Readmissions for warfarin-related bleeding in pediatric patients after hospital discharge.
Warfarin therapy in pediatric patients can be difficult to manage with bleeding as a primary adverse event. Therapy initiation can be difficult as doses to achieve therapeutic outcomes are being determined. Evaluation of readmission for bleeding in pediatric patients discharged on warfarin therapy may be useful to prevent adverse events. The Pediatric Health Information System (PHIS) was queried to identify all patients <19 years of age who were discharged from a pediatric hospital on warfarin therapy. Patients who were readmitted with bleeding in the first 30 days after discharge were identified and patient variables, hospital stay variables, and medications at discharge were identified. Univariate and multivariate analysis was performed to identify independent risk factors for bleeding readmission. A total of 4,883 patients met study criteria (56% male, mean age 10.1 + 5.9 years). The two most common indications for warfarin therapy were cardiac valve replacement (23.6%) and Fontan procedure (19.5%). Ninety-seven patients (1.99%) were readmitted with bleeding within 30 days of discharge [median time 9 days (IQR 5-16 days)]. Multivariate analysis identified Asian race (OR 4.0, P < 0.01); mitral valve replacement (OR 2.5, P < 0.01); escitalopram at discharge (OR 4.2, P = 0.02); levofloxacin at discharge (OR 8.3, P < 0.01); lansoprazole at discharge (OR 1.7, P = 0.047); and length of stay (OR 1.01, P = 0.047) as significant for bleeding readmission. Pediatric patients discharged on warfarin may be readmitted for bleeding within 30 days if risk factors are present. Risk factors include patient genetic profile, drug interactions, and indications with higher goal INR values.


Metabolic characteristics revealing cell differentiation of nasopharyngeal carcinoma by combining NMR spectroscopy with Raman spectroscopy.
The staging system of nasopharyngeal carcinoma (NPC) has close relationship with the degree of cell differentiation, but most NPC patients remain undiagnosed until advanced phases. Novel metabolic markers need to be characterized to support diagnose at an early stage. Metabolic characteristics of nasopharyngeal normal cell NP69 and two types of NPC cells, including CNE1 and CNE2 associated with high and low differentiation degrees were studied by combining 1H NMR spectroscopy with Raman spectroscopy. Statistical methods were also utilized to determine potential characteristic metabolites for monitoring differentiation progression. Metabolic profiles of NPC cells were significantly different according to differentiation degrees. Various characteristic metabolites responsible for different differentiated NPC cells were identified, and then disordered metabolic pathways were combed according to these metabolites. We found disordered pathways mainly included amino acids metabolisms like essential amino acids metabolisms, as well as altered lipid metabolism and TCA cycle, and abnormal energy metabolism. Thus our results provide evidence about close relationship between differentiation degrees of NPC cells and the levels of intracellular metabolites. Moreover, Raman spectrum analysis also provided complementary and confirmatory information about intracellular components in single living cells. Eight pathways were verified to that in NMR analysis, including amino acids metabolisms, inositol phosphate metabolism, and purine metabolism. Methodology of NMR-based metabolomics combining with Raman spectroscopy could be powerful and straightforward to reveal cell differentiation development and meanwhile lay the basis for experimental and clinical practice to monitor disease progression and therapeutic evaluation.


Chlorate poisoning: mechanism of toxicity.
Intoxications with chlorate salts are characterized by methaemoglobin formation, haemolysis and renal insufficiency. The toxic effects on the erythrocyte can be reproduced in vitro. Incubation of human and rabbit erythrocytes with chlorates induces a concentration-dependent oxidation of haemoglobin. This methaemoglobin formation is followed by denaturation of the globin, a cross-linking of erythrocyte membrane proteins and an inactivation of membrane enzymes. The high sensitivity of glucose-6-phosphate dehydrogenase to denaturation by chlorate explains the inefficacy of methylene blue to reduce methaemoglobin formed, as the antidotal effect of methylene blue depends on NADPH formed mainly by the oxidation of glucose-6-phosphate. The observed changes occur only in the presence of methaemoglobin which forms a destabilising complex with chlorate. Methaemoglobin thus autocatalytically increases methaemoglobin formation and destruction of the erythrocyte. As the rabbit is known to have a high methaemoglobin-reduction capacity, human and rabbit erythrocytes were compared. In vitro, the rabbit erythrocyte is less sensitive to oxidative attack than the human red cell. In vivo, an oral dose of sodium chlorate (1 g/kg body wt.) resulted in high serum (16 +/- 4 mM) and urine concentrations (246 +/- 99 mM) in the rabbit. Methaemoglobin was not formed nor could a nephrotoxic effect be observed. These experiments also indicate that the nephrotoxicity of chlorate is mediated by methaemoglobin catalysis.


Hybrid Bacterial Foraging and Particle Swarm Optimization for detecting Bundle Branch Block.
Abnormal cardiac beat identification is a key process in the detection of heart diseases. Our present study describes a procedure for the detection of left and right bundle branch block (LBBB and RBBB) Electrocardiogram (ECG) patterns. The electrical impulses that control the cardiac beat face difficulty in moving inside the heart. This problem is termed as bundle branch block (BBB). BBB makes it harder for the heart to pump blood effectively through the heart circulatory system. ECG feature extraction is a key process in detecting heart ailments. Our present study comes up with a hybrid method combining two heuristic optimization methods: Bacterial Forging Optimization (BFO) and Particle Swarm Optimization (PSO) for the feature selection of ECG signals. One of the major controlling forces of BFO algorithm is the chemotactic movement of a bacterium that models a test solution. The chemotaxis process of the BFO depends on random search directions which may lead to a delay in achieving the global optimum solution. The hybrid technique: Bacterial Forging-Particle Swarm Optimization (BFPSO) incorporates the concepts from BFO and PSO and it creates individuals in a new generation. This BFPSO method performs local search through the chemotactic movement of BFO and the global search over the entire search domain is accomplished by a PSO operator. The BFPSO feature values are given as the input for the Levenberg-Marquardt Neural Network classifier.


Natriuretic peptides in therapy for decompensated heart failure.
Congestive heart failure (CHF) is the most frequent cause of hospitalization for patients >65 years of age and continues to be a major public health burden among the ageing population. Unlike therapy for chronic CHF, there has been only modest progress in medical treatment for acutely decompensated CHF over the past several decades. Moreover, current treatment-consisting generally of diuretic, inotropic, and vasodilatory agents-is associated with many limitations in clinical practice. Natriuretic peptides provide a promising mechanism of action in the pathophysiologic background for CHF treatment based on their vasodilatory and diuretic properties and effective inhibition of the renin-angiotensin-aldosterone system, which is activated early in the course of CHF. Nesiritide (Natrecor® or Noratak®) is a recombinant natriuretic peptide that has the same 32 amino-acid sequence as human B-type natriuretic peptide. Nesiritide has been shown to improve dyspnea and hemodynamic parameters in patients with decompensated heart failure. Ularitide is a synthetic form of urodilatin, a natriuretic peptide hormone secreted by the kidney. Recent clinical studies suggest that ularitide may play a role in managing decompensated heart failure. This review provides an update on natriuretic peptides and their therapeutic potential in advanced CHF.


Post-Traumatic Stress Disorder/Developmental Trauma Disorder/Complex Post-Traumatic Stress Disorder and Complementary and Integrative Medicine/Functional Medicine.
Response to PTSD treatments differ based on the age the abuse occurred, the type of abuse, and the chronicity of the abuse. Even when modifications to treatment are made based on the developmental age when the abuse occurred, therapies may be insufficient. In addition, when diagnostic criteria are modified to identify more children, some children continue to escape detection. Developmental Trauma Disorder, (akin to the RDoC), may be more suitable to identify epigenetic and inflammatory effects of early abuse that may be responsible for the nonresponsive to treatment. Complementary and Integrative Medicine interventions (meditation, EFT, EMDR, PUFAs, etc.) may reverse these effects.


Effect of vasoactive intestinal polypeptide (VIP) antagonism on rat jejunal fluid and electrolyte secretion induced by cholera and Escherichia coli enterotoxins.
The enteric nervous system is important in the pathophysiology of intestinal fluid secretion induced by cholera toxin (CT), Escherichia coli heat labile (LT), and heat stable (STa) toxins. The neurotransmitters involved are not fully elucidated. Vasoactive intestinal polypeptide (VIP), a potent intestinal secretagogue present in the enteric nervous system, is increased after exposure of the cat intestine to CT. Whether VIP is involved in the pathogenesis of cholera and other toxins in not known. To study in vivo the effect of VIP antagonism on jejunal fluid secretion induced by CT, LT, and STa. CT, LT (25 microg), or 0.9% NaCl was instilled in an isolated 25 cm segment of rat jejunum, and the VIP antagonist (VIPa) [4Cl-D-Phe(6), Leu(17)]-VIP (0.2 or 2 microg/kg/min) or 0.9% NaCl was given intravenously. Two hours later, single pass in vivo jejunal perfusion was performed to assess fluid movement. In STa experiments, intravenous VIPa or 0.9% NaCl was given and 30 minutes later the jejunal segment was perfused with a solution containing STa 200 microg/l. VIPa had no effect on basal intestinal fluid absorption. CT induced net fluid secretion (median -68 microl/min/g dry intestinal weight (interquartile range -80 to -56)) which was dose dependently reversed by VIPa (6.2 (-16 to 34) and 29 (17 to 42); p<0.01). Similarly, LT induced secretion (-63 (-73 to -30)) was attenuated by VIPa (0.2 microg/kg/min) (-15 (-24 to -1); p<0.01) and totally reversed to normal levels by VIPa (2 microg/kg/min) (37 (28-56); p<0. 01 compared with LT and not significant compared with normal controls). STa induced secretion (-17 (-19 to -2)) was also reversed by VIPa (12 (9-23) and 14 (0-26); p<0.01). VIP plays an important role in CT, LT, and STa induced intestinal secretion and may be the final putative neurotransmitter in the pathophysiology of these toxins.


Deletion mapping the yeast TRP5 control region.
The yeast gene TRP5 is regulated by the general control system of amino acid biosynthesis. A TRP5-lacZ translational fusion was constructed in order to facilitate assay for TRP5 promoter function and regulation. The chromosomally integrated fusion was derepressed 4-5-fold by lysine limitation. Thus, the TRP5-lacZ fusion is regulated by general control. Deletions were constructed in vitro in the 5'-flanking region of cloned TRP5-lacZ. These deletions localized the promoter region to within 188 base pairs of the transcription start site. Two separable subregions of the promoter were localized by further deletion mapping. The boundaries of the promoter regions are approximately -188 to -114 and -91 to -29. The TATA box is contained within the downstream promoter region. Regulatory regions essential for general control overlap with these promoter elements. Each of two separable regulatory regions contains a copy of the TGACT repeat (Donahue, T. F., Daves, R. S., Lucchini, G., and Fink, G. R. (1983) Cell 32, 89-98) previously implicated in regulation of HIS4 by general control.


