Equity in public health spending in Ethiopia: a benefit incidence analysis.
Inequality in access and utilization of health services because of socioeconomic status is unfair, and it should be monitored and corrected with appropriate remedial action. Therefore, this study aimed to estimate the distribution of benefits from public spending on health care across socioeconomic groups in Ethiopia using a benefit incidence analysis. We employed health service utilization data from the Living Standard Measurement Survey, recurrent government expenditure data from the Ministry of Finance and health services delivery data from the Ministry of Health's Health Management Information System. We calculated unit subsidy as the ratio of recurrent government health expenditure on a particular service type to the corresponding number of health services visits. The concentration index (CI) was applied to measure inequality in health care utilization and the distribution of the subsidy across socioeconomic groups. We conducted a disaggregated analysis comparing health delivery levels and service types. Furthermore, we used decomposition analysis to measure the percentage contribution of various factors to the overall inequalities. We found that 61% of recurrent government spending on health goes to health centres (HCs), and 74% was spent on outpatient services. Besides, we found a slightly pro-poor public spending on health, with a CI of -0.039, yet the picture was more nuanced when disaggregated by health delivery levels and service types. The subsidy at the hospital level and for inpatient services benefited the wealthier quintiles most. However, at the HC level and for outpatient services, the subsidies were slightly pro-poor. Therefore, an effort is needed in making inpatient and hospital services more equitable by improving the health service utilization of those in the lower quintiles and those in rural areas. Besides, policymakers in Ethiopia should use this evidence to monitor inequity in government spending on health, thereby improving government resources allocation to target the disadvantaged better.


Rahnella perminowiae sp. nov., Rahnella bonaserana sp. nov., Rahnella rivi sp. nov. and Rahnella ecdela sp. nov., isolated from diverse environmental sources, and emended description of the genus Rahnella.
Bacteria isolated from onion bulbs suffering from bacterial decay in the United States and Norway were previously shown to belong to the genus Rahnella based on partial housekeeping gene sequences and/or fatty acid analysis. However, many strains could not be assigned to any existing Rahnella species. Additionally, strains isolated from creek water and oak as well as a strain with bioremediation properties were assigned to Rahnella based on partial housekeeping gene sequences. The taxonomic status of these 21 strains was investigated using multilocus sequence analysis, whole genome analyses, phenotypic assays and fatty acid analysis. Phylogenetic and phylogenomic analyses separated the strains into five clusters, one of which corresponded to Rahnella aceris. The remaining four clusters could be differentiated both genotypically and phenotypically from each other and existing Rahnella species. Based on these results, we propose the description of four novel species: Rahnella perminowiae sp. nov. (type strain SL6T=LMG 32257T=DSM 112609T), Rahnella bonaserana sp. nov. (H11bT=LMG 32256T=DSM 112610T), Rahnella rivi sp. nov. (FC061912-KT=LMG 32259T=DSM 112611T) and Rahnella ecdela sp. nov. (FRB 231T=LMG 32255T=DSM 112612T).


Salicylic Acid Improves Antioxidant Defense System and Photosynthetic Performance in Aristotelia chilensis Plants Subjected to Moderate Drought Stress.
Salicylic acid (SA) has been shown to ameliorate drought stress. However, physiological and biochemical mechanisms involved in drought stress tolerance induced by SA in plants have not been well understood. Thus, this study aimed to study the role of SA application on enzymatic and non-enzymatic antioxidants, photosynthetic performance, and plant growth in A. chilensis plants subjected to moderate drought stress. One-year-old A. chilensis plants were subjected to 100% and 60% of field capacity. When plants reached moderate drought stress (average of stem water potential of -1.0 MPa, considered as moderate drought stress), a single SA application was performed on plants. Then, physiological and biochemical features were determined at different times during 14 days. Our study showed that SA application increased 13.5% plant growth and recovered 41.9% AN and 40.7% gs in drought-stressed plants on day 3 compared to drought-stressed plants without SA application. Interestingly, SOD and APX activities were increased 85% and 60%, respectively, in drought-stressed SA-treated plants on day 3. Likewise, SA improved 30% total phenolic content and 60% antioxidant capacity in drought-stressed A. chilensis plants. Our study provides insight into the SA mechanism to tolerate moderate drought stress in A. chilensis plants.


Characterization of corticotropin-releasing hormone binding protein in human plasma by chemical cross-linking and its binding during pregnancy.
A human plasma CRH-binding protein (CRH-BP) was identified and characterized by chemical cross-linking of 125I-Tyr-hCRH to human plasma using disuccinimidyl suberate. The apparent mol wt of the cross-linked complex determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by autoradiography was approximately 43,000. The mol wt was slightly lower in the nonreduced state, suggesting the presence of intramolecular disulfide bonds. Subtracting the mol wt of 125I-Tyr-CRH, the BP appeared to have a mol wt of approximately 38,000. Binding was specific since the appearance of the 43,000 dalton band was not affected by unlabeled ACTH, vasopressin, serum albumin, or gamma-globulin, but was inhibited by unlabeled hCRH dose dependently. Pretreatment of plasma with 0.1 mol/L HCl, 0.01 mol/L NaOH, 10 mmol/L dithiothreitol, or trypsin before cross-linking abolished its ability to bind 125I-Tyr-hCRH. Rat, rabbit, or goat plasma or human cerebrospinal fluid did not bind 125I-Tyr-CRH. It is unlikely that CRH-BP is a CRH receptor, because the estimated mol wt of the CRH-BP is smaller than the reported size of CRH receptors, and the CRH-BP did not bind to ovine CRH. The binding of 125I-Tyr-CRH to CRH-BP decreased in the third trimester of pregnancy, when plasma CRH levels were markedly elevated. However, after dissociating endogenous CRH from the CRH-BP, the binding was almost the same as in nonpregnant subjects. In addition, CRH-BP inhibited CRH-induced ACTH secretion from cultured rat anterior pituitary cells. We conclude that most of the increased plasma CRH found in pregnant women is bound to CRH-BP, and so is inactive, therefore plasma ACTH levels do not increase to above the normal range.


Barriers to utilization of chronic peritoneal dialysis in network #1, New England.
The percentage of prevalent end-stage renal disease (ESRD) patients maintained on chronic peritoneal dialysis (CPD) therapy in the United States declined from 15% in 1991 to 8.1% in 2002. Previous studies indicate that nephrologists in the United States feel 32.6% of prevalent ESRD patients should be on CPD therapy. The present study was designed to better understand the reasons for the discrepancy in actual versus desired prevalence of CPD utilization. The medical directors of all dialysis centers in New England were mailed a questionnaire about the nephrologists' opinions concerning the percentage of patients that should be maintained on CPD therapy, reasons that limited patients' selection of CPD as initial therapy, and concerns about the current status of CPD therapy. The nephrologists were also invited to free text any other comments or concerns. A total of 117 questionnaires were sent; 59 (50.4%) were returned. These medical directors cared for a median of 10 (range 1 - 100) patients on CPD therapy, meaning 15% of dialysis patients in New England are maintained on CPD therapy. The medical directors felt that 29% (range 10% - 50%) of prevalent ESRD patients should be maintained on CPD therapy. The most common reasons cited by the nephrologists as barriers to CPD therapy included patient preference (54%), contraindications to performing CPD therapy (32%), poor social support (31%), significant comorbid disease (20%), late referrals and acute hospital starts (19%), problems with education re chronic kidney disease (12%), and problems with the structure and organization of CPD facilities (12%). These same medical directors stated that concerns about technique failure (25%), long-term viability of CPD therapy (25%), and mortality rates of CPD patients (17%) impacted on their use of CPD therapy as renal replacement therapy for patients with ESRD. Nephrologists in New England felt that 29% of prevalent ESRD patients should be maintained on CPD therapy, yet the actual incidence of CPD utilization in New England is 15%. A variety of factors were cited by the nephrologists as important reasons limiting CPD utilization. These nephrologists were also concerned about technique failure and long-term viability of CPD therapy. It is necessary that we look closely at each domain cited by the nephrologists if CPD therapy is to remain a viable option for patients with ESRD in the United States.


Primer: using decision analysis to improve clinical decision making in urology.
Many clinical decisions in urology involve uncertainty about the course of disease or the effectiveness of treatment. Many decisions also involve trade-offs; for example, an improvement in patient survival at the cost of an increased risk of treatment-related adverse effects. Decision analysis is a formal, quantitative method for systematically comparing the benefits and harms of alternative clinical strategies under circumstances of uncertainty. The basic steps in performing a decision analysis are to define the clinical scenario or problem, identify the clinical strategies to be considered in the decision, enumerate all of the important sequelae of each strategy and their associated probabilities, define the outcome of interest, and assign a value to each possible outcome. Health outcomes can be defined in a number of ways, including quality-adjusted survival. A key aspect of decision analysis is allowing the values of particular health outcomes to vary from patient to patient, depending on individual preferences. Decision analysis has already been used to assess a variety of prevention, screening and treatment decisions in urology, and there is much potential for its future application. Greater incorporation of decision-analytic techniques into urology research and clinical practice might improve decision making, and thereby improve patient outcomes.


Exploration of MnFeO3/Multiwalled Carbon Nanotubes Composite as Potential Anode for Lithium Ion Batteries.
MnFeO3, investigated for its application in sensors, catalysis, and semiconductors, was explored for the first time as anode for lithium ion batteries in the form of MnFeO3/multiwalled carbon nanotubes (MWCNT) composite. A scalable and highly reproducible sonochemical process was adopted to form the composite, wherein the interweaved MWCNT ensures better electronic conductivity and pinning of pristine MnFeO3 particles with a conductive coating. MnFeO3/MWCNT composite anode exhibits superior electrochemical properties than pristine MnFeO3 anode in such a manner that a steady-state reversible capacity of 840 mAh g-1 was obtained at 0.5 A g-1 even after 50 cycles against an inferior capacity of 200 mAh g-1 offered by MnFeO3. Further, MnFeO3/MWCNT composite anode shows excellent rate capability and reversibility by way of delivering appreciable capacity values of 2960 and 410 mAh g-1 at 0.5 and 10 A g-1, respectively. These results suggest that the currently synthesized MnFeO3/MWCNT nanocomposite anode could be considered as a promising candidate for next-generation hybrid energy storage applications. The study is bestowed with the identification and demonstration of earth-abundant, environment-friendly, and low-cost metals, specifically, Mn- and Fe-based composite anodes for high capacity and high rate lithium ion battery applications, which is noteworthy.


