodular Basal Cell Carcinoma-Study on 68 Cases.
Basal cell carcinoma (BCC) is the most common skin cancer, with an increasing incidence in Europe particularly in young individuals. Nodular basal cell carcinoma is the most common subtype and accounts for approximately 57.6-78.7% of all BCCs. We performed an observational, morphological study which involved 68 patients with the diagnosis of nodular BCC. The localization and diameter of the lesion, histological subtype of the lesion, dermoscopic patterns, Fitzpatrick skin type and sex of each patient were recorded. The most common dermoscopic pattern seen in nodular BCCs was irregular vascularity and, arborizing vessels (>0.2mm in diameter) being the most frequent irregular vascular pattern. The second most common dermoscopic feature in patients with nodular BCCs was translucency. The most common dermoscopic features of the 12 pigmented BCCs were: pigmented islands (blue-gray globules and blue-gray ovoid nests); the pigmented distribution pattern (with (maple leaf-like structures and spoke wheel-like areas); arborizing vessels and white streaks/white areas. The histopathological analysis of the 68 BCCs revealed that the nodular type was the most frequently identified for 71.7% of cases The differential diagnosis between basal cell carcinoma and other skin lesions and inflammatory skin diseases is very important, since serious morbidity may result from an undiagnosed tumor.


Place of death among foreign-born individuals: a national population-based register study.
Relatively little is known about where foreign-born individuals die in Sweden and how birth region might influence place of death. Thus, there is a need for population-based studies investigating place of death and associated factors among foreign-born individuals. The aim of this study was to identify variations in place of death among foreign-born individuals residing in Sweden and to compare place of death between the foreign- and domestic-born population. We also examine the association between place of death, underlying cause of death and sociodemographic characteristics among the foreign-born population. A population-based register study. All deceased individuals ⩾18 years of age in Sweden with a registered place of death between 2012 and 2019 (n = 682,697). Among these, 78,466 individuals were foreign-born. Univariable multinomial logistic regression modelling and multivariable multinomial logistic regression analyses were performed. Overall, hospital was the most common place of death among the foreign-born population. However, there were variations in place of death related to region of birth. Compared to domestic-born, a higher proportion of foreign-born individuals dies at home, the majority of whom were born on the African continent. Region of birth is one of the several factors associated with place of death among foreign-born individuals. Further research is needed to explore both preferences and barriers to place of death among foreign-born individuals.


Size dependence of bubble wetting on surfaces: breakdown of contact angle match between small sized bubbles and droplets.
For a bubble on a smooth and rigid substrate, its contact angle is always assumed to be supplementary to the droplet contact angle under the same wetting conditions. Here we revisit bubble wetting on smooth solid surfaces via both free energetic analysis and molecular dynamics (MD) simulations. Our study shows a fundamental difference between bubble wetting and droplet wetting: the size dependence of the isothermal compressibility of the gas bubble leads to a size-dependent bubble contact angle. Based on theoretical analysis we develop a new relationship between the bubble contact angle and droplet contact angle, which is verified with MD simulations for nano-sized bubbles and droplets. In general, our studies show that for bubbles having a size greater than 10 micrometers, the traditional relation of the bubble contact angle being supplementary to the droplet contact angle holds. But when the bubble size decreases to several micrometers or even to the nanoscale size, the relation of contact angle match breaks down, and the deviation from contact angle match increases with decreasing bubble size. This study reveals a unique wetting behavior of bubbles, implying that the wetting of micro- and nano-bubbles deserves serious consideration.


