An Insulating Al2O3 Overlayer Prevents Lateral Hole Hopping Across Dye-Sensitized TiO2 Surfaces.
Three chromophores of the general form [Ru(bpy')2(4,4'-(PO3H2)2-2,2'-bipyridine)]2+, where bpy' is 4,4'-(C(CH3)3)2-2,2'-bipyridine (Ru(dtb)2P); 4,4'-(CH3O)2-2,2'-bipyridine (Ru(OMe)2P), and 2,2'-bipyridine (RuP) were anchored to mesoporous thin films of TiO2 nanocrystallites at saturation surface coverages to investigate lateral self-exchange RuIII/II intermolecular hole hopping in 0.1 M LiClO4/CH3CN electrolytes. Hole hopping was initiated by a potential step 500 mV positive of the E1/2 (RuIII/II) potential or by pulsed laser (532 nm, 8 ns fwhm) excitation and monitored by visible absorption chronoabsorptometry and time-resolved absorption anisotropy measurements, respectively. The hole hopping rate constant kR extracted from the potential step data revealed self-exchange rate constants that followed the trend: TiO2|Ru(OMe)2P (ket = 1.4 × 106 s-1) > TiO2|RuP (7.1 × 105 s-1) > TiO2|Ru(dtb)2P (6.5 × 104 s-1). Analysis of the anisotropy data with Monte Carlo simulations provided hole hopping rate constants for TiO2|RuP and TiO2|Ru(dtb)2P that were within experimental error the same as that measured with the potential step. The hole hopping rate constants were found to trend with the TiO2(e-)|RuIII → TiO2|RuII charge recombination rate constants. The atomic layer deposition of an ∼10 Å layer of Al2O3 on top of the dye-sensitized films was found to prevent hole hopping by both initiation methods even though the chromophore surface coverage exceeded the percolation threshold and excited-state injection was efficient. The dramatic hole hopping turnoff was attributed to a larger outer-sphere reorganization energy for self-exchange due to the restricted access of electrolyte to the redox active chromophores. The implications of these findings for solar energy conversion applications are discussed.


Embryonic vascular development: immunohistochemical identification of the origin and subsequent morphogenesis of the major vessel primordia in quail embryos.
The development of the embryonic vasculature is examined here using a monoclonal antibody, QH-1, capable of labelling the presumptive endothelial cells of Japanese quail embryos. Antibody labelling is first seen within the embryo proper at the 1-somite stage. Scattered labelling of single cells appears ventral to the somites and at the lateral edges of the anterior intestinal portal. The dorsal aorta soon forms a continuous cord at the ventrolateral edge of the somites and continues into the head to fuse with the ventral aorta forming the first aortic arch by the 6-somite stage. The rudiments of the endocardium fuse at the midline above the anterior intestinal portal by the 3-somite stage and the ventral aorta extends craniad. Intersomitic arteries begin to sprout off of the dorsal aorta at the 7-somite stage. The posterior cardinal vein forms from single cells which segregate from somatic mesoderm at the 7-somite stage to form a loose plexus which moves mediad and wraps around the developing Wolffian duct in later stages. These studies suggest two modes of origin of embryonic blood vessels. The dorsal aortae and cardinal veins apparently arise in situ by the local segregation of presumptive endothelial cells from the mesoderm. The intersomitic arteries, vertebral arteries and cephalic vasculature arise by sprouts from these early vessel rudiments. There also seems to be some cell migration in the morphogenesis of endocardium, ventral aorta and aortic arches. The extent of presumptive endothelial migration in these cases, however, needs to be clarified by microsurgical intervention.


Insulin receptors from guinea pig liver and brain: structural and functional studies.
We studied the structural and functional characteristics of insulin receptors from guinea pig liver and brain. Binding to crude membrane preparations of liver and brain was time, temperature, and pH dependent. Maximal specific binding to liver crude membrane preparations was 16.4 +/- 0.5%, and that to brain crude membrane preparations was 10.4 +/- 1.8%. Specificity studies demonstrated typical affinities for insulin receptors with chicken insulin greater than porcine insulin greater than human proinsulin greater than desoctapeptide insulin in both liver and brain. Antiinsulin receptor antiserum inhibited binding of [125I]insulin to both liver and brain crude membrane preparations. Electrophoresis performed under reducing conditions after affinity cross-linking of liver and brain insulin receptors with [125I]insulin revealed labeled proteins (alpha-subunit) with apparent mol wt of 136,000 in liver and 121,000 in brain. Treatment of liver and brain receptors with both endoglycosidase H and endoglycosidase F increased the electrophoretic mobility of the alpha-subunit. [125I]Insulin cross-linked receptors from both liver and brain adsorbed to and eluted from wheat germ agglutinin columns in a similar manner, as demonstrated by binding and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In solubilized lectin-purified receptor preparations from liver and brain, insulin stimulated the phosphorylation of the beta-subunit and exogenous substrates. When the delta-kinase activity, as measured by exogenous substrate phosphorylation, of the brain and liver preparations was normalized to the maximal bound to free ratio of the preparations, the delta-kinase activity was about 4-fold greater in brain than in liver. These studies suggest that the differences between brain and liver insulin receptor alpha-subunits previously demonstrated in rats are also present in guinea pigs.


Advancement in Nanoparticle-based Biosensors for Point-of-care In vitro Diagnostics.
Recently, there has been great progress in the field of extremely sensitive and precise detection of bioanalytes. The importance of the utilization of nanoparticles in biosensors has been recognized due to their unique properties. Specifically, nanoparticles of gold, silver, and magnetic plus graphene, quantum dots, and nanotubes of carbon are being keenly considered for utilization within biosensors to detect nucleic acids, glucose, or pathogens (bacteria as well as a virus). Taking advantage of nanoparticles, faster and sensitive biosensors can be developed. Here, we review the nanoparticles' contribution to the biosensors field and their potential applications.


Efficacy of Treatment for Latent Tuberculosis in Patients Undergoing Treatment with a Tumor Necrosis Factor Antagonist.
Current guidelines recommend that all patients undergoing treatment with a tumor necrosis factor-α antagonist should receive screening for latent tuberculosis and appropriate treatment before initiating the inhibitor. However, no well-designed study has shown the efficacy of treating these patients for latent tuberculosis. To compare the risk of active tuberculosis between tumor necrosis factor antagonist users who have received treatment for latent tuberculosis with those who have not. We performed a national-level retrospective cohort study in South Korea, a country with an intermediate tuberculosis burden, by analyzing claims recorded between January 1, 2011, and December 31, 2013, in an obligatory national health insurance claims database. The primary outcome, the incidence of active tuberculosis, was measured as the occurrence of an International Statistical Classification of Diseases and Related Health Problems, 10th edition, diagnosis of tuberculosis and prescription of at least two antituberculosis drugs at least twice within 90 days. Among 10,863 eligible new tumor necrosis factor antagonist users, 2,461 (22.7%) received treatment for latent tuberculosis. The incidence rate of tuberculosis per 1,000 person-years was lower for the treated group (4.07; 95% confidence interval [CI], 1.55-6.60) than for the untreated group (12.34; 95% CI, 9.96-14.72). The risk for tuberculosis was significantly reduced by preventive chemotherapy (incidence rate ratio, 0.33; 95% CI, 0.17-0.63). Treatment for latent tuberculosis was highly effective in preventing the development of tuberculosis among tumor necrosis factor antagonist users.


Is there a relationship between small, dense LDL and lipoprotein--associated phospholipase A2 mass in dialysis patients?
We aimed to measure small, dense LDL (sdLDL) and lipoprotein-associated phospholipase A2 (Lp-PLA2) concentrations and to evaluate their relationship with other risk factors of atherosclerotic heart disease in dialysis patients. Study group consisted of 30 peritoneal dialysis and 20 hemodialysis patients with 20 healthy control subjects. sdLDL was measured by homogeneous LDL assay after precipitation of Apo B containing lipoproteins with heparin-magnesium. Lp-PLA2 mass was measured by immunoturbidimetric assay. sdLDL concentrations in the samples collected before hemodialysis and peritoneal dialysis treatment were significantly higher than the control group (p < 0.05). Lp-PLA2 concentrations of both pre-hemodialysis and peritoneal dialysis groups were higher than control group (p < 0.05). There was not a significant correlation between sdLDL and Lp-PLA2. sdLDL concentrations are significantly decreased after a hemodialysis session. sdLDL and Lp-PLA2 concentrations are increased independently in the end stage renal failure patients who are receiving dialysis treatment.


Techniques and results of laparoscopic antireflux surgery in Germany.
This study aimed to evaluate the development and outcomes of laparoscopic antireflux surgery in Germany using a nationwide representative survey. A written questionnaire including 34 detailed questions and 288 structured items about diagnostic and therapeutic approaches, number of procedures, complications, and mortality was sent to 546 randomly selected German surgeons (33% of the registered general surgeons) at the end of 2000. The response rate was 72%, and a total of 2,540 antireflux procedures were reported. According to the survey, 81% of all procedures were performed laparoscopically, and 0.1% were performed thoracoscopically. As reported, 65% were total fundoplications, 31% were partial fundoplications, and 4% were other procedures. Of the surgeons who had experience with laparoscopic antireflux techniques (29%), 71% preferred a 5-trocar technique, and 91% used the Harmonic Scalpel for dissection. There were significant technical variations among the surgical procedures (e.g., use and size of the bougie, length of the wrap, additional gastropexy, fixation of the wrap). The overall complication rate for laparoscopic fundoplication was 7.7% (5.7% surgical and 2% nonsurgical complications), including rates of 0.6% for esophageal perforations and 0.6% for splenic lesions. The conversion rate was 2.9%; the reoperation rate was 1.6%; and the overall hospital mortality rate was 0.13%. The authors observed a striking learning curve difference in complication rates between hospitals performing fewer than 10 laparoscopic antireflux techniques annually and those performing more than 10 fundoplications per year (14% vs 5.1%, p < 0.001). Long-term dysphagia and interventions occasioned by dysphagia occurred significantly more often after total fundoplications than after partial fundoplications (6.6% vs 2.4%; p < 0.001). Similar findings were reported for Nissen versus floppy Nissen procedures. The overall failure rate, however, was similar for both groups (Nissen 8.7%; partial 9%, difference not significant). Until now, no unique laparoscopic antireflux technique has been accepted, and a number of different antireflux procedures with numerous modifications have been reported. The morbidity and mortality rates reported in this article compare very well with those in the literature, and 1-year-follow-up results are promising.


