Clinically unsuspected tonsillar sarcoidosis in a child revealed by routine histologic examination.
In most hospitals, making a microscopic examination to tonsil and adenoid specimens from pediatric patients who present recurrent infections has become a standard practice. However, studies have shown that systematic examination of tonsils and adenoids was not needed for individual aged 21 or less. In this context, we describe the third report of an unsuspected tonsillar sarcoidosis revealed by histologic examination. A 5-year-old white girl was referred to our department because of frequent nasal and pharyngeal infections. Both tonsillectomy and adenoïdectomy were performed. Histologic evaluation revealed noncaseous epithelioid granulomas morphologically compatible with a diagnosis of sarcoidosis. Our observation illustrates the benefit of histological analysis in every tonsillectomy and adenoïdectomy specimen.


Oral intake of titanium dioxide nanoparticles affect the course and prognosis of ulcerative colitis in mice: involvement of the ROS-TXNIP-NLRP3 inflammasome pathway.
Titanium dioxide (TiO2), no matter in nanoscale or micron sizes, has been widely used in food industry as additives for decades. Given the potential impact of TiO2 on the gastrointestinal epithelial and parenchymal cells, including goblet cells, the public consumers may suffer the risk of diseases caused by its widespread dissemination in food products. We therefore set out to investigate the impact of TiO2 NPs on the course and prognosis of ulcerative colitis by oral gavaging TiO2 NPs at the doses levels of 0, 30, 100, and 300 mg/kg during the induction (7 days, from day 1 to day 7) and recovery (10 days, from day 8 to day 17) phases of colitis in mice. The ulcerative colitis (UC) disease model was established by administrating of 2.5% dextran sulfate sodium (DSS) solution. Our results show that TiO2 NPs significantly enhanced the severity of DSS-induced colitis, decreased the body weight, increased the disease activity index (DAI) and colonic mucosa damage index (CMDI) scores, shortened the colonic length, increased the inflammatory infiltration in the colon. The most significant changes occurred in the low dose (30 mg/kg) group of TiO2 NPs exposure during the development phase of UC and the high dose (300 mg/kg) group of TiO2 NPs during UC self-healing phase. Increased reactive oxygen species (ROS) level and upregulation of anti-oxidant enzymes including total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-PX) and catalase (CAT), demonstrate that the TiO2 NP exposure has triggered oxidative stress in mice. Moreover, the upregulation of caspase-1 mRNA and increased expression of thioredoxin interacting protein (TXNIP) further demonstrate the involvement of the ROS-TXNIP-NLR family pyrin domain containing 3 (NLRP3) inflammasome pathway in aggravating the development of UC. Oral intake of TiO2 NPs could affect the course of acute colitis in exacerbating the development of UC, prolonging the UC course and inhibiting UC recovery.


A 28.6-kD small heat shock protein (MnHSP28.6) protects Macrobrachium nipponense against heavy metal toxicity and oxidative stress by virtue of its anti-aggregation activity.
Small heat shock proteins (sHSPs) are ATP-independent chaperones and involved into various physiological and stress processes. In the present study, a 28.6-kD sHSP coding gene, MnHSP28.6, was cloned and characterized from the oriental river prawn Macrobrachium nipponense. Tissue distribution analysis via qPCR and western blot revealed that MnHSP28.6 predominantly expressed in muscle. The temporal transcription of MnHSP28.6 in muscle after bacterial challenge, heavy metal exposure and doxorubicin (DOX) injection was investigated by qPCR. The results showed that the expression of MnHSP28.6 were strongly enhanced by both Cd2+ and Cu2+ exposure, as well as DOX injection, but not by bacterial infection. Aggregation assays showed that recombinant MnHSP28.6 could effectively prevent temperature-induced aggregation of citrate synthase, and reduction-induced aggregation of insulin in vitro. MnHSP28.6 also could protect muscle extracts from heat-induced protein denaturation and superoxide dismutase (SOD) inactivation. Expressing MnHSP28.6 in E. coli conferred host cell impressive protection against H2O2 compared to control. These results suggest a protective role of MnHSP28.6 in maintaining protein homeostasis, preventing aggregation, promoting resistance to heavy metal and keeping redox balance.


Ruxolitinib-ECP combination treatment for refractory severe chronic graft-versus-host disease.
Glucocorticoid-refractory (SR) chronic (c) graft-versus-host disease (GVHD) is a multisystem immunological disease and the leading cause of non-relapse mortality (NRM) in patients surviving longer than 2 years after allogeneic hematopoietic cell transplantation. Both ruxolitinib (RUX) and extracorporeal photopheresis (ECP) have shown activity for SR-cGVHD which motivated us to treat refractory cGHVD patients with the RUX-ECP combination. In this retrospective survey, 23 patients received RUX-ECP as salvage therapy for SR-cGVHD. The best response (CR or PR) at any time point during treatment was 74% (17/23) including 9% (2/23) CR and 65% (15/23) PR. The 24-months-survival was 75% (CI 56.0-94.1). Newly diagnosed cytopenia occurred in 22% (5/23) and CMV reactivation was observed in 26% (6/23) of the patients. Serum levels of soluble interleukin-2 receptor (sIL-2R) correlated with response. Our retrospective analysis shows that the RUX-ECP combination is safe and has activity in a fraction of patients with SR-cGVHD, which needs validation in a prospective trial.


Interactions of glycerol monooleate and dimethylsulphoxide with phospholipids. A differential scanning calorimetry and 31P-NMR study.
1. A comparative study has been made of the effects of the fusogens glycerol monooleate and dimethyl-sulphoxide on the polymorphic phase behaviour of dipalmitoyl phosphatidylcholine and dipalmitoyl phosphatidylethanolamine by differential scanning calorimetry and 31P-NMR techniques. 2. Glycerol monooleate induces a reduction in the temperature, cooperativity and enthalpy of the gel to liquid-crystal transitions of dipalmitoyl phosphatidylcholine and dipalmitoyl phosphatidylethanolamine, whereas dimethylsulphoxide induces an increase in the temperature and enthalpy and a reduction in the cooperativity of the gel to liquid-crystal transitions for those same phospholipids. 3. Glycerol monooleate induces the formation of isotropic and hexagonal (HII) phases when mixed with either dipalmitoyl phosphatidylcholine or dipalmitoyl phosphatidylethanolamine. By contrast, in the presence of dimethylsulphoxide, those same phospholipids retain the lamellar configuration observed in the absence of fusogen. 4. These results are discussed in terms of the mechanisms of chemically induced cell fusion.


Glycoprotein IIb/IIIa antagonist, murine 7E3 F(ab') 2, and tissue plasminogen activator in focal ischemia: evaluation of efficacy and risk of hemorrhage with combination therapy.
Tissue hypoperfusion during cerebral ischemia results from occlusion of large and small vessels. Combination treatment strategies using fibrinolytics to thrombolyse an embolic clot and antiplatelet agents to prevent reocclusion and the formation of new platelet thrombi in the microcirculation may offer advantages over single-agent therapy. The authors report on the effects of tissue plasminogen activator (rt-PA), a glycoprotein (GP) IIb/IIIa receptor antagonist, 7E3 F(ab') 2, or a combination of the two agents in a focal embolic model of cerebral ischemia in Wistar rats. Focal ischemia was produced by introducing an autologous thrombus into the right side middle cerebral artery. Forty-six male Wistar rats were randomly divided into 6 groups: control (n = 8), 7E3 F(ab') 2 (n = 9, 6 mg/kg), rt-PA (n = 9, 10 mg/kg), rt-PA (n = 6, 20 mg/kg), and 7E3 F(ab') 2 with either 10 mg/kg (n = 10) (low-dose combination) or 20 mg/kg (n = 6) (high-dose combination) rt-PA. Evaluation of neurobehavioral scores, cerebral angiography, bleeding time, and measurement of brain infarction volume were used to determine efficacy. All actively treated groups showed a significant reduction in the infarct volume. Animals treated with 7E3 F(ab') 2 showed reduced infarction volumes (24.0 +/- 5.1%) compared with controls (42.43 +/- 5.6%, P < 0.02). Treatment with rt-PA significantly reduced infarction volume (20.7 +/- 3.3, = 0.01) at 10 mg/kg and at 20 mg/kg (19.5 +/- 8.2%, P < 0.05). Compared with vehicle-treated animals, the low-dose combination (16.4 +/- 5.5, P < 0.003) and high-dose combination (23.7 +/- 6.2%, P < 0.05) showed significant reduction in infarction volume. Cerebral angiography revealed significantly better recanalization in the combination group (5/6 animals in the high dose and 4/6 in low dose) compared with animals treated with 7E3 F(ab') 2 (3/10) or rt-PA alone (2/6). Bleeding time significantly increased from 11.25 +/- 1.9 minutes in the control group to 17 +/- 3.1 minutes in the rt-PA group, 24.5 +/- 2.6 minutes in the 7E3 F(ab') 2 group, 25.7 +/- 3.1 minutes in the low-dose combination group, and 32.5 +/- 4.7 minutes in the high-dose combination group. The incidence of intercerebral hemorrhage was highest in the high-dose combination group (6 of 6 animals) and lowest in the single treatment with 7E3 F(ab') 2 alone (1 of 10 animals) ( P < 0.05). Our data show that murine 7E3 F(ab') 2 alone has therapeutic effects when used after cerebral ischemia. Although this study suggests that higher doses of thrombolytic combined with anti-GPIIb/IIIa therapy may increases the risk of intracranial hemorrhage, the data also support the notion that anti-GPIIb/IIIa agents can safely be combined with low doses of thrombolytic agent to produce significant attenuation of neuronal damage with no increase in the incidence of cerebral hemorrhage.


Anterior hyaloidal fibrovascular proliferation after extracapsular cataract extraction in diabetic eyes.
Four patients with proliferative diabetic retinopathy developed anterior hyaloidal fibrovascular proliferation after extracapsular cataract extraction and posterior chamber lens implantation. This complication of cataract extraction has been described after vitrectomy in diabetic eyes. Risk factors for this entity after extracapsular cataract extraction include proliferative diabetic retinopathy, iris neovascularization, and anterior ischemic retina. Anterior hyaloidal fibrovascular proliferation was observed an average of 12 months postoperatively and affected vision in one of four patients. No progression was seen within an average of six months of follow-up, and no complications such as traction retinal detachment and vitreous hemorrhage developed.


