Metaproteomics reveals functional differences in intestinal microbiota development of preterm infants.
Development of the gastrointestinal tract and immune system can be modulated by the gut microbiota. Establishment of the intestinal microbiota, in its turn, is affected by host and environmental factors. As such, development of the gut microbiota is greatly impacted in preterm infants, who have an immature gut and are exposed to factors like hospitalization, caesarean section, antibiotics, and respiratory support. We analyzed fecal microbiota composition and activity of ten preterm infants (gestational age 25-30 weeks; birthweight 630-1750 g) during the first six postnatal weeks through metaproteomics (LC-MS/MS) and 16S-rRNA gene sequencing. A gestational-age-dependent microbial signature is observed, enabling microbiota-based differentiation between extremely preterm (25-27 weeks gestation) and very preterm (30 weeks gestation) infants. In very preterm infants, the intestinal microbiota developed toward a Bifidobacterium-dominated community and was associated with high abundance of proteins involved in carbohydrate and energy metabolism. Extremely preterm infants remained predominantly colonized by facultative anaerobes and were associated with proteins involved in membrane transport and translation. Delayed colonization by obligate anaerobes could be associated with antibiotic treatment and respiratory support. We speculate that gestational age and its associated intensity of care (e.g. antibiotics and respiratory support) affects intestinal microbiota composition and activity in preterm infants. As the gut microbiota plays a major role in development of the neonate, gestational age and its associated factors could set the stage for early and later life health complications via interference with microbiota development.


Selenium Deficiency Promotes Dilatation of the Aorta by Increasing Expression and Activity of Vascular Smooth Muscle Cell Derived Matrix Metalloproteinase-2.
Selenium (Se) is a key part of the body's oxidation defence system. However, it is unclear whether Se affects the development of aortic aneurysm (AA). An animal experiment was conducted to clarify the role of Se in AA development. C57BL/6N male mice were fed with a Se deficient (Se-D, < 0.05 mg/kg), Se adequate (Se-A, 0.2 mg/kg), or Se supplemented (Se-S, 1 mg/kg) diet for 8 weeks. Subsequently, an AA murine model (Se-D, n = 11; Se-A, n = 12; Se-S, n = 15) was established using angiotensin II (Ang II, 1 mg/kg/min) for 4 weeks plus β-aminopropionitrile (BAPN, 1 mg/mL) for the first 2 weeks. Saline replaced Ang II, and BAPN was removed during the modelling process for sham mice (Se-A, n = 9). To determine whether Se deficiency promotes aortic dilation via matrix metalloproteinase-2 (MMP-2), the non-specific MMP inhibitor doxycycline (Dox, 100 mg/kg/day) was given to Se-D AA mice (n = 7) for 2 weeks. Maximum aortic diameter in Se-D AA model mice was significantly increased compared with Se-A AA model mice. MMP-2 expression and activity in aortic media of Se-D AA model mice was significantly increased compared with Se-A AA model mice. A large number of vascular smooth muscle cells (VSMCs) were found aggregating in the media of non-dilated aorta of Se-D AA model mice, which was completely inhibited by Dox. The percentage of VSMCs in aortic media of Se-D AA model mice was significantly higher than in Se-A AA model mice. Maximum aortic diameter and occurrence rate of AA in Se-D AA model mice with Dox were significantly reduced compared with Se-D AA model mice. Se deficiency promoted dilatation of the aorta in AA model mice by increasing expression and activity of VSMC derived MMP-2, causing abnormal aggregation and proliferation of VSMCs in aortic media.


Emulsion stability and demulsification during the direct extraction of penicillin broth.
In this article, we present the factors which influence the stability of the emulsion forming under the circumstances of the direct extraction of penicillin fermentation broth and the conditions of demulsification. A laboratory method has been developed for testing demulsifiers and a quantitative evaluation of the properties determining the separation of phases has been worked out as well. It has been found that an emulsion of oil in water (o/w) forms and that this is very stable; it can be broken only by the presence of demulsifier and by using a field of centrifugal force. We have discovered that the most effective demulsifiers are cation-active surfactants for 1-4 g/L broth concentration. Furthermore, it is advantageous if the demulsifier contains a nonionic surfactant and wetting agent as well. From the 19 surface-active compounds studied in the laboratory, we found that the NADAR 107 A and ARMOGARD D-5306 demulsifiers contained the best properties for the extraction of the penicillin broth.


Radiographic evaluation of the effect of initial periodontal therapy on thickness of the maxillary sinus mucosa.
The thickness of the radiographic image of the maxillary sinus mucosa on intraoral radiographs was evaluated in 13 patients with advanced periodontal disease, prior to and 12 months following initial periodontal therapy. Before treatment, a relationship was observed between the thickness of the sinus mucosa and the mean probing depths of the teeth in the involved sextant. As many as 79% of the available sextants showed swelling of the mucosa prior to periodontal therapy, compared to only 17% after treatment. This report supports previous studies indicating that advanced periodontal disease may cause swelling of the maxillary sinus mucosa and that periodontal therapy will significantly reduce such swelling.


Prenatal diagnosis of atraumatic fetal subdural hematoma.
We present a case of atraumatic subdural hematoma diagnosed by ultrasound at 22 weeks. A hyperechogenic round mass was identified in the posterior fossa. Further investigation with fetal brain magnetic resonance imaging confirmed the diagnosis. After medical consultation, the parents opted for pregnancy termination. The pathology report confirmed the ultrasonographic and magnetic resonance imaging diagnosis.


High-dose topotecan with granulocyte-colony stimulating factor in fluoropyrimidine-refractory colorectal cancer: a phase II and pharmacodynamic study.
The premise for this study was that topotecan (TPT) resistance in preclinical studies is associated with low level expression of the p-glycoprotein (Pgp) multi-drug transporter conferred by the multi-drug resistant (MDR) phenotype, which might be overcome in clinical practice by administering moderately (2.3-fold) higher doses of TPT that have shown to be feasible with granulocyte colony-stimulating factor (G-CSF) support. This phase II study evaluated the anti-tumor activity of TPT administered at its highest possible solid tumor dose with G-SCF in patients with fluoropyrimidine-refractory advanced colorectal carcinoma. The study also sought to identify pharmacodynamic (PD) determinants of both activity and toxicity. TPT was administered as a 30-minute infusion daily for five days every three weeks at a dose of 3.5 mg/m2/day to patients with advance colorectal carcinoma who developed progressive disease either during treatment with fluoropyrimidine-based chemotherapy for advanced disease or within six months after receiving fluoropyrimidine-based adjuvant chemotherapy. This dose of TPT was previously determined to be the maximal tolerated dose (MTD) with G-CSF support in a phase I study involving solid tumor patients with similar risk factors for myelosuppression. Plasma sampling with performed during course 1 to characterize the pharmacokinetic (PK) and PD behavior of TPT. Seventeen patients who received 89 courses of TPT and G-CSF were evaluable for toxicity; 16 patients were evaluable for anti-tumor response. Toxicity, particularly myelosuppression, was substantial. At the 3.5 mg/m2/day dose level, absolute neutrophil counts (ANC) were less than 500/microliters for longer than 5 days in 17% of courses involving seven of seventeen (41%) patients. Severe neutropenia associated with fever occurred in 12.3% of courses; and platelet counts below 25,000/microliters were noted in 26.9% of courses. These toxicities resulted in dose reductions in seven of 17 (41%) patients. Nevertheless, 90% of the planned total dose of TPT was administered. No major responses were observed, though minor activity was noted in several patients. Both the median time to progression and the median survival time were short--2.5 and 4 months respectively. Although interindividual variability in the disposition of total TPT was observed, the lack of objective responses precluded PD assessments related to disease activity. Total TPT exposure was significantly higher than drug exposure achieved in similar patients at an identical dose in a previous phase I study of TPT and G-CSF, which may explain why more severe myelosuppressive effects occurred in the present study. There were no PD relationships evident between relevant PK parameters and the percent decrements in platelets and ANC's during course 1, although patients with severe toxic effects (ANC below 500/microliters for more than five days and/or platelets < 25,000/microliters) had higher drug exposure than patients with less severe toxicity (P < 0.018 and P = 0.09, respectively). Based on these results, the true response rate of TPT at its solid tumor MTD with G-CSF support is unlikely to approach 20%. Although a response rate of less than 20% might be viewed as significant in this disease setting and might be confirmed with sufficient statistical certainty by treating additional patients, the substantial toxicity, inconvenience, and cost associated with this high dose TPT/G-CSF regimen does not warrant the acceptance of a lower level of anti-tumor activity as a criterion for further development.


Dynamic Assessment of Fluid Responsiveness in Surgical ICU Patients Through Stroke Volume Variation is Associated With Decreased Length of Stay and Costs: A Systematic Review and Meta-Analysis.
Static indices, such as the central venous pressure, have proven to be inaccurate predictors of fluid responsiveness. An emerging approach uses dynamic assessment of fluid responsiveness (FT-DYN), such as stroke volume variation (SVV) or surrogate dynamic variables, as more accurate measures of volume status. Recent work has demonstrated that goal-directed therapy guided by FT-DYN was associated with reduced intensive care unit (ICU) mortality; however, no study has specifically assessed this in surgical ICU patients. This study aimed to conduct a systematic review and meta-analysis on the impact of employing FT-DYN in the perioperative care of surgical ICU patients on length of stay in the ICU. As secondary objectives, we performed a cost analysis of FT-DYN and assessed the impact of FT-DYN versus standard care on hospital length of stay and mortality. We identified all randomized controlled trials (RCTs) through MEDLINE, EMBASE, and CENTRAL that examined adult patients in the ICU who were randomized to standard care or to FT-DYN from inception to September 2017. Two investigators independently reviewed search results, identified appropriate studies, and extracted data using standardized spreadsheets. A random effect meta-analysis was carried out. Eleven RCTs were included with a total of 1015 patients. The incorporation of FT-DYN through SVV in surgical patients led to shorter ICU length of stay (weighted mean difference [WMD], -1.43d; 95% confidence interval [CI], -2.09 to -0.78), shorter hospital length of stay (WMD, -1.96d; 95% CI, -2.34 to -1.59), and trended toward improved mortality (odds ratio, 0.55; 95% CI, 0.30-1.03). There was a decrease in daily ICU-related costs per patient for those who received FT-DYN in the perioperative period (WMD, US$ -1619; 95% CI, -2173.68 to -1063.26). Incorporation of FT-DYN through SVV in the perioperative care of surgical ICU patients is associated with decreased ICU length of stay, hospital length of stay, and ICU costs.


