Natural Melanin/Alginate Hydrogels Achieve Cardiac Repair through ROS Scavenging and Macrophage Polarization.
The efficacy of cardiac regenerative strategies for myocardial infarction (MI) treatment is greatly limited by the cardiac microenvironment. The combination of reactive oxygen species (ROS) scavenging to suppress the oxidative stress damage and macrophage polarization to regenerative M2 phenotype in the MI microenvironment can be desirable for MI treatment. Herein, melanin nanoparticles (MNPs)/alginate (Alg) hydrogels composed of two marine-derived natural biomaterials, MNPs obtained from cuttlefish ink and alginate extracted from ocean algae, are proposed. Taking advantage of the antioxidant property of MNPs and mechanical support from injectable alginate hydrogels, the MNPs/Alg hydrogel is explored for cardiac repair by regulating the MI microenvironment. The MNPs/Alg hydrogel is found to eliminate ROS against oxidative stress injury of cardiomyocytes. More interestingly, the macrophage polarization to regenerative M2 macrophages can be greatly promoted in the presence of MNPs/Alg hydrogel. An MI rat model is utilized to evaluate the feasibility of the as-prepared MNPs/Alg hydrogel for cardiac repair in vivo. The antioxidant, anti-inflammatory, and proangiogenesis effects of the hydrogel are investigated in detail. The present study opens up a new way to utilize natural biomaterials for MI treatment and allows to rerecognize the great value of natural biomaterials in cardiac repair.


The detection of monocytes in human renal biopsies: a prospective study.
A total of 52 non-transplant and 16 transplant renal biopsies were examined for the presence of monocytes in the glomeruli using the non-specific esterase reaction. Four of the non-transplant and 4 of the transplant group were positive. The 4 non-transplant samples all showed the presence of granular IgG and C3 together with electron dense deposits in the basement membrane. In contrast the positive transplant samples showed vascular rejection with little immune protein deposition and no deposits. One patient with focal glomerulosclerosis had large clumps of esterase positive material in the glomeruli in association with deposits of C3 and the presence of foam cells.


Antigenic phenotype of the lymphocytic component of medullary carcinoma of the breast.
Medullary carcinoma of the breast, which is usually associated with a dense lymphocytic infiltrate, carries a better prognosis than do most other histologic subtypes of breast carcinoma. We studied cryostat-cut fresh frozen sections from 12 patients with medullary carcinoma and, as controls, nine patients with infiltrating ductal carcinoma in order to determine and compare the antigenic phenotype of the lymphocytic components of these tumors. We used a large panel of monoclonal antibodies and polyclonal antisera for T-cells (Leu-1, Leu-2a, Leu-3a, Leu-9, T-3, T-6, T-10, T-11, and TQ-1), pre-B and B-cells (BA-1, B-1, B-2, B-4, and J5), NK cells (Leu-7 and Leu-11b), and cell activation associated antigens (T-9, HLA-Dr, and Tac). The most commonly encountered antigens on the lymphocytic components of both medullary carcinoma and infiltrating ductal carcinoma were: T-3, T-11, Leu-1, Leu-2a, Leu-3a, and Leu-9. There was little staining for NK-, pre-B-, or B-cell associated antigens in either type of carcinoma. However, the lymphocytes in the control cases tended to express HLA-Dr and T-10 more often than did the lymphocytes in the cases of medullary breast carcinoma. Our data indicate that: the antigenic phenotypes of the lymphocytic infiltrates of medullary carcinoma and those of infiltrating ductal carcinoma of the breast are essentially similar; and the lymphocytes in these carcinomas are composed predominantly of peripheral T-lymphocytes. We therefore conclude that the favorable biologic behavior of medullary carcinoma of the breast cannot readily be explained by the immunophenotype of its lymphocytic component.


Loss of eIF4E Phosphorylation Engenders Depression-like Behaviors via Selective mRNA Translation.
The MAPK/ERK (mitogen-activated protein kinases/extracellular signal-regulated kinase) pathway is a cardinal regulator of synaptic plasticity, learning, and memory in the hippocampus. One of major endpoints of this signaling cascade is the 5' mRNA cap binding protein eIF4E (eukaryotic Initiation Factor 4E), which is phosphorylated on Ser 209 by MNK (MAPK-interacting protein kinases) and controls mRNA translation. The precise role of phospho-eIF4E in the brain is yet to be determined. Herein, we demonstrate that ablation of eIF4E phosphorylation in male mice (4Eki mice) does not impair long-term spatial or contextual fear memory, or the late phase of LTP. Using unbiased translational profiling in mouse brain, we show that phospho-eIF4E differentially regulates the translation of a subset of mRNAs linked to inflammation, the extracellular matrix, pituitary hormones, and the serotonin pathway. Consequently, 4Eki male mice display exaggerated inflammatory responses and reduced levels of serotonin, concomitant with depression and anxiety-like behaviors. Remarkably, eIF4E phosphorylation is required for the chronic antidepressant action of the selective serotonin reuptake inhibitor fluoxetine. Finally, we propose a novel phospho-eIF4E-dependent translational control mechanism in the brain, via the GAIT complex (gamma IFN activated inhibitor of translation). In summary, our work proposes a novel translational control mechanism involved in the regulation of inflammation and depression, which could be exploited to design novel therapeutics.SIGNIFICANCE STATEMENT We demonstrate that downstream of the MAPK (mitogen-activated protein kinase) pathway, eukaryotic Initiation Factor 4E (eIF4E) Ser209 phosphorylation is not required for classical forms of hippocampal LTP and memory. We reveal a novel role for eIF4E phosphorylation in inflammatory responses and depression-like behaviors. eIF4E phosphorylation is required for the chronic action of antidepressants, such as fluoxetine in mice. These phenotypes are accompanied by selective translation of extracellular matrix, pituitary hormones, and serotonin pathway genes, in eIF4E phospho-mutant mice. We also describe a previously unidentified translational control mechanism in the brain, whereby eIF4E phosphorylation is required for inhibiting the translation of gamma IFN activated inhibitor of translation element-containing mRNAs. These findings can be used to design novel therapeutics for depression.


Phenotypic Variability in Leukoencephalopathy with Brain Calcifications and Cysts: Case Report of Siblings from an Irish Traveller Family with a Homozygous SNORD118 Mutation.
Leukoencephalopathy with brain calcifications and cysts (LCC) is a rare cerebral microangiopathy, the cause of which was recently determined to be recessively inherited mutations in the SNORD118 gene. We report the case of a 32-year-old Irish Traveller woman who presented to the emergency department in convulsive status epilepticus with abnormal neuroimaging features characteristic of LCC. Her medical history consisted of epilepsy, intellectual impairment, previous craniotomies for excision of cerebral cysts and resection of a tibial osteogenic sarcoma. Whole exome sequencing identified a previously described homozygous variant, NR_033294.1 n.*5C>G, in the 3' UTR of the SNORD118 gene. Her sister was subsequently found to be homozygous for the same variant but with a significantly milder clinical phenotype consisting of migraine without aura and mild, non-specific, cerebral white matter changes on neuroimaging. Knowledge of the existence of LCC within this population means that targeted genetic testing for this specific mutation should be considered in Irish Traveller patients presenting with the characteristic clinical and radiological features. Given the striking phenotypic variability seen within this family, LCC should also be considered in Irish Traveller patients even in the absence of the complete radiological triad.


Interleukin-4 and lipopolysaccharide synergize to induce vascular cell adhesion molecule-1 expression in human lung microvascular endothelial cells.
Recent studies suggest that increased vascular cell adhesion molecule-1 (VCAM-1) expression on vascular endothelium in bronchial mucosa biopsies correlates with interleukin-4 (IL-4) levels in bronchiolar lavage fluid of allergic asthmatics. The severity of asthma in patients allergic to house dust mite has also been shown to correlate with lipopolysaccharide (LPS), rather than allergen, concentration in dust. We hypothesized that to induce effective VCAM-1 expression in human lung microvascular endothelial cells (HLMVEC), IL-4 may require the presence of a co-stimulus such as LPS. To test this hypothesis we measured, by enzyme-linked immunosorbent assay, induction of cell adhesion molecule expression on, and human eosinophil adhesion to, cultured HLMVEC monolayers pretreated with IL-4 alone or combined with LPS. IL-4 synergized with LPS to induce VCAM-1 expression at 24, 48, or 72 h, whereas IL-4 alone induced expression at 72 h only. IL-4 did not induce expression of intercellular adhesion molecule-1 or E-selectin or alter LPS-induced expression of either. Pre-exposure of HLMVEC to LPS or IL-4 (1 h), followed by IL-4 or LPS, respectively (23 h), also induced VCAM-1 expression. Eosinophil adhesion to HLMVEC monolayers treated with IL-4 and LPS together, but not alone, significantly (P < 0.001) increased from 9.6 +/- 1.5% (control) to 26.9 +/- 3.3% and was inhibited by a monoclonal antibody against the VCAM-1 ligand, very late antigen-4. Analysis of VCAM-1 mRNA revealed synergism between IL-4 and LPS which may, in part, contribute to enhanced VCAM-1 expression. These results suggest that the presence of a co-stimulus such as LPS may be necessary for IL-4 to effectively induce VCAM-1 expression in lung microvasculature.


Effect of the GSTM1 genotype on the biomarkers of exposure to polycyclic aromatic hydrocarbons: Meta-analysis.
The role of glutathione S-transferase Mu 1 (GSTM1) in the biomonitoring of polycyclic aromatic hydrocarbons (PAHs) is not clear. Our purpose has been to evaluate the influence of GSTM1 genotypes on 1-hydroxypyrene (1-OHP), deoxyribonucleic acid (DNA) adducts, and micronucleus frequency in both occupational and non-occupational populations of null and active GSTM1 carriers. We conducted a meta-analysis on 25 articles that met our strict inclusion criteria (11 studies on 1-OHP, 9 on DNA adducts, and 5 on the micronucleus frequency). In the case of occupationally exposed workers, micronucleus frequency was only significantly higher in the null GSTM1 carriers than in the active GSTM1 carriers. In the non-occupationally exposed general population, 1-OHP and micronucleus frequency were significantly higher in the null GSTM1 carriers. The results of Egger's test and funnel plot analysis indicated no significant publication bias. In conclusion, GSTM1 genotypes may affect the urinary 1-OHP in the non-occupationally exposed general population, and micronucleus frequency in both occupational workers and non-occupational population. Int J Occup Med Environ Health 2017;30(2):177-201.


