Annual Hematocrit Profiles in Two Subspecies of White-Crowned Sparrow: A Migrant and a Resident Comparison.
Hematocrit is an easily measured parameter that can be used to assess changes in oxygen carrying capacity necessitated by fluctuations in metabolic demands. Most hematocrit studies draw conclusions from changes in hematocrit that occur over a small sampling interval without an understanding of the variation that exists across the annual cycle. White-crowned sparrows provide an excellent model system due to the existence of a resident subspecies (Zonotrichia leucophrys nuttalli) that serves as a natural control for a migrant subspecies (Zonotrichia leucophrys gambelii). Comparing these two subspecies allows for the investigation of adaptive physiological changes at each life-history stage (i.e., migration, breeding, molt, etc.) in response to changing metabolic demands. Of particular interest, this subspecies comparison, by both calendar month and life-history stage, allows for the separation of adaptive increases in hematocrit due to migration from the natural seasonal variation in hematocrit. Hematocrit levels for males and females ranged throughout the year between 42%-47% and 40%-47% in the resident and between 45%-58% and 45%-56% in the migrant. In both subspecies, hematocrit levels were elevated during the breeding season compared to the nonbreeding season, and levels were reduced in females during egg laying. When grouped by life-history stage, hematocrit levels were always higher in the migrant compared to the resident. During the months in which migration occurred, hematocrit levels were 10%-12% higher in the migrant compared to the resident subspecies. These data suggest differential regulation of hematocrit between the two subspecies that may be attributed to phenotypic plasticity or genetic differences.


Zero valent iron core-iron oxide shell nanoparticles as small magnetic particle imaging tracers.
Nanoparticle tracers with small sizes and large magnetization are critical for biomedical imaging and especially for magnetic particle imaging (MPI). Small size is important for accessing future intracellular and neurological in vivo applications Here, we show <15 nm nanoparticles made of zero valent iron cores, iron oxide shells and coated with a strongly binding brush co-polymer are effective MPI tracers. The small nanoparticle cores create a hydrodynamic diameter that is half of the state-of-the-art iron oxide tracers while the strongly magnetic zero valent iron maintains similar MPI signal magnitude and resolution.


[Effect of corticotropin and hydrocortisone on the Ca2+-ATPase activity of skeletal muscle sarcoplasmic reticulum].
The effect of corticotropin (ACTH1-39), synacthen (ACTH1-24) and hydrocortisone-hemisuccinate on the activity of Ca-ATPase of skeletal muscle sarcoplasmic reticulum (SR) and calcium (Ca) accumulation in SR vesicles has been studied. It has been shown that ACTH1-39 (I U per 100 g body weight) increased the activity of Ca-ATPase in skeletal muscle SR of rats, while hydrocortisone (5 mg per 100 g body weight) did not change the activity of Ca-ATPase in skeletal muscle SR. However, both hormones increase the total activity of ATPase. ACTH1-39 and ACTH1-24 (0.05-0.0005 U/ml) and hydrocortisone (2.8 X 10(-7)-2.8 X 10(-9) mol/l) increased in vitro Ca-ATPase isolated from rabbit skeletal muscle SR and accumulation of Ca is SR vesicles. At the same time, hydrocortisone reduced calcium/phosphorus ratio, while ACTH1-39 and ACTH1-24 increased it, i.e. hydrocortisone facilitated Ca accumulation in SR requiring more ATP energy, whereas ACTH facilitated Ca accumulation in SR requiring less ATP energy.


