The relation of maternal blood arsenic to anemia during pregnancy.
To clarify the relationship of prenatal arsenic exposure to hemoglobin concentrations and anemia during pregnancy, a longitudinal study was conducted of 364 participants during early pregnancy from October 2006 to March 2011 in Tehran, Iran. Maternal whole blood (taken between 8-12 and 20-24 weeks of gestation, and at delivery) and umbilical cord blood samples were collected for arsenic measurement. The mean concentration of maternal blood arsenic in the first trimester of pregnancy was significantly lower in anemic women compared with non-anemic participants (mean ± SD: 12.4 ± 3.4 versus 14.8 ± 4.0 μg/L, respectively, p < 0.001). Maternal whole blood arsenic levels in the first and third trimesters were significantly (p < 0.05) correlated with hemoglobin concentrations measured throughout gestation (r = 0.312, 0.424, and 0.183). Multiple logistic regression analysis demonstrated that increased maternal blood arsenic levels in the first trimester were significantly negatively associated to anemia during pregnancy (OR = 0.85, CI: 0.77-0.94, p < 0.01). The present study showed that prenatal blood arsenic exposure was not a risk factor for the occurrence of anemia.


Predictors of prolonged vancomycin-resistant enterococci colonization in acute stroke patients admitted to an intensive care unit: A retrospective cohort study.
To investigate the factors affecting the duration of vancomycin-resistant enterococci (VRE) colonization in stroke patients.A total of 52 stroke patients with VRE colonization were enrolled. We divided the groups into several factors and confirmed whether each factor affected VRE colonization. Independent t test, bivariate correlation analysis, and Cox proportional hazards model were used to confirm statistical significance.Among 52 patients, 28 were ischemic stroke and 24 were hemorrhagic stroke. The mean duration of the VRE colonization was 39.08 ± 44.22 days. The mean duration of VRE colonization of the ischemic stroke patients was 25.57 ± 30.23 days and the hemorrhagic stroke patients was 54.83 ± 52.75 days. The mean intensive care unit (ICU) care period was 15.23 ± 21.98 days. Independent sample t test showed the hemorrhagic stroke (P < .05), use of antibiotics (P < .01), oral feeding (P < .01) were associated with duration of VRE colonization. Bivariate correlation analysis showed duration of ICU care (P < .001) was associated with duration of VRE colonization. Cox proportional hazard model showed oral feeding (P = .001), use of antibiotics (P = .003), and duration of ICU care (P = .001) as independent factors of duration of VRE colonization.Careful attention should be given to oral feeding, duration of ICU care, and use of antibiotics in stroke patients, especially hemorrhagic stroke patients, for intensive rehabilitation at the appropriate time.


The invisible soldiers: understanding how the life experiences of girl child soldiers impacts upon their health and rehabilitation needs.
There are estimated 120,000 girl child soldiers worldwide. Recruitment makes girls vulnerable to the violence of war, torture, psychological trauma and sexual abuse with huge impact on their physical, mental and reproductive health. Despite this, girl soldiers often remain an invisible and marginalised group frequently neglected from disarmament, demobilisation and reintegration programmes. This is not just a local issue: with former child soldiers seeking asylum as refugees there is an increasing need for health workers in the destination countries to understand their health needs in order to inform appropriate holistic service provision. This review provides an overview of how the duties and life experiences of girl soldiers, including gender-specific abuses, impacts upon their health and concludes with a summary of recommendations as to how their rehabilitation needs can be addressed.


Background-protein effects on fluorophotometric data.
Fluorescent tracers are commonly used in fluorophotometric studies of ocular fluids and tissues that contain background protein. Background-protein concentrations were found to decrease or increase significantly the measure of fluorescence emitted from solutions containing sodium fluorescein, fluorescein-labeled dextran, or fluorescein-labeled horseradish peroxidase. The effect of background protein on fluorescence was expressed as a function of the specific fluorescent tracer, tracer concentration, and background-protein concentration; it can be corrected in the analysis of fluorophotometric data. Fluorophotometric studies--particularly those in which the background-protein level is expected to be abnormally high, such as postoperative and pathologic studies--may need to include either a data correction based on measured effects of background protein on tracer fluorescence or, in the case of clinical investigations, recognize at least the potential for a range of possible interpretations.


Early outcomes in patients undergoing transcatheter versus surgical pulmonary valve replacement.
To identify predictors of morbidity and mortality in patients undergoing either transcatheter pulmonary valve replacement (TPVR) or surgical pulmonary valve replacement (SPVR) in an effort to quantify any early benefit of TPVR over SPVR. Using a risk-adjusted propensity score model, we compare early major morbidity and mortality between patients undergoing SPVR and TPVR at our institution between January 2006 and January 2014. 145 patients in the SPVR cohort and 78 patients in the TPVR cohort were included. Primary pulmonary regurgitation was more common in the SPVR group (76.6% vs 23.1%, p<0.001) and primary pulmonary stenosis was more common in the TPVR group (9.7% vs 44.9%, p< 0.001). In unadjusted analysis, major morbidity and mortality occurred in 11.7% of SPVR patients versus 3.8% of TPVR patients (p=0.04). However, following risk adjustment and inclusion of a propensity score, no significant difference was seen between the two modalities. A larger right ventricular end-diastolic dimension (RVEDVI) was the only preoperative variable associated with the primary end point (OR 1.013/10 mL/m2 increase, p=0.03). Hospital length of stay was significantly longer in patients undergoing SPVR (6.9±1.0 days SPVR vs 1.2±0.3 days TPVR, p<0.0001), with similar hospital costs between groups (mean: US$44 660±5071 SPVR vs US$48 355±1000 TPVR, p=0.7). Following risk adjustment, no significant differences were observed between SPVR and TPVR strategies. TPVR was associated with a shorter hospitalisation; however, total hospitalisation costs were similar between groups.


[Keratopathy versus allergic eye disease: misdiagnosis leading to keratitis].
A case report of involutional ectropion associated with exposure keratopathy - which complicated to exposure keratitis due to incorrect management is presented. Upon consulting the local pharmacy the patient was wrongly given anti-allergic eye drops. Patients with involutional ectropion have high risk of dry eye disease and may rarely be complicated with keratitis. Distinguishing between exposure keratopathy and allergic eye disease is pivotal as management differs and wrong therapy may lead to serious eye disease.


Effects of 60Co gamma-rays, ultraviolet light, and mitomycin C on Halobacterium salinarium and Thiobacillus intermedius.
Lethal effects of 60Co gamma-rays, UV light, and mitomycin C on two kinds of bacteria, Halobacterium salinarium which grows in highly concentrated salt media and Thiobacillus intermedius which requires reduced sulfur compounds, were studied and compared with those on Escherichia coli B/r. D37 values for H. salinarium, T. intermedius and E. coli B/r were 393, 150, and 92 Gy, respectively, by exposure to 60Co gamma-rays. They were 212, 38, and 10 J/m2, respectively, by exposure to UV light and 2.36, 0.25, and 0.53 microgram/ml/h, respectively, by exposure to mitomycin C. Against these agents, H. salinarium was much more resistant than T. intermedius and E. coli B/r.


Comparison of Clinical Outcomes Between Laparoscopic and Open Extensive Resection for Complicated Appendicitis: Retrospective Observational Study.
The feasibility and safety of laparoscopic extensive resection (ER) for complicated appendicitis (CA) has not been clarified. We assessed the feasibility of laparoscopic ER versus open ER for CA. We retrospectively enrolled consecutive 983 patients who underwent emergency surgery for appendicitis, including 91 patients who underwent ER for CA, between April 2007 and October 2019. Thirty-three patients underwent laparoscopic ER, and 58 patients underwent open ER. There were no significant differences in the reasons for performing ER between laparoscopic ER and open ER. The rates of suspicious for malignant tumor did not differ between laparoscopic and open ER [15.2% (5/33) vs. 17.2% (10/58)]. Blood loss was less in laparoscopic ER than in open ER (P=0.028). Superficial surgical site infection was less frequent in laparoscopic ER than in open ER (P=0.047). In addition, laparoscopic ER tended to be associated with a shorter hospital stay, lower rate of postoperative ileus, and higher rate of intra-abdominal abscess. Laparoscopic ER is feasible, and it is associated with less intraoperative blood loss and a lower frequency of postoperative superficial surgical site infection than open ER.


Metabolomics for improving pregnancy outcomes in women undergoing assisted reproductive technologies.
In order to overcome the low effectiveness of assisted reproductive technologies (ART) and the high incidence of multiple births, metabolomics is proposed as a non-invasive method to assess oocyte quality, embryo viability, and endometrial receptivity, and facilitate a targeted subfertility treatment. To evaluate the effectiveness and safety of metabolomic assessment of oocyte quality, embryo viability, and endometrial receptivity for improving live birth or ongoing pregnancy rates in women undergoing ART, compared to conventional methods of assessment. We searched the Cochrane Gynaecology and Fertility Group Trials Register, CENTRAL, MEDLINE, Embase, CINAHL and two trial registers (November 2016). We also examined the reference lists of primary studies and review articles, citation lists of relevant publications, and abstracts of major scientific meetings. Randomised controlled trials (RCTs) on metabolomic assessment of oocyte quality, embryo viability, and endometrial receptivity in women undergoing ART. Two review authors independently assessed trial eligibility and risk of bias, and extracted the data. The primary outcomes were rates of live birth or ongoing pregnancy (composite outcome) and miscarriage. Secondary outcomes were clinical pregnancy, multiple and ectopic pregnancy, cycle cancellation, and foetal abnormalities. We combined data to calculate odds ratios (ORs) for dichotomous data and 95% confidence intervals (CIs). Statistical heterogeneity was assessed using the I² statistic. We assessed the overall quality of the evidence for the main comparisons using GRADE methods. We included four trials with a total of 802 women, with a mean age of 33 years. All assessed the role of metabolomic investigation of embryo viability. We found no RCTs that addressed the metabolomic assessment of oocyte quality or endometrial receptivity.We found low-quality evidence of little or no difference between metabolomic and non-metabolomic assessment of embryos for rates of live birth or ongoing pregnancy (OR 1.11, 95% CI 0.83 to 1.48; I² = 0%; four RCTs; N = 802), or miscarriage (OR 0.96, 95% CI 0.52 to 1.78; I² = 0%; two RCTs; N = 434). A sensitivity analysis excluding studies at high risk of bias did not change the interpretation of the results for live birth or ongoing pregnancy (OR 0.99, 95% CI 0.71 to 1.38; I² = 0%; two RCTs; N = 621). Our findings suggested that if the rate of live birth or ongoing pregnancy was 36% in the non-metabolomic group, it would be between 32% and 45% with the use of metabolomics.We found low-quality evidence of little or no difference between groups in rates of clinical pregnancy (OR 1.22, 95% CI 0.92 to 1.62; I²= 26%; four trials; N = 802), or multiple pregnancy (OR 1.52, 95% CI 0.71 to 3.23; I² = 0%; two RCTs, N = 181). There was very low-quality evidence of little or no difference between groups in ectopic pregnancy rates (OR 3.37, 95% CI 0.14 to 83.40; one RCT; N = 309), and foetal abnormalities (no events; one RCT; N = 125), and very low-quality evidence of higher rates of cycle cancellation in the metabolomics group (OR 1.78, 95% CI 1.18 to 2.69; I² = 51%; two RCTs; N = 744). Data were lacking on other adverse effects. A sensitivity analysis excluding studies at high risk of bias did not change the interpretation of the results for clinical pregnancy (OR 1.14, 95% CI 0.83 to 1.57; I² = 0%; two RCTs; N = 621).The overall quality of the evidence ranged from very low to low. Limitations included serious risk of bias (associated with poor reporting of methods, attrition bias, selective reporting, and other biases), imprecision, and inconsistency across trials. According to current trials in women undergoing ART, there is insufficient evidence to show that metabolomic assessment of embryos before implantation has any meaningful effect on rates of live birth, ongoing pregnancy, or miscarriage rates. The existing evidence varied from very low to low-quality. Data on adverse events were sparse, so we could not reach conclusions on these. At the moment, there is no evidence to support or refute the use of this technique for subfertile women undergoing ART. Robust evidence is needed from further RCTs, which study the effects on live birth and miscarriage rates for the metabolomic assessment of embryo viability. Well designed and executed trials are also needed to study the effects on oocyte quality and endometrial receptivity, since none are currently available.