Gauge factor and stretchability of silicon-on-polymer strain gauges.
Strain gauges are widely applied to measure mechanical deformation of structures and specimens. While metallic foil gauges usually have a gauge factor slightly over 2, single crystalline silicon demonstrates intrinsic gauge factors as high as 200. Although silicon is an intrinsically stiff and brittle material, flexible and even stretchable strain gauges have been achieved by integrating thin silicon strips on soft and deformable polymer substrates. To achieve a fundamental understanding of the large variance in gauge factor and stretchability of reported flexible/stretchable silicon-on-polymer strain gauges, finite element and analytically models are established to reveal the effects of the length of the silicon strip, and the thickness and modulus of the polymer substrate. Analytical results for two limiting cases, i.e., infinitely thick substrate and infinitely long strip, have found good agreement with FEM results. We have discovered that strains in silicon resistor can vary by orders of magnitude with different substrate materials whereas strip length or substrate thickness only affects the strain level mildly. While the average strain in silicon reflects the gauge factor, the maximum strain in silicon governs the stretchability of the system. The tradeoff between gauge factor and stretchability of silicon-on-polymer strain gauges has been proposed and discussed.


[Small hand muscle atrophy as an initial sign in HTLV-I associated myelopathy].
A 68-year-old female had been well until the age of 52 when she noticed weakness and atrophy of her right small hand muscles. She began to have gait disturbance at the age of 63. On admission, neurological examinations revealed atrophy and weakness of the small hand muscles on both sides as well as spastic paraparesis. As the antibody titer for human T-lymphotropic virus type I (HTLV-I) was elevated both in the serum and CSF, a diagnosis of HTLV-I associated myelopathy (HAM) was made. Electrophysiological studies showed neurogenic changes and suggested anterior horn cell involvement. After oral administration of prednisolone, her spasticity and gait disturbance improved slightly. Small hand muscle atrophy can be one of the initial signs of HAM, and may mimic amyotrophic lateral sclerosis and cervical spondylosis.


Evaluation of eight biomarkers to predict short-term mortality in patients with acute severe dyspnea.
Being able to better predict risk and optimal care for patients presenting with acute dyspnea is critical. Prognostic biomarkers are well known: amino-terminal pro-B-type Natriuretic Peptide, troponin, C-reactive protein, procalcitonin. Some were more recently developed: mid-regional pro-A-type natriuretic peptide (Mid Pro-ANP), mid-regional-pro-adrenomedullin (MR-proADM), pro-endothelin, copeptin. The aim of the paper was to evaluate prognostic value of clinical findings and 8 biomarkers in patients with severe acute dyspnea. We designed a prospective cohort study targeting patients admitted in the Emergency Department and in Intensive Care Unit of a University Hospital. Inclusion criteria were acute dyspnea with SpO2 less than 92% and/or respiratory rate (RR) greater than or equal to 25 bpm. Clinical and biological data, including biomarker levels, were recorded. The contribution of the biomarkers in the prognosis was assessed using AUC-ROC curves and by multiple logistic regression. Three hundred and eighty four patients (median age 74 years, 28-day mortality 17%) were enrolled. All biomarkers were available for 317 patients. Main diagnoses were sepsis in 141 cases (36.7%), and acute heart failure in 84 (21.9%) cases. All biomarkers were correlated with prognosis. Pro-ADM (AUC-ROC=0.731; 95% CI: 0.658-0.804) showed the best accuracy. The parameters independently associated with prognosis led to a clinical/biological model with an AUC=0.809 and a good calibration (P (HLchi2)=0.9). Three biomarkers added prognostic information to the model: MR-proADM (P=0.005), copeptin (P=0.006) and troponin (P=0.05). Biomarkers can contribute to determine the day-28 outcome of patients with acute severe dyspnea.


Two homochiral organocatalytic metal organic materials with nanoscopic channels.
Two homochiral organocatalytic MOMs were prepared using tetra- and octa-carboxylate ligands, respectively. The nanoscopic channels in these MOMs are lined by organonocatalytic chiral phosphoric acid derivatives of binol and ocMOM-1 exhibited improved enantioselectivity over the parent ligand in the context of transfer hydrogenation of a series of benzoxazines.


Venae spermaticae post aures: The early modern angiology-neurology of virility.
The famous discussion of Scythian cross-dressers in Hippocrates' Airs Waters Places (Aer.) 22 puzzled perhaps most medieval and Renaissance medical authorities. The text wrestled with a pre-Hippocratic, encephalocentric theory of spermatogenesis. Modern reception of the convoluted hypothesis put forward here gradually distilled three etiologies of failing virility: impotence, subfertility, and unmanliness. A gradual shift is discernable from increasingly Galenic neuro-andrological theories (sixteenth century) to neuropsychiatric (late-seventeenth through eighteenth century), phrenological and psychopathological (early- and late-nineteenth century), and finally early psycho-endocrinological (early-twentieth century) ideas about masculinity. Aer. 22 was a ubiquitously recurring reference across all of these episodes, indeed well beyond medicine, rendering it a highly sensitive index of change in neurodevelopmental and neuropsychiatric thinking. The pre-Enlightenment, neurology-centric onset of this extended modern history of sexual/gender medicine is briefly discussed, as well as its phrenological afterlife.


Interplay of Itch and Psyche in Psoriasis: An Update.
Itch or pruritus is defined as an unpleasant subjective sensation leading to the need or to the idea of scratching. A number of studies have shown that pruritus is often responsible for marked morbidity, quality of life impairment, and even for increased mortality. Patients suffering from chronic pruritus had also decreased self-esteem, suffer from anxiety or depression and have problems to cope with negative feelings. Several studies documented that itching is a very prevalent symptom of psoriasis affecting more than 70% of individuals and for many patient it is the most bothersome symptom of the disease. While assessing various aspects of itch in psoriatic patients it was found that individuals with pruritus had a significantly lower health-related QoL; patients with pruritus, moreover, were more depressed than those without itching. In conclusion, pruritus is closely related to decreased psychosocial well-being of patients with chronic pruritic skin diseases, including psoriasis. It is important to underscore that itch may interfere with various aspects of patient functioning, emotions and social status and should therefore be adequately addressed while treating patients with psoriasis.


Risk factors for early language delay in children within a minority ethnic, bilingual, deprived environment (Born in Bradford's Better Start): a UK community birth cohort study.
Preschool language skills and language delay predict academic and socioemotional outcomes. Children from deprived environments are at a higher risk of language delay, and both minority ethnic and bilingual children can experience a gap in language skills at school entry. However, research that examines late talking (preschool language delay) in an ethnically diverse, bilingual, deprived environment at age 2 is scarce. Data from Born in Bradford's Better Start birth cohort were used to identify rates of late talking (≤10th percentile on the Oxford-Communicative Development Inventory: Short) in 2-year-old children within an ethnically diverse, predominantly bilingual, deprived UK region (N=712). The relations between known demographic, maternal, distal and proximal child risk factors, and language skills and language delay were tested using hierarchical linear and logistic regression. A total of 24.86% of children were classified as late talkers. Maternal demographic factors (ethnicity, born in UK, education, financial security, employment, household size, age) predicted 3.12% of the variance in children's expressive vocabulary. Adding maternal language factors (maternal native language, home languages) and perinatal factors (birth weight, gestation) to the model predicted 3.76% of the variance. Adding distal child factors (child sex, child age) predicted 11.06%, and adding proximal child factors (receptive vocabulary, hearing concerns) predicted 49.51%. Significant risk factors for late talking were male sex (OR 2.07, 95% CI 1.38 to 3.09), receptive vocabulary delay (OR 8.40, 95% CI 4.99 to 14.11) and parent-reported hearing concerns (OR 7.85, 95% CI 1.90 to 32.47). Protective factors were increased household size (OR 0.85, 95% CI 0.77 to 0.95) and age (OR 0.82, 95% CI 0.70 to 0.96). Almost one in four children living in an ethnically diverse and deprived UK area have early language delay. Demographic factors explained little variance in early vocabulary, whereas proximal child factors held more predictive value. The results indicate further research on early language delay is warranted for vulnerable groups.


Cholecystectomy after endoscopic sphincterotomy for common bile duct stones: is surgery necessary?
It has been more than 30 years since the introduction of endoscopic sphincterotomy for the management of choledocholithiasis. Once introduced, this endoscopic intervention subsequently enabled clinicians to witness the natural history of leaving the gallbladder in situ once the common duct calculi were removed. Because many people were free of symptoms once the common bile duct was cleared of stones, patients and physicians alike soon questioned whether it was necessary to remove the gallbladder at all. Despite more than two decades of clinical research and numerous published reports, the answer to this question remains elusive. Similarly, the management algorithm for choledocholithiasis in patients with an intact gallbladder remains controversial. We review the available key data regarding this question. Importantly, there are only three prospective, randomized trials that have examined the need for cholecystectomy after endoscopic sphincterotomy, with case studies constituting most of the published reports. Consequently, the literature on this topic remains inconclusive, weakened by its retrospective approach, considerable variability between the patients studied, inconsistent inclusion and exclusion criteria, and frequently poor patient follow-up. Nonetheless, the preponderance of data favor removing the gallbladder after endoscopically clearing the common bile duct of gallstones because an estimated 25% of patients will experience recurrent symptoms within a 2-year follow up period. Recognizing the existence of various mitigating clinical factors, we advocate adopting a selective wait-and-see approach for high-risk patients, especially those with a life expectancy of less than 2 years or severely debilitating comorbidities.


Systematic mutagenesis of potential glycosylation sites of lysosomal acid lipase.
Lysosomal acid lipase (LAL; EC 126.96.36.199) is a key enzyme in the intracellular lipid metabolism. It hydrolyzes exogenous triglycerides and cholesterol esters taken up by various cell types. LAL has six potential N-glycosylation sites and one potential O-glycosylation site. Elimination of each of the six Asn-(X)-Ser/Thr sites by site-directed mutagenesis and expression in baculovirus-infected Spodoptera frugiperda cells resulted in two single-mutant enzymes without lipolytic activities (N134Q and N246Q) and four mutants with preserved activities. The two inactive mutants were not detectable on immunoblot analysis, indicating that they were not secreted. Six double mutants in all possible combinations except for the two inactive single mutants were produced and expressed. Double mutants in combination with the N9 glycosylation site showed reduced activities as compared to the other mutants or the wild-type enzyme. Kinetic data of LAL glycosylation mutants indicate that substrate affinity of N9Q was not changed, but k (cat) of N9 mutants was reduced distinctly compared to the wild-type enzyme. Peanut agglutinin lectin did not recognize LAL, demonstrating that the protein has no core1 structure (Galbeta 1-3 GalNAc) of O-glycosylation. These data indicate that at least two of the six N-glycosylation sites are used in native lipase. N134 and N246 were found to be essential for LAL activity. We conclude that glycosylation plays an important role in the formation of functional LAL.