Metal-free nitrogen-containing carbon nanotubes prepared from triazole and tetrazole derivatives show high electrocatalytic activity towards the oxygen reduction reaction in alkaline media.
High-performance oxygen reduction reaction (ORR) catalysts based on metal-free nitrogen-containing precursors and carbon nanotubes are reported. The investigated systems allow the evaluation of the effect of nitrogen-containing groups towards ORR and the results show that the catalysts are compatible with the conditions encountered in alkaline fuel cells, exhibiting good catalytic activity and stability compared with conventional Pt/C electrocatalyst.


COVID-19, the Brain, and the Future: Is Infection by the Novel Coronavirus a Harbinger of Neurodegeneration?
The possible impact of viral infections on the development or pathogenesis of neurodegenerative disorders remains largely unknown. However, there have been reports associating the influenza virus pandemic and long-term infection with the Japanese encephalitis virus with the development of post-encephalitic Parkinsonism or von Economo's encephalitis. In the last couple of years, there has been a worldwide pandemic caused by the novel coronavirus or severe acute respiratory syndrome coronavirus (SARS-CoV)-2, which causes a severe acute respiratory syndrome and is found to be associated with symptoms or complications of the central nervous system. Its possible involvement with the central nervous system is in line with emerging scientific evidence stating that the human respiratory coronaviruses can enter the brain, infect neural cells, persist in the brain, and cause activation of myelin-reactive T cells. Currently, there is a dearth of scientific information on the acute or possible long-term impact of infection with SARS-CoV-2 on the development of dementia and/or neurodegenerative diseases. This is related to the fact that the virus is 'new,' and its effects on humans are still being studied. This narrative review examines the extant literature for understanding the impact of coronavirus infections on the brain as there is a possibility that coronavirus disease 2019 (COVID-19) could increase the risk for the development of neurodegenerative diseases or hasten their progression.


Exponential random graph models to evaluate the movement of backyard chickens after the avian influenza crisis in 2004-2005, Thailand.
The aim of this study was to use exponential random graph models (ERGMs) to explain networks of movement of backyard chickens in provinces which had been hotspots for avian influenza outbreaks in Thailand during 2004-2005. We used structured questionnaires to collect data for the period January to December 2009 from participants who were involved in the backyard chicken farming network in three avian influenza hotspots (Ratchaburi, Suphan Buri, and Nakhon Pathom provinces) in Thailand. From 557 questionnaires, we identified nodes, points of entry and exit from nodes, and activities relating to backyard chicken farming and movement of chickens, and generated ERGMs based on non-festive periods (Model 1) and the Chinese New Year period (Model 2). In Model 1, k-star (the central node is connected to k other nodes) connections were predominant (P < 0.001). In Model 2, the frequency of movement increased by 10.62 times, k-star connections were still predominant (P < 0.001), and the model was scale-free. Hubs were formed from owners/observers in the arenas/training fields, farmers who raised chickens for consumption only, and traders. In conclusion, our models indicated that, if avian influenza was introduced during non-festive periods, the authorities would need to regularly restrict the movement of chickens. However, during high-frequency periods of movement of backyard chickens, authorities would also need to focus on the network hubs. Our research can be used by the relevant authorities to improve control measures and reduce the risk or lessen the magnitude of disease spread during an avian influenza epidemic.


Effects of different physical factors on osteogenic differentiation.
Osteoblasts are essential for bone formation and can perceive external mechanical stimuli, which are translated into biochemical responses that ultimately alter cell phenotypes and respond to environmental stimuli, described as mechanical transduction. These cells actively participate in osteogenesis and the formation and mineralisation of the extracellular bone matrix. This review summarises the basic physiological and biological mechanisms of five different physical stimuli, i.e. light, electricity, magnetism, force and sound, to induce osteogenesis; further, it summarises the effects of changing culture conditions on the morphology, structure and function of osteoblasts. These findings may provide a theoretical basis for further studies on bone physiology and pathology at the cytological level and will be useful in the clinical application of bone formation and bone regeneration technology.


Telomere Length Dynamics and DNA Damage Responses Associated with Long-Duration Spaceflight.
Telomere length dynamics and DNA damage responses were assessed before, during, and after one-year or shorter duration missions aboard the International Space Station (ISS) in a comparatively large cohort of astronauts (n = 11). Although generally healthy individuals, astronauts tended to have significantly shorter telomeres and lower telomerase activity than age- and sex-matched ground controls before and after spaceflight. Although telomeres were longer during spaceflight irrespective of mission duration, telomere length shortened rapidly upon return to Earth, and overall astronauts had shorter telomeres after spaceflight than they did before; inter-individual differences were identified. During spaceflight, all crewmembers experienced oxidative stress, which positively correlated with telomere length dynamics. Significantly increased frequencies of chromosomal inversions were observed during and after spaceflight; changes in cell populations were also detected. We propose a telomeric adaptive response to chronic oxidative damage in extreme environments, whereby the telomerase-independent Alternative Lengthening of Telomeres (ALT) pathway is transiently activated in normal somatic cells.


Embracing diverse worldviews to share planet Earth.
Leading societies toward a more sustainable, equitably shared, and environmentally just future requires elevating and strengthening conversations on the nonmaterial and perhaps unquantifiable values of nonhuman nature to humanity. Debates among conservationists relating to the appropriateness of valuing ecosystems in terms of their human utility have eclipsed the more important and impactful task of expressing conservation concerns in terms that are meaningful to diverse stakeholders. We considered the wide global diversity of perspectives on the biosocial complex-the relationships and interactions between all living species on Earth-and argue that humanity's best chance for effective conservation is to take a pluralistic approach that engages seriously with the worldviews of all stakeholders. Many worldviews-particularly those in indigenous cultures-place a higher value on the spiritual and nonmaterial aspects than what is often represented by the discourse surrounding Western conservation policy. Alternative framings of the biosocial complex that recognize nature's intrinsic value can be powerful motivators for social change and for local-scale conservation efforts. At a national and international level, changing ethical framings of human relationships with nature have started influencing conceptions of human rights relating to the environment and of the rights of nature itself. This change has led to an increased role of the judiciary in promoting environmental sustainability and promoting justice for groups who are most often affected by environmental harms. We hope our essay will motivate the scientific community to change its own perception of what a sound and sustainable relationship between humanity and other species should be and will help citizens become active environmental subjects, connected to the ecosystems around them.


The prevalence and abundance of helminth parasites in stray dogs from the city of Queretaro in central Mexico.
The prevalence of helminth species in stray dogs, from the capital city of the state of Queretaro, was evaluated. A total of 378 dogs were captured and examined for the presence of helminths from January to December 2008. The results showed that 275 (72.8%) of examined dogs were infected with one or more helminth species. Single infections were observed in 139 (50.5%) of infected dogs and 136 (49.5%) harboured mixed infections. Out of the 378 dogs examined, 208 (55.2%) presented nematodes and 182 (48.1%) cestodes. The prevalences (confidence interval) and mean intensities of infection ( ± SD) of nematodes and cestodes encountered were: Ancylostoma caninum 42.9% (37.9-47.8) and 22.1 ( ± 34.3); Toxocara canis 15.1% (11.8-19.0) and 8.3 ( ± 15.0); Spirocerca lupi 4.5% (2.7-7.1) and 3.9 ( ± 4.8); Toxascaris leonina 2.3% (1.1-4.5) and 4.8 ( ± 3.5); Physaloptera praeputialis 1.9% (0.8-3.8) and 9.7 ( ± 14.9); Dirofilaria immitis 1.3% (0.4-3.1) and 5.6 ( ± 2.1); Oslerus osleri 0.3% (0.0-1.6) and 5 ( ± 0.0); Dipylidium caninum 44.9% (40.0-50.0) and 18.1 ( ± 27.7); Taenia spp. 6.9% (4.7-9.9) and 6.9 ( ± 7.1). There were no significant differences in prevalences observed either between female (68.5%) and male (76.8%) or between young (70.6%) and adult (74.2%) animals. No differences were observed in the ANOVA test for the mean intensity of infection of any of the parasites (P>0.05).


Health-related quality of life prospectively evaluated by the 8-item short form after endovascular repair versus open surgery for abdominal aortic aneurysms.
Open repair for infra-renal abdominal aortic and iliac artery aneurysms (AAAs) is a robust treatment. On the other hand, endovascular aneurysm repair (EVAR) has been widespread because of its less invasiveness. However, patients after EVAR frequently require postoperative radiographic examinations and may feel anxiety for their endoleaks. We prospectively evaluated Health-related Quality of Life of the patients with these two fashions using the 8-item Short Form (SF-8). From 2011 to 2013, 89 consecutive elective cases of AAAs were treated. They were prospectively divided into EVAR and open repair groups but not randomly. The exclusion criteria were as follows: perioperative status for other surgeries, infectious aneurysm, severely deteriorated conditions, and patients who cannot answer for these questionnaire or show their consent. The SF-8 questionnaire was completed through interviews preoperatively, and at 1, 3, 6, and 12 months after treatment. The SF-8 questionnaire was completed for 55 cases [EVAR group (ER): 25, open repair group (OR): 30]. There was no significant difference between these groups regarding patients' characteristics except congestive heart disease. The preoperative scores of the SF-8 were similar in both groups except physical function and social function, which were lower in ER (p < 0.05). There was no operative death in both groups. Operative duration and hospital stay in EVAR were significantly shorter than those in OR (p < 0.05). Follow-up rate at 1, 3, 6, and 12 months was 100, 100, 68.0, and 64.0% in ER, and 100, 90.0, 80.0, and 66.6% in OR, respectively. During follow-up, both groups had no AAAs associated death. Regarding changes of the SF-8 scales, there were some trends at physical component summary score (PCS) and mental component summary score (MCS) in ER. The PCS decreased at 1 month, gradually increased at 3 months, and levelled off until 12 months. The MCS increased at 1 and 3 months, but gradually went down and almost stayed at the same level as preoperative one at 12 months. In OR, PCS and MCS decreased at 1 month and after that increased gradually at 3 and 6 months, and stayed the same at 12 months. The MCS recovered to preoperative score earlier than the PCS. In this study, EVAR did not show any significant mental disturbance based on the SF-8 for 1-year comparing to open repair.