Possible implication for an indirect interaction between basic fibroblast growth factor and (Na,K)ATPase.
The (Na,K)ATPase is responsible for generating the ionic gradients and membrane potentials by the exchange of intracellular Na+ for K+. It has been recently shown that (Na,K)ATPase is involved in the exocytic pathway of basic fibroblast growth factor (bFGF), although it is not known that bFGF is secreted to the outside of cell through direct interaction with (Na,K)ATPase. To understand the role for (Na,K)ATPase in the secretory pathway of bFGF, we have sought to identify the cytoplasmic domains of the alpha 1 isoform of (Na,K)ATPase interacting with bFGF by yeast two-hybrid system. We have also investigated the interaction between the alpha 2 isoform of (Na,K)ATPase and bFGF to find out whether the interaction is isoform-specific. We found that none of the cytoplasmic domains of (Na,K)ATPase isoforms interacted with bFGF. The result suggests that the interaction between bFGF and (Na,K)ATPase might be indirect, thus requiring other proteins which are involved in the formation of protein complexes for the interaction, although we cannot exclude the possibility that the interaction requires the element of the whole alpha subunit structure that was not present in the isolated alpha subunit cytoplasmic domains.


Feasibility of autonomic nerve-preserving surgery for advanced rectal cancer based on analysis of micrometastases.
Autonomic nerve preservation has been advocated as a means of preserving urinary and sexual function after surgery for rectal cancer, but may compromise tumour clearance. The aim of this study was to determine the incidence of micrometastasis in the connective tissues surrounding the pelvic plexus. The study included 20 consecutive patients who underwent rectal surgery with bilateral lymph node dissection for advanced cancer. A total of 78 connective tissues medial and lateral to the pelvic plexus and 387 lymph nodes were sampled during surgery. All connective tissue samples and 260 lymph nodes were examined for micrometastases by reverse transcriptase-polymerase chain reaction (RT-PCR) after operation. All patients were followed prospectively for a median of 36.0 months. Of 245 histologically negative lymph nodes, 38 (15.5 per cent) were shown by RT-PCR to harbour micrometastases. However, micrometastases to tissues surrounding the pelvic plexus were detected in only two (3 per cent) of 78 tissues, that is in two of 20 patients. Clinical follow-up showed that the two patients had a poor prognosis owing to distant metastases. Autonomic nerve-preserving surgery may be feasible for advanced rectal cancer, but study of more patients positive for micrometastases is required.


Advantages and disadvantages of various upper and lower rate responses.
The advantages and disadvantages of several types of upper and lower rate responses are presented. The optimal response is dependent upon the programmable parameters and the relationship to natural cardiac cycles. The ideal physiologic pacemaker will provide several different choices for rate response. In addition, it will provide the physician with the means to verify the physiologic effects of the particular response.


Endoscopic therapy for radiation proctitis-induced hemorrhage in patients with prostatic carcinoma using argon plasma coagulator application.
Recurrent hemorrhage in patients with severe radiation proctitis is very common. It is often refractory to medical therapy. Endoscopic and surgical treatment may be required when conservative medical therapy fails. The aim of this study was to assess the therapeutic results of the Argon Plasma Coagulator (APC) (ERBE USA, Inc., Marietta, GA, USA) application in patients with radiation proctitis-induced hemorrhage. Forty patients with radiation-induced proctitis causing severe bleeding, who had failed conservative medical management were treated endoscopically. Twenty-one patients in this group required blood transfusions. APC application was used in 40 patients with only one failure. The failed patient underwent formalin application using 4% formalin solution with resolution of the bleeding. Argon plasma coagulation application is a safe, well-tolerated treatment option and, historically, has been superior to Nd:YAG laser ablation.


Antiviral Drug-Resistant Influenza B Viruses Carrying H134N Substitution in Neuraminidase, Laos, February 2016.
In February 2016, three influenza B/Victoria/2/87 lineage viruses exhibiting 4- to 158-fold reduced inhibition by neuraminidase inhibitors were detected in Laos. These viruses had an H134N substitution in the neuraminidase and replicated efficiently in vitro and in ferrets. Current antiviral drugs may be ineffective in controlling infections caused by viruses harboring this mutation.


Neurologic lesions in young captive lions associated with vitamin A deficiency.
Ataxia and incoordination occurred in 7 lion cubs in a lion park. Postmortem examination of 3 cubs revealed thickened skull bones which compressed the brain and lead to prolapse of the posterior vermis of the cerebellum through the foramen magnum. In 2 of the lions compression of the anterior cervical spinal cord caused marked damage particularly in the dorsal funiculi. In both cubs the central canal of the spinal cord was abnormal being extended laterally. The pathological changes in the bones and the brain together with low liver vitamin A levels lead to a diagnosis of hypovitaminosis A.


Acceptance of pneumococcal vaccination in older adults: A general population-based survey.
Pneumococcal infection is a leading cause of disability and death globally. The Hong Kong Government has launched two programmes for pneumococcal vaccination - The Vaccination Subsidy Scheme (VSS) and the Government Vaccination Programme (GVP). This study aimed to examine the enabling factors, obstacles and perception of pneumococcal vaccination, and their association with its uptake in a general Chinese population. We performed a population-based, telephone survey in the general public aged 65 or above via simple random sampling. A validated survey based on the Health Belief Model (HBM) was used. Their socio-demographic information; history of previous participation in the GVP or VSS; and self-perceived health status were captured. Binary logistic regression models were constructed to examine the factors independently associated with vaccination. A total of 1,000 respondents were enrolled in the study, with 402 (40.2%) respondents having intention to join the GVP/VSS in 12 months. Respondents with long-term medical consultant and medication (adjusted odds ratios [aOR] = 1.541, 95% confidence interval (CI): 1.008-2.356, p = 0.046); high levels of perceived susceptibility of infections (aOR = 3.624, 95 %CI: 2.318-5.665, p < 0.001); high levels of perceived benefits of vaccine (aOR = 1.699, 95 %CI: 1.153-2.504, p < 0.001); recommendations from government (aOR = 8.025, 95 %CI: 4.771-13.497, p < 0.001) or physicians (aOR = 7.399, 95 %CI: 3.472-15.764, p = 0.008); and high levels of self-efficacy (aOR = 3.045, 95 %CI: 1.458-6.362, p = 0.003) were more likely to have intention to participate in the vaccination programme. The acceptance rate of pneumococcal vaccination programme remained suboptimal in the population. The government and physicians should be involved in the promotion of pneumococcal vaccination and GVP/VSS by increasing perceived benefits and self-efficacy, and reducing barriers towards vaccination among the target population. More studies are required to confirm our findings in other settings.


Quality of care and cancer survivorship: the challenge of implementing the institute of medicine recommendations.
As the population ages, maintaining the quality of care for new patients with cancer will be challenged by an anticipated shortage of health professionals to care for the increased number of newly diagnosed and surviving patients with cancer.


Genomic insights into biased allele loss and increased gene numbers after genome duplication in autotetraploid Cyclocarya paliurus.
Autopolyploidy is a valuable model for studying whole-genome duplication (WGD) without hybridization, yet little is known about the genomic structural and functional changes that occur in autopolyploids after WGD. Cyclocarya paliurus (Juglandaceae) is a natural diploid-autotetraploid species. We generated an allele-aware autotetraploid genome, a chimeric chromosome-level diploid genome, and whole-genome resequencing data for 106 autotetraploid individuals at an average depth of 60 × per individual, along with 12 diploid individuals at an average depth of 90 × per individual. Autotetraploid C. paliurus had 64 chromosomes clustered into 16 homologous groups, and the majority of homologous chromosomes demonstrated similar chromosome length, gene numbers, and expression. The regions of synteny, structural variation and nonalignment to the diploid genome accounted for 81.3%, 8.8% and 9.9% of the autotetraploid genome, respectively. Our analyses identified 20,626 genes (69.18%) with four alleles and 9191 genes (30.82%) with one, two, or three alleles, suggesting post-polyploid allelic loss. Genes with allelic loss were found to occur more often in proximity to or within structural variations and exhibited a marked overlap with transposable elements. Additionally, such genes showed a reduced tendency to interact with other genes. We also found 102 genes with more than four copies in the autotetraploid genome, and their expression levels were significantly higher than their diploid counterparts. These genes were enriched in enzymes involved in stress response and plant defense, potentially contributing to the evolutionary success of autotetraploids. Our population genomic analyses suggested a single origin of autotetraploids and recent divergence (~ 0.57 Mya) from diploids, with minimal interploidy admixture. Our results indicate the potential for genomic and functional reorganization, which may contribute to evolutionary success in autotetraploid C. paliurus.


A potent peptidomimetic inhibitor of botulinum neurotoxin serotype A has a very different conformation than SNAP-25 substrate.
Botulinum neurotoxin serotype A is the most lethal of all known toxins. Here, we report the crystal structure, along with SAR data, of the zinc metalloprotease domain of BoNT/A bound to a potent peptidomimetic inhibitor (K(i)=41 nM) that resembles the local sequence of the SNAP-25 substrate. Surprisingly, the inhibitor adopts a helical conformation around the cleavage site, in contrast to the extended conformation of the native substrate. The backbone of the inhibitor's P1 residue displaces the putative catalytic water molecule and concomitantly interacts with the "proton shuttle" E224. This mechanism of inhibition is aided by residue contacts in the conserved S1' pocket of the substrate binding cleft and by the induction of new hydrophobic pockets, which are not present in the apo form, especially for the P2' residue of the inhibitor. Our inhibitor is specific for BoNT/A as it does not inhibit other BoNT serotypes or thermolysin.


In-vitro contractility of human seminiferous tubules in response to testosterone, dihydrotestosterone and estradiol.
The effects of steroids (testosterone, dihydrotestosterone and estradiol) on human seminiferous tubules in vitro were ascertained by recording the intratubular pressure with a servonull micropressure measuring device. We describe here the first response of the human seminiferous tubule to steroids. Testosterone and dihydrotestosterone had a biphasic effect on tubular contractility. Higher doses of both testosterone and dihydrotestosterone induced contractions of the seminiferous tubules whereas lower doses of these compounds induced relaxation. Estradiol (10(-9) M to 10(-6) M) induced relaxation of the seminiferous tubules in a dose-dependent manner. The results from these experiments suggested that steroids may be involved in the control of contraction of the human seminiferous tubule and may regulate the movement of spermatozoa from the testes.


Jugular foramen capillary hemangioma masquerading as a paraganglioma.
Capillary hemangiomas are benign vascular lesions that are common in head and neck, but hemangiomas of jugular foramen and temporal bone are rare with only a few cases reported in the literature. We present a case report of this rare disease entity highlighting the subtle radiographic nuances that can benefit clinicians when encountered with similar unusual clinical scenario. Although radiographic features of capillary hemangioma can be distinctive, they are not specific. In this case, the lack of significant involvement of the jugular bulb and the absence of the typical pattern of osseous erosion of the jugular carotid spine led to the alternative diagnosis of a rare capillary hemangioma of the jugular foramen.