Interaction of haemoglobin and cytochrome c with aliphatic alcohols as studied by 1H NMR spectroscopy.
Association of haeme proteins, haemoglobin and cytochrome c, with eight aliphatic alcohols (methanol, ethanol. two isomeric propanols and four butanols) was studied by 1H NMR spectroscopy. NMR spectra of alcohols were monitored at 60 MHz at increasing concentration of the proteins. Selective broadening of the NMR signals of individual segments of alcohols was observed only in the case of alcohol-haemoglobin systems. Its quantitative evaluation and interpretation in terms of formation of low affinity intermolecular alcohol--protein complexes led to the conclusion that haemoglobin associates with alcohol molecules in a way depending on the length and isomeric branching of the alkyl chains; in particular, the methylene and methine groups vicinal to the hydroxyl are subject to stronger immobilization than the terminal methyls or other groups. Thus, the model of hydrophobic complexes stabilized by hydrogen bonds described previously for association of bovine serum albumin with alcohols (Lubas et al., Biochemistry, 18, 4943-4951, 1979) seems to apply also to haemoglobin association. In the case of cytochrome c association, 1H NMR data alone are insufficient for structural evaluation of the mechanism of formation of the alcohol--cytochrome c complexes.


Enhanced cadmium phytoremediation of Glycine max L. through bioaugmentation of cadmium-resistant bacteria assisted by biostimulation.
This study examined the potential of three strains of cadmium-resistant bacteria, including Micrococcus sp., Pseudomonas sp. and Arthrobacter sp., to promote root elongation of Glycine max L. seedlings, soil cadmium solubility and cadmium phytoremediation in G. max L. planted in soil highly polluted with cadmium with and without nutrient biostimulation. Micrococcus sp. promoted root length in G. max L. seedlings under toxic cadmium conditions. Soil inoculation with Arthrobacter sp. increased the bioavailable fraction of soil cadmium, particularly in soil amended with a C:N ratio of 20:1. Pot culture experiments observed that the highest plant growth was in Micrococcus sp.-inoculated plants with nutrient biostimulation. Cadmium accumulation in the roots, stems and leaves of G. max L. was significantly enhanced by Arthrobacter sp. with nutrient biostimulation. A combined use of G. max L. and Arthrobacter sp. with nutrient biostimulation accelerated cadmium phytoremediation. In addition, cadmium was retained in roots more than in stems and leaves and G. max L. had the lowest translocation factor at all growth stages, suggesting that G. max L. is a phytostabilizing plant. We concluded that biostimulation-assisted bioaugmentation is an important strategy for improving cadmium phytoremediation efficiency.


Isolated Mitochondria Transfer Improves Neuronal Differentiation of Schizophrenia-Derived Induced Pluripotent Stem Cells and Rescues Deficits in a Rat Model of the Disorder.
Dysfunction of mitochondria, key players in various essential cell processes, has been repeatedly reported in schizophrenia (SZ). Recently, several studies have reported functional recovery and cellular viability following mitochondrial transplantation, mostly in ischemia experimental models. Here, we aimed to demonstrate beneficial effects of isolated active normal mitochondria (IAN-MIT) transfer in vitro and in vivo, using SZ-derived induced pluripotent stem cells (iPSCs) differentiating into glutamatergic neuron, as well as a rodent model of SZ. First, we show that IAN-MIT enter various cell types without manipulation. Next, we show that IAN-MIT transfer into SZ-derived lymphoblasts induces long-lasting improvement in various mitochondrial functions including cellular oxygen consumption and mitochondrial membrane potential (Δ ψ m). We also demonstrate improved differentiation of SZ-derived iPSCs into neurons, by increased expression of neuronal and glutamatergic markers β3-tubulin, synapsin1, and Tbr1 and by an activation of the glutamate-glutamine cycle. In the animal model, we show that intra-prefrontal cortex injection of IAN-MIT in adolescent rats exposed prenatally to a viral mimic prevents mitochondrial Δ ψ m and attentional deficit at adulthood. Our results provide evidence for a direct link between mitochondrial function and SZ-related deficits both in vitro and in vivo and suggest a therapeutic potential for IAN-MIT transfer in diseases with bioenergetic and neurodevelopmental abnormalities such as SZ.


Rare protein-altering variants in ANGPTL7 lower intraocular pressure and protect against glaucoma.
Protein-altering variants that are protective against human disease provide in vivo validation of therapeutic targets. Here we use genotyping data from UK Biobank (n = 337,151 unrelated White British individuals) and FinnGen (n = 176,899) to conduct a search for protein-altering variants conferring lower intraocular pressure (IOP) and protection against glaucoma. Through rare protein-altering variant association analysis, we find a missense variant in ANGPTL7 in UK Biobank (rs28991009, p.Gln175His, MAF = 0.8%, genotyped in 82,253 individuals with measured IOP and an independent set of 4,238 glaucoma patients and 250,660 controls) that significantly lowers IOP (β = -0.53 and -0.67 mmHg for heterozygotes, -3.40 and -2.37 mmHg for homozygotes, P = 5.96 x 10-9 and 1.07 x 10-13 for corneal compensated and Goldman-correlated IOP, respectively) and is associated with 34% reduced risk of glaucoma (P = 0.0062). In FinnGen, we identify an ANGPTL7 missense variant at a greater than 50-fold increased frequency in Finland compared with other populations (rs147660927, p.Arg220Cys, MAF Finland = 4.3%), which was genotyped in 6,537 glaucoma patients and 170,362 controls and is associated with a 29% lower glaucoma risk (P = 1.9 x 10-12 for all glaucoma types and also protection against its subtypes including exfoliation, primary open-angle, and primary angle-closure). We further find three rarer variants in UK Biobank, including a protein-truncating variant, which confer a strong composite lowering of IOP (P = 0.0012 and 0.24 for Goldman-correlated and corneal compensated IOP, respectively), suggesting the protective mechanism likely resides in the loss of interaction or function. Our results support inhibition or down-regulation of ANGPTL7 as a therapeutic strategy for glaucoma.


Monte Carlo approach to calculate proton stopping in warm dense matter within particle-in-cell simulations.
A Monte Carlo approach to proton stopping in warm dense matter is implemented into an existing particle-in-cell code. This approach is based on multiple electron-electron, electron-ion, and ion-ion binary collision and accounts for both the free and the bound electrons in the plasmas. This approach enables one to calculate the stopping of particles in a more natural manner than existing theoretical treatment. In the low-temperature limit, when "all" electrons are bound to the nucleus, the stopping power coincides with the predictions from the Bethe-Bloch formula and is consistent with the data from the National Institute of Standard and Technology database. At higher temperatures, some of the bound electrons are ionized, and this increases the stopping power in the plasmas, as demonstrated by A. B. Zylstra et al. [Phys. Rev. Lett. 114, 215002 (2015)]PRLTAO0031-900710.1103/PhysRevLett.114.215002. At even higher temperatures, the degree of ionization reaches a maximum and thus decreases the stopping power due to the suppression of collision frequency between projected proton beam and hot plasmas in the target.


Excretory/secretory products from Trichinella spiralis adult worms ameliorate myocardial infarction by inducing M2 macrophage polarization in a mouse model.
Ischemia-induced inflammatory response is the main pathological mechanism of myocardial infarction (MI)-caused heart tissue injury. It has been known that helminths and worm-derived proteins are capable of modulating host immune response to suppress excessive inflammation as a survival strategy. Excretory/secretory products from Trichinella spiralis adult worms (Ts-AES) have been shown to ameliorate inflammation-related diseases. In this study, Ts-AES were used to treat mice with MI to determine its therapeutic effect on reducing MI-induced heart inflammation and the immunological mechanism involved in the treatment. The MI model was established by the ligation of the left anterior descending coronary artery, followed by the treatment of Ts-AES by intraperitoneal injection. The therapeutic effect of Ts-AES on MI was evaluated by measuring the heart/body weight ratio, cardiac systolic and diastolic functions, histopathological change in affected heart tissue and observing the 28-day survival rate. The effect of Ts-AES on mouse macrophage polarization was determined by stimulating mouse bone marrow macrophages in vitro with Ts-AES, and the macrophage phenotype was determined by flow cytometry. The protective effect of Ts-AES-regulated macrophage polarization on hypoxic cardiomyocytes was determined by in vitro co-culturing Ts-AES-induced mouse bone marrow macrophages with hypoxic cardiomyocytes and cardiomyocyte apoptosis determined by flow cytometry. We observed that treatment with Ts-AES significantly improved cardiac function and ventricular remodeling, reduced pathological damage and mortality in mice with MI, associated with decreased pro-inflammatory cytokine levels, increased regulatory cytokine expression and promoted macrophage polarization from M1 to M2 type in MI mice. Ts-AES-induced M2 macrophage polarization also reduced apoptosis of hypoxic cardiomyocytes in vitro. Our results demonstrate that Ts-AES ameliorates MI in mice by promoting the polarization of macrophages toward the M2 type. Ts-AES is a potential pharmaceutical agent for the treatment of MI and other inflammation-related diseases.


Pulmonary cystic disease: comparison of Pneumocystis carinii pneumatoceles and bullous emphysema due to intravenous drug abuse.
A rare pulmonary manifestation of the acquired immunodeficiency syndrome or intravenous (IV) drug abuse is upper lobe cystic disease--pneumatoceles in Pneumocystis carinii pneumonia (PCP) and bullous emphysema in IV drug abuse. Because these disorders overlap, the radiographic findings in 56 patients were compared. During a 12-month period, 16 patients less than 40 years of age were found to have bullous emphysema; the 10 who were IV drug abusers constituted group 1. In the same time period, 40 patients with PCP were encountered; the eight (20%) who had or developed pneumatoceles constituted group 2. In both groups, the conventional radiographic manifestations of upper lobe cystic disease were similar. Eight patients underwent computed tomography of the chest. In five patients with bullous disease, the distribution of the bullous lesions was peripheral, with sparing of the central portions of the lungs. In contrast, PCP pneumatoceles in three patients were dispersed throughout the lung parenchyma.


The Target of Rapamycin and Mechanisms of Cell Growth.
Mammalian target of rapamycin (mTOR, now referred to as mechanistic target of rapamycin) is considered as the master regulator of cell growth. A definition of cell growth is a build-up of cellular mass through the biosynthesis of macromolecules. mTOR regulation of cell growth and cell size is complex, involving tight regulation of both anabolic and catabolic processes. Upon a growth signal input, mTOR enhances a range of anabolic processes that coordinate the biosynthesis of macromolecules to build cellular biomass, while restricting catabolic processes such as autophagy. mTOR is highly dependent on the supply of nutrients and energy to promote cell growth, where the network of signalling pathways that influence mTOR activity ensures that energy and nutrient homeostasis are retained within the cell as they grow. As well as maintaining cell size, mTOR is fundamental in the regulation of organismal growth. This review examines the complexities of how mTOR complex 1 (mTORC1) enhances the cell's capacity to synthesis de novo proteins required for cell growth. It also describes the discovery of mTORC1, the complexities of cell growth signalling involving nutrients and energy supply, as well as the multifaceted regulation of mTORC1 to orchestrate ribosomal biogenesis and protein translation.