The relationship between palatability to invertebrates and the successional status of a plant.
The palatability of common plants from three stages of secondary sere have been assessed by a bioassay method. Foliage was exposed to five taxonomically very different herbivores (Agriolimax, Schistocera, Spodoptera, Myzus and Trialeurodes). Palatability was measured by foliage consumption or, for sap suckers, by survival and reporduction. The results of these experiments supported the predictions of Feeny's 'Apparency theory', but indicated considerable variations in palatability within plant communities and between herbivores.


Design and performance of a mass spectrometric facility for measuring helium isotopes in natural waters and for low-level tritium determination by the 3He ingrowth method.
The design and performance of a mass spectrometric system for the measurement of helium isotopes and very low tritium concentrations in natural waters are described and discussed in the light of analytical precision and accuracy. The system consists of a VG 3000 mass spectrometer with a fully automated inlet system for preparation and purification of the samples. Along with this mass spectrometric system, different custom-fabricated units are described, especially designed for taking samples, extracting helium or degassing tritium samples prior to the mass spectrometric analysis. The 3He detection limit of the system is close to 10(-16) cm3 STP corresponding to a tritium level of 0.003 TU for a 500 g water sample stored six months for 3He regrowth. A vertical oceanic tritium profile from the south hemisphere is presented as an illustration of the system's capability to detect very low tritium concentrations in the environment.


[The open observational study of aceclofenac and vinpocetine effectiveness and tolerability in treatment of patients with chronic cerebrovascular disease after COVID-19 (AQUA study)].
To estimate the frequency of long-COVID in patients with chronic cerebrovascular disease, to identify the risk factors for the development of this condition and to analyze effectiveness and tolerability of Vinpocetine and Aertal in treatment of this disease. The study included 97 patients (64.5±5.2 years), among which 42 were diagnosed with long-COVID. The effectiveness of treatment was analyzed with NRS-P, Post-COVID-19 Functional Status (PCFS), Global Rating of Change Scale (GROC). Predictors of long-COVID was female gender (p=0.022), severe COVID-19 (p=0.035), comorbidities: cardiovascular diseases (p=0.032), endocrinopathies (p=0.041), affective disorders (p=0.021). Significant changes in the functional status of patients were recorded after 20 days of treatment (PCFS), in pain after 10 days (NRS-P). The most pronounced clinical effect (PCFS) was obtained after 1 mth of therapy with vinpocetine and 20 days with aceclofenac (NRS-P). After 30 days 25/59.5% of patients noted a «pronounced» improvement in their own well-being (GROC) without the development of significant side effects. 43.3% of patients with chronic cerebrovascular disease and certain predictors develop long-COVID. Aceclofenac and vinpocetine are effective in relieving a number of symptoms of long-COVID, which requires further study.


Giant Inflammatory Cervical Ganglion Due to Ectopic Rib Head: Report of a Rare Diagnosis Mimicking a Cervical Schwannoma.
Cervical schwannomas may be common in patients with cervicobrachialgia. We report a case of an apparent C8 schwannoma in a 55-year-old female that was discovered to be an inflammatory enlarged cervical ganglion. Such a rare presentation may be explained by the particular conformation of the left C7-Th1 neuroforamen, compressed by an ectopic cranially located first rib head, which was visible only with a cervical computed tomography scan. No similar finding is reported in the literature, and this interesting case may provide new insight into the differential diagnosis of cervical spinal lesions.


A NPxY-independent beta5 integrin activation signal regulates phagocytosis of apoptotic cells.
Integrin receptors are heterodimeric transmembrane receptors with critical functions in cell adhesion and migration, cell cycle progression, differentiation, apoptosis, and phagocytosis of apoptotic cells. Integrins are activated by intracellular signaling that alter the binding affinity for extracellular ligands, so-called inside to outside signaling. A common element for integrin activation involves binding of the cytoskeletal protein talin, via its FERM domain, to a highly conserved NPxY motif in the beta chain cytoplasmic tails, which is involved in long-range conformation changes to the extracellular domain that impinges on ligand affinity. When the human beta-5 (beta5) integrin cDNA was expressed in alphav positive, beta5 and beta3 negative hamster CS-1 cells, it promoted NPxY-dependent adhesion to VTN-coated surfaces, phosphorylation of FAK, and concomitantly, beta5 integrin-EGFP protein was recruited into talin and paxillin-containing focal adhesions. Expression of a NPxY destabilizing beta5 mutant (Y750A) abrogated adhesion and beta5-Y750A-EGFP was excluded from focal adhesions at the tips of stress fibers. Surprisingly, expression of beta5 Y750A integrin had a potent gain-of-function effect on apoptotic cell phagocytosis, and further, a beta5-Y750A-EGFP fusion integrin readily bound MFG-E8-coated 10 microm diameter microspheres developed as apoptotic cell mimetics. The critical sequences in beta5 integrin were mapped to a YEMAS motif just proximal to the NPxY motif. Our studies suggest that the phagocytic function of beta5 integrin is regulated by an unconventional NPxY-talin-independent activation signal and argue for the existence of molecular switches in the beta5 cytoplasmic tail for adhesion and phagocytosis.


Potent α-amylase inhibitors and radical (DPPH and ABTS) scavengers based on benzofuran-2-yl(phenyl)methanone derivatives: Syntheses, in vitro, kinetics, and in silico studies.
Thirty benzofuran-2-yl(phenyl)methanones 1-30 were synthesized and characterized their structures by spectroscopic techniques. Substituted phenacyl bromide and different derivatives of 2-hydroxy-benzaldehyde treated in the presence of anhydrous K2CO3 in acetonitrile at room temperature to afford the desired benzofurans 1-30. All compounds were screened for their in vitro α-amylase inhibitory and radical scavenging (DPPH and ABTS) activities. Results revealed that para substituted compounds were found to be more active than the others with IC50 values ranges for α-amylase inhibition (IC50 = 18.04-48.33 µM), DPPH (IC50 = 16.04-32.33 µM) and ABTS (IC50 = 16.99-33.01 µM) radical scavenging activities. Activities results were compared with the standards acarbose (IC50 = 16.08 ± 0.07 µM) for α-amylase, ascorbic acid (IC50 = 15.08 ± 0.03 and 15.09 ± 0.17 µM) for DPPH and ABTS radical scavenging activities, respectively. Kinetic studies predicted that all compounds followed non-competitive mechanism of inhibition. Molecular docking results showed good protein-ligand interactions profile against the corresponding target. To the best of our knowledge, out of thirty molecules, ten compounds 18-20, 22, and 25-30 were structurally new.


Cutis laxa: intersection of elastic fiber biogenesis, TGFβ signaling, the secretory pathway and metabolism.
Cutis laxa (CL), a disease characterized by redundant and inelastic skin, displays extensive locus heterogeneity. Together with geroderma osteodysplasticum and arterial tortuosity syndrome, which show phenotypic overlap with CL, eleven CL-related genes have been identified to date, which encode proteins within 3 groups. Elastin, fibulin-4, fibulin-5 and latent transforming growth factor-β-binding protein 4 are secreted proteins which form elastic fibers and are involved in the sequestration and subsequent activation of transforming growth factor-β (TGFβ). Proteins within the second group, localized to the secretory pathway, perform transport and membrane trafficking functions necessary for the modification and secretion of elastic fiber components. Key proteins include a subunit of the vacuolar-type proton pump, which ensures the efficient secretion of tropoelastin, the precursor or elastin. A copper transporter is required for the activity of lysyl oxidases, which crosslink collagen and elastin. A Rab6-interacting goglin recruits kinesin motors to Golgi-vesicles facilitating the transport from the Golgi to the plasma membrane. The Rab and Ras interactor 2 regulates the activity of Rab5, a small guanosine triphosphatase essential for the endocytosis of various cell surface receptors, including integrins. Proteins of the third group related to CL perform metabolic functions within the mitochondria, inhibiting the accumulation of reactive oxygen species. Two of these proteins catalyze subsequent steps in the conversion of glutamate to proline. The third transports dehydroascorbate into mitochondria. Recent studies on CL-related proteins highlight the intricate connections among membrane trafficking, metabolism, extracellular matrix assembly, and TGFβ signaling.


Effects of a family intervention in reducing HIV risk behaviors among high-risk Hispanic adolescents: a randomized controlled trial.
To determine the efficacy of a family intervention in reducing human immunodeficiency virus (HIV) risk behaviors among Hispanic delinquent adolescents. Randomized controlled trial. Miami-Dade County Public School System and Miami-Dade County's Department of Juvenile Services, Florida. A total of 242 Hispanic delinquent youth aged 12 to 17 years and their primary caregivers completed outcome assessments at baseline and 3 months after intervention. Participants were randomized to either Familias Unidas (120 participants), a Hispanic-specific, family intervention designed to reduce HIV risk behaviors among Hispanic youth, or a community practice control condition (122 participants). Self-reported measures included unprotected sexual behavior, engaging in sex while under the influence of alcohol and/or drugs, number of sexual partners, and incidence of sexually transmitted diseases. Family functioning (eg, parent-adolescent communication, positive parenting, and parental monitoring) was also assessed via self-report measures. Compared with community practice, Familias Unidas was efficacious in increasing condom use during vaginal and anal sex during the past 90 days, reducing the number of days adolescents were under the influence of drugs or alcohol and had sex without a condom, reducing sexual partners, and preventing unprotected anal sex at the last sexual intercourse. Familias Unidas was also efficacious, relative to community practice, in increasing family functioning and most notably in increasing parent-adolescent communication and positive parenting. These results suggest that culturally tailored, family-centered prevention interventions may be appropriate and efficacious in reducing HIV risk behaviors among Hispanic delinquent adolescents. clinicaltrials.gov Identifier: NCT01257022.


Characterization of dissolved organic matter using high-performance liquid chromatography (HPLC)-size exclusion chromatography (SEC) with a multiple wavelength absorbance detector.
High-performance liquid chromatography-size exclusion chromatography (HPLC-SEC) coupled with a multiple wavelength absorbance detector (200-445 nm) was used in this study to investigate the apparent molecular weight (AMW) distributions of dissolved organic matter (DOM). Standard DOM, namely humic acid, fulvic acid and hydrophilic acid, from the Suwannee River were tested to ascertain the performance and sensitivity of the method. In addition to four compounds groups: humic substances (Peak 1, AMW 16 kD), fulvic acids (Peak 2, AMW 11 kD), low AMW acids (Peak 3, AMW 5 kD), and low AMW neutral and amphiphilic molecules, proteins and their amino acid building blocks (Peak 4, AMW 3 kD), an new group that appears to include low AMW, 6-10 kD, humic substances was found based on investigating the spectra at various elution times. The spectroscopic parameter S(>365) (slope at wavelengths >365 nm) was determined to be a good predictor of the AMW of the DOM. The detector wavelength played an important role in evaluating the AMW distribution. For some fractions, such as the humic and low AMW non-aromatic substances, the error in measurement was ± 30% as determined by two-dimensional chromatograms detected at an artificially selected wavelength. HPLC-SEC with multiple wavelength absorbance detection was found to be a useful technique for DOM characterization. It characterized the AMW distributions of DOM more accurately and provided additional, potentially important information concerning the properties of DOM with varying AMWs.