Iloprost: intracellular Ca(2+)-dependent contractile effect on isolated smooth muscle cells from guinea-pig ileum.
Prostaglandin E2 (PGE2) and iloprost induced a concentration-dependent contraction of smooth muscle cells isolated from the circular layer of guinea-pig ileum. PGE2- and iloprost-induced contractions were inhibited by the selective EP1-receptor antagonist, SC19220 (1-acetyl-2-(8-chloro-10, 11-dihydrodibenz (b,f) (1,4) oxazepine-10-carbonyl)-hydrazine), indicating the involvement of the EP1 subtype of the PGE2 receptor. When cells were incubated for 10 min in the presence of strontium (4 mM L-1), an inhibitor of the release of Ca2+ from intracellular store, the contractile effect of PGE2 and iloprost was inhibited. In contrast, incubation of cells in Ca/2+)-free medium, Ca(2+)-free medium plus EGTA, or in the presence of nifedipine, an organic Ca(2+)-channel blocker, did not alter the PGE2- and iloprost-induced contraction. These observations suggest that the myogenic effect of PGE2 and iloprost on intestinal smooth muscle is dependent on the release of intracellular calcium.


Unusual complication of coarctation of the aorta.
The majority of older patients with uncorrected coarctation of the aorta die before the age of 50 years from many complications. We report our experience in treating this type of congenital malformation in a 40-year-old man who developed aortic endarteritis as a rare complication.


Nitrogen dioxide formation during inhaled nitric oxide therapy.
Nitrogen dioxide (NO2) is a toxic by-product of inhalation therapy with nitric oxide (NO). The rate of NO2 formation during NO therapy is controversial. The formation of NO2 was studied under dynamic flows emulating a base case NO ventilator mixture containing 80 ppm NO in a 90% oxygen matrix. The difficulty in measuring NO2 concentrations below 2 ppm accurately was overcome by the use of tunable diode laser absorption spectroscopy. Using a second-order model, the rate constant, k, for NO2 formation was determined to be (1.19 +/- 0.11) x 10(-11) ppm-2s-1, which is in basic agreement with evaluated data from atmospheric literature. Inhaled NO can be delivered safely in a well-designed, continuous flow neonatal ventilatory circuit, and NO2 formation can be calculated reliably using the rate constant and circuit dwell time.


Uterine expression of prostaglandin H2 synthase in late pregnancy and during parturition in prostaglandin F receptor-deficient mice.
PG production in uterine tissues is important for many physiological processes in late pregnancy, including parturition. We examined the expression of the PGH2 synthases, cyclooxygenase-1 (COX-1) and COX-2, in uterine tissues during late pregnancy, using PGF receptor-deficient (FP-/-) mice. Female FP-/- mice are unable to deliver normal fetuses at term, as they do not undergo luteolysis necessary for parturition. In wild-type mice, COX-1 messenger RNA (mRNA) was expressed in the endometrial epithelium, myometrium, and decidua throughout late pregnancy. The expression of COX-1 mRNA in the endometrial epithelium and myometrium decreased both in wild-type mice undergoing natural parturition and in FP-/- mice undergoing ovariectomy-induced parturition, but expression of COX-1 mRNA was enhanced in FP-/- mice at the expected term. In wild-type mice, COX-2 mRNA was not expressed in the myometrium before parturition, but was markedly induced during parturition. This induction of COX-2 was absent in FP-/- mice at the expected term, but was found during ovariectomy-induced parturition in these mice. Expression of COX-2 proteins was confirmed by immunohistochemical analysis. Thus, in uterine tissues, myometrial expression of COX-2 is closely associated with the occurrence of parturition, but uterine expression of COX-1 is induced much earlier and kept at a high level until parturition occurs. These results suggest that COX-1-derived PGs are responsible for the induction of luteolysis, and that COX-2-derived PGs play a role in the final pathway of parturition.


[Analysis of clinical phenotype and genotype of unstable Hemoglobin Rush].
To analyze the hematological and genetic characteristics of unstable hemoglobin Rush (Hb Rush) and compound heterozygote of Hb Rush and thalassemia. Peripheral blood samples and genomic DNA from three patients (including two ethnic Dai and one Han Chinese) with anemia of undetermined origin were collected. Hematological phenotypes of these patients were determined through red blood cell analysis and hemoglobin electrophoresis. Genotypes of alpha- and beta-globin genes, -158 XmnⅠ polymorphic site of Gγ promoter region, and haplotypes of 7 polymorphic restriction sites in the beta-globin gene cluster were determined using PCR-based methods and DNA sequencing. All patients have presented hypochromic microcytic anemia and hemoglobin fraction with significant increased measurement (30.5%-59.2%) in the region of fetal hemoglobin during alkaline medium electrophoresis. DNA analysis suggested that all patients have carried mutations leading to the unstable hemoglobin Rush (HBB codon 101, GAG>CAG, Glu>Gln). Two of them were compound heterozygotes of Hb Rush and thalassemia mutations of -α 3.7,CD17 and Hb E, respectively. Hb Rush mutation was associated with various haplotypes of the β-globin gene cluster. No significant association was found between increased abnormal hemoglobin fraction in the region of Hb F and the polymorphism of Gγ promoter or large deletion of the beta-globin gene cluster. This study has confirmed the distribution of Hb Rush among various Chinese populations and is the third report of its kind. Hb Rush can result in increased measurement of hemoglobin fraction in the region of fetal hemoglobin (Hb F) during routine hemoglobin electrophoresis under alkaline condition. Hb Rush heterozygote alone can lead to hypochromic microcytic anemia and thalassemia-like phenotype. Prenatal diagnosis of Hb Rush is necessary for carriers.


Budesonide/formoterol in a single inhaler versus inhaled corticosteroids alone in the treatment of asthma.
The aim of this study was to evaluate the efficacy (expressed as effect on lung function) and tolerability of Symbicort (budesonide/formoterol in a single inhaler) in children with asthma. This was a double-blind, double-dummy, randomized, parallel-group, multicenter trial. After a 2-4-week run-in period, 286 asthmatic children (177 boys, 109 girls; mean age, 11 years; mean forced expiratory volume in 1 sec (FEV(1)), 75% predicted normal), previously treated with inhaled corticosteroids (average dose 548 microg/day), were randomized to 12 weeks' treatment with either budesonide/formoterol 80/4.5 microg, two inhalations twice daily (n = 148), or an equivalent dose of budesonide 100 microg, two inhalations twice daily (n = 138). Efficacy variables included morning and evening peak expiratory flow (PEF), spirometery, asthma symptoms, and use of rescue medication (beta(2)-agonists). Serial FEV(1) assessments were carried out on a subgroup of children (budesonide/formoterol, n = 41; budesonide, n = 40) at randomization and at week 12. Relative to baseline, morning PEF (primary variable) increased to a significantly greater extent with budesonide/formoterol than with budesonide alone (7.22% predicted normal vs 3.45% predicted normal; P < 0.001). Evening PEF also increased significantly with budesonide/formoterol (6.13% predicted normal vs. 2.73% predicted normal; P < 0.001), as did mean FEV(1) and serial FEV(1) measured over 12 hr (both P < 0.05). Similar improvements in asthma symptoms and rescue medication use were observed in both groups. The two treatment groups were similar in terms of their adverse-event profile and rates of discontinuation. Budesonide/formoterol in a single inhaler provided rapid improvements in PEF and FEV(1) compared to inhaled budesonide alone. These improvements were sustained throughout the study period. Budesonide/formoterol was well-tolerated in children with moderate persistent asthma.


Prospective randomized controlled study of a microfluidic chip technology for sperm selection in male infertility patients.
The purpose of this study is to evaluate the impact of a microfluidic approach for spermatozoon selection in male infertility patients undergoing intracytoplasmic sperm injection (ICSI). This research enrolled 128 individuals who had ICSI for male-factor infertility. The patients were separated into two groups according to the method used to pick the spermatozoa: group I (n = 64), which used traditional swim-up procedures, and group II (n = 64), which used the Fertile Chip for spermatozoon selection during ICSI therapy. Fertilization rates and embryo quality were the major outcomes. The rates of pregnancy, clinical pregnancy and live birth were used as secondary outcomes. As a result, there was no statistically significant difference between the two groups in terms of fertilization rate, total grade 1 and 2 embryos. Implantation rate was significantly higher in the Fertile Chip group than in the control group (50% vs. 31%, p = 0.02). The Fertile Chip group had considerably greater pregnancy rates, clinical pregnancy rates (CPR) and live birth rates than the control group (62.5% vs. 45.3%, p = 0.038; 59.4% vs. 35.9%, p = 0.006 and 46.8% vs. 25%, p = 0.009). Fertile Chip had no effect on fertilization rates or embryo quality in male-factor infertility couples. However, the Fertile Chip group had a statistically higher pregnancy rate, CPR and live birth rate.


Comparison of the effects of lovastatin and gemfibrozil on lipids and glucose control in non-insulin-dependent diabetes mellitus.
Patients with non-insulin dependent diabetes mellitus have an increased incidence of coronary artery disease which may, in part, be associated with abnormalities in plasma lipids. In a double-blind, parallel, randomized study, lovastatin and gemfibrozil were compared in 102 diabetic patients with primary hypercholesterolemia; two-thirds of the patients were treated with oral hypoglycemic agents and one-third received diet therapy alone for their diabetes. Mean pretreatment total and low-density lipoprotein (LDL) cholesterol values were 273 and 193 mg/dl, respectively. Lovastatin significantly reduced total, LDL and very low density lipoprotein cholesterol (20, 26 and 28%, respectively) and raised high-density lipoprotein (HDL) cholesterol (14%). Gemfibrozil significantly reduced triglycerides and very low density lipoprotein cholesterol (36 and 41%, respectively) and, to a lesser extent, total cholesterol (9%); it also increased HDL cholesterol (21%). Lovastatin therapy was not associated with a significant change in triglycerides, and gemfibrozil did not significantly lower LDL cholesterol. The decrease in the ratio of total to HDL cholesterol tended to be greater with lovastatin than with gemfibrozil (26.5 and 20.4%, respectively; p = 0.053). Changes in lipid profiles with both agents were of a degree similar to those reported in nondiabetic patients. Neither agent had a clinically important effect on fasting glucose or hemoglobin A1c. Both drugs were well tolerated with the exception of 2 patients treated with gemfibrozil who developed symptoms of cholecystitis.