Mechanistic study of carvacrol processing and stabilization as glassy solid solution and microcapsule.
Essential oils and other liquid active pharmaceutical ingredients (APIs) are frequently microencapsulated to improve shelf life, handling, and for tailoring release. A glassy solid solution (GSS), a single-phase system, where the excipient is plasticized by the API, could be an alternative formulation system. Thus this study focuses on the investigation of two formulation strategies using carvacrol as a model compound, namely a microcapsule (MC) and a glassy solid solution (GSS). Applying the solubility parameter approach, polyvinylpyrrolidone (PVP) was chosen as a suitable matrix material for a GSS system, whereas maltodextrin and sucrose served as excipients for a microcapsule (MC) system. Differential scanning calorimetry (DSC) measurements of the excipients' glass transition temperatures and the melting point of carvacrol verified plasticizing properties of carvacrol on PVP. Batch mixing processes, as preliminary experiments for future extrusion processes, were performed to prepare GSSs and MCs with various amounts of carvacrol, followed by crushing and sieving. Maximally 4.5% carvacrol was encapsulated in the carbohydrate material, whereas up to 16.3% were stabilized as GSS, which is an outstanding amount. However, grinding of the samples led to a loss of up to 30% of carvacrol.


Glomerular filtration rate (GFR) estimated from serum creatinine predicts total (urine and peritoneal) creatinine clearance in patients on peritoneal dialysis.
The aim of this study was to examine the accuracy of the Modification of Diet in Renal Disease (MDRD) equation and the Cockcroft and Gault formula (CCrCG) in predicting total creatinine clearance achieved by residual renal function plus peritoneal dialysis in patients on chronic peritoneal dialysis. Total creatinine clearance was defined as peritoneal creatinine clearance (PCcr) plus the average of urine urea and creatinine clearances (cGFR). Correlation analysis and Bland-Altman plot were used to establish the degree of correlation and agreement between the estimations of creatinine clearance achieved by PCcr and the average of cGFR and estimated creatinine clearance based on serum creatinine by using either MDRD equation or the Cockcroft and Gault formula. In one hundred fifty-six measurements, mean clearances by [cGFR + PCcr], CCrCG and MDRD were: 7.9 ± 3.1, 10.6 ± 5.2 and 8.5 ± 4.9 ml/min/1.73 m(2), respectively. There was a good correlation between [cGFR + PCcr] and MDRD (r = 0.776, P < 0.05) and [cGFR + PCcr] and CCrCG (r = 0.735, P < 0.05). The mean MDRD was not significantly different from the mean clearance by [cGFR + PCcr] (difference 0.4 ± 2.9 ml/min/1.73 m(2), agreement limit -5.4-6.3 ml/min/1.73 m(2)). The CCrCG formula gave a larger difference from the mean [cGFR + PCcr] (2.8 ± 10.5 ml/min/1.73 m(2)) and a much wider agreement limit (-3.7-9.3 ml/min/1.73 m(2)). In male patients, MDRD formula provided an estimate of clearance that was similar to the mean [cGFR + PCcr] (7.9 ± 3.8 ml/min/1.73 m(2) vs. 8.2 ± 3.2 ml/min/1.73 m(2), respectively; difference 0.10 ± 1.9 ml/min/1.73 m(2), limits of agreement -3.9-3.7 ml/min/1.73 m(2)). By contrast, in female patients, the MDRD equation significantly overestimated the clearance (difference between mean estimated and mean measured clearance 1.4 ± 4.1 ml/min/1.73 m(2), limits of agreement -6.6-9.5 ml/min/1.73 m(2) P < 0.05). In conclusion, the GFR estimated by MDRD formula is similar to [cGFR + PCcr] especially in males. GFR by the CCrCG formula tended to overestimate the highest values of [cGFR + PCcr].


Evaluation of rabbit sperm acrosomal integrity and fertilizing ability by use of vital stains.
Three staining procedures to detect sperm acrosome integrity were compared via electron microscopy. Stains were applied to epididymal, freshly ejaculated, in vivo capacitated, and sonicated sperm cells in addition to spermatozoa displaying sequentially removed plasma and outer and inner acrosomal membranes. Sequential membrane removal procedures resulted in removal of plasma membranes from 73% of all sperm cells, removal of plasma and outer acrosomal membranes from 74% of all sperm cells, and removal of plasma and outer and inner acrosomal membranes from 87% of all sperm cells as determined by electron microscopy. Live/dead staining results were not statistically different from subjective microscopic motility evaluations (P less than 0.005) for epididymal, sonicated, freshly ejaculated, and in vivo capacitated sperm samples. All three stains assessed were similarly capable of detecting the acrosome status of freshly ejaculated and of sonicated spermatozoa compared to data obtained by electron microscopy (P = 0.010). However, only the Bryan-Akruk stain afforded data that were closely correlated with data obtained via electron microscopy for all sperm types assessed; the latter included in vivo capacitated spermatozoa and sperm cells rendered free of plasma membranes. Results confirmed an earlier report by successfully effecting sequential removal of rabbit acrosomal membranes and documented use of the Bryan-Akruk acrosomal stain for evaluation of sperm cell populations for fertilizing ability. These findings should prove useful in further investigations of mechanisms involved in achievement of fertilizing ability by rabbit spermatozoa.


Medicines availability at a Swaziland hospital and impact on patients.
The burden of non-communicable diseases (NCDs) in low- and middle-income countries is increasing. Where patients are expected to make increased out-of-pocket payments this can lead to treatment interruptions or non-adherence. Swaziland is no exception in this regard. The aim of the study was to investigate the availability of medicines for NCDs in a hospital and the impact of out-of-pocket spending by patients for medicines not available at the hospital. The study was conducted at Raleigh Fitkin Memorial Hospital in Manzini, Swaziland. Exit interviews to assess availability of a selected basket of medicines were conducted with 300 patients diagnosed with diabetes, hypertension or asthma. The stock status record of a basket of medicines for these conditions in 2012 was assessed at the Central Medical Stores. Results were analysed using the Statistical Package for Social Sciences version 20.0. Most of the patients (n = 213; 71%) confirmed not receiving all of their prescribed medicines at each visit to the hospital in the past six months. On average patients spent 10–50 times more on their medicines at private pharmacies compared to user fees in the health facility. Stock-outs at the Central Medical Stores ranging from 30 days to over 180 days were recorded during the course of the assessment period (12 months), and were found to contribute to inconsistent availability of medicines in the health facility. Out-of-pocket expenditure is common for patients with chronic conditions using this health facility, which suggests the possibility of patients defaulting on treatment due to lack of affordability.


Designing allosteric peptide ligands targeting a globular protein.
Patented signal analytic algorithms applied to hydrophobically transformed, numerical amino acid sequences have previously been used to design short, protein-targeted, L or D retro-inverso peptides. These peptides have demonstrated allosteric and/or indirect agonist effects on a variety of G-protein and tyrosine kinase coupled membrane receptors with 30% to over 80% hit rates. Here we extend these approaches to a globular protein target. We designed eight peptide ligands targeting an ELISA antibody responsive protein, beta-galactosidase, betaGAL. Three of the eight 14mer peptides allosterically activated betaGAL with ELISA methodology. Using Bayesian statistics, this 38% hit rate would have occurred 2 x 10(-9) by chance. These peptides demonstrated binding site competitive or noncompetitive interactions, suggesting allosteric site multiplicity with respect to their betaGAL binding-mediated ELISA signal. Kinetic studies demonstrated the temperature dependence of the betaGAL peptide binding functions. Using the van't Hoff relation, we found evidence for enthalpy-entropy compensation. This relation is often found for hydrophobic interactions in aqueous media, and is consistent with the postulated hydrophobic series encoding underlying our protein-targeted, peptide design methods. It appears that our algorithmic, hydrophobic autocovariance eigenvector template approach to the design of allosteric peptides targeting membrane receptors may also be applicable to the design of peptide ligands targeting nonmembrane involved globular proteins.


MRI and planimetric CT follow-up study of patients with severe tick-borne encephalitis.
The aim of the study was to evaluate the magnetic resonance imaging (MRI) and planimetric computed tomography (CT) of brain lesions in patients with a history of tick-borne encephalitis (TBE); to assess the influence of steroid treatment on the brain and whether lesions were age-dependent. A total of 19 patients with abnormal initial imaging in the acute stage of the disease had a follow-up MRI after 1 year; 34 patients hospitalized for TBE encephalitis/encephalomyelitis had planimetric CT after 10 years. On MRI cortico-subcortical atrophy with widening of anterior horns of the lateral ventricles and vascular changes was more marked on follow-up examination. Virchow-Robin spaces dilatation, widening of the lateral ventricles, periventricular lesions, and cortico-subcortical atrophy correlated with age. Results of planimetric CT study showed increased percentage of tracings, widened anterior horns, lateral ventricles, and III ventricle, which suggest new non-age-related atrophic lesions. Radiological lesions in the acute phase of TBE and after recovery are non-specific. Cortico-subcortical atrophy with widening of the anterior horns of the lateral ventricles and vascular changes are most common. Long-term follow-up confirms the formation of new non-age-related cerebral atrophic lesions due to TBE. The logit model may serve as a background for the hypothesis concerning an accelerated local atrophy of the brain tissues in patients with a history of severe TBE.


Trichinella spiralis, T. britovi, and T. nativa: infectivity, larval distribution in muscle, and antibody response after experimental infection of pigs.
The infectivity of Trichinella spiralis, T. nativa, and T. britovi was experimentally compared in pigs. Blood sampling was performed weekly, and muscle juices were obtained at slaughter 10 weeks after inoculation. Muscle larvae were found in all of four pigs inoculated with T. spiralis [mean 190 larvae per gram (lpg)] and in three of four pigs inoculated with T. britovi (mean 7 lpg). No larvae were found in pigs inoculated with T. nativa. For T. spiralis and T. britovi, the neck muscle (m. splenius) appears to be a predilection site in addition to the tongue, the diaphragm, and the jaw. High antibody responses were found in all experimental groups, independent of the antigen used, and even in pigs in which no muscle larvae were recovered. The strong and consistent antibody response found with meat juice indicates the usefulness of this material where a blood sample is not obtainable, e.g. meat samples from wild animals. Immunoblotting (Western blots) on slaughter sera revealed no species specificity when comparing homologous versus heterologous staining.