Coadministration of Canagliflozin and Phentermine for Weight Management in Overweight and Obese Individuals Without Diabetes: A Randomized Clinical Trial.
To assess the efficacy and safety of coadministration of canagliflozin (CANA) and phentermine (PHEN) compared with placebo (PBO) and CANA or PHEN monotherapies in individuals who were overweight and obese without type 2 diabetes. This 26-week, phase 2a, randomized, double-blind, PBO-controlled, multicenter, parallel-group study enrolled individuals who were obese or overweight without type 2 diabetes (N = 335, aged 18-65 years, BMI ≥30 to <50 kg/m2 or BMI ≥27 to <50 kg/m2 with hypertension and/or dyslipidemia). Participants were randomized (1:1:1:1) to receive PBO, CANA 300 mg, PHEN 15 mg, or coadministration of CANA 300 mg and PHEN 15 mg (CANA/PHEN) orally once daily. The primary end point was percent change in body weight from baseline to week 26; key secondary end points were the proportion of participants achieving weight loss ≥5% and change from baseline in systolic blood pressure. CANA/PHEN provided statistically superior weight loss from baseline versus PBO at week 26 (least squares mean difference -6.9% [95% CI -8.6 to -5.2]; P < 0.001). CANA/PHEN also provided statistically superior achievement of weight loss ≥5% and reduction in systolic blood pressure compared with PBO. CANA/PHEN was generally well tolerated, with a safety and tolerability profile consistent with that of the individual components. CANA/PHEN produced meaningful reductions in body weight and was generally well tolerated in individuals who were overweight or obese without type 2 diabetes. Further studies are warranted to evaluate potential use of this combination for long-term weight management.


Prediction of carcinoma after resection in subjects with ampullary adenomas on endoscopic biopsy.
The endoscopic treatment of ampullary adenomas is established; however, the false-negative rate of endoscopic biopsy for carcinoma is 20% to 30%, and it remains uncertain whether identifiable features predict malignancy. Our aim in this study was to evaluate the predictable factors of malignancy in ampullary adenomas on endoscopic biopsy. Ninety-one subjects diagnosed with ampullary adenoma on endoscopic biopsy were confirmed after endoscopic or surgical resection of ampullary lesions between 1995 and 2011 respectively. Clinical, laboratory, radiologic, and endoscopic findings were compared between patients with adenoma and carcinoma after resection. We examined the predictors of malignancy in ampullary adenoma on endoscopic biopsy. The malignancy rate in ampullary adenomas on endoscopic biopsy was 26.4%. Univariate analysis revealed that presence of symptoms, villous components, high-grade dysplasia (HGD), papilla enlargement on computed tomography, duct dilatation on radiologic imaging, bilirubin>2 mg/dL, aspartate aminotransferase>40 IU/L, alanine aminotransferase>40 IU/L, and alkaline phosphatase>90 U/L were associated with malignancy in patients over 65 years of age. HGD [odds ratio, 6.86 (95% confidence interval, 1.58-29.79)] and ductal dilatation [odds ratio, 11.12 (95% confidence interval, 2.27-54.37)] were independently associated with malignancy in multivariate analysis. The sensitivity and negative predictive value for ≥1 risk factors were 95.83% and 96.77%, respectively. The presence of 2 risk factors resulted in a high specificity (96%) and positive predictive value (84%) for malignancy. HGD and ductal dilatation are significant predictors of malignancy in ampullary adenomas. When these risk factors are present, precautions should be taken in the consideration of malignancy in patients with ampullary adenoma.