Ephedra herb reduces adriamycin-induced testicular toxicity by upregulating the gonadotropin-releasing hormone signalling pathway.
We investigated the protective effects of ephedra herb (HEPH) on adriamycin-induced testicular toxicity in rats and explored the potential mechanisms underlying these effects. A rat model of adriamycin injury was established, and sperm motility-related indicator and oxidative stress levels in the testis were evaluated. Serum levels of sex hormones and levels of testicular cell apoptosis were detected by enzyme-linked immunosorbent assay and flow cytometry, respectively. Western blotting (WB), immunofluorescence analyses, and reverse transcription-polymerase chain reaction (RT-PCR) were performed to evaluate the gonadotropin-releasing hormone (GnRH) signalling pathway- and meiosis-related genes and proteins. In subsequent in vitro experiments, adriamycin was used to stimulate GC-1 cells, which were treated with HEPH, ephedrine, or pseudoephedrine. Cell viability was assessed using flow cytometry to detect apoptosis and reactive oxygen species, whereas the GnRH signalling pathway and levels of meiosis-related genes and proteins were evaluated by InCell WB, a high-content imaging system, and RT-PCR. Per in vivo experiments, HEPH restored testicular weight and function, sperm characteristics, serum and tissue hormonal levels, and antioxidant defences and significantly activated the GnRH signalling pathway- and meiosis-related protein levels. All protective effects of HEPH against adriamycin-induced injury were antagonised by the GnRH antagonist cetrorelix. In vitro, HEPH, ephedrine, and pseudoephedrine significantly reduced adriamycin-induced GC-1 cell apoptosis and reactive oxygen species levels and increased the expression of GnRH signalling pathway- and meiosis-related proteins. The effect of pseudoephedrine was greater than that of ephedrine, and these findings may be an important basis for understanding the effects of HEPH.


[Biologically active azomethines. Delépine reaction with 1-chloromethylisatin; preparation of some 1-aminomethylisatinazomethines (author's transl)].
The authors describe the synthesis of I-aminomethylisatin (3) from [I-chloromethylisatin] (1) by means of the Delépine reaction. On condensation with aromatic aldehydes, 3 yields the azomethines 5--7. The azomethine 5 is converted into the corresponding thiosemicarbazone 9. Testing for mitodepressive activity showed that the compounds 5--7 are active. On testing in vitro for tuberculostatic effects, the compound 9 proved exceptionally potent.


Anatomic and functional recovery of the fovea after foveal translocation surgery without large retinotomy and simultaneous excision of a neovascular membrane.
To document the anatomic and functional recovery of the fovea after foveal translocation surgery with scleral shortening and simultaneous excision of a neovascular membrane in a patient with age-related macular degeneration. Case report. The visual acuity of a 54-year-old woman with age-related macular degeneration improved from 20/200 to 20/50 after excision of subretinal neovascular membrane and foveal translocation surgery in the right eye. Fixation shifted inferonasally 0.6 disk diameters, corresponding to the direction of foveal translocation, as shown by scanning laser ophthalmoscope microperimetry. Postoperative optical coherence tomography through fixation disclosed normal foveal concavity and intact retinal pigment epithelium. Anatomic and functional recovery of the fovea was confirmed in a patient with age-related macular degeneration after foveal translocation surgery with scleral shortening and simultaneous excision of a neovascular membrane.


Correlation between the triggering of proliferation and the potentiation of NK activity induced by protein A in human lymphocytes.
Various preparations of Staphylococci protein A (SpA) obtained either from strain Cowan-1 or strain A676 and two SpA low molecular fragments (AB and B) were tested for their mitogenic and NK-stimulating activity on human peripheral blood lymphocytes. Though all 4 preparations of SpA and both of its fragments were able to react with human IgG, apparently with both Fab and Fc sites of IgG, only the SpA preparations derived from A676 strain triggered the proliferation and potentiated the NK-activity of treated cells. The parallelism between the mitogenic and NK-stimulating activities of SpA suggests that both activities might be under the control of the same portion of the SpA molecule located in the non-immunoglobulin binding region of the molecule.


Molecular determinants for nuclear receptors selectivity: chemometric analysis, dockings and site-directed mutagenesis of dual peroxisome proliferator-activated receptors α/γ agonists.
A series of previously synthesized chiral derivatives of clofibric and phenylacetic acids, acting as dual agonists towards the peroxisome proliferator-activated receptors (PPARs) α and γ, was taken into account, and the efficacy of these compounds was analyzed by means of 2D-, 3D-QSAR and docking studies with the goal to gain deeper insights into the three-dimensional determinants governing ligands selectivity for PPARs. By multiregressional analysis a correlation between the lipophilicity and PPARα activity was found, whereas for PPARγ the correlation was achieved once efficacy was related to the presence of polar groups on agonists scaffold. Docking of these compounds further corroborated this hypothesis, and then provided a valid support for subsequent chemometric analysis and pharmacophore models development for both receptors subtypes. Computational results suggested site directed mutagenesis experiments which confirmed the importance of amino acid residues in PPAR activity, allowing the identification of critical hotspots most likely taking over PPARs selectivity.


Probe-based confocal laser endomicroscopy: a new method for quantitative analysis of pit structure in healthy and Crohn's disease patients.
Probe-based confocal laser endomicroscopy enables microscopic examination of the digestive mucosa. (1) To identify and validate quantitative endomicroscopic criteria for evaluation of the colonic mucosa and (2) to compare these criteria between healthy and Crohn's disease patients in clinical remission. Six healthy controls and ten Crohn's disease patients in clinical remission were included in this prospective study. Methylene blue-stained biopsies of the right colon and corresponding endomicroscopic images were analyzed. Major axis, minor axis, and major axis/minor axis ratio of crypt lumens were quantified. Quantitative assessment was performed on 21 ± 4 crypt lumens per patient. Major axis/minor axis ratio values measured with endomicroscopy or methylene blue-stained biopsies were linearly correlated (r=0.63, p=0.01). All macroscopically inflamed mucosa had values of major axis/minor axis ratio higher than the median of controls. Interestingly, 50% (3/6) of Crohn's disease patients with macroscopically normal mucosa had also a higher ratio than pooled controls. Histological analysis showed that 6/7 patients with major axis/minor axis ratio superior to 1.7 had microscopic inflammation. Probe-based confocal laser endomicroscopy allows quantitative analysis of colonic pit structure. Endomicroscopic analysis of major axis/minor axis ratio allows the detection of microscopic residual inflammation with greater accuracy than standard endoscopy in Crohn's disease patients in clinical remission.


Functional expression system for cytochrome P450 genes using the reductase domain of self-sufficient P450RhF from Rhodococcus sp. NCIMB 9784.
Cytochrome P450RhF from Rhodococcus sp. NCIMB 9784 is a self-sufficient P450 monooxygenase. We report here a simple system for the functional expression of various P450 genes using the reductase domain of this P450RhF, which comprises flavin mononucleotide- and nicotinamide adenine dinucleotide phosphate binding motifs and a [2Fe2S] ferredoxin-like center. Vector pRED was constructed, which carried the T7 promoter, cloning sites for a P450, a linker sequence, and the P450RhF reductase domain, in this order. The known P450 genes, encoding P450cam from Pseudomonas putida (CYP101A) and P450bzo from an environmental metagenome library (CYP203A), were expressed on vector pRED as soluble fusion enzymes with their natural spectral features in Escherichia coli. These E. coli cells expressing the P450cam and P450bzo genes could convert (+)-camphor and 4-hydroxybenzoate into 5-exo-hydroxycamphor and protocatechuate (3,4-dihydroxybenzoate), respectively (the expected products). Using this system, we also succeeded in directly identifying the function of P450 CYP153A as alkane 1-monooxygenase for the first time, i.e., E. coli cells expressing a P450 CYP153A gene named P450balk, which was isolated form Alcanivorax borkumensis SK2, converted octane into 1-octanol with high efficiency (800 mg/l). The system presented here may be applicable to the functional identification of a wide variety of bacterial cytochromes P450.


Effect of vein-bionic surface textures on the tribological behavior of cylindrical roller thrust bearing under starved lubrication.
To reveal the effect of vein-bionic surface textures on the tribological behavior of cylindrical roller thrust bearings (CRTBs) under starved lubrication, six kinds of leaves (Forsythia, Clausena lansiu, Ash, Purple leaf plum, Pipal and Apricot) were chose and their simplified patterns were fabricated on the shaft washers of CRTBs using laser surface texturing. The coefficients of friction (COFs) of vein-bionic textured bearings were measured using a vertical universal wear test rig. Their mass losses and worn surfaces were also characterized. The results show that: There is important influence of the symmetry of vein-bionic textures and the number of secondary veins on the friction and wear properties of vein-bionic textured CRTBs under starved lubrication. Compared to the smooth group, the COFs and mass losses of vein-bionic textured bearings are all reduced. Among all groups, the tribological performance of bearings with a pattern inspired from Ash is the best. Its wear loss is reduced by 16.23% and its COF is reduced by 15.79%. This work would provide a valuable reference for the raceway design and optimization of roller rolling element bearings.


Wolff Parkinson white pattern in Danon disease: When preexcitation is not what it seems.
Danondisease is a rare genetic disorder with an X-linked dominant inheritance affecting both skeletal and cardiac muscle. Its characteristic cardiac phenotype consists on a severe, non-obstructive and concentric hypertrophic cardiomyopathy (HCM) usually associated with a Wolff-Parkinson-White (WPW) type preexcitation pattern. Whether this corresponds to the presence of an AV or another type of accessory pathways, such as fasciculoventricular pathways (FVP) remains controversial in the literature. However, we describe the case of a teenager with Danon disease and preexcitation who develops a first degree AV block without any change in his QRS morphology, fact that favors the hypothesis of the presence of a FVP. This finding has important clinical implications in the management and prognosis of these complex patients. The absence of an AV accessory pathway decreases their risk of potential SCD in the context of a fast atrial arrhythmia and their chances of having a reentrant AV tachycardia.