Inhibition of nitric oxide synthase induces a selective reduction in tumor blood flow that is reversible with L-arginine.
The effect of i.v. administration of the nitric oxide synthase (NOS) inhibitor N(omega)-nitro-L-arginine (L-NNA) on tumor blood flow compared with normal tissue blood flow was studied in anesthetized BD9 rats bearing subcutaneous P22 carcinosarcomas. Blood flow was measured by the tissue uptake of radiolabeled iodoantipyrine. The reversibility of blood flow changes was tested by subsequent administration of L-arginine, the natural substrate for NOS. The effect of L-NNA was compared to that of the imidazolineoxyl N-oxide C-PTIO, a carboxyl derivative of 2-phenyl-4,4,5,5,-tetramethylimidazoline-1-oxyl-3-oxide and a nitric oxide scavenger. Drug-induced changes in mean arterial blood pressure (MABP) were monitored and used to calculate relative drug-induced changes in tissue vascular resistance. Heart rate was measured from blood pressure traces. L-NNA significantly decreased heart rate and increased MABP in a dose-dependent manner. Significant dose-dependent reductions in blood flow with L-NNA were observed in tumor, skeletal muscle, spleen, and skin overlying the tumor. No significant effect was found for normal skin, brain, heart, kidney, and small intestine. At 1 mg/kg, the effect of L-NNA was selective for the tumor, with a significant decrease in tumor blood flow to 0.45 of the control level and no significant effect in any of the normal tissues. Higher doses did not produce any further reduction in tumor blood flow, presumably due to an increase in tumor perfusion pressure arising from the increase in MABP at these doses. Vascular resistance was increased to some extent in all of the tissues studied but, overall, was greatest in the tumor. At 1 mg/kg, there was a 2-2.5-fold increase in tumor vascular resistance but no significant increase in any of the normal tissues. At the highest dose used (10 mg/kg), the increases in vascular resistance in the skeletal muscle and spleen were equivalent to that in the tumor. Administration of L-arginine 15 min after L-NNA completely reversed the decrease in tumor blood flow observed for 1 mg/kg L-NNA alone. In contrast to the effect of L-NNA, constant i.v. infusion of C-PTIO had no effect on tumor or normal tissue blood flow. These results indicate that nitric oxide is important for maintaining a vasodilatory tone in tumors and that inhibition of NOS may provide a means for enhancing therapeutic regimens that would benefit from a selective reduction in tumor blood flow.


Tubotympanic cholesteatoma.
Chronic suppurative otitis media is defined as a chronic inflammation of the mucoperiosteal lining of the middle ear cleft. It is described as a persistent disease that is insidious in onset, often capable of causing severe destruction with irreversible sequelae, and clinically present with hearing loss and discharge. It has been classified into tubotympanic (safe) and atticoantral (unsafe) perforation. Cholesteatoma always occur in the atticoantral type and in marginal perforation. We report a case of cholesteatoma that occurred as a tubotympanic type of perforation.


Polyaniline/Pure Carbon Assemblies as Efficient Self-standing Metal-free Oxygen Electrodes in Alkaline Media for Zn-Air Batteries.
A facile design and fabrication of self-standing metal-free polyaniline (PANI)@carbon nanotubes (CNTs) composite membrane was initially proposed by straightforward noncovalent wrapping the polymer around pure CNTs. Without introduction of extra heteroatoms into CNTs, the optimized PANI@CNTs composite exhibits a much better electrocatalytic performance for oxygen evolution reaction (OER) than pure CNTs via favorable interfacial modification with PANI to largely expose the active sites of on the surface of pure CNTs. Besides, it displays good oxygen reduction reaction (ORR) performance. When directly utilized as bifunctional air electrode without extra additive agents, the composite membrane-enabled rechargeable Zn-air batteries not only deliver a high peak power density (201.9 W g-1 ) and a large energy density (850.3 Wh kgZn -1 ), but also present robust cycling performance for 216 cycles with a high energy efficiency of 57.8%.


Using the theory of planned behavior to determine factors influencing processed foods consumption behavior.
The purpose of this study is to identify how level of information affected intention, using the Theory of Planned Behavior. The study was conducted survey in diverse community centers and shopping malls in Seoul, which yielded N = 209 datasets. To compare processed foods consumption behavior, we divided samples into two groups based on level of information about food additives (whether respondents felt that information on food additives was sufficient or not). We analyzed differences in attitudes toward food additives and toward purchasing processed foods, subjective norms, perceived behavioral control, and behavioral intentions to processed foods between sufficient information group and lack information group. The results confirmed that more than 78% of respondents thought information on food additives was insufficient. However, the group who felt information was sufficient had more positive attitudes about consuming processed foods and behavioral intentions than the group who thought information was inadequate. This study found people who consider that they have sufficient information on food additives tend to have more positive attitudes toward processed foods and intention to consume processed foods. This study suggests increasing needs for nutrition education on the appropriate use of processed foods. Designing useful nutrition education requires a good understanding of factors which influence on processed foods consumption.


Fabrication of nor-seco-cucurbit[10]uril based supramolecular polymers via self-sorting.
A nor-seco-CB[10] (ns-CB[10]) based linear supramolecular polymer is firstly fabricated via self-sorting strategy. Through self-sorting of the monomer, ns-CB[10] and CB[7], the unfavorable factors for supramolecular polymerization are avoided. Therefore, supramolecular polymer with high molecular weight is successfully fabricated, and the molecular weight can be controllably regulated.