[Metabolic and nutritional management after extended radical operation for pancreatobiliary carcinoma].
The physiology after extended radical operation in patients with pancreatobiliary carcinomas and the metabolic and nutritional management were studied. Twenty-four patients who underwent pancreatoduodenectomy with extended dissection were compared with 17 patients with semi-extended dissection and 44 patients with limited or no dissection. Extended dissection meant complete dissection of the nerve plexus around the superior mesenteric artery and para-aortic node dissection. The frequency of defecation (2.7 times/day) and the blood osmolarity in the extended dissection group were significantly higher than those in the other groups during the first week after operation. The level of serum protein was significantly lower in the extended dissection group. Insulin dosage during the first 14 days after surgery was significantly greater in the extended dissection group, yet no difference was recognized in the amount of glucose administered among the 3 groups. The conclusion was as follows; frequent diarrhea, a large amount of lymph loss and increased urine volume due to an osmotic diuresis were the main causes of volume loss. So a large volume of fluid containing a high concentration of protein should be injected immediately after extended dissection to normalize serum osmotic pressure. Because of increased insulin requirement and decreased endogenous insulin production, the administration of large amount of glucose immediately after operation should be undertaken carefully.


Racial differences in MLH1 and MSH2 mutation: an analysis of yellow race and white race based on the InSiGHT database.
MLH1 and MSH2 mutations underlie 90% of hereditary nonpolyposis colorectal cancer (HNPCC) mutations. The International Society of Gastrointestinal Hereditary Tumors (InSiGHT) has established an international database of mutations associated with HNPCC. Based on the InSiGHT database and the original references that reported the mutations, we analyzed the distributions of MLH1 and MSH2 mutations in yellow race and white race respectively and compared them subsequently. We found: (1) the distributions of mutation individuals in exon 1, 17 and 19 of MLH1 gene and in exon 2 of MSH2 gene showed significant differences between the two race groups (p < 0.05); (2) the distributions of mutation types in exon 2, 7 and 18 of MLH1 and exon 10 and 16 of MSH2 showed significant differences (p < 0.05); and (3) three mutations (c.649C > T, c.1625A > T and c.1721T > C) in MLH1 and five mutations (c.23C > T, c.187dupG, c.505A > G, c.1168C > T and c.2211-6T > C) in MSH2 have much higher frequency in yellow race than those in white race. Furthermore, three mutations (c.1453G > C, c.1742C > T and c.1758dupC) in MLH1 and two mutations (c.1255C > A and c.1886A > G) in MSH2 were only found in yellow race, which implies that specific mutations in yellow race need more attention when screening mutations in these two genes.


Animal models of glaucoma.
Glaucoma is a heterogeneous group of disorders that progressively lead to blindness due to loss of retinal ganglion cells and damage to the optic nerve. It is a leading cause of blindness and visual impairment worldwide. Although research in the field of glaucoma is substantial, the pathophysiologic mechanisms causing the disease are not completely understood. A wide variety of animal models have been used to study glaucoma. These include monkeys, dogs, cats, rodents, and several other species. Although these models have provided valuable information about the disease, there is still no ideal model for studying glaucoma due to its complexity. In this paper we present a summary of most of the animal models that have been developed and used for the study of the different types of glaucoma, the strengths and limitations associated with each species use, and some potential criteria to develop a suitable model.


Development of an alternative saliva test for diagnosis of SARS-CoV-2 using TRIzol: Adapting to countries with lower incomes looking for a large-scale detection program.
The use of saliva for the diagnosis of SARS-CoV-2 has shown to be a good alternative to nasopharyngeal swabs (NPS), since it permits self-collection, avoids the exposure of healthy persons to infected patients, reduces waiting times, eliminates the need of personal protective equipment and is non-invasive. Yet current saliva testing is still expensive due to the need of specialized tubes containing buffers to stabilize the RNA of SARS-CoV-2 and inactivate the virus. These tubes are expensive and not always accessible in sufficient quantities. We now developed an alternative saliva testing method, using TRIzol for extraction, viral inactivation, and storage of SARS-CoV-2 RNA, combined with RT-qPCR, which was comparable in its performance to NPS. Paired saliva samples and NPS were taken from 15 asymptomatic healthcare workers and one patient with SARS-CoV-2. Further 13 patients with SARS-CoV-2 were only saliva-tested. All the tests were performed according to CDC 2019-Novel Coronavirus (2019-nCoV) Real-Time RT-PCR Diagnostic Panel. Saliva (4 mL) was taken in sterile 50 mL tubes, 1.5 mL TRIzol were added and mixed. Our results show that 5 μL of saliva RNA extracted with TRIzol allow for an adequate detection of the virus in patients positive for SARS-CoV-2 and was equally sensitive to NPS in TRIzol. We conclude that saliva testing using TRIzol is a recommendable method for diagnosis of SARS-CoV-2 since it has several advantages over currently used saliva tests: it can be done with normal sterile tubes, does not need cold-chain handling, is stable at room temperature, is non-invasive and less costly, making it more accessible for low-income countries. Cheaper saliva testing using TRIzol is especially relevant for low-income countries to optimize diagnosis and help define quarantine durations for families, healthcare workers, schools, and other public workplaces, thus decreasing infections and mortality caused by SARS-CoV-2.


Food Acquisition through Private and Public Social Networks and Its Relationship with Household Food Security among Various Socioeconomic Statuses in South Korea.
This study was conducted to understand food acquisition practices from social networks and its relationship with household food security. In-depth interviews and a survey on food security were conducted with twenty-nine mothers and one father in metropolitan areas of South Korea. Many families acquired food from their extended families, mainly participants' mothers. Between low-income and non-low-income households, there was a pattern of more active sharing of food through private networks among non-low-income households. Most of the low-income households received food support from public social networks, such as government and charity institutions. Despite the assistance, most of them perceived food insecurity. We hypothesized that the lack of private social support may exacerbate the food security status of low-income households, despite formal food assistance from government and social welfare institutions. Interviews revealed that certain food items were perceived as lacking, such as animal-based protein sources and fresh produce, which are relatively expensive in this setting. Future programs should consider what would alleviate food insecurity among low-income households and determine the right instruments and mode of resolving the unmet needs. Future research could evaluate the quantitative relationship between private resources and food insecurity in households with various income statuses.


Antibiofilm activity, pH and solubility of endodontic sealers.
To evaluate antibiofilm activity against Enterococcus faecalis, pH and solubility of AH Plus, Sealer 26, Epiphany SE, Sealapex, Activ GP, MTA Fillapex (MTA-F) and an experimental MTA-based Sealer (MTA-S). Sealer samples were manipulated and stored for 2 or 7 days. Prepared sealers were evaluated by a modified direct contact test (DCT) for 5 h, 10 h or 15 h with biofilm previously induced on bovine dentine for 14 days. In the control group, the biofilm was not exposed to the sealers. The number of colony-forming units (CFU mL(-1) ) in the remaining biofilm was determined. Sealer solubility was assessed by the percentage of mass loss after 15 h of immersion in distilled water. Sealer pH was measured at 5 h, 10 h and 15 h. Statistical analysis was performed using Kruskal-Wallis and Dunn or anova and Tamhane's T2 tests, at 5% significance. At 2 days post-manipulation, the DCT showed that Sealapex and MTA-F were associated with a reduction in the number of bacteria in all 3 contact periods evaluated, compared with the control group (P < 0.05). At 7 days, Sealapex had the greatest antibiofilm action at 10 h and 15 h. Sealapex had the highest pH values 2 and 7 days post-manipulation. Regarding the solubility, at 2 days the highest values were observed for MTA-F, MTA-S, Sealapex and Activ GP (P < 0.05). At 7 days, MTA-S and MTA-F had greater solubility than the other materials (P < 0.05). AH Plus had the lowest solubility for both post-manipulation periods (P < 0.05). Sealapex and MTA-F were associated with a reduction in the number of bacteria in biofilms and had greater solubility. The high solubility and pH may be related to the antibacterial activity of these materials.


Very low sensitivity of wet mount microscopy compared to PCR against culture in the diagnosis of vaginal trichomoniasis in Uganda: a cross sectional study.
Trichomonas vaginalis (TV) causes the Trichomoniasis Syndrome composed of vaginitis in women, urethritis in men and tube infection in both sexes. This infection is strongly associated with premature rupture of membranes, preterm delivery, low birth weight, promoting HIV sexual transmission and infertility. Prevention of these complications requires accurate early detection and effective treatment of infected individuals. In the resource limited settings, the wet mount microscopy (WMM) is often the only available test for laboratory detection of TV, but its accuracy and that of polymerase chain reaction (PCR) tools in Uganda remain poorly studied. The aim of this cross-sectional study was to compare the diagnostic accuracy of the WMM and PCR against culture as reference standard for the direct diagnosis of TV among symptomatic women. Three high vaginal swabs were collected from each of one hundred fifty women presenting with symptoms suggestive of active vaginal trichomoniasis at the sexually transmitted diseases clinic of Mulago National Referral Hospital Kampala, Uganda. The swabs were tested for TV with WMM, in-house PCR and TV culture. Results were analysed using excel 2007, SPSS v16, and Meta-disc software to determine the diagnostic accuracy of the tests. The sensitivity, specificity and kappa agreement of the WMM was 25% (95% CI 5.5-57.2%), 100% (95% CI 97-100) and 0.38, respectively. Corresponding values for the PCR were 91.7% (95% CI 61.5-99.8), 99.3% (95% CI 96-100) and 0.91, respectively. Among the TV symptomatic women, the sensitivity of the WMM was very low, with two-thirds of the patients missing a diagnosis while the in-house PCR was highly sensitive and specific. Feasibility studies aimed at incorporating PCR tools in algorithms for diagnosis of TV infection in resource-limited settings are recommended.


[Intracardiac ectopic thyroid].
Intracardiac ectopic thyroid tissue was removed in a 51 years old woman, after echography has discovered a tumor in the right ventricle. There was a normal thyroid gland in the neck and thyroid function tests were normal. Intra-cardiac ectopic thyroid tissue is very rare; it is due to an abnormality of embryological development, when thyroid anlage is in close contact with the embryonic heart.


New Insights about Chronic Pelvic Pain Syndrome (CPPS).
Chronic pelvic pain syndrome (CPPS) is one of the common diseases in urology and gynecology. CPPS is a multifactorial disorder where pain may originate in any of the urogynecological, gastrointestinal, pelvic musculoskeletal, or nervous systems. The symptoms of CPPS appear to result from an interplay between psychological factors and dysfunction in the immune, neurological, and endocrine systems. The aim of this article was to present new insight about CPPS in order to raise awareness of nursing and medical staff in the identification and diagnosis of the syndrome and to promote an appropriate treatment for each woman who suffers from CPPS. A literature review about the factors associated with CPPS and therapeutic interventions for CPPS was conducted. CPPS represents a chronic pain syndrome that combines anatomic malfunction of the pelvic floor muscles with malfunction of pain perception linked with psychological and cognitive factors. The therapeutic interventions in CPPS cases should, consequently, follow a multidisciplinary approach.