Potent inhibition of serum-stimulated responses in vascular smooth muscle cell proliferation by 2-chloro-3-(4-hexylphenyl)-amino-1,4-naphthoquinone, a newly synthesized 1,4-naphthoquinone derivative.
Atherosclerosis, a disease of the large arteries, is the primary cause of heart disease and stroke. The abnormal proliferation of vascular smooth muscle cells (VSMCs) in arterial walls is an important pathogenetic factor of vascular disorders like atherosclerosis and restenosis after angioplasty. In the present study, the possible anti-proliferative effect of a synthetic 1,4-naphthoquinone derivative, 2-chloro-3-(4-hexylphenyl)-amino-1,4-naphthoquinone (NQ304) was investigated on rat aortic VSMCs. NQ304 was shown to potently inhibit 5% fetal bovine serum (FBS)-induced the growth of VSMCs. Pre-treatment of VSMCs with NQ304 (1-10 microM) for 24 h resulted in significant cell number decreases, i.e., inhibition percentages were 44.75+/-10.77, 73.85+/-6.38 and 89.77+/-6.52% at NQ304 concentrations of 1, 5 and 10 microM, respectively. NQ304 was also found to significantly inhibit 5% FBS-induced DNA synthesis in a concentration-dependent manner. Furthermore, NQ304 elevated p21(cip1) and p27(kip1) mRNA levels and caused G0/G1 phase arrest in cell cycle progression. However, no evidence of NQ304-induced apoptotic or necrotic cell death was obtained, as determined by flow cytometry analysis and DNA fragmentation assays. To investigate the mechanism underlying the anti-proliferative effect of NQ304, we examined the effects of NQ304 on c-fos mRNA expression, activator protein-1 (AP-1) binding activity and extracellular signal-regulated kinase1/2 (ERK1/2) and Akt activation. Pre-treatment of VSMCs with NQ304 (1-10 microM) was found to significantly inhibit the 5% FBS-induced phosphorylations of ERK1/2 and Akt, the activation of AP-1 and the expression of c-fos. These data suggest that the anti-proliferative and cell cycle arresting effects of NQ304 on serum-induced VSMCs may be mediated by AP-1 activation downregulation via the suppression of phosphatidylinositol 3-kinase (PI3K)/Akt and ERK1/2 signaling pathways, and it may contribute to the prevention of atherosclerosis through inhibition of VSMC proliferation.


Quantum Complementarity Approach to Device-Independent Security.
Complementarity is an essential feature of quantum mechanics. The preparation of an eigenstate of one observable implies complete randomness in its complementary observable. In quantum cryptography, complementarity allows us to formulate security analyses in terms of phase-error correction. However, the concept becomes much subtler in the device-independent regime that offers security without device characterization. Security proofs of device-independent quantum cryptography tasks are often complex and quite different from those of their more standard device-dependent cousins. The existing proofs pose huge challenges to experiments, among which large data-size requirement is a crux. Here, we show the complementarity security origin of the device-independent tasks. By linking complementarity with quantum nonlocality, we recast the device-independent scheme into a quantum error correction protocol. Going beyond the identical-and-independent-distribution case, we consider the most general attack. We generalize the sample entropy in classical Shannon theory for the finite-size analysis. Our method exhibits good finite-size performance and brings the device-independent scheme to a more practical regime. Applying it to the data in a recent ion-trap-based device-independent quantum key distribution experiment, one could reduce the requirement on data size to less than a third. Furthermore, the operational meaning of complementarity naturally extends device-independent scenarios to advantage key distillation, easing experiments by tolerating higher loss and lower transmittance.


The Effect of Intermittent Head Cooling on Aerobic Performance in the Heat.
Thermoregulation is critical for athletes, particularly those for those who must perform in the heat. Most strategies aimed at reducing heat stress have cooled participants before or during activity. The objective of this study is to investigate whether seven minutes of head cooling applied between bouts of aerobic exercise in hot (35 ± 1.0 °C) and dry (14.68 ±4.29% rh) environmental conditions could positively effect participants peak power output (PP) on a maximal effort graded exercise test (GXT). Twenty-two recreational active men ages 18 to 23 (19.8 ± 1.6 yrs.) completed three performance trials over a 21 day period. During the first trial, participants were familiarized with procedures and completed a maximal effort GXT on a cycle ergometer to establish maximal baseline performances. The second and third trials, which were counterbalanced, consisted of a cooling and placebo condition. During both of these trials, participants cycled 40 minutes at 65% of their maximum VO2, in hot (35 ± 1.0 °C) and dry (17-20% rh) environmental conditions. Immediately after this initial bout of activity, participants were given seven minutes of recovery in which head cooling was applied during the cooling condition and withheld during the placebo condition. Participants then completed a maximal effort GXT. Significant differences (p < 0.001) in participants peak power output (W) were measured when cooling was applied compared to the placebo condition (304.23(W) ± 26.19(W) cooling, 291.68(W) ± 26.04(W) placebo). These results suggest that a relatively brief period of intermittent cooling may enhance subsequent aerobic performance.


A comparison between sorbent and Reiter sonicate in the absorbed fluorescent treponemal antibody test.
Some syphilitic sera still fluoresce with Reiter treponemes as the antigen after treatment with the sorbent used in the FTA-ABS test; this finding indicates incomplete removal of group antitreponemal antibody. Levels of this antibody in normal sera have been studied in relation to the titration of sorbent for use in the test. A comparison has been made of the results of FTA-ABS tests with sorbent and Reiter sonicate and the TPI test on 1141 selected problem sera. Results with the sonicate displayed closer agreement (60.9%) with those of the TPI test than did tests with sorbent 40.8%). The use of sonicate as the sorbing agent is thought to improve the performance of the FTA-ABS test without diminishing its sensitivity.


Inoperable pulmonary aspergilloma: percutaneous CT-guided injection with glycerin and amphotericin B paste in 15 cases.
Fifteen patients with active inoperable pulmonary aspergilloma underwent percutaneous injection of a special therapeutic paste of glycerin and amphotericin B. This paste was warmed just prior to injection, and filling of the lesional cavity was achieved in one session if it was possible to obtain anaerobic conditions for destruction of the aspergilloma. Injection was performed with computed tomographic guidance with use of an 18-gauge flexible needle and with administration of anti-coughing analgesia. Follow-up was continued for 7 months on average. Filling of the lesion cavities required three sessions on average because of cough or bronchospasm. In 12 cases the aspergilloma regressed within 3 months and results at serology became negative. In three cases, there was no change in the cavity, but hemoptysis did not recur. Results in this series confirm the feasibility and efficacy of this palliative treatment.


Potential impacts of electric vehicles on air quality in Taiwan.
The prospective impacts of electric vehicle (EV) penetration on the air quality in Taiwan were evaluated using an air quality model with the assumption of an ambitious replacement of current light-duty vehicles under different power generation scenarios. With full EV penetration (i.e., the replacement of all light-duty vehicles), CO, VOCs, NOx and PM2.5 emissions in Taiwan from a fleet of 20.6 million vehicles would be reduced by 1500, 165, 33.9 and 7.2Ggyr(-1), respectively, while electric sector NOx and SO2 emissions would be increased by up to 20.3 and 12.9Ggyr(-1), respectively, if the electricity to power EVs were provided by thermal power plants. The net impacts of these emission changes would be to reduce the annual mean surface concentrations of CO, VOCs, NOx and PM2.5 by about 260, 11.3, 3.3ppb and 2.1μgm(-3), respectively, but to increase SO2 by 0.1ppb. Larger reductions tend to occur at time and place of higher ambient concentrations and during high pollution events. Greater benefits would clearly be attained if clean energy sources were fully encouraged. EV penetration would also reduce the mean peak-time surface O3 concentrations by up to 7ppb across Taiwan with the exception of the center of metropolitan Taipei where the concentration increased by <2ppb. Furthermore, full EV penetration would reduce annual days of O3 pollution episodes by ~40% and PM2.5 pollution episodes by 6-10%. Our findings offer important insights into the air quality impacts of EV and can provide useful information for potential mitigation actions.