Cardiac Progenitor Cells in Myocardial Infarction Wound Healing: A Critical Review.
Coronary artery disease is a major cause of morbidity and mortality as the loss of functional myocardium drives progressive ventricular remodeling and subsequent heart failure. Medical management has significantly improved outcomes for acute myocardial infarction (MI); however, improved strategies are needed to regenerate functional myocardium and prevent the progression to heart failure. Cytotherapy using cardiac progenitor cells (PCs) to regenerate functional myocardium holds tremendous potential; however, a better understanding of PC biology is needed. Reports of cardiac regeneration in lower animals have been reported in the last decade. However, just recently, two separate models of mammalian cardiac regeneration have been published and offer potential to better define PC biology, including PC recruitment, differentiation, proliferation, and integration. Numerous clinical trials have been completed or are ongoing to evaluate possible cytotherapy options in the treatment of acute and chronic ischemic cardiac disease. To date, results have demonstrated improvements in cardiac function as a result of paracrine effects of cytotherapy, but regeneration of functional myocardium has yet to be observed. Future translation of cardiac PC biology from these models is necessary to promote regenerative cardiac healing following MI and to prevent the progression to heart failure following the loss of functional myocardium. Knowledge gained from mammalian models of cardiac regeneration will allow for the development of therapeutic regimens in the treatment of heart failure.


Cataracts among cancer survivors.
To determine the frequency of cataracts in cancer survivors and their association with patients' demographic characteristics, treatment, and cancer type and the perceived effect cancer had had on their overall health. This was a descriptive, cross-sectional review of the results of a survey of long-term cancer survivors who had been treated at the authors' institution. Of 3936 respondents to the survey, 168 (4%) reported having had cataracts. Cataracts were most frequent in survivors of hematologic diseases (chronic leukemia, 17%; myeloma, 13%; acute leukemia, 9%; and lymphoma, 7%). There were no notable associations between cataracts and gender, age, ethnicity, marital status, education completed, or work status. Cancer survivors with cataracts were more likely to report that cancer had affected their overall health (56% vs 39%). There was a trend of association between cataracts and prior treatment with bone marrow transplantation, but not corticosteroids. Cataracts affect a minority of long-term cancer survivors, but those who reported them were more likely to report that cancer had had a lasting effect on their overall health. Vision evaluation for all cancer survivors is recommended.


Genotoxicity assessment using micronuclei assay in rheumatoid arthritis patients.
This study investigated whether: (i) rheumatoid arthritis (RA) patients have more micronuclei (MN) than healthy controls; (ii) methotrexate (MTX) treated RA patients have more MN than those not using MTX, and (iii) folic acid supplementation decreases the number of MN in MTX treated patients. MN assays were performed in oral mucosa sweeps of 50 consecutive MTX treated RA patients, 30 consecutive RA patients not receiving MTX and 39 healthy controls. MTX treated RA patients were then randomly placed in a cross-over design to receive folic acid supplementation, and MN assays were repeated after 6 weeks. The MTX-RA patients had a mean age of 46 +/- 10 yrs and a mean disease duration of 12 +/- 9 yrs; 80% were women. The MTX dose range was 8.7 +/- 1.5 mg/week and the mean duration of use was 16 +/- 18 months. In the non-MTX RA group, the mean age was 48 +/- 14 yrs, the mean disease duration was 13 +/- 9 yrs, and 87% were women. At baseline, the number of MN were significantly higher in RA patients as compared with controls (3.31 +/- 2.3 vs 0.8 +/- 0.8, p <0.001). No difference in MN numbers was observed between users and non-users of MTX. Folic acid supplementation did not decrease the MN number in the MTX treated RA patients. Genotoxicity, as assessed by the MN assay, is increased in RA patients. These results suggest that genotoxicity is associated with RA itself and not with MTX use. Folic acid supplementation had no effect on the number of MN.


Open gastrostomy for noninvasive ventilation users with neuromuscular disease.
To report open gastrostomy for ventilator-assisted or -supported patients with altered nutritional status as a result of severe dysphagia and without tracheostomy, translaryngeal intubation, or general anesthesia. Avoiding intubation and general anesthesia decreases the risk of respiratory complications and can prolong noninvasive respiratory management. The procedure was performed for 62 noninvasive intermittent positive-pressure ventilation users: 44 with amyotrophic lateral sclerosis, 10 with muscular dystrophy including 6 with Duchenne muscular dystrophy, and 8 with other conditions. All had vital capacities <40% of predicted normal. Noninvasive intermittent positive-pressure ventilation was provided in ambient air before, during, and after the procedure. Oxyhemoglobin saturation was maintained at 95% or greater and end-tidal CO2 <40 cm H2O by noninvasive intermittent positive-pressure ventilation and mechanically assisted coughing. There were no complications of the procedure. All patients gained weight subsequently. Mean postgastrostomy survival was 38.8 +/- 6.2 mos with 26 of the patients still alive. Eighteen of the 62 patients had no ventilator-free breathing ability before, during, or after the gastrostomy. Fifty-one patients eventually lost all ventilator-free breathing abilities without tracheostomy. Open gastrostomy can be performed safely without airway intubation or general anesthesia for patients with little or no autonomous breathing ability. It permitted continued survival without tracheostomy despite loss of all ventilator-free breathing abilities for 51 patients.


Kratom: Substance of Abuse or Therapeutic Plant?
Kratom is the common term for Mitragyna speciosa and its products. Its major active compounds are mitragynine and 7-hydroxymitragynine. An estimated 2.1 million US residents used kratom in 2020, as a "legal high" and self-medication for pain, opioid withdrawal, and other conditions. Up to 20% of US kratom users report symptoms consistent with kratom use disorder. Kratom use is associated with medical toxicity and death. Causality is difficult to prove as almost all cases involve other psychoactive substances. Daily, high-dose use may result in kratom use disorder and opioid-like withdrawal on cessation of use. These are best treated with buprenorphine.


Implementation of team-based learning on a large scale: Three factors to keep in mind.
Team-based learning (TBL) is a structured form of small group learning that can be scaled up for delivery in large classes. The principles of successful TBL implementation are well established. TBL has become widely practiced in medical schools, but its use is typically limited to certain courses or parts of courses. Implementing TBL on a large scale, across different courses and disciplines, is the next logical step. The Lee Kong Chian School of Medicine (LKCMedicine), a partnership between Nanyang Technological University, Singapore and Imperial College London, admitted its first students in 2013. This new undergraduate medical program, developed collaboratively by faculty at both institutions, uses TBL as its main learning and teaching strategy, replacing all face-to-face lectures. TBL accounts for over 60% of the curriculum in the first two years, and there is continued learning through TBL during campus teaching in the remaining years. This paper describes our experience of rolling out TBL across all years of the medical curriculum, focusing on three success factors: (1) "team-centric" learning spaces, to foster active, collaborative learning; (2) an e-learning ecosystem, seamlessly integrated to support all phases of the TBL process and (3) teaching teams in which experts in pedagogical process (TBL Facilitators) co-teach with experts in subject matter (Content Experts).


Willingness to engage in casual sex : The role of parental qualities and perceived risk of aggression.
Sexually dimorphic mate selection strategies were examined in 200 university students reporting their willingness to engage in casual sexual encounters with hypothetical individuals of the opposite sex. Using a questionnaire format, the possibility of forming a long-term relationship was manipulated, while risk of disease, pregnancy, and detection was eliminated across all conditions. In addition, potential partners varied in level of attractiveness, and in personality and behavioral characteristics. As expected, men reported a greater anticipated willingness to engage in sexual intercourse across all conditions compared with women. The possibility of forming a long-term relationship elevated women's, but not men's, willingness for sexual intercourse. While a potential partner's attractiveness had a significant positive overall effect on responses, reducing their relative attractiveness had a greater negative impact on men's responses. Reference to the parental qualities of a potential partner significantly increased women's, but not men's, anticipated willingness for sexual intercourse. Describing a hypothetical partner as non-aggressive (safe) marginally increased women's willingness (p<.09) and did not affect men's responses. The wording of items relevant to this condition may have resulted in the potential partner sounding "wimpy" rather than nonaggressive, and this may have reduced the expected effect of this manipulation. The possibility that women may trade off personality and behavioral characteristics with attractiveness to a greater degree than men when assessing potential mates is considered.


Short- and Long-Term Immunological Responses in Chronic HCV/HIV Co-Infected Compared to HCV Mono-Infected Patients after DAA Therapy.
Direct-acting antivirals (DAAs) treatment, although highly efficacious for the treatment of hepatitis C virus (HCV) infection, may not completely reconstitute the HCV-mediated dysregulated immune system, especially in patients co-infected with human immunodeficiency virus (HIV) and HCV. We aimed to evaluate the impact of HCV eradication following DAA therapy on the immune system and liver disease improvement through comparative monitoring of 10 HCV mono-infected and 10 HCV/HIV co-infected patients under combined antiretroviral therapy (cART). Early and late longitudinal phenotypic changes in peripheral blood mononuclear cell (PBMC) subsets, T-cell activation, differentiation and exhaustion, as well as inflammatory biomarkers, indoleamine 2-3 dioxygenase (IDO) activity, and liver stiffness, APRI and FIB-4 scores were assessed. Samples were obtained at baseline (T0), week 1 (T1), week 2 (T2), week 12 (T3, end of treatment, EOT), and month 9 (T4, end of follow-up, 36 weeks post EOT). All patients achieved a sustained virological response (SVR 12) after DAA treatment. Overall, changes of the T-cell immune phenotypes were greater in HCV/HIV co-infected than in HCV mono-infected, due to an increase in CD4+ and CD8+ T-cell percentages and of CD8+ T-cell activation and memory markers, in particular at the end of follow-up. On the other end, HCV mono-infected showed changes in the activation profile and in the memory CD4+ T-cell compartment. In HCV/HIV co-infected, a decrease in the IDO activity by DAA treatment was observed; conversely, in HCV mono-infected, it resulted unmodified. Regarding inflammatory mediators, viral suppression was associated with a reduction in IP-10 levels, while interferon regulatory factor (IRF)-7, interferon (IFN)-β, and interferon (IFN)-γ levels were downregulated during therapy and increased post therapy. A decrease in liver stiffness, APRI, and FIB-4 scores was also observed. Our study suggests that, although patients achieved HCV eradication, the immune activation state in both HCV mono-infected and HCV/HIV co-infected patients remains elevated for a long time after the end of DAA therapy, despite an improvement of liver-specific outcomes, meanwhile highlighting the distinct immunophenotypic and inflammatory biomarker profile between the groups of patients.