3D and 4D ultrasound in fetal cardiac scanning: a new look at the fetal heart.
Over the last decade we have been witness to a burgeoning literature on three-dimensional (3D) and four-dimensional (4D) ultrasound-based studies of the fetal cardiovascular system. Recent advances in the technology of 3D/4D ultrasound systems allow almost real-time 3D/4D fetal heart scans. It appears that 3D/4D ultrasound in fetal echocardiography may make a significant contribution to interdisciplinary management team consultation, health delivery systems, parental counseling, and professional training. Our aim is to review the state of the art in 3D/4D fetal echocardiography through the literature and index cases of normal and anomalous fetal hearts.


TRAF6 inhibits Th17 differentiation and TGF-beta-mediated suppression of IL-2.
Transforming growth factor-beta (TGF-beta) has an essential role in the generation of inducible regulatory T (iTreg) and T helper 17 (Th17) cells. However, little is known about the TGF-beta-triggered pathways that drive the early differentiation of these cell populations. Here, we report that CD4(+) T cells lacking the molecular adaptor tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) exhibit a specific increase in Th17 differentiation in vivo and in vitro. We show that TRAF6 deficiency renders T cells more sensitive to TGF-beta-induced Smad2/3 activation and proliferation arrest. Consistent with this, in TRAF6-deficient T cells, TGF-beta more effectively down-regulates interleukin-2 (IL-2), a known inhibitor of Th17 differentiation. Remarkably, TRAF6-deficient cells generate normal numbers of Foxp3-expressing cells in iTreg differentiation conditions where exogenous IL-2 is supplied. These findings show an unexpected role for the adaptor molecule TRAF6 in Smad-mediated TGF-beta signaling and Th17 differentiation. Importantly, the data also suggest that a main function of TGF-beta in early Th17 differentiation may be the inhibition of autocrine and paracrine IL-2-mediated suppression of Th17 cell generation.


[Bladder wall neourethra technique improves early urinary continence after laparoscopic radical prostatectomy].
To study the effect of the bladder wall neourethra (BWN) technique on early urinary continence after laparoscopic radical prostatectomy (LRP). We prospectively selected 40 cases of LRP performed in our hospital from August 2020 to August 2021 and randomly divided them into a BWN group (n = 20) and a control group (n = 20). We recorded the urinary continence rate of the two groups of patients at 7, 30, 90 and 180 days, and measured the maximum urethral pressure (MUP), functional urethral length (FUL) and functional urethral area (UFA) and observed the shape of the neourethra closure by MRI at 1 month after catheter removal. The urinary continence rates were significantly higher in the BWN than in the control group at 7 days (90.0% vs 25.0%, P < 0.001), 30 days (95.0% vs 35.0%, P < 0.001), 90 days (100% vs 60.0%, P < 0.05) and 180 days (100% vs 90.0%, P > 0.05) after catheter removal. No statistically significant difference was observed in MUP between the two groups (P > 0.05). FUL and FUA were remarkably higher in the BWN than in the control group (P < 0.01). MRI showed tight closure of the neourethra in the BWN group in the urine storage period. The BWN technique can significantly prolong FUL and improve early urinary continence after LRP.


Oxidative stress and cellular and tissue damage in organogenic outbred mouse embryos after moderate perigestational alcohol intake.
Perigestational alcohol consumption by CF-1 mouse, from before mating up to the period of embryo organogenesis, leads to retarded early embryo development and neural tube defects. Here, we addressed if perigestational alcohol ingestion up to Day 10 of pregnancy induces oxidative stress and changes in macromolecules and organ tissues of early organogenic embryos. Adult CF-1 female mice were administered 10% ethanol in their drinking water for 17 days prior to mating and until Day 10 of gestation, whereas control females were administered ethanol-free water. Our results demonstrated significantly reduced Catalase abundance and activity and increased glutathione content in the embryos of ethanol-treated females. The nitrite level was significantly reduced, but TBARS (thiobarbituric acid reactive substances) content, an index of lipid peroxidation, did not change. Embryos derived from ethanol-treated females also showed higher abundance of 3-nitrotyrosine (3-NT)-containing proteins in all tissues, compared to the control group. Apoptosis was significantly increased in the ectoderm and mesoderm, but not in the heart-although this organ did contain more cleaved Caspase-3-positive cardiomyocytes per area of ventricular myocardium than controls. In sum, moderate perigestational alcohol ingestion up to Day 10 of gestation in mice induces oxidative stress by altering radical nitrogen species and antioxidant enzymatic and non-enzymatic mechanisms in embryos. Further, generalized protein nitration, due to unbalanced nitric oxide levels associated with tissue-specific apoptosis, was detected in embryos, suggesting that oxidative mechanisms may play an important role in the perigestational alcohol-induced malformation of organogenic embryos exposed to ethanol.


Facing Africa: Describing Noma in Ethiopia.
Noma affects the most marginalized communities in the world, beginning as oral ulceration and rapidly progressing to orofacial gangrene. With a mortality rate estimated to be as high as 90% and with very few able to access treatment in its active phase, very little is understood about the disease. This retrospective review of patients treated by Facing Africa for deformity and functional impairment secondary to noma between May 2015 and 2019 highlights some of the difficulties encountered by those afflicted. Eighty new patients with historical noma defects were identified and were seen over the course of nine surgical missions, with notes providing valuable geographical, socioeconomic, and psychosocial information. The mean self-reported age of onset was 5 years and 8 months, with a median time of 18 years from onset to accessing treatment. Before intervention, 65% covered their face in public, 59% reported difficulty eating, 81% were unhappy with their appearance, and 71% experienced bullying. We aimed at emphasizing the significant burden, both psychologically and physically of noma, demonstrating the disparity between recent decades of progress in the well-being of Ethiopians in general and the access to health care and mental health support for some of those most in need.


Characterization of IKI1 and IKI3 genes conferring pGKL killer sensitivity on Saccharomyces cerevisiae.
The Saccharomyces cerevisiae iki mutants show an insensitive phenotype to the pGKL killer toxin, and we have cloned some IKI genes by complementation of this phenotype [Kishida et al., Biosci. Biotech. Biochem., 60, 798-801 (1996)]. Here, we identified and characterized the IKI1 and IKI3 genes. DNA sequencing of the genes showed that both have 100% identity with hypothetical genes identified by the yeast genome project, YHR187w (481,911-480,985 in chromosome VIII) for IKI1, and YLR384c (888,852-892,898 in chromosome XII) for IKI3. Both are novel genes with no significant identity with other known genes and they do not belong to any homology domain group, gene family, or superfamily. The disruption of IKI1 is not lethal, but growth of the disruptant was slower than that of the wild type at all temperatures examined. The disruptant was the killer-insensitive phenotype. The sequence of the IKI1 gene predicted a hydrophilic protein with a molecular mass of 35 kDa (309 amino acids). A 35-kDa protein band was also detected by immunoblotting the 25,000 x g pellet fraction of the wild type yeast cell lysate. Disruption of the IKI3 gene is also non-lethal and it has the killer-insensitive phenotype. Iki3p may contain a transmembrane domain near the NH2-terminal region (97-113 residues in a total of 1349 amino acids).


Altered top-down cognitive control and auditory processing in tinnitus: evidences from auditory and visual spatial stroop.
Tinnitus is the perception of a sound in the absence of external stimulus. Currently, the pathophysiology of tinnitus is not fully understood, but recent studies indicate that alterations in the brain involve non-auditory areas, including the prefrontal cortex. Here, we hypothesize that these brain alterations affect top-down cognitive control mechanisms that play a role in the regulation of sensations, emotions and attention resources. The efficiency of the executive control as well as simple reaction speed and processing speed were evaluated in tinnitus participants (TP) and matched control subjects (CS) in both the auditory and the visual modalities using a spatial Stroop paradigm. TP were slower and less accurate than CS during both the auditory and the visual spatial Stroop tasks, while simple reaction speed and stimulus processing speed were affected in TP in the auditory modality only. Tinnitus is associated both with modality-specific deficits along the auditory processing system and an impairment of cognitive control mechanisms that are involved both in vision and audition (i.e. that are supra-modal). We postulate that this deficit in the top-down cognitive control is a key-factor in the development and maintenance of tinnitus and may also explain some of the cognitive difficulties reported by tinnitus sufferers.


Salmonella pathogenicity island 2 mediates protection of intracellular Salmonella from reactive nitrogen intermediates.
Salmonella typhimurium causes an invasive disease in mice that has similarities to human typhoid. A type III protein secretion system encoded by Salmonella pathogenicity island 2 (SPI2) is essential for virulence in mice, as well as survival and multiplication within macrophages. Reactive nitrogen intermediates (RNI) synthesized by inducible nitric oxide synthase (iNOS) are involved in the control of intracellular pathogens, including S. typhimurium. We studied the effect of Salmonella infection on iNOS activity in macrophages. Immunofluorescence microscopy demonstrated efficient colocalization of iNOS with bacteria deficient in SPI2 but not wild-type Salmonella, and suggests that the SPI2 system interferes with the localization of iNOS and Salmonella. Furthermore, localization of nitrotyrosine residues in the proximity was observed for SPI2 mutant strains but not wild-type Salmonella, indicating that peroxynitrite, a potent antimicrobial compound, is excluded from Salmonella-containing vacuoles by action of SPI2. Altered colocalization of iNOS with intracellular Salmonella required the function of the SPI2-encoded type III secretion system, but not of an individual "Salmonella translocated effector." Inhibition of iNOS increased intracellular proliferation of SPI2 mutant bacteria and, to a lesser extent, of wild-type Salmonella. The defect in systemic infection of a SPI2 mutant strain was partially restored in iNOS(-/-) mice. In addition to various strategies to detoxify RNI or repair damage due to RNI, avoidance of colocalization with RNI is important in adaptation of a pathogen to an intracellular life style.