11 Long noncoding RNA UCA1 functions as miR-135a sponge to promote the epithelial to mesenchymal transition in glioma.
The dysregulation of long noncoding (lncRNA) UCA1 may play an important role in tumor progression. However, the function in gliomas is unclear. Therefore, this experiment was designed to explore the pathogenesis of glioma based on lncRNA UCA1. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of lncRNA UCA1, miR-135a, and HOXD9 in gliomas tissues. The effect of lncRNA UCA1 and miR-135a on tumor cell proliferation and migration invasiveness was examined by CCK-8 and transwell assays. Target gene prediction and screening, luciferase reporter assay were used to verify downstream target genes of lncRNA UCA1. Expression of E-cadherin, N-cadherin, vimentin, and HOXD9 was detected by RT-qPCR and Western blotting. The tumor changes in mice were detected by in vivo experiments in nude mice. lncRNA UCA1 was highly expressed in glioma tissues and cell lines. lncRNA UCA1 expression was associated with significantly poor overall survival in gliomas. Moreover, lncRNA UCA1 significantly enhanced cell proliferation and migration, and promoted the occurrence of EMT. In addition, lncRNA UCA1 promoted the development of EMT by positively regulating HOXD9 expression as a miR-135a sponge. In vivo experiments indicated that UCA1 exerted its biological functions by modulating miR-135a and HOXD9. In conclusion, lncRNA UCA1 can induce the activation of HOXD9 by inhibiting the expression of miR-135a and promote the occurrence of EMT in glioma.


Systematic double-catheter epidural venography in the diagnosis of lumbar disc herniation.
In epidural venography systematic use of two catheters and simultaneous injection of contrast medium does improve the opacification of the entire lumbar epidural venous system and the reliability of the X-rays. The combined catheterization offers the possibility of over 20 different procedures. The position of the catheters can be chosen according to diagnostic problems or technical catheterization problems during the examination. The method should be regarded as extremely reliable in diagnosing lumbar disc herniation. A small straight vein, which has not been described before, is often shown in the middle of the vertebral canal. Metrizamide may be used as a contrast agent.


Tuberculum and diaphragma sella meningioma--surgical technique and visual outcome in a series of 20 cases operated over a 2.5-year period.
A retrospective analysis of 20 cases of tuberculum sella meningioma with emphasis on the surgical technique and visual outcome. Between 2003 and 2006 twenty patients with tuberculum and diaphragma sella meningioma were treated at the Tel Aviv medical center. There were 17 females and 3 males. The age range was 28-83. Most patients presented with visual deterioration. Surgery was performed using the subfrontal approach. The visual function before and after surgery was evaluated as the main outcome parameter of the surgical treatment of these tumours. In 16 patients complete tumour resection was achieved and in 4 subtotal removal was performed. Visual acuity improved in 32% of the eyes and deterioration was observed in two eyes (5%). Visual field improved in 28% of the eyes and deteriorated in 14%. There was no complete vision loss as a result of surgery. There was no mortality in our series. Tuberculum and diaphragma sella meningioma can be safely resected using the subfrontal approach with preservation and even improvement of visual function after surgery. Early surgery with better pre-operation visual function and smaller tumour size were associated with a better outcome.


Diet composition has a differential effect on immune tolerance in insect larvae exposed to Mesorhabditis belari, Enterobacter hormaechei and its metabolites.
In insects, diet plays an important role in growth and development. Insects can vary their diet composition based on their physiological needs. In this study we tested the influence of diet composition involving varying concentrations of macronutrients and zinc on the immune-tolerance following parasite and pathogen exposure in Spodoptera litura larvae. We also tested the insecticidal potential of Mesorhabditis belari, Enterobacter hormaechei and its secondary metabolites on Spodoptera litura larvae. The results shows macronutrient composition does not directly affect the larval tolerance to nematode infection. However, Zinc supplemented diet improved the immune tolerance. While larvae exposed to bacterial infection performed better on carbohydrate rich diet. Secondary metabolites from bacteria produced an immune response in dose dependent mortality. The study shows that the larvae maintained on different diet composition show varied immune tolerance which is based on the type of infection.


Contribution of conjugated linoleic acid to the suppression of inducible nitric oxide synthase expression and transcription factor activation in stimulated mouse mesangial cells.
That both infiltrating macrophages and resident mesangial cells express inducible nitric oxide synthase (iNOS) and produce nitric oxide (NO) excessively is crucial to the progress of glomerulonephritis. Although several reports have mentioned the protective impacts of conjugated linoleic acid (CLA) in stimulated macrophages, the role of CLA in glomerular mesangial cells is unknown. The aim of the present study was to explore the ability of CLA to regulate iNOS expression and NO production in stimulated glomerular mesangial cells. Additionally, we evaluated the effect of CLA on activation of transcription factors which mediate iNOS expression. Exogenous CLA dose-dependently diminished iNOS mRNA and protein expression as well as NO production in lipopolysaccharide (LPS) plus interferon-gamma (IFN-gamma)-stimulated SV-40-transformed mouse mesangial cells. Electrophoretic mobility shift assay experiments demonstrated that CLA (100 microM) dramatically reduced activation of nuclear factor-kappaB (NF-kappaB), activator protein-1 (AP-1) and cAMP response element binding protein (CREB) induced by LPS/IFN-gamma. Moreover, addition of 100 microM CLA significantly diminished LPS-IFN-gamma-induced protein degradation of inhibitor kappaB-alpha (IkappaB-alpha) and the protein expression of phosphorylated IkappaB-alpha in the cytosolic fraction as well as nuclear p65 expression (P < 0.05). In summary, inhibition of NF-kappaB, AP-1 and CREB activation by CLA may be associated with the molecular basis for which CLA suppresses iNOS expression and NO production in stimulated mesangial cells.


Robot Helps When Robot Fits: Examining the Role of Baby Robots in Fertility Promotion.
Considering China is facing a precipitous decline in its population, there is an emerging trend of developing baby robots to encourage people's willingness to become "parents". Based on the decomposed theory of planned behavior and the theory of uncanny valley, this study empirically investigated whether a baby robot could perform as a prominent antecedent of fertility intention in China, and how this relates to its visual appearance. Consistent with prior research, the current study used a between-subjects design to show (1) a baby robot could significantly improve people's fertility attitude through temporal visual stimulation; (2) fertility attitude, subjective norms from peers, and perceived behavioral control of finance could significantly contribute to fertility intention. Theoretical contributions and implications are discussed in this study.


Management of misangulated implants for a maxillary overdenture with spherical abutments: a clinical report.
Misangulated and malpositioned implants pose a significant challenge for the prosthodontic treatment of edentulous patients. Most reports of maxillary overdenture patients have described the use of a bar to splint malaligned implants, followed by successful fabrication of the prosthesis. Few reports have discussed the use of individual abutments in such situations. This clinical report describes the successful use of spherical/ball abutments for the management of 4 malaligned implants in the edentulous maxilla for an overdenture. The rationale and technique for the use of spherical abutments for overdenture fabrication in such situations are described.


Fumonisins: current research trends in developmental toxicology.
Fumonisin B1 (FB1) is a mycotoxin produced byFusarium verticillioides that is found in maize and maize-based foods. Reproductive studies in CD1 mice, rats and rabbits initially found no evidence that fumonisins are teratogenic. However, more recent findings suggest that they might increase the risk of neural tube defects (NTDs) in populations consuming large amounts of fumonisin-contaminated corn. When ≥15 mg/kg body weight fumonisin B1 (FB1) was given to pregnant LM/Bc mice by intraperitoneal (ip) injection, all litters were positive for NTDs. To determine if NTD induction is unique to the inbred LM/Bc mouse strain, NTD induction in LM/Bc and CD1 mice was compared: (a) in a study in whichF. verticillioides culture material providing ≤150 ppm FB1 was fed to female mice before and during gestation, and (b) in a study in which FB1 was given by ip injection to CD1 dams on gestation days 7 and 8, the critical time for NTD development. In the feeding study, one of five LM/Bc litters from dams fed the 150 ppm FB1 diet was positive for NTDs whereas no NTDs were found in the CD1 litters. In the ip injection study, 40% of the litters at the highest dose tested, 45 mg/kg body weight, were positive for NTDs and one of nine low-dose (15 mg/kg body weight) litters was also positive. Thus, FB1 induced NTDs in both LM/Bc and CD1 mice although the latter strain appears less sensitive. Comparative investigations using these strains will be useful for elucidating the mechanisms underlying fumonisin-induced NTDs in mice and determining the suitability of mouse models for studying the relationships between fumonisins and NTDs in humans.


Multidisciplinary physician survey assessing knowledge of the female athlete triad and relative energy deficiency in sport.
Short and long-term health consequences surrounding Low Energy Availability can be mitigated by recognizing the risk factors and making early diagnosis of the Female Athlete Triad (Triad) and Relative Energy Deficiency in Sport (RED-S). While awareness of the Triad among physicians and allied health professionals has been studied, there are very few studies that assess physician awareness of both the Triad and RED-S. Our study assesses Low Energy Availability, the Triad, and RED-S knowledge with an electronic survey, educational handout, and follow up survey among physicians across multiple specialties at a single academic institution. Among 161 respondents, respective Triad and RED-S awareness among surveyed specialties was highest in Orthopedic surgeons (100%, 100%), followed by Physical Medicine & Rehabilitation (70%, 53%), Family Medicine (67%, 48%), Internal Medicine (54%, 36%), Obstetrics and Gynecology (46%, 32%), Pediatrics (45%, 29%), Endocrinology (33%, 33%), and Other (33%, 33%). Comparing the initial survey results to the follow-up survey results, there was an increase from 37 to 72% of physicians who correctly identified that the presence of low BMI or recent weight loss is not a required component of the Triad or RED-S. Both the initial and follow-up survey revealed a continued misperception surrounding the use of hormonal contraception to resume menstrual cycles, with 33% of physicians on initial survey and 44% of physicians on follow-up survey incorrectly answering that question. Multidisciplinary physicians have various levels of knowledge surrounding the Triad and RED-S, and there is a need for improved physician awareness, diagnosis, and treatment of the Triad and RED-S. Misperceptions exist surrounding the role of hormonal contraception in female athletes with the Triad and RED-S to regain and regulate menses.


Cell polarity: centrosomes release signals for polarization.
New findings reveal that, in Caenorhabditis elegans embryos, the centrosome provides signals that induce cell polarization, independently of its function as the microtubule-organizing center.


Mathematical expression of the effects of changes in body size on pulmonary function and structure.
The biological meaning of the mass coefficient "a" and mass exponent "b" of the power function relating body mass "M" and a morphometric or physiologic variable "y" is discussed (y = aMb). The mass coefficient represents the effect of intensive or qualitative factors on the considered function or structure. The theoretical mass exponent is a criterion for the constancy of the mass coefficient and the qualitative sameness of the compared animals. The Theory of Homomorphism shows that the power function is a mathematical-physical model for analyzing structure and function in animals of different size.