Reliability and validity of maternal recall of injuries in Pacific children: findings from the Pacific Islands Families Study.
Childhood injury is one of the leading causes of morbidity and mortality worldwide. Many epidemiological studies use self-report injury data to understand the pattern of injury, and to identify risk factors and potential injury countermeasures, but the veracity of these data is not without question. To investigate the reliability and validity of the use of maternal recall of childhood injuries in a birth cohort study of Pacific mothers residing in New Zealand. As part of the Pacific Islands Families Study (PIFS), this study included 1,354 Pacific children born in Auckland in 2000 whose mothers completed a questionnaire at 6-weeks, 1-year, 2-years, 4-years, and 6-years postpartum. Maternal reports of child injuries and medical attendance events reported were matched to listings held within the National New Zealand Health Information Service's National Medical Discharge Summary (NMDS) database. Overall, 120 child injury events were listed in the NMDS database and 139 in the PIFS questionnaires. Kappa statistics demonstrated a modest level of agreement between the NMDS database listings and the mothers reporting of childhood injuries over the six years postpartum. However, McNemar's test of symmetry revealed no systemic under-reporting by the mothers, suggesting that the use of maternal proxy reporting of childhood injuries is a valid measure in this population. While maternal proxy reporting of Pacific childhood injuries was found to be a valid measure, some evidence of misinterpretation of questions was found; suggesting continued vigilance and development of maternal completed childhood injury questionnaires is warranted.


[Amputation neuroma as a rare cause of so-called post-cholecystectomy syndrome].
At the instance of a 30-year-old female patient a casuistic contribution to the differential diagnosis of the so-called "postcholecystectomy syndrome" by means of ERC is given. On condition after cholecystectomy an amputation neuroma had again led to colics. Amputation neuromas are rare, but not unknown causes for complaints after operations at the bile ducts. The origin of such a neuroma at the extrahepatic bile ducts is discussed.


Translational research in nicotine dependence.
Nicotine addiction accounts for 4.9 million deaths each year. Furthermore, although smoking represents a significant health burden in the United States, at present there are only three FDA-approved pharmacotherapies currently on the market: (1) nicotine replacement therapy, (2) bupropion, and (3) varenicline. Despite this obvious gap in the market, the complexity of nicotine addiction in addition to the increasing cost of drug development makes targeted drug development prohibitive. Furthermore, using combinations of mouse and human studies, additional treatments could be developed from off-the-shelf, currently approved medication lists. This article reviews translational studies targeting manipulations of the cholinergic system as a viable therapeutic target for nicotine addiction.


On comparing heterogeneity across biomarkers.
Microscopy reveals complex patterns of cellular heterogeneity that can be biologically informative. However, a limitation of microscopy is that only a small number of biomarkers can typically be monitored simultaneously. Thus, a natural question is whether additional biomarkers provide a deeper characterization of the distribution of cellular states in a population. How much information about a cell's phenotypic state in one biomarker is gained by knowing its state in another biomarker? Here, we describe a framework for comparing phenotypic states across biomarkers. Our approach overcomes the current limitation of microscopy by not requiring costaining biomarkers on the same cells; instead, we require staining of biomarkers (possibly separately) on a common collection of phenotypically diverse cell lines. We evaluate our approach on two image datasets: 33 oncogenically diverse lung cancer cell lines stained with 7 biomarkers, and 49 less diverse subclones of one lung cancer cell line stained with 12 biomarkers. We first validate our method by comparing it to the "gold standard" of costaining. We then apply our approach to all pairs of biomarkers and use it to identify biomarkers that yield similar patterns of heterogeneity. The results presented in this work suggest that many biomarkers provide redundant information about heterogeneity. Thus, our approach provides a practical guide for selecting independently informative biomarkers and, more generally, will yield insights into both the connectivity of biological networks and the complexity of the state space of biological systems.


Protocol for a multicenter prospective cohort study evaluating arthroscopic and non-surgical treatment for microinstability of the hip joint.
Microinstability of the hip joint is a proposed cause of hip pain and reduced function in young individuals. The underlying mechanism is thought to be extraphysiological hip motion due to bony deficiency and/or soft tissue deficiency or decreased soft tissue function. Recently, the condition has gained increased attention, and despite the fact that treatment today includes both non-surgical and surgical approaches, there is limited evidence on diagnostic specificity and treatment effects. The aim of this study is to evaluate clinical outcomes of both non-surgical and surgical treatment for microinstability of the hip joint. A multicenter prospective cohort study is planned to evaluating the outcome of physical therapy aimed at stabilizing the hip joint, as well as arthroscopic plication of the hip joint capsule, if the physical therapy fails. Outcomes will be evaluated using hip-specific patient-reported outcome measures: the short version of the International Hip Outcome Tool and the Copenhagen Hip and Groin Outcome Score, strength and function tests, health-related quality of life as determined using the European Quality of Life-5 Dimensions and the European Quality of Life-Visual Analog Scale, sports activity levels according to the Hip Sport Activity Scale, and reported complications. Patients will be evaluated at 6, 12 and 24 months after each treatment. It is important to evaluate the clinical outcomes of both non-surgical and surgical treatment for suspected microinstability of the hip joint, and the planned prospective evaluation will contribute to the understanding of non-surgical as well as surgical treatment outcomes, including complications. Clinicaltrials.gov: NCT04934462 . Registered June 22 2021.


[Operative guidelines for the shoe industry: health surveillance].
Medical surveillance of workers exposed to occupational risk factors means secondary prevention and entails medical activities which are related to the assessed risk. In particular, the chief risk factors evaluated in the footwear industry frequently imply medical surveillance of exposed workers. These risk factors include organic solvents and chemicals, leather dust, noise, repetitive movements and upper limb overload, vibrations, manual lifting action and video display terminal operation. We consider some operative standardized and validated protocols for medical surveillance of these industry employees.


Generation of biallelic F0 mutants in medaka using the CRISPR/Cas9 system.
Several animal models generated by genome editing methods develop somatic mosaic mutations including wild-type genome sequence in F0 generation because it is difficult to use editing tools at the one-cell stage. Producing complete knockout animals quickly is a great advantage in determining the function of target genes. This study investigated the generation of F0 knockout medaka using the CRISPR/Cas9 system. To determine whether this editing system induced mutations in the medaka genome at the one-cell stage, recombinant Cas9 protein, tracrRNA and crRNA for dead end (dnd), which is essential for germ cell development, were injected into one-cell stage embryos of olvas-DsRedExpress transgenic medaka. This allowed germ cells to be visualized by DsRed fluorescence. Genomic DNA extracted from embryos at the one-cell stage was analyzed by sequencing. Predictably, biallelic mutated sequence patterns in the target sites of dnd were found in the injected embryos. To investigate the phenotypes of the mutated fish, fluorescent and histological observations of germ cells were carried out using fry and adults. The mutations resulted in a complete loss of germ cells, suggesting loss of function of dnd in the injected embryos. Therefore, this system appears to be extremely effective for the production of F0 knockout medaka.


[Pharmacological action of Gambir.].
Gambir, which is called Asen-yaku in Japan, is mainly used as a stegnotic as well as an antiflatuent agent. The above data suggests, however, Gambir may also have anti-aging properties against the metabolic syndrome (MS) that has recently attracted concerns in the health community. While eating in moderation and appropriate exercise are naturally important in minimizing the MS, Gambir can play a role in improving each of the factors Prof. Kawamori presented as indicators of MS, including: 1. Improvement of visceral obesity, 2. Anti-hyperlipidemic activity including reduction of triglycerides and cholesterols, 3. Normalization of blood glucose level, and 4. Normalization of blood pressure.


The CREB constitutive activation domain interacts with TATA-binding protein-associated factor 110 (TAF110) through specific hydrophobic residues in one of the three subdomains required for both activation and TAF110 binding.
The cAMP response element-binding protein (CREB) mediates both basal and PKA-inducible transcription through two separate and independently active domains, the constitutive activation domain (CAD) and the kinase-inducible domain, respectively. The CREB CAD interacts with the general transcription factor TFIID through one or more of the TATA-binding protein-associated factors (TAFs), one of which is TAF110. The CAD is composed of three subdomains, rich in either serine, hydrophobic amino acids, or glutamine. In the present study, analysis of deletion mutants of the CAD showed that all three CAD subdomains were required for effective interaction with TAF110 in a yeast two-hybrid assay. Therefore, a library of random point mutations within the CAD was analyzed in a reverse two-hybrid screen to identify amino acids that are essential for interaction with the TAF. Interaction defects resulted solely from mutations of hydrophobic amino acid residues within the hydrophobic cluster to charged amino acid residues. Together, the deletion and mutation analyses suggest that the entire CAD provides an environment for a specific hydrophobic interaction with TAF110 that is crucial for interaction. Our results provide further evidence for a model of basal activation by CREB involving interaction with TAF110 that promotes recruitment or stabilization of TFIID binding to the promoter, which facilitates pre-initiation complex assembly.


[Survival of patients with laryngeal cancer and some prognostic factors].
Tumour growth and its progression to a metastatic phenotype involves a serious of genetic events with abnormal activation of oncogenes or inactivation of tumour suppressor genes and others genes connected with proliferation, apoptosis and neovascularisation. The aims of the study were to determine the possible prognostic value of angiogenesis, proliferation index Ki67, p53 and bcl-2 proteins expression in patients with laryngeal cancer. The group of 151 patients with laryngeal cancer, surgically treated with minimum 5 years observation, was multi-variously analysed. Paraffin--embedded tissue sections from each case were stained with a monoclonal antibody raised against FVIII antigen, p53 and bcl-2 proteins and Ki67 proliferation antigen using a peroxidase labelled streptavidin--biotin kit in standard immunohistochemistry techniques. In univariate analysis: staging IV, tumour size T4, nodal metastasis N2 and N3, local and nodal recurrences, high expression of Ki67 and P53, high (over median) IA measured as number of microvessels with FVIII expression were significantly associated with shortened overall survival. Disease-free survival was related to: proliferation index Ki67, expression of P53 protein and angiogenesis measured as microvessels density with expression of FVIII antigen. In multivariate analysis the most important death risk factors for overall survival were: tumour size, nodal metastasis, local and nodal recurrences, P53 protein expression and IA measured as number of microvessels with FVIII expression. In multivariate analysis of disease-free survival only P53 protein expression, proliferative index Ki67 and expression of FVIII had independent prognostic value. Intensity of angiogenesis, proliferation index of Ki67 antigen and expression of P53 protein were independent predictors of patients with laryngeal cancer outcome. In contrary Bcl2 protein seems to be useless in these patients.