Pre-operative chronic opioid or glucocorticoid use and mortality after noncardiac surgery: A retrospective cohort study.
The chronic use of opioids and glucocorticoids is associated with serious side effects. Moreover, both medications are related to poor long-term postoperative outcomes. The study aimed to investigate the association between pre-operative chronic opioid and glucocorticoid use and 90-day mortality after noncardiac surgery. Retrospective, population-based cohort study. Single tertiary academic hospital. The study enrolled adult (≥18 years of age) patients admitted to Seoul National University Bundang Hospital, between January 2012 and December 2018 for planned, elective, noncardiac surgery. The study compared the 90-day mortality for patients using opioids or glucocorticoids chronically (≥3 months) prior to surgery and for opioid-naïve and glucocorticoid-naïve patients. A total of 112 606 patients were included in the study. Among them, 107 843 (95.9%) were opioid-naïve and glucocorticoid-naïve patients; 3373 (3.0%), 1199 (1.1%) and 191 patients (0.2%) were chronic users of opioids, glucocorticoids or both, respectively. In the multivariable model, compared with opioid-naïve and glucocorticoid-naïve patients, the odds of dying within 90 days were significantly higher for chronic users of opioids [3.56-fold; 95% confidence intervals (CIs) 2.36 to 5.38; P < 0.001], glucocorticoids (4.17-fold; 95% CI 3.28 to 5.29; P < 0.001) and combined opioids and glucocorticoids (7.66-fold; 95% CI 3.91 to 15.01; P < 0.001). Chronic pre-operative use of opioids and glucocorticoids, together or individually, were associated with increased 90-day mortalities after noncardiac surgery, compared with opioid-naïve and glucocorticoid-naïve patients. Our results suggest that chronic pre-operative use of opioids and glucocorticoids should be managed carefully.


Monoamine metabolites and ventricular fluid pressure in children.
Samples of ventricular CSF were obtained from 20 children in whom ventricular fluid pressure was continuously monitored. The concentrations of the monoamine metabolites, 5-hydroxyindolylacetic acid, homovanillic acid and 3-methoxy-4-hydroxyphenylglycol, in the CSF were not related to the ventricular fluid pressure. The mean concentration of 3-methoxy-4-hydroxyphenylglycol was higher (p less than 0.01) in 9 children aged 1 day to 6 months that in 12 children aged 8 months to 11 years.


Generation of a functional and durable vascular niche by the adenoviral E4ORF1 gene.
Vascular cells contribute to organogenesis and tumorigenesis by producing unknown factors. Primary endothelial cells (PECs) provide an instructive platform for identifying factors that support stem cell and tumor homeostasis. However, long-term maintenance of PECs requires stimulation with cytokines and serum, resulting in loss of their angiogenic properties. To circumvent this hurdle, we have discovered that the adenoviral E4ORF1 gene product maintains long-term survival and facilitates organ-specific purification of PECs, while preserving their vascular repertoire for months, in serum/cytokine-free cultures. Lentiviral introduction of E4ORF1 into human PECs (E4ORF1(+) ECs) increased the long-term survival of these cells in serum/cytokine-free conditions, while preserving their in vivo angiogenic potential for tubulogenesis and sprouting. Although E4ORF1, in the absence of mitogenic signals, does not induce proliferation of ECs, stimulation with VEGF-A and/or FGF-2 induced expansion of E4ORF1(+) ECs in a contact-inhibited manner. Indeed, VEGF-A-induced phospho MAPK activation of E4ORF1(+) ECs is comparable with that of naive PECs, suggesting that the VEGF receptors remain functional upon E4ORF1 introduction. E4ORF1(+) ECs inoculated in implanted Matrigel plugs formed functional, patent, humanized microvessels that connected to the murine circulation. E4ORF1(+) ECs also incorporated into neo-vessels of human tumor xenotransplants and supported serum/cytokine-free expansion of leukemic and embryonal carcinoma cells. E4ORF1 augments survival of PECs in part by maintaining FGF-2/FGF-R1 signaling and through tonic Ser-473 phosphorylation of Akt, thereby activating the mTOR and NF-kappaB pathways. Therefore, E4ORF1(+) ECs establish an Akt-dependent durable vascular niche not only for expanding stem and tumor cells but also for interrogating the roles of vascular cells in regulating organ-specific vascularization and tumor neo-angiogenesis.