Identification of the rice genes and metabolites involved in dual resistance against brown planthopper and rice blast fungus.
Brown planthopper (BPH) and blast disease jointly or individually cause big yield losses every year. To identify genes and metabolites with potential contributions to the dual resistance against both biotic-stress factors, we carried out a transcriptome and metabolome analysis for susceptible and resistant rice varieties after BPH and rice blast infestations. Coexpression network analysis identified a modular pattern that had the highest correlation coefficients (0.81) after the BPH and rice blast (-0.81) treatments. In total, 134 phenylpropanoid biosynthesis pathway-related genes were detected in this group. We found that the flavanone 3-hydroxylase gene (OsF3H) had opposite expression trends in response to BPH and rice blast infestations whereas the OsF3'H had similar expression patterns. Genetics analysis confirmed that the OsF3H gene knockdown lines demonstrated the opposite resistance phenotypes against BPH and rice blast, whereas the OsF3'H knockout lines enhanced rice resistance against both pests. Consistently, our metabolomics analysis identified the metabolite eriodictyol, one putative essential product of these two genes, that was more highly accumulated in the resistant rice variety of RHT than in the susceptible variety MDJ. This study highlights a useful strategy for identifying more genes and metabolites that have potential synergistic effects on rice against to multiple biotic stresses.


Raman spectra of the phycoviolobilin cofactor in phycoerythrocyanin calculated by QM/MM methods.
The Raman spectrum of the phycoviolobilin cofactor of the alpha-subunit of phycoerythrocyanin was computed using a hybrid quantum mechanical/molecular mechanics (QM/MM) method in order to evaluate the performance of the QM/MM approach for calculating the vibrational spectra of protein-bound tetrapyrroles as found in phytochrome photoreceptors. A good overall agreement between the experimental and the calculated spectra was achieved. In addition, calculation of the vibrational properties of several snapshots extracted from a molecular dynamics simulation allowed us to investigate in detail the effect of the protein environment on the vibrational spectra. Heterogeneous broadening of most of the experimental bands could be reproduced in a satisfactory manner as the sum of individual spectra obtained by normal-mode-analysis (NMA). An exception is the bandwidth of the peak at 1646 cm(-1), which is underestimated by the NMA sum as well as by the instantaneous normal mode analysis (INMA) approach.


The protective role of tangible support on post-traumatic stress disorder symptoms in urban women survivors of violence.
We examined social support as a protective factor in the relationship between lifetime exposure to traumatic events and Post-Traumatic Stress Disorder (PTSD) symptomatology among urban women. Seventy-six women who sought care in a trauma center for injuries from physical or sexual violence completed an interview. When tangible support, rather than total social support, and the interaction of tangible support and lifetime trauma were tested, tangible support moderated the relationship between lifetime trauma and PTSD. Given the complex etiology of lifetime trauma, risk for future trauma and the health needs of women who have experienced trauma, a broader range of intervention strategies that include attention to tangible support need to be developed and evaluated.


Telomerase activity in female and male rat germ cells undergoing meiosis and in early embryos.
Telomerase is a ribonucleoprotein that synthesizes telomeric DNA at the ends of eukaryotic chromosomes. It has been hypothesized that telomerase activity is necessary for cellular immortalization and that telomerase activity is present in cells of germline origin. The objective of the present study was to determine the level of telomerase activity in the following rat cells: 1) oocytes from follicles at different stages of development, 2) spermatogenic cells, and 3) early embryos. Telomerase activity was quantitated using a recently developed, sensitive polymerase chain reaction-based assay and a human kidney cell line (293) as a standard. Telomerase activity was found in oocytes from early antral and preovulatory follicles, as well as in ovulated oocytes. The level of enzyme activity in early antral and preovulatory follicles was comparable to that of the 293 cells, while levels in ovulated oocytes were 50-fold lower. Telomerase activity was present in even lower levels in pachytene spermatocytes and round spermatids, and no telomerase activity was detected in spermatozoa from either the caput or the cauda epididymis. After fertilization, telomerase activity was present in 4-cell embryos. Telomerase activity was also detected in several rat somatic tissues. These data demonstrate that telomerase activity is present in germ cells at several stages of differentiation, with the exception of spermatozoa, and suggest that telomerase activity may be important during meiosis. The high levels of telomerase activity in individual oocytes may serve as a marker for monitoring the effects of hormonal agents, aging, and toxins on oocyte quality.


[Tarsal gland of the ticks Ixodes persulcatus and Ixodes ricinus (Ixodidae)].
A complicated multicellular gland is situated in tarsi of all the legs, occupying one third to half of the segment. Glandular cells form a single-layer sack; inner surface of the sack (gland cavity) is enveloped by a multilayer membrane. Cuticular rods connecting muscles with the claw pass inside this cavity. Glandular cells are characterized by the presence of numerous apical microvilli associated with accumulations of mitochondria, and secretory vacuoles enclosed in cellular membranes. The basal part of each cell contains lipid vacuoles and glycogen granules. The possibility of the track contact pheromone's production by the tarsal gland is discussed.


A new strategy based on recombinant viruses as a tool for assessing drug susceptibility of human immunodeficiency virus type 1.
The emergence of drug-resistant variants during antiretroviral therapy is a serious obstacle to sustained suppression of the human immunodeficiency virus type 1 (HIV-1). For that reason, resistance assays are essential to guide clinicians in the selection of optimal treatment regimens. Genotypic assays are less expensive and results are available faster than phenotypic assays. However, in heavily experienced patients with multiple treatment failures interpretation of complex mutation patterns remains difficult, and in these cases phenotypic assays are recommended. This report describes a novel recombinant virus assay where protease (PR) and reverse transcriptase (RT) sequences derived from the plasma isolated from patients are introduced into the back-bone of an HIV molecular clone that expresses Renilla luciferase protein in the place of nef gene. All drug resistance profiles analyzed correlate with previously reported data and showed high reproducibility. This assay, in addition to a fast (completed in 10 days), precise, reproducible and automated method, presents several advantages as compared to other phenotypic assays. The system described below allows the generation of recombinant viruses with multiples cycles of replication carrying a reporter gene in their genomes. These features increase the sensitivity of the test, an important aspect to be considered in the evaluation of less fit viral isolates. In conclusion, the assay permits the quantitation of the level of resistance of clinical HIV-1 isolates to PR and RT inhibitors.


Dynamic shaping of cellular membranes by phospholipids and membrane-deforming proteins.
All cellular compartments are separated from the external environment by a membrane, which consists of a lipid bilayer. Subcellular structures, including clathrin-coated pits, caveolae, filopodia, lamellipodia, podosomes, and other intracellular membrane systems, are molded into their specific submicron-scale shapes through various mechanisms. Cells construct their micro-structures on plasma membrane and execute vital functions for life, such as cell migration, cell division, endocytosis, exocytosis, and cytoskeletal regulation. The plasma membrane, rich in anionic phospholipids, utilizes the electrostatic nature of the lipids, specifically the phosphoinositides, to form interactions with cytosolic proteins. These cytosolic proteins have three modes of interaction: 1) electrostatic interaction through unstructured polycationic regions, 2) through structured phosphoinositide-specific binding domains, and 3) through structured domains that bind the membrane without specificity for particular phospholipid. Among the structured domains, there are several that have membrane-deforming activity, which is essential for the formation of concave or convex membrane curvature. These domains include the amphipathic helix, which deforms the membrane by hemi-insertion of the helix with both hydrophobic and electrostatic interactions, and/or the BAR domain superfamily, known to use their positively charged, curved structural surface to deform membranes. Below the membrane, actin filaments support the micro-structures through interactions with several BAR proteins as well as other scaffold proteins, resulting in outward and inward membrane micro-structure formation. Here, we describe the characteristics of phospholipids, and the mechanisms utilized by phosphoinositides to regulate cellular events. We then summarize the precise mechanisms underlying the construction of membrane micro-structures and their involvements in physiological and pathological processes.


[Manometry in esophageal achalasia].
Manometric findings in achalasia are pathognomic already in early clinical stages of the disease. The authors evaluate the importance of manometry in the diagnosis and therapy, in particular in early stages of the disease. During manometry we obtain data on the function of the lower oesophageal sphincter and the body of the oesophagus. Impaired relaxation of the sphincter is evaluated, as well as increased tonus of the sphincter and tertiary contraction of the body of the oesophagus. In patients with achalasia we implement laparoscopically extramucous myotomy. In 1997 we started a prospective manometric study of dysphagic complaints. We examined 304 patients on account of different diseases of the oesophagus incl. 16(5.2%) where we proved or confirmed achalasia in stage I, II or III according to the radiological classification. These patients were indicated for laparoscopic myotomy. In one instance we had to convert the operation to an open one. In two instances we added partial fundoplasty according to Thal on account of perforation of the oesophageal mucosa. Four patients were subjected after a 5-12-month interval to remyotomy. Twice because of the development of a fibrous stricture at the site of myotomy and twice for an obviously inadequate original myotomy. The history of dysphagia in patients with primary operations was on average 37.3 months. Manometric examination of patients with functional dysphagia makes it possible to detect achalasia in early stages and to indicate in time surgical treatment. In case of a relapse or persistence of complaints manometry makes it possible to express objectively the cause which is most frequently an atonic oesophagus with inadequate evacuating capacity, stricture at the site of myotomy or inadequate myotomy.


[Standard control for diabetes in older adults based on practice guidelines--the target values of blood glucose, blood pressure and lipids].
As for standard controls for life style diseases in older adults, the standard control for hypertension in elderly is defined in detail by the guideline for hypertension, however, that for diabetes or dyslipidemia is not clearly defined by each guideline although each has additional descriptions for elderly. The reports about 'Diabetes in Older Adults' and 'Standards of Medical Care in Diabetes 2013' have been published from American Diabetes Association (ADA), and the standard controls for diabetes might be reviewed in the light of these reports in Japan. Here we would like to consider the standard control and recent trends for diabetes in older adults on the basis of the current practice guidelines.