Mechanical regulation of histone modifications and cell plasticity.
Cell plasticity is important in development and tissue remodeling. Cells can sense physical and chemical cues from their local microenvironment and transduce the signals into the nucleus to regulate the epigenetic state and gene expression, resulting in a change in cell phenotype. In this review, we highlight the role of mechanical cues in regulating stem cell differentiation and cell reprogramming through the modulation of histone modifications. The effects of various mechanical cues, including matrix stiffness, mechanical stretch, and shear stress, on cell fate during tissue regeneration and remodeling will be discussed. Taken together, recent work demonstrates that the alterations in histone modifications by mechanical stimuli can facilitate epigenetic changes during cell phenotypic switching, which has potential applications in the development of biomaterials and bioreactors for cell engineering.


Potential anticancer activity and mechanism of action of nanoformulated curcumin in experimental Ehrlich ascites carcinoma-bearing animals.
To study the potential use of nanoformulations of curcumin (CUR); CUR-loaded pluronic nanomicelles (CURnp1), and CUR-loaded poly(lactic-co-glycolic acid) nanoparticles (CURnp2) as antitumor agents in Ehrlich ascites carcinoma-bearing animals, and their mechanism of action. CURnp1 and CURnp2 were prepared, characterized and tested against Ehrlich ascites carcinoma-bearing mice. Superoxide dismutase, catalase (CAT), glutathione, malondialdehyde, histopathological, immunohistochemical studies, cell cycle and caspase-3 were investigated. CURnp1 destroyed tumors via increasing superoxide dismutase, CAT and glutathione, decreasing malondialdehyde through inducing apoptosis by decreasing Ki-67 and Bcl2 expression and activating caspase-3 leading to inhibition of proliferation and cell cycle arrest with progression at G1/S phase. The study demonstrated for the first time superiority of CURnp1 over native CUR and CURnp2 as anticancer agents.


Bioconversion of ethyl (R)-4-cyano-3-hydroxybutyate into (R)-ethyl-3-hydroxyglutarate via an indirect pathway by Rhodococcus boritolerans.
(R)-Ethyl-3-hydroxyglutarate, (R)-3, is an intermediate in the synthesis of the statin side chain. Here, a new two-step, indirect biotransformation pathway involving the formation of ethyl (R)-4-carbamoyl-3-hydroxybutanoate, (R)-2, as an intermediate for (R)-3 production was developed using Rhodococcus boritolerans with ethyl (R)-4-cyano-3-hydroxybutyate, (R)-1, as substrate. Maximum conversion was with 10 g (R)-1/l, 7 g cells/l (dry wt), pH 7.5 and 25°C. A yield of 98 ± 0.5% (w/w) was attained within 8 h.


Venous thromboembolism during pregnancy and postpartum period.
Venous thromboembolism (VTE) is one of the leading causes of maternal mortality. Rates of VTE during pregnancy and the postpartum period have not decreased over the past two decades and pregnancyassociated VTE continues to pose a significant health challenge. Pregnant and postpartum women are at a higher risk for VTE owing to many factors. There are hormonally mediated and pregnancy-specific alterations of coagulation that favor thrombosis, including increased production of clotting factors. There are physiologic and anatomic mechanisms that also contribute, including a decreased rate of venous blood flow from the lower extemities as pregnancy progresses. Cesarean delivery also introduces VTE risk. In addition, studies have demonstrated that pregnancy-associated complications such as pre-eclampsia or peri-partum infections are associated with increased VTE rates. In this review, we discuss the recent epidemiological studies, pathogenesis, risk factors and clinical presentation as well as therapeutic options for VTE during pregnancy and the postpartum period. We also provide proposed diagnostic algorithms for diagnosis and management of VTE during pregnancy and the postpartum period based on updated evidence. Finally, we highlight knowledge gaps to guide future research.


[Interest of a sterilised anti-burning gel in radiation dermatitis: results of a comparative study].
Trial objectives were to assess effectiveness and tolerance of sterilized Avène thermal spring water anti burning gel (ATSW gel) in prevention of radiation dermatitis in adults irradiated (6 weeks) for breast (n=61) or head and neck (n=8) cancer. Patients included in this open labelled, 2 parallel groups, multicentric study, were randomly assigned to apply five times daily for ten weeks either the Avène spring water gel (n=35) or trolamine cream (n=34). The median of emergence of the first objective radiation dermatitis signs was 31 days in the ATSW gel group and 29 days in the control group (p=0,924). The median incidence for pruritus in patients of the ETA gel group was 46 days versus 27 days (p=0,028) and 44 days versus 24 days for pain (p=0,426). Global efficacy was <<very good>> in 46,7 % of patients of the ETA gel group versus 17,2 % (p=0,029) and tolerance was <<very good>> in 65,5 % of the ETA gel group versus 40,7 % (p=0,107). No radionecrosis was observed. In conclusion, the efficacy of the Avène spring water gel was similar to the control product in prophylaxis of radiation dermatitis. Tolerance was better and the pruritus was significantly more delayed in patients who applied the Avène spring water gel than in controls.


Nationwide temporal trends in incidence of hospitalization and surgical intestinal resection in pediatric inflammatory bowel diseases in the United States from 1997 to 2009.
Data are limited on temporal trends in outcomes of hospitalization and surgery in pediatric Crohn's disease (CD) and ulcerative colitis (UC). Thus, we evaluated the U.S. nationwide temporal trends for incidence of hospitalization and intestinal resection along with associated resource utilization. We used the Kids' Inpatient Database (1997, 2000, 2003, 2006, and 2009) to identify all admissions for children aged 18 years or younger with a primary CD (International Classification of Diseases, Ninth Revision [ICD-9]: 555.X) or UC (ICD-9: 556.X) diagnosis or a secondary CD or UC diagnosis and procedural code of intestinal resection. Poisson regression analysis was performed to evaluate time trends in the incidence of hospitalization, intestinal resection, and hospital resource utilization. The annual incidence of hospitalization was 5.7 and 3.5 per 100,000 children for CD and UC, respectively, with significant increases over time for CD (annual percent increase [API], 3.8%; 95% confidence interval [CI], 3.0%-4.5%) and UC (API, 4.5%; 95% CI, 4.3%-4.7%). Median hospital days per hospitalization for CD and UC remained stable, whereas median charge per hospitalization increased for CD (API, 4.1%; 95% CI, 2.6%-5.6%) and UC (API, 4.7%; 95% CI, 3.5%-5.9%). The annual incidence of intestinal resection remained stable for UC at 0.6 per 100,000 children but climbed for CD (API, 2.1%; 95% CI, 0.1-4.2). The annual incidence of hospitalization is climbing in pediatric inflammatory bowel diseases, accompanied by rising intestinal resection rates for CD and stable colectomy rates for UC. With escalating resource utilization, the economic and health burden of pediatric inflammatory bowel diseases is substantial.


Locally advanced paraganglioma of the urinary bladder: a case report.
Paraganglioma of the urinary bladder is a rare tumor. Herein we sought to describe a case of locally advanced paraganglioma of the urinary bladder managed by partial cystectomy and extended pelvic lymph node dissection. The case of a 43-year old Haitian male with locally advanced paraganglioma of the urinary bladder is presented in detail. Through surgical extirpation, our patient was rendered disease-free. Eighteen months later the patient is doing well without symptoms but is noted to have subcentimeter bilateral pulmonary nodules and retroperitoneal lymph nodes. No further therapy has been initiated at this time. Patients with localized tumors have an extremely favorable prognosis and may be managed by less aggressive modalities, whereas patients with metastatic disease have a significant reduced survival rate despite aggressive treatment.


Electronic Vaping Product Use among Young Adults Who Receive Care at a Major Medical Institution.
Background: National estimates of electronic vaping product (EVP) use exist, but little is known about young adult EVP users who interact with the healthcare setting. Methods: Cross-sectional survey of 18-25 year olds receiving care in our ambulatory medical practice. Population differences were evaluated with the chi square test reporting unadjusted odds ratios (ORs). Results: Response rate was 16.6% (n = 1,017/6,119). The prevalence of ever EVP use was 46.0% of whom 13.9% used every day. Each additional day of alcohol use (past 30 days) was associated with increased odds of being an EVP user (OR = 1.06, 95% CI 1.02-1.09), and cannabis use (past 30 days) was associated with a higher odds of being an EVP user compared to non-cannabis users (OR = 40.0, 95% CI 17.4 - 111.8). Observing a biological parent (OR = 2.89, 95% CI 1.98-4.24), step parent (OR = 2.03, 95% CI 1.02-4.19) and full sibling (OR = 2.31, 95% CI 1.78-3.00) using inhaled substances (past 30 days) was associated with increased odds of being an ever EVP user. Ever EVP users had lower odds than never users to report that EVPs with nicotine are "a little" or "a lot" more harmful than smoking "regular" tobacco cigarettes (OR = 0.53, 95% CI 0.37 - 0.76). Conclusion: Our survey is limited by a low response rate but confirms observed associations between EVP use and substance use and social influences. Our data also suggest that professionals should regularly screen for EVP use among young people, especially those with exposure to family members who used inhaled substances.


[Negative-pressure pulmonary edema after general anaesthesia. Imaging diagnostic procedure].
Negative-pressure pulmonary edema is not a rare complication, e.g. in general anaesthesia and the diagnosis is made predominantly by clinical findings. When clinical findings are not clear radiology is necessary. This case report with detailed radiologic diagnostics, including follow-up, shows which radiologic signs are important for the clinical assessment to obtain a precise diagnosis and to start an adequate therapy.


A variant tandemly repeated nucleotide sequence in Balbiani ring 2 of Chironomus tentans.
pCtBR2-2 is a genomic clone from Chironomus tentans that hybridized in situ to Balbiani ring 2 (BR2) on salivary gland polytene chromosome IV. DNA sequencing indicated that the insert contained nearly four copies of a 180 bp tandemly repeated nucleotide sequence that was distinctly different from a previously reported BR2 repeat. Sequence titration experiments detected about 70 copies of the 180 bp repeat per haploid genome, which would correspond to approximately 34% of a 37 kb BR2 gene. Each 180 bp repeat included a conserved 90 bp segment whose sequence was internally nonrepeating (INR), and a variable 90 bp repeated (R) segment comprised of three 30 bp repeats that may have evolved from a 9 bp consensus sequence. Results presented here raise the distinct possibility that other BR genes may contain significantly different repeated sequences that have not been identified.