Prevention of Carotid Artery Atherosclerosis: What is the Evidence?
Carotid artery atherosclerosis (CAA) represents a significant form of atherosclerosis with stroke as a major consequence. Whether it is a unique form of atherosclerosis is not established. However, this is not of major clinical relevance as no specific preventive measures over and above the established ones for cardiovascular risk are well established. Major risk factors for CAA are elevated low-density lipoprotein cholesterol (LDL-C), diabetes mellitus, tobacco use, hypertension, and increased inflammation. Identification of CAA prior to a clinical event centers on imaging studies. Studies with magnetic resonance imaging result in the best definition of CAA plaque morphology. Medical measures that result in prevention are especially centered on statins (marked reduction of the LDL-C) and hypertension control. Nonprocedural therapeutic measures to avoid and delay complications involve antiplatelet medications. Benefits from other measures such as increasing high-density lipoprotein cholesterol and increased exercise appear desirable but require more clinical evidence. In conclusion, there are enough evidence-based medicine results to demand intensive medical preventive measures and not just relegate the patient with asymptomatic or symptomatic CAA to decision-making only involving the surgeon and interventionalist.


Estimating the completeness of death registration.
Summary Death registration statistics, even when incomplete, can provide valuable information about mortality. In particular, the age structure of deaths can be used to estimate the completeness of registration, provided that this completeness does not vary substantially with age. Two methods of estimating the completeness of death registration from the distribution of deaths by age are described. The first is derived from stable population theory and requires an estimate of the rate of natural increase of the population, as well as assuming stability. However, the technique can also be used to generate simultaneously estimates of the rate of natural increase and of death registration completeness. The second method which requires two census age distributions and intercensal deaths by age, estimates the relative enumeration completeness of the two censuses as well as the completeness of death registration and requires only that the population be closed. Results are sensitive to overstatement of age. The methods are illustrated by being applied to figures from Thailand for the period 1960-70 and are found to work satisfactorily.


TIMI, PURSUIT, and GRACE risk scores: sustained prognostic value and interaction with revascularization in NSTE-ACS.
Regarding prognosis, patients with a non-ST elevation acute coronary syndrome (ACS) are a very heterogeneous population, with varying risks of early and long-term adverse events. Early risk stratification at admission seems to be essential for a tailored therapeutic strategy. We sought to compare the prognostic value of three ACS risk scores (RSs) and their ability to predict benefit from myocardial revascularization performed during initial hospitalization. We studied 460 consecutive patients admitted to our coronary care unit with an ACS [age: 63+/-11 years, 21.5% female, 55% with myocardial infarction (MI)]. For each patient, the Thrombolysis In Myocardial Infarction (TIMI), Platelet glycoprotein IIb/IIIa in Unstable agina: Receptor Suppression Using Integrilin (PURSUIT), and Global Registry of Acute Coronary Events (GRACE) RSs were calculated using specific variables collected at admission. Their prognostic value was evaluated by the combined endpoint of death or MI at 1 year. The best cut-off value for each RS, calculated with receiver operating characteristic curves, was used to assess the impact of myocardial revascularization on the combined incidence of death or MI. Death or MI at 1 year was 15.4% (32 deaths/49 MIs). The best predictive accuracy for death or MI at 1 year was obtained by the GRACE RS (AUC) [area under the curve: 0.715; confidence interval (CI: 0.672-0.756)] but the performance of the PURSUIT RS (AUC: 0.630; CI: 0.584-0.674), and TIMI RS (AUC: 0.585; CI: 0.539-0.631) was also good. We found a statistically significant interaction between the risk stratified by the best cut-off value for the GRACE and PURSUIT RSs and myocardial revascularization, with a better prognosis for the high-risk patients. The high-risk patients represented 36.7, 28.7, and 57.8% of the population, for the GRACE, PURSUIT, and TIMI RSs, respectively. The RSs studied demonstrated a good predictive accuracy for death or MI at 1 year and enabled the identification of high-risk subsets of patients who will benefit most from myocardial revascularization performed during initial hospital stay.