Short communication: Effects of an immunomodulatory feed additive on phagocytic capacity of neutrophils and relative gene expression in circulating white blood cells of transition Holstein cows.
High-producing dairy cows typically experience immunosuppression with dysregulated neutrophil function (e.g., compromised phagocytosis) during the transition period (3 wk before to 3 wk after parturition), which is causally associated with increased risk of infections. Enhanced neutrophil immune competence has significant bearing with the wellbeing of transition dairy cattle. In the current study, we investigated the effect of OmniGen-AF (OG; Phibro Animal Health, Quincy, IL) and its dose in modulation of neutrophil function of transition cows. Forty-eight multiparous cows were stratified by parity, somatic cell count, and expected calving date and randomly assigned to 3 treatments: OG fed at 0 g/head per day (CON), 60 g/head per day (OG60; recommended dose), and 90 g/head per day (OG90; 1.5× recommended dose). The OG was added from dry off (61.8 ± 1.69 d before parturition) to 28 d in milk (DIM), and removed from all treatment groups at 29 to 35 DIM (the last week of the experimental period). Neutrophil phagocytic ability against Staphylococcus aureus and Escherichia coli was improved and tended to be improved, respectively, by OG from d 28 before parturition to 28 DIM. Cows in OG60 had higher neutrophil phagocytic ability against S. aureus and E. coli compared with CON cows from d 28 before parturition to 28 DIM. Neutrophil phagocytosis of S. aureus and E. coli was higher and tended to be higher for OG60 compared with CON on 35 DIM. The relative gene expression of CXCL8 and SELL were upregulated and tended to be upregulated by OG from 60 d before parturition to 28 DIM; this was due to cows in OG60 having greater SELL and CXCL8 gene expression than CON. Expression of SELL in circulating white blood cells of OG60-treated cows was greater than OG90 and the relative expression of CXCL8 gene tended to be greater for OG60 compared with CON on 35 DIM. In conclusion, feeding OG at the recommended dose of 60 g/head per day from dry off was effective in maintaining peripheral blood neutrophil function in transition dairy cows, and it is not necessary to feed OG beyond the recommended dose.


Osteogenesis imperfecta.
Major advances have occurred in the classification of OI and in the definition of underlying molecular defects. A clearer understanding of the pathogenesis of OI and of the relationships between the phenotypes and genotypes should emerge. The study of induced mutations in selected regions of the collagen genes with expression in cultured cells or transgenic mice should hasten this process. These advances will also provide a basis for studies into the large number of other genetically determined connective tissue disorders that are grouped together as the skeletal dysplasias. The results of recent studies in OI are providing a unique insight into many aspects of collagen and connective tissue biochemistry, physiology and pathology.


Preparation of silicon-modified antimicrobial polyethylene endotracheal tubes.
Antimicrobial coating of polyethylene endotracheal tubes (PE ETTs) has proven to be an effective method to prevent endoluminal biofilm formation. A transparent silicon-modified antimicrobial PE ETT was obtained by coating PE with a SiO2 /γ-methacryloxypropyl trimethoxy silane (KH-570)/methyltriethoxysilane (MTES)/Ag-SiO2 solution prepared by chemically mixing Ag-SiO2 with SiO2 /KH-570/MTES in solution via a dip-coating method, with tetraethyl orthosilicate (TEOS) as the inorganic silicon source, followed by drying. All the films were characterized by various techniques, including the pencil hardness test, infrared spectroscopy, scanning electron microscopy, UV-vis analysis, and inductively coupled plasma mass spectrometry (ICP-MS). The results indicated that the TEOS/KH-570/MTES/Ag-SiO2 (15:6:1:0.6-1.0) films, which exhibited simple in-solution film formation on PE ETTs, had a homogeneous morphology, high transmittance above 87%, high hardness of 5H and strong adhesion to the tubes. The concentration of Ag+ ion dissolved out from the antibacterial coating is very low in ICP-MS results. The antibacterial test results show that the antibacterial coatings have excellent antibacterial property with antibacterial ratio up to 93.5% when Ag-SiO2 content is 2.6%. In pyrogen test and hemolytic test, the body temperature of rabbits rise 0.03°c for 3 h after inserting antibacterial PE ETT, and the hemolytic ratio is 0.7512%, which conform to the requirements of biomedical material. The results preliminarily proved that the antibacterial materials could be a good candidate of medical catheter material application or medical device surface coating materials. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 91-98, 2017.


Cohesion, order and information flow in the collective motion of mixed-species shoals.
Despite the frequency with which mixed-species groups are observed in nature, studies of collective behaviour typically focus on single-species groups. Here, we quantify and compare the patterns of interactions between three fish species, threespine sticklebacks (Gasterosteus aculeatus), ninespine sticklebacks (Pungitius pungitius) and roach (Rutilus rutilus) in both single- and mixed-species shoals in the laboratory. Pilot data confirmed that the three species form both single- and mixed-species shoals in the wild. In our laboratory study, we found that single-species groups were more polarized than mixed-species groups, while single-species groups of threespine sticklebacks and roach were more cohesive than mixed shoals of these species. Furthermore, while there was no difference between the inter-individual distances between threespine and ninespine sticklebacks within mixed-species groups, there was some evidence of segregation by species in mixed groups of threespine sticklebacks and roach. There were differences between treatments in mean pairwise transfer entropy, and in particular we identify species-differences in information use within the mixed-species groups, and, similarly, differences in responses to conspecifics and heterospecifics in mixed-species groups. We speculate that differences in the patterns of interactions between species in mixed-species groups may determine patterns of fission and fusion in such groups.


Metabolic and adrenergic characteristics of young men with insulin resistance.
The primary site of insulin resistance, as measured by the euglycaemic glucose clamp technique, is skeletal muscle. We used the euglycaemic hyperinsulinaemic glucose clamp technique to assess insulin sensitivity (glucose disposal rate, GDR). We aimed at clarifying the demographic, metabolic, haemorrheological, haemodynamic, and by mental stress test the adrenergic characteristics of 21-year-old men grouped in tertiles according to their insulin (I) sensitivity index (GDR/I); insulin resistant group (GDR/I < 5.5 a.u., n = 17), intermediate group (5.5 < GDR/I < 9.5 a.u., n = 16) and insulin sensitive group (GDR/I > 9.5 a.u., n = 17). Insulin resistance was characterized by higher body mass index (p = 0.002, analysis of variance), triglycerides (p = 0.001), total cholesterol/high density lipoprotein cholesterol ratio (p = 0.002), haemoglobin (p = 0.013), haematocrit (p = 0.017) and resting heart rate (p = 0.041) but not resting blood pressure or catecholamines in arterialized blood. However, the mental stress caused by announcement of a forthcoming arithmetic stress test increased diastolic blood pressure and plasma epinephrine dependent on insulin resistance (p = 0.006 and p = 0.012, respectively) with a similar trend also for the maximal increases in heart rate and plasma norepinephrine during arithmetic. Thus, in healthy young men, insulin resistance is not associated with differences in baseline blood pressure but is characterized by higher body weight, disorders in blood lipids and haemorrheology and a hyperadrenergic response to mental stress that even involves blood pressure. We suggest that the sympathetic nervous system may be involved in the pathophysiology of the characteristic insulin resistance or metabolic cardiovascular syndrome in young men.


99m Tc-labeled DTPA-colchicine dimer with improved tumor uptake.
This work reports the synthesis, radiolabeling, and biological studies of 99m Tc-diethylene triamine pentaacetic acid (DTPA)-colchicine dimer in tumor-bearing mice. The novel colchicine dimer was successfully synthesized by conjugation of DTPA to 2 colchicine biomolecules. The ligand could be labeled by 99m Tc in high yield to get 99m Tc-DTPA-colchicine dimer, which was hydrophilic and stable at room temperature. Biodistribution and imaging studies in tumor-bearing mice showed that 99m Tc-DTPA-colchicine dimer accumulated in the tumor with improved uptake and retention. The results indicate the need for synthetic modification of the parent colchicine derivative and the 99m Tc-chelate with a view to improve the tumor-targeting efficacy and in vivo kinetic profiles.


The pathology of oral cancer.
Oral cancer is a serious public health problem, with over 200,000 new cases reported annually worldwide, two-thirds of which occur in developing countries. The overall mortality rate for intra-oral cancer remains high at approximately 50%, even with modern medical services, probably due to the advanced stage of the disease at presentation. This review outlines recent advances in our understanding of the roles and interactions of major risk factors for oral cancer worldwide, notably tobacco, alcohol and betel quid and the genetic polymorphisms determining their metabolism that may predispose patients to oral carcinoma. Oral epithelial lesions with malignant potential are described. We discuss the histopathology of oral cancer, its grading and the staging of the disease at clinical, microscopic, immunohistological and molecular levels. A recommended minimum dataset for pathology reports is described. The available strategies and current prospects for controlling oral cancer in the community are summarised.


Development of a novel 99m Tc-labeled small molecular antagonist for CXCR4 positive tumor imaging.
The chemokine receptor 4 (CXCR4) has been an attractive molecular target for tumor imaging, because it is overexpressed in many tumor types and involved in tumor progression and metastasis. The purpose of this study is to examine the CXCR4 targeting properties of 99m Tc-labeled AMD3465, a small molecule antagonist of CXCR4. 99m Tc-AMD3465 was prepared in high yield (>95%) and stable in mice serum at least for 4 hours. In vitro cell binding experiments were performed with Chinese hamster ovary (CHO), MCF-7 (breast cancer), and CHO-CXCR4 (CHO stably transfected to express CXCR4) cell lines. Small animal single photon emission computed tomography/computed tomography imaging studies in nude mice bearing MCF-7 and CHO xenografts showed that the uptakes of the radiotracer in MCF-7 tumors were significantly higher than those in the CXCR4-negative CHO tumors (P < 0.05), and the MCF-7 tumors uptake could be blocked with an excess of unlabeled AMD3465 (P < 0.05). These results suggested that 99m Tc-AMD3465 could be a potential single photon emission computed tomography radiotracer for CXCR4 imaging.


Human regulatory subunit RI beta of cAMP-dependent protein kinases: expression, holoenzyme formation and microinjection into living cells.
The human regulatory subunit RI beta of cAMP-dependent protein kinases was expressed in Escherichia coli as a fusion protein with glutathione S-transferase. Purification was performed by affinity chromatography on glutathione-agarose beads after cleavage with thrombin. The human recombinant RI beta protein migrated at 55 kDa on SDS-PAGE and displayed immunoreactivity with an anti-human RI beta antiserum. Furthermore, the purified recombinant RI beta protein was shown to exist as a dimer that was able to form holoenzyme with the catalytic subunit C alpha. The rate of RI beta 2C alpha 2 holoenzyme formation was faster in the presence than in the absence of MgATP. The kinase activity measured before and after adding cAMP to the holoenzyme showed that the presence of cAMP resulted in holoenzyme dissociation and release of active C alpha-subunit, due to cAMP binding to RI beta. Compared to a RI alpha 2C alpha 2 holoenzyme, the RI beta 2C alpha 2 holoenzyme exhibited a more than twofold higher sensitivity to cAMP. The subcellular localization of RI beta was analyzed in quiescent REF-52 fibroblasts and Wistar rat thyroid (WRT) cells after microinjection of fluorescently labeled proteins into the cytoplasm. A cytoplasmic distribution was observed when free RI beta was injected, whereas free C alpha injected into the cytoplasm appeared in the nucleus. When holoenzymes with labeled RI beta and unlabeled C alpha, or unlabeled RI beta and labeled C alpha, were injected, unstimulated cells showed fluorescence in the cytoplasm of both cell types. REF-52 cells stimulated with 8-bromo-cAMP (8-Br-cAMP) and WRT cells treated with thyrotropin (TSH) showed fluorescence mainly in the cytoplasm when RI beta was the labeled subunit of the in vivo dissociated holoenzyme. In contrast, nuclear fluorescence was evident from the release and translocation of labeled C alpha from the holoenzyme complex after stimulation with 8-Br-cAMP or TSH.