Eating green for health or social benefits? Interactions of attitudes with self-identity on the consumption of vegetarian meals among U.S. and Chinese college students.
Encouraging greater consumption of vegetarian foods could be a strategy to improve plant-based food intake among non-vegetarians. Prior research on vegetarianism has focused mostly on people's motivations to be a vegetarian. However, the factors that motivate non-vegetarians to consume vegetarian meals remain largely unknown. The current research tested associations between attitudes, self-identity, and vegetarian meal consumption among 746 U.S. college students and 484 Chinese college students. Two types of attitudes were assessed: attitudes towards vegetarian food (ATF), which represents the personal benefits (including healthiness, tastiness, and enjoyableness) and attitudes towards people who are vegetarians (ATP), which represents the social benefits (perceived as being environmentally friendly, nice, and good-looking). Results showed that U.S. college students were more likely to be either vegetarians or non-vegetarians, while more Chinese college students tended to report being semi-vegetarians. In both samples, ATF and ATP were positively associated with self-identity and vegetarian meal consumption. Moderation analyses suggested that associations between attitudes and consumption were significant only among people who do not hold a definite self-identity as a vegetarian. In addition, ATP was significantly associated with vegetarian meal consumption among U.S. non- and semi-vegetarians alike, but among Chinese non-vegetarians only. These findings suggest that self-identity and cross-cultural differences are important to consider in promoting consumption of vegetarian meals through improving the public's attitudes towards vegetarian food and vegetarians.


Codon usage and protein sequence pattern dependency in different organisms: A Bioinformatics approach.
Although it is known that synonymous codons are not chosen randomly, the role of the codon usage in gene regulation is not clearly understood, yet. Researchers have investigated the relation between the codon usage and various properties, such as gene regulation, translation rate, translation efficiency, mRNA stability, splicing, and protein domains. Recently, a universal codon usage based mechanism for gene regulation is proposed. We studied the role of protein sequence patterns on the codons usage by related genes. Considering a subsequence of a protein that matches to a pattern or motif, we showed that, parts of the genes, which are translated to this subsequence, use specific ratios of synonymous codons. Also, we built a multinomial logistic regression statistical model for codon usage, which considers the effect of patterns on codon usage. This model justifies the observed codon usage preference better than the classic organism dependent codon usage. Our results showed that the codon usage plays a role in controlling protein levels, for genes that participate in a specific biological function. This is the first time that this phenomenon is reported.


Musculoskeletal Tuberculosis: New Insights on Diagnosis Strategy and Treatment.
Skeletal tuberculosis (TB) is rare. We aimed to report on diagnostic strategy and treatment of skeletal TB. In this multidisciplinary single-center medical records review study, all adult patients admitted between January 2009 and December 2019 with microbiologically proven skeletal TB were included. Demographic, medical history, laboratory, imaging, pathologic findings, treatment, and follow-up data were extracted from medical records. Among 184 patients identified with TB, 21 (16 women, 42 years [27, 48 years]) had skeletal involvement. Skeletal TB included spondylitis (n = 11), lytic bone lesions (n = 7), sacroiliitis (n = 5), arthritis (n = 3), osteitis (n = 2), and diffuse muscle abscesses without bone lesion (n = 1). Lytic lesions involved both axial and peripheral skeleton at multiple sites in most cases. 18F-fluorodeoxyglucose positron emission tomography was performed in 13 patients and helped to detect multifocal asymptomatic lesions and to target biopsy. All patients were treated with anti-TB therapy for 7 to 18 months. Fifteen patients (71.4%) received steroids as an adjunct therapy. Eleven patients needed an orthopedic immobilization corset, and 3 patients underwent surgery. All patients clinically improved under treatment, but 2 relapsed over a median follow-up of 24 months (12-30 months). No patient died or suffered long-term disabilities. Our study emphasizes the diversity of skeletal involvement in TB. 18F-fluorodeoxyglucose positron emission tomography scanner at diagnosis is key to assess the extension of skeletal involvement and guide extraskeletal biopsy. Neurological complications might be prevented by adding corticosteroids to anti-TB therapy.


Connecting cognition and consumer choice.
We describe what can be gained from connecting cognition and consumer choice by discussing two contexts ripe for interaction between the two fields. The first-context effects on choice-has already been addressed by cognitive science yielding insights about cognitive process but there is promise for more interaction. The second is learning and representation in choice where relevant theories in cognitive science could be informed by consumer choice, and in return, could pose and answer new questions. We conclude by discussing how these two fields of research stand to benefit from more interaction, citing examples of how interfaces of cognitive science with other fields have been illuminating for theories of cognition.


IFN-gamma induces calcium transients and increases the capacitative calcium entry in human neutrophils.
We have previously reported that long-term priming of human polymorphonuclear neutrophilic granulocytes (PMN) with interferon-gamma (IFN-gamma) increased the fMLP-stimulated calcium influx. We now show that also after short-term incubation with IFN-gamma, PMN calcium metabolism is modulated. Single adherent cells in three different calcium-containing buffers (high, normal, and low [Ca2+]) were stimulated with the bacterial peptide fMLP or the Ca-ATPase inhibitor thapsigargin (Tg) after about 5 min preincubation with IFN-gamma. The results of this protocol indicated that IFN-gamma increases both calcium influx and calcium sequestration. Store dependent Ca2+ influx, directly measured on readdition of calcium to Tg-treated cells incubated in EGTA buffer, was significantly enhanced in IFN-gamma-treated cells. This effect of IFN-gamma was enhanced by the tyrosine kinase inhibitor herbimycin A. Strikingly, in low extracellular calcium concentrations, IFN-gamma induced calcium transients in 20%-60% of the cells. The proportion of PMN responding with Ca2+ transients increased with decreasing extracellular calcium concentration. Average lagtime from addition of IFN-gamma to a response that could be measured was 7.3 sec, and average increase in [Ca2+] above the basal level was 790 nM. These IFN-gamma-induced transients could not be depressed by herbimycin A. Thus, IFN-gamma can increase capacitative calcium influx, induce calcium transients, and possibly affect calcium sequestration in human PMN.


Slowed vertical saccades as a hallmark of hereditary spastic paraplegia type 7.
Anecdotal oculomotor disturbances have been described in spastic paraplegia type 7 (SPG7). We investigated oculomotor and vestibular dysfunction in five patients with genetically verified SPG7. All five patients exhibited significantly slower velocities of vertical saccades compared to controls, but significantly faster than in progressive supranuclear palsy, with upward saccades being particularly affected. Horizontal saccades, cerebellar oculomotor markers, and vestibuloocular reflex seem to be variably affected. Thus, albeit subclinical in some cases, slowing of the vertical saccades may belong to the phenotype of SPG7 and may serve as a valuable biomarker for differentiation from spastic ataxias and atypical parkinsonism.


Peptide Nucleic Acids as miRNA Target Protectors for the Treatment of Cystic Fibrosis.
Cystic Fibrosis (CF) is one of the most common life shortening conditions in Caucasians. CF is caused by mutations in the CF Transmembrane Conductance Regulator (CFTR) gene which result in reduced or altered CFTR functionality. Several microRNAs (miRNAs) downregulate the expression of CFTR, thus causing or exacerbating the symptoms of CF. In this context, the design of anti-miRNA agents represents a valid functional tool, but its translation to the clinic might lead to unpredictable side effects because of the interference with the expression of other genes regulated by the same miRNAs. Herein, for the first time, is proposed the use of peptide nucleic acids (PNAs) to protect specific sequences in the 3'UTR (untranslated region) of the CFTR messenger RNA (mRNA) by action of miRNAs. Two PNAs (7 and 13 bases long) carrying the tetrapeptide Gly-SerP-SerP-Gly at their C-end, fully complementary to the 3'UTR sequence recognized by miR-509-3p, have been synthesized and the structural features of target PNA/RNA heteroduplexes have been investigated by spectroscopic and molecular dynamics studies. The co-transfection of the pLuc-CFTR-3´UTR vector with different combinations of PNAs, miR-509-3p, and controls in A549 cells demonstrated the ability of the longer PNA to rescue the luciferase activity by up to 70% of the control, thus supporting the use of suitable PNAs to counteract the reduction in the CFTR expression.


Magnetite Nanoparticles Induce Genotoxicity in the Lungs of Mice via Inflammatory Response.
Nanomaterials are useful for their characteristic properties and are commonly used in various fields. Nanosized-magnetite (MGT) is widely utilized in medicinal and industrial fields, whereas their toxicological properties are not well documented. A safety assessment is thus urgently required for MGT, and genotoxicity is one of the most serious concerns. In the present study, we examined genotoxic effects of MGT using mice and revealed that DNA damage analyzed by a comet assay in the lungs of imprinting control region (ICR) mice intratracheally instilled with a single dose of 0.05 or 0.2 mg/animal of MGT was approximately two- to three-fold higher than that of vehicle-control animals. Furthermore, in gpt delta transgenic mice, gpt mutant frequency (MF) in the lungs of the group exposed to four consecutive doses of 0.2 mg MGT was significantly higher than in the control group. Mutation spectrum analysis showed that base substitutions were predominantly induced by MGT, among which G:C to A:T transition and G:C to T:A transversion were the most significant. To clarify the mechanism of mutation caused by MGT, we analyzed the formation of DNA adducts in the lungs of mice exposed to MGT. DNA was extracted from lungs of mice 3, 24, 72 and 168 h after intratracheal instillation of 0.2 mg/body of MGT, and digested enzymatically. 8-Oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and lipid peroxide-related DNA adducts were quantified by stable isotope dilution liquid chromatography-mass spectrometry (LC-MS/MS). Compared with vehicle control, these DNA adduct levels were significantly increased in the MGT-treated mice. In addition to oxidative stress- and inflammation related-DNA adduct formations, inflammatory cell infiltration and focal granulomatous formations were also observed in the lungs of MGT-treated mice. Based on these findings, it is suggested that inflammatory responses are probably involved in the genotoxicity induced by MGT in the lungs of mice.


Identification and characterization of the major huperzine a metabolite in rat blood.
Huperzine A (Hup A) is under investigation as a treatment of Alzheimer's disease because of its properties of reversible and specific AChE inhibition. It has additional interesting pharmacological effects such as the protection of primary neuronal cells isolated from embryonic rat brains from glutamate-induced toxicity. We have isolated a new compound which has similar absorbance characteristics as Hup A from blood of rats administered Hup A. Monitoring the effluent from reversed-phase high-performance liquid chromatography (RP-HPLC) of blood collected 60 min after Hup A treatment at an absorbance of 308 nm (lambdamax for Hup A), yielded a peak height and area for this compound that was approximately 1.4-fold the initial Hup A peak. The compound was isolated from RP-HPLC fractions from blood and liver for analysis by mass spectrometry and nuclear magnetic resonance (NMR). The compound gave an (M+H)+ ion with m/z 259 in positive ion mode, yielding a molecular weight (MW) of 258. If derived from Hup A (MW 242), the change in MW indicates a mass gain of 16. This would be consistent with the addition of a single oxygen or a hydroxylation. To determine the location of the modification, it was examined by 1H NMR, and it was found that the added mass was due to a single epoxidation yielding 13,14-epoxy Hup-A.