Consistent platelet inhibition with ticagrelor 60 mg twice-daily following myocardial infarction regardless of diabetes status.
Diabetes increases cardiovascular risk and reduces pharmacodynamic response to some oral antiplatelet drugs. This study aimed to determine whether ticagrelor 60 mg twice daily (bid) provided potent and consistent platelet inhibition in patients with vs without diabetes in the PEGASUS-TIMI 54 platelet function substudy. Out of 180 patients studied, 58 patients were randomised to and had received at least four weeks of ticagrelor 60 mg bid, with 20 (34 %) having diabetes, 58 patients received ticagrelor 90 mg bid, with 12 (21 %) having diabetes, and 64 patients received placebo, with 18 (28 %) having diabetes. Blood was sampled pre- and 2 hours post-maintenance dose. In patients treated with ticagrelor 60 mg bid, on-treatment platelet reactivity to ADP, as determined by light transmission aggregometry (LTA), VerifyNow and VASP, was similar in patients with vs without diabetes (LTA post-dose, ADP 20 µM: 29 ± 14 vs 34 ± 10 %, respectively; p = 0.19). A consistent inhibitory effect of ticagrelor 60 mg bid was observed pre- and post-dose regardless of diabetes status, even in insulin-treated patients. Patients with diabetes did not have an increased incidence of high platelet reactivity in either ticagrelor group. Platelet reactivity was similar in patients with diabetes treated with ticagrelor 60 mg vs 90 mg bid. Pharmacokinetics of ticagrelor were not affected by diabetes status. In conclusion, ticagrelor 60 mg bid is equally effective at reducing platelet reactivity in patients with and without diabetes, yielding a consistently high level of platelet inhibition regardless of diabetes status.


Long-term follow-up of cyclosporine-treated renal allograft recipients.
Results in 355 Cs-treated renal graft recipients have been analyzed. The majority of graft losses occurred early. Prior sensitization and repeat grafts were clear-cut early risks for cadaver recipients but not live-related donor grafts. In neither group was presensitization clearly a risk factor for late losses, although repeat grafts were much more at risk late. The majority of late losses was due not to chronic rejection but to deaths from cardiovascular disease and cancer, and a surprisingly high number from noncompliance.


GLOBAL MITOCHONDRIAL DNA PHYLOGEOGRAPHY OF HOLARCTIC BREEDING DUNLINS (CALIDRIS ALPINA).
Comparison of mitochondrial DNA (mtDNA) control-region sequences of 155 dunlins from 15 breeding populations confirmed the existence of five major phylogeographic groups in the circumpolar breeding range of this migratory shorebird species. Time estimates of the origin of groups, based on sequence divergences and a molecular clock for birds, suggest a scenario of repeated fragmentation of populations in isolated tundra refugia during the late Pleistocene. The distribution of about three-quarters of all detected molecular variance between phylogeographic groups attests to the strongly subdivided genetic population structure in dunlins that is being maintained by natal philopatry. Each mtDNA phylogeographic group can be related to a morphometrically defined subspecies, but several other recognized subspecies are not supported by monophyletic mtDNA lineages within their purported ranges. More detailed analysis of several European populations reveals low amounts of gene flow and the partitioning of a substantial fraction of molecular variance between them. This ongoing evolution of population-genetic structuring within the European phylogeographic group most likely started with the last retreat of the ice sheets some 10,000 years ago. Dunlins thus provide one of the clearest examples of the linkage between historical and contemporary components of mtDNA phylogeographic structuring in birds.


Susac syndrome: a case report with initial presentation of incomplete bitemporal hemianopia.
Susac syndrome (SS) is a rare microangiopathy affecting the precapillary arterioles of the brain, inner ear, and retina. We present a novel case of SS, presenting as acute incomplete bitemporal field loss in addition to temporally spaced neurological and vestibulocochlear symptoms. A 39-year-old female was referred to the ophthalmology clinic with acute incomplete bitemporal hemianopia and worsening hemicrania. History revealed progressive hearing loss, subjective short-term memory impairment, and vertigo temporally spaced over the preceding 12 months. Magnetic resonance brain revealed multiple small colosal lesions and liner 'spoke' lesions. Fundus fluorescein angiography revealed multiple branch retinal artery occlusions in the right eye. Audiometry confirmed bilateral sensorineural hearing loss. Treatment included intravenous corticosteroids and rituximab. This case highlights the importance of early consideration and evaluation of SS in individuals presenting with atypical ocular disturbances, where no clear cause can be elicited, in order to limit the sequelae of disease.


Three heads are better than one: cooperative learning brains wire together when a consensus is reached.
Theories of human learning converge on the view that individuals working together learn better than do those working independently. Little is known, however, about the neural mechanisms of learning through cooperation. We addressed this research gap by leveraging functional near-infrared spectroscopy to record the brain activity of triad members in a group simultaneously. Triads were instructed to analyze an ancient Chinese poem either cooperatively or independently. Four main findings emerged. First, we observed significant within-group neural synchronization (GNS) in the left superior temporal cortex, supramarginal gyrus, and postcentral gyrus during cooperative learning compared with independent learning. Second, the enhancement of GNS in triads was amplified when a consensus was reached (vs. elaboration or argument) during cooperative learning. Third, GNS was predictive of learning outcome at an early stage (156-170 s after learning was initiated). Fourth, social factors such as social closeness (e.g. how much learners liked one other) were reflected in GNS and co-varied with learning engagement. These results provide neuroscientific support for Piaget's theory of cognitive development and favor the notion that successful learning through cooperation involves dynamic consensus-building, which is captured in neural patterns shared across learners in a group.


Relationship Between Respiratory Dynamics and Body Mass Index in Patients Undergoing General Anesthesia with Laryngeal Mask Airway (LMA) and Comparison Between Lithotomy and Supine Positions.
BACKGROUND This study aimed to compare respiratory dynamics in patients undergoing general anesthesia with a laryngeal mask airway (LMA) in lithotomy and supine positions and to validate the impact of operational position on effectiveness of LMA ventilation. MATERIAL AND METHODS A total of 90 patients (age range, 18-65 years) who underwent general anesthesia were selected and divided into supine position (SP group) and lithotomy position groups (LP group). Vital signs and respiratory dynamic parameters of the 2 groups were measured at different time points and after implantation of an LMA. The arterial blood gas was monitored at 15 min after induction. The intraoperative changes of hemodynamic indexes and postoperative adverse reactions of LMA were recorded. The possible correlation between body mass index (BMI) and respiratory dynamic indexes was analyzed. RESULTS With prolonged duration of the operation, the inspiratory plateau pressure (Pplat), inspiratory resistance (RI), and work of breathing (WOB) gradually increased, while chest-lung compliance (Compl) and partial pressure of carbon dioxide in end-expiratory gas (PetCO2) gradually decreased (all P value <0.05). The mean airway pressure (Pmean), Pplat, and expiratory resistance (Re) in the LP group were significantly higher than in the SP group (P<0.05), while the peak inspiratory flow (FImax), peak expiratory flow (FEmax), WOB, and Compl in the LP group were significantly lower than in the SP group (P<0.05). BMI was positively correlated with peak airway pressure (PIP/Ppeak), Pplat, and airway resistance (Raw) and was negatively correlated with Compl; the differences among patients in lithotomy position were more remarkable (P<0.05). CONCLUSIONS The inspiratory plateau pressure and airway resistance increased with prolonged duration of the operation, accompanied by decreased chest-lung compliance. Peak airway pressure and airway resistance were positively correlated with BMI, and chest-lung compliance was negatively correlated with BMI. Changes among patients in lithotomy position were more remarkable than those in supine position.


Apheresis in food allergies.
The prevalence of IgE-mediated food allergy and anaphylaxis has risen rapidly in developed countries, and countries with rapid industrialization may follow. Therapies include elimination diets, Oral ImmunoTherapy, and the administration of biologics, but high serum IgE levels may preclude their use. Consequently, decreasing IgE becomes a rational approach and could be obtained by immunoapheresis. The aim of this review is to evaluate the rationale and advantages of immunoapheresis. The majority of the available adsorbers remove aspecifically all classes of immunoglobulins. Recently, IgE-specific adsorbers have been approved. Data on immunoapheresis for the treatment of allergic diseases with pathologically elevated IgE levels are emerging. In atopic dermatitis, this therapy alone seems to be beneficial. IgE-selective apheresis appears to be sufficient to reduce the risk of anaphylaxis in multiple food allergy (MFA) and, when IgE titers are high, to open the way to treatment with Omalizumab. Prospective studies, with well designed protocols, are needed to assess the efficacy, tolerability, and cost-effectiveness of immunoapheresis in the field of food allergy.


Electrocardiographic Morphology-Voltage-P-Wave-Duration (MVP) Score to Select Patients for Continuous Atrial Fibrillation Screening to Prevent Stroke.
Morphology-voltage-P-wave-duration (MVP) score combining P-wave duration (PWD), P-wave voltage in lead I (PWVI), and interatrial block (IAB) has been demonstrated to predict atrial fibrillation (AF). Therefore, this study aimed to examine MVP score and its P-wave components as potential predictors of AF screening effects on stroke prevention. This was a secondary analysis of the LOOP Study (Atrial Fibrillation detected by Continuous ECG Monitoring using Implantable Loop Recorder to prevent Stroke in High-risk Individuals) which randomized older persons (aged 70 to 90 years) with additional stroke risk factors to either continuous monitoring with implantable loop recorder and anticoagulation upon detection of AF episodes ≥6 minutes (the intervention group), or usual care. A total of 5,759 participants were included in the present analysis, where PWD, PWVI, and IAB were determined through a computerized analysis of 12-lead electrocardiogram and further employed to calculate baseline MVP score (0 to 6) for each participant. In total, 305 (5.3%) had stroke or systemic embolism during follow-up, with a higher risk in the group with MVP score 5 to 6 than those having score 0 to 2 (hazard ratio (HR) 1.54 [95% confidence interval (CI) 1.01 to 2.35]). This risk increase was mainly upheld by participants with IAB (HR 1.62 [95% CI 1.11 to 2.36] for IAB vs no IAB) and with longer PWD (HR 1.37 [95% CI 1.07 to 1.75] for >110 vs ≤110 ms). Compared with usual care, implantable loop recorder screening did not significantly reduce the risk of stroke or systemic embolism in any MVP risk categories (HR 0.80 [95% CI 0.60 to 1.08] for MVP score 0 to 2, 0.54 [95% CI 0.16 to 1.85] for MVP score 3 to 4, and 0.89 [95% CI 0.35 to 2.25] for MVP score 5 to 6; pinteraction = 0.78). In conclusion, a higher MVP score was associated with an increased stroke risk, but it did not demonstrate an association with effects of AF screening on stroke prevention. These findings should be considered hypothesis-generating and warrant further study.