New Insights into the Interaction between Graphene Oxide and Beta-Blockers.
As a nano-adsorbent, magnetic graphene oxide (GO/Fe3O4) was synthesized to potentially adsorb propranolol (PRO) from water. The synthetic material was characterized by SEM, TEM, VSM, FTIR, XRD, zeta potential, and XPS. The environmental factors, such as pH, humic acid concentration, PRO concentration, and contact time, were investigated regarding their effect on the adsorption process. The kinetics data fitted the pseudo first-order and second-order kinetics equations. The Langmuir equation, the Freundlich equation, and the Sips equation were used to analyze the adsorption isotherms. Electrostatic attraction, hydrogen bonding, and the π-π interaction all contributed to the adsorption process of PRO onto GO/Fe3O4. The discovery of this study emphasized the feasibility of GO/Fe3O4 removal of PRO and expanded the scope of the application of GO.


Which Foetal-Pelvic Variables Are Useful for Predicting Caesarean Section and Instrumental Assistance?
To assess the variables useful to predict caesarean delivery (CD) and instrumental assistance, through the analysis of a large number of foetal-pelvic variables, using discriminant analysis. One hundred and fourteen pregnant women were included in this single-centre prospective study. For each mother-foetus pair, 43 pelvic and 18 foetal variables were measured. Partial least squares-discriminant analysis was performed to identify foetal-pelvic variables that could statistically separate the 3 delivery modality groups: spontaneous vaginal delivery (SVD), CD, and instrument-assisted delivery (IAD). For the SVD versus CD model, voluminous foetuses and women with a narrow pelvic inlet had a greater risk for requiring CD. The most efficient variables for discrimination were the transverse diameter and foetal weight. The antero-posterior inlet and obstetric conjugate were considered in this model, with the former being a useful variable but not the latter. For the SVD versus IAD model, the most important variables were the foetal variables, particularly the bi-parietal diameter. Women with a reduced antero-posterior outlet diameter and a narrow pubic arch were more at risk of requiring an IAD. The antero-posterior inlet was an efficient variable unlike the obstetric conjugate. The obstetric conjugate diameter should no longer be considered a useful variable in estimating the arrest of labour. Antero-posterior inlet diameter was a sagittal variable that should be taken into account. The comparison of sub-pubic angle and bi-parietal and antero-posterior outlet diameters was useful in identifying a risk of requiring instrumental assistance.


Action and mechanism of action of veratrine on renin secretion from rat kidney slices.
It is well known that norepinephrine released from the renal nerves stimulates the secretion of renin by a beta adrenergic mechanism. In the present experiments, we investigated the effects of renin secretion of veratrine, which depolarizes nerve terminals and thereby causes transmitter release. The rat renal cortical slice preparation was used. Veratrine (10-200 microM) stimulated renin secretion in a concentration-dependent manner. Veratrine-stimulated secretion was antagonized by timolol (0.9 and 9.0 microM) and by tetrodotoxin (0.5 and 5.0 microM), a sodium channel blocker. Neither drug abolished completely the stimulatory effect of veratrine. Moreover, veratrine stimulated renin secretion in slices prepared from previously denervated kidneys; this response was not antagonized by timolol. These results are consistent with the hypothesis that veratrine stimulates renin secretion by at least two mechanisms. One component probably consists of veratrine-induced depolarization of renal nerve terminals, release of norepinephrine and activation of juxtaglomerular cell beta adrenergic receptors; the other component appears to be independent of nerve terminals in the preparation. We conclude that the tetrodotoxin-sensitive component of veratrine-stimulated renin secretion in this preparation is an in vitro model of renal nerve-stimulated renin secretion; it should be useful in investigating substances which affect renin secretion by presynaptic modulation of transmitter release.


Impact of Point-of-care Testing on Length of Stay of Patients in the Emergency Department: A Cluster-randomized Controlled Study.
Crowding is a frequent concern in the emergency department (ED). Laboratory point-of-care testing (POCT) has been proposed to decrease patients' length of stay (LOS). Our objective was to determine whether an extended panel of POCT solutions could reduce LOS. This was a single-center, prospective, open-label, controlled cluster-randomized study. Blood test processing was randomized into 1-week inclusion periods: interventional arm (laboratory analyses performed on POCT analyzers implemented in the ED) or control arm (central laboratory). The primary endpoint was LOS of patients in the ED. Secondary endpoints were time to result (TTR), ED crowding surrogates, and average total cost of an ED visit in each arm. A total of 23,231 patients were included and 20,923 were analyzed for the main outcome measure. Mean ± SD age was 46 ± 20 years, and 7,905 (36%) underwent blood sampling. Mean ± SD LOSs were 203 ± 161 and 210 ± 168 minutes in the POCT and control arms, respectively. LOS reduction for the entire ED population was -9 minutes (95% confidence interval [CI] = -22 to 5, p = 0.22) compared to the control arm and -17 minutes (95% CI = -34.0 to 0.6, p = 0.06) for patients undergoing blood sampling. The mean ± SD TTRs were 28 ± 31 and 79 ± 34 minutes in the POCT and control arms, respectively (TTR reduction = -51 minutes, 95% CI = -54 to -48 minutes, p < 0.001). The implementation of an extended panel of POCT solutions in an ED did not significantly reduce the LOS, but reduced the TTR.


Is monopolar electrocautery safe and effective for control of the cystic artery during laparoscopic cholecystectomy?
Laparoscopic cholecystectomy is one of the most common surgical procedures. Here we report our experience with the use of monopolar electrocautery to control the cystic artery during laparoscopic cholecystectomy. Data regarding the site, number, size, and method of control of the cystic artery during laparoscopic cholecystectomy were prospectively collected. Other data collected included the operative time, intraoperative difficulties, and postoperative complications. The study included 158 laparoscopic cholecystectomies. Two arteries were controlled in 25 patients (15.8%) and one artery in 122 patients (77.2%), while the cystic artery was not identified in 11 patients (7%). The artery was graded as small, medium, and large in 43, 72, and 32 patients, respectively. Patients with unidentified cystic artery were excluded from our data analysis. The artery was controlled using monopolar electrocautery in 114 patients (77.5%) and by metal clips in 33 patients (22.5%). The cystic artery was controlled lateral to the cystic lymph node in the majority of patients (68%). Neither bleeding nor bile duct injury was encountered throughout the study period. Electrocautery is safe and effective for control of the cystic artery during laparoscopic cholecystectomy. A future randomized study is needed to confirm the findings of the present study.


Some problems and potentialities of present-day psychoanalysis.
In a critical review of the current historical situation of psychoanalysis and its unique problems, the author considers a variety of specific but interacting factors. The potentialities for advance as therapy and science, their interrelationship, and the possible channels for such advance are examined. The social, clinical, and scientific importance of derivative 'psychotherapies' and of rationally flexible boundaries of 'indication' are discussed. As differentiated from rational conservatism, the phenomenon of analysts' irrational resistance to potential change in basic tenets of technique or theory is held to be a critically formidable impediment to the further development of psychoanalysis.


Single-Crystal BiFeO3 Nanoplates with Robust Antiferromagnetism.
Freestanding and single-crystal BiFeO3 (BFO) nanoplates have been successfully synthesized by a fluoride ion-assisted hydrothermal method, and the thickness of the nanoplates can be effectively tailored from 80 to 380 nm by the concentration of fluoride ions. It is revealed that BFO nanoplates grew via an oriented attachment of layer by layer, giving rise to the formation of the inner interface within the nanoplates. In particular, antiferromagnetic (AFM) phase-transition temperature (Néel temperature, TN) of the BFO nanoplates is significantly enhanced from typical 370 to ∼512 °C, whereas the Curie temperature (TC) of the BFO nanoplates is determined to be ∼830 °C, in good agreement with a bulk value. The combination of scanning transmission electron microscopy, electron energy loss spectroscopy, and the first-principle calculations reveals that the interfacial tensile strain remarkably improves the stability of AFM ordering, accounting for the significant enhancement in TN of BFO plates. Correspondingly, the tensile strain induced the polarization and oxygen octahedral tilting has been observed near the interface. The findings presented here suggest that single-crystal BFO nanoplate is an ideal system for exploring an intrinsic magnetoelectric property, where a tensile strain can be a very promising approach to tailor AFM ordering and polarization rotation for an enhanced coupling effect.


[Bacteraemia due to extended-spectrum beta-lactamases (ESBL) and other beta-lactamases (ampC and carbapenemase) producing Enterobacteriaceae: association with health-care and cancer].
Bloodstream infections due to multire-sistant Enterobacteriaceae are a major matter of concern nowadays. The present study evaluated the impact of these infections in our area. Prospective observational study of a cohort of patients with bacteraemia due to extended-spectrum beta-lactamases (ESBL) and other beta-lactamases producing organisms among hospitalized patients in Cruces Hospital for 2 years. We conducted a descriptive analysis, a subgroup analysis (cancer vs. non-cancer patients) and a mortality analysis. During the study period, 3409 episodes of bacteraemia were diagnosed, of which 124 (3.6%) were ESBL and other beta-lactamases producing Enterobacteriaceae. 40.3% of the cases were nosocomial, 15.3% community acquired and 44.4% were health-care associated. 44.4% of the cohort had cancer as underlying disease. The most commonly isolated organism was E. coli (83% of cases), regardless of the source of infection. 58.1% of patients received inadequate empirical therapy. 7 day-mortality was 10.5% and 30 day-mortality was 21.8%. None of the analyzed variables showed association with 7 and 14 day-mortality, but the presence of solid cancer (p= 0.032) and advanced HIV infection (p = 0.027), were significantly associated with higher 30 day-mortality. More than half of bacteraemia episodes affected outpatients and most of them were health-care associated episodes. Even though more than half of the patients received inadequate empirical treatment, this was not related to higher mortality. We only found an association between 30 day-mortality and the presence of underlying solid malignancy or advanced HIV infection.


E-rosette formation of lymphocytes from patients with atopic dermatitis.
The total number of circulating T lymphocytes in 47 patients with atopic dermatitis was a significantly lower than in 98 healthy persons. However, when the T lymphocytes were investigated for their affinity to sheep erythrocytes (E-rosette formation), no difference was found between patients and healthy persons, when using several different techniques varying in length of incubation of sheep erythrocytes and lymphocytes, presence of fetal calf serum, glassware, media, increased mechanical force at resuspension, and different observers. Our findings are discussed with reference to earlier publications of a reduced percentage of E-rosette forming lymphocytes in patients with atopic dermatitis.