Feasibility of a prehabilitation program before major abdominal surgery: a pilot prospective study.
To assess the feasibility of a prehabilitation program and its effects on physical performance and outcomes after major abdominal surgery. In this prospective pilot study, patients underwent prehabilitation involving three training sessions per week for 3 weeks preoperatively. The feasibility of delivering the intervention was assessed based on recruitment and adherence to the program. Its impacts on fitness (oxygen uptake (VO2)) and physical performance (Timed Up and Go Test, 6-Minute Walk Test) were evaluated. From May 2017 to January 2020, 980 patients were identified and 44 (4.5%) were invited to participate. The main obstacles to patient recruitment were insufficient time (<3 weeks) prior to scheduled surgery (n = 276, 28%) and screening failure (n = 312, 32%). Of the 44 patients, 24 (55%) declined to participate, and 20 (23%) were included. Of these, six (30%) were not adherent to the program. Among the remaining 14 patients, VO2 at ventilatory threshold significantly increased from 9.7 to 10.9 mL/min/kg. No significant difference in physical performance was observed before and after prehabilitation. Although prehabilitation seemed to have positive effects on exercise capacity, logistic and patient-related difficulties were encountered. The program is not feasible in its current form for all-comers.


Development of enhanced antibody response toward dual delivery of nano-adjuvant adsorbed human Enterovirus-71 vaccine encapsulated carrier.
This study introduces a new approach for enhancing immunity toward mucosal vaccines. HEV71 killed vaccine that is formulated with nanosize calcium phosphate adjuvant and encapsulated onto chitosan and alginate delivery carriers was examined for eliciting antibody responses in serum and saliva collected at weeks 0, 1, 3, 5, 7 and 9 for viral-specific IgA & IgG levels and viral neutralizing antibody titers. The antibody responses induced in rabbits by the different formulations delivered by a single (buccal) route were compared to those of dual immunization (intradermal / mucosal) and un-immunized control. Chitosan-loaded vaccine adjuvant induced elevated IgA antibody, while Alginate-adjuvant irreversible bonding sequestered the vaccine and markedly reduced immunogenicity. The induced mucosal and parenteral antibody profiles appeared in an inverse manner of enhanced mucosal IgA antibody accompanied by lower systemic IgG following a single oral immunization route. The combined intradermal and oral dual-immunized group developed an elevated salivary IgA, systemic IgG, and virus neutralizing response. A reduced salivary neutralizing antibody titer was observed and attributed to the continual secretion exchanges in saliva. Designing a successful mucosal delivery formulation needs to take into account the vaccine delivery site, dosage, adjuvant and carrier particle size, charge, and the reversibility of component interactions. The dual immunization seems superior and is a important approach for modulating the antibody response and boosting mucosal protection against HEV71 and similar pathogens based on their transmission mode, tissue tropism and shedding sites. Finally, the study has highlighted the significant role of dual immunization for simultaneous inducing and modulating the systemic and mucosal immune responses to EV71.


RNA footprinting analysis using ion pair reverse phase liquid chromatography.
Hydroxyl radical footprinting is a powerful technique often employed in characterization of the tertiary interactions between proteins and nucleic acids. Following the generation of a nucleic acid "ladder" either by chemical or enzymatic reactions, the radiolabeled products are traditionally separated by denaturing gel electrophoresis and further quantified by phosphorimaging techniques. Here we report the use of ion pair reverse phase liquid chromatography to analyze the products of an RNA footprinting reaction using fluorescently labeled RNA molecules. This technique offers several advantages over existing procedures, including rapid analysis, automation, and direct quantification of the cleavage products without the need to employ radiolabeling. To illustrate the resolving power of this technique, we have analyzed the products of base hydrolysis, generated from a fluorescently labeled RNA molecule and have subsequently used this method to define the solvent accessibility of the substrate strand as it docks with the hairpin ribozyme.


Zinc Oxide Nanoparticles Cytotoxicity and Release from Newly Formed PMMA-ZnO Nanocomposites Designed for Denture Bases.
The goal of the study was to investigate the level of zinc oxide nanoparticles (ZnO NPs) release from polymethyl methacrylate (PMMA)-ZnO nanocomposites (2.5%, 5%, and 7.5% w/w), as well as from the ZnO NPs layer produced on pure PMMA, and the impact of the achieved final ZnO NPs concentration on cytotoxicity, before the potential use as an alternative material for denture bases. The concentration of ZnO nanoparticles released to the aqueous solution of Zn2+ ions was assessed using optical emission spectrometry with inductively coupled plasma (ICP-OES). In the control group (pure PMMA), the released mean for ZnO was 0.074 mg/L and for individual nanocomposites at concentrations of 2.5%, 5%, and 7.5% was 2.281 mg/L, 2.143 mg/L, and 3.512 mg/L, respectively. The median for the ZnO NPs layer produced on PMMA was 4.878 mg/L. In addition, in vitro cytotoxicity of ZnO NPs against the human HeLa cell line was determined through the reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) dye. The cytotoxicity studies demonstrate that ZnO nanoparticles in the concentrations up to 20 mg/L have no adverse effect on HeLa cells. When compared with the released and cytotoxic concentrations of ZnO NPs, it can be expected that ZnO released from dental prostheses to the oral cavity environment will have no cytotoxic effect on host cells.


Vibratory acoustic stimulation and fetal gasping.
Vibratory acoustic stimulation (VAS) has been used to shorten the duration of antepartum fetal heart rate monitoring. Questions have been asked regarding the possible effects of VAS on the fetus. VAS was used to investigate whether the acute effect of VAS is associated with gasping in the normal fetus. Thirty-seven normal patients at 37-42 weeks' gestation with singleton fetuses were studied. All had normal amniotic fluid volume on ultrasound. These 37 subjects had a five-minute baseline sonographic assessment of fetal breathing and body movements. A fetal gasp was defined as an isolated, slow, irregularly occurring, deep, inspiratory-type movement, or series of them, of the chest and abdomen. Three-second VAS was then delivered with an artificial larynx placed directly over the fetal head. Fetal breathing, body and gasping movements were assessed at the time of this stimulus. A significant increase in fetal body movements (P < .001), a significant decrease in fetal breathing (P < .003) and absence of gasping movements were noted. The results suggest that gasping does not occur in response to VAS in the normal, term fetus.


Protective effects of a dimeric derivative of ferulic acid in animal models of Alzheimer's disease.
Ferulic acid is a compound with potent anti-oxidant and anti-inflammatory activities. We previously reported the protective effects of ferulic acid administration against two animal models of Alzheimer's disease (AD): intracerebroventricular (i.c.v.) injection of Aß1-42 in mice and APP/PS1 mutant transgenic mice. In this study using the same AD animal models, we examined the effect of KMS4001, one of dimeric derivatives of ferulic acid. Intragastric pretreatment of mice with KMS4001 (30mg/kg/day) for 5 days significantly attenuated the Aß1-42 (i.c.v.)-induced memory impairment both in passive avoidance test and in Y-maze test. APP/PS1 mutant transgenic mice at KMS4001 doses of 3 and 30mg/kg/day via drinking water showed the significantly enhanced novel-object recognition memory at both 1.5 and 3 months after the start of KMS4001 treatment. Treatment of APP/PS1 mutant transgenic mice with KMS4001 for 3 months at the doses of 3 and 30mg/kg/day markedly decreased Aβ1-40 and Aβ1-42 levels in the frontal cortex. The KMS4001 dose-response relationships for Aβ decrease and for improvement in novel-object recognition test corresponded to each other. Taken together, these results suggest that KMS4001 could be an effective drug candidate against AD.


CO2 assimilation, ribulose-1,5-bisphosphate carboxylase/oxygenase, carbohydrates and photosynthetic electron transport probed by the JIP-test, of tea leaves in response to phosphorus supply.
Although the effects of P deficiency on tea (Camellia sinensis (L.) O. Kuntze) growth, P uptake and utilization as well as leaf gas exchange and Chl a fluorescence have been investigated, very little is known about the effects of P deficiency on photosynthetic electron transport, photosynthetic enzymes and carbohydrates of tea leaves. In this study, own-rooted 10-month-old tea trees were supplied three times weekly for 17 weeks with 500 mL of nutrient solution at a P concentration of 0, 40, 80, 160, 400 or 1000 microM. This objective of this study was to determine how P deficiency affects CO2 assimilation, Rubisco, carbohydrates and photosynthetic electron transport in tea leaves to understand the mechanism by which P deficiency leads to a decrease in CO2 assimilation. Both root and shoot dry weight increased as P supply increased from 0 to 160 microM, then remained unchanged. P-deficient leaves from 0 to 80 muM P-treated trees showed decreased CO2 assimilation and stomatal conductance, but increased intercellular CO2 concentration. Both initial and total Rubisco activity, contents of Chl and total soluble protein in P-deficient leaves decreased to a lesser extent than CO2 assimilation. Contents of sucrose and starch were decreased in P-deficient leaves, whereas contents of glucose and fructose did not change significantly except for a significant increase in the lowest P leaves. OJIP transients from P-deficient leaves displayed a rise at the O-step and a depression at the P-step, accompanied by two new steps at about 150 mus (L-step) and at about 300 mus (K-step). RC/CSo, TRo/ABS (or Fv/Fm), ETo/ABS, REo/ABS, maximum amplitude of IP phase, PIabs and PItot, abs were decreased in P-deficient leaves, while VJ, VI and dissipated energy were increased. P deficiency decreased photosynthetic electron transport capacity by impairing the whole electron transport chain from the PSII donor side up to the PSI, thus decreasing ATP content which limits RuBP regeneration, and hence, the rate of CO2 assimilation. Energy dissipation is enhanced to protect P-deficient leaves from photo-oxidative damage in high light.


The realities and medical expense of hospitalization that originates in outpatient medicine treatment.
Problems associated with outpatient pharmacotherapy may require hospitalization. However, such hospitalization may be prevented if pharmacist's pharmaceutical care (PC) is given. We investigated the reasons for hospitalization in medical institutions and medical expenses were calculated. Inpatient diagnoses, treatment, etc. in the previous year in the past were examined, and cases of hospitalization due to drug therapy were extracted. Next, the possibility of preventing hospitalization with PC practice was examined. Among 1552 cases, outpatient pharmacotherapy was the reason for hospitalization in 27 cases. Noncompliance was the underlying cause in about 40% of hospitalizations. It was thought that in 22 cases hospitalization could have been prevented by pharmacist's PC. The average hospitalization medical expense was 295,805 yen per patient. It is necessary to perform regular consultation recommendations, interventions with the family, home care, etc. for proactive PC.