Assembling Carbon Pores into Carbon Sheets: Rational Design of Three-Dimensional Carbon Networks for a Lithium-Sulfur Battery.
The conversion reaction-based lithium-sulfur battery features an attractive energy density of 2600 W h/kg. Nevertheless, the unsatisfied performance in terms of poor discharge capacity and cycling stability still hinders its practical applications. Recently, porous carbon materials have been widely reported as promising sulfur reservoirs to promote the sluggish reaction kinetics of sulfur conversion, tolerate volume expansion of sulfur, and suppress polysulfide shuttling. However, porous carbon with a simply designed nanostructure is hard to satisfy all of these aspects simultaneously. Herein, we have applied a dual-template strategy that assembles carbon pores into carbon sheets to prepare three-dimensional (3D) nitrogen-doped porous carbon nanosheets (N-PCSs) as the multifunctional sulfur host for the Li-S battery. By arranging carbon pores within an interconnected 3D architecture, the porous carbon sheets enable rapid electron/ion transfer. Moreover, the micro/mesopores and nitrogen dopant in N-PCS provide both physical and chemical restrictions to polysulfide species. With these advances, the N-PCS/S cathode delivers a large initial discharge capacity of 1360 mA h/g at 0.1 C. When performed at 0.5 C for 1000 cycles, the cathode can still remain ∼50% of its capacity with a low decay rate of 0.05% per cycle, showing the important role of the 3D carbon material in the Li-S battery.


Tumor-derived vaccines containing CD200 inhibit immune activation: implications for immunotherapy.
There are over 400 ongoing clinical trials using tumor-derived vaccines. This approach is especially attractive for many types of brain tumors, including glioblastoma, yet so far the clinical response is highly variable. One contributor to poor response is CD200, which acts as a checkpoint blockade, inducing immune tolerance. We demonstrate that, in response to vaccination, glioma-derived CD200 suppresses the anti-tumor immune response. In contrast, a CD200 peptide inhibitor that activates antigen-presenting cells overcomes immune tolerance. The addition of the CD200 inhibitor significantly increased leukocyte infiltration into the vaccine site, cytokine and chemokine production, and cytolytic activity. Our data therefore suggest that CD200 suppresses the immune system's response to vaccines, and that blocking CD200 could improve the efficacy of cancer immunotherapy.


Triple-Cation-Based Perovskite Photocathodes with AZO Protective Layer for Hydrogen Production Applications.
Metal halide perovskites are actively pursued as photoelectrodes to drive solar fuel synthesis. However, currently, these photocathodes suffer from limited stability in water, which hampers their practical application. Here, we report a high-performance solution-processable photocathode composed of cesium formamidinium methylammonium triple-cation lead halide perovskite protected by an Al-doped ZnO (AZO) layer combined with a Field's metal encapsulation. Careful selection of charge transport layers resulted in an improvement in photocurrent, fill factor, device stability and reproducibility. The dead pixels count reduced from 25 to 6% for the devices with an AZO layer, and in photocathodes with an AZO layer the photocurrent density increased by almost 20% to 14.3 mA cm-2. In addition, we observed a 5-fold increase in the device lifetime for photocathodes with AZO, which reached up to 18 h before complete failure. Finally, the photocathodes are fabricated using low-cost and scalable methods, which have promise to become compatible with standard solution-based processes.


The Relationship Between Rural Health Clinic Use and Potentially Preventable Hospitalizations and Emergency Department Visits Among Medicare Beneficiaries.
High rates of potentially preventable hospitalizations and emergency department (ED) visits indicate limited primary care access. Rural Health Clinics (RHCs) are intended to increase access to primary care. The goal of this study was to evaluate the role of RHCs and their impact on potentially preventable hospitalizations and ED visits among Medicare beneficiaries based on actual individual-level utilization patterns. With Medicare Part A and Part B claims data from 2007 to 2010, we constructed a series of individual-level negative binomial regression models to examine the relationship between RHC use and the number of potentially preventable hospitalizations and ED visits. RHC use was associated with a 27% increase in potentially preventable hospitalizations and a 24% increase in potentially preventable ED visits among older Medicare enrollees. Among younger, disabled Medicare beneficiaries, RHC use was associated with a 14% increase in potentially preventable hospitalizations and an 18% increase in potentially preventable ED visits. Potentially preventable hospitalizations and ED visits were more common among beneficiaries who were black or who had more chronic conditions. The results of our study highlight that the Medicare population using RHCs is at especially high risk for potentially preventable hospitalizations and ED visits. The mechanisms behind this are not well understood and should receive continued attention from policy makers and researchers.