The cortical energy needed for conscious perception.
The brain's information processing power is limited by its energy supply but the allocation of cortical energy use between conscious and unconscious information processing is unknown. We calculate, from electrophysiological data in primates, that conscious perception reflects surprisingly small local alterations in mean cortical neuronal firing rate and energy consumption: perceiving visual stimulus movement, altered tactile vibration frequency, or tone stream separation, changes local cortical energy use by less than 6%. Our estimations of energy use suggest that a "design strategy", of encoding signals using separate neurons that increase and decrease their firing rate, serves to minimise changes of energy use in the cortical areas mediating perception and may result in stimulus perception failing to be detected by BOLD functional imaging.


Rapid Killing and Biofilm Inhibition of Multidrug-Resistant Acinetobacter baumannii Strains and Other Microbes by Iodoindoles.
Multi-drug resistant Acinetobacter baumannii is well-known for its rapid acclimatization in hospital environments. The ability of the bacterium to endure desiccation and starvation on dry surfaces for up to a month results in outbreaks of health care-associated infections. Previously, indole and its derivatives were shown to inhibit other persistent bacteria. We found that among 16 halogenated indoles, 5-iodoindole swiftly inhibited A. baumannii growth, constrained biofilm formation and motility, and killed the bacterium as effectively as commercial antibiotics such as ciprofloxacin, colistin, and gentamicin. 5-Iodoindole treatment was found to induce reactive oxygen species, resulting in loss of plasma membrane integrity and cell shrinkage. In addition, 5-iodoindole rapidly killed three Escherichia coli strains, Staphylococcus aureus, and the fungus Candida albicans, but did not inhibit the growth of Pseudomonas aeruginosa. This study indicates the mechanism responsible for the activities of 5-iodoindole warrants additional study to further characterize its bactericidal effects on antibiotic-resistant A. baumannii and other microbes.


Sexual Function and Satisfaction in the Context of Obesity.
Sexual dysfunction is commonly associated with overweight/obesity, but the underlying physiological and psychosocial mechanisms are not fully understood. This review contextualizes the obesity-sexual (dys)function relationship, describes recent insights from the medical and social science literature, and suggests opportunities for continued research. Although sexual dysfunction has been historically evaluated as a consequence/outcome of obesity, it is increasingly considered as a harbinger of future metabolic comorbidities, including type 2 diabetes and cardiovascular disease. Body image dissatisfaction is a consistent predictor for lower sexual satisfaction across BMI categories, likely mediated by cognitive distraction during partnered sex. To fully capture the relationship between obesity and sexual dysfunction, multidisciplinary research approaches are warranted. While clinically significant weight loss tends to improve sexual functioning for women and men, higher body image satisfaction may independently promote sexual function and satisfaction without concomitant weight loss.


Angiogenic factors in relation to clinical effect in a phase II trial of weekly paclitaxel.
Several anticancer agents including paclitaxel have an inhibitory effect on angiogenesis. To compare the overall response rate and time to progression with changes in circulating angiogenic factors during palliative treatment with weekly paclitaxel. Patients with metastatic BC, ECOG 0-2, received weekly paclitaxel, concomitant with trastuzumab if HER2+ BC (n = 7). Circulating vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were determined at base-line and before start of new course. Fifty-five of 63 included patients were evaluable. The overall response rate including stable disease ≥24 weeks (CR + PD + SD) was obtained in 25 of the evaluable patients (45%). The median time to progression (TTP) was 5.3 months and overall survival (OS) 16.7 months. Patients with triple negative breast cancer (TNBC) showed a trend towards higher base-line VEGF compared with hormone receptor positive or HER2+ tumours and had shorter TTP. Significant differences in VEGF and bFGF levels at 12 weeks were found between patients with longer versus shorter TTP (VEGF: p = 0.046, bFGF: p = 0.005) and between patients gaining versus lacking clinical benefit (VEGF: p = 0.05, bFGF: p = 0.02). The clinical utility of circulating VEGF may be a useful tool for monitoring treatment efficacy.


Different roles of electrostatics in heat and in cold: adaptation by citrate synthase.
Electrostatics plays a major role in heat adaptation by thermophilic proteins. Here we ask whether electrostatics similarly contributes to cold adaptation in psychrophilic proteins. We compare the sequences and structures of citrate synthases from the psychrophile Arthobacter Ds2-3R, from chicken, and from the hyperthermophile Pyrococcus furiosus. The three enzymes share similar packing, burial of nonpolar surface area, and main-chain hydrogen bonding. However, both psychrophilic and hyperthermophilic citrate synthases contain more charged residues, salt bridges, and salt-bridge networks than the mesophile. The electrostatic free-energy contributions toward protein stability by individual charged residues show greater variabilities in the psychrophilic citrate synthase than in the hyperthermophilic enzyme. The charged residues in the active-site regions of the psychrophile are more destabilizing than those in the active-site regions of the hyperthermophile. In the hyperthermophilic enzyme, salt bridges and their networks largely cluster in the active-site regions and at the dimer interface. In contrast, in the psychrophile, they are more dispersed throughout the structure. On average, salt bridges and their networks provide greater electrostatic stabilization to the thermophilic citrate synthase at 100 degrees C than to the psychrophilic enzyme at 0 degrees C. Electrostatics appears to play an important role in both heat and cold adaptation of citrate synthase. However, remarkably, the role may be different in the two types of enzyme: In the hyperthermophile, it may contribute to the integrity of both the protein dimer and the active site by possibly countering conformational disorder at high temperatures. On the other hand, in the psychrophile at low temperatures, electrostatics may contribute to enhance protein solvation and to ensure active-site flexibility.


Proton pump inhibitor induced collagen expression in colonocytes is associated with collagenous colitis.
To elucidate the role of proton pump inhibitors (PPIs) in collagenous disease, direct effect of PPI on colonocytes was examined. Collagenous colitis is a common cause of non-bloody, watery diarrhea. Recently, there has been increasing focus on the use of proton PPIs as a risk factor for developing collagenous colitis. Mouse CT26 colonic cells were treated with PPI and/or PPI-induced alkaline media. Expression of fibrosis-associated genes was examined by RT-PCR. In human materials, collagen expression was examined by immunohistochemistry. CT26 cells expressed a Na+-H+ exchanger gene (solute carrier family 9, member A2). Treatment with PPI and/or PPI-induced alkaline media caused growth inhibition and oxidative stress in CT26 cells. The treatment increased expression of fibrosis inducing factors, transforming growth factor β and fibroblast growth factor 2. The treatment also decreased expression of a negative regulator of collagen production, replication factor C1, resulting in increased expression of collagen types III and IV in association with lipid peroxide. In biopsy specimens from patients with collagenous colitis, type III and IV collagen were increased. Increase of type III collagen was more pronounced in PPI-associated collagenous colitis than in non-PPI-associated disease. From these findings, the reaction of colonocytes to PPI might participate in pathogenesis of collagenous colitis.


A novel Markov Blanket-based repeated-fishing strategy for capturing phenotype-related biomarkers in big omics data.
We propose a novel Markov Blanket-based repeated-fishing strategy (MBRFS) in attempt to increase the power of existing Markov Blanket method (DASSO-MB) and maintain its advantages in omic data analysis. Both simulation and real data analysis were conducted to assess its performances by comparing with other methods including χ(2) test with Bonferroni and B-H adjustment, least absolute shrinkage and selection operator (LASSO) and DASSO-MB. A serious of simulation studies showed that the true discovery rate (TDR) of proposed MBRFS was always close to zero under null hypothesis (odds ratio = 1 for each SNPs) with excellent stability in all three scenarios of independent phenotype-related SNPs without linkage disequilibrium (LD) around them, correlated phenotype-related SNPs without LD around them, and phenotype-related SNPs with strong LD around them. As expected, under different odds ratio and minor allel frequency (MAFs), MBRFS always had the best performances in capturing the true phenotype-related biomarkers with higher matthews correlation coefficience (MCC) for all three scenarios above. More importantly, since proposed MBRFS using the repeated fishing strategy, it still captures more phenotype-related SNPs with minor effects when non-significant phenotype-related SNPs emerged under χ(2) test after Bonferroni multiple correction. The various real omics data analysis, including GWAS data, DNA methylation data, gene expression data and metabolites data, indicated that the proposed MBRFS always detected relatively reasonable biomarkers. Our proposed MBRFS can exactly capture the true phenotype-related biomarkers with the reduction of false negative rate when the phenotype-related biomarkers are independent or correlated, as well as the circumstance that phenotype-related biomarkers are associated with non-phenotype-related ones.


Prognostic significance of acute kidney injury stage 1B in hospitalized patients with cirrhosis: A US nationwide study.
Understanding the prognostic significance of acute kidney injury (AKI) stage 1B [serum creatinine (sCr) ≥1.5 mg/dL] compared with stage 1A (sCr < 1.5 mg/dL) in a US population is important as it can impact initial management decisions for AKI in hospitalized cirrhosis patients. Therefore, we aimed to define outcomes associated with stage 1B in a nationwide US cohort of hospitalized cirrhosis patients with AKI. Hospitalized cirrhosis patients with AKI in the Cerner-Health-Facts database from January 2009 to September 2017 (n = 6250) were assessed for AKI stage 1 (≥1.5-2-fold increase in sCr from baseline) and were followed for 90 days for outcomes. The primary outcome was 90-day mortality; secondary outcomes were in-hospital AKI progression and AKI recovery. Competing-risk multivariable analysis was performed to determine the independent association between stage 1B, 90-day mortality (liver transplant as a competing risk), and AKI recovery (death/liver transplant as a competing risk). Multivariable logistic regression analysis was performed to determine the independent association between stage 1B and AKI progression. In all, 4654 patients with stage 1 were analyzed: 1A (44.3%) and 1B (55.7%). Stage 1B patients had a significantly higher cumulative incidence of 90-day mortality compared with stage 1A patients, 27.2% versus 19.7% ( p < 0.001). In multivariable competing-risk analysis, patients with stage 1B (vs. 1A) had a higher risk for mortality at 90 days [sHR 1.52 (95% CI 1.20-1.92), p = 0.001] and decreased probability for AKI recovery [sHR 0.76 (95% CI 0.69-0.83), p < 0.001]. Furthermore, in multivariable logistic regression analysis, AKI stage 1B (vs. 1A) was independently associated with AKI progression, OR 1.42 (95% CI 1.14-1.72) ( p < 0.001). AKI stage 1B patients have a significantly higher risk for 90-day mortality, AKI progression, and reduced probability of AKI recovery compared with AKI stage 1A patients. These results could guide initial management decisions for AKI in hospitalized patients with cirrhosis.