Attachment-related psychodynamics.
Because there has been relatively little communication and cross-fertilization between the two major lines of research on adult attachment, one based on coded narrative assessments of defensive processes, the other on simple self-reports of 'attachment style' in close relationships, we here explain and review recent work based on a combination of self-report and other kinds of method, including behavioral observations and unconscious priming techniques. The review indicates that considerable progress has been made in testing central hypotheses derived from attachment theory and in exploring unconscious, psychodynamic processes related to affect-regulation and attachment-system activation. The combination of self-report assessment of attachment style and experimental manipulation of other theoretically pertinent variables allows researchers to test causal hypotheses. We present a model of normative and individual-difference processes related to attachment and identify areas in which further research is needed and likely to be successful. One long-range goal is to create a more complete theory of personality built on attachment theory and other object relations theories.


How Polyomaviruses Exploit the ERAD Machinery to Cause Infection.
To infect cells, polyomavirus (PyV) traffics from the cell surface to the endoplasmic reticulum (ER) where it hijacks elements of the ER-associated degradation (ERAD) machinery to penetrate the ER membrane and reach the cytosol. From the cytosol, the virus transports to the nucleus, enabling transcription and replication of the viral genome that leads to lytic infection or cellular transformation. How PyV exploits the ERAD machinery to cross the ER membrane and access the cytosol, a decisive infection step, remains enigmatic. However, recent studies have slowly unraveled many aspects of this process. These emerging insights should advance our efforts to develop more effective therapies against PyV-induced human diseases.


Neutralization of Smac/Diablo by inhibitors of apoptosis (IAPs). A caspase-independent mechanism for apoptotic inhibition.
Numerous members of the IAP family can suppress apoptotic cell death in physiological settings. Whereas certain IAPs directly inhibit caspases, the chief proteolytic effectors of apoptosis, the protective effects of other IAPs do not correlate well with their caspase inhibitory activities, suggesting the involvement of alternative cytoprotective abilities. To examine this issue, we have characterized the protective effects of an ancestral, baculoviral IAP (Op-IAP) in mammalian cells. We show that although Op-IAP potently inhibited Bax-mediated apoptosis in human cells, Op-IAP failed to directly inhibit mammalian caspases. However, Op-IAP efficiently bound the IAP antagonist Smac/Diablo, thereby preventing Smac/Diablo-mediated inhibition of cellular IAPs. Whereas reduction of Smac/Diablo protein levels in the absence of Op-IAP prevented Bax-mediated apoptosis, overexpression of Smac/Diablo neutralized Op-IAP-mediated protection, and an Op-IAP variant unable to bind Smac/Diablo failed to prevent apoptosis. Finally, Op-IAP catalyzed the ubiquitination of Smac/Diablo, an activity that contributed to Op-IAP-mediated inhibition of apoptosis. These data show that cytoprotective IAPs can inhibit apoptosis through the neutralization of IAP antagonists, rather than by directly inhibiting caspases.


Saliva Interleukin-6 in patients with inflammatory bowel disease.
The inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory conditions that affect the gastrointestinal tract. In regulation of this inflammatory process, Interleukin-6 (IL-6) has a major role. Overproduction of IL-6 by immunocompetent cells contributes to development of the inflammatory condition. Elevated levels of IL-6 in saliva could be expected, because the saliva-producing cells are part of the digestive system. IL-6 concentrations in saliva and plasma were studied in patients with CD (n=15), UC (n=7) and reference persons (RP) (n=19) by use of an ELISA method. A significant difference in saliva IL-6 concentration between CD patients (median 16.9 ng/L; p<0.05) and RP (median 6.3 ng/L) was found. A significant difference in plasma IL-6 concentration between CD (median 10.3 ng/L; p<0.001) or UC (median 7.8 ng/L; p<0.001) and RP (median 0.8 ng/L) was observed. In patients with CD, plasma IL-6 correlated significantly with C-reactive protein (CRP) as well as albumin. In patients with UC, saliva IL-6 and plasma IL-6 correlated significantly with AI (activity index) scores as well as albumin. In patients with UC, a significant correlation between the saliva and plasma IL-6 concentrations was found. IL-6 was found in saliva in patients with IBD, documenting the general involvement of the gastrointestinal tract extending to the mouth cavity, and measuring IL-6 may be an additional method for evaluating and monitoring the disease activity.


Red-Shifted Aminated Derivatives of GFP Chromophore for Live-Cell Protein Labeling with Lipocalins.
Fluorogens are an attractive type of dye for imaging applications, eliminating time-consuming washout steps from staining protocols. With just a handful of reported fluorogen-protein pairs, mostly in the green region of spectra, there is a need for the expansion of their spectral range. Still, the origins of solvatochromic and fluorogenic properties of the chromophores suitable for live-cell imaging are poorly understood. Here we report on the synthesis and labeling applications of novel red-shifted fluorogenic cell-permeable green fluorescent protein (GFP) chromophore analogs.


Microfluidic Screening Reveals Heparan Sulfate Enhances Human Mesenchymal Stem Cell Growth by Modulating Fibroblast Growth Factor-2 Transport.
Cost-effective expansion of human mesenchymal stem/stromal cells (hMSCs) remains a key challenge for their widespread clinical deployment. Fibroblast growth factor-2 (FGF-2) is a key hMSC mitogen often supplemented to increase hMSC growth rates. However, hMSCs also produce endogenous FGF-2, which critically interacts with cell surface heparan sulfate (HS). We assessed the interplay of FGF-2 with a heparan sulfate variant (HS8) engineered to bind FGF-2 and potentiate its activity. Bone marrow-derived hMSCs were screened in perfused microbioreactor arrays (MBAs), showing that HS8 (50 μg/ml) increased hMSC proliferation and cell number after 3 days, with an effect equivalent to FGF-2 (50 ng/ml). In combination, the effects of HS8 and FGF-2 were additive. Differential cell responses, from upstream to downstream culture chambers under constant flow of media in the MBA, provided insights into modulation of FGF-2 transport by HS8. HS8 treatment induced proliferation mainly in the downstream chambers, suggesting a requirement for endogenous FGF-2 accumulation, whereas responses to FGF-2 occurred primarily in the upstream chambers. Adding HS8 along with FGF-2, however, maximized the range of FGF-2 effectiveness. Measurements of FGF-2 in static cultures then revealed that this was because HS8 caused increased endogenous FGF-2 production and liberated FGF-2 from the cell surface into the supernatant. HS8 also sustained levels of supplemented FGF-2 available over 3 days. These results suggest HS8 enhances hMSC proliferation and expansion by leveraging endogenous FGF-2 production and maximizing the effect of supplemented FGF-2. This is an exciting strategy for cost-effective expansion of hMSCs. Stem Cells Translational Medicine 2017;6:1178-1190.


Recurrence of Ocular Toxoplasmosis after Vitrectomy: Case Report and Review.
The purpose of this study is to report one case of ocular toxoplasmosis (OT) recurrence after vitrectomy and review the scientific basis about it. A 58-year-old male patient with previous OT, properly treated, underwent vitrectomy due to macular hole. During follow-up, patient evolved with recurrence of the OT. After 1 year, patient presents visual acuity of 20/200 and extensive macular scar. There is no consensus on using perioperative antiparasitic therapy aiming recurrence prophylaxis. Studies with better statistical design are necessary to evaluate the recurrence risk after ocular surgeries and the possible recommendation of prophylaxis, especially in countries where the strains are more virulent and the recurrence more common.


Neuroprotective effect of resveratrol against brain ischemia reperfusion injury in rats entails reduction of DJ-1 protein expression and activation of PI3K/Akt/GSK3b survival pathway.
In the current study, we aimed to investigate the mechanistic role of DJ-1/PI3K/Akt survival pathway in ischemia/reperfusion (I/R) induced cerebral damage and to investigate if the resveratrol (RES) mediates its ischemic neuroptotection through this pathway. RES administration to Sham rats boosted glutathione level and superoxide dismutase activity and downregulated inducible nitric oxide synthase expression without affecting redox levels of DJ-1 forms or components of PI3K/Akt pathway including PTEN, p-Akt or p/p-GSK3b. However, RES pre-administration to I/R rats reduced infarction area, oxidative stress, inflammation and apoptosis. Concomitantly, RES ameliorated the decreased levels of oxidized forms of DJ-1 and enhancing its reduction, increased the nuclear protein expression of Nfr-2 and led to activation of PI3K/Akt survival pathway. In conclusion, overoxidation of DJ-1 is a major factor that contributes to post-I/R cerebral damage and its reduction by RES could explain the neuroprotection offered by RES.


The impact of transmission-emission misregistration on the interpretation of SPET/CT myocardial perfusion studies and the value of misregistration correction.
Previous studies indicate that the quality of single photon emission tomography/computed tomography (SPET/CT) myocardial perfusion imaging (MPI) is degraded by even mild transmission-emission misregistrations. The purpose of the current study was to investigate the impact of SPET/CT misalignment on the interpretation of MPI and examine the value of a commercial software application for registration correction. A total of 255 technetium-99m ((99m)Tc)-tetrofosmin stress/rest MPI examinations in 150 patients were reviewed for SPET/CT misalignment. After registration correction by the software, images were reassessed for interpretation differences from the misregistered study. The diagnostic benefit of reregistration was determined by taking into account the non-attenuation compensated image pattern, combined stress-rest evaluation, gated-SPET data and patient's history. In a phantom experiment and in 3 representative clinical cases, SPET/CT misalignment was purposely created by the software by sequential slice shifts and its effect was evaluated quantitatively. Misregistration ≥1 pixel in at least one direction was observed in 24% of studies. Interpretation of MPI changed after registration correction in 11% of cases with misalignment <1 pixel, in 18% with 1-2 and in 73% with ≥2 pixels. The diagnostic information seemed to improve after registration correction in 58% of studies irrespective of the degree of misregistration. Software-simulated misregistration had dissimilar effects in the phantom and the 3 selected clinical cases. The impact of SPET/CT misregistration on MPI interpretation although influenced by the degree and direction of slice misplacement, it is also case-specific and hardly predictable. Registration restoration by the software seems worthwhile regardless of misregistration magnitude.