Opioid peptides selective for receptor types modulate cocaine-induced behavioral responses in mice.
The effects of intracerebroventricular injection of mu-, kappa- and delta-selective opioid agonists on cocaine-induced behavior were investigated in mice using multidimensional behavioral analysis. Cocaine (3.0 mg/kg) produced a marked increase in linear locomotion, circling, rearing and/or grooming, although the mu-opioid agonist [D-Ala2, NMePhe4, Gly-ol] enkephalin (DAMGO) (0.003 and 0.01 microgram), the kappa-opioid agonist dynorphin A- (1-13) (3.0 and 12.5 micrograms) or the delta-opioid agonist [D-Pen2, L-Pen5]enkephalin (DPLPE) (0.3 and 1.0 micrograms) did not significantly affect behavioral responses. DAMGO (0.003 and 0.01 microgram) and dynorphin A- (1-13) (12.5 micrograms) inhibited the cocaine (3.0 mg/kg)-induced increase in linear locomotion, circling and/or rearing. In contrast, DPLPE (1.0 micrograms) enhanced the cocaine (3.0 mg/kg)-induced increase in circling. The effects of DAMGO (0.003 microgram), dynorphin A- (1-13) (12.5 micrograms) and DPLPE (1.0 micrograms) were fully reversed by receptor-selective opioid antagonists, such as beta-funaltrexamine (5.0 micrograms), Mr2266 (5.6 mg/kg) and naltrindole (10.0 mg/kg), respectively. These results suggest that the activation of mu- and kappa-opioid receptors inhibits cocaine-induced behavior, while that of delta-opioid receptors enhances the behavior.


The low expression of miR-451 predicts a worse prognosis in non-small cell lung cancer cases.
miR-451 is a tumor suppressive microRNA with several target genes, including Macrophage migration inhibitory factor (MIF). As little is known about the expression and clinicopathological significance of mir-451 in NSCLC, we performed a clinicopathological study of 370 NSCLC cases to clarify them. Cell biological experiments were also performed on NSCLC cell lines to confirm the tumor-suppressive role of miR-451 and whether or not MIF is targeted by miR-451. We analyzed 370 NSCLC cases for the miR-451 expression by quantitative real-time polymerase chain reaction and the MIF expression by immunohistochemistry. Eighty-four background lung tissue samples were also evaluated for the miR-451 expression. The clinicopathological and genetic factors surveyed were the disease-free survival, smoking status, histological type, disease stage, EGFR gene mutations and ALK rearrangements. In 286 adenocarcinoma cases, the invasive status (adenocarcinoma in situ, minimally invasive adenocarcinoma and invasive adenocarcinoma) was also evaluated. Five NSCLC cell lines (H23, H441, H522, H1703, and H1975) were cultured and evaluated for their miR-451 and MIF expression. The cell lines with lower miR-451 and higher MIF expressions were then selected and transfected with miR-451-mimic to observe its effects on MIF expression, Akt and Erk status, cell proliferation, and cell migration. The miR-451 expression was down-regulated in cancer tissues compared with background lung tissues (P<0.0001). Factors such as advanced disease stage, positive pleural invasion and nodal status and being a smoker were significantly correlated with a lower expression of miR-451 (P<0.05 each), while EGFR gene mutations and ALK rearrangements were not. In adenocarcinoma, invasive and minimally invasive adenocarcinoma showed lower expression of miR-451 than adenocarcinoma in situ (P<0.0005, respectively). A survival analysis showed that a lower expression of miR-451 was an independent predictor of a poor prognosis for NSCLC (P<0.05). The MIF expression was inversely correlated with the miR-451 expression. Out of 5 NSCLC cell lines examined, H441 and H1975 showed higher MIF and lower miR-451 expressions. After the transfection of miR-451-mimic, the MIF expression and phosphorylated Akt expression of these cell lines was suppressed, as were cell proliferation and cell migration. This clinicopathological study of 370 NSCLC cases and the cell biological studies of NSCLC cell lines clarified the tumor-suppressive role of miR-451 and its prognostic value. We also validated MIF as a target of miR-451 in NSCLC.