Engineering preliminaries to obtain reproducible mixtures of atelocollagen and polysaccharides.
The critical stage in producing blends of biomacromolecules consists in the mixing of component solutions to generate homogenous diluted colloidal systems. Simple experimental investigations allow the establishment of the design rules of recipes and the procedures for preparing homogenous and compositionally reproducible mixtures. Starting from purified solutions of atelocollagen, hyaluronan and native gellan, having as low as possible inorganic salts content, initial binary and ternary mixtures can be prepared up to a total dry matter content of 0.150 g/dL, in no co-precipitating conditions. Two pH manipulation ways are feasible for homogenous mixing: (i) unbuffered prior correction at pH 5.5, and (ii) "rigid" buffering at pH 9.0, using organic species. Atelocollagen including co-precipitates can be obtained in the presence of one or both polysaccharides, preferably in pH domains far from the isoelectric point of scleroprotein. A critical behavior has been observed in mixtures containing gellan, due to its macromolecular dissimilarities compared with atelocollagen. In optimal binary mixtures, the coordinates of threshold points on the phase diagrams are 0.028% w/w atelocollagen/0.025% w/w hyaluronan, and 0.022% w/w atelocollagen/0.020% w/w gellan. Uni- or bi-phasic ternary systems having equilibrated ratios of co-precipitated components can be prepared starting from initial mixtures containing up to 0.032 g/dL atelocollagen, associated with, for example, 0.040 g/dL hyaluronan and 0.008 g/dL gellan, following the first pH manipulation way.


Metoprolol and mephenytoin oxidation polymorphisms in Far Eastern Oriental subjects: Japanese versus mainland Chinese.
We examined genetically determined oxidation polymorphisms of metoprolol and mephenytoin in 200 unrelated, healthy Japanese subjects and in 98 mainland Chinese subjects simultaneously. This examination was done according to the respective reported phenotyping criteria by use of the urinary metabolic ratio of metoprolol and of the percentage of excretion of 4-hydroxymephenytoin 8 hours after dose administration. The frequencies of occurrence of poor metabolizers (PMs) in the Japanese versus the Chinese subjects were 0.5% versus 0% for metoprolol and 22.5% versus 17.4% for mephenytoin, respectively. There were no statistically significant differences in these frequencies between the two Oriental populations. However, Chinese extensive metabolizers (EMs) showed a significantly lower excretion of alpha-hydroxymetoprolol (p less than 0.01) and 4-hydroxymephenytoin (p less than 0.001) than that of Japanese EMs, and the mode of the distribution histogram of the Chinese EMs for the two test probes was skewed compared with that of the Japanese EMs. The findings indicate that the two Far Eastern Oriental subject groups have a lower frequency of PM phenotype of debrisoquin/sparteine-type oxidation and a greater incidence of PM phenotype of mephenytoin oxidation compared with the respective frequencies reported from white subjects. However, the explanation for the observation that the metabolic capacities of the test drugs differed between the EMs of the two populations who had a similar ethnic origin and who resided in the same geographic area remains obscure.


Death and Cardiac Arrest in U.S. Triathlon Participants, 1985 to 2016: A Case Series.
Reports of race-related triathlon fatalities have raised questions regarding athlete safety. To describe death and cardiac arrest among triathlon participants. Case series. United States. Participants in U.S. triathlon races from 1985 to 2016. Data on deaths and cardiac arrests were assembled from such sources as the U.S. National Registry of Sudden Death in Athletes (which uses news media, Internet searches, LexisNexis archival databases, and news clipping services) and USA Triathlon (USAT) records. Incidence of death or cardiac arrest in USAT-sanctioned races from 2006 to 2016 was calculated. A total of 135 sudden deaths, resuscitated cardiac arrests, and trauma-related deaths were compiled; mean (±SE) age of victims was 46.7 ± 12.4 years, and 85% were male. Most sudden deaths and cardiac arrests occurred in the swim segment (n = 90); the others occurred during bicycling (n = 7), running (n = 15), and postrace recovery (n = 8). Fifteen trauma-related deaths occurred during the bike segment. Incidence of death or cardiac arrest among USAT participants (n = 4 776 443) was 1.74 per 100 000 (2.40 in men and 0.74 in women per 100 000; P < 0.001). In men, risk increased substantially with age and was much greater for those aged 60 years and older (18.6 per 100 000 participants). Death or cardiac arrest risk was similar for short, intermediate, and long races (1.61 vs. 1.41 vs. 1.92 per 100 000 participants). At autopsy, 27 of 61 decedents (44%) had clinically relevant cardiovascular abnormalities, most frequently atherosclerotic coronary disease or cardiomyopathy. Case identification may be incomplete and may underestimate events, particularly in the early study period. In addition, prerace medical history is unknown in most cases. Deaths and cardiac arrests during the triathlon are not rare; most have occurred in middle-aged and older men. Most sudden deaths in triathletes happened during the swim segment, and clinically silent cardiovascular disease was present in an unexpected proportion of decedents. Minneapolis Heart Institute Foundation.


Aging characteristics of colorectal cancer based on gut microbiota.
Aging is one of the factors leading to cancer. Gut microbiota is related to aging and colorectal cancer (CRC). A total of 11 metagenomic data sets related to CRC were collected from the R package curated Metagenomic Data. After batch effect correction, healthy individuals and CRC samples were divided into three age groups. Ggplot2 and Microbiota Process packages were used for visual description of species composition and PCA in healthy individuals and CRC samples. LEfSe analysis was performed for species relative abundance data in healthy/CRC groups according to age. Spearman correlation coefficient of age-differentiated bacteria in healthy individuals and CRC samples was calculated separately. Finally, the age prediction model and CRC risk prediction model were constructed based on the age-differentiated bacteria. The structure and composition of the gut microbiota were significantly different among the three groups. For example, the abundance of Bacteroides vulgatus in the old group was lower than that in the other two groups, the abundance of Bacteroides fragilis increased with aging. In addition, seven species of bacteria whose abundance increases with aging were screened out. Furthermore, the abundance of pathogenic bacteria (Escherichia_coli, Butyricimonas_virosa, Ruminococcus_bicirculans, Bacteroides_fragilis and Streptococcus_vestibularis) increased with aging in CRCs. The abundance of probiotics (Eubacterium_eligens) decreased with aging in CRCs. The age prediction model for healthy individuals based on the 80 age-related differential bacteria and model of CRC patients based on the 58 age-related differential bacteria performed well, with AUC of 0.79 and 0.71, respectively. The AUC of CRC risk prediction model based on 45 disease differential bacteria was 0.83. After removing the intersection between the disease-differentiated bacteria and the age-differentiated bacteria from the healthy samples, the AUC of CRC risk prediction model based on remaining 31 bacteria was 0.8. CRC risk prediction models for each of the three age groups showed no significant difference in accuracy (young: AUC=0.82, middle: AUC=0.83, old: AUC=0.85). Age as a factor affecting microbial composition should be considered in the application of gut microbiota to predict the risk of CRC.


Vasostatin-1 as a potential novel circulating biomarker in patients with chronic systolic heart failure: A pilot study.
Previous studies have shown that circulating chromogranin A (CgA) increases in patients with chronic systolic heart failure (HF). Aim of the present study is to evaluate the potential role of circulating vasostatin-1 (VS-1), a cardioregulatory fragment of CgA, as prognostic marker in patients with chronic HF. The plasma levels of CgA and VS-1 were determined in 80 patients with chronic systolic HF. Patients were followed-up to evaluate the occurrence of cardiovascular (CV) events. CgA and VS-1 plasma levels were significantly higher in patients with CV events at follow-up. VS-1, but not CgA, was associated to NT-proBNP. No significant association of CgA and VS-1 with left ventricular ejection fraction (LVEF) was observed. CgA, NT-proBNP and age, but not VS-1, were independent predictors of CV events. In patients with chronic systolic HF those who experienced CV events had higher levels of VS-1 and CgA. Given its established effect on cardiac cells, the association of VS-1 levels with NT-proBNP levels but not with LVEF, suggests that this fragment might provide complementary information to NT-proBNP and CgA in HF patients.


Beta-endorphin levels in women with elevated prolactin and following bromocriptine therapy.
1. Plasma levels of beta-endorphin were not significantly different in women with normal plasma prolactin or women with hyperprolactinemia. 2. A bromocriptine induced decrease in plasma prolactin was not accompanied by a decrease in beta-endorphin. 3. This study suggests that no direct link exists between plasma prolactin levels and endogenous beta-endorphin.


A proteomic analysis of storage stress responses in Ipomoea batatas (L.) Lam. tuberous root.
During post-harvest storage, tuberous roots of sweet potato (Ipomoea batatas L. Lam.) usually undergo a biotic and abiotic stress influencing protein expression pattern and substance contents. This research compared the change of total proteins and carbohydrate content in tuberous roots of sweet potato during the storage period. The result of the two-dimensional electrophoresis analysis demonstrated that there were 25 differentially expressed proteins between day 0 and day 75 during the storage. Among these proteins, 11 proteins were down-regulated and the other 14 were up-regulated. The results from MALDI-TOF-TOF/MS analyses and mascot database searching showed that 11 of the 25 differentially expressed proteins were identified as store-stress regulated proteins. It was also found that the proteins involved in the energy metabolism and the stress-response were drastically up-regulated, whereas those in biomacromolecule synthesis were markedly down-regulated. Meanwhile, under the experimental conditions, the content of the starch and the cellulose was decreased by more than a quarter and the amylase activity was increased moderately.


A rapid and inexpensive one-tube genomic DNA extraction method from Agrobacterium tumefaciens.
Many methods have been used to isolate genomic DNA, but some of them are time-consuming and costly, especially when extracting a large number of samples. Here we described an easy protocol using two simple solutions for DNA extraction from A. tumefaciens cells. Compared with the standard protocol, this protocol allows rapid DNA isolation with comparable yield and purity at negligible cost. Following this protocol, we have demonstrated: (1) gDNA extraction was achieved within 15 min; (2) this method was cost-effective, since it only used calcium chloride and lysozyme; SDS, phenol, chloroform and proteinase K were not necessary; (3) the method gave high yield of gDNA (130 ng/loopful culture) compared with standard protocol that was suitable for restriction analysis; (4) the protocol can be carried out in a single test tube and the cells directly from solid media can be used. Thus, this protocol offers an easy, efficient and economical way to extract genomic DNA from A. tumefaciens.