U.S. Government quality control program for Limulus amebocyte lysate and endotoxin.
The U.S. Government has licensed seven Limulus Amebocyte Lysate manufacturers. Each manufacturer must determine the sensitivity of each lot by using the U.S. Standard Endotoxin, EC-5 which is identical to the U.S. Pharmacopeia (USP) Endotoxin Standard (Lot F). A licensed firm must be inspected annually and submit a protocol along with potency testing results on each lot of lysate before it can be released. The FDA tests each lot for at least potency before releasing it to be marketed. The release criteria for both the gelation and chromogenic lysate tests are discussed.


Loss of GD1-positive Lactobacillus correlates with inflammation in human lungs with COPD.
The present study assesses the relationship between contents of GD1 (glycerol dehydratase)-positive Lactobacillus, presence of Lactobacillus and the inflammatory response measured in host lung tissue in mild to moderate chronic obstructive pulmonary disease (COPD). We hypothesise that there will be a loss of GD1 producing Lactobacillus with increasing severity of COPD and that GD1 has anti-inflammatory properties. Secondary care, 1 participating centre in Vancouver, British Columbia, Canada. 74 individuals who donated non-cancerous portions of their lungs or lobes removed as treatment for lung cancer (normal lung function controls (n=28), persons with mild (GOLD 1) (n=21) and moderate (GOLD 2) COPD (n=25)). Primary outcome measure was GD1 positivity within each group and whether or not this impacted quantitative histological measures of lung inflammation. Secondary outcome measures included Lactobacillus presence and quantification, and quantitative histological measurements of inflammation and remodelling in early COPD. Total bacterial count (p>0.05) and prevalence of Lactobacillus (p>0.05) did not differ between groups. However, the GD1 gene was detected more frequently in the controls (14%) than in either mild (5%) or moderate (0%) COPD (p<0.05) samples. Macrophage and neutrophil volume fractions (0.012±0.005 (mean±SD) vs 0.026±0.017 and 0.005±0.002 vs 0.015±0.014, respectively) in peripheral lung tissue were reduced in samples positive for the GD1 gene (p<0.0035). A reduction in GD1 positivity is associated with an increased tissue immune inflammatory response in early stage COPD. There is potential for Lactobacillus to be used as a possible therapeutic, however, validation of these results need to be completed before an anti-inflammatory role of Lactobacillus in COPD can be confirmed.


Synthesis of ceramides and cerebrosides containing both alpha-hydroxy and nonhydroxy fatty acids from lignoceroyl-CoA by rat brain microsomes.
The conversion of [1-14C]lignoceroyl-CoA to nonhydroxy- and alpha-hydroxyceramides and cerebrosides by brain microsomes of developing rat in the presence of NADPH was investigated. A new technique of thin layer chromatography for the separation of these lipids and unreacted substrate was developed for this assay. The synthesis of nonhydroxy- and hydroxyceramides was significantly stimulated by the addition of heat-stable factor, a factor which is essential in the alpha-hydroxylation of free lignoceric acid (I. Singh and Y. Kishimoto, manuscript in preparation). The addition of sphingosine also stimulated the ceramide synthesis to a great extent. When the microsomes or heat-stable factor were crude, the ceramides formed were further converted to cerebrosides, apparently by UDP-galactose contamination. The purification of these subcellular components resulted in the formation of only ceramides which, in turn, were converted to cerebrosides by the addition of UDP-galactose. These observations indicate that hydroxyceramide is the precursor of hydroxycerebroside and is formed by alpha-hydroxylation of lignoceroyl-CoA and N-acylation of sphingosine. However, lignoceroyl-CoA, like free lignoceric acid, does not appear to be the immediate substrate of the alpha-hydroxylation.


Oxidation of isoprothiolane by ozone and chlorine: Reaction kinetics and mechanism.
Isoprothiolane (IPT) was one of the most commonly used pesticides around the world. It was reported to be the highest concentration and frequency of detection of 13 most commonly used pesticides in Mekong Delta recently. The oxidation degradation kinetic of ozone and chlorine with IPT and the identification of the degradation products was investigated in this research. The results showed that both ozone and chlorine oxidized IPT rapidly under typical water treatment condition, and that both reactions followed second order reaction kinetics. The ozone reaction rates exhibited no pH dependence with the rate constant of 247.1 (±11.0) M-1s-1 at 25 °C, whereas chlorine reaction rates increased dramatically with decreasing pH. The rate constant for hypochloric acid was 73.3 (±3.1) M-1s-1 at 25 °C, while the reaction of hypochlorite was negligible. The degradation products by chlorine and ozone were identified by LC-MS/MS and the reaction pathways were proposed. The thioether and the carbon-carbon double bond in IPT were the reactive sites during chlorine and ozone oxidation. The thioether group was oxidized into sulfoxide and further sulfone group, and the carbon-carbon double bone were cleaved to form diisopropyl ester of malonic acid, diisopropyl ester of tartronic acid and diisopropyl ester of ketomalonic acid monohydrate. Compared to ozone reaction, it was more complicated for chlorine reaction, which yielded chlorine substituted, hydroxylated and dithiolane ring-opening products.