Levels and spatial distribution of perfluorinated compounds (PFCs) in superficial sediments from the marine reserves of the Tuscan Archipelago National Park (Italy).
Surface sediments from marine reserves of the Tuscan Archipelago National Park (Italy), including remote islands not directly affected by anthropogenic influences, were analyzed for two dominant perfluorinated compounds (PFCs), namely perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA), using LC-ESI-MS/MS. The concentrations of PFOS were low, with medians ranging from 0.25 to 1.50 ng/g dry wt, whereas PFOA was always below the detection limit of 0.1 ng/g dry wt. The present paper can be considered a baseline study useful in future environmental monitoring programs.


Tissue-specific expression of the human CYP19 (aromatase) gene in ovary and adipose tissue of transgenic mice.
In humans, the CYP19 (aromatase P450) gene is expressed in a number of tissues, including gonads, placenta, adipose tissue, skin and brain. The 5'-untranslated regions (UTR) of CYP19 mRNA transcripts in these tissues are encoded by different tissue-specific first exons, which are alternatively spliced onto a common site just upstream of the start of translation in exon II. In ovary, the 5'-UTR of CYP19 transcripts is encoded by exon IIa, which lies just upstream of exon II, while in adipose, the 5'-UTR of CYP19 transcripts is encoded by exon I.4, which lies >20 kb upstream of exon II. To map genomic sequences required for ovary- and adipose-specific CYP19 expression, fusion genes containing 2700, 278 and 43 bp of DNA flanking the 5'-end of ovary-specific exon IIa, or 348 bp of 5'- flanking DNA and 170 bp of adipose-specific exon I.4 were linked to the human growth hormone (hGH) gene, as reporter, and introduced into transgenic mice. We observed that CYP19(IIa):hGH fusion genes containing as little as 278 bp of exon IIa 5'-flanking sequence were expressed at high levels in an ovary-specific manner in transgenic mice, while the CYP19(IIa)(-43):hGH fusion gene was not expressed in any tissue. These results suggest that sequences between -43 and -278 bp upstream of exon IIa mediate ovary-specific CYP19 gene expression. In mice carrying the CYP19(I.4)(-348):hGH fusion gene, transgene expression was detected in skin and in mammary adipose, but not in any of the other tissues examined. These results indicate that genomic elements within -348 and +170bp of adipose-specific exon I.4 mediate adipose- and skin-specific CYP19 gene expression. Studies are in progress using transgenic mice to further define the response elements that mediate ovary and adipose-specific hCYP19 gene expression.


Concise Review: Stem Cell Microenvironment on a Chip: Current Technologies for Tissue Engineering and Stem Cell Biology.
Stem cells have huge potential in many therapeutic areas. With conventional cell culture methods, however, it is difficult to achieve in vivo-like microenvironments in which a number of well-controlled stimuli are provided for growing highly sensitive stem cells. In contrast, microtechnology-based platforms offer advantages of high precision, controllability, scalability, and reproducibility, enabling imitation of the complex physiological context of in vivo. This capability may fill the gap between the present knowledge about stem cells and that required for clinical stem cell-based therapies. We reviewed the various types of microplatforms on which stem cell microenvironments are mimicked. We have assigned the various microplatforms to four categories based on their practical uses to assist stem cell biologists in using them for research. In particular, many examples are given of microplatforms used for the production of embryoid bodies and aggregates of stem cells in vitro. We also categorized microplatforms based on the types of factors controlling the behaviors of stem cells. Finally, we outline possible future directions for microplatform-based stem cell research, such as research leading to the production of well-defined environments for stem cells to be used in scaled-up systems or organs-on-a-chip, the regulation of induced pluripotent stem cells, and the study of the genetic states of stem cells on microplatforms. Stem cells are highly sensitive to a variety of physicochemical cues, and their fate can be easily altered by a slight change of environment; therefore, systematic analysis and discrimination of the extracellular signals and intracellular pathways controlling the fate of cells and experimental realization of sensitive and controllable niche environments are critical. This review introduces diverse microplatforms to provide in vitro stem cell niches. Microplatforms could control microenvironments around cells and have recently attracted much attention in biology including stem cell research. These microplatforms and the future directions of stem cell microenvironment are described.


Recovery of Smelter-Impacted Peat and Sphagnum Moss: a Microbial Perspective.
Peatlands store approximately one-half of terrestrial soil carbon and one-tenth of non-glacial freshwater. Some of these important ecosystems are located near heavy metal emitting smelters. To improve the understanding of smelter impacts and potential recovery after initial pollution controls in the 1970s (roughly 50 years of potential recovery), we sampled peatlands along a distance gradient of 134 km from a smelter in Sudbury, Ontario, Canada, an area with over a century of nickel (Ni) and copper (Cu) mining activity. This work is aimed at evaluating potential shifts in bacterial and archaeal community structures in Sphagnum moss and its underlying peat within smelter-impacted poor fens. In peat, total Ni and Cu concentrations were higher (0.062-0.067 and 0.110-0.208 mg/g, respectively) at sites close to the smelter and exponentially dropped with distance from the smelter. This exponential decrease in Ni concentrations was also observed in Sphagnum. 16S rDNA amplicon sequencing showed that peat and Sphagnum moss host distinct microbiomes with peat accommodating a more diverse community structure. The microbiomes of Sphagnum were dominated by Proteobacteria (62.5%), followed by Acidobacteria (11.9%), with no observable trends with distance from the smelter. Dominance of Acidobacteria (32.4%) and Proteobacteria (29.6%) in peat was reported across all sites. No drift in taxonomy was seen across the distance gradient or from the reference sites, suggesting a potential microbiome recovery toward that of the reference peatlands microbiomes after decades of pollution controls. These results advance the understanding of peat and Sphagnum moss microbiomes, as well as depict the sensitivities and the resilience of peatland ecosystems.


What do geriatricians think about Comprehensive Geriatric Assessment? A survey of Australian and New Zealand geriatricians.
Despite Comprehensive Geriatric Assessment (CGA) being central to the work of geriatricians, little is known about geriatricians' views on CGA. This study was designed to understand how geriatricians conceptualise and practise CGA, and whether differences exist between groups (more experienced geriatricians vs. less experienced geriatricians and registrars; those practising in rural vs. metropolitan environments; in private vs. public sectors). An anonymous 90-item electronic questionnaire was emailed to members of the Australian and New Zealand Society for Geriatric Medicine. There were 243 respondents (response rate 19%). Respondents stated that core features of CGA were multidimensional assessment (89%), implementation of a management plan (84%), and involvement of a geriatrician (70%). Important features in predicting CGA success were ability to implement health management recommendations (55%), and ease of communication with general practitioners (46%), and with the multidisciplinary team (45%). Functional decline (88%) and frailty (88%) were thought to predict patients likely to benefit from CGA, compared to age (48%) or multimorbidity (19%). Junior consultants and registrars were less likely to prioritise the importance of clinical leadership (10% vs. 30%), and more likely to report the importance of a structured format (17% vs. 7%) to CGA effectiveness. There was some agreement about the core features of CGA and who is likely to benefit, but little agreement on features that predict CGA success. Further research that explores these points of difference would be helpful.


FOXC2/ADAM12-dependent radiosensitivity of head and neck squamous cell carcinoma cells.
Radiotherapy greatly benefits patients with tumors, but not all patients show favorable treatment response. This study investigated the impact of forkhead box protein C2 (FOXC2)-mediated a disintegrin and metalloprotease 12 (ADAM12) on the radiosensitivity of head and neck squamous cell carcinoma (HNSCC). After transfection and ionizing radiation, the biological activities of HNSCC cells were assessed. The relationship between ADAM12 and FOXC2 was verified. A xenograft model was used to evaluate the effect of FOXC2 knockdown on HNSCC growth in the context of radiation therapy. FOXC2 and ADAM12 were upregulated in irradiated CAL-27 and HN4 cells. Knockdown of FOXC2 suppressed the malignant behaviors of CAL-27 and HN4 cells and inhibited the growth of transplanted tumors in nude mice. FOXC2 could bind ADAM12 promoter. Overexpression of ADAM12 reversed the promotion of FOXC2 silencing on the radiosensitivity of HNSCC cells. FOXC2 regulates the radiosensitivity of HNSCC by targeting ADAM12.


DNA synthesis during meiosis of eight-spored strains of Chlamydomonas reinhardi.
In strain 137F of Chlamydomonas reinhardi, the zygospores undergo one round of nuclear DNA replication followed by three divisions to produce octospores. The third division without replication has been interpreted by Sueoka et al. (1967, 1969) to mean that the gametes and vegetative cells have at least binemic chromosomes. We have repeated their experiments using the same strain. However, the meiotic products were inviable--unable to undergo postmeiotic vegetative growth, DNA replication or division. On the other hand, using a variant of strain 137C which also has three divisions during germination we have shown that meiosis is normal. Zygospores from this strain undergo two rounds of nuclear DNA replication prior to the formation of octospores. These meiotic products are viable and capable of postmeiotic vegetative growth, replication and division. Since the third division without DNA replication subsequent to the two meiotic divisions leads to inviable products, and the strain which has viable products after three divisions does not lack the additional replication, meiosis in Chlamydomonas reinhardi provides no evidence of a bineme chromosome structure.


Proton nmr relaxation study of the dynamics of anthopleurin-A in solution.
Spin-spin and spin-lattice 1H-nmr relaxation times of the sea anemone polypeptide anthopleurin-A were measured at frequencies of 200, 300, 400, and 500 MHz. Relaxation times were fitted iteratively by least squares regression to the isotropic tumbling model, Woessner's model for anisotropic motion, and Lipari and Szabo's "model-independent" model. Data for aromatic and aliphatic methine protons could not be fitted satisfactority using the isotropic model. Good fits were obtained, however, using the model-independent approach, indicating that high-frequency internal motions of the polypeptide backbone were significant. In addition, a range of tau c values from 2.2 to 3.2 ns was obtained for various methine protons, suggesting that overall rotational reorientation of the molecule was anisotropic. Methyl group relaxation data were fitted satisfactorily by Woessner's model. Some assessment has been made of the effect of experimental errors on the quality of fit to the data, as well as of the contribution of experimental values at certain frequencies to definition of the spectral density function.