Prosthodontic practice during the COVID-19 pandemic: prevention and implications.
The objective of this review is to identify preventive measures for COVID-19 to safeguard dental professionals providing prosthodontic dental care. Electronic searches were performed in PubMed, Scopus, and Cochrane databases using the following descriptors and/or words: "COVID-19," "SARS-CoV-2," "Dental practice," "Prosthodontics," and "Dental infection control." Prosthodontists are at high risk for exposure to the novel coronavirus through aerosols and possibly contaminated surfaces and indirect contact with dental laboratories and dental technicians through impressions, dental stone casts, and fixed and removable prosthetic appliances. Therefore, preventive measures should be implemented, including performing emergency treatments only, rescheduling patients with suspected disease, disinfecting surfaces and prosthodontic materials with biocidal substances, and using protective equipment such as N95 masks, disposable gowns, and face-shields.


Stability of metallo-porphyrin networks under oxygen reduction and evolution conditions in alkaline media.
Transition metal atoms stabilised by organic ligands or as oxides exhibit promising catalytic activity for the electrocatalytic reduction and evolution of oxygen. Built-up from earth-abundant elements, they offer affordable alternatives to precious-metal based catalysts for application in fuel cells and electrolysers. For the understanding of a catalyst's activity, insight into its structure on the atomic scale is of highest importance, yet commonly challenging to experimentally access. Here, the structural integrity of a bimetallic iron tetrapyridylporphyrin with co-adsorbed cobalt electrocatalyst on Au(111) is investigated using scanning tunneling microscopy and X-ray absorption spectroscopy. Topographic and spectroscopic characterization reveals structural changes of the molecular coordination network after oxygen reduction, and its decomposition and transformation into catalytically active Co/Fe (oxyhydr)oxide during oxygen evolution. The data establishes a structure-property relationship for the catalyst as a function of electrochemical potential and, in addition, highlights how the reaction direction of electrochemical interconversion between molecular oxygen and hydroxyl anions can have very different effects on the catalyst's structure.


Caregiving among American Indians and Alaska Natives with cancer.
Caregivers are an important source of support for oncology patients during cancer diagnosis and treatment, often helping patients manage barriers to care. Our study had three goals: to describe the characteristics of caregivers for American Indian and Alaska Native (AI/AN) oncology patients, to assess the similarities and differences between the perceptions of caregivers and patients regarding barriers to cancer care, and to compare AI/AN caregivers to non-AI/AN caregivers on perceived barriers to cancer care. We conducted a structured interview that assessed perceived barriers to cancer care with a paired sample of 98 adult caregivers and 98 AI/AN oncology patients and to assess the degree of agreement between these two groups. We also investigated whether AI/AN and non-AI/AN caregivers had differing perceptions of barriers to cancer care. Caregivers reported that their role was very meaningful and not highly stressful. Caregivers and patients agreed 70 % of the time on specific barriers to cancer care. Both groups overwhelmingly reported financial and family or work issues as major barriers to care, whereas trust in providers was the least frequently endorsed barrier. A comparison of AI/AN and non-AI/AN caregivers revealed that AI/AN caregivers identified confidentiality among clinical staff as a significant barrier, whereas non-AI/AN caregivers perceived financial barriers as more significant. Finances, family, and work are perceived as the largest barriers to the receipt of cancer care for AI/AN oncology patients. Both patients and caregivers trusted health-care providers. Assessing barriers to care early in the assessment process may result in better engagement with cancer treatment by patients and their caregivers.


Effect of mimicking prepartum concentration of estradiol-17 beta on the inflammatory response to endotoxin in gilts.
The effect of mimicking prepartum concentration of estradiol-17 beta on the inflammatory response to endotoxin in gilts was studied. The study was performed in a split-litter design and comprised 5 pairs of littermates. A catheter was inserted into the jugular vein 2 days prior to the start of the study. In each pair, 1 littermate was treated IM with 2.5 mg of estradiol-17 beta/75 kg of body weight, and the other littermate was given peanut oil IM as a control. The day after treatment, all gilts were challenge-exposed with a Salmonella typhimurium-derived endotoxin (1 microgram/kg, IV) and the inflammatory response to challenge exposure was monitored. There was no effect of estradiol treatment on the transient clinical signs of endotoxemia or on the increase in rectal temperature. The increase in blood concentrations of prostaglandin F2 alpha metabolite and cortisol after endotoxin challenge exposure was not affected by estradiol. Decrease in number of circulating blood mononuclear cells and polymorphonuclear leukocytes was not changed by estradiol treatment. Taken together, mimicking prepartum concentration of estradiol did not affect either the magnitude or the kinetics of the inflammatory response to endotoxin in gilts. Relevance of these findings to development of endotoxin-mediated diseases, such as the postpartum agalactia syndrome, needs further study.


Introductory statement on the progress of The National Large Bowel Cancer Project: its goals, objectives, and programs.
The introductory lecture updates the state of the art bearing on cancer of the large bowel. Topics discussed include etiological factors, the pathology of the disease, the role of animal models, the early diagnosis of the disease, including biochemical markers, with emphasis on immunology, and finally therapy, including surgery, radiotherapy, chemotherapy, and the immunological approaches to therapy as identified in the ongoing activities of the National Large Bowel Cancer Project. Interesting aspects of complementing the traditional ways of treating colorectal disease are noted in the discussion of new approaches to chemotherapeutic treatment based on rational developments obtained throught the study of cell kinetics and cell turnover. It is pointed out that this and other interrelationships considered in the multidisciplinary experimental and clinical approaches provide important leads toward the understanding of the mechanisms of disease, discovery of causes and means of prevention, methods of earlier diagnosis, improved rational modalities of treatment, and, one hopes, more successful management.


Ratiometric Hg2+ /Ag+ Probes with Orange Red-White-Blue Fluorescence Response Constructed by Integrating Vibration-Induced Emission with an Aggregation-Induced Emission Motif.
Two novel ratiometric fluorometric probes 6 a and 6 b have been designed and synthesized for the detection of Hg2+ and Ag+ , respectively. Each of these probes is comprised of a 9,14-diphenyl-9,14-dihydrodibenzo[a,c]phenazine (DPAC) skeleton, a tetraphenylethylene (TPE) unit, and two thymine/adenine groups. In this proof-of-concept work, the DPAC unit featuring vibration-induced emission (VIE) characteristics serves as a dual-emission chromogen, whereas the TPE moiety, which is noted for its aggregation-induced emission (AIE) properties, functions mainly as a signal amplifier. The coordination between the thymine/adenine groups and Hg2+ /Ag+ leads to the formation of aggregates, which restricts the intramolecular vibrations of DPAC and the intramolecular rotations of TPE, activating the AIE effect of TPE and resulting in the bent form of DPAC. Accordingly, the overall fluorescence changed from moderate orange-red (Iorange-red ) to intense blue light (Iblue ) passing through the white-light region, concurrently with an enhancement of fluorescence at 475 nm and a dramatic increase in the ratio of Iblue /Iorange-red . Furthermore, the superb sensitivity of 6 a/6 b towards Hg2+ /Ag+ has been demonstrated by the detection limit, which is as low as 6.1 nm and 0.1 μm, respectively. Both of these values are below the maximum concentration in drinking water permitted by the U.S. Environmental Protection Agency, demonstrating their great potential to be applied for real-world metal-ion sensing.


Sebaceous carcinoma: review of the literature.
Sebaceous carcinoma is an uncommon adnexal neoplasm with a documented capability for regional and distant metastasis. Traditionally, sebaceous carcinoma has been associated with high rates of recurrence after excision. To review the current literature on sebaceous carcinoma and detail its epidemiology, pathogenesis, clinical presentation, histopathology, diagnostic workup, treatment, and prognosis. Literature review using PubMed search for articles related to sebaceous carcinoma. Sebaceous carcinoma typically presents as a painless pink or yellow nodule. Diagnosis requires histopathologic examination, and immunohistochemical analysis often assists in the differentiation of sebaceous carcinoma from other benign and malignant skin neoplasms. Sebaceous carcinoma should prompt a workup for Muir-Torre syndrome. Periorbital sebaceous carcinoma has an increased tendency for regional metastasis, although cancer-specific mortality rates are similar among all anatomic locations. Surgery is the preferred treatment for local disease. Limited data suggest that Mohs micrographic surgery may provide superior clinical outcomes, but more research is needed regarding the long-term outcomes. Radiation and systemic chemotherapy are reserved for recurrent or metastatic disease.


RNA-seq analysis and compound screening highlight multiple signalling pathways regulating secondary cell death after acute CNS injury in vivo.
Understanding the molecular mechanisms that regulate secondary cell death after acute central nervous system (CNS) injury is critical for the development of effective neuroprotective drugs. Previous research has shown that neurotoxic processes including excitotoxicity, oxidative stress and neuroinflammation can cause secondary cell death. Nevertheless, clinical trials targeting these processes have been largely unsuccessful, suggesting that the signalling pathways underlying secondary cell death remain incompletely understood. Due to their suitability for live imaging and their amenability to genetic and pharmacological manipulation, larval zebrafish provide an ideal platform for studying the regulation of secondary cell death in vivo Here, we use RNA-seq gene expression profiling and compound screening to identify signalling pathways that regulate secondary cell death after acute neural injury in larval zebrafish. RNA-seq analysis of genes upregulated in cephalic mpeg1+ macrophage-lineage cells isolated from mpeg1:GFP transgenic larvae after neural injury suggested an involvement of cytokine and polyamine signalling in secondary cell death. Furthermore, screening a library of FDA approved compounds indicated roles for GABA, serotonin and dopamine signalling. Overall, our results highlight multiple signalling pathways that regulate secondary cell death in vivo, and thus provide a starting point for the development of novel neuroprotective treatments for patients with CNS injury.This article has an associated First Person interview with the two first authors of the paper.