Interaction of SPIN90 with syndapin is implicated in clathrin-mediated endocytic pathway in fibroblasts.
SPIN90, a 90-kDa Nck-interacting protein with a SH3 domain, plays a role in sarcomere formation and myofibril assembly, and its phosphorylation is modulated by cell adhesion and Erk activation. Here we demonstrate that SPIN90 participates in receptor-mediated endocytic pathway in fibroblasts. We identified syndapin (synaptic dynamin-binding protein) as a SPIN90 interacting protein using yeast two-hybrid screening. SPIN90 directly binds the SH3 domain of syndapin via its proline rich domain in vitro and in vivo and also associates with clathrin. Over-expression of SPIN90-full length in COS-7 cells inhibited transferrin uptake, a marker of endocytosis. Interestingly, SPIN90-PRD, a syndapin-binding domain, significantly inhibited endocytosis, and the inhibition was reversed by co-expression of syndapin. Depleting SPIN90 through antibody microinjection or Knocking it down using siRNAs also significantly inhibited transferrin internalization. Moreover, early endosomal marker proteins (EEA1 and Rab5) appeared to closely associate or partially co-localize with SPIN90 in endosomes and an internalized FITC-dextran and Texas Red-EGF were found on the endosomes in association with SPIN90. Time-lapse video showed that GFP-SPIN90 travels with moving vesicles within living cells. Taken together, these findings suggest that SPIN90 is implicated in receptor-mediated endocytic pathway in fibroblasts.


Stereotactic body radiotherapy for lung metastases as oligo-recurrence: a single institutional study.
The purpose of this study was to investigate clinical outcomes following stereotactic body radiotherapy (SBRT) for lung metastases as oligo-recurrence. From May 2003 to June 2014, records for 66 patients with 76 oligo-recurrences in the lungs treated with SBRT were retrospectively reviewed. Oligo-recurrence primary sites and patient numbers were as follows: lungs, 31; colorectal, 13; head and neck, 10; esophagus, 3; uterus, 3; and others, 6. The median SBRT dose was 50 Gy (range, 45-60 Gy) administered in a median of 5 (range, 5-9) fractions. All patients received SBRT, with no acute toxicity. Surviving patients had a median follow-up time of 36.5 months. The 3-year rates of local control, overall survival and disease-free survival were 90.6%, 76.0% and 53.7%, respectively. Longer disease-free interval from initial treatment to SBRT, and non-colorectal cancer were both associated with favorable outcomes. Disease progression after SBRT occurred in 31 patients, most with distant metastases (n = 24) [among whom, 87.5% (n = 21) had new lung metastases]. Among these 21 patients, 12 were judged as having a second oligo-recurrence. Additional SBRT was performed for these 12 patients, and all 12 tumors were controlled without disease progression. Three patients (4.5%) developed Grade 2 radiation pneumonitis. No other late adverse events of Grade ≥2 were identified. Thus, SBRT for oligo-recurrence achieved acceptable tumor control, with additional SBRT also effective for selected patients with a second oligo-recurrence after primary SBRT.