The effect of superoxide dismutase and catalase on the extended preservation of the ex vivo heart for transplantation.
The applicability of heart transplantation remains limited in part by the inability to preserve the excised heart for long periods of time. Free radical scavengers have been shown to protect the anoxic myocardium by preventing damage to the cell membrane and may, therefore, be effective in extending successful preservation of donor hearts. We perfused 10 sheep hearts for 8 hours in an ex vivo perfusion system. The effect of superoxide dismutase combined with catalase, 60,000 units/L, was studied in five sheep, and five received placebo. Control determinations and determinations after 8 hours of preservation were obtained with the heart perfused with autologous blood at 37 degrees C at an aortic perfusion pressure of 60 mm Hg and flow of 180 to 200 ml/min. After control readings, the hearts were arrested and perfused with a cold (6 degrees to 8 degrees C) oxygenated buffered crystalloid solution with or without superoxide dismutase and catalase at a perfusion pressure of 30 cm H2O for 8 hours. Left and right ventricular compliance was measured sequentially with separate intraventricular balloons. After 8 hours of ex vivo preservation, hearts receiving superoxide dismutase and catalase had significantly better left and right ventricular performance, higher myocardial oxygen consumption, and lower lactate production than the control group. The hearts preserved with superoxide dismutase and catalase showed significantly better left and right ventricular compliance, much less increase in heart weight, and no change in the diastolic pressures. The results suggest that superoxide dismutase combined with catalase may be effective in extending ex vivo preservation of hearts for cardiac transplantation.


Clinical results of Cochlear™ BIA300 in children: Experience in two tertiary referral centers.
To evaluate clinical outcomes of the Cochlear™ BIA300 in the pediatric population. Historical cohort study. Two tertiary referral centers. All patients implanted with the BIA300 from November 2011 to January 2014 and 17 years or younger during surgery were included in this cohort study. Number of soft tissue reaction scores according to Holgers, local and systemic treatment of soft tissue reactions, revision surgeries and implant loss. Since introduction of the BIA300, 79 children have been implanted in both centers. During the mean follow-up of 11.7 months per implant, 15.7% of 115 implants received at least two local treatments for peri-abutment soft tissue reactions. Moreover, in 32 implants an adverse soft tissue reaction (Holgers 2 or higher) was noted at least once. In 28.7% of implants one or multiple revision surgeries were required. Implant loss occurred in 4 patients (3.5% of all implants), additionally, in five children the abutment had to be removed because of persistent soft tissue problems. The current study confirms good implant survival for these implants in pediatric patients. The number of adverse soft tissue reactions found in the current study resembles numbers reported on previous generation implants and abutments in children. However, for revision surgery (soft tissue revision and/or abutment change), an increase in frequency is noticed compared to reported results on previous generation implants and abutments, whether this is the result of the new implant or other factors cannot be concluded on the current series. The total aspect of the presented data are of importance in the decision making for a specific type of percutaneous bone anchored hearing implant.


Rapid kinetics reveal surprising flavin chemistry in bifurcating electron transfer flavoprotein from Acidaminococcus fermentans.
Electron bifurcation uses free energy from exergonic redox reactions to power endergonic reactions. β-FAD of the electron transfer flavoprotein (EtfAB) from the anaerobic bacterium Acidaminococcus fermentans bifurcates the electrons of NADH, sending one to the low-potential ferredoxin and the other to the high-potential α-FAD semiquinone (α-FAD•-). The resultant α-FAD hydroquinone (α-FADH-) transfers one electron further to butyryl-CoA dehydrogenase (Bcd); two such transfers enable Bcd to reduce crotonyl-CoA to butyryl-CoA. To get insight into the mechanism of these intricate reactions, we constructed an artificial reaction only with EtfAB containing α-FAD or α-FAD•- to monitor formation of α-FAD•- or α-FADH-, respectively, using stopped flow kinetic measurements. In the presence of α-FAD, we observed that NADH transferred a hydride to β-FAD at a rate of 920 s-1, yielding the charge-transfer complex NAD+:β-FADH- with an absorbance maximum at 650 nm. β-FADH- bifurcated one electron to α-FAD and the other electron to α-FAD of a second EtfAB molecule, forming two stable α-FAD•-. With α-FAD•-, the reduction of β-FAD with NADH was 1500 times slower. Reduction of β-FAD in the presence of α-FAD displayed a normal kinetic isotope effect (KIE) of 2.1, whereas the KIE was inverted in the presence of α-FAD•-. These data indicate that a nearby radical (14 Å apart) slows the rate of a hydride transfer and inverts the KIE. This unanticipated flavin chemistry is not restricted to Etf-Bcd but certainly occurs in other bifurcating Etfs found in anaerobic bacteria and archaea.


Coelomic System of the Sea Urchin Strongylocentrotus pallidus (Echinodermata, Echinoidea) and the Issue of Coelomic Metamery in Echinoderms.
The representatives of the main phylogenetic clades of Bilateria are characterized by metamery. In Deuterostomia, metamery is presented in hemichordates and chordates. Sea urchins have 7 metameric coelomic rings located along the oral-aboral axis of the body. A similar coelomic metamery is also a sign of representatives of other classes of echinoderms. We hypothesize that the metameric coelomic rings in echinoderms are inherent of the common ancestor of Deuterostomia. Asymmetry in the structure of echinoderm coeloms is the result of ancestral forms lying on the right side of the body, which led to a reduction of the coeloms on the right side. During the sedentary lifestyle, the left-side coeloms formed metameric coelomic rings.


A comparison of hippocampal microglial responses in aged and young rodents following dependent and non-dependent binge drinking.
Alcoholism is a highly visible and prevalent issue in the United States. Although binge-drinking is assumed to be a college-age problem, older adults (ages 65+) consume binge amounts of alcohol and have alcohol use disorders (AUDs). Moreover, individuals with alcohol dependence in their youth often continue to drink as they age. As such, this study tested the hypothesis that the effects of alcohol on hippocampal microglia are exacerbated in aged versus younger rodents in two AUD models. Briefly, adult (2-3 months) and aged (15+ months) Sprague-Dawley rats were administered alcohol or control diet using the Majchrowicz model to study alcohol-induced neurodegeneration. To study the effects of non-dependent binge consumption on microglia, adolescent (6-8 weeks) and aged (18+ months) C57/BL6N were subjected to the Drinking in the Dark paradigm. Microglia number and densitometry were assessed using immunohistochemistry. Hippocampal subregional and model/species-specific effects of alcohol were observed, but overall, aging did not appear to increase the alcohol-induced microglia reactivity as measured by Iba-1 densitometry. However, analysis of microglial counts revealed a significant decrease in the number microglia cells in both the alcohol-induced neurodegeneration and DID model across age groups. In the dentate gyrus, the loss of microglia was exacerbated by aging, particularly in mice after DID, non-dependent model. Using qRT-PCR, the persistence of alcohol and aging effects was assessed following the DID model. Allograft Inflammatory Factor 1 mRNA was increased in both young and aged mice by alcohol exposure; however, only in the aged mice did the alcohol effect persist. Overall, these data imply that the microglial response to alcohol is complex with evidence of depressed numbers of microglia but also increased reactivity with advanced age.


Developments, complications and limitations of catheter-mediated electrical ablation of posterior accessory atrioventricular pathways.
Nineteen patients with posterior accessory pathways and disabling, refractory arrhythmias, underwent catheter ablation using standard defibrillator pulses at energy settings of 150 to 400 J. Accessory pathway ablation was successful in 13 of 19 (68%). Effective catheter ablation correlated with local ventriculoatrial (VA) intervals determined from the coronary sinus catheter at the site of earliest retrograde atrial activation during orthodromic reciprocating tachycardia. In 12 of the 13 successfully ablated patients, the local VA interval was less than 80 ms. In 4 of the 6 unsuccessfully treated patients, the local VA interval was greater than or equal to 80 ms, p less than 0.01. Transient abnormalities noted with the procedure included sinus bradycardia (3 patients), atrioventricular block (5), accelerated junctional rhythm (3), ectopic atrial tachycardia (2), myocardial depression (1), "ischemic" appearing T-wave inversions (10) and hemodynamically insignificant small pericardial effusions (5) Creatine kinase-MB increased from 3 +/- 2 U/liter to 26 +/- 18 U/liter (p less than 0.001), 4 to 8 hours after ablation. In addition, electrical shorts occurring during the ablation procedure in 2 patients were identified and corrected only with oscilloscopic monitoring of voltage and current waveforms. Significant adverse sequelae were seen in 4 patients. Three patients required sternotomy for control of cardiac tamponade secondary to a ruptured coronary sinus and 1 patient had a small posterior left ventricular infarction related to spasm of a right coronary artery extension branch. Coronary sinus rupture correlated with the ratio of catheter diameter to coronary sinus diameter.(ABSTRACT TRUNCATED AT 250 WORDS)


Ethnic drinking cultures and alcohol use among Asian American adults: findings from a national survey.
To investigate the influence of ethnic drinking cultures on alcohol use by Asian Americans and how this influence may be moderated by their level of integration into Asian ethnic cultures. A nationally representative sample of 952 Asian American adults extracted from the Wave 2 National Epidemiologic Survey of Alcohol and Related Conditions data was used. Multiple logistic and linear regression models were fitted, some of which were stratified by nativity. Controlling for financial stress, discrimination and demographic variables, a hypothesized, positive relationship between ethnic drinking cultures and alcohol outcomes held for most drinking outcomes. A hypothesis on the moderating effect of integration into ethnic cultures indicated by ethnic language use was supported for US-born Asian Americans. Ethnic drinking cultures may significantly influence alcohol use by Asian Americans. The influence of ethnic drinking cultures may be conditioned by the degree of integration into the ethnic cultures. To inform alcohol interventions for reducing harmful and hazardous alcohol use among immigrants, future research needs to explore the cultural and social processes occurring in immigrant communities that might significantly influence drinking.


Age differences in brain structural and metabolic responses to binge ethanol exposure in fisher 344 rats.
An overarching goal of our research has been to develop a valid animal model of alcoholism with similar imaging phenotypes as those observed in humans with the ultimate objective of assessing the effectiveness of pharmacological agents. In contrast to our findings in humans with alcohol use disorders (AUD), our animal model experiments have not demonstrated enduring brain pathology despite chronic, high ethanol (EtOH) exposure protocols. Relative to healthy controls, older individuals with AUD demonstrate accelerating brain tissue loss with advanced age. Thus, this longitudinally controlled study was conducted in 4-month old (equivalent to ~16-year-old humans) and 17-month old (equivalent to ~45-year-old humans) male and female Fisher 344 rats to test the hypothesis that following equivalent alcohol exposure protocols, older relative to younger animals would exhibit more brain changes as evaluated using in vivo structural magnetic resonance imaging (MRI) and MR spectroscopy (MRS). At baseline, total brain volume as well as the volumes of each of the three constituent tissue types (i.e., cerebral spinal fluid (CSF), gray matter, white matter) were greater in old relative to young rats. Baseline metabolite levels (except for glutathione) were higher in older than younger animals. Effects of binge EtOH exposure on brain volumes and neurometabolites replicated our previous findings in Wistar rats and included ventricular enlargement and reduced MRS-derived creatine levels. Brain changes in response to binge EtOH treatment were more pronounced in young relative to older animals, negating our hypothesis. Higher baseline glutathione levels in female than male rats suggest that female rats are perhaps protected against the more pronounced changes in CSF and gray matter volumes observed in male rats due to superior metabolic homeostasis mechanisms. Additional metabolite changes including low inositol levels in response to high blood alcohol levels support a mechanism of reversible osmolarity disturbances due to temporarily altered brain energy metabolism.