[Hematoma of the rectus sheath as a gynecologic problem].
We report a case of 54 years old female who presented an acute onset of abdominal pain after physical training. Left rectus sheath haematoma may clinically mimic torsion of ovarian cyst. Case was treated surgically, haematoma was found, peritoneal cavity was also controlled.


Robustness of chlorzoxazone as an in vivo measure of cytochrome P450 2E1 activity.
Chlorzoxazone is metabolized by cytochrome P450 2E1 (CYP2E1) to a single oxidized metabolite, 6-hydroxychlorzoxazone. The aim of the study was to test the robustness of chlorzoxazone as an in vivo probe of CYP2E1 activity in humans, with emphasis on investigating short-term and long-term intra-individual variabilities and effects of different doses of the drug. In addition, the influences of body build, drug metabolizing enzyme genotype, blood sampling time, and moderate recent ethanol intake were investigated. The 6-hydroxychlorzoxazone:chlorzoxazone (metabolic) ratio in plasma was measured at 2 h in 28 male and nine female volunteers following a single oral dose of 500 mg chlorzoxazone. Similarly, the metabolic ratios at 4 h and 6 h were measured in 20 of the males. The metabolic ratio at 2 h was also determined 1.5 and 2.5 years later in 13 and seven males, respectively, and weekly for 3 weeks in seven males, after a dose of 500 mg, once at higher (750 mg) and lower (250 mg) doses, and once (500 mg) following moderate ethanol intake (0.5 g kg(-1) body weight) the preceding evening. Genotypes were determined for CYP2E1 as well as for N-acetyltransferase 2 and glutathione transferase M1. Excluding an outlier (ratio = 1.6) the metabolic ratio at 2 h ranged from 0.12 to 0.61 (n = 36). A positive correlation with body weight (r = 0.61, P < 0.001) suggested dose-dependent metabolism of chlorzoxazone. The metabolic ratio decreased with increasing chlorzoxazone dose (P = 0.01), again suggesting dose-dependent metabolism. Long-term (yearly intervals) and short-term (weekly intervals) intra- and interindividual variabilities in metabolic ratio were similar (30% and 63%vs 28% and 54%, respectively). Both inter- and intra-individual variabilities tended to decrease with increasing dose of chlorzoxazone. There was no significant influence of moderate ethanol intake the preceding evening, or of CYP2E1 genotype on the metabolic ratio. The relatively low intra-individual variability in the metabolism of chlorzoxazone suggests that a single-sample procedure may suffice to assess CYP2E1 activity in vivo. However, chlorzoxazone metabolism is dose-dependent at commonly used doses and it is therefore advisable to adjust the dose for body weight. Moderate intake of ethanol the preceding evening did not significantly affect the chlorzoxazone metabolic ratio.


RVX-297- a novel BD2 selective inhibitor of BET bromodomains.
Bromodomains are epigenetic readers that specifically bind to the acetyl lysine residues of histones and transcription factors. Small molecule BET bromodomain inhibitors can disrupt this interaction which leads to potential modulation of several disease states. Here we describe the binding properties of a novel BET inhibitor RVX-297 that is structurally related to the clinical compound RVX-208, currently undergoing phase III clinical trials for the treatment of cardiovascular diseases, but is distinctly different in its biological and pharmacokinetic profiles. We report that RVX-297 preferentially binds to the BD2 domains of the BET bromodomain and Extra Terminal (BET) family of protein. We demonstrate the differential binding modes of RVX-297 in BD1 and BD2 domains of BRD4 and BRD2 using X-ray crystallography, and describe the structural differences driving the BD2 selective binding of RVX-297. The isothermal titration calorimetry (ITC) data illustrate the related differential thermodynamics of binding of RVX-297 to single as well as dual BET bromodomains.


Presentations of bladder exstrophy in a resource-limited setting and the role of Mainz II continent diversion for late referrals or failed primary closures: a multicentric report.
Primary closure techniques that have been updated and longterm follow-up for CBE (classic bladder exstrophy) may be out of reach for many patients living in resource-limited settings. Late referrals to medical care and primary closures that lack the necessary skills and facilities for comprehensive treatment are still common. Alternative and long-term surgical solutions may improve the lives of these unfortunate patients. During surgical outreach missions, patients with CBE, either non-operated or with a previous unsuccessful bladder closure, who were referred from vast under-resourced rural areas to three Eastern African hospitals, were studied. The following information is provided: mode of presentation, clinical history, diagnostic workout, management, and outcome. There were 25 cases (M/F ratio 17/8) ranging in age from two days to twenty years. Five of the seventeen patients who were not treated (35%) were under 120 days old and eligible for primary closure in a qualified tertiary center when one was available in the country. There were twelve late referred cases (ranging from 120 days to 20 years). Between the ages of ten months and twelve years, eight children arrived following a failed primary closure. In all of them, the bladder plate was too altered to allow closure. Following a preoperative diagnostic workout, a Mainz II continent internal diversion was proposed to fourteen patients with acceptable bowel control and postponed in the other three. Three cases were lost before treatment because parents refused the procedure. Twelve cases ranging in age from three to twenty years (mean seven years) were operated on. Eight people were followed for a total of 53.87 months (range: 36-120). Except for three people who complained of occasional night soiling, day and night continence were good. The average voiding frequency during the day was four and 1.3 at night. There was no evidence of a metabolic imbalance, urinary infection, or significant upper urinary tract dilatation. Two fatalities could not be linked to urinary diversion. Four patients were not followed up on. Due to the limited number of specialist surgical facilities, CBE late referral or failed closure is to be expected in a resource-limited context. In lieu of the primary closure, a continent internal diversion will be proposed and encouraged even at the level of a non-specialist hospital to improve the quality of life of these unfortunate patients. It is recommended that patients be warned about the procedure's potential long-term risks, which will necessitate a limited but regular follow-up.


Contribution of PsbS Function and Stomatal Conductance to Foliar Temperature in Higher Plants.
Natural capacity has evolved in higher plants to absorb and harness excessive light energy. In basic models, the majority of absorbed photon energy is radiated back as fluorescence and heat. For years the proton sensor protein PsbS was considered to play a critical role in non-photochemical quenching (NPQ) of light absorbed by PSII antennae and in its dissipation as heat. However, the significance of PsbS in regulating heat emission from a whole leaf has never been verified before by direct measurement of foliar temperature under changing light intensity. To test its validity, we here investigated the foliar temperature changes on increasing and decreasing light intensity conditions (foliar temperature dynamics) using a high resolution thermal camera and a powerful adjustable light-emitting diode (LED) light source. First, we showed that light-dependent foliar temperature dynamics is correlated with Chl content in leaves of various plant species. Secondly, we compared the foliar temperature dynamics in Arabidopsis thaliana wild type, the PsbS null mutant npq4-1 and a PsbS-overexpressing transgenic line under different transpiration conditions with or without a photosynthesis inhibitor. We found no direct correlations between the NPQ level and the foliar temperature dynamics. Rather, differences in foliar temperature dynamics are primarily affected by stomatal aperture, and rapid foliar temperature increase during irradiation depends on the water status of the leaf. We conclude that PsbS is not directly involved in regulation of foliar temperature dynamics during excessive light energy episodes.


[A study of participation of Hdj1 co-chaperone in the modulation of sleep and behavior using micro RNA technology in vivo].
Data obtained for the last 12 years and modern hypotheses on key function of sleep and the role of Heat Shock Protein 70 kDa (HSP70) molecular chaperones family in sleep modulation are insufficient to determine assotiation of sleep quantity to the level of chaperones in the basic "center" of sleep in the ventrolateral preoptic area (VLPA) of the hypothalamus. In the present study, to reduce the content of Hdj1 major co-chaperone of Hsp70 in the VLPA we employed a novel approach based on lentiviral construction containing specific Hdj1-shRNA. The immunoblotting data showed that in 6 weeks after infection the level of Hdj1 in VLPA was reduced by 80% that was accompanied by a considerable increase in the quantity of slow-wave sleep and a marked decrease in the level of anxiety; earlier we found that elevation of Hsp70 level in the rat brain resulted in similar changes. It is suggested that the increase in quantity of slow wave sleep and the decrease in the level of anxiety can be related to a sustained disorder in the integration between molecular systems based on chaperones Hdj1 and Hsp70 and to a compensatory increase in the Hsp70 chaperone activity/level in VLPA.


Capillaroscopy in psoriatic and rheumatoid arthritis: a useful tool for differential diagnosis.
Impairment of capillaries permeability and changes of microcirculation are associated with inflammatory arthritis. In order to demonstrate microvascular differences between psoriatic arthritis (PsA) and rheumatoid arthritis (RA) we analyzed capillaroscopic abnormalities such as megacapillaries, haemorrhages, ramifications, and avascular areas in patients affected by these two rheumatic disorders. Moreover to identify specific capillaroscopy patterns we analyzed the following parameters: venous limb diameter, arterial limb diameter, capillary loop diameter, amplitude of the capillary loop, linear density of capillaries (on 2 mm), and number of twisted capillaries (on 4 mm). Through a comparative morphometric analysis of capillaroscopy, our study demonstrated the presence of specific microvascular differences between PsA and RA providing an additional diagnostic tool for the differential diagnosis. We also suggest that capillaries structural abnormalities might reflect endothelial injury due to systemic inflammation during chronic arthritis.


Recruiting families for an intervention study to prevent second-hand smoke exposure in children.
We evaluated the effectiveness of different recruitment strategies used in a study aimed at eliminating/reducing second-hand smoke (SHS) exposure in Dutch children 0-13 years of age with a high risk of asthma. The different strategies include: 1) questionnaires distributed via home addresses, physicians or schools of the children; 2) cohorts from other paediatric studies; 3) physicians working in the paediatric field (family physicians, paediatricians and Youth Health Care (YHC) physicians); and 4) advertisements in a local newsletter, at child-care facilities, and day-care centres. More than 42,782 families were approached to take part in the screening of which 3663 could be assessed for eligibility. Of these responders, 196 families met the inclusion criteria for the study. However, only 58 (one third) could be randomised in the trial, mainly because of no interest or time of the parents. The results showed that recruiting families who expose their children to SHS exposure is very challenging, which may be explained by lack of 'recognition' or awareness that SHS occurs in homes. The presence of asthma in the family, respiratory symptoms in the children, and even incentives did not increase parental motivation for participation in the study. The recruitment process for an intervention program addressing SHS exposure in children was considerably more challenging and time consuming than anticipated. Barriers at both a parents level and a doctor's level can be discriminated.