"Atypical" Spitz's nevus, "malignant" Spitz's nevus, and "metastasizing" Spitz's nevus: a critique in historical perspective of three concepts flawed fatally.
Our purpose in undertaking this Arbeit was to review all articles published about "atypical" Spitz's nevus, "malignant" Spitz's nevus, and "metastasizing" Spitz's nevus, to criticize them in a fashion that illuminates, and to come to conclusions compellingly about those subjects. We found that an overwhelming majority of neoplasms that claimed to be "atypical Spitz's nevus," "metastasizing Spitz's nevus," and "malignant Spitz's nevus" were, in fact, melanomas ( Table 1). Moreover, in our estimation, those designations, and variants of them, like "atypical Spitz's lesion," "atypical dermal melanocytic lesion with features of Spitz's nevus," "atypical Spitzoid melanocytic neoplasm," and "problematic Spitzoid melanocytic lesion," are mere evasions from a diagnosis, straightforwardly, of either Spitz's nevus or melanoma. Diagnoses in pathology equally bogus are "minimal deviation melanoma," "borderline melanoma," "nevoid melanoma," "potentially low-grade melanocytic neoplasm," and "melanocytic lesion of uncertain biologic potential." Rather than admit uncertainty forthrightly, those who employ circumlocutions like those just mentioned resort to linguistic maneuvers that, at first blush, seem to be "academic" and constructed in such a way as to appear to convey confidence, rather than tentativeness, on the part of a histopathologist. On further scrutiny, however, each of those cliches is revealed to be devoid of content. For example, "malignant" Spitz's nevus and "metastasizing" Spitz's nevus not only are contradictions in terms, but they are outrageous violations of fundamental principles of classic Virchowian pathology, and "atypical" Spitz's nevus not only is a redundancy because the neoplasm was so atypical to Spitz, herself, she insisted (from the time she spawned the idea in 194 through 1951 it was a "malignant melanoma," but is abject intellectually, those who invoke it never setting forth, in clear-cut fashion, criteria for what constitutes a "typical" Spitz's nevus in contradistinction to an "atypical" one.


HTLV-1a tax gene and long terminal repeat sequences from Argentinean strains reveal disagreement with tax restriction fragment length polymorphism subtyping.
Sequence and cluster analysis have shown two HTLV-1a tax gene subgroups, tax A and tax B, which are related to long terminal repeat (LTR) molecular subtypes. On the basis of subgroup-specific nucleotide substitutions, restriction fragment length polymorphism (RFLP) analysis of the tax gene for subtyping HTLV-1a isolates was proposed. In this study we genetically characterized the tax gene from 63 HTLV-1-positive Argentinean individuals, including 14 patients with HTLV-1-associated myelopathy/tropical spastic paraparesis and 49 healthy HTLV-1 carriers. RFLP analysis showed that 48 samples yielded the tax A profile (76.19%) and that 15 samples contained the uncut tax B profile (23.81%). However, the LTR and tax sequence analysis revealed that in fact only 2 from the 15 samples belonged to the HTLV-1aB subgroup, presenting four tax B subgroup-specific nucleotide substitutions. The tax gene cluster analysis also confirmed that the majority of Argentinean strains belonged to the Transcontinental HTLV-1aA subgroup. These results indicate that the tax gene RFLP assay which has been proposed and used by some authors to screen HTLV-1a subgroups, is not a suitable tool to perform molecular epidemiological characterization of HTLV-1a populations.


Hydrodynamics of Irregular-Shaped Graphite Particles in Coaxial Two-Phase Jet Flow.
Expanded graphite particle is characterized by the low density in comparison with those of bead glass and copper particles. Hydrodynamics of the irregular-shaped graphite particle swirling flows in a coaxial chamber are investigated via an improved kinetic frictional stress model. A drag force coefficient considering the effects of irregular shapes based on the artificial neural network algorithm is adopted to describe the momentum transfer between nonspherical particles and gas phases. The proposed model, algorithm, and source code for modeling and simulation are validated by measurement using spherical glass beads, and acceptable agreement is obtained. Lower sphericity particles enhance the anisotropic particle dispersions and induces the redistributions of the Reynolds stresses of the two-phase flow. Irregular-shaped particles are more sensitive to the gas followability instead of own inertia, whereas spherical particles are easier to be affected by the inlet effects. The interlock force between nonspherical particles takes great effect on particle flow than the spherical particle. The axial-axial normal stresses of sphericities of 0.63 and 0.72 are approximately 3.4 times larger than those of shear stress of spherical particle, and their axial velocities locating at near central regions are 3.0 times larger than those of sphericities.


Isolation of a new triterpene derivative and in vitro and in vivo anticancer activity of ethanolic extract from root bark of Zizyphus nummularia Aubrev.
The various parts of Zizyphus nummularia has been used traditionally in several disease conditions. However, its anticancer activity and mechanism of action remain to be elucidated. Considering this, the objective of this study was to isolate, identify and screen for possible anticancer activity in vitro and in vivo of the ethanolic extract (EE) and isolated identified compound (IC) from Z. nummularia root bark. The in vitro activity against human breast cancer, leukaemia, ovarian cancer, colon adenocarcinoma and human kidney carcinoma cell lines was determined. The in vivo activity in female Swiss albino mice against Ehrlich ascites carcinoma (EAC) was determined. The isolated compound is a new triterpene derivative. EE/IC showed cytotoxicity against different cell lines. The administration of EE/IC decreased tumour parameters such as tumour volume, viable tumour cell count and increased body weight, haematological parameters and life span in comparison to the EAC control mice.


Long-term observations of patients with infantile spinal muscular atrophy with respiratory distress type 1 (SMARD1).
We describe 6 unrelated patients affected by infantile spinal muscular atrophy with respiratory distress type 1 (SMARD1) with prolonged survival upon mechanical ventilation (4.5-11 years), which has not been reported before. Biallelic mutations in the IGHMBP2 gene proved the diagnosis of SMARD1 in all patients. Disease onset was in the first 2 months in the described patients, starting with generalised hypotonia, failure to thrive, and early breathing difficulties. Diaphragmatic palsy was diagnosed and permanent ventilation was initiated 2-8 months after onset. Within months a more distal muscular atrophy became evident associated with joint contractures (talipes), hand drops, and fatty finger pads. Motor development remained minimal, loss of function was observed within the first year after which no further progression was recorded. Voiding dysfunction with reflux nephropathy was observed in 3 patients and has not been reported before. Further evidence of autonomic nerve dysfunction resulting in cardiac arrhythmia, hypertension, and excessive sweating was given in 2 patients. Investigative results were largely compatible with those obtained in classic SMA. However, neurogenic atrophy muscle was more pronounced in distal muscles, if examined, and there was evidence of peripheral nerve involvement at least in some patients.


The different patterns of blood pressure elevation by rofecoxib and nabumetone.
Hypertension and knee osteoarthritis (OA) are frequent comorbidities. Nonsteroidal anti-inflammatory drugs (NSAIDs) are often used to relieve pain in such patients. In the last decade selective NSAIDs are used more commonly since they lead to less gastrointestinal complications. As has been shown, the treatment with NSAIDs may cause a mild rise of arterial blood pressure (BP). The influence of selective NSAIDs on BP, particularly in hypertensive patients has still to be investigated. The aim of this study was to determine arterial BP changes in patients suffering from stable arterial hypertension and knee OA and treated with rofecoxib or nabumetone. Two groups of patients with knee OA and stable arterial hypertension received either 25 mg rofecoxib once daily or namebutone 2000 mg once daily during the first week of treatment and 1000 mg for the following 3 weeks. Twenty-four hour arterial BP monitoring was performed prior to initiation of treatment and at the end of a 4-week period. The results were that no changes were found in the mean systolic and diastolic characteristics of BP in the rofecoxib treatment group during day time (delta systolic BP -0.4 mm Hg and delta diastolic BP -0.4 mm Hg), while nocturnal BP increased significantly: delta systolic BP +15.7 mm Hg and delta diastolic BP +8.5 mm Hg. The mean systolic arterial pressure in the nabumeton group raised delta systolic BP 2.9 mm Hg in the daytime and 5 mm Hg during the night-time after the treatment. The mean diastolic arterial pressure also rose delta diastolic 3.2 mm Hg and 4.9 mm Hg at day and night hours respectively. In conclusion rofecoxib treatment did not change arterial BP during day time hours, however, there was a distinct increase in night-time systolic and diastolic BP leading to a disappearance of the physiological diurnal variation. Nabumetone caused a moderate increase of day and night BP, without changes in biological diurnal variation.


Vernalization-mediated chromatin changes.
Proper flowering time is vital for reproductive fitness in flowering plants. In Arabidopsis, vernalization is mediated primarily through the repression of a MADS box transcription factor, FLOWERING LOCUS C (FLC). The induction of a plant homeodomain-containing protein, VERNALIZATION INSENSITIVE 3 (VIN3), by vernalizing cold is required for proper repression of FLC. One of a myriad of changes that occurs after VIN3 is induced is the establishment of FLC chromatin at a mitotically repressed state due to the enrichment of repressive histone modifications. VIN3 induction by cold is the earliest known event during the vernalization response and includes changes in histone modifications at its chromatin. Here, the current understanding of the vernalization-mediated chromatin changes in Arabidopsis is discussed, with a focus on the roles of shared chromatin-modifying machineries in regulating VIN3 and FLC gene family expression during the course of vernalization.


Homing receptors and metastasis.
As discussed in the preceding sections, there are several indications that the lymphocyte homing receptors involved in the normal process of lymphocyte recirculation are also relevant to the behavior of metastatic cells. Cell fusion experiments indicate that previously nonmetastatic cells can acquire metastatic capacity from fusion with normal lymphocytes. Murine T lymphomas that bear high levels of functional homing receptors can metastasize to peripheral lymphoid organs, whereas those lymphomas lacking homing receptors cannot. Virtually all lymph node metastases of lymphomas contain a high proportion of MEL-14hi cells, even if the primary tumor has been selected to be relatively deficient in these cells. Further investigations of the biology of lymphocyte homing receptors will reveal whether or not there are additional lymphocyte homing receptors and will clarify the role of lymphocyte homing receptors in metastasis. Antibodies against three lymphocyte homing receptors could therefore be useful for diagnosis and treatment of metastatic disease.


ADAM12 and PAPP-A: Candidate regulators of trophoblast invasion and first trimester markers of healthy trophoblasts.
Proper placental development and function is crucial for a healthy pregnancy, and there has been substantial research to identify markers of placental dysfunction for the early detection of pregnancy complications. Low first-trimester levels of a disintegrin and metalloproteinase 12 (ADAM12) and pregnancy-associated plasma protein-A (PAPP-A) have been consistently associated with the subsequent development of preeclampsia and fetal growth restriction. These molecules are both metalloproteinases secreted by the placenta that cleave insulin-like growth factor binding proteins (IGFBPs), although ADAM12 also has numerous other substrates. Recent work has identified ADAM12, and particularly its shorter variant, ADAM12S, as a regulator of the migration and invasion of trophoblasts into the lining of the uterus, a critical step in normal placental development. While the mechanisms underlying this regulation are not yet clear, they may involve the liberation of heparin-binding EGF-like growth factor (HB-EGF) and/or IGFs from IGFBPs. In contrast, there has been relatively little functional work examining PAPP-A or the IGFBP substrates of ADAM12 and PAPP-A. Understanding the functions of these markers and the mechanisms underlying their association with disease could improve screening strategies and enable the development of new therapeutic interventions.