Modification of plasma membrane proton pumps in cucumber roots as an adaptation mechanism to salt stress.
The effect of salt stress (50mM NaCl) on modification of plasma membrane (PM) H(+)-ATPase (EC 220.127.116.11) activity in cucumber roots was studied. Plants were grown under salt stress for 1, 3 or 6 days. In salt-stressed plants, weak stimulation of ATP hydrolytic activity of PM H(+)-ATPase and significant stimulation of proton transport through the plasma membrane were observed. The H(+)/ATP coupling ratio in the plasma membrane of plants subjected to salt stress significantly increased. The greatest stimulation of PM H(+)-ATPase was in 6-day stressed plants. Increased H2O2 accumulation under salt stress conditions in cucumber roots was also observed, with the greatest accumulation observed in 6-day stressed plants. Additionally, during the sixth day of salinity, there appeared heat shock proteins (HSPs) 17.7 and 101, suggesting that repair processes and adaptation to stress occurred in plants. Under salt stress conditions, fast post-translational modifications took place. Protein blot analysis with antibody against phosphothreonine and 14-3-3 proteins showed that, under salinity, the level of those elements increased. Additionally, under salt stress, activity changes of PM H(+)-ATPase can partly result from changes in the pattern of expression of PM H(+)-ATPase genes. In cucumber seedlings, there was increased expression of CsHA10 under salt stress and the transcript of a new PM H(+)-ATPase gene isoform, CsHA1, also appeared. Accumulation of the CsHA1 transcript was induced by NaCl exposure, and was not expressed at detectable levels in roots of control plants. The appearance of a new PM H(+)-ATPase transcript, in addition to the increase in enzyme activity, indicates the important role of the enzyme in maintaining ion homeostasis in plants under salt stress.


Drawing the borders of the mesophotic zone of the Mediterranean Sea using satellite data.
The 30-150 m bathymetric range is commonly adopted in the literature to constrain the mesophotic zone. However, such depth interval varies depending on sunlight penetration, which is primarily a function of solar radiation incidence and water clarity. This is especially obvious in the Mediterranean Sea with its peculiar biophysical properties. Integrating information on light regime in the estimation of the bathymetric range of the mesophotic zone would provide a more robust definition, orienting conservation actions targeting its ecosystems. We present a first assessment of the spatial and vertical extension of the mesophotic zone in the Mediterranean Sea based upon light penetration, comparing our prediction with literature data. Our study also represents a baseline to monitor future variations in the bathymetric interval associated with the mesophotic zone in the Mediterranean Sea in relation to global changes.


The application of microsatellites in molecular pathology.
Present within the genome are large numbers of seemingly unimportant DNA segments arranged in repetitive units. Furthermore, these stretches of DNA contain variations or polymorphisms that are characteristic for an individual and results in a unique DNA fingerprint. Approximately 30% of the DNA repeat sequences are arranged as short tandem repeat sequences, which are called microsatellites. Microsatellites may consist of 1, 2 or 3 nucleotides; dinucleotides being the commonest. Microsatellites are characterised by being: stably inherited and hence highly conserved from one generation to the next, and unique to an individual and the same in different cells from the same individual. As a result of the above features, microsatellites can be used for personal identification, population genetic analysis and construction of evolutionary trees. In addition, they are located in several important gene loci and this allows microsatellites to be used as markers of disease and to provide information about individual gene status, especially in tumors. This can be accomplished by assessing allelic imbalance or loss of heterozygosity of a particular gene by analysing microsatellites located at specific loci in the gene. Recently, mutations within microsatellites have been described as a result of defective DNA repair mechanisms, resulting in the phenomenon of microsatellite instability. This has been implicated in the aetiopathogenesis of several hereditary and non-hereditary conditions. There are several ways of analysing microsatellites, the popular using radioactively-labelled primers and autoradiography. This method has several drawbacks, especially the use of radioactivity and interpretative/technical problems. The use of fluorescently-labelled primers, automated DNA sequencing coupled with a computer software package obviates these problems. This technique has the added advantage of analysing several microsatellites in large numbers of cases, simultaneously. Thus, microsatellite analysis has become an important investigative tool for the molecular biologist and has provided new information in many diseases.


Neurological aspects of organophosphate poisoning.
Besides their well-known anticholinesterase action resulting in a typical acute cholinergic crisis, organophosphorus (OP) agents are capable of producing several subacute or chronic neurological syndromes. The acute over-stimulation at the neuromuscular junction results in muscle fiber necrosis. The significance of this OP-induced myopathy in human intoxication is unknown. Organophosphate-induced delayed neuropathy (OPIDN) arises 1-3 weeks after exposure to some OP compounds all capable of remarkably inhibiting a distinct esterase called neuropathy target esterase (NTE) during a critical time period. An experimental hen model has been designed to screen new OP compounds as to their delayed neurotoxic effects. The recently described intermediate syndrome emerges 1-4 days after an apparently well-treated cholinergic crisis. It main clinical features are sudden respiratory paralysis, cranial motor nerve palsies, and proximal limb muscle and neck flexor weakness. Whether or not this is a separate entity in OP agent toxicology remains to be seen. Further studies are required to further determine its clinical and paraclinical characteristics and the actual type of underlying neuromuscular dysfunction involved.


Don't forget about syphilis.
Syphilis has extremely variable manifestations that produce an extremely broad differential diagnosis. Care must be taken to consider syphilis in dermatologic and other systemic disorders as is relevant.


Investigation on Quantitative Structure Activity Relationships of a Series of Inducible Nitric Oxide.
A series of 2-dihydro-4-quinazolin with potent highly selective inhibitors of inducible nitric oxide synthase activities was subjected to quantitative structure activity relationships (QSAR) analysis. Statistically significant equations with high correlation coefficient (r 2 = 0.8219) were developed. The k-nearest neighbor model has showed good cross-validated correlation coefficient and external validation values of 0.7866 and 0.7133, respectively. The selected electrostatic field descriptors the presence of blue ball around R1 and R4 in the quinazolinamine moiety showed electronegative groups favorable for nitric oxide synthase activity. The QSAR models may lead to the structural requirements of inducible nitric oxide compounds and help in the design of new compounds.


Protein-ligand dynamics. A 96 picosecond simulation of a myoglobin-xenon complex.
A 96 picosecond dynamics trajectory of myoglobin with five xenon-probe ligands in internal cavities is examined to study the effect of protein motions on ligand motion and internal cavity fluctuations. Average structural and energetic properties indicate that the simulation is well behaved. The average protein volume is similar to the volume of the X-ray model and the main-chain atom root-mean-square deviation between the X-ray model and the average dynamical structure is 1.25 A. The protein volume oscillates 3 to 4% around the volume of the X-ray structure. These fluctuations lead to changes in the internal free volume and in the size, shape and location of atom-sized cavity features. Transient cavities produced in the simulation have a crucial role in the movement of two of the ligands. One of the ligands escapes to the protein surface, whilst a second ligand travels through the protein interior. Complex gating processes involving several protein residues are responsible for producing the necessary pores through which the ligand passes between transient cavities or packing defects.


New insights into anti-Müllerian hormone role in the hypothalamic-pituitary-gonadal axis and neuroendocrine development.
Research into the physiological actions of anti-Müllerian hormone (AMH) has rapidly expanded from its classical role in male sexual differentiation to the regulation of ovarian function, routine clinical use in reproductive health and potential use as a biomarker in the diagnosis of polycystic ovary syndrome (PCOS). During the past 10 years, the notion that AMH could act exclusively at gonadal levels has undergone another paradigm shift as several exciting studies reported unforeseen AMH actions throughout the Hypothalamic-Pituitary-Gonadal (HPG) axis. In this review, we will focus on these findings reporting novel AMH actions across the HPG axis and we will discuss their potential impact and significance to better understand human reproductive disorders characterized by either developmental alterations of neuroendocrine circuits regulating fertility and/or alterations of their function in adult life. Finally, we will summarize recent preclinical studies suggesting that elevated levels of AMH may potentially be a contributing factor to the central pathophysiology of PCOS and other reproductive diseases.


Seasonal fluctuations of Zn, Pb, As and Cd contents in the biomass of selected grass species growing on contaminated soils: Implications for in situ phytostabilization.
Phytostabilization aims to immobilize contaminants at the rhizosphere level using the root system of adapted plants. In order to exploit wild grasses with potential for phytostabilization, a screening throughout the year was conducted at a site contaminated by Pb and Zn. Three plant species were chosen: Agrostis capillaris, Arrhenatherum elatius and Calamagrostis epigeios. Rhizospheric soil and biomass was used for chemical characterization. Above- and below-ground was analyzed. For each sample, arbuscular mycorrhiza fungi colonization was determined. The highest concentrations of Pb were found in the A. capillaris rhizosphere (3417 mg kg-1), and in A. elatius for Zn (3876 mg kg-1). CaCl2-extractable Zn in the rhizosphere of C. epigeios was the lowest and Pb was lower for A. elatius. CaCl2-extractable Cd was neither species-dependent nor time-dependent. Arsenic was not species-dependent. The fractionation of target elements did not show differences between separate sampling campaigns and Pb was the only element that showed differences during the year. A. capillaris showed the best capacity to take up elements. The colonization by AMF did not show significant differences for different sampling times, or interactions between time and species, however differences were found for different species, i.e., C. epigeios showed significantly lower colonization by arbuscular mycorrhiza fungi. Our results indicate that A. capillaris appears to be a good indigenous candidate for phytostabilization.


Therapeutic potentiation of the immune system by costimulatory Schiff-base-forming drugs.
Immune responses are orchestrated by CD4 T lymphocytes, which receive a cognitive signal when clonally distributed receptors are occupied by major histocompatibility complex (MHC) class II-bound peptides on antigen-presenting cells (APCs). The APCs provide costimulatory signals, through macromolecules such as CD80, that regulate outcomes in terms of T-cell activation or anergy. We have studied essential complementary chemical events in the form of Schiff base formation between carbonyls and amines that are constitutively expressed on presenting cell and T-cell surfaces and provide a new target for manipulation of immune responses. Here we show that small Schiff base-forming molecules can substitute for the physiological donor of carbonyl groups and provide a costimulatory signal to CD4 Th-cells through a mechanism that activates clofilium-sensitive K+ and Na+ transport. One such molecule, tucaresol, enhances CD4 Th-cell responses, selectively favouring a Th1-type profile of cytokine production. In vivo tucaresol potently enhances CD4 Th-cell priming and CD8 cytotoxic T-cell priming to viral antigens, and has substantial therapeutic activity in murine models of disease.