The role of mobile health in prevention, diagnosis, treatment and self-care of COVID-19 from the healthcare professionals' perspectives.
To facilitate disease management, understanding the attitude of healthcare professionals regarding the use of this tool can help mobile health (mHealth) program developers develop appropriate interventions. To assess the perspective of healthcare professionals regarding the contribution of mobile-based interventions in the prevention, diagnosis, self-care, and treatment (PDST) of COVID-19. This is a survey study conducted in 2020 in Iran with 81 questions. In this study mHealth functionalities were categorized into four dimensions including innovative, monitoring and screening, remote services, and education and decision-making. The data were analyzed using descriptive statistics, ANOVA, and the Kruskal-Wallis test to compare the attitudes of the different job groups. In total, 123 providers participated, and 87.4% of them reported that mHealth technology is moderate to most helpful for the management of COVID-19. Healthcare professionals believed that mHealth technology could be most helpful in self-care and least helpful in the diagnosis of COVID-19. Regarding the functionalities of the mobile application, the results showed that the use of patient decision aids can be most helpful in self-care and the use of computer games can be least helpful in treatment. The participants believed that mHealth is more effective in monitoring and screening dimensions and less effective in providing remote services. This study showed that healthcare professionals believed that mHealth technology could have a better contribution to self-care for patients with COVID-19. Therefore, it is better to plan and invest more in the field of self-care to help patients to combat COVID-19. The results of this study revealed which mhealth functionalities work better in four domains of prevention, treatment, self-care, and diagnosis of COVID-19. This can help healthcare authorities to implement appropriate IT-based interventions to combat COVID-19.


Cross-linking and self-assembly synthesis of tannin-based carbon frameworks cathode for Zn-ion hybrid supercapacitors.
Carbon frameworks with well-developed porosity present broad application prospects in energy-related materials, and green preparation still face challenges. Herein, the tannins-derived framework-like carbon material is obtained by cross-linking and self-assembly strategy.The phenolic hydroxyl and quinones in tannin cross-linking react with the amine groups in the methenamine by simple stirring, which drives the self-assembly of tannins and methenamine,contributing to the reaction products being precipitated in solution as aggregates with framework-like structure. The porosity and micromorphology of framework-like structures are further enriched by the thermal stability difference between tannin and methenamine. The methenamine of framework-like structures is entirely removed by the sublimation and decomposition and the tannin is transformed into carbon materials inheriting framework-like structures after the carbonization, which offers the path for rapid electron transport. The framework-like structure, excellent specific surface area and nitrogen doping give the assembled Zn-ion hybrid supercapacitors a superior specific capacitance of 165.3 mAh·g-1 (350.4 F·g-1). This device could be charged to 1.87 V to power the bulb by using solar panels. This study proves that the tannin-derived framework-like carbon is a promising electrode of the Zn-ion hybrid supercapacitors, which is beneficial for value-added and industrial supercapacitors application of green feedstocks.


Chronic relapsing demyelinating encephalomyelitis associated with persistent spontaneous canine distemper virus infection.
This is the first report of spontaneous canine distemper virus (CDV) infection in a dog associated with chronic progressive multiphasic neurological disease. Initial neurological deficits in the pelvic limbs progressed rapidly to paraplegia with almost complete remission after 9 weeks. Then another acute episode occurred with severe thoracic limb deficits and cerebellar dysfunction and progressive neurological deterioration over 3 months with rising serum neutralizing (SN) anti-CDV titers in the serum and cerebrospinal fluid (CSF). Three neuropathologically distinct lesions of spinal cystic necrosis, chronic demyelinating foci in the cerebellum and acute demyelinating encephalitis in the pons were identified. Persistent CDV antigen was demonstrated immunocytochemically only in acute lesions and atypically restricted to neurons. However, the immunological mechanism associated with the distinct remissions and exacerbations and CDV antigen clearance from chronic demyelinating lesions but persistence in acute lesions, despite a vigorous anti-CDV serologic response, was not defined.


Clinical and post-mortem assessment of the cause of death.
Analysis of the clinical and post-mortem assessment of the underlying cause of death in 742 autopsies showed that over- and underdiagnosis cancelled each other out in the majority of the main diagnostic groups, so there was little difference in the total number of cases recorded in the different groups after clinical and post-mortem investigation. However, in the individual case the reliability of the clinical diagnosis varied greatly with the nature of the diagnosis and its degree of certainty. Reliability was for example high with clinically certain arteriosclerotic heart disease and low with cerebrovascular disease. Underdiagnosis of lung cancer is still a problem. Lack of interest in autopsy investigation may be reflection of lack of clinical involvement or therapeutic frustration rather than the use of sophisticated diagnostic procedures, as has been assumed by previous authors. It is suggested that the idea of selection of cases for autopsy should be replaced by selection of autopsies for microscopic investigation on the basis of the macroscopic post-mortem findings. It is suggested also that clinicians might profitably attend autopsies on patients in their sphere of interest that were not admitted under their care.


New Approaches for the Synthesis of 2,3,5,6-Tetrahydrobenzo[d]thiazole Derivatives and their Anti-Proliferative, c-Met Enzymatic Activity and Tyrosine Kinases Inhibitions.
Due to their biological applications, many tetrahydrobenzo[d]thiazole derivatives were considered the most important class of heterocyclic compounds. There are many drugs known in the market containing the thiazole moiety responsible for the high drug activity. This work aimed to produce novel heterocyclic compounds such as pyrazole, isoxazole, thiophene, chromeno[ 7,8-d]thiazole, and thiazolo[4,5-h]quinoline derivatives. The newly synthesized heterocyclic compounds were evaluated against anticancer cell lines followed by c-Met enzymatic activity and tyrosine kinases inhibition for the most active compounds. In this work, the 3-phenyl-2-thioxo-2,3,5,6-tetrahydrobenzo[d]thiazol-7(4H)-one (3) was synthesized through the reaction of cyclohexane-1,3-dione with phenyl isothiocyanate and elemental sulfur. Compound 3 showed interesting activity toward some chemical reagents producing new heterocyclic compounds that can not be obtained another way. The newly synthesized compounds were evaluated towards the six cancer cell lines. The most active compounds were selected and tested toward the c-Met enzyme by taking foretinib as the positive control. Also, the inhibitions toward the PC-3 cell line using the reference SGI-1776 were measured. Finally, the inhibitions towards the five tyrosine kinases were also tested. The synthesized quinoline and chromene derivatives were evaluated toward the c-Met enzyme using foretinib as the positive control. The obtained results showed that twelve compounds exhibited IC50 values less than 1.30 nM. On the other hand, sixteen compounds showed higher inhibitions than the reference SGI-1776 (IC50 4.86 nM) toward the PC-3 cell line. Novel, heterocyclic compounds were synthesized with a high impact on biological activities. All synthesized compounds were screened for their anti-proliferative effect, and most of them revealed high potent effects. In addition, the c-Met and prostate cancer cell line PC-3 inhibitions for the most active compounds showed that these compounds exhibited high inhibitions. Anti-proliferative activity of selected compounds toward cancer cell lines classified according to the disease showed that most compounds exhibited high inhibitions.


Large deforming buoyant embolus passing through a stenotic common carotid artery: a computational simulation.
Arterial embolism is responsible for the death of lots of people who suffers from heart diseases. The major risk of embolism in upper limbs is that the ruptured particles are brought into the brain, thus stimulating neurological symptoms or causing the stroke. We presented a computational model using fluid-structure interactions (FSI) to investigate the physical motion of a blood clot inside the human common carotid artery. We simulated transportation of a buoyant embolus in an unsteady flow within a finite length tube having stenosis. Effects of stenosis severity and embolus size on arterial hemodynamics were investigated. To fulfill realistic nonlinear property of a blood clot, a rubber/foam model was used. The arbitrary Lagrangian-Eulerian formulation (ALE) and adaptive mesh method were used inside fluid domain to capture the large structural interfacial movements. The problem was solved by simultaneous solution of the fluid and the structure equations. Stress distribution and deformation of the clot were analyzed and hence, the regions of the embolus prone to lysis were localized. The maximum magnitude of arterial wall shear stress during embolism occurred at a short distance proximal to the throat of the stenosis. Through embolism, arterial maximum wall shear stress is more sensitive to stenosis severity than the embolus size whereas role of embolus size is more significant than the effect of stenosis severity on spatial and temporal gradients of wall shear stress downstream of the stenosis and on probability of clot lysis due to clot stresses while passing through the stenosis.


Unilateral total lobectomy: is it sufficient surgical treatment for patients with AMES low-risk papillary thyroid carcinoma?
Controversy continues regarding the optimal extent of primary thyroid resection in most patients with papillary thyroid carcinoma (PTC), who are at minimal risk of cause-specific mortality (CSM). This study was designed to compare CSM and recurrence rates after either unilateral lobectomy (UL) or bilateral lobar resection (BLR) in patients with PTC considered low risk by AMES criteria. Outcome was studied in 1685 patients initially treated during 1940 through 1991 and followed for up to 54 postoperative years (mean, 18 years). One thousand six hundred fifty-six patients (98%) had complete primary tumor resection; 634 (38%) had involvement of regional nodes. One hundred ninety-five patients (12%) had UL; BLR accounted for 1468 (near-total 60%; total thyroidectomy 18%). Thirty-year rates for CSM and distant metastasis were 2% and 3%, respectively. Twenty-year rates for local recurrence and nodal metastasis were 4% and 8%, respectively. There were no significant differences in CSM or distant metastasis rates between UL and BLR (P > .2). After UL, 20-year rates for local recurrence and nodal metastasis were 14% and 19%, significantly higher (P = .0001) than the 2% and 6% rates seen after BLR. UL was not associated with higher CSM rates, but it was associated with a significantly higher risk of locoregional recurrence. Thus BLR probably represents a preferable initial surgical approach to patients with low-risk PTC.


Acute antibody-mediated rejection after lung transplantation.
Antibody-mediated rejection (AMR) after lung transplantation remains enigmatic, and there is no consensus on the characteristic clinical, immunologic and histologic features. We performed a retrospective, single-center cohort study and identified cases of acute AMR based on the presence of circulating donor-specific human leukocyte antigen (HLA) antibodies (DSA), histologic evidence of acute lung injury, C4d deposition and clinical allograft dysfunction. We identified 21 recipients with acute AMR based on the aforementioned criteria. AMR occurred a median 258 days after transplantation; 7 recipients developed AMR within 45 days of transplantation. All patients had clinical allograft dysfunction, DSA, histology of acute lung injury and capillary endothelial C4d deposition. Fifteen recipients improved clinically and survived to hospital discharge, but 6 died of refractory AMR. One survivor had bronchiolitis obliterans syndrome at the time of AMR diagnosis; 13 of the 14 remaining survivors developed chronic lung allograft dysfunction (CLAD) during follow-up. Overall, 15 recipients died during the study period, and the median survival after the diagnosis of AMR was 593 days. Acute AMR can be a fulminant form of lung rejection, and survivors are at increased risk of developing CLAD. The constellation of acute lung injury, DSA and capillary endothelial C4d deposition is compelling for acute AMR in recipients with allograft dysfunction. This clinicopathologic definition requires validation in a multicenter cohort, but may serve as a foundation for future studies to further characterize AMR.