[The asphyxia of the fetus--cardiotocography and ultrasound methods of diagnosis].
The asphyxia of the fetus remains a main cause for neonatal morbility and mortality. And the possibility of it developing antenatal or intrapartal. The main objective of the antenatal fetus examination tests is the timely diagnosis of the signs of the asphyxia of the fetus.


Erythrophagocytosis by blasts in a case of de novo acute monoblastic leukemia with rare but characteristic t(8;16).
Erythrophagocytosis by leukemic blasts is a rare phenomenon. We report a case of a female diagnosed with acute monoblastic leukemia with leukemic blasts that were CD34 and CD117 negative, showing erythrophagocytosis, vacoulations, and a rare t(8;16) on bone marrow karyotype which is associated with a poor prognosis despite intensive chemotherapy. Meticulous bone marrow examination in such a scenario may point towards the presence of t(8;16) and help clinicians take a well-informed clinical decision.


An updated review of the literature: risk factors for bladder cancer with focus on occupational exposures.
Workplace exposures account for 5 to 25% of all bladder cancer cases. A critical review of the literature between 1938 and 2004 was performed, with a focus on occupational exposures. Occupational exposure to bladder carcinogens, particularly to beta-naphthylamine occur in a number of industries, including aromatic amine manufacture, rubber and cable manufacture, and dyestuff manufacture and use. Risks to workers in a number of new occupations and industries are reviewed. Nonoccupational risk factors that are known or at one time have been thought to increase the risk of bladder cancer are also discussed.


Right Valsalva Sinus Aneurysm Protruding Into the Right Ventricle: A Case Report.
A separation between the aortic media and annulus fibrosus causes a rare cardiac abnormality called sinus of Valsalva aneurysm (SVA) that may be congenital or acquired. It is more prevalent in the right coronary sinus (65%-85%) but it has been seen rarely in non-coronary (10%-30%) or Left coronary sinus (<5%). The most common complication is rupture of the Aneurysm. We present an 80-year-old male with expanding right Valsalva sinus aneurysm and protruding into right ventricle. The conventional treatment is surgical repair under cardio-pulmonary bypass or percutaneous catheter closure. The aneurysm was successfully excised surgically under direct guidance of trans-esophageal echocardiography (TEE).


Type I tympanoplasty: influencing factors.
Type I tympanoplasties utilizing an underlay technique with temporalis fascia performed at the Medical University associated hospitals over a 5-year period were reviewed. Cases were excluded if follow-up was less than 18 months or if a previous tympanoplasty had been performed. The remaining 71 cases, 40 adults and 25 children, were analyzed for influencing factors. The overall success rate was 89%. The age of the patient, the length of time the ear had been dry, and the presence of infection at the time of surgery had no influence on the success rate. The two factors which adversely influenced the success rate were the presence of a near total or total perforation and the presence of bilateral perforations.


Effective spin Hamiltonian of a gated triple quantum dot in the presence of spin-orbit interaction.
We derive and study the effective spin Hamiltonian of a gated triple quantum dot that includes the effects of spin-orbit interaction and an external magnetic field. In the analysis of the resulting spin interaction in linear and in general triangular geometry of the dots, we show that the pairwise spin interaction does depend on the position of the third dot. The spin-orbit induced anisotropy, in addition to changing its strength, also changes its symmetry with the motion of the third quantum dot outside the linear arrangement. Our results present a simplified model that may be used in the design of quantum computers based on three-spin qubits.


[Clinical study of open vertebroplasty in treating thoracolumbar metastatic tumor].
To explore the clinical application and therapeutic effect of open vertebroplasty for thoracolumbar metastatic tumor. From September 2003 to December 2009, 21 patients with thoracolumbar metastatic tumor underwent the surgical procedure of posterior spinal cord decompression and open vertebroplasty combined with short-segmental pedicle screw fixation during the same intervention. There were 14 males and 7 females, ranging in age from 48 to 73 years with the mean of 59.5 years and ranging in course of disease from 1 to 4 months with an average of 2.5 months. The primary focus of the tumor of 19 cases were established, lung carcinoma was in 8 cases, breast cancer in 4 cases, prostate carcinoma in 4 cases, hepatocarcinoma in 2 cases and thyroid carcinoma in 1 case. The primary focus of 2 cases could not be established. The spinal function according to Frankel grade, grade B was in 4 cases, C in 6, D in 5, E in 6. The lumbar-back pain, height of anterior and posterior vertebral body, Cobb angle and spinal function were recorded before and after operation. The operation of all patients was successful, there were no severe complications and aggravation of spinal function. The VAS score of lumbar-back pain decreased from 8.78 +/- 0.45 preoperatively to 2.25 +/- 0.36 postoperatively. Among 16 cases combined with pathological fracture, the height of anterior spinal vertebral body increased from (12.7 +/- 2.1) mm preoperatively to (19.5 +/- 3.9) mm postoperatively; the height of posterior spinal vertebral body increased from (14.1 +/- 1.8) mm preoperatively to (20.3 +/- 2.3) mm postoperatively; Cobb angle decreased from (26.0 +/- 8.9) degrees preoperatively to (6.0 +/- 0.9) degrees postoperatively. There was significant difference above items between before and after operation (P < 0.05). The spinal function according to Frankel grade at final follow up, grade C was in 2 cases, D in 4, E in 15. All patients were followed up from 5 to 28 months with an average of 14 months, there was no loosening and breakage of internal fixity, 15 cases died during follow-up period. The surgical intervention can effectively preserve spinal instability and alleviate the spinal cord symptoms, improve the life quality of patients. It may provide an alternative treatment for patients in poor general health and shorter life expectancy.


The effect of a moving distractor on the initiation of smooth-pursuit eye movements.
As a step toward understanding the mechanism by which targets are selected for smooth-pursuit eye movements, we examined the behavior of the pursuit system when monkeys were presented with two discrete moving visual targets. Two rhesus monkeys were trained to select a small moving target identified by its color in the presence of a moving distractor of another color. Smooth-pursuit eye movements were quantified in terms of the latency of the eye movement and the initial eye acceleration profile. We have previously shown that the latency of smooth pursuit, which is normally around 100 ms, can be extended to 150 ms or shortened to 85 ms depending on whether there is a distractor moving in the opposite or same direction, respectively, relative to the direction of the target. We have now measured this effect for a 360 deg range of distractor directions, and distractor speeds of 5-45 deg/s. We have also examined the effect of varying the spatial separation and temporal asynchrony between target and distractor. The results indicate that the effect of the distractor on the latency of pursuit depends on its direction of motion, and its spatial and temporal proximity to the target, but depends very little on the speed of the distractor. Furthermore, under the conditions of these experiments, the direction of the eye movement that is emitted in response to two competing moving stimuli is not a vectorial combination of the stimulus motions, but is solely determined by the direction of the target. The results are consistent with a competitive model for smooth-pursuit target selection and suggest that the competition takes place at a stage of the pursuit pathway that is between visual-motion processing and motor-response preparation.


National screening program for transitional ages in Korea: a new screening for strengthening primary prevention and follow-up care.
Screening can effectively reduce mortality and morbidity in some diseases. In Korea, a practical national screening program for chronic disease was launched in 1995 and several problems were discussed. The program focused primarily on disease detection without follow-up care. In addition, the test items were uniform regardless of subject's age, sex, or risk factors; and people with low socioeconomic status were excluded. To improve the quality of program, a new national screening program called the "National Screening Program for Transitional Ages (NSPTA)" was initiated in 2007. It targeted two age groups, ages 40 and 66, because these ages are important transition periods in one's lifecycle. Follow-up care and education for lifestyle modification has been intensified; screening tests for mental health problems and osteoporosis have been introduced. The pool of eligible participants has been expanded to include people supported by Medicaid. This review aimed to describe the contents, process, and characteristics of the NSPTA and to compare it with the previous program. In addition, some preliminary results from 2007 to 2009 were presented. Lastly, we suggest several points that need to be considered to improve the program such as enhancement of participation rates, necessity of specialized committee and research for current screening program to be supported by evidence.


The microRNA profile of prostate carcinoma obtained by deep sequencing.
Prostate cancer is a leading cause of tumor mortality. To characterize the underlying molecular mechanisms, we have compared the microRNA (miRNA) profile of primary prostate cancers and noncancer prostate tissues using deep sequencing. MiRNAs are small noncoding RNAs of 21 to 25 nucleotides that regulate gene expression through the inhibition of protein synthesis. We find that 33 miRNAs were upregulated or downregulated >1.5-fold. The deregulation of selected miRNAs was confirmed by both Northern blotting and quantitative reverse transcription-PCR in established prostate cancer cell lines and clinical tissue samples. A computational search indicated the 3'-untranslated region (UTR) of the mRNA for myosin VI (MYO6) as a potential target for both miR-143 and miR-145, the expression of which was reduced in the tumor tissues. Upregulation of myosin VI in prostate cancer was previously shown by immunohistochemistry. The level of MYO6 mRNA was significantly induced in all primary tumor tissues compared with the nontumor tissue from the same patient. This finding was matched to the upregulation of myosin VI in established prostate cancer cell lines. In luciferase reporter analysis, we find a significant negative regulatory effect on the MYO6 3'UTR by both miR-143 and miR-145. Mutation of the potential binding sites for miR-143 and miR-145 in the MYO6 3'UTR resulted in a loss of responsiveness to the corresponding miRNA. Our data indicate that miR-143 and miR-145 are involved in the regulation of MYO6 expression and possibly in the development of prostate cancer.


Fluoxetine synergizes with temozolomide to induce the CHOP-dependent endoplasmic reticulum stress-related apoptosis pathway in glioma cells.
Although temozolomide (TMZ) is the most effective chemotherapy agent for glioma, chemotherapy resistance has limited its clinical use. Fluoxetine (FLT), which is widely used in cancer-related depression, has exhibited potent anticancer properties in different cancer cell types. The aim of this study was i) to evaluate the antitumor mechanism of FLT, and ii) to further evaluate the effects of a combination of FLT and TMZ on glioma cells. Glioma cell lines were exposed to FLT and/or TMZ. Cell viability and apoptosis were examined by CCK-8 assay, flow cytometry and caspase-3 activity assay, respectively. The expression of endoplasmic reticulum-stress (ERS) apoptosis-related proteins was measured using real-time PCR and western blotting. Synergism between the two drugs was evaluated by the combination index (CI) through CompuSyn software. FLT significantly and dose-dependently inhibited the proliferation of various glioma cell lines, and rat glioma C6 cells had a highly sensitive response to the addition of FLT. FLT treatment increased the early apoptosis rate, induced typical apoptotic morphology in the C6 cells and activated caspase-3 with no change in the mitochondrial membrane potential. Further study showed that FLT activated the ERS marker, CHOP. This induction was associated with activation of the PERK-eIF2α-ATF4 and ATF6 cascade. Concomitantly, GADD34, a downstream molecule of CHOP, was also increased. Combined FLT and TMZ treatment showed a synergistic cytotoxic effect in the C6 glioma cells. Knockdown of CHOP expression abolished the synergistic effect of FLT and TMZ in the C6 cells, which suggests that FLT may sensitize glioma cells to TMZ through activation of the CHOP-dependent apoptosis pathway. These results revealed that FLT induced glioma cell apoptosis and sensitized glioma cells to TMZ through activation of the CHOP‑dependent apoptosis pathway. The present study provides a primary basis for using the combination of these drugs in patients with advanced glioma.