Movements of cats on a rotating cylinder: role of the substantia nigra pars reticulata and the deeper layers of the superior colliculus.
Recently it has been shown that the substantia nigra pars reticulata (SNR) is required for adjusting the body position. In this study the role of the SNR in the execution of movements was investigated. Therefore, the effects of bilateral SNR injections of picrotoxin (500 ng/0.5 microliter) and muscimol (200 ng/1 microliter) were investigated on movements of cats which were trained to cross a rotating cylinder. SNR injection of picrotoxin suppressed the movements that were executed by cats injected with distilled water (0.5 microliter), i.e. 'normal movements'. While crossing the rotating cylinder, picrotoxin-injected cats mainly executed movements that almost never occurred in distilled water treated cats. Picrotoxin-injected cats executed 'special movements', i.e. forward locomotion in which the hindlimbs were affected, and 'counter-movements'. While executing the latter movements no forward locomotion occurred at all; the cats solely executed lateral fore- and hindlimb movements opposite to the direction in which the cylinder rotated. SNR application of muscimol enhanced the execution of 'normal movements'. Since the SNR sends information to the deeper layers of the superior colliculus (dl-SC) via GABAergic fibers, it was also investigated whether pharmacological stimulation (muscimol) and inhibition (picrotoxin) of the GABAergic dl-SC activity affected these movements on the rotating cylinder: no changes were observed after injecting otherwise effective doses of muscimol (75 ng/1 microliter) and picrotoxin (100 ng/0.5 microliter). In order to compare the function of the SNR and dl-SC in programming a different type of movements, the effects of GABAergic agents in the dl-SC (picrotoxin 100 ng/0.5 microliter and muscimol 75 ng/1 microliter) and the SNR (picrotoxin 500 ng/0.5 microliter and muscimol 200 ng/1 microliter) were investigated on the feline ability to execute goal-directed movements in an experimental set-up that prevented the occurrence of targeting movements which were continuously guided by external, i.e. auditory, visual, tactile and olfactory stimuli. For that purpose cats were trained to step out of a startbox on a rotating cylinder, i.e. the target. Dl-SC injection of muscimol or SNR application of picrotoxin prevented the cats from stepping out of the startbox on the rotating cylinder. In contrast, cats injected with muscimol into the SNR or picrotoxin into the dl-SC stepped out of the startbox, although dl-SC application of picrotoxin elicited forelimb misplacements: frequently the cats placed their forelimbs alongside of, but not on the cylinder when trying to leave the startbox.(ABSTRACT TRUNCATED AT 400 WORDS)


Study on degradation of cooking fume by compound filter material and UV photodegradation.
Environmental contamination issues have steadily surfaced with the rapid development of the cooking industry. In this paper, the front end of the cooking fume exhaust was filtered by the filter material, and then, the ultraviolet photolysis technology was used for in-depth treatment. The filter material filtration performance of glass fiber, molecular sieve, and composite filter material was studied by the filter efficiency, filter resistance, and quality factor three filter performance indexes. The results show that the filter wind speed has a significant influence on the filter material fume filtration characteristics. The filtration efficiency of the pre-filter material changes the least with the increase of the wind speed when the wind speed is 18 m·s-1 and the filter material tilt Angle is 60°; meanwhile, the pressure drop of the two kinds of filter material is reduced, and the quality factor is improved. Under the optimal wind speed and angle, the composite filter material of glass fiber and molecular sieve combined with UV photolysis technology was used to study the treatment of formaldehyde and acrolein, which are two volatile organic pollutants with high content in cooking fume, and the mineralization mechanism of formaldehyde and acrolein under UV light was analyzed. The results showed that the removal rates of formaldehyde and acrolein could reach 99.84% and 99.75%, respectively.


Characterization of the Interaction Between Pancreatic Trypsin and an Enteric Copolymer as a Tool for Several Biotechnological Applications.
Protein-polyelectrolyte complexes are very interesting systems since they can be applied in many long-established and emerging areas of biotechnology. From nanotechnology to industrial processing, these complexes are used for many purposes: to build multilayer particles for biosensors; to entrap and deliver proteins for pharmaceutical applications; to isolate and immobilize proteins. The enteric copolymer poly(methacrylic acid-co-methyl methacrylate) 1:2 (MMA) has been designed for drug delivery although its chemical properties allow to use it for other applications. Understanding the interaction between trypsin and this polymer is very important in order to optimize the mechanism of formation of this complex for different biotechnological applications.The formation of the trypsin-MMA complex was studied by spectroscopy and isothermal titration calorimetry. Structural analysis of trypsin was carried out by catalytic activity assays, circular dichroism and differential scanning calorimetry. Isothermal titration calorimetry experiments showed that the insoluble complex contains 12 trypsin molecules per MMA molecule at pH 5 and they interact with high affinity to form insoluble complexes. Both electrostatic and hydrophobic forces are involved in the formation of the complex. The structure of trypsin is not affected by the presence of MMA, although it interacts with some domains of trypsin affecting its thermal denaturation as seen in the differential scanning calorimetry experiments. Its catalytic activity is not altered. Dynamic light scattering demonstrated the presence of a soluble trypsin-copolymer complex at pH 5 and 8. Turbidimetric assays show that the insoluble complex can be dissolved by low ionic strength and/or pH in order to obtain free native trypsin.


Very accelerated partial breast irradiation Phase I-II multicenter trial (VAPBI): Feasibility and early results.
This is a multicenter Phase I-II trial endorsed by the GEC-ESTRO Breast Working Group, to analyze if very accelerated partial breast irradiation (VAPBI) with multicatheter interstitial brachytherapy is feasible and safe compared with the standard APBI treatment in 4-5 days for early stage breast carcinomas. We have included 81 patients with pT1-2 pN0 invasive carcinomas after breast-conserving surgery. Between August 2017 and July 2019, 33 women received high-dose-rate brachytherapy, four fractions of 6.25 Gy in 2-3 days, and 48 patients received three fractions of 7.45 Gy in 2 days. Thirty-six patients were implanted perioperatively and 45 postoperatively. Mean age was 68 (51-90). Free surgical margins were of 2 mm or greater. Acute effects were 11% dermatitis, 18.5% hematoma, 3.7% infection, and 14.8% pain. At a median followup of 20 months (range 8-35), no relapse has occurred. Pigmentation changes in the entrance and exit of tubes were visible in 16%, but 1 year later, few cases remained. Patients developed G1-2 induration or fibrosis in 18.5% and 2.5%, respectively. No patient developed telangiectasia. The cosmetic outcome was good/excellent in 97.5% and fair in 2.5%. VAPBI with multicatheter interstitial brachytherapy using four fractions of 6.25 Gy or three fractions of 7.45 Gy in two or 3 days is feasible. No excess has been observed in acute effects. At a mean followup of 20 months, late side effects seem to be similar to standard fractionation. VAPBI in two to 3 days is beneficial for the patients and reduces the workload of the brachytherapy units.


The current status of FLASH particle therapy: a systematic review.
Particle therapies are becoming increasingly available clinically due to their beneficial energy deposition profile, sparing healthy tissues. This may be further promoted with ultra-high dose rates, termed FLASH. This review comprehensively summarises current knowledge based on studies relevant to proton- and carbon-FLASH therapy. As electron-FLASH literature presents important radiobiological findings that form the basis of proton and carbon-based FLASH studies, a summary of key electron-FLASH papers is also included. Preclinical data suggest three key mechanisms by which proton and carbon-FLASH are able to reduce normal tissue toxicities compared to conventional dose rates, with equipotent, or enhanced, tumour kill efficacy. However, a degree of caution is needed in clinically translating these findings as: most studies use transmission and do not conform the Bragg peak to tumour volume; mechanistic understanding is still in its infancy; stringent verification of dosimetry is rarely provided; biological assays are prone to limitations which need greater acknowledgement.


Treatment of early-onset dystonia: update and a new perspective.
Dystonia is a rare disease of childhood, often leading to devastating functional impairment. Medical treatment is reviewed, although its efficacy is often limited. Recent advances in functional neurosurgery have opened up a new field in the management of dystonic patients, and the results of deep brain stimulation are given particular emphasis.


Open ended circulation pattern: a rare case of a protective coronary artery variation and review of the literature.
Persistent intercoronary communications, forming the so-called open ended coronary circulation pattern, are rare findings of coronary angiography. A case of intercoronary connection between the left anterior descending artery (LAD) and the right coronary artery (RCA), with an obstructive lesion, and no evidence of myocardial infarction is presented. This is an exceptional variant, only 20 cases of which were found in the literature. The potential protective role of this anomaly against occlusive coronary artery disease is discussed and similar reports are reviewed.


4-(1H-Pyrrolo-[2,3-b]pyridin-2-yl)pyridine.
The asymmetric unit of the title compound, C12H9N3, contains two independent mol-ecules in which the dihedral angle between the pyridine and aza-indole rings are 8.23 (6) and 9.89 (2)°. In the crystal, both types of mol-ecule are connected by pairs of N-H-N hydrogen bonds into inversion dimers.


Characterization of the novel HLA-DPA1*02:01:21 allele by sequencing-based typing.
HLA-DPA1*02:01:21 differs from HLA-DPA1*02:01:01:03 by one nucleotide substitution in codon 190 in exon 4.


Local inflammatory and thrombotic responses differ in a murine model of partial and complete hindlimb ischemia/reperfusion.
These experiments were designed to quantitatively compare the patterns of tissue thrombosis, cytokine response, and tissue viability in a murine model of partial (PI) versus complete hindlimb ischemia (CI), alone or with reperfusion (RE). The control tension tourniquet was used to establish either PI or CI in the unilateral mouse hindlimb for 3 hours followed by 0, 4, and 24 hours of RE. Muscle viability, local neutrophil chemoattractant protein, interleukin 6, interleukin 1beta, D-dimer, thrombin-antithrombin III complex, plasminogen activator inhibitor 1, and tissue plasminogen activator levels were measured in protein extracts for each experimental interval. Tissue viability after CI and 24 hours of RE was significantly less than tissue subjected to PI and 24 hours of RE (96% +/- 16 PI, 64% +/- 4 CI, P=.02). The local cytokine response was initially elevated in the PI group but dissipated by 24RE. In contrast, the local cytokine response to CI alone was small but greatly increased by 24RE. The thrombotic response to PI was increased throughout ischemia/reperfusion. While thrombosis during CI alone was negligible, reperfusion led to a significant thrombotic response. Biochemical markers for tissue viability, thrombosis, and cytokine-mediated inflammation differ significantly in mice subjected to moderate and severe hindlimb ischemia/reperfusion. These biochemical markers may facilitate stratification of patients in clinical trials for treatment of ischemia/reperfusion injury and contribute to interpretation of their outcomes.