Competition for nitrogen between European beech and sycamore maple shifts in favour of beech with decreasing light availability.
Plant species use different strategies for maximizing growth and fitness under changing environmental conditions. At the ecosystem level, seedlings in particular compete with other vegetation components for light and nitrogen (N), which often constitute growth-limiting resources. In this study, we investigated the effect of light availability on the competition for N between seedlings of European beech and sycamore maple and analysed the consequences of this competition for the composition of N metabolites in fine roots. Our results show different strategies in N acquisition between beech and sycamore maple. Both species responded to reduced light availability by adapting their morphological and physiological traits with a decrease in biomass and net assimilation rate and an increase in specific leaf area and leaf area ratio. For beech seedlings, competition with sycamore maple led to a reduction in organic N uptake capacity. Reduced light availability led to a decrease in ammonium, but an increase in glutamine-N uptake capacity in sycamore maple. However, this response was stronger compared with that of beech and was accompanied by reduced growth. Thus, our results suggest better adaptation of N acquisition to reduced light availability in beech compared with sycamore maple seedlings.


[Lipoma: a rare differential gastrointestinal tumor diagnosis].
This is a case report of a female patient who during a routine follow-up after a gastrectomy showed a tumor of the ileo-cecal valve, which--according to all radiologic diagnostic procedures--was highly suspected to be a malignant tumor. However, the histologic diagnosis was benign lipoma. The incidence and the characteristics of gastrointestinal lipomas in the actual literature will be reviewed.


Suffering and interpersonal meaning: commentary.
I would like to suggest that to describe suffering as a psychological phenomenon is still too general. It leaves the door open to the belief that suffering is an individual phenomenon, experienced because of dynamics arising out of the individual psyche as the pain arises out of the individual body. Instead of describing suffering as a psychological phenomenon, we should describe it as an interpersonal, even communal phenomenon.... If the task of reestablishing, continuing, and creating interpersonal meaning within the context of suffering is accepted, the problem often arises concerning how the health professional can accomplish this task with the patient under the extraordinary circumstances that pain and illness, as well as the health-care environment, provide. Beyond sensitive and thoughtful dialogue, we may have to return to a sense of ceremony within health care, especially since the rationalistic naiveté of nineteenth-century positivism did so much to encourage the belief that the best health care is the one that does things efficiently and "unceremoniously"....


Image-guided transsacral approach to presacral lesions of nerve root origin: technical note.
The utility of image guidance in fashioning a posterior transsacral operative corridor for approaching small presacral neural lesions has not previously been reported. A 61-year-old woman presented with unilateral sciatica and worsening leg weakness. Subsequent investigations disclosed a well-defined, 1.4-cm lesion in continuity with the S1 nerve root distal to the anterior sacral foramen. A minimally invasive approach was undertaken with use of the StealthStation (Medtronic Sofamor Danek, Inc., Memphis, TN). The amount of sacral bone resection was preplanned to ensure the most direct posterior access route. Intraoperative navigation was used to guide the trajectory of bone drilling. After adequate exposure was achieved, the lesion was resected using standard microsurgical techniques under continuous intraoperative electrophysiological monitoring. An image-guided transsacral approach is a viable option for accessing small to moderately sized lesions of nerve root origin located within the presacral space.


Glycogen storage disease type II: clinical overview.
Glycogen storage disease type II has a broad continuous clinical spectrum in terms of onset, involvement of organs and life expectancy. Infantile onset is the most severe form, presenting with prominent cardiomyopathy, hypotonia, hepatomegaly and death before 12 months of life. Late onset form has onset at any age, lack of severe (or absence of) cardiac involvement, progressive skeletal muscle dysfunction and less dismal short-term prognosis. In addition to muscle and heart involvement, other tissues are affected liver, spleen, endothelium, lung, brain, anterior horns, peripheral nerves. In fact some patients with infantile form have hearing loss, abnormal brain myelination and central fever and some adult patients show aneurysms of brain arteries due to accumulation of glycogen in vessels. As for other treatable lysosomal diseases, the advent of enzyme replacement therapy will change the natural history of this disease and also will increase our knowledge concerning clinical heterogeneity.


Lab-on-a-Contact Lens Platforms Fabricated by Multi-Axis Femtosecond Laser Ablation.
Contact lens sensing platforms have drawn interest in the last decade for the possibility of providing a sterile, fully integrated ocular screening technology. However, designing scalable and rapid contact lens processing methods while keeping a high resolution is still an unsolved challenge. In this article, femtosecond laser writing is employed as a rapid and precise procedure to engrave microfluidic networks into commercial contact lenses. Functional microfluidic components such as flow valves, resistors, multi-inlet geometries, and splitters are produced using a bespoke seven-axis femtosecond laser system, yielding a resolution of 80 µm. The ablation process and the tear flow within microfluidic structures is evaluated both experimentally and computationally using finite element modeling. Flow velocity drops of the 8.3%, 20.8%, and 29% were observed in valves with enlargements of the 100%, 200%, and 300%, respectively. Resistors yielded flow rate drops of 20.8%, 33%, and 50% in the small, medium, and large configurations, respectively. Two applications were introduced, namely a tear volume sensor and a tear uric acid sensor (sensitivity 16 mg L-1 ), which are both painless alternatives to current methods and provide reduced contamination risks of tear samples.


Cost-Utility Analysis of Molar Single Implant Versus Fixed Dental Prosthesis.
To calculate the incremental cost-effectiveness ratio (ICER) of prosthetic treatment of a single missing intermediate molar by performing cost-utility analysis on implants, insurance fixed dental prostheses (IFDPs), and private fixed dental prostheses (PFDPs). Transition probability (based on the results of past research) and the Markov model were used for cost-utility analysis, and Monte Carlo simulations were performed for sensitivity analysis. The utility values for various types of missing teeth were collected in September 2017, and dental prosthetic treatment was performed in general members of the Japanese population, distributed by sex and age. The time trade-off (TTO) method, which is an index scale (0-1), was used for measuring the utility values. The utility value was the highest when measured at the state in which implant treatment was performed and the lowest when measured in the untreated missing-tooth state. This model showed that compared to FDPs, implant treatment resulted in higher quality-adjusted life years (QALYs). However, the estimated cost over 30 years was lower for IFDPs. The results also showed that PFDPs were in a more extended, dominant state than both IFDPs and implants. The implant-to-IFDP ICER was €2,454.37. The results suggest that implants can be used to obtain higher utility values in comparison to IFDPs and PFDPs. The ICER threshold for 1 QALY in Japan is approximately €37,037 to €44,444, and the implant-to-IFDP ICER was found to be below that found in this study. Accordingly, it appears that implants offer superior cost-effectiveness.


Advance prediction of transthoracic impedance in human defibrillation and cardioversion: importance of impedance in determining the success of low-energy shocks.
The purposes of this study were to evaluate a method that predicts transthoracic impedance in advance of defibrillating shocks in humans and to assess the importance of transthoracic impedance in low-energy defibrillation. Via defibrillator electrodes we applied 31 kHz current to the chest during the defibrillator charge cycle, before the defibrillating shock was actually delivered. The current flow was limited by transthoracic impedance; a microprocessor monitored the predischarge current flow and determined the predischarge impedance by calibration against known resistance values. Actual impedance to the defibrillating shock was also determined and compared with the predicted impedance. With this approach we predicted impedance in 19 patients who received 66 shocks for ventricular and atrial arrhythmias. Predicted impedance (y) correlated very well with actual impedance (x):y = .90x + 11.3; r = .97. To determine the importance of impedance in defibrillation and cardioversion, we prospectively gathered data from 96 patients who received shocks of various energies for ventricular or atrial arrhythmias. In patients with high transthoracic impedance (greater than 97 omega), low-energy shocks (less than or equal to 100 J) for ventricular defibrillation had only a 20% success rate as opposed to a 70% success rate for low-energy shocks in patients with low or average impedance (p less than .05). We conclude that transthoracic impedance can be accurately predicted in advance of defibrillation and cardioversion. This method permits the preshock identification of patients with high impedance in whom attempts to defibrillate with low-energy shocks are inappropriate.


Outcome of 20-gauge transconjunctival cannulated sutureless vitrectomy using silicone oil or air tamponade.
The purpose of this study was to assess the outcome of pars plana vitrectomy using a 20-gauge transconjunctival cannulated sutureless system with air or silicone oil tamponade in cases of retinal detachment of different etiologies. A prospective study was performed in 60 eyes from consecutive 60 patients who underwent 20-gauge transconjunctival cannulated sutureless vitrectomy (30 eyes with air tamponade and 30 eyes with silicone oil tamponade), with the inclusion of a further 30 patients who underwent conventional 20-gauge vitrectomy and served as a control group. The main outcome measures were intraocular pressure, wound leakage, and comfort score. Preoperative intraocular pressure increased from 17.67 ± 5.6 mmHg preoperatively to 18.78 ± 6.1 mmHg on the first postoperative day in group A and decreased from 16.97 ± 4.9 mmHg to 15.88 ± 5.3 mmHg in group B. These changes were not statistically significant (P > 0.05). The comfort score ranged from 1 to 5 (1 = very bad, 2 = bad, 3 = good, 4 = very good, and 5 = excellent), with a mean of 4.4 ± 0.94 in group A and 4.35 ± 0.99 in group B on the first postoperative day, and no significant difference in scores between the groups at any follow-up visit. There was intraoperative wound leakage in two cases (6.7%) in group A which required suturing and one case (3.3%) in group B, but the difference was not statistically significant (P > 0.05). There was no wound leakage at follow-up in either group. No cases of hypotony, endophthalmitis, or unsealed sclerotomies were noted. Pars plana vitrectomy using a 20-gauge transconjunctival cannulated sutureless system combines the advantages of smaller-gauge vitrectomy systems with the economic advantage of not needing to purchase any additional handheld instruments. It can be used with both air and silicone oil tamponade in most cases of retinal detachment.