Engaging Health Professions Educators in an Initiative to Create and Disseminate Micro Virtual Asynchronous Educator Development Content During COVID-19.
Most teaching activities pivoted to virtual during COVID-19. Demanding schedules necessitated brief, asynchronous, and widely disseminated professional development to encourage connection and reinforce educator identity. We created and disseminated micro virtual asynchronous educator development while engaging educators from interprofessional backgrounds to co-create teaching tips. We undertook educational evaluation to understand the impact of our educational initiative, measured along 2 professional development dimensions offering contexts for learning-the individual or independent experience, and the group or collective experience-which served as an organizing framework from which to interpret our results. Between June 2020 and July 2021, 74 educators at our institution were asked to participate in our "One Minute Teaching Tips" initiative by providing a brief tip or pearl. Each tip was edited, prepared as a high-quality infographic, and shared via: (1) website; (2) digital monitors; (3) newsletter; and (4) Twitter (now X). Quantitative metrics measuring website and Twitter engagement were analyzed descriptively and to determine distinctions among key variables. Participants answered a brief survey and directed content analysis was utilized to analyze the open-ended responses. Fifty educators (67.5%) participated. Among those, 45 (90%) completed the survey. Tips were accessed via website 1447 times, averaging 28.9/week. The average tweet garnered 43.2 engagements. Six categories aligned with the individual dimension: participants engaged meaningfully, considered prior experience, relied on educational principles, focused on interest or passion, reflected on teaching practices, and experienced reinforced professional identity. Six categories aligned with the collective dimension: participants felt the initiative supported institutional need, was visible to the community, encouraged engagement with other tips, supported inclusive participation, brought value within the community, and showcased education. Our initiative aligns with a contemporary understanding of professional development and was impactful along individual and collective dimensions. Similar initiatives could be developed in alignment with accreditation requirements.


Role of the kidney in controlling acid-base balance.
The kidney is responsible for the maintenance of an important sector of the regulation of acid-base balance, i.e., that related to the maintenance of the alkaline reserve of the body and to excretion of fixed acids. In this review, the basic mechanisms of H-ion secretion along the nephron, responsible for bicarbonate reabsorption, titratable acid formation and ammonia excretion, are discussed. The mechanisms responsible for tubule acidification along proximal tubule, thick ascending limb, cortical distal tubule and collecting duct are reviewed, having in mind the function of the apical and basolateral membranes. Finally, the pathophysiological aspects of urinary acidification are discussed, focusing on renal tubular acidosis models (induced by maleate and amphotericin B treatment) and their cellular mechanisms, as well as the role of adrenal steroids in urinary acidification.


Analysis of the blood bacterial composition of patients with acute coronary syndrome and chronic coronary syndrome.
Emerging evidence revealed that the blood microbiota plays a role in several non-communicable diseases, including cardiovascular disease. However, the role of circulating microbes in atherosclerosis remains understudied. To test this hypothesis, we performed this study to investigate the microbial profile in the blood of Chines atherosclerosis volunteers. A total of seventy Acute Coronary Syndrome patients, seventy Chronic Coronary Syndrome patients, and seventy healthy individuals were examined using high-throughput Illumina Novaseq targeting the V3-V4 regions of the 16S rRNA gene. The relationship between atherosclerosis and blood microbiome, clinical variables, and their functional pathways were also investigated. Our study observed significantly higher alpha diversity indices (Chao1, p = 0.001, and Shannon, p = 0.004) in the acute coronary syndrome group compared with chronic coronary syndrome and healthy group, although a significantly lower alpha diversity was observed in the chronic coronary syndrome compared to acute coronary syndrome and healthy group. Beta diversity based on principal coordinate analysis demonstrated a major separation among the three groups. In addition, using linear discriminant analysis, a significant distinct taxon such as Actinobacteria _ phylum, and Staphylococcus_ genus in the healthy group; Firmicutes_ phylum, and Lactobacillus_ genus in the chronic coronary syndrome group, and Proteobacteria and Acidobacteriota _ phyla in acute coronary syndrome group were observed among three groups. Clusters of Orthologous Genes grouped and Kyoto Encyclopedia of Genes and Genomes pathways suggested a significant variation among all groups (p < 0.05). The blood microbiota analysis provides potential biomarkers for the detection of coronary syndromes in this population.


The insular formations of the dolphin brain: quantitative cytoarchitectonic studies of the insular component of the limbic lobe.
The large insula of the bottlenose dolphin consists of radial gyri arising, in fanlike fashion, from the transverse insular gyrus, and is covered completely by the frontal, parietal, and temporal opercula . On cytoarchitectonic grounds, the dolphin insula is divided into anterior, middle, and posterior sectors that may be the equivalent of the three similar sectors present in the primate insula. Rostrocaudally, these sectors become increasingly more homogeneous and less laminated. Within each sector progressive differentiation occurs in the direction of the circular sulcus. A transitional cortex, the peripaleocortex in the transverse insular gyrus, is interposed between the prepiriform and the periamygdalar cortex and the proisocortex of the insula proper. This peripaleocortex consists of outer and inner cellular strata separated by a hypocellular lamina dissecans. The outer cell stratum is continuous with layers II and III of the insular proisocortex ; the more prominent inner stratum is continuous with proisocortical layers V and VI; the intervening lamina dissecans becomes partially filled, mostly with modified pyramidal cells of medium size that may constitute an incipient layer IV. A band of myelinated fibers corresponding to the external band of Baillarger is found within the lamina dissecans. The anterior insular sector is characterized by distinct lamination and a well-defined, ribbonlike layer Va. In the middle sector, the cortex is internodense and lamination is less clear. The posterior sector is even less laminated and tends to be externodense . Within each sector, lamination becomes clearer in the direction of the circular sulcus. Furthermore, the rostrocaudal architectonic changes suggest a possible transition from a motor-type to a sensory-type cortex. Beyond the insula, the architecture of the opercular cortices reflect, in turn, the influences of the insular sectors.


Studies on a male eland X kudu hybrid.
An accidental mating between a male eland and a female kudu produced an animal with primarily eland phenotypic characteristics. Despite pronounced male behaviour the animal was azoospermic. Histological examination of the testis showed complete lack of germ cells. Chromosome studies with analysis of Giemsa bands showed that the parental karyotypes differed by two reciprocal translocations and one pericentric inversion, involving chromosomes 1 and 3, 5 and 11, and 9 respectively. All other chromosomes had identical banding patterns.


Correlation between photoreceptor layer integrity and visual function in patients with Stargardt disease: implications for gene therapy.
To perform a clinical characterization of Stargardt patients with ABCA4 gene mutation, and to investigate the correlation between the inner and outer segment (IS/OS) junction morphology and visual acuity, fundus lesions, electroretinogram abnormalities, and macular sensitivity. Sixty-one patients with Stargardt disease (STGD) were given a comprehensive ophthalmic examination. Inner-outer photoreceptor junction morphology evaluated by spectral-domain optical coherence tomography was correlated with visual acuity, fundus lesions, fundus autofluorescence, full-field and multifocal electroretinography responses, and microperimetric macular sensitivities. We classified STGD patients into three groups: (1) IS/OS junction disorganization in the fovea, (2) IS/OS junction loss in the fovea, and (3) extensive loss of IS/OS junction. Mutation analysis of the ABCA4 gene was carried out by sequencing the complete coding region. A significant difference in visual acuity was observed between IS/OS groups 1 and 2 and between IS/OS groups 2 and 3 (P < 0.0001). A significant difference in microperimetry sensitivity was observed between IS/OS groups 2 and 3, and between IS/OS groups 1 and 3 (P < 0.0001). There was also a statistically significant correlation between IS/OS abnormalities and the extent of fundus lesions (Spearman P ≤ 0.01), as well as with the type of ERG and multifocal ERG results (Spearman P ≤ 0.01). Finally, the degree of IS/OS junction preservation showed a statistically significant correlation with the extension of foveal abnormalities assessed by fundus autofluorescence imaging (Spearman P ≤ 0.01). The G1961E mutation was more frequent in the patients without extensive loss of IS/OS junction (P = 0.01) confirming its association with a milder STGD phenotype. The results of this study suggest that a comprehensive approach in the examination of Stargardt patients has the potential to improve the understanding of vision loss and may provide a sensitive measure to evaluate the efficacy of future experimental therapies in patients with STGD.


Multiple criteria optimization joint analyses of microarray experiments in lung cancer: from existing microarray data to new knowledge.
Microarrays can provide large amounts of data for genetic relative expression in illnesses of interest such as cancer in short time. These data, however, are stored and often times abandoned when new experimental technologies arrive. This work reexamines lung cancer microarray data with a novel multiple criteria optimization-based strategy aiming to detect highly differentially expressed genes. This strategy does not require any adjustment of parameters by the user and is capable to handle multiple and incommensurate units across microarrays. In the analysis, groups of samples from patients with distinct smoking habits (never smoker, current smoker) and different gender are contrasted to elicit sets of highly differentially expressed genes, several of which are already associated to lung cancer and other types of cancer. The list of genes is provided with a discussion of their role in cancer, as well as the possible research directions for each of them.


[The Luys' body].
In 1865, Jules Luys (1828-1897) described the 'accessory band of the superior olive' (red nucleus). In 1877, A. Forel completed the description and gave the name of Corpus Luysii (CL) to this grey sub-thalamic formation. In 1927, P. Martin's attribute the Hemiballismus to the destruction of the C.L. and specifies the function of the nucleus foreseen by Luys, which play a crucial role in the synthesis of automatic motor action. The new stimulation techniques of this nucleus in the treatment of Parkinson's disease would have opened a third life for the C.L. if its name hade not be changed into 'nucleus subthalamicus'. Jules Luys, a good anatomist, one of the pioneers in France of microscope and photography, ruined his reputation by his ramblings on hysteria and hypnosis which allowed the 'action of medications at distance', the 'storage of cerebral activities within magnetic crowns' and gave prominence to 'brain emanations'.


Self-assembly of molecular capsules in polar solvents.
[structure: see text] We present a novel type of molecular capsule formed by self-organization of calix[4]arenes with several oppositely charged functional groups located at their upper rims. In highly polar solvents, the complementary half-spheres form stable 1:1 complexes with association constants of up to 7 x 10(5) M(-)(1) in methanol. The cavity inside the capsules is large enough for the inclusion of small aliphatic or (hetero)aromatic guest molecules.