IQ-CPR Meter for Chest Compression Monitoring During Simulated Cardiopulmonary Resuscitation; a Comparative Study.
Adequate chest compression is crucial for cardiopulmonary resuscitation (CPR). There are several chest compression monitoring devices with different costs. This study aimed to evaluate the agreement rate of Improved Quality of Cardiopulmonary Resuscitation meter (IQ-CPR meter) and automated external defibrillator (AED) in chest compression quality monitoring. In this comparative study, participants were instructed to perform chest compression on the CPR manikins with the set rate of 110 times/minute for two minutes. The CPR manikins had two monitors: AED (R series®, Zoll company) and IQ-CPR meter. AED showed the depth and speed of chest compression on the screen, while IQ-CPR meter showed the depth of each chest compression by color light for quality of chest compression depth. Video-based analysis was used to compare the chest compression quality monitoring between the 2 devices. There were 27 participants in the study with a mean age and body mass index (standard deviation; SD) of 26.00 (5.65) years, and 22.93 (3.62) kg/m2 (70.37% male). The median (1st to 3rd quartile range) of chest compression experience was 3 (1.00-6.50) years. The mean (SD) of chest compression rate was 107 (5.29) times/minute. Based on Cohen's Kappa correlation, agreement between the IQ-CPR meter and the AED was 66.54%. The IQ-CPR meter had fair agreement with the computerized chest compression monitoring device with lower cost and simple, real time audiovisual feedback.


Steroidal spiro-gamma-lactones that inhibit 17 beta-hydroxysteroid dehydrogenase activity in human placental microsomes.
The important enzyme 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) is known to regulate intracellular levels of biologically active steroids, namely, androgens and estrogens. In an effort to develop potent inhibitors of 17 beta-HSD for reducing the levels of active steroids, we found that steroidal spiro-gamma-lactones inhibit 17 beta-HSD activity. In this report, we describe the synthesis of 11 spiro-gamma-lactone analogs containing a steroidal C-18 or C-19 nucleus and compare their relative inhibitory effects on 17 beta-HSD activity in the human placenta microsomes that catalyze the interconversion of androgens and estrogens. To void the interaction of the cytosolic 17 beta-HSD activity that is specific for the interconversion of estrone and estradiol, we used 4-androstenedione as substrate. Analysis of the inhibitory effect exerted by these analogs on microsomal 17 beta-HSD activity indicates that spiro-gamma-lactones containing the C-18 nucleus are more potent inhibitors than C-19 nucleus analogs. The best inhibition was obtained with the phenolic spiro-gamma-lactone 7 (3-hydroxy-19-nor-17 alpha-pregna-1,3,5(10)-triene 21,17-carbolactone), which has an IC50 value of 0.27 microM, and was much lower than the competitive effect of the unlabeled substrate 4-androstenedione, which has an IC50 value of 1.40 microM. Preincubation with lactone 7 did not inactivate 17 beta-HSD activity. The results thus suggest that lactone 7 is a reversible in inhibitor. Lactone 7 is selective for microsomal 17 beta-HSD activity, as no inhibition was observed for cytosolic 17 beta-HSD activity.


Alkaline phosphatase LapA regulates quorum sensing-mediated virulence and biofilm formation in Pseudomonas aeruginosa PAO1 under phosphate depletion stress.
Our previous study demonstrated that the expression of lapA was induced under phosphate depletion conditions, but its roles in virulence and biofilm formation by Pseudomonas aeruginosa remain largely unknown. This study presents a systematic investigation of the roles of lapA in virulence induction and biofilm formation by constructing a lapA-deficient strain with P. aeruginosa PAO1. The results showed that deletion of the lapA gene evidently reduced elastase activity, swimming motility, C4-HSL, and 3-oxo-C12-HSL production, and increased rhamnolipid production under phosphate depletion stress. Moreover, lapA gene deletion inhibited PAO1 biofilm formation in porcine skin explants by reducing the expression levels of las and rhl quorum sensing systems and extracellular polymeric substance synthesis. Finally, lapA gene deletion also reduced the virulence of PAO1 in Caenorhabditis elegans in fast-kill and slow-kill infection assays. This study provides insights into the roles of lapA in modulating P. aeruginosa virulence and biofilm formation under phosphate depletion stress.


GATA proteins work together with friend of GATA (FOG) and C-terminal binding protein (CTBP) co-regulators to control adipogenesis.
GATA transcription factors have been implicated in controlling adipogenesis in Drosophila and in mammals. In mammals, both GATA2 and GATA3 have been shown to be present in preadipocytes, and their silencing allows the onset of adipogenesis. Overexpression of GATA proteins blocks adipogenesis in cellular assays. GATA factors have been found to operate through recruiting cofactors of the Friend of GATA (FOG) family. FOG proteins, in turn, recruit co-regulators, including C-terminal binding proteins (CTBPs). We have investigated whether FOGs and CTBPs influence adipogenesis. We found that both FOG1 and FOG2 are expressed in cells prior to adipogenesis but are down-regulated as adipogenesis proceeds. Overexpression of FOG1 or FOG2 interferes with adipogenesis. Mutant versions of FOG2 unable to bind CTBP or GATA proteins are impaired in their inability to inhibit adipogenesis. Finally, a mutant version of GATA2, unable to associate with FOGs, also displays abnormal activity and causes enhanced cell proliferation. These results implicate FOGs and CTBPs as partners of GATA proteins in the control of adipocyte proliferation and differentiation.


Effect of muscle strengthening on peripheral facial palsy: A randomized controlled trial.
To evaluate the effect of muscle strengthening intervention in peripheral facial palsy (PFP). A randomized controlled trial was conducted at five hospitals. Fifty-one subjects with PFP who showed a response of less than 20% on electroneurography (ENoG) were enrolled. Subjects in a muscle-strengthening-intervention group (MS Group) underwent a selective muscle contraction intervention (SMCI). Subjects in another group not receiving muscle strengthening intervention (Non-MS Group). Both groups underwent three interventions: Prohibition of maximum effort movements, Stretching of the affected facial muscles, and Mirror biofeedback therapy. The outcomes were measured by the Sunnybrook Facial Grading System (FGS) at 6 months after onset (primary endpoint) and at 12 months after onset (secondary endpoint). The subjects in the MS Group and Non-MS Group were further divided into subgroups showing ENoG responses of 10% or less and ENoG responses of over 10%, as a sub-analysis. No significant differences between the MS Group and Non-MS Group at either the primary endpoint or secondary endpoint. Among the subjects in the treatment group with an ENoG response of over 10% at the primary endpoint, the FGS Composite Score and FGS Voluntary Movement score were both significantly higher in the MS Group than in Non-MS Group. Although the MS Group had a significantly lower FGS Resting Symmetry Score, there was no significant difference between the two groups in the FGS Synkinesis Score. SMCI improved paralysis in subjects exhibiting an ENoG response of over 10% within the 6 months from onset without any deterioration of synkinesis.


Go with the flow-clinical importance of flow curves during mechanical ventilation: A narrative review.
Most clinicians pay attention to tidal volume and airway pressures and their curves during mechanical ventilation. On the other hand, inspiratory-expiratory flow curves also provide a plethora of information, but much less attention is paid to them. Flow curves chronologically show the velocity and direction of inspiration and expiration and are influenced by the respiratory mechanics, the patient's effort, and the mode of ventilation and its settings. When the ventilator setting does not synchronize with the patient's respiratory pattern, the patient can easily have worsening breathing effort, patient-ventilator asynchrony, which can lead to prolonged ventilator support or lung injury. The information provided by the flow curves during mechanical ventilation, such as respiratory mechanics, the patient's effort, and patient-ventilator interactions, are very helpful when adjusting the ventilator setting. If clinicians can monitor and assess the flow curves information appropriately, it can be a useful diagnostic and therapeutic tool at the bedside. There may be association between inspiratory effort and flow, and this may further guide us, especially in the weaning process and when patients are not synchronizing with the ventilator. In this review, we try to gather information about "flow" that is scattered around in the literature and textbooks in one place. We will summarize the different flow waveforms utilized in commonly used ventilator modes with their advantages and disadvantages, information gained by the flow curves (i.e., flow-time, flow-volume, and flow-pressure), how to detect and manage asynchronies, and some ideas for future uses. Flow waveforms shapes and patterns are very beneficial for the management of patients undergoing mechanical ventilatory support. Attention to those waveforms can potentially improve patient outcomes. Clinicians should be familiar with this information and how to act upon them.


Estrogen replacement therapy and breast cancer risk.
Assessment of the effects of menopausal estrogens on the risk of breast cancer is obviously complex, with proper evaluations requiring attention to the effects of selection, recall, and surveillance biases; confounding factors; detailed exposure relations; and subgroup variations. Although much discussion has ensued over the extent to which variations between studies might be due to a variety of methodological differences, it is likely that the limited statistical power of many studies may be largely responsible for the divergent effects observed, particularly with regard to assessing the effect of long-term usage. Thus, in case-control studies in which population controls have been used and for which there have been a sufficient number of women using estrogens for approximately 10 or more years, it appears as though such an exposure may be associated with some elevated risk, possibly on the order of 30-80 percent (16, 34, 36-38)--a magnitude of risk that is obviously extremely difficult to detect in most epidemiologic studies. Evaluation of risks associated with short-term use is even more difficult, which has led most investigators to conclude that usage of less than 5 years is associated with no detectable excess risk. Problems with statistical power also plague evaluations of more detailed measures of use, including dosage and type of preparations, although there is some indication that nonconjugated preparations may be associated with a higher risk than other types of estrogens (16, 20, 36, 44, 51). In addition, there is some evidence that recent use may be associated with a modest elevation in risk (32, 33, 53), although effects of surveillance bias are difficult to resolve. Interpretation of the effect is complicated by several studies which have found estrogens to be associated with an increased risk of breast cancer incidence but a decreased risk of death, with the mortality ratios ranging from approximately 0.5 to 0.8 (33, 92, 93). Although one of these studies hypothesized that the relation with mortality may reflect a tendency for women with clinically recognized breast cancers and those at high risk not to be prescribed estrogens for long periods of time, studies showing that estrogen users have more favorable tumor characteristics at diagnosis than nonusers (20, 36) suggest that screening biases may be involved. The numerous contradictions regarding effects of menopausal estrogens from observational studies have heightened interest in the results of several ongoing controlled clinical trials.(ABSTRACT TRUNCATED AT 400 WORDS)


Prognostic Role of Anemia in COVID-19 Patients: A Meta-Analysis.
The prevalence and prognostic implications of anemia in patients infected by the SARS-CoV-2 remains unclear. We performed a systematic review and meta-analysis to assess the prevalence and mortality risk in COVID-19 patients with anemia. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed in abstracting data and assessing validity. We searched MEDLINE and Scopus to locate all the articles published up to 1 September 2021, reporting data on the adjusted OR (aOR) for mortality among COVID-19 patients with anemia. The pooled prevalence of anemia among COVID-19 patients was calculated using a random effects model and presenting the related 95% confidence interval (CI), while the mortality risk was estimated using the Mantel-Haenszel random effects models with odds ratio (aOR) and related 95% CI. Statistical heterogeneity was measured using the Higgins I2 statistic. Five studies, enrolling 9.623 COVID-19 patients [3.707 males (38.5%)], met the inclusion criteria and were included in the final analysis. The pooled prevalence of anemia was 25.6% of cases (95% CI: 8.3-56.5%), with high heterogeneity (I2 = 98.9%). Meta-regression showed that the anemia prevalence was influenced by a direct correlation with age (p = 0.007) and chronic kidney disease (p = 0.004) as moderating variables. Conversely, an inverse relationship was observed with male gender (p < 0.0001). Anemia was significantly associated with higher risk of short-term mortality (aOR: 1.69, 95% CI: 1.28-2.24, p < 0.001), with low heterogeneity (I2 = 0%). Anemia represents a major comorbidity in about 25% of COVID-19 patients and it is associated with about 70% higher risk of short-term mortality.