[Vascular beta-adrenergic remodeling in rat transgenic model over-expressing endothelial beta3-adrenoceptors].
In rat thoracic aorta, the stimulation of endothelial beta3-adrenoceptors (beta-AR) produces a vasorelaxation through activation of a NO synthase pathway and an increase in cGMP levels. In hypertension, a global decrease of the beta-AR response has been described. In spontaneously hypertensive rats (SHR), we have shown that beta3-adrenoceptor-mediated relaxation was not modified in SHR aorta at the age of 12 weeks, in spite of an upregulation of beta3-adrenoceptors. In order to determine the consequences of an over-expression of the beta3-AR, we have developed a transgenic rat over-expressing specifically in endothelial cells the human beta3-AR (Tg beta3). By real-time quantitative PCR, we have determined the expression level of the different beta-AR subtypes. We confirmed an over-expression of the beta3-AR transcripts in Tg beta3 (ratio = 3.39 +/- 0.8; n=3 for Tg beta3 vs wild type [WT] animals). Surprisingly, we observed in Tg beta3 a decrease of beta1-AR transcripts (ratio = 0.76 +/- 0.03; n=3 for Tg beta3 vs WT animals) and no variation for beta2-AR transcripts (ratio = 1.95 +/- 0.60; n=3 for Tg beta3 vs WT animals). In aorta rings from WT and Tg beta3, the isoproterenol-induced relaxation was similar (WT: Emax = 82 +/- 6%, n=6; Tg beta3: Emax = 85 +/- 6, n=6). By contrast, in the presence of 10 microM nadolol, a beta1-, beta2-AR antagonist, the isoproterenol-induced response was significantly increased in Tg beta3 (WT: Emax = 68 +/- 6%, n=6: Tg beta3: Emax = 86 +/- 3; p < 0.01 vs WT). This effect was loss on denuded aortic rings. In conclusion, our study reported similar results to those obtained in hypertension in which a decrease of the beta-AR expression was associated to an elevation of the beta3-AR density. Moreover, this over-expression in our transgenic model is associated to a potential response induced by beta3-AR. Therefore, an activation of beta3-AR could supply the beta1- / beta2-AR decrease. Then, our transgenic model should be used to characterize the physiological consequences of this over-expression as well as to determine the putative involvement of this receptor in the pathogenesis of hypertension.


Integrated nanomaterials for extreme thermal management: a perspective for aerospace applications.
Nanomaterials will play a disruptive role in next-generation thermal management for high power electronics in aerospace platforms. These high power and high frequency devices have been experiencing a paradigm shift toward designs that favor extreme integration and compaction. The reduction in form factor amplifies the intensity of the thermal loads and imposes extreme requirements on the thermal management architecture for reliable operation. In this perspective, we introduce the opportunities and challenges enabled by rationally integrating nanomaterials along the entire thermal resistance chain, beginning at the high heat flux source up to the system-level heat rejection. Using gallium nitride radio frequency devices as a case study, we employ a combination of viewpoints comprised of original research, academic literature, and industry adoption of emerging nanotechnologies being used to construct advanced thermal management architectures. We consider the benefits and challenges for nanomaterials along the entire thermal pathway from synthetic diamond and on-chip microfluidics at the heat source to vertically-aligned copper nanowires and nanoporous media along the heat rejection pathway. We then propose a vision for a materials-by-design approach to the rational engineering of complex nanostructures to achieve tunable property combinations on demand. These strategies offer a snapshot of the opportunities enabled by the rational design of nanomaterials to mitigate thermal constraints and approach the limits of performance in complex aerospace electronics.


Nasal absorption enhancement of insulin using PEG-grafted chitosan nanoparticles.
The objective of this work was to explore the potential of polyethylene glycol-grafted chitosan (PEG-g-chitosan) nanoparticles as a system for improving the systemic absorption of insulin following nasal administration. Insulin-loaded PEG-g-chitosan nanoparticles were prepared by the ionotropic gelation of PEG-g-chitosan solution using tripolyphosphate ions as the crosslinking agent. The nanoparticles were in the size range 150-300 nm, had a positive electrical charge (+16 to +30 mV) and were associated with insulin (loading efficiency 20-39%). The physicochemical properties of nanoparticles were affected by the composition of the copolymer. In vitro insulin release studies showed an initial burst followed by a slow release of insulin. Intranasal administration of PEG-g-chitosan nanoparticles in rabbits enhanced the absorption of insulin by the nasal mucosa to a greater extent than a suspension of insulin-PEG-g-chitosan and control insulin solution. PEG-g-chitosan nanoparticles are promising vehicles for insulin transport through the nasal mucosa.


Neuromuscular disease-specific questionnaire to assess quality of life in patients with chronic inflammatory demyelinating polyradiculoneuropathy.
To date, generic questionnaires have been used to investigate quality of life (QoL) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) patients. Although these measures are very useful, they are not usually precise enough to measure all specific characteristics of the disease. Our aim was to investigate QoL using the neuromuscular disease-specific questionnaire (individualized neuromuscular quality of life, INQoL) in a large cohort of patients with CIDP. Our study comprised 106 patients diagnosed with CIDP. INQoL questionnaire, Medical Research Council (MRC) sum score, Inflammatory Neuropathy Cause and Treatment (INCAT) disability score, Visual Analogue Pain Scale, Beck Depression Inventory, and Krupp's Fatigue Severity Scale were used in our study. Physical domains of INQoL were more affected than mental, and the overall score was 57 ± 25. Significant predictors of higher INQoL score in our patients with CIDP were severe fatigue (β = 0.35, p < 0.01), higher INCAT disability score at time of testing (β = 0.29, p < 0.01), and being unemployed/retired (β = 0.22, p < 0.05). QoL was reduced in our cohort of CIDP patients, which was more pronounced in physical segments. Patients with fatigue, more severe disability, and unemployed/retired need special attention of neurologists because they could be at greater risk to have worse QoL.


MYC-Regulated Mevalonate Metabolism Maintains Brain Tumor-Initiating Cells.
Metabolic dysregulation drives tumor initiation in a subset of glioblastomas harboring isocitrate dehydrogenase (IDH) mutations, but metabolic alterations in glioblastomas with wild-type IDH are poorly understood. MYC promotes metabolic reprogramming in cancer, but targeting MYC has proven notoriously challenging. Here, we link metabolic dysregulation in patient-derived brain tumor-initiating cells (BTIC) to a nexus between MYC and mevalonate signaling, which can be inhibited by statin or 6-fluoromevalonate treatment. BTICs preferentially express mevalonate pathway enzymes, which we find regulated by novel MYC-binding sites, validating an additional transcriptional activation role of MYC in cancer metabolism. Targeting mevalonate activity attenuated RAS-ERK-dependent BTIC growth and self-renewal. In turn, mevalonate created a positive feed-forward loop to activate MYC signaling via induction of miR-33b. Collectively, our results argue that MYC mediates its oncogenic effects in part by altering mevalonate metabolism in glioma cells, suggesting a therapeutic strategy in this setting. Cancer Res; 77(18); 4947-60. ©2017 AACR.


Hemolysis of human erythrocytes by hypochlorous acid is modulated by amino acids, antioxidants, oxidants, membrane-perforating agents and by divalent metals.
The optimal conditions under which hypochlorous acid (NaOCl) either hemolyzes human RBC or kills monkey kidney epithelial cells (BGM) in culture had been investigated. While in Hank's balanced salt solution (HBSS), micromolar amounts of NaOCl caused full hemolysis and also killed BGM cells, in D-MEM or RPMI media rich in amino acids, 25-40 mM of hypochlorite were needed to induce cell injury. Cells exposed to high amounts of NaOCl became highly refractory to strong detergents. Hemolysis by NaOCl was strongly inhibited by a large variety of antioxidants. RBC treated by subtoxic concentrations either of peroxide, peroxyl radical, NO, cholesterol, PLA2, PLC as well as by N2, argon or by mixture of CO2 (10%) and O2 (90%) became much more susceptible to lysis by NaOCl. On the other hand, while RBC treated by Fe2+, Co2+, and V2+ and to a lesser extent with Cu2+ became highly resistant to NaOCl hemolysis presumably due to NaOCl decomposition, no such effect was found either with Co2+ or by Mn2+. RBC treated by azide to destroy catalase and then incubated with peroxide and with NaOCl failed to undergo hemolysis due to the ability of peroxide to decompose NaOCl. The inhibitory effects of the divalent metals on NaOCl-induced hemolysis were also substantiated by measuring the decrease in pH and by cyclic voltammetry. The findings that like peroxide, NaOCl also synergizes with membrane-perforating agents and with a protease to kill epithelial cells further implicate such "cocktails" in cell injury in inflammatory conditions. Taken together, because of the capacity of many agents to scavenge NaOCl, tissue damage by NaOCl-generated neutrophils can take place primarily if activated neutrophils closely adhere to target cells to avoid the scavenging effects of amino acids and of antioxidants. Therefore, the significance of the data which had tested the cytotoxic effects of NaOCl using cells suspended only in salt solutions, should be reconsidered.


NNMT promotes epigenetic remodeling in cancer by creating a metabolic methylation sink.
Nicotinamide N-methyltransferase (NNMT) is overexpressed in a variety of human cancers, where it contributes to tumorigenesis by a mechanism that is still poorly understood. Here we show using metabolomics that NNMT impairs the methylation potential of cancer cells by consuming methyl units from S-adenosyl methionine to create the stable metabolic product 1-methylnicotinamide. As a result, NNMT-expressing cancer cells have an altered epigenetic state that includes hypomethylated histones and other cancer-related proteins combined with heightened expression of protumorigenic gene products. Our findings thus point to a direct mechanistic link between the deregulation of a metabolic enzyme and widespread changes in the methylation landscape of cancer cells.