Tamarix arabica and Salvadora persica as antibacterial agents.
Despite the harsh conditions and limited water resources of the Arabian Peninsula, plants that live in this environment contain a variety of bioactive compounds and have been used in traditional medicines for thousands of years. We investigated the effects of ethanol extracts of Tamarix arabica and Salvadora persica on Gram-negative and Gram-positive bacteria. The investigations were include; the inhibition of the bacterial growth, determination of MIC and MBC, detection of kill-time, potassium and phosphorus leakages and detection of the bioactive compounds by the GC-MS analysis. The tested extracts in combination, at a 1:1 volume ratio, showed high inhibitory effects, as reflected by the minimum inhibitory concentrations and minimum bactericidal concentrations. The new EC plate was used to determined MBC and kill-time. Further, the detection of phosphate and potassium leakage indicated a loss of selective permeability of the cytoplasmic membrane after treatment with these extracts. The bioactive compounds in the ethanol extracts of T. arabica and S. persica may offer a less expensive and natural alternative to pharmaceuticals.


Validation of the Arabic version of vocal tract discomfort scale.
Aim: To explore the internal consistency, criterion validity, and discriminative validity of the Arabic version of the vocal tract discomfort scale (VTDS-Arab); and to establish cut-off scores for the VTDS-Arab.Methodology: An overall of 202 participants (31 patients with voice disorders of organic and functional causes, and 171 healthy subjects, mean age 25.3 ± 6.7) were recruited in this study. Participants completed the VTDS-Arab scale and the Arabic version of the voice handicap index (VHI-Arab).Results: The VTDS-Arab had a positive internal consistency confirmed by Cronbach's α = 0.91. The criterion validity of the VTDS-Arab was confirmed by the strong positive correlation between the total scores of the VTDS-Arab and the VHI-Arab (r = 0.64, p < .001). Patients scored higher than the healthy subjects in all the subscales of the VTDS-Arab (p < .001) which confirmed the discriminative validity of the VTDS-Arab. Age and gender were not found to affect the scores of the VTDS as confirmed by Pearson r test (r = 0.02, p = .80) and insignificant p values of Levene's test (F1, 200 = 0.43, p = .51), respectively, which supports the validity of the VTDS-Arab. The study posited interpretations for the ranges of scores of the VTDS-Arab based, where the cut-off score for the VTDS-Arab total was 26.Conclusion: The VTDS-Arab is a reliable and a clinically valid tool that can be used in the evaluation of voice disorders alongside other subjective and objective tools of evaluation.


Detection of zoonotic and livestock-specific assemblages of Giardia duodenalis in free-living wild lizards.
Giardia duodenalis is a zoonotic parasite that infects the gut of a wide range of vertebrates, including numerous wildlife species. However, little is known about this protozoan parasite in reptiles. Fecal samples from 31 wild lizards were collected in Galicia (northwest Spain) and screened for the presence of Giardia by PCR amplification and sequencing of the ITS1-5.8S-ITS2 region in the ribosomal unit. This allowed detection of the parasite in 5 samples (16.1%), and enabled identification of G. duodenalis assemblage A2 in two samples of Iberian rock lizard (Iberolacerta monticola), G. duodenalis assemblage B in other two samples of I. monticola, and G. duodenalis assemblage E in one sample of Bocage's wall lizard (Podarcis bocagei). The results obtained after PCR amplification and sequencing of the SSU-rDNA gene confirmed the presence of G. duodenalis assemblage A in two samples of I. monticola. This is the first report of G. duodenalis in free-living lizards, although further studies are needed to distinguish between actual infection and mechanical dissemination of cysts. The detection of zoonotic and livestock-specific assemblages of G. duodenalis demonstrates the wide environmental contamination by this parasite, possibly due to human activities.


Anisotropic energy distribution in three-dimensional vibrofluidized granular systems.
We examine the energy flows in a three-dimensional model of a granular system consisting of N inelastic hard spheres contained in an open cylinder of radius R under the influence of gravity. Energy is supplied to the system in the vertical direction by a vibrating base and is transferred to the perpendicular directions through particle-particle collisions. We examine how the local and global dissipation of energy by particle-particle and particle-wall collisions depends on the number of particles, the velocity of the vibrating base, and the restitution coefficients.


When Something Seems Amiss: Radiology-Pathology Correlation of Metaplastic Breast Cancer.
Metaplastic breast cancer is difficult to diagnose, resistant to conventional treatment, and biologically aggressive. A suspicious timeline and discordance between imaging findings and histopathologic tissue diagnosis should trigger additional workup. New, large lesions or rapidly growing lesions with complex echogenicity on ultrasound warrant correlation with image-guided biopsy for a definitive diagnosis. Lesions that appear aggressive on imaging, with negative biopsy findings, may represent false negatives due to sampling bias from intratumoral heterogeneity. In such cases, it may be advisable to obtain an excisional biopsy. These tumors are known to progress even with neoadjuvant chemotherapy. Immunotherapy, however, may be effective even for metastatic disease. A multidisciplinary approach and a high index of suspicion may, therefore, confer survival benefits in circumstances where the imaging phenotype does not fit with the timeline or pathologic diagnosis. This report describes five cases of metaplastic breast cancer diagnosed at our institution to highlight the importance of a timely and accurate diagnosis of this rare but aggressive breast malignancy.


Self-splicing of the group I intron from Anabaena pre-tRNA: requirement for base-pairing of the exons in the anticodon stem.
In the cyanobacterium Anabaena, the precursor to tRNA(Leu) has a 249-nucleotide group I intron inserted between the wobble and second bases of the anticodon; the intron self-splices during transcription in vitro [Xu, M. Q., Kathe, S. D., Goodrich-Blair, H., Nierzwicki-Bauer, S. A., & Shub, D. A. (1990) Science 250, 1566-1570]. By studying splicing of isolated pre-tRNA, we confirm that splicing occurs by the two-step transesterification mechanism characteristic of group I introns, resulting in excision of the intron and accurate ligation of the 5' and 3' exons. The first step, guanosine-dependent cleavage of the phosphodiester bond at the 5' splice site, occurs with kcat congruent to 14 min-1 and kcat/Km = 5 x 10(4) M-1 min-1 (32 degrees C, 15 mM MgCl2), unexpectedly efficient for a small group I intron. (kcat/Km is comparable to that of the Tetrahymena pre-rRNA intron, and kcat is an order of magnitude higher than any previously reported for a group I intron). The second step, ligation of the exons, is so slow (k = 0.3 min-1) that it is rate-limiting for splicing in vitro except at very low guanosine concentrations. Disruption of the base pairs that make up the anticodon stem of the tRNA dramatically reduces the rate of the first step of splicing, while compensatory mutations that restore base pairing generally restore activity. We suggest that the very short P1 helix of this pre-tRNA, with only three base pairs preceding the 5' splice site, is unstable without the additional base pairs in the anticodon stem.(ABSTRACT TRUNCATED AT 250 WORDS)


Diversity and dynamics of relevant nanoplanktonic diatoms in the Western English Channel.
In the ocean, Bacillariophyta are one of the most successful protistan groups. Due to their considerable biogeochemical implications, diatom diversity, development, and seasonality have been at the center of research, specifically large-sized species. In comparison, nanoplanktonic diatoms are mostly disregarded from routine monitoring and are often underrepresented in genetic reference databases. Here, we identified and investigated the temporal dynamics of relevant nanodiatoms occurring in the Western English Channel (SOMLIT-Astan station). Coupling in situ and laboratory approaches, we revealed that nano-species from the genera Minidiscus and Thalassiosira are key components of the phytoplankton community that thrive in these coastal waters, but they display different seasonal patterns. Some species formed recurrent blooms whilst others were persistent year round. These results raise questions about their regulation in the natural environment. Over a full seasonal cycle at the monitoring station, we succeeded in isolating viruses which infect these minute diatoms, suggesting that these mortality agents may contribute to their control. Overall, our study points out the importance of considering nanodiatom communities within time-series surveys to further understand their role and fate in marine systems.


The impact of acute high-intensity interval exercise on biomarkers of cardiovascular health in type 2 diabetes.
High-intensity interval training (HIIT) interventions improve cardiovascular health, yet the acute effects on circulating and functional biomarkers of cardiovascular function are unclear in individuals with type 2 diabetes (T2D). To explore this, we conducted two investigations to examine the acute response to HIIT in individuals with T2D. Study 1 measured blood pressure, endothelial-dependent dilation, circulating measures of endothelial activation, and troponin T, 30 min and 2 h after HIIT (7 × 1-min intervals) in T2D (n = 8) and age-matched normoglycemic controls (CTL; n = 8). Study 2 assessed circulating measures of endothelial activation and troponin T, 30 min, and 24 h after HIIT (10 × 1-min intervals) in ten previously trained T2D men. In study 1, markers of endothelial function and activation within the first 2 h after HIIT did not differ from baseline between T2D and CTL participants, except at 30 min after HIIT for glucose, which was reduced more in T2D than CTL (by -0.8 ± 1.2 mmol/L, p = 0.04), and VCAM-1, which was reduced more 30 min after HIIT in CTL compared to T2D (by -187 ± 221 ng/mL, p = 0.05). Study 2 saw no significant difference in any circulating markers of endothelial activation and troponin T, 30 min, and 24 h after HIIT in trained T2D males. Exploratory findings from these two studies suggest that acute HIIT does not substantially alter circulating and functional markers of cardio(vascular) health in individuals with T2D who are unaccustomed (study 1) and accustomed to HIIT (study 2).


The Value of IGF-1 and IGFBP-1 in Patients With Heart Failure With Reduced, Mid-range, and Preserved Ejection Fraction.
Previous studies have reported inconsistent results regarding the implications of deranged insulin-like growth factor 1 (IGF-1)/insulin-like growth factor-binding protein 1 (IGFBP-1) axis in patients with heart failure (HF). This study evaluates the roles of IGF1/IGFBP-1 axis in patients with HF with reduced ejection fraction (HFrEF), mid-range ejection fraction (HFmrEF), or preserved ejection fraction (HFpEF). Consecutive patients with HFrEF, HFmrEF, and HFpEF who underwent comprehensive cardiac assessment were included. The primary endpoint was the composite endpoint of all-cause death and HF rehospitalization at one year. A total of 151 patients with HF (HFrEF: n = 51; HFmrEF: n = 30; HFpEF: n = 70) and 50 control subjects were included. The concentrations of IGFBP-1 (p < 0.001) and IGFBP-1/IGF-1 ratio (p < 0.001) were significantly lower in patients with HF compared to controls and can readily distinguish patients with and without HF (IGFBP-1: areas under the curve (AUC): 0.725, p < 0.001; IGFBP-1/IGF-1 ratio: AUC:0.755, p < 0.001; respectively). The concentrations of IGF-1, IGFBP-1, and IGFBP-1/IGF-1 ratio were similar among HFpEF, HFmrEF, and HFrEF patients. IGFBP-1 and IGFBP-1/IGF-1 ratio positively correlated with N-terminal probrain natriuretic peptide (NT-proBNP) levels (r = 0.255, p = 0.002; r = 0.224, p = 0.007, respectively). IGF-1, IGFBP-1, and IGFBP-1/IGF-1 ratio did not predict the primary endpoint at 1 year for the whole patients with HF and HF subtypes on both univariable and multivariable Cox regression. The concentrations of plasma IGFBP-1 and IGFBP-1/IGF-1 ratio can distinguish patients with and without HF. In HF, IGFBP-1 and IGFBP-1/IGF-1 ratio positively correlated with NT-proBNP levels.