Identifying populations potentially exposed to agricultural pesticides using remote sensing and a Geographic Information System.
Pesticides used in agriculture may cause adverse health effects among the population living near agricultural areas. However, identifying the populations most likely to be exposed is difficult. We conducted a feasibility study to determine whether satellite imagery could be used to reconstruct historical crop patterns. We used historical Farm Service Agency records as a source of ground reference data to classify a late summer 1984 satellite image into crop species in a three-county area in south central Nebraska. Residences from a population-based epidemiologic study of non-Hodgkin lymphoma were located on the crop maps using a geographic information system (GIS). Corn, soybeans, sorghum, and alfalfa were the major crops grown in the study area. Eighty-five percent of residences could be located, and of these 22% had one of the four major crops within 500 m of the residence, an intermediate distance for the range of drift effects from pesticides applied in agriculture. We determined the proximity of residences to specific crop species and calculated crop-specific probabilities of pesticide use based on available data. This feasibility study demonstrated that remote sensing data and historical records on crop location can be used to create historical crop maps. The crop pesticides that were likely to have been applied can be estimated when information about crop-specific pesticide use is available. Using a GIS, zones of potential exposure to agricultural pesticides and proximity measures can be determined for residences in a study.


A shared kappa reciprocal fragment and a high frequency of secondary Jk5 rearrangements among influenza hemagglutinin specific B cell hybridomas.
Ig kappa-chain gene rearrangement results in the displacement or loss of the DNA immediately 5' of Jk. This retained DNA is found on a different size fragment than in the germline (a reciprocal fragment), and contains the reciprocal joint of rearranged Vk and Jk genes, the back-to-back fusion of the heptamer/nonamer recombination signals. B cells of independent origin rarely have reciprocal fragments of the same size. However, we report that 9 of 15 B cell hybridomas of independent origin have reciprocal fragments of the same size (8-kb BamHI fragments) unrelated to their productive rearrangements. An 8-kb reciprocal fragment has also occurred on about 25% of the kappa alleles of normal splenic B cells. We find that the reciprocal fragments in two of these hybridomas contain the reciprocal joints of Jk1 genes and different Vk8 genes. In addition, we find that at least 8 of the 12 Jk4 or Jk5 expressing hybridomas have undergone double recombinations on their productive kappa alleles. The implications of these findings on the high frequency of 8-kb reciprocal rearrangements and on Vk rearrangement are discussed.


Identification of the Key Genes and Pathways in Esophageal Carcinoma.
Objective. Esophageal carcinoma (EC) is a frequently common malignancy of gastrointestinal cancer in the world. This study aims to screen key genes and pathways in EC and elucidate the mechanism of it. Methods. 5 microarray datasets of EC were downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) were screened by bioinformatics analysis. Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and protein-protein interaction (PPI) network construction were performed to obtain the biological roles of DEGs in EC. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the expression level of DEGs in EC. Results. A total of 1955 genes were filtered as DEGs in EC. The upregulated genes were significantly enriched in cell cycle and the downregulated genes significantly enriched in Endocytosis. PPI network displayed CDK4 and CCT3 were hub proteins in the network. The expression level of 8 dysregulated DEGs including CDK4, CCT3, THSD4, SIM2, MYBL2, CENPF, CDCA3, and CDKN3 was validated in EC compared to adjacent nontumor tissues and the results were matched with the microarray analysis. Conclusion. The significantly DEGs including CDK4, CCT3, THSD4, and SIM2 may play key roles in tumorigenesis and development of EC involved in cell cycle and Endocytosis.


Intermediate structures for higher level arrangements: catching disk-like micelles in decane phosphonic acid aqueous solutions.
It has been proposed that disk-like micelles may be precursors to the formation of lamellar liquid crystals. The possibility of obtaining n-decane phosphonic acid (DPA) disk-like micelles in aqueous solution without the addition of a second ionic surfactant led us to study in detail the low-concentration range of this system by both a battery of experimental techniques and molecular dynamics (MD) simulations. The experimental results indicate that premicelles with some capacity to solubilize dyes are formed at 0.05 mM. The critical micelle concentration (cmc) was found to be 0.260 ± 0.023 mM, much lower than that previously reported in the literature. Spherical micelles, which immediately grow, leading to disk-like micelles, are probably formed at this concentration. At 0.454 ± 0.066 mM, disk-like micelles become unstable, giving rise to the formation of an emulsion of lamellar mesophase that dominates the system beyond 0.670 ± 0.045 mM. These experimental results were corroborated by MD simulations which, additionally, allow describing the structure of the obtained micelles at atomic level. The analysis of the MD trajectories revealed the presence of strong intermolecular hydrogen bonds between the surfactant headgroups, producing a compact polar layer with low water content. The formation of such H-bond network could explain the ability of this surfactant to form disk-like micelles at concentrations close to the cmc.


Differential diagnosis between AML infiltration, lymphoma and tuberculosis in a patient presenting with fever and mediastinal lymphadenopathy: A case report.
The diagnosis of tuberculosis in immunocompromised hosts is often difficult as the hosts have atypical tuberculosis symptoms. The current study presents a case of scrofula and pulmonary tuberculosis with acute myelocytic leukemia (AML). As the disease became aggravated, the patient presented with fever, hemophagocytosis in the bone marrow, lymphadenopathy of the supraclavicular fossa, and mediastinal and nodular shadow in the chest by computed tomography. The symptoms presented successively or were coexistent, which made differentiation between tuberculosis, lymphoma, AML infiltration or other infections challenging. The diagnosis of tuberculosis was based on clinical and radiographic observations, morphological observation of the biopsies and the positive effect of antituberculosis drugs, while Ziehl-Neelsen stainings for acid fast bacilli were negative. The patient was treated with antituberculosis drugs, while receiving chemotherapy for AML. It is important to distinguish tuberculosis in adults with AML from other causes of fever, mediastinal masses in radiographic observations and hemophagocytosis in the bone marrow.


The initial response of blood leukocytes to incubation with perfluorocarbon blood substitute emulsions.
Due to their enhanced oxygen carrying characteristics, perfluorocarbon emulsions are valuable adjuncts to coronary revascularization procedures. However, the effects of perfluorocarbon emulsions on white blood cell function are unclear. The purpose of this study was to determine the effects of three perfluorocarbon emulsions on the adhesion characteristics of leukocytes. Heparinized blood from donor rats was mixed with either Phosphate Buffered Saline (PBS), PFB-1, PFB-2 (both non-complement activating perflubron emulsions, Alliance Pharmaceutical Corp.) or Fluosol (20% w/v PFC, Alpha Therapeutic) in a ratio of one part emulsion to six parts blood. The blood-emulsion mixtures were incubated for ten minutes at 37 degrees C, then passed down nylon wool leukocyte adhesion columns. Blood samples were counted for: Leukocytes, Granulocytes and Lymphocytes. % Cell Adherence was calculated as: (1-[WBC-out]/[WBC-in]). We found that, compared to PBS control, the granulocyte adherence to the nylon fiber was significantly increased for both Fluosol-20 and PFB-1 (P < 0.05). In contrast, PFB-2 (designed for reduced cell surface activity) caused no significant change in leukocyte adhesion. In fact, a modest decrease in granulocyte adhesion was observed with PFB-2. These findings suggest a direct effect of some, but not all, PFC emulsions on blood leukocyte function.


Prognosis of Coronary Artery Bypass Grafting in Preschool-Aged Patients with Myocardial Ischemia Due to Giant Aneurysm of Kawasaki Disease.
Coronary artery bypass grafting (CABG) for severe cardiac sequelae of Kawasaki disease (KD) complicated by myocardial ischemia is feasible even in childhood. However, no report has summarized the prognosis of CABG in preschool-aged children. Therefore, we evaluated the outcomes of seven preschool-aged children who underwent CABG for the cardiac sequelae of KD in our hospital. The median age at KD onset and CABG was 36 and 59 months, respectively. The median period from KD onset to CABG was 12 months. The median post-operative observation period was 108 months. CABG between the left internal thoracic artery and left anterior descending artery was performed in all patients. In all patients, postoperative cardiac catheter examination revealed good graft patency and no anastomotic stenosis. Further, pre-operative abnormality of coronary flow reserve returned to normal after CABG. Currently, only one patient is taking warfarin. Regarding school-life management, no patient has exercise limitations, except for one patient who had acute myocardial infarction before CABG. Further, the risk of graft stenosis or occlusion was evaluated in the included patients. However, no accidents have been reported to date, and myocardial ischemia and school-life management have improved. Thus, CABG is an effective treatment in preschool-aged children.


Experimental Assessment of the Effects of Temperature and Food Availability on Particle Mixing by the Bivalve Abra alba Using New Image Analysis Techniques.
The effects of temperature and food addition on particle mixing in the deposit-feeding bivalve Abra alba were assessed using an experimental approach allowing for the tracking of individual fluorescent particle (luminophore) displacements. This allowed for the computations of vertical profiles of a set of parameters describing particle mixing. The frequency of luminophore displacements (jumps) was assessed through the measurement of both waiting times (i.e., the time lapses between two consecutive jumps of the same luminophore) and normalized numbers of jumps (i.e., the numbers of jumps detected in a given area divided by the number of luminophores in this area). Jump characteristics included the direction, duration and length of each jump. Particle tracking biodiffusion coefficients (Db) were also computed. Data originated from 32 experiments carried out under 4 combinations of 2 temperature (Te) and 2 food addition (Fo) levels. For each of these treatments, parameters were computed for 5 experimental durations (Ed). The effects of Se, Fo and Ed were assessed using PERmutational Multivariate ANalyses Of VAriance (PERMANOVAs) carried out on vertical depth profiles of each particle mixing parameter. Inversed waiting times significantly decreased with Ed whereas the normalized number of jumps did not, thereby suggesting that it constitutes a better proxy of jump frequency when assessing particle mixing based on the measure of individual particle displacements. Particle mixing was low during autumn temperature experiments and not affected by Fo, which was attributed to the dominant effect of low temperature. Conversely, particle mixing was high during summer temperature experiments and transitory inhibited by food addition. This last result is coherent with the functional responses (both in terms of activity and particle mixing) already measured for individual of the closely related clam A. ovata originating from temperate populations. It also partly resulted from a transitory switch between deposit- and suspension-feeding caused by the high concentration of suspended particulate organic matter immediately following food addition.