Morphological Transformation Reactions of Photocatalytic Metalloporphyrin-Containing Coordination Polymer Particles from Seed Structures.
Coordination polymer particles have attracted a great deal of attention due to their characteristic properties and diverse applications in the fields of gas storage, catalysis, optics, sensing, electronics, photochemistry, and biology. Herein, we investigated shape transformation reactions of zinc 5, 10, 15, 20-tetra(4-pyridyl)-21 H, 23 H-porphine (ZnTPyP)-containing coordination polymer particles (ZnTPyP-CPPs) from seed structures by delicately controlling the Gibbs energy of the self-assembly system. We obtained a morphological transformation from 1 D short nanorods to 1 D long nanorods and 3 D nano-octahedral structures, and from 3 D nano-octahedral structures to 1 D nanorod structures. We illustrated a new method to design and synthesize metalloporphyrin-containing CPPs in a controllable manner. Furthermore, photocatalytic properties of ZnTPyP-CPPs were tested, showing good catalytic abilities towards the photodegradation of methylene blue (MB) under visible light illumination.


[Straight back syndrome. Case report].
Straight back syndrome results from the shortening of the distance between the sternum and thoracic spine leading to a compression of the heart. The syndrome is caused by the lack of spine kyphosis or cobbler's chest. Straight back syndrome produces sometimes clinical symptoms suggesting acquired heart abnormalities. However, hemodynamic cardiac functioning is normal. Prognosis is this syndrome is favourable. Straight back syndrome caused by the lack of thoracic spine kyphosis was diagnosed in a 26-year patient admitted to the hospital with suspected heart abnormality and epilepsy.


New methods for the in vitro investigations of the flow patterns in artificial hearts.
With the 3 applied methods one can investigate and obtain most of the interesting aspects of the flow within blood pumps: an integral picture of the flow, the development and position of stagnation flow, the time course of the velocity in points of special interest, the turbulence, and an integral picture of the mean boundary layer flow. The measurements have shown that the flow in the blood pumps is turbulent, the turbulence can be considered harmless, because its intensity is much weaker than that of a valve; there is a correspondence between the hotfilm method and the dye-washout method, and that there is a correspondence between the dye-washout method and the in vivo clot formation. Pumps, which have been designed according to these measurements, have been implanted in a series of calves. The pumps now have a smooth continuous inner surface and usually show no thrombus formation at all (anticoagulants are used) at the postmortem. Some animals do very well, such as the one in Figure 16 during his daily walk of 500 M on the treadmill. The animal is in its 45th day of survival and remains well to date.


Metabolism-related gene vaccines and immune infiltration in ovarian cancer: A novel risk score model of machine learning.
The present study aims to develop a metabolic gene signature to evaluate the survival rate of ovarian cancer (OC) patients and analyze the potential mechanisms of metabolic genes in OC because the difficulty in early detection of OC often leads to poor treatment outcomes. A non-negative matrix factorization algorithm was applied to determine molecular subtypes according to metabolism genes. To build a risk prognosis model, least absolute shrinkage and selection operator multivariate Cox analysis was carried out with weighted correlation network analysis (WCGNA). Glycolytic flux and mitochondrial function were evaluated by conducting seahorse analysis. On the basis of metabolism-related genes, the two subtypes of OC samples present in The Cancer Genome Atlas database were distinguished. An analysis of WGCNA identified 1056 genes. Lastly, a 10-gene signature (CMAS, ADH1B, PLA2G2D, BHMT, CACNA1C, AADAC, ALOX12, CYP2R1, SCN1B and ME1) was constructed that demonstrated promising performance in predicting outcome in patients with OC. The RiskScore of the gene signature was linked to microenvironment cell infiltration and immune checkpoint. Higher RiskScores were associated with poorer results for OC patients. Seahorse analysis shows the influence of CMAS in cell energy metabolism. In the present study, a novel marker for evaluating the survival of OC patients was developed through the creation of a gene signature incorporating metabolism-related genes. Our knowledge of immunotherapy and microenvironment cell infiltration may be enriched by evaluating metabolism-related gene modification patterns.


Robotic endoscopy. A review of the literature.
Purpose To present new endoscopic robotic devices in the context of minimally invasive procedures with high precision and automation. Methods Review of the literature by December 2018 on robotic endoscopy. Results We present the studies and investments for robotic implementation and flexible endoscopy evolution. We divided them into forceps manipulation platforms, active endoscopy and endoscopic capsule. They try to improve forceps handling and stability and to promote active movement. Conclusion The implementation and propagation of robotic models depend on doing what the endoscopist is unable to. The new devices are moving forward in this direction.