Interstitial duplication of 2q32.1-q33.3 in a patient with epilepsy, developmental delay, and autistic behavior.
Duplications of the 2q33 region are rare; to date, only 13 patients have been reported to have this chromosomal abnormality. The reported duplications are of varying size, and the patients shared developmental delay and minor dysmorphic findings. In this study, we identified a duplication of 2q32.1-q33.3 in a patient with psychomotor developmental delay, epilepsy, and autistic behavior. The duplicated region of this patient was reciprocal to the 2q32-q33 deletion syndrome. Chromosomal microarray testing confirmed the 19.5 Mb of duplication that includes over 100 genes, some of which could have functional relevance to the neurological features of this patient. The SATB homeobox 2 gene (SATB2)-the primary gene responsible for the 2q32-q33 deletion syndrome-may be one of them, because of its expression in the cortical projection neurons of the developing brain. The duplication of the potassium channel tetramerisation domain-containing 18 gene (KCTD18) and the ADAM metallopeptidase domain 23 gene (ADAM23) may also contribute to the phenotype. FISH analysis confirmed a tandem configuration of the duplicated segments. This result is in agreement with our previous study, in which we observed that duplicated segments as interstitial duplications are generally inserted in the tandem configuration.


Disruption of Apicoplast Biogenesis by Chemical Stabilization of an Imported Protein Evades the Delayed-Death Phenotype in Malaria Parasites.
Malaria parasites (Plasmodium spp.) contain a nonphotosynthetic plastid organelle called the apicoplast, which houses essential metabolic pathways and is required throughout the parasite life cycle. The biogenesis pathways responsible for apicoplast growth, division, and inheritance are of key interest as potential drug targets. Unfortunately, several known apicoplast biogenesis inhibitors are of limited clinical utility because they cause a peculiar "delayed-death" phenotype in which parasites do not stop replicating until the second lytic cycle posttreatment. Identifying apicoplast biogenesis pathways that avoid the delayed-death phenomenon is a priority. Here, we generated parasites targeting a murine dihydrofolate reductase (mDHFR) domain, which can be conditionally stabilized with the compound WR99210, to the apicoplast. Surprisingly, chemical stabilization of this exogenous fusion protein disrupted parasite growth in an apicoplast-specific manner after a single lytic cycle. WR99210-treated parasites exhibited an apicoplast biogenesis defect beginning within the same lytic cycle as drug treatment, indicating that stabilized mDHFR perturbs a non-delayed-death biogenesis pathway. While the precise mechanism-of-action of the stabilized fusion is still unclear, we hypothesize that it inhibits apicoplast protein import by stalling within and blocking translocons in the apicoplast membranes.IMPORTANCE Malaria is a major cause of global childhood mortality. To sustain progress in disease control made in the last decade, new antimalarial therapies are needed to combat emerging drug resistance. Malaria parasites contain a relict chloroplast called the apicoplast, which harbors new targets for drug discovery. Unfortunately, some drugs targeting apicoplast pathways exhibit a delayed-death phenotype, which results in a slow onset-of-action that precludes their use as fast-acting, frontline therapies. Identification of druggable apicoplast biogenesis factors that will avoid the delayed-death phenotype is an important priority. Here, we find that chemical stabilization of an apicoplast-targeted mDHFR domain disrupts apicoplast biogenesis and inhibits parasite growth after a single lytic cycle, suggesting a non-delayed-death target. Our finding indicates that further interrogation of the mechanism-of-action of this exogenous fusion protein may reveal novel therapeutic avenues.


Triboelectric Nanogenerator as a Probe for Measuring the Charge Transfer between Liquid and Solid Surfaces.
The phenomenon of triboelectricity involves the flow of charged species across an interface, but conclusively establishing the nature of the charge transfer has proven extremely difficult, especially for the liquid-solid cases. Herein, we developed a self-powered droplet triboelectric nanogenerator (droplet-TENG) with spatially arranged electrodes as a probe for measuring the charge transfer process between liquid and solid interfaces. The information on the electric signal on spatially arranged electrodes shows that the charge transfer between droplets and the solid is an accumulation process during the dropping and that the electron is the dominant charge-transfer species. Such a droplet-TENG showed a high sensitivity to the ratio of solvents in the mixed organic solution, and we postulated this is due to the possibility of generation of a hydrogen bond, affecting the electric signal on the spatially arranged electrodes. This work demonstrated a chemical sensing application based on the self-powered droplet triboelectric nanogenerator.


Sex differences in the molecular signature of the developing mouse hippocampus.
A variety of neurological disorders, including Alzheimer's disease, Parkinson's disease, major depressive disorder, dyslexia and autism, are differentially prevalent between females and males. To better understand the possible molecular basis for the sex-biased nature of neurological disorders, we used a developmental series of female and male mice at 1, 2, and 4 months of age to assess both mRNA and protein in the hippocampus with RNA-sequencing and mass-spectrometry, respectively. The transcriptomic analysis identifies 2699 genes that are differentially expressed between animals of different ages. The bulk of these differentially expressed genes are changed in both sexes at one or more ages, but a total of 198 transcripts are differentially expressed between females and males at one or more ages. The number of transcripts that are differentially expressed between females and males is greater in adult animals than in younger animals. Additionally, we identify 69 transcripts that show complex and sex-specific patterns of temporal regulation through postnatal development, 8 of which are heat-shock proteins. We also find a modest correlation between levels of mRNA and protein in the mouse hippocampus (Rho = 0.53). This study adds to the substantial body of evidence for transcriptomic regulation in the hippocampus during postnatal development. Additionally, this analysis reveals sex differences in the transcriptome of the developing mouse hippocampus, and further clarifies the need to include both female and male mice in longitudinal studies involving molecular changes in the hippocampus.


[Consensus of Chinese experts on diagnosis and treatment processes of acute myocardial infarction in the context of prevention and control of COVID-19 (first edition)].
The SARS-CoV-2 epidemic starting in Wuhan in December, 2019 has spread rapidly throughout the nation. The control measures to contain the epidemic also produced influences on the transport and treatment process of patients with acute myocardial infarction (AMI), and adjustments in the management of the patients need to be made at this particular time. AMI is characterized by an acute onset with potentially fatal consequence, a short optimal treatment window, and frequent complications including respiratory infections and respiratory and circulatory failure, for which active on-site treatment is essential. To standardize the management and facilitate the diagnosis and treatment, we formulated the guidelines for the procedures and strategies for the diagnosis and treatment of AMI, which highlight 5 Key Principles, namely Nearby treatment, Safety protection, Priority of thrombolysis, Transport to designated hospitals, and Remote consultation. For AMI patients, different treatment strategies are selected based on the screening results of SARS-CoV-2, the time window of STEMI onset, and the vital signs of the patients. During this special period, the cardiologists, including the interventional physicians, should be fully aware of the indications and contraindications of thrombolysis. In the transport and treatment of AMI patients, the physicians should strictly observe the indications for patient transport with appropriate protective measurements of the medical staff.


Blogged nursing: analysis of the phenomenon and contextualization in the Spanish setting.
Blogging within the health profession has grown in the recent past. This article aims to perform an analysis of the theoretical aspects of blogging, the use by professional nurses and students, benefits for patients, and, finally, an approach to the activities of Spanish nursing blogs. Blogs have great advantages as social communication tools. Immediacy in content update, closeness to information consumers, and compatibility with other Web 2.0 tools are points to be highlighted. Nurses use blogs for education and communication with other health professionals, students, and patients. For patients, therapeutic effects have been demonstrated in using blogging to share their health problems and express their experiential viewpoints. There are about 80 blogs written by Spanish nurses; most of them originated in the period between 2010 and 2012. These blogs are targeted to professionals (59%), patients (20%), or mixed (13%). There is a great heterogeneity in content: informative style (20%), opinion (28%), narrative (9%), experiential (2%), or humorous (2%). Nursing language is present in 15%, research and evidence-based practice in 13%, and protocols, guidelines, and procedures in 11% of them. We propose the need to plan institutional strategies for effective use of Web 2.0 resources as well as the need to unify criteria to provide quality content.


Modulators of alternative splicing as novel therapeutics in cancer.
Alternative splicing (AS), the process of removing introns from pre-mRNA and re-arrangement of exons to give several types of mature transcripts, has been described more than 40 years ago. However, until recently, it has not been clear how extensive it is. Genome-wide studies have now conclusively shown that more than 90% of genes are alternatively spliced in humans. This makes AS one of the main drivers of proteomic diversity and, consequently, determinant of cellular function repertoire. Unsurprisingly, given its extent, numerous splice isoforms have been described to be associated with several diseases including cancer. Many of them have antagonistic functions, e.g., pro- and anti-angiogenic or pro- and anti-apoptotic. Additionally several splice factors have been recently described to have oncogene or tumour suppressors activities, like SF3B1 which is frequently mutated in myelodysplastic syndromes. Beside the implications for cancer pathogenesis, de-regulated AS is recognized as one of the novel areas of cell biology where therapeutic manipulations may be designed. This editorial discusses the possibilities of manipulation of AS for therapeutic benefit in cancer. Approaches involving the use of oligonucleotides as well as small molecule splicing modulators are presented as well as thoughts on how specificity might be accomplished in splicing therapeutics.