Microguidewire Looping to Traverse Stented Parent Arteries of Intracranial Aneurysms.
Stents are widely used in coil embolization of intracranial aneurysms, but on occasion, a microcatheter must traverse a stented segment of artery (so-called trans-cell technique) to select an aneurysm, or double stenting may necessary. In such situations, microguidewire passage and microcatheter delivery through a tortuous stented parent artery may pose a technical challenge. Described herein is a microguidewire looping technique to facilitate endovascular navigation in these circumstances. To apply this technique, the microguidewire tip is looped before entering the stented parent artery and then advanced distally past the stented segment, with the loop intact. Rounding of the tip prevents interference from stent struts during passage. A microcatheter is subsequently passed into the stented artery for positioning near the neck of aneurysm, with microguidewire assistance. The aneurysm is then selected, steering the microcatheter tip (via inner microguidewire) into the dome. This technique proved successful during coil embolization of nine saccular intracranial aneurysms (internal carotid artery [ICA], 6; middle cerebral artery, 2; basilar tip, 1), performing eight trans-cell deliveries and one additional stenting. Selective endovascular embolization was enabled in all patients, resulting in excellent clinical and radiologic outcomes, with no morbidity or mortality directly attributable to microguidewire looping. Microguidewire looping is a reasonable alternative if passage through a stented artery is not feasible by traditional means, especially at paraclinoid ICA sites.


Renal artery stenosis stenting with unmasking and embolisation of a renal arteriovenous fistula.
A man in his 70s was presented to the emergency department with uncontrollable hypertension and worsening renal function on a background of atherosclerosis-related bilateral renal artery stenosis. Following progressive deterioration in renal function and refractory hypertension, the patient was referred to interventional radiology for consideration of renal artery stenting. Following stenting of the right renal artery, a large renal arteriovenous fistula became apparent, which required emergent embolisation. Both procedures were successful, with excellent clinical and radiological responses.


Roles of sulfuric acid in elemental mercury removal by activated carbon and sulfur-impregnated activated carbon.
This work addresses the discrepancy in the literature regarding the effects of sulfuric acid (H(2)SO(4)) on elemental Hg uptake by activated carbon (AC). H(2)SO(4) in AC substantially increased Hg uptake by absorption particularly in the presence of oxygen. Hg uptake increased with acid amount and temperature exceeding 500 mg-Hg/g-AC after 3 days at 200 °C with AC treated with 20% H(2)SO(4). In the absence of other strong oxidizers, oxygen was able to oxidize Hg. Upon oxidation, Hg was more readily soluble in the acid, greatly enhancing its uptake by acid-treated AC. Without O(2), S(VI) in H(2)SO(4) was able to oxidize Hg, thus making it soluble in H(2)SO(4). Consequently, the presence of a bulk H(2)SO(4) phase within AC pores resulted in an orders of magnitude increase in Hg uptake capacity. However, the bulk H(2)SO(4) phase lowered the AC pore volume and could block the access to the active surface sites and potentially hinder Hg uptake kinetics. AC treated with SO(2) at 700 °C exhibited a much faster rate of Hg uptake attributed to sulfur functional groups enhancing adsorption kinetics. SO(2)-treated carbon maintained its fast uptake kinetics even after impregnation by 20% H(2)SO(4).


Response to the COVID-19 Outbreak in The Emergency Department Designed for Emerging Infectious Diseases in Korea.
According to the recent coronavirus disease 2019 (COVID-19) pandemic experience, many emergency departments experience difficulties in responding to emerging infectious diseases and this has led to a public health crisis. Our emergency department (ED) is designed to respond to mass outbreaks of infection. Three major preparations were taken to respond to infectious disease; first, to improve the emergency department facilities; second, to created programs to respond to each phase of an epidemic of COVID-19; lastly, to implemented education and training to promote the safety of medical staff. We would like to share the actual responses and statistics of patients visiting emergency department during COVID-19 periods of pandemic. This research was conducted through a retrospective chart analysis provided by a public medical center with 502 beds since the first report of a COVID-19 confirmed case on January 19, 2020 to June 15, 2020 in Seoul, the capital of Korea. Our emergency department was designed based on Korean Regional Emergency Center Facility Standards, and modified throughout each phases of COVID-19 outbreak. Patients suspected to be infectious are screened in the triage, separating them from general patients, and then receive isolation treatment in isolated wards. A total of 4,352 patients visited the ED. 3,202 screenings were conducted with 5 confirmed cases. Another 1,150 patients were treated with general emergent symptoms. There were no problems such as closure of the emergency department or isolation of medical staff while managing COVID-19 confirmed patients. Improving emergency department facilities, create an operational program to respond to each phase of COVID-19 outbreak and implement educational programs enabled large number of screening tests and hospitalization for COVID-19 suspected patients while maintaining general medical services. Research in emergency department designs and operational programs should increase to combine research data with better ideas to respond not only during regular periods but also during periods of pandemic.


The Identification of Araliaceae Species by ITS2 Genetic Barcoding and Pollen Morphology.
The genetic barcode ITS2 (ITS: internal transcribed spacer) and pollen morphology were used for the identification of the pharmacologically valuable wild Araliaceae species Panax ginseng, Oplopanax elatus, Aralia elata, Aralia continentalis, Eleutherococcus senticosus, and Eleutherococcus sessiliflorus inhabiting the natural forests of Primorye, Russia. The ITS2 locus successfully identified all six species, which supports the use of ITS2 as a standard barcode for medicinal plants. However, the ITS2 locus was insufficient for intra-specific discrimination in these species, neither within Primorye nor from other world representatives within GenBank. Araliaceae pollen was confirmed to undergo size-reducing metamorphosis. The final morphotypes were species-specific for each of the six species but could not discriminate intra-species geographic localities within Primorye. The morphologies of the final pollen morphotypes from homologous species inhabiting other parts of the world are not yet known. Therefore, whether pollen is applicable for Araliaceae intra-species discrimination between Primorye and other world localities could not be established. Based on these findings, we propose that the ITS2 genetic barcode and the final pollen morphotypes are suitable for the identification of Araliaceae species. However, further studies will be needed to determine the suitability of genetic and pollen traits for Araliaceae geographic authentication.


Clofibrate-induced changes in glucagon and insulin secretion in patients with angiographically documented coronary artery disease.
This study examines insulin and glucagon secretion in the basal state and in response to clofibrate therapy in patients with angiographically proven coronary artery disease. When compared with weight matched subjects without coronary artery disease, neither insulin nor glucagon secretion were abnormal in response to L-arginine stimulation. However, in response to clofibrate, a marked reduction in insulin secretion and simultaneous elevation in glucagon secretion characterized all patients. Our data suggest the hypothesis that altered insulin and glucagon secretion in response to clofibrate therapy may participate in the reduction of new coronary events reported to occur during therapy with this drug.


Further studies on horn aberrations in Dall's sheep (Ovis dalli dalli) from Yukon Territory, Canada.
The prevalence of horn aberrations in Dall's sheep from the Kluane Lake area of Yukon Territory observed during July 1982 represented 1% of the total population and 7% of rams 6 yr or older. Ewes were not considered in these percentages because they were too difficult to inspect by aerial survey. When these data were combined with other data collected from 1977 through 1981, the prevalence equalled 2.4% of the total population and slightly exceeded 16% in mature rams (greater than or equal to 6 yr). The anomaly followed necrosis of the terminal region of the horn core and the sequestering of portions of the core within the sheath as the sheath continued to grow. Sheath that was produced after the core was anatomically altered resulted in abnormal growth patterns of the horn. Rams with aberrant horns could not maintain homeostatic temperatures within horn cores when horns were experimentally exposed to -80 C for 30 min. Histologic examination of superficial and cornual vascular systems did not reveal any structural alterations that would restrict blood flow within cores of affected horns. Examination of museum specimens consisting of 130 skulls from rams and 81 from ewes collected from Alaska, USA, Yukon Territory, Canada, and Northwest Territories, Canada, established only one ewe and no rams with the horn aberration. The skull was from a ewe and had both horns affected and was collected from the Joe River Drainage, Yukon Territory in 1912.


Gene-Diet Interactions on Metabolic Disease-Related Outcomes in Southeast Asian Populations: A Systematic Review.
Diabetes and obesity are chronic diseases that are a burden to low- and middle-income countries. We conducted this systematic review to understand gene-diet interactions affecting the Southeast Asian population's risk of obesity and diabetes. The literature search was performed on Google Scholar and MEDLINE (PubMed) search engines independently by four reviewers who evaluated the eligibility of articles based on inclusion criteria. Out of 19,031 articles, 20 articles examining gene-diet interactions on obesity and/or diabetes-related traits met the inclusion criteria. Three (Malaysia, Indonesia, and Singapore) out of eleven Association of Southeast Asian Nations (ASEAN) countries have conducted studies on gene-diet interactions on obesity and diabetes. From the 20 selected articles, the most common interactions were observed between macronutrients and genetic risk score (GRS) on metabolic disease-related traits in the Malay, Chinese, and Indian ethnicities. Overall, we identified 29 significant gene-diet interactions in the Southeast Asian population. The results of this systematic review demonstrate ethnic-specific gene-nutrient interactions on metabolic-disease-related traits in the Southeast Asian population. This is the first systematic review to explore gene-diet interactions on obesity and diabetes in the Southeast Asian population and further research using larger sample sizes is required for better understanding and framing nutrigenetic approaches for personalized nutrition.


Multilocus sequence typing and variations in the oprD gene of Pseudomonas aeruginosa isolated from a hospital in China.
To provide information about the genetic relationships and mechanism underlying carbapenem resistance in Pseudomonas aeruginosa clinical isolates of a hospital in China. One hundred and sixty P. aeruginosa strains were isolated from a hospital in China. Susceptibility to 14 antimicrobial agents was determined by antimicrobial susceptibility testing. Multilocus sequence typing was used to characterize the genetic backgrounds of these clinical isolates. Forty-five strains were randomly selected for further evaluation of their carbapenem resistance mechanism. Their oprD gene was compared with the PAO1 sequence. Multilocus sequence typing analysis demonstrated that these isolates were highly diverse; 68 sequence types were identified, of which 28 were novel sequence types. Polygenic and eBURST analysis demonstrated genetically similar clones with dissimilar resistance profiles. Among the 45 randomly selected strains associated with carbapenem resistance, 2 were metallo β-lactamase producers; all the 45 strains were not AmpC overproducers. Sequence analysis revealed a high diversity in the oprD sequences among isolates. Strains susceptible to imipenem and meropenem with shortened L7 and L8 loops in oprD were the major strain types observed in this hospital. This study indicated that oprD provided the main mechanism for carbapenem resistance. The shortened L7 and L8 loops are responsible for carbapenem susceptibility.