Posterior maxillary segmental osteotomy for prosthodontic rehabilitation of vertically excess maxilla -a review.
The purpose of this systematic review was to analyze the literature of the various surgical options available for the correction posterior maxillary alveolar ridge excess without going for radical approaches. It also analyzed the effectiveness of posterior maxillary segmental osteotomy in prosthetic rehabilitation in terms of stability, success rates, function, occlusion, aesthetics and long term postoperative complications. A systematic search of Medline/Pubmed and Web of Science databases of English articles published till December 2017 for the treatment of vertical excess in the posterior maxilla for prosthetic reasons was performed. A total of 37 articles met the inclusion criteria. Posterior maxillary segmental osteotomy (PMSO) was performed as a single stage procedure in 23 cases with minimal post- operative discomfort in all cases. The amount of superior positioning of the osteotomised maxilla ranged between 4 mm to 9 mm which provides sufficient space for prosthodontic rehabilitation. PMSO is fairly competent in treating vertical ridge excess of posterior maxilla, makes space for prosthesis and is associated with fewer postoperative problems when a multidisciplinary team approach is put into service.


Endogenous versus exogenous carbohydrate oxidation measured by stable isotopes in pre-pubescent children plus 13C abundances in foods consumed three days prior.
The purposes of the present study were to (a) examine resting metabolism, substrate utilization, and endogenous versus exogenous carbohydrate (CHO) oxidation before and after 30-g rapidly-digesting carbohydrate (RDC) ingestion using indirect calorimetry and breath test analysis of stable isotope concentrations in pre-pubescent children and (b) report the 13C abundances in foods consumed for three days prior. Nineteen children (n = 10 boys, n = 9 girls) at Tanner stage I or II participated (mean age ± 95% CI = 9.84 ± 0.77 y) in this study. Food was administered to the children for three days preceding their scheduled breath tests. Breath tests and indirect calorimetry were performed after an 8-h fast before and 60 min following consumption of a 30-g simple RDC drink consisting of maltodextrin and sucrose. Open circuit spirometry and indirect calorimetry monitored resting metabolism and CHO oxidation. Separate breath samples were taken every 15 min. Samples of all foods and breath samples were analyzed for 13C and 12C abundances with a stable-isotope mass spectrometer. 13C in expired breath samples were -23.81 ± 1.64‰ at baseline and increased every 15 min after consumption of the CHO drink (p < 0.001-0.009). Cumulative total, endogenous, and exogenous CHO utilization increased during the post-prandial period (p < 0.001). Endogenous CHO oxidation was consistently greater than exogenous CHO oxidation (p < 0.001-0.002).Blood glucose was elevated from baseline at 30- and 60-min post-prandial (p < 0.001). Insulin did not change over time (p = 0.184). The foods provided during the 3-day controlled diet effectively minimized 13C variation prior to metabolic testing. The 13C abundances of foods reported herein should serve as practical recommendations to reduce 13C intake before breath tests. While endogenous CHO oxidation remained greater in proportion to exogenous CHO oxidation, these findings suggest that even a relatively small amount of RDC can increase exogenous CHO oxidation and blood glucose in normal-weight children. To further examine shifts in endogenous versus exogenous CHO utilization, we recommend that future studies take steps to minimize 13C variation before breath tests and examine changes in substrate metabolism at rest and during exercise in normal weight and overweight pre-pubescent children. NCT03185884.


Imitation and local enhancement: detrimental effects of consensus definitions on analyses of social learning in animals.
Development of a widely accepted vocabulary referring to various types of social learning has made important contributions to decades of progress in analyzing the role of socially acquired information in the development of behavioral repertoires. It is argued here that emergence of a consensus vocabulary, while facilitating both communication and research, has also unnecessarily restricted research on social learning. The article has two parts. In the first, I propose that Thorndike's (1898, 1911) definition of imitation as "learning to do an act from seeing it done" has unduly restricted studies of the behavioral processes involved in the propagation of behavior. In part 2, I consider the possibility that success in labeling social learning processes believed to be less cognitively demanding than imitation (e.g. local and stimulus enhancement, social facilitation, etc.) has been mistaken for understanding of those processes, although essentially nothing is known of their stimulus control, development, phylogeny or substrate either behavioral or physiological.


Phase Stability and Mechanical Properties of Al₈Fe₄RE via First-Principle Calculations.
We report on the phase stability, elastic, electronic, and lattice dynamic properties of 17 Al₈Fe₄RE (RE = Sc, Y, La⁻Lu) intermetallic compounds (IMCs) using first-principle calculations. The calculated lattice constants coincided with the experimental results. The calculated enthalpy formation indicated that all the 17 IMCs are stable. The elastic constants and various moduli indicated that Al₈Fe₄RE can be used as a strengthening phase due to its high Young's modulus and shear modulus. The 3D surfaces of Young's modulus for Al₈Fe₄RE showed anisotropic behavior, and the values of hardness for the IMCs were high (about 14 GPa). The phonon spectra showed that only Al₈Fe₄Y had a soft mode, which means the other IMCs are all dynamically stable.


Predisposing, enabling and need factors associated with skilled delivery care utilization among reproductive-aged women in Kersa district, eastern Ethiopia.
Skilled delivery care utilization in Ethiopia is still very low compared with the goal set by the global community for countries with the highest maternal mortality. As a result, the country is overburdened with high maternal morbidity and mortality. We aimed to explore the predisposing, enabling, and need factors associated with skilled delivery care utilization among reproductive-aged women in Kersa district, eastern Ethiopia. A community-based cross-sectional study was conducted with a total of 1294 women. The participants were selected using systematic sampling techniques. An interviewer-administered structured questionnaire aided by an electronic survey tool was used to collect data. Univariate analyses were conducted to describe the study sample. Bivariate and multivariate logistic regression analyses were carried out to elicit the association of predisposing, enabling, and need factors associated with skilled delivery care utilization. Separate multivariate models were fitted for primiparous and multiparous women categories. Odds ratios with 95% confidence intervals were used to assess statistical significance. More than a quarter (30.8%) of the women surveyed used skilled delivery care for their most recent birth. Significant predisposing factors were as follows: presence of educated family member; receiving education on maternal health; previous use of skilled delivery care; and best friend's use of maternal care. Place of residence was the enabling factor that predicted skilled delivery care use. Antenatal care attendance and pregnancy intention were significant need factors associated with skilled delivery care utilization. The findings of the study highlight the need for a concerted effort to establish community-based peer education programs; improve access to family planning services (to reduce unintended pregnancies); increase antenatal care uptake; and facilitate access to skilled delivery care in rural areas.


Crystallization and preliminary analysis of crystals of apolipophorin III isolated from Locusta migratoria.
Crystals of apolipophorin III, isolated from the locust Locusta migratoria, have been reproducibly grown from ammonium sulfate solutions and are well suited for an x-ray crystallographic analysis. Locust apolipophorin III is a glycosylated protein with a molecular weight of 19,100 and interacts with lipophorin, the major lipoprotein complex in insects. The crystals belong to the space group P6122 or P6522 with unit cell dimensions of a = b = 67.5 A, c = 155.6 A and diffract to a nominal resolution of 2.5 A. They are physically robust and are stable in the x-ray beam for over a week. A complete native x-ray data set has been collected and processed to 3.0-A resolution.


Labyrinthine fistulas: Surgical outcomes and an additional diagnostic strategy.
To evaluate perioperative findings and audiological and vestibular outcomes in patients operated for cholesteatoma with labyrinthine fistulas. Also to assess radiological fistula size. Patients who underwent surgery for a labyrinthine fistula caused by a cholesteatoma between 2015 and 2020 in a tertiary referral center were retrospectively investigated. Fistula size was determined on preoperative CT scan. Bone and air conduction pure tone average thresholds were obtained pre- and postoperatively. Clinical outcomes, such as vertigo and otorrea were also evaluated. Main purpose was to determine whether there is a correlation between fistula size and postoperative hearing. Furthermore, perioperative findings and vestibular outcomes are evaluated. 21 patients (22 cases) with a labyrinthine fistula were included. There was no significant change after surgery in bone conduction pure tone average (preoperatively 27.6 dB ± 26.7; postoperatively 30.3 dB ± 34.3; p = 0.628) or air conduction pure tone average (preoperatively 58.7 dB ± 24.3; postoperatively 60.2 dB ± 28.3; p = 0.816). Fistula size was not correlated to postoperative hearing outcome. There were two patients with membranous labyrinth invasion: one patient was deaf preoperatively, the other acquired total sensorineural hearing loss after surgery. Sensorineural hearing loss after cholesteatoma surgery with labyrinthine fistula is rare. Fistula size and postoperative hearing loss are not correlated, however, membranous labyrinthine invasion seems to be related to poor postoperative hearing outcomes. Therefore, additional preoperative radiological work up, by MRI scan, in selected cases is advocated to guide the surgeon to optimize preoperative counselling.


The structure and expression of the murine gene encoding granulocyte-macrophage colony stimulating factor: evidence for utilisation of alternative promoters.
Two overlapping genomic clones containing the murine granulocyte-macrophage colony stimulating factor (GM-CSF) gene have been isolated. On the basis of transfection experiments, we have established that a 9-kb BamHI fragment from one of these recombinants encodes biologically active GM-CSF. As deduced from nucleotide sequence analysis, the GM-CSF gene comprises four exons encompassing 2.5 kb of genomic DNA. Primer extension analysis of GM-CSF mRNA identifies a transcriptional initiation site 35 bp upstream of a single translational initiation codon in-frame with the GM-CSF coding sequences and 28 bp downstream of a TATA promoter consensus sequence. Pre-GM-CSF molecules encoded by mRNAs originating from this promoter would include a hydrophobic leader sequence typical for a secreted protein. Intriguingly, sequences present at the 5' end of a GM-CSF cDNA clone previously isolated in our laboratory are not contained within either of the genomic clones and must therefore be transcribed from a promoter located at least 10 kb 5' of the main body of the gene. mRNAs transcribed from this alternative upstream promoter possess an additional initiating codon and potentially encode a pre-GM-CSF polypeptide with an atypical NH2-terminal leader peptide. Comparison of the nucleotide sequence of the GM-CSF gene with that of other haemopoietic growth factor genes has revealed a common decanucleotide (5'-GPuGPuTTPyCAPy-3') within their respective 5'-flanking regions which may be involved in their co-ordinate regulation.