Expression and function of two nicotinic subunits in insect neurons.
Nicotinic acetylcholine receptors (nAChRs) in insects are neuron-specific oligomeric proteins essential for the central transmission of sensory information. Little is known about their subunit composition because it is difficult to express functional insect nAChRs in heterologous systems. As an alternative approach we have examined the native expression of two subunits in neurons of the nicotinic-resistant, tobacco-feeding insect Manduca sexta. Both the alpha-subunit MARA1 and the beta-subunit MARB can be detected by in situ hybridization in the majority of cultured neurons with an overlapping, but not identical, distribution. Changes in intracellular Ca(2+) evoked by nicotinic stimulation are more strongly correlated to the expression of MARA1 than MARB and are independent of cell size. Unlike the previously reported critical role of MARA1 in mediating nicotinic Ca(2+) responses, down-regulation of MARB by RNA interference (RNAi) did not reduce the number of responding neurons or the size of evoked responses, suggesting that additional subunits remain to be identified in Manduca.


Profiling of myelin proteins by 2D-gel electrophoresis and multidimensional liquid chromatography coupled to MALDI TOF-TOF mass spectrometry.
The myelin sheath is an electrically insulating layer that consists of lipids and proteins. It plays a key role in the functioning of the nervous system by allowing fast saltatory conduction of nerve pulses. Profiling of the proteins present in myelin is an indispensable prerequisite to better understand the molecular aspects of this dynamic, functionally active membrane. Two types of protein, the myelin basic protein and the proteolipid protein, account for nearly 85% of the protein content in myelin. Identification and characterization of the other "minor" proteins is, in this respect, a real challenge. In the present work, two proteomic strategies were applied in order to study the protein composition of myelin from the murine central nervous system. First, the protein mixture was separated by 2D-gel electrophoresis and, after spot excision and in-gel digestion, samples were analyzed by mass spectrometry. Via this approach, we identified 57 protein spots, corresponding to 38 unique proteins. Alternatively, the myelin sample was digested by trypsin and the resulting peptide mixture was further analyzed by off-line 2D-liquid chromatography. After the second-dimension separation (nanoLC), the peptides were spotted "on-line" onto a MALDI target and analyzed by MALDI TOF-TOF mass spectrometry. We identified 812 peptides by MALDI MS/MS, representing 93 proteins. Membrane proteins, low abundant proteins, and highly basic proteins were all represented in this shotgun proteomic approach. By combining the results of both approaches, we can present a comprehensive proteomic map of myelin, comprising a total of 103 protein identifications, which is of utmost importance for the molecular understanding of white matter and its disorders.


Co-ligation of CD44 on naive human tonsillar B cells induces progression towards a germinal center phenotype.
The precise signaling pathways to induce a germinal center (GC) phenotype and somatic mutations in human B cells are presently not understood. Major phenotypical hallmarks of a human GC B cell are up-regulated expression of CD10 and CD95 together with a heterogeneous expression of CD77. Activation of resting human tonsillar B cells using anti-CD40 and anti-IgM antibodies normally only induces up-regulation of CD38 and CD71 but has no effect on the typical GC markers. However, we show here that an additional co-ligation of the glycoprotein CD44 on such tonsillar B cells up-regulated the typical human GC markers CD10, CD38, CD77 and CD95, and down-regulated CD24 and CD39 as well as induced progression towards apoptosis in these cells; all characteristics of GC B cells. These data indicate a functional role of CD44 during activation of human naive B lymphocytes and in the generation of GC B cells.


Prevention of rat colon cancer metastases by perioperative immunostimulation.
Major intra-abdominal operations result in profound immunodepression. In addition, manipulation of malignant tumors may release tumor cells into the systemic and portal circulations. The additive effects of immunodepression and tumor cell release may enhance the metastatic potential of tumors. Perioperative correction of immune depression by levamisole can restore lymphocyte proliferation levels in rats. We have developed a model in which rat colon carcinoma cells transplanted into the portal venous system consistently induce hepatic metastases by 4 weeks and death within 9 weeks. Rats pretreated with levamisole (4 mg/kg administered intraperitoneally) the day before and the day of tumor implantation developed fewer metastases (41% of animals treated with levamisole compared with 6% of animals not treated with levamisole had less than or equal to two metastases per liver). Twenty percent of the rats treated with levamisole developed no hepatic metastases. Comparison of median liver weights between the group treated with levamisole and the nontreated, tumor-bearing group was highly significant (p less than 0.005). We conclude that the perioperative period is critical for the implantation and growth of metastases and that perioperative immunostimulation may be a factor in decreasing the incidence of metastases. This model may have relevance to the adjuvant treatment of human colon cancer.


Schizotypal personality traits and atypical lateralization in motor and language functions.
Atypical cerebral lateralization in motor and language functions in regard to schizotypal personality traits in healthy populations, as well as among schizophrenic patients, has attracted attention because these traits may represent a risk factor for schizophrenia. Although the relationship between handedness and schizotypal personality has been widely examined, few studies have adopted an experimental approach. This study consisted of three experiments focusing on motor and language functional lateralization in regard to schizotypal personality in the absence of mental illness: line-drawing, finger tapping, and a semantic go/no-go task. The results suggested that positive schizotypal personality might be related to functional non-lateralization in regard to at least some functions (e.g., spatial motor control and semantic processing in the present study). Subjects with high schizotypal personality traits performed equally with their right and left-hands in the line-drawing task and they reacted equally with their right and left-hands in a semantic go/no-go task involving semantic auditory stimuli presented in both ears. However, those low in schizotypal personality traits showed typical lateralization in response to these tasks. We discuss the implications of these findings for schizotypal atypical lateralization.


Preventable causes of cancer in Texas by race/ethnicity: insufficient physical activity.
According to the 2018 Third Expert Report from the World Cancer Research Fund/American Institute for Cancer Research, there is strong evidence that physical activity of all types and intensities protects against colon, endometrial and breast cancers. We aimed to estimate the percentage and number of incident cancer cases diagnosed in Texas in 2015 that were attributable to insufficient physical activity, and we examined for differences across racial/ethnic subgroups to reveal important causes of and potential avenues for reductions to cancer health disparities. We calculated population attributable fractions for cancers attributable to insufficient physical activity using prevalence data from the Texas Behavioral Risk Factor Surveillance System and relative risk estimates associated with insufficient physical activity from prior studies. Cancer incidence data were gathered from the Texas Cancer Registry. Overall, approximately 2.0% of all new cancers or 2094 excess cancer cases diagnosed in 2015 in Texans aged ≥25 years were attributable to insufficient physical activity, with more cancers in women (3.2%) than in men (0.8%). Of all cancer sites, the highest population attributable fraction for insufficient physical activity was observed for endometrial cancers (21.7% compared with 12.7% for colon cancers, 10.9% for premenopausal breast cancers and 2.0% for postmenopausal breast cancers). Hispanics (2.6%) and non-Hispanic blacks (2.5%) had higher proportions of cancers attributable to insufficient physical activity than non-Hispanic whites (1.8%). Public health programmes should stress physical activity as a means of cancer prevention, especially among minority groups, who may have disproportionately higher percentages of cancers attributable to insufficient physical activity.


The use of morphine to control pain in advanced cancer: an investigation of clinical usage in Bangladesh.
In 2007, 13% of all deaths worldwide were due to cancer, and of these 72% occurred in low- and middle-income countries. Opioids are essential for the successful delivery of palliative care and pain control. This paper reports data from a cross-sectional survey that aimed to investigate the use of morphine in advanced cancer in palliative care setting in Bangladesh, in order to inform clinical practice and fledgling service development. The study was a single semi-structured qualitative interview study. Cancer patients, family members and palliative care specialists (20 in total) were interviewed in two medical settings. Transcripts were transcribed verbatim, translated and cross-checked with two local interpreters. Data were imported into NVIVO 8 for coding. A coding frame was generated following line by line coding. Relational codes were established following peer review of coding units and the resulting frame. Despite having been under the pain and palliative care clinics only six out of 10 patients had received morphine. Lack of morphine availability resulted in physical suffering of patients and emotional distress of their families. Lack of availability of morphine was identified as the main barrier to pain control. International attention and collaboration with local policy makers is needed to simplify narcotic regulations and increase the availability of morphine.


Noc Corrals Migration of FtsZ Protofilaments during Cytokinesis in Bacillus subtilis.
Bacteria that divide by binary fission form FtsZ rings at the geometric midpoint of the cell between the bulk of the replicated nucleoids. In Bacillus subtilis, the DNA- and membrane-binding Noc protein is thought to participate in nucleoid occlusion by preventing FtsZ rings from forming over the chromosome. To explore the role of Noc, we used time-lapse fluorescence microscopy to monitor FtsZ and the nucleoid of cells growing in microfluidic channels. Our data show that Noc does not prevent de novo FtsZ ring formation over the chromosome nor does Noc control cell division site selection. Instead, Noc corrals FtsZ at the cytokinetic ring and reduces migration of protofilaments over the chromosome to the future site of cell division. Moreover, we show that FtsZ protofilaments travel due to a local reduction in ZapA association, and the diffuse FtsZ rings observed in the Noc mutant can be suppressed by ZapA overexpression. Thus, Noc sterically hinders FtsZ migration away from the Z-ring during cytokinesis and retains FtsZ at the postdivisional polar site for full disassembly by the Min system.IMPORTANCE In bacteria, a condensed structure of FtsZ (Z-ring) recruits cell division machinery at the midcell, and Z-ring formation is discouraged over the chromosome by a poorly understood phenomenon called nucleoid occlusion. In B. subtilis, nucleoid occlusion has been reported to be mediated, at least in part, by the DNA-membrane bridging protein, Noc. Using time-lapse fluorescence microscopy of cells growing in microchannels, we show that Noc neither protects the chromosome from proximal Z-ring formation nor determines the future site of cell division. Rather, Noc plays a corralling role by preventing protofilaments from leaving a Z-ring undergoing cytokinesis and traveling over the nucleoid.