Molecular evolution allows bypass of the requirement for activation loop phosphorylation of the Cdc28 cyclin-dependent kinase.
Many protein kinases are regulated by phosphorylation in the activation loop, which is required for enzymatic activity. Glutamic acid can substitute for phosphothreonine in some proteins activated by phosphorylation, but this substitution (T169E) at the site of activation loop phosphorylation in the Saccharomyces cerevisiae cyclin-dependent kinase (Cdk) Cdc28p blocks biological function and protein kinase activity. Using cycles of error-prone DNA amplification followed by selection for successively higher levels of function, we identified mutant versions of Cdc28p-T169E with high biological activity. The enzymatic and biological activity of the mutant Cdc28p was essentially normally regulated by cyclin, and the mutants supported normal cell cycle progression and regulation. Therefore, it is not a requirement for control of the yeast cell cycle that Cdc28p be cyclically phosphorylated and dephosphorylated. These CDC28 mutants allow viability in the absence of Cak1p, the essential kinase that phosphorylates Cdc28p-T169, demonstrating that T169 phosphorylation is the only essential function of Cak1p. Some growth defects remain in suppressed cak1 cdc28 strains carrying the mutant CDC28 genes, consistent with additional nonessential roles for CAK1.


Leaching of indium from obsolete liquid crystal displays: comparing grinding with electrical disintegration in context of LCA.
In order to develop an effective recycling system for obsolete Liquid Crystal Displays (LCDs), which would enable both the leaching of indium (In) and the recovery of a pure glass fraction for recycling, an effective liberation or size-reduction method would be an important pre-treatment step. Therefore, in this study, two different types of liberation methods: (1) conventional grinding, and (2) electrical disintegration have been tested and evaluated in the context of Life Cycle Assessment (LCA). In other words, the above-mentioned methods were compared in order to find out the one that ensures the highest leaching capacity for indium, as well as the lowest environmental burden. One of the main findings of this study was that the electrical disintegration was the most effective liberation method, since it fully liberated the indium containing-layer, ensuring a leaching capacity of 968.5mg-In/kg-LCD. In turn, the estimate for the environmental burden was approximately five times smaller when compared with the conventional grinding.


The reverse shoulder prosthesis in the treatment of fractures of the proximal humerus in the elderly.
We have previously described the short-term outcome of the use of reverse shoulder arthroplasty in the treatment of acute complex proximal humeral fractures in the elderly. We now report the clinical and radiological outcome of 36 fractures at a mean of 6.6 years (1 to 16). Previously, at a mean follow-up of 6 years (1 to 12) the mean Constant score was 58.5; this was reduced to 53 points with the further follow-up. A total of 23 patients (63%) had radiological evidence of loosening of the glenoid component. Nevertheless, only one patient had aseptic loosening of the baseplate at 12 years' follow-up. The reduction in the mean Constant score with longer follow-up and the further development of scapular notching is worrying. New developments in design, bearing surfaces and surgical technique, and further follow-up, will determine whether reverse shoulder arthroplasty has a place in the management of complex proximal humeral fractures in the elderly.


Accuracy of myocardial sodium/iodide symporter gene expression imaging with radioiodide: evaluation with a dual-gene adenovirus vector.
The sodium/iodide symporter (NIS) gene allows convenient reporter imaging with gamma-cameras and free radioiodide. In this study, we investigated the accuracy of this technique for assessing myocardial gene expression in living rats by using a dual-gene adenovirus that expresses both NIS protein and enhanced green fluorescent protein (EGFP). Rats underwent myocardial injection with the dual-gene adenovirus (Ad.EGFP.NIS) or a control virus (Ad.EGFP). 123I scintigraphy was performed at day 4, and ratios of cardiac counts to mediastinal count were measured. The site of radiouptake was localized by use of dual-isotope 201Tl images, and radioiodide efflux rates were evaluated by dynamic imaging. The dependence of cardiac radiouptake on viral titers and the sensitivity of detection of cardiac radiouptake were investigated at various viral titers. The radioactivity, EGFP, and NIS protein expression sites were compared microscopically. The correlation of image-based uptake with fluorometric measurements of EGFP concentrations was assessed by regression analysis. 123I scintigraphy demonstrated clear focal myocardial uptake at the Ad.EGFP.NIS injection site, with relatively slow washout rates (3.3% +/- 0.8%/h), despite the absence of organification. Image-based cardiac uptake increased in a viral titer-dependent manner, with a detection threshold of between 3 x 10(6) and 1 x 10(7) plaque-forming units. Western blotting showed titer-dependent increases in myocardial NIS protein expression. Tissue radioactivity levels approached 12.5-fold control levels and correlated closely with image-based uptake (r = 0.91; P < 0.0001). Histologic analysis confirmed the colocalization of radiouptake, EGFP fluorescence, and NIS staining. Image-based uptake showed a strong correlation with fluorometric measurements of myocardial EGFP concentrations (r = 0.81; P < 0.0001). Our results demonstrate that convenient myocardial gene imaging with gamma-cameras and radioiodide is feasible with the NIS gene. Moreover, the use of this technique with a dual-gene vector appears to allow accurate assessment of the level of myocardial expression of a second gene of interest.


Variability of sputum inflammatory mediators in COPD and α1-antitrypsin deficiency.
There is inherent daily variability of sputum inflammatory mediators in stable-state patients with usual chronic obstructive pulmonary disease (COPD). The variability of pulmonary inflammation in patients with α(1)-antitrypsin deficiency (A1ATD) is unknown. Our study aimed to quantify this variability, in comparison to patients with usual COPD, in order to facilitate power calculations for proof of concept trials of putative specific anti-inflammatory agents in both groups. Sputum interleukin (IL)-8, myeloperoxidase (MPO), leukotriene B(4) (LTB(4)) and differential cell counts were measured in 12 usual COPD patients and 12 A1ATD patients on nine occasions over a 1-month period. All samples were obtained in the stable clinical state. There was significant daily variability in all mediators in all patients. A1ATD patients had higher sputum concentrations of IL-8 and LTB(4) compared with usual COPD, but lower levels of MPO and absolute neutrophil counts. Patients with usual COPD had more intra-patient variability, A1ATD patients demonstrated greater inter-patient variability. There are increased concentrations of pulmonary inflammatory mediators but fewer sputum neutrophils in A1ATD compared with usual COPD. The daily variability of inflammatory mediators and cell counts was significantly reduced in both groups by averaging sequential samples. This can be utilised to perform power calculations for future proof of concept studies; averaging three sequential samples appears optimum.


Mechanisms of Antimicrobial Resistance in ESKAPE Pathogens.
The ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) are the leading cause of nosocomial infections throughout the world. Most of them are multidrug resistant isolates, which is one of the greatest challenges in clinical practice. Multidrug resistance is amongst the top three threats to global public health and is usually caused by excessive drug usage or prescription, inappropriate use of antimicrobials, and substandard pharmaceuticals. Understanding the resistance mechanisms of these bacteria is crucial for the development of novel antimicrobial agents or other alternative tools to combat these public health challenges. Greater mechanistic understanding would also aid in the prediction of underlying or even unknown mechanisms of resistance, which could be applied to other emerging multidrug resistant pathogens. In this review, we summarize the known antimicrobial resistance mechanisms of ESKAPE pathogens.


Glutathionyl systems and metabolic dysfunction in obesity.
Oxidative stress is associated with obesity. However, glutathione (GSH), one of the body's most abundant antioxidants, plays dual and seemingly contradictory roles in the development of obesity and its comorbidities. Glutathione has complex metabolic and biochemical fates and is a cofactor for several enzymes that function in modifying obesity-related responses. For example, depletion of GSH increases energy metabolism and reduces adipose accretion, while elevation of GSH peroxidase activity induces insulin resistance. This review summarizes the literature linking GSH and its related enzymes, GSH peroxidase, glutaredoxins, and glutathione S-transferases, to obesity and its pertinent endpoints (e.g., energy metabolism, inflammation, and insulin resistance).


Effect of antibiotic therapy on nasal nitric oxide concentration in children with acute sinusitis.
Recently, it has been demonstrated that paranasal sinuses are an important site of nitric oxide (NO) production in the upper airways. The aim of this study was to evaluate the NO nasal concentration in children with acute maxillary sinusitis before and after treatment with antibiotic therapy. We performed NO nasal measurements in 16 children 4 to 13 yr of age with acute maxillary sinusitis and compared values with 16 age- and sex-matched healthy control subjects. The diagnosis of acute sinusitis was done by clinical signs and symptoms in addition to radiographic examination. NO nasal concentrations were measured by a chemiluminescence analyzer. Nasal NO steady state during oral breathing was recorded. The mean +/- SEM NO nasal concentration in children with sinusitis was 70 +/- 8.7 parts per billion (ppb) and increased significantly to 220 +/- 15 ppb (p < 0.001) after antibiotic therapy (amoxicillin/clavulanate). NO values after recovery from sinusitis were similar to those of healthy control subjects (245 +/- 15 ppb, p = NS). NO nasal measurements were also performed before and after antibiotic treatment in nine children 4 to 12 yr of age with symptoms of upper respiratory tract infection but no symptoms of sinusitis. In these children NO nasal levels were 249 +/- 32 ppb and did not change (p = NS) after antibiotic therapy. We conclude that during acute maxillary sinusitis the concentration of nasal NO is largely decreased, probably because of an impaired flow of NO from the paranasal sinuses, and that NO returns to normal levels after antibiotic therapy.


Molluscicidal activity of Nicotiana tabacum extracts on the invasive snail Pomacea canaliculata.
Botanical molluscicides for controlling the invasive snail Pomacea canaliculata have attracted worldwide attention because of their cost and environmental friendliness. Aqueous extracts from discarded tobacco leaf (Nicotiana tobacum) were evaluated for molluscicidal activity against different-sized P. canaliculata under laboratory conditions. The results showed that over 90% of the snails died in 1 g/L tobacco extract within 4 days, and the survival of P. canaliculata was inversely proportional to the snail size, tobacco extract concentration and length of exposure time. Adult males were more susceptible to tobacco extract than females. The snails had few chances to feed or mate in 0.5 g/L tobacco extract, and reproduction was greatly limited in 0.2 g/L. The growth of juvenile snails was inhibited in 0.2 g/L tobacco extract, but adults were unaffected. The antioxidant capacity of P. canaliculata in response to tobacco extract can be size- and sex-dependent, and the activities of superoxide dismutase, catalase, and acetylcholinesterase and the contents of glutathione and malondialdehyde were increased in adult males. These results suggest that discarded tobacco leaves can be useful as a molluscicide for controlling the invasive snail P. canaliculata based on its effects on survival, behaviour, food intake, growth performance and antioxidant capacity.