Associations between cigarette smoking and the risk of four leading cancers in Miyagi Prefecture, Japan: a multi-site case-control study.
Although cigarette smoking is a well-known risk factor of lung cancer, associations of cigarette smoking with the risk of other sites have not been fully elucidated in Japan. To simultaneously evaluate the associations of cigarette smoking with the risks of cancers of the stomach, lung, colon, and rectum, which have been the leading cancer sites in recent years in Miyagi Prefecture, Japan, we conducted a hospital-based case-control study. Study subjects consisted of 614 stomach, 515 lung, 324 colon, and 164 rectal cancer cases and 2444 hospital controls admitted to a single hospital in Miyagi Prefecture from 1997 to 2001. Information on smoking habit and other lifestyle factors was collected using a self-administered questionnaire. Distributions of referral base among cases and controls were also investigated. For each site, odds ratios (ORs) and 95% confidence intervals (95% CIs) for smoking habit were estimated with adjustment for age, year of survey, history of alcohol drinking, family history of index cancer, and occupational history, respectively, using an unconditional logistic regression model. Cigarette smoking (ever vs. never) was associated with an increased risk of stomach (OR = 1.62; 95% CI 1.20-2.19) and lung (OR = 3.82; 95% CI 2.49-5.86) cancer among males and lung cancer among females (OR = 2.02; 95% CI 1.28-3.18). For female stomach cancer, the association with cigarette smoking was uncertain (OR = 0.65, P = 0.1533). For rectal cancer, a significant increased risk was observed in both-sex-combined analysis. There was no association between cigarette smoking and the risk of colon cancer. Detailed analysis showed that the association of cigarette smoking with cancer risk might be modified by the patient referral pattern, i.e., screened or not screened. The present results indicate that the association of cigarette smoking with cancer risk may differ among sites and sexes. In terms of the population attributable risk, a large proportion of leading cancers in males appears to be related to cigarette smoking.


[Understanding failure of obstetric referral to the Cotonou University gynaecology and obstetrics clinic].
Since 2000, in the context of the Millennium development goals, Benin has reinforced its obstetric referral system in order to reduce maternal mortality. However, structural, sociocultural and economic problems continue to affect this strategy. The Cotonou University gynaecology and obstetrics clinic (CUGO), at the top of the health pyramid, is emblematic of this situation. This study was designed to elucidate the stakes involved in referral to this hospital based on analysis of the perceptions and experiences of referral personnel. Essentially qualitative data collection was conducted by means of in-depth semi-structured interviews from July to December 2015 involving 37 people, including referred women, healthcare personnel and caregivers. The poor quality of information given to women concerning the reasons for referral, the fear of caesarean section, considered to be inevitable, and the difficult relationships with health workers contribute to failure to comply with referral. Rumours concerning reception, waiting times and hospitalization conditions are other factors that must be taken into account. Finally, the distance from the woman's home is a decisive element in acceptance of referral by women and their families. Referral is generally perceived as necessary in the case of complications during pregnancy, by both referred women and healthcare personnel. However, differences in points of view are observed when the woman is referred to CUGO.


[Fifteen years of use of anti-TNF antibodies in moderate to severe Crohn's disease: how to make the best of this experience].
After fifteen years of use, the anti-TNF antibodies have become the corner stone of the treatment of moderate and severe Crohn's disease. The skill acquired over the years through experimental trials and clinical experience leads to increased therapeutic efficacy and minimized risks. These antibodies are introduced increasingly earlier in Crohn's disease as well as in a broader range of patients, aiming at changing the natural history of the diseases by avoiding the development of intestinal tissue damage and complications.


Proliferative and inductive effects of Cyclosporine a on gingival fibroblast of child and adult.
Gingival overgrowth is a serious side-effect that accompanies the use of Cyclosporin A (CsA). Up to 97% of the transplant recipient children, who were submitted to CsA therapy, have been reported to suffer from this side-effect. Several conflicting theories have been proposed to explain the fibroblast's function in CsA-induced gingival overgrowth. The aim of this study is to assess the proliferation of gingival fibroblasts and levels of released cytokines after being exposed to CsA, in both adults and pediatric groups, and to make a comparison between the results of the two groups. The adult fibroblast samples were derived from four healthy adults, aged 35 to 42 years and pediatric samples were obtained from four healthy children, age between four and eleven years. Tissue samples were plated in Dulbecco's Modified Eagle Medium (DMEM) containing 10% fetal bovine serum (FBS), Streptomycin and Penicillin. The samples were cultured in 25 cm(2) plates containing 5% CO2, and incubated at 37°C. The cells used for all the experiments were at the fourth passage. The concentration of PGE2, IL-1β, IL-6, IL-8, TNF-α, and TGF-β1 was determined by the enzyme-linked immunosorbent assay (ELISA) and the proliferation rate was assessed by the MTT assay. Alpha error levels were set as 0.05. CsA stimulated significantly higher levels of IL-6, IL-8 and TGF-β1 in adult gingival fibroblasts than it did in the control group; whereas, the expression of IL-1β and PGE2 in the fibroblasts exposed to CsA was significantly weaker (P < 0.05). The fibroblasts in the two groups did not reveal any noticeable difference in the production of TNF-α. Furthermore, cell proliferation in the CsA group was not significantly higher than that in the control group. No significant differences in cytokines TNF-α and IL-1β were noted between the two groups. The results indicated that CsA stimulated cell proliferation in the pediatric fibroblast cell line. Comparison between the results in the adult and pediatric groups demonstrated that the levels of IL-1β, IL-6, IL-8, and PGE2 were significantly higher in the pediatric group than in the adult group; however, statistics showed no significant difference in the levels of TNF-α and TGF-β1 and CsA-induced proliferation between these two groups. The mechanism of a CsA-induced fibroblast overgrowth may converge on the steps involving fibroblast proliferation and cytokine network including IL-6, IL-8, IL-1β, TGF-β1, and PGE2, in both adults and pediatrics. As the prevalence and intensity of drug-induced gingival overgrowth is more serious in the pediatrics. As group than in adults, we suggest that more studies be conducted on the pediatric group.


Genetic diversity in chlorella viruses flanking kcv, a gene that encodes a potassium ion channel protein.
The chlorella virus PBCV-1 encodes a 94-amino acid protein named Kcv that produces a K+-selective and slightly voltage-sensitive conductance when expressed in heterologous systems. As reported herein, (i) Northern analysis of kcv expression in PBCV-1-infected cells revealed a complicated pattern suggesting that the gene might be transcribed as a di- or tri-cistronic mRNA both at early and late times after virus infection. (ii) The protein kinase inhibitors H-89, A3, and staurosporine inhibited PBCV-1 Kcv activity in Xenopus oocytes, suggesting that Kcv activity might be controlled by phosphorylation or dephosphorylation. (iii) The PBCV-1 genomic sequence revealed a gene encoding a putative protein kinase (pkx) adjacent to kcv. These findings prompted us to examine the kcv flanking regions in 16 additional chlorella viruses and transcription in two of these viruses, as well as the effect of the three protein kinase inhibitors on two Kcv homologs in Xenopus oocytes. The results indicate (i) pkx is always located 5' to kcv, but the spacing between the two genes varies from 31 to 1588 nucleotides. More variation occurs in the kcv 3' flanking region of the 16 viruses. (ii) The kcv gene is expressed as a late mono-cistronic mRNA. (iii) Unlike the affect on PBCV-1 Kcv, the three protein kinase inhibitors have little or no effect on the activity of the two Kcv homologs in oocytes. (iv) A comparison of the kcv 5' upstream sequences from the 16 viruses identified a highly conserved 10-nucleotide sequence that is present in the promoter region of all of the viruses.


Paraneoplastic syndromes in prostate cancer.
Prostate cancer is the second most common urological malignancy to be associated with paraneoplastic syndromes after renal cell carcinoma. These syndromes tend to occur in the setting of late stage and aggressive tumors with poor overall outcomes. Recognition of these syndromes is clinically important as it might lead to the detection of underlying malignancy and impact on the treatment options available. The literature features around 100 cases of paraneoplastic syndromes associated with prostate cancer and these include endocrine manifestations, neurological entities, dermatological conditions, and other syndromes. Over 70% of cases document the syndrome as the initial clinical manifestation of prostate cancer, while in just under 20% the syndrome was an initial sign of disease progression to the castrate-resistant state. The vast majority of cases involved advanced metastatic malignancy. The syndromes generally resolve upon institution of treatment for the underlying prostate cancer, but some syndromes require specific therapies. Some syndromes are associated with serum markers that are readily detectable and demonstration of these putative markers within prostate cancer tissue at an individual level would firmly link the paraneoplastic syndrome with its underlying prostatic malignancy. The causes of paraneoplastic syndromes in prostate cancer are incompletely understood, and further research into their biology might shed more light on the complex molecular mechanisms that underpin prostate cancer and its lethal potential.


Differential Effect of APOE ɛ4 Status and Elevated Pulse Pressure on Functional Decline in Cognitively Normal Older Adults.
The APOE ɛ4 allele and increased vascular risk have both been independently linked to cognitive impairment and dementia. Since few studies have characterized how these risk factors affect everyday functioning, we investigated the relationship between APOE ɛ4 genotype and elevated pulse pressure (PP) on functional change in cognitively normal participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI). 738 normally aging participants underwent APOE genotyping, and baseline PP was calculated from blood pressure indices. The Functional Activities Questionnaire (FAQ) was completed by participants' informant at baseline and 6, 12, 24, 36, and 48-month follow-up visits. Multiple linear regression and multilevel modeling were used to examine the effects of PP and APOE ɛ4 genotype on cross-sectional and longitudinal FAQ scores, respectively. Adjusting for demographic and clinical covariates, results showed that both APOE ɛ4 status and elevated PP predicted greater functional difficulty trajectories across four years of follow-up. Interestingly, however, elevated PP was associated with greater functional decline over time in ɛ4 non-carriers versus carriers. Results show that, although APOE ɛ4 status is the prominent predictor of functional difficulty for ɛ4 carriers, an effect of arterial stiffening on functional difficulty was observed in non-carriers. Future studies are needed in order to clarify the etiology of the association between PP and different brain aging processes, and further explore its utility as a marker of dementia risk. The present study underscores the importance of targeting modifiable risk factors such as elevated PP to prevent or slow functional decline and pathological brain aging.