Advanced chemical design with supported metal complexes for selective catalysis.
This review covers several recent topics of novel catalyst design with supported metal complexes on oxide surfaces for selective catalysis such as chiral self-dimerization to create asymmetric oxidative coupling catalysis, surface functionalization with achiral reagents to promote asymmetric catalysis, and molecular imprinting to design shape-selective catalysis. The new concepts and designs find wide applications to a variety of selective catalysts.


Fine needle aspiration cytology and immunocytochemistry of large cell lymphomas expressing the Ki-1 antigen.
Cytomorphology and immunocytochemistry were used to diagnose two cases of large cell anaplastic lymphomas that expressed the Ki-1 antigen. Smears stained with the May-Grünwald-Giemsa stain showed a cytomorphologic spectrum that varied from immunoblastlike cells to large tumor cells with pleomorphic nuclei. The tumor cells had a distinct basophilic cytoplasm, which often contained vacuoles. Giant cells with wreathlike multilobulated bizarre nuclei were also observed. Immunocytochemistry on a cytocentrifuged specimen showed that the tumor cells were of a T-helper phenotype; all strongly expressed the Ki-1 antigen and receptors for HLA-DR and IL-2.


[The autopsy of Reinhard Heydrich].
Reinhard Heydrich died on 4 June, 1942, eight days after assassination attempted on him in Prague by two members of the Czechoslovak army in Great Britain. The text of his autopsy report became available only in 2004. From the pathologist's view, the autopsy and the report show several unusual features: - The autopsy was performed early, only some 4 hours after death. - It was performed not in an autopsy room, but in the hospital director's office. - There was only a partial autopsy; the head and the neck organs were not examined. - The report lacks description of external examination; only the operation wounds are described. - The weights of the organs are not given. - And particularly: The autopsy did not reveal the cause of death.


[Smallpox--historical or real threat].
Presently, there is no real possibility of natural re-emergence of smallpox virus, which was eradicated globally more then 25 years ago. During the last decade the possibility of use of smallpox virus as a biological weapon by a criminal organisation was emphasised. The re-emergence of smallpox virus would lead to unprecedented disaster. Theoretical models indicated that only extremely strict and enforced interventions could stop the spread of epidemic, but the assumptions of these models were unrealistic. Presently, there are limited stocks of the first generation smallpox vaccine left in the world. This vaccine, as well as the second-generation vaccine are associated with multiple adverse events, including fatalities and may not be accepted by society. Much safer vaccines are now being developed. Strategic plan of prophylactic vaccinations requires defining the groups to be immunised in the first place and whether immunisation should start before or after a first smallpox case would occur.


Do schizophrenic patients who managed to get to university have a non-developmental form of illness?
Many people who develop schizophrenia have impairments in intellectual and social functioning that are detectable from early childhood. However, some patients do not exhibit such deficits, and this suggests that they may have suffered less neurodevelopmental damage. We hypothesized that the aetiology and form of schizophrenia may differ in such patients. We therefore studied a group of schizophrenic patients who were functioning well enough to enter university prior to illness onset. The casenotes of 46 university-educated patients and 48 non-university-educated patients were rated on several schedules including the OPCRIT checklist, and the two groups were compared using univariate statistical techniques. Principal components analysis was then performed using data from all patients, and the factor scores for each principal component were compared between groups. Univariate analyses showed the university-educated patients had an excess of depressive symptoms, and a paucity of core schizophrenic symptoms. Four principal components emerged in the principal components analysis: mania, biological depression, schizophrenic symptoms, and a reactive depression. University-educated patients scored significantly higher on the reactive depression principal component, and lower on the schizophrenic symptoms principal component, than the non-university-educated patients.