Factors influencing the levels of work engagement in physicians from Poland, Serbia and Bulgaria.
Lowered work engagement and burnout are a growing problem in recent years, especially among physicians. Cynicism, lack of energy and decreased efficacy may lead to the occurrence of severe depression. These phenomena influence almost every aspect of affected person's life, both professional and extraprofessional, and decrease its quality. The aim of our study was to evaluate the influence of family life and other factors on levels of work engagement and risk of depression. Our study was conducted on a group of 417 physicians from Poland, Serbia and Bulgaria using a paper questionnaire. The collected data was subjected to statistical analyses using Statsoft Statistica v. 10.0 software. There was no significant correlation between work engagement and sex or age. The highest score on work engagement was in Serbia (m=4.41; Mann-Whitney's U test with p<0.05). The highest score of BDI was in Bulgaria (m=14.73; Mann-Whitney's U test with p<0.05). There was no significant correlation exceeding r=0.5 between UWES and SWING scales. WHI+/WHI- ratio correlates significantly with a BDI scale (Spearman's r=-0.49; p<0.05). Family life of physicians seem to have minor or even no influence on their work engagement and risk of burnout. The negative influence of work on family life may increase the risk of depression, and that effect is not susceptible to either positive or negative interactions of family life with work. The country with the lowest expenditure on a healthcare have also the lowest levels of work engagement.


Comparison Between Urinalysis Results and Self-Reported Heroin Use Among Patients Undergoing Methadone Maintenance Treatment in China.
The validity and concordance of two main measures of drug use behavior, self-report and urinalysis, has long been discussed. More understanding is needed about the underlying factors associated with discordance between these two methods. Describe the pattern and associated factors of discordance between self-reported heroin use and the urinalysis results of opiate use among methadone maintenance therapy (MMT) patients in China. A total of 2,448 MMT patients from 68 clinics in five provinces of China participated in a survey, which collected information on demographics, drug use and MMT-related factors, depressive symptoms, and drug avoidance self-efficacy. The most recent urine morphine test result was obtained from medical records and compared with self-reported heroin use. Participants who had urinalysis within 14 days of the survey were included in the analysis. Among the 1,092 participants, 70 (6.4%) self-reported heroin use and 195 (17.9%) had positive urinalysis results. The over-reporters group had significantly higher education, and the under-reporters had significantly higher level of drug-avoidance self-efficacy and lower level of depressive symptoms. Among the participants who either self-reported heroin use or had positive urinalysis results, being young, having higher education, and having lower level of depressive symptoms were associated with discordance between self-reports and urinalysis results. The combination of both measures in assessing drug use behavior seems necessary. The validity of self-report should be considered differently based on demographic and psychosocial characteristics.


Transport of the Glucosamine-Derived Browning Product Fructosazine (Polyhydroxyalkylpyrazine) Across the Human Intestinal Caco-2 Cell Monolayer: Role of the Hexose Transporters.
The transport mechanism of fructosazine, a glucosamine self-condensation product, was investigated using a Caco-2 cell model. Fructosazine transport was assessed by measuring the bidirectional permeability coefficient across Caco-2 cells. The mechanism of transport was evaluated using phlorizin, an inhibitor of sodium-dependent glucose cotransporters (SGLT) 1 and 2, phloretin and quercetin, inhibitors of glucose transporters (GLUT) 1 and 2, transcytosis inhibitor wortmannin, and gap junction disruptor cytochalasin D. The role of hexose transporters was further studied using downregulated or overexpressed cell lines. The apparent permeability (Pa,b) of fructosazine was 1.30 ± 0.02 × 10-6 cm/s. No significant (p > 0.05) effect was observed in fructosazine transport by adding wortmannin and cytochalasin D. The presence of phlorizin, phloretin, and quercetin decreased fructosazine transport. The downregulated GLUT cells line was unable to transport fructosazine. In human intestinal epithelial Caco-2 cells, GLUT1 or GLUT2 and SGLT are mainly responsible for fructosazine transport.


Research progress of novel bio-denitrification technology in deep wastewater treatment.
Excessive nitrogen emissions are a major contributor to water pollution, posing a threat not only to the environment but also to human health. Therefore, achieving deep denitrification of wastewater is of significant importance. Traditional biological denitrification methods have some drawbacks, including long processing times, substantial land requirements, high energy consumption, and high investment and operational costs. In contrast, the novel bio-denitrification technology reduces the traditional processing time and lowers operational and maintenance costs while improving denitrification efficiency. This technology falls within the category of environmentally friendly, low-energy deep denitrification methods. This paper introduces several innovative bio-denitrification technologies and their combinations, conducts a comparative analysis of their denitrification efficiency across various wastewater types, and concludes by outlining the future prospects for the development of these novel bio-denitrification technologies.


How ischaemic region shape affects ST potentials in models of cardiac tissue.
This numerical study uses a simple bidomain model of cardiac tissue to compare the effect of three different ischaemic region geometries (rectangular, cylindrical and semi-ellipsoidal) on the extracellular epicardial potentials during the ST segment. Results are obtained using anisotropic conductivities based on experimentally derived data. The model is then altered, to include heterogeneous conductivities in the ischaemic region and larger border zone widths, in order to better reproduce realistic scenarios. Initial results for the rectangular and cylindrical ischaemic shapes show a central depression over the ischaemic region, for low ischaemic thicknesses, which separates into three depressions as the ischaemic thickness increases. For ischaemic thicknesses above 70% an elevation appears over the ischaemic region and this increases in magnitude as the ischaemia becomes transmural. Results for the semi-ellipsoidal shape, however, differ, with the central depression separating into only two depressions as the thickness increases. Changing the conductivity inside the ischaemic region significantly affects results for each geometry, with depression staying over the ischaemic region for much higher levels of ischaemia (up to 90% thickness). Increasing the intramural border zone thickness did not significantly affect the epicardial potential distributions.


[Treatment of decubitus ulcer with Crilanomer and dextranomer].
In a clinical study on decubital ulcers, 95 patients in 10 hospitals were treated with dextranomer and crilanomer. The size of the ulcer surface and the physician's evaluation of the healing status at the end of treatment served as the most important criteria for our assessment of the curative effect. Both preparations proved equivalent in the statistical test. Crilanomer revealed slightly better results than dextranomer with regard to the physician's overall evaluation al well as odor, exudation, and cleansing. Both modes of treatment were accompanied by local incompatibility reactions of a minor degree; there were no systemic side effects in either preparation.


Mycobacterium bovis in the European badger (Meles meles): epidemiological findings in tuberculous badgers from a naturally infected population.
This study investigates the course of tuberculosis in a naturally infected badger population, its impact on the population and the risk of spread to other species in the light of capture data and post-mortem findings from 47 tuberculous badgers, stratified by age group and sex, accrued since 1975. The findings are compared with those for 260 badgers from the same population in whom no evidence of infection was detected. Detailed estimates of seasonal variations in bodyweight for uninfected male and female cub, yearling and adult badgers are presented and compared to the weights at post-mortem examination of the tuberculous badgers, in whom poor condition and weight loss were the principal presenting signs. Lesions were seen especially in the lungs and associated lymph nodes, and in the kidneys. Organisms were detected intermittently in faeces, urine, sputum and discharging bite wounds. Infected animals could survive for nearly 2 years and produce cubs successfully.


Model for dissipative highly nonlinear waves in dry granular systems.
A model is presented for the characterization of dissipative effects on highly nonlinear waves in one-dimensional dry granular media. The model includes three terms: Hertzian, viscoelastic, and a term proportional to the square of the relative velocity of particles. The model outcomes are confronted with different experiments where the granular system is subject to several constraints for different materials. Excellent qualitative and quantitative agreement between theory and experiments is found.


Revision endoscopic sinus surgery: the Thomas Jefferson University experience.
Since its introduction, functional endoscopic sinus surgery (FESS) has demonstrated success rates of 76% to 98%. A small group of the patients in whom initial FESS and optimal medical therapy fail require revision endoscopic sinus surgery (RESS). This group has recently been studied by several authors, and we have evaluated a group of 90 RESS patients selected from 753 consecutive primary FESS patients. Patients were followed for a mean of 22.8 months. Extent of disease, history of polyps, allergy, previous traditional endonasal sinus surgery, male gender, chronic steroid use, and the presence of a deviated septum all appeared to adversely affect RESS outcome. The surgeon's knowledge of the sinus anatomy is critical, especially in revision sinus cases in which landmarks are distorted or absent. In our review, RESS was associated with a 1% major complication rate and was successful in 67% of patients. Computer-assisted endoscopic sinus surgery integrates preoperative imaging with realtime endoscopic visualization, augments the surgeon's knowledge of anatomy, and helps to minimize patient risk.


Evaluation of the Efficacy of a Hydrolyzed Collagen Supplement for Improving Skin Moisturization, Smoothness, and Wrinkles.
We sought to assess the efficacy of a hydrolyzed collagen supplement (Lapi Gelatine, Empoli, Italy) for improving skin moisturization and elasticity as well as the appearance of wrinkles. A monocentric, randomized, controlled study was performed; the study included 52 volunteers who were divided into two groups. Twenty-six subjects took the collagen supplement and the other 26 participants received maltodextrin for a period of 56 days. Skin moisturization, skin elasticity, and wrinkle depth were instrumentally evaluated. Clinical parameters, including skin softness, skin firmness, skin smoothness, and the visibility of wrinkles were subjectively evaluated by a dermatologist. Finally, the gastrointestinal tolerability was evaluated during the period of treatment. Improvements in skin moisturization, skin elasticity and wrinkle depth were measured in the participants taking the hydrolyzed collagen after 28 days. In all enrolled participants, the results of the analysis of variance showed a statistically significant effect of the interaction between product and time. The evolution over time of the investigated parameters was significantly different between the participants taking the hydrolyzed collagen and the participants taking the maltodextrin. Furthermore, it was well tolerated and no adverse effects were recorded.


Improvement of axial dystonia with the administration of clozapine.
A 45-year-old white male with a positive family history for various neurological disorders (not including dystonias), and a long history of neuroleptic exposure on account of a chronic schizoaffective illness, developed severe torsion trunkal movement to the left which were accompanied by inversion of the left arm and outward extension of the right arm, as well as left torticollis. The axial dystonia, which was refractory to treatment, was disabling interfering with the activities of daily living, posture and gait. Radiological studies revealed marked dextroscoliosis. The administration of clozapine in dosages of 200 mg p.o. in the morning and 250 mg p.o. at bedtime, resulted in a significant improvement of the neck and trunk dystonia. After the discontinuation of the clozapine, an exacerbation of the movement disorder back to baseline levels prior to the use of this agent, was observed. Subsequent therapy with thioridazine in a dosage of 600 mg/day did not mask or treat the dystonia. The clinical implications of these findings are discussed.


Magnetic Resonance Imaging of Nonneoplastic Musculoskeletal Pathologies in the Pelvis.
Musculoskeletal pathologies in the pelvis encompass a wide variety of lesions including femoroacetabular impingement, athletic pubalgia, ischiofemoral impingement, and apophyseal avulsion injuries. Magnetic resonance imaging is the noninvasive imaging modality of choice for the diagnosis and management of these lesions. In this article, the authors discuss the nonneoplastic musculoskeletal lesions in the pelvis, with illustrations and relevant case examples.