HLA-DRB1 Amino Acid Positions 11/13, 71, and 74 Are Associated With Inflammation Level, Disease Activity, and the Health Assessment Questionnaire Score in Patients With Inflammatory Polyarthritis.
Rheumatoid arthritis (RA) susceptibility HLA-DRB1 haplotypes based on amino acid positions 11/13, 71, and 74 predict radiographic damage. The mechanism of action is unknown, but it may be mediated by inflammation. We undertook this study to systematically investigate the effect of these amino acids on nonradiographic measures of disease activity/outcomes. We tested the association of RA susceptibility HLA-DRB1 amino acids with the C-reactive protein (CRP) level, the tender joint count (TJC), the swollen joint count (SJC), the Disease Activity Score in 28 joints (DAS28), and the Health Assessment Questionnaire (HAQ) score in the Norfolk Arthritis Register (NOAR) and Early Rheumatoid Arthritis Study (ERAS) cohorts. Longitudinal modeling of disease activity/outcomes was performed using generalized linear latent and mixed models. Mediation analysis was performed using directed acyclic graphs to investigate the paths from genetic factors to outcome. A total of 2,158 patients were available for analysis in the NOAR cohort. Valine at position 11 showed the strongest association with the CRP level (P = 2.21 × 10-6 ), the SJC (P = 7.51 × 10-6 ), and the DAS28 (P = 0.002); it was marginally associated with the HAQ score (P = 0.044) but not with the TJC. The same amino acid and haplotype risk hierarchy observed for susceptibility and radiographic severity was observed for the CRP level and nonradiographic measures of disease activity/outcome, apart from the TJC. The results were replicated in the ERAS cohort. The effect of valine at position 11 on the SJC was mainly mediated by anti-citrullinated protein antibody status, the effect of which was mainly mediated by inflammation; however, the effect of valine at position 11 was also independent of the CRP level (P = 1.6 × 10-4 ). Genetic markers of RA susceptibility located within HLA-DRB1 determine the levels of clinical and systemic inflammation independently, and also determine all objective measures of disease activity and outcome.


Neighbor Affinity-Based Core-Attachment Method to Detect Protein Complexes in Dynamic PPI Networks.
Protein complexes play significant roles in cellular processes. Identifying protein complexes from protein-protein interaction (PPI) networks is an effective strategy to understand biological processes and cellular functions. A number of methods have recently been proposed to detect protein complexes. However, most of methods predict protein complexes from static PPI networks, and usually overlook the inherent dynamics and topological properties of protein complexes. In this paper, we proposed a novel method, called NABCAM (Neighbor Affinity-Based Core-Attachment Method), to identify protein complexes from dynamic PPI networks. Firstly, the centrality score of every protein is calculated. The proteins with the highest centrality scores are regarded as the seed proteins. Secondly, the seed proteins are expanded to complex cores by calculating the similarity values between the seed proteins and their neighboring proteins. Thirdly, the attachments are appended to their corresponding protein complex cores by comparing the affinity among neighbors inside the core, against that outside the core. Finally, filtering processes are carried out to obtain the final clustering result. The result in the DIP database shows that the NABCAM algorithm can predict protein complexes effectively in comparison with other state-of-the-art methods. Moreover, many protein complexes predicted by our method are biologically significant.


Herpes simplex-specific IgG subclass response in herpetic keratitis.
The measurement of the local IgG response in ocular Herpes simplex virus infection presents particular problems due to the difficulty in obtaining sufficient tear samples and the possible transudation of IgG from the serum to the inflamed eye. Using specific monoclonal antibodies to Human IgG subclasses in an enzyme-linked immunoabsorbant assay (ELISA) the local IgG antibody response in Herpes simplex keratitis was analysed. All serum samples from patients and controls contained quantifiable levels of HSV specific IgG1 and IgG4 antibody. Comparison of serum antibody levels with tear levels for patients showed that HSV specific IgG1 serum concentrations were 16.1 fold or more higher than in tears, whereas IgG4 concentrations were only 6.5 fold higher in serum than in tears. This difference was not apparent in the control group. Radioimmunoprecipitation assay of 35S-methionine labelled HSV antigens revealed only minor differences in the protein profiles produced by immunoprecipitation using serum or tear antibody. These results suggest a role for IgG4 antibodies in mucosal immunity in the eye as has been suggested for the mucosal surface of the lung.


Vapor-phase Beckmann rearrangement of oxime molecules over H-Faujasite zeolite.
The Beckmann rearrangement (BR) plays an important role in a variety of industries. The mechanism of this reaction rearrangement of oximes with different molecular sizes, specifically, the oximes of formaldehyde (H(2)C=NOH), Z-acetaldehyde (CH(3)HC=NOH), E-acetaldehyde (CH(3)HC=NOH) and acetone (CH(3))(2)C=NOH, catalyzed by the Faujasite zeolite is investigated by both the quantum cluster and embedded cluster approaches at the B3LYP level of theory using the 6-31G (d,p) basis set. To enhance the energetic properties, single point calculations are undertaken at MP2/6-311G(d,p). The rearrangement step, using the bare cluster model, is the rate determining step of the entire reaction of these oxime molecules of which the energy barrier is between 50-70 kcal mol(-1). The more accurate embedded cluster model, in which the effect of the zeolitic framework is included, yields as the rate determining step, the formaldehyde oxime reaction rearrangement with an energy barrier of 50.4 kcal mol(-1). With the inclusion of the methyl substitution at the carbon-end of formaldehyde oxime, the rate determining step of the reaction becomes the 1,2 H-shift step for Z-acetaldehyde oxime (30.5 kcal mol(-1)) and acetone oxime (31.2 kcal mol(-1)), while, in the E-acetaldehyde oxime, the rate determining step is either the 1,2 H-shift (26.2 kcal mol(-1)) or the rearrangement step (26.6 kcal mol(-1)). These results signify the important role that the effect of the zeolite framework plays in lowering the activation energy by stabilizing all of the ionic species in the process. It should, however, be noted that the sizeable turnover of a reaction catalyzed by the Brønsted acid site might be delayed by the quantitatively high desorption energy of the product and readsorption of the reactant at the active center.


[Thoracic aortic aneurysm with chronic disseminated intravascular coagulation treated successfully with orally administered camostat mesilate, warfarin and aspirin].
We describe a case of thoracic aortic aneurysm complicated by chronic disseminated intravascular coagulation (DIC). Initially the DIC was controlled successfully by administration of gabexate mesilate and dalteparin. However, because these drugs were given intravenously, the patient could not be discharged. Subsequently, the DIC was treated successfully by changing to orally administered camostat mesilate, warfarin and aspirin, which allowed the patient to leave hospital.


Breast pain and imaging.
Breast pain is a common reason for consultation and a source of anxiety for patients. Cyclical breast pain can be distinguished from non-cyclical pain and breast pain with other symptoms. Many causes, usually benign are possible and the clinical enquiry and physical examination are essential to establish predisposing factors. Although imaging is not always needed for isolated breast pain, it is still useful for the diagnosis of specific causes such as tension cysts, giant adenofibromas or Mondor's thrombophlebitis. Ultrasound is the first line investigation before mammography, MRI or biopsy, which may be indicated for suspicious abnormalities. Some cancers may be associated with pain, which implies that radiologists and physicians should always take breast pain seriously.


Preliminary experiences of intralesional immunotherapy in cutaneous metastatic melanoma.
Antigen presenting cells are inactive within tumor tissue because of local immunosuppression. Tumor infiltrating lymphocyte signal activation transducing mechanisms are also seriously impaired. Administration of granulocyte macrophage-colony stimulating factor may lead to antigen-presenting cell recovery and interleukin-2 may restore local tumor infiltrating lymphocyte activation. Moreover, interleukin-2 increases the systemic lymphocyte population, an event which seems to correlate with a better prognosis. The present phase I-II study was carried out to examine whether intralesional injection of granulocyte macrophage-colony stimulating factor followed by subcutaneous interleukin-2 would induce a clinical response in advanced, pretreated and elderly melanoma patients. Fourteen patients over 60 years of age received intralesional granulocyte macrophage-colony stimulating factor (150 micrograms per lesion on day 1), generally divided between the two largest cutaneous lesions, followed by perilesional subcutaneous interleukin-2 (3.000.000/IU) for 5 days (3 to 7) every 3 weeks. All patients received 6 courses of treatment unless progression occurred. Clinical evaluation of the treated cutaneous lesions was assessed at the baseline and before every cycle. Distant lesions were checked every two cycles. Four clinical responses (2 partial responses and 2 minimal responses) (28.5%), which also involved lesions that had not been directly treated, and seven cases of stable disease were observed. The response duration for partial response and minimal response was 9, 4, 4 and 2.5+ months, respectively. Stable disease (50%) recorded in the 7 patients was short term, 3-6 months. Three patients rapidly progressed after 2, 2, and 1 therapy cycles, respectively. The patient who reached the best partial response had a fairly high absolute lymphocyte count (1600 to 2400/mm3). The second one, who reached a complete remission after subsequent locoregional chemotherapy and hyperthermia, had a low absolute lymphocyte count which had doubled, however, by the end of treatment. Blood lymphocyte values in the other patients were too varied to allow any correlation with clinical response. Therapy was well tolerated and only mild fever was observed, with the exception of one patient who had grade 3 fever, with muscle pain and arthralgia. Considering the very low toxicity observed, this treatment might be indicated in elderly patients for whom systemic therapy is no longer a viable option. Improved scheduling and timing could result from further studies.


Gastric cancer: Metabolic and metabolomics perspectives (Review).
Gastric cancer is one of the most malignant tumors worldwide and remains a major health threat in Asia-Pacific regions, while its pathological mechanism is generally unknown. Recent research has advanced the understanding of the relationship between metabolic reprogramming and carcinogenesis. In particular, metabolic regulation and cancer research are being further brought into sharp focus with the emergence of metabolomics. Not only can metabolomics provide global information on metabolic profiles of specific tumors, but it can also act as a promising tool to discover biomarkers regarding diagnosis, metastatic surveillance and chemotherapeutic sensitivity prediction. Meanwhile, metabolism-based anticancer therapies will be further discovered. Up to now, accumulative studies have highlighted the application of metabolomics in gastric cancer research regarding different aspects; therefore we summarized the current available results of how metabolic changes are linked to gastric carcinogenesis, and how metabolomics holds promise for the diagnosis, metastatic surveillance, treatment and prognosis prediction of gastric cancer.


Operative technique for a successful laparoscopic en-bloc resection of gastrogastric fistula following roux-en-Y gastric bypass.
Gastrogastric fistulas are rare complications following Roux-en-Y gastric bypass surgery and are characterized by a fistulous connection between the gastric pouch and the remnant stomach. The presentation is often variable and a high-index of suspicion must be maintained for accurate and timely diagnosis. In this case report, we provide a detailed review of the technical steps taken to successfully resect a gastrogastric fistula en-bloc laparoscopically with an unremarkable post-operative course.


Reconstruction of anterior iliac crest after bone graft harvest decreases pain: a randomized, controlled clinical trial.
A substantial number of patients report persistent pain after graft harvest from the anterior iliac crest. There have been several retrospective case series published that suggest that iliac crest reconstruction using a variety of techniques may decrease graft site pain. This study, a randomized, controlled clinical trial at a university hospital, tested the hypothesis that reconstruction of the iliac crest will reduce graft harvest site pain. A randomized, controlled clinical trial using the McGill Pain Inventory as the primary outcome measure was performed to evaluate the effect of anterior iliac crest reconstruction after graft harvest. Thirty patients who were treated with anterior cervical discectomy and fusion or cervical corpectomy and fusion with autologous iliac crest graft were randomized to one of two groups. Patients in Group 1 were treated with reconstruction of the iliac crest with commercially available tricalcium phosphate bone void filler after graft harvest. Patients in Group 2 were treated without graft site reconstruction. Graft site pain was assessed immediately after surgery, 6 weeks after surgery, and 3 months after surgery. Treatment groups were well matched with regard to patient age, sex, and smoking history. Although patients in each group reported persistent pain 6 weeks and 3 months after graft harvest, patients in the reconstruction group reported significantly less severe pain at 6 weeks and tended to have less pain at 3 months after surgery. Reconstruction of the iliac crest with tricalcium phosphate bone void filler significantly decreases the severity of postoperative pain 6 weeks after surgery.


First recurrence of small cell lung cancer presenting as subacute monoarticular arthritis.
We describe a case of recurrent small cell lung cancer presenting as an acute monoarticular arthritis. This patient had recently undergone comprehensive review and surveillance imaging under a local oncology unit, 18 months after undergoing chemoradiotherapy for limited disease small cell lung cancer. He had presented to the emergency department on multiple occasions and been managed as an outpatient for a provisional diagnosis of spontaneous haemarthrosis in the setting of rivaroxaban therapy. Subsequent investigation revealed occult fracture of the distal femur with joint effusion, secondary to isolated metastatic disease from recurrent small cell lung cancer. This case demonstrates the importance of reconsidering differential diagnoses when a patient's symptoms do not respond to appropriate treatment as expected. It also highlights the limitations of surveillance protocols and the influence that recent specialist input can have on diagnostic processes.


A closer look at pupil diversity and evolution in frogs and toads.
The eyes of frogs and toads (Anura) are among their most fascinating features. Although several pupil shapes have been described, the diversity, evolution, and functional role of the pupil in anurans have received little attention. Studying photographs of more than 3200 species, we surveyed pupil diversity, described their morphological variation, tested correlation with adult habits and diel activity, and discuss major evolutionary patterns considering iris anatomy and visual ecology. Our results indicate that the pupil in anurans is a highly plastic structure, with seven main pupil shapes that evolved at least 116 times during the history of the group. We found no significant correlation between pupil shape, adult habits, and diel activity, with the exception of the circular pupil and aquatic habits. The vertical pupil arose at least in the most-recent common ancestor of Anura + Caudata, and this morphology is present in most early-diverging anuran clades. Subsequently, a horizontal pupil, a very uncommon shape in vertebrates, evolved in most neobatrachian frogs. This shape evolved into most other known pupil shapes, but it persisted in a large number of species with diverse life histories, habits, and diel activity patterns, demonstrating a remarkable functional and ecological versatility.


Antiadhesive properties of glycoclusters against Pseudomonas aeruginosa lung infection.
Pseudomonas aeruginosa lung infections are a major cause of death in cystic fibrosis and hospitalized patients. Treating these infections is becoming difficult due to the emergence of conventional antimicrobial multiresistance. While monosaccharides have proved beneficial against such bacterial lung infection, the design of several multivalent glycosylated macromolecules has been shown to be also beneficial on biofilm dispersion. In this study, calix[4]arene-based glycoclusters functionalized with galactosides or fucosides have been synthesized. The characterization of their inhibitory properties on Pseudomonas aeruginosa aggregation, biofilm formation, adhesion on epithelial cells, and destruction of alveolar tissues were performed. The antiadhesive properties of the designed glycoclusters were demonstrated through several in vitro bioassays. An in vivo mouse model of lung infection provided an almost complete protection against Pseudomonas aeruginosa with the designed glycoclusters.


The envoy® totally implantable hearing system, st. Croix medical.
The Totally Implantable Envoy® System is currently undergoing clinical trials in both the United States and Europe. The fully implantable hearing device is intended for use in patients with sensorineural hearing loss. The device employs piezoelectric transducers to sense ossicle motion and drive the stapes. Programmable signal processing parameters include amplification, compression, and variable frequency response. The fully implantable attribute allows users to take advantage of normal external ear resonances and head-related transfer functions, while avoiding undesirable earmold effects. The high sensitivity, low power consumption, and high fidelity attributes of piezoelectric transducers minimize acoustic feedback and maximize battery life (Gyo, 1996; Yanagihara, (1987) and 2001). The surgical procedure to install the device has been accurately defined and implantation is reversible.


Food Polyphenols Fail to Cause a Biologically Relevant Reduction of COX-2 Activity.
Epidemiologic studies show a correlation between the dietary intake of food polyphenols and beneficial health effects. Several in vitro studies indicate that the anti-inflammatory potential of polyphenols is, at least in part, mediated by a modulation of the enzymes of the arachidonic acid cascade, such as the prostaglandin forming cyclooxygenases (COXs). Evidence that this mode of action can be transferred to the situation in vivo is scarce. This study characterized effects of a subset of polyphenols on COX-2 expression and activity in vitro and compared the potency with known drugs. Next, the in vivo relevance of the observed in vitro effects was tested. Enzyme assays and incubations of polyphenols with the cancer cell line HCA-7 and lipopolysaccharide (LPS) stimulated primary monocytes support the hypothesis that polyphenols can effect COX-2 expression and activity in vitro. The effects were most pronounced in the monocyte assay for wogonin, apigenin, resveratrol and genistein with IC50 values of 1.5 μM, 2.6 μM, 2.8 μM and 7.4 μM. However, these values are 100- to 1000-fold higher in comparison to those of the known pharmaceuticals celecoxib, indomethacin and dexamethasone. In an animal model of LPS induced sepsis, pretreatment with polyphenols (i. p. 100 mg/kg bw) did not result in decreased plasma or tissue prostaglandin levels, whereas the positive control celecoxib effectively attenuated LPS induced prostaglandin formation. These data suggest that despite the moderate potency in vitro, an effect of polyphenols on COX-2 during acute inflammation is unlikely, even if a high dose of polyphenols is ingested.


Development of Near-Isogenic Lines in a Parthenogenetically Reproduced Thrips Species, Frankliniella occidentalis.
Although near-isogenic lines (NILs) can standardize genetic backgrounds among individuals, it has never been applied in parthenogenetically reproduced animals. Here, through multiple rounds of backcrossing and spinosad screening, we generated spinosad resistant NILs in the western flower thrips, Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae), with a haplo-diploid reproduction system. The resultant F. occidentalis NIL-R strain maintained a resistance ratio over 30,000-fold, which was comparable to its parental resistant strain, Spin-R. More importantly, F. occidentalis NIL-R shared 98.90% genetic similarity with its susceptible parental strain Ivf03. By developing this toolset, we are able to segregate individual resistance and facilitate the mechanistic study of insecticide resistances in phloem-feeding arthropods, a group of devastating pest species reproducing sexually as well as asexually.


Ethnic differences in sympathetic nervous system-mediated energy expenditure.
The impact of sympathetic nervous system (SNS) activity on energy expenditure (EE) was evaluated in nondiabetic Caucasian and Pima Indian men while on a weight-maintenance diet using two approaches as follows. 1) The relationship between 24-h EE, measured in a respiratory chamber, and 24-h urinary norepinephrine was studied in 36 Caucasians [32 +/- 8 (SD) yr, 95 +/- 41 kg, 22 +/- 13% fat] and 33 Pimas (29 +/- 6 yr, 103 +/- 28 kg, 30 +/- 9% fat). There was no difference between the two groups in 24-h EE (2,422 vs. 2,523 kcal/24 h) and in urinary norepinephrine (28 vs. 31 micrograms/24 h), even after adjusting for body size and composition. Twenty-four-hour EE correlated significantly with 24-h urinary norepinephrine in Caucasians (r = 0.78, P less than 0.001) but not in Pimas (r = 0.03), independent of fat-free mass (FFM), fat mass, and age. 2) The effect of beta-adrenoceptor blockade with propranolol (120 micrograms/kg FFM bolus and 1.2 micrograms.kg FFM-1.min-1 for 45 min) on the resting metabolic rate (RMR) was evaluated in 36 Caucasians (30 +/- 6 yr, 103 +/- 36 kg, 25 +/- 11% fat) and 32 Pimas (28 +/- 6 yr, 100 +/- 34 kg, 27 +/- 10% fat). The RMR was similar in the two groups (2,052 vs. 1,973 kcal/24 h) even after adjustment for FFM, fat mass, and age and dropped significantly after propranolol infusion in Caucasians (-3.9%, P less than 0.001) but not in Pimas (-0.8%, P = 0.07).(ABSTRACT TRUNCATED AT 250 WORDS)


Do the stigmata of recent haemorrhage have additional prognostic value in patients with bleeding duodenal ulcer?
To assess the additional prognostic value of endoscopic stigmata of recent haemorrhage (SRH) in addition to clinical data, a pilot study was conducted on 207 duodenal ulcer patients from the OMGE survey. The incidence of SRH was compared in 145 patients who settled and 62 who re-bled. Only active bleeding emerged as significantly commoner in the latter group. Two computer-assisted predictions of further bleeding (before and after addition of the stigmata to a clinical database) were compared with the final outcome. Little improvement, in terms of prognosis for further bleeding, was obtained when SRH data were added. Similar findings were observed in a smaller series from Marburg, FRG.


A phenothiazine derivative in the treatment of spasticity.
The efficacy of a selective fusimotor suppressant, the phenothiazine (+/-)-10-3-dimethylamino-2-methylpropyl)-2-valeroylphenothiazine, has been assessed in a double-blind crossover trail in eight patients suffering from cerebral spasticity and one patient suffering from spinal spasticity. Dosage was 40 mg daily. Independent clinical and electromyographic methods of assessment were used. The active agent produced a small but significant reduction in spasticity, although this was of clinical value in only a few patients. There were few side-effects. It is recommended that further studies using higher dosages be undertaken.