[Expression of the F3h gene in various wheat organs].
In plants, the F3h gene encodes akey enzyme of flavonoid biosynthesis pathway, flavanone 3-hydroxylase. In most plant species, F3h is a single-copy gene, whereas in the genome of bread wheat (Triticum aestivum L., 2n = 6x = 42, BBAADD), four copies of this gene were found. Using RT-PCR, transcription of these copies was studied in various organs of several wheat genotypes. Three homoeologous copies (F3h-A1, F3h-B1, F3h-D1) manifested similar expression patterns and were specifically transcribed in caryopsis pericarp, culm, coleoptile and leaf colored with anthocyanins. The paralogous copy F3h-B2 in the B-genome was expressed only in wheat roots and probably is involved in biosynthesis of some uncolored flavonoid compounds unrelated to anthocyanin biosynthesis.


Antigenic type-specificity of swine isolates of Streptococcus equisimilis.
Isolates of a Lancefield Group C organism, Streptococcus equisimilis, of sow reproductive tract and young swine joint origin were found to possess type-specific antigens. Capillary precipitin and immunodiffusion tests, done with acid extracts and cross-absorbed rabbit antisera, revealed four serotypes among 62 of 64 isolates. Extracts of two swine isolates of S. equisimilis and other Lancefield Group C strains including S. equi, S. zooepidemicus and three previously established types of S. equisimilis of human origin did not react with any of the four type-specific sera. Antigens responsible for type-specificity were heat-stable and sensitive to trypsin.


Circulating pregnancy-associated plasma protein a predicts outcome in patients with acute coronary syndrome but no troponin I elevation.
Risk stratification in troponin (cTn)-negative acute coronary syndrome (ACS) remains a clinical challenge. We investigated the predictive value of circulating pregnancy-associated plasma protein A (PAPP-A), a novel marker of atherosclerotic plaque activity, in these patients. Two hundred consecutive hospitalized ACS patients were included, of whom 136 (69 men and 67 women; mean+/-SD age, 66+/-16 years) remained cTnI-negative for up to 24 hours. PAPP-A was measured at admission, 6 to 12 hours, and 24 hours. During 6-month follow-up, 26 (19.1%) of the cTnI-negative patients reached a primary end point (cardiovascular death, myocardial infarction, or revascularization). At a cutoff level of 2.9 mIU/L, elevated PAPP-A was an independent predictor of adverse outcome (adjusted risk ratio [RR], 4.6; 95% confidence interval, 1.8 to 11.8; P=0.002). Another independent predictor was admission CRP >2.0 mg/L (RR, 2.6; P=0.03). Measurement of plasma PAPP-A, a zinc-binding matrix metalloproteinase, is a strong independent predictor of ischemic cardiac events and need of revascularization in patients who present with suspected myocardial infarction but remain troponin negative.


Insufficient lymph node assessment in gastric adenocarcinoma.
This study aimed to investigate the sufficient (≥ 16) lymph node assessment in 449 patients with gastric adenocarcinoma and literature review. Four hundred and forty-nine patients with pathologically confirmed locoregional invasive gastric adenocarcinoma from 2004 to 2013 were included. A standard surgical resection was performed for all the patients with (n = 16) or without (n = 433) neoadjuvant treatment. In this study, 301 men and 148 women with a median age of 58 (range 21-88) years were included. The median total numbers of examined lymph nodes were 9 (range 0-55). Ninety-five patients (21.2%) had adequate (≥ 16) lymph node examination, and 70 patients (15.6%) had no examined lymph nodes. In univariate analysis, total or near total gastrectomy (P < 0.001), advanced node stage (P < 0.001), primary tumor size > 6 cm (P < 0.001), and the presence of perineural invasion (P = 0.039) were associated with more average number of examined lymph nodes. On multivariate analysis, node stage (P < 0.001) and type of surgery (P = 0.008) were independent predictive factors. In this study, approximately one in five patients with gastric adenocarcinoma had sufficient lymph node assessment. More studies are suggested for identifying a true inadequate lymph node dissection from insufficient lymph node assessment.


13 C-metabolic flux analysis of human adenovirus infection: Implications for viral vector production.
Adenoviruses are human pathogens increasingly used as gene therapy and vaccination vectors. However, their impact on cell metabolism is poorly characterized. We performed carbon labeling experiments with [1,2-13 C]glucose or [U-13 C]glutamine to evaluate metabolic alterations in the amniocyte-derived, E1-transformed 1G3 cell line during production of a human adenovirus type 5 vector (AdV5). Nonstationary 13 C-metabolic flux analysis revealed increased fluxes of glycolysis (17%) and markedly PPP (over fourfold) and cytosolic AcCoA formation (nearly twofold) following infection of growing cells. Interestingly, infection of growth-arrested cells increased overall carbon flow even more, including glutamine anaplerosis and TCA cycle activity (both over 1.5-fold), but was unable to stimulate the PPP and was associated with a steep drop in AdV5 replication (almost 80%). Our results underscore the importance of nucleic and fatty acid biosynthesis for adenovirus replication. Overall, we portray a metabolic blueprint of human adenovirus infection, highlighting similarities with other viruses and cancer, and suggest strategies to improve AdV5 production. Biotechnol. Bioeng. 2017;114: 195-207. © 2016 Wiley Periodicals, Inc.


Maturation of lipid metabolism in the fetal and newborn sheep heart.
At birth, the fetus experiences a dramatic change in environment that is accompanied by a shift in myocardial fuel preference from lactate and glucose in fetal life to fatty acid oxidation after birth. We hypothesized that fatty acid metabolic machinery would mature during fetal life in preparation for this extreme metabolic transformation at birth. We quantified the pre- (94-day and 135-day gestation, term ∼147 days) and postnatal (5 ± 4 days postnatal) gene expression and protein levels for fatty acid transporters and enzymes in hearts from a precocial species, the sheep. Gene expression of fatty acid translocase (CD36), acyl-CoA synthetase long-chain 1 (ACSL1), carnitine palmitoyltransferase 1 (CPT1), hydroxy-acyl dehydrogenase (HADH), acetyl-CoA acetyltransferase (ACAT1), isocitrate dehydrogenase (IDH), and glycerol phosphate acyltransferase (GPAT) progressively increased through the perinatal period, whereas several genes [fatty acid transport protein 6 (FATP6), acyl-CoA synthetase long chain 3 (ACSL3), long-chain acyl-CoA dehydrogenase (LCAD), very long-chain acyl-CoA dehydrogenase (VLCAD), pyruvate dehydrogenase kinase (PDK4), phosphatidic acid phosphatase (PAP), and diacylglycerol acyltransferase (DGAT)] were stable in fetal hearts and had high expression after birth. Protein expression of CD36 and ACSL1 progressively increased throughout the perinatal period, whereas protein expression of carnitine palmitoyltransferase 1a (fetal isoform) (CPT1a) decreased and carnitine palmitoyltransferase 1b (adult isoform) (CPT1b) remained constitutively expressed. Using fluorescent-tagged long-chain fatty acids (BODIPY-C12), we demonstrated that fetal (125 ± 1 days gestation) cardiomyocytes produce 59% larger lipid droplets (P < 0.05) compared with newborn (8 ± 1 day) cardiomyocytes. These results provide novel insights into the perinatal maturation of cardiac fatty acid metabolism in a precocial species.NEW & NOTEWORTHY This study characterized the previously unknown expression patterns of genes that regulate the metabolism of free fatty acids in the perinatal sheep myocardium. This study shows that the prenatal myocardium prepares for the dramatic switch from carbohydrate metabolism to near complete reliance on free fatty acids postnatally. Fetal and neonatal cardiomyocytes also demonstrate differing lipid storage mechanisms where fetal cardiomyocytes form larger lipid droplets compared with newborn cardiomyocytes.


A systems-level approach reveals new gene regulatory modules in the developing ear.
The inner ear is a complex vertebrate sense organ, yet it arises from a simple epithelium, the otic placode. Specification towards otic fate requires diverse signals and transcriptional inputs that act sequentially and/or in parallel. Using the chick embryo, we uncover novel genes in the gene regulatory network underlying otic commitment and reveal dynamic changes in gene expression. Functional analysis of selected transcription factors reveals the genetic hierarchy underlying the transition from progenitor to committed precursor, integrating known and novel molecular players. Our results not only characterize the otic transcriptome in unprecedented detail, but also identify new gene interactions responsible for inner ear development and for the segregation of the otic lineage from epibranchial progenitors. By recapitulating the embryonic programme, the genes and genetic sub-circuits discovered here might be useful for reprogramming naïve cells towards otic identity to restore hearing loss.


Relaxor Pb(Mg(1/3)Nb(2/3))O3: a ferroelectric with multiple inhomogeneities.
Despite intensive studies on Pb(Mg(1/3)Nb(2/3))O(3) (PMN) relaxor, understanding the exact nature of its giant dielectric response and of its physical ground state is a fundamental issue that has remained unresolved for decades. Here, we report a comprehensive study of PMN relaxor crystal, and show that (i) its anomalous dielectric behavior in a broad temperature range results from the reorientation of polarization in the crystal, and (ii) the PMN relaxor is essentially a nanosized ferroelectric material with multiscale inhomogeneities of domain structure in addition to the well-known inhomogeneities of chemical composition and local symmetry. Such inhomogeneities are believed to play a crucial role in producing the huge and enigmatic physical effects in relaxor system, and may be used to design other new systems with giant effects such as a relaxor system.


Language impairment in Huntington's disease.
Language alterations in Huntington's disease (HD) are reported, but their nature and correlation with other cognitive impairments are still under investigation. This study aimed to characterize the language disturbances in HD and to correlate them to motor and cognitive aspects of the disease. We studied 23 HD patients and 23 controls, matched for age and schooling, using the Boston Diagnostic Aphasia Examination, Boston Naming Test, the Token Test, Animal fluency, Action fluency, FAS-COWA, the Symbol Digit Modalities Test, the Stroop Test and the Hooper Visual Organization Test (HVOT). HD patients performed poorer in verbal fluency (p<0.0001), oral comprehension (p<0.0001), repetition (p<0.0001), oral agility (p<0.0001), reading comprehension (p=0.034) and narrative writing (p<0.0001). There was a moderate correlation between the Expressive Component and Language Competency Indexes and the HVOT (r=0.519, p=0.011 and r=0.450, p=0.031, respectively). Language alterations in HD seem to reflect a derangement in both frontostriatal and frontotemporal regions.