[Influence of occupational activity on serum vitamin antioxidants content in patients after hemorrhagic fever with renal syndrome].
Studies covered changes in serum vitamin antioxidant content in patients with hemorrhagic fever with renal syndrome male workers, in accordance with occupational activity type. Findings are that during the disease and convalescence period the drivers examined demonstrated reliably lower levels of vitamins A, E and beta-carotene vs. those in male office workers having no contact with occupational hazards.


Errors of diagnosis in pediatric practice: a multisite survey.
We surveyed pediatricians to elicit their perceptions regarding frequency, contributing factors, and potential system- and provider-based solutions to address diagnostic errors. Academic, community, and trainee pediatricians (N = 1362) at 3 tertiary care institutions and 109 affiliated clinics were invited to complete the survey anonymously through an Internet survey administration service between November 2008 and May 2009. The overall response rate was 53% (N = 726). More than one-half (54%) of respondents reported that they made a diagnostic error at least once or twice per month; this frequency was markedly higher (77%) among trainees. Almost one-half (45%) of respondents reported diagnostic errors that harmed patients at least once or twice per year. Failure to gather information through history, physical examination, or chart review was the most-commonly reported process breakdown, whereas inadequate care coordination and teamwork was the most-commonly reported system factor. Viral illnesses being diagnosed as bacterial illnesses was the most-commonly reported diagnostic error, followed by misdiagnosis of medication side effects, psychiatric disorders, and appendicitis. Physicians ranked access to electronic health records and close follow-up of patients as strategies most likely to be effective in preventing diagnostic errors. Pediatricians reported making diagnostic errors relatively frequently, and patient harm from these errors was not uncommon.


Therapeutic effects of physostigmine during systemic inflammation.
Usually, physostigmine is used as antidote for anticholinergic poisons in order to improve hemodynamics and cardiac output. In addition, it causes beneficial effects during sepsis when added timely. Here, we studied whether physostigmine improves hemodynamics when treatment during systemic inflammation was delayed. Two series of randomized studies with overall 44 rats were conducted. Systemic inflammation was induced by lipopolysaccharide (LPS) infusion (0.5 mg LPS/kg×h). Physostigmine (PHY) was intravenously applied after an LPS infusion period of 90 minutes (50 µg PHY/kg within 10 minutes) with (series 1) and without (series 2) additional volume loading. Hemodynamic parameters, blood gases, and parameters for tissue damage were periodically determined for up to 180 minutes. Even though volume was additionally administered (series 1), LPS caused a reduction of peripheral blood flow. Treatment with PHY improved hemodynamics in macrocirculation (mean arterial blood pressure) and microcirculation (peripheral blood flow). PHY neither affected alterations in blood gases, electrolyte homeostasis, and glucose metabolism nor prevented intestinal damage induced by LPS. In series 2, without any additional volume loading, PHY likewise resulted in an improvement of the LPS-induced alterations in macro- and microcirculation, but finally worsened the LPS-mediated effects on plasma parameters for tissue damage such as creatine kinase, probably due to the lack of volume and a further damage to the heart. The present results demonstrated that hemodynamic responses to PHY may not only be visible in patients with anticholinergic drug overdose but also be visible in septic patients, provided that fluid intake of these patients is adequate.


Solar neutrinos--from puzzle to paradox.
The solar neutrino puzzle is deepening into a paradox that refutes the basic logic of the reaction chain that powers the sun by the fusion of protons into heavy elements. Experiments now reveal a serious anomaly in the relative neutrino fluxes from the different steps in the chain. Neutrinos from boron-8 at the end of the chain are seen but hardly any are seen from beryllium-7, without which the observed boron-8 cannot be made. The only apparent way to avoid a paradoxical "missing link" in the sun's energy chain is a nonzero neutrino mass, an idea that can be tested in future experiments.


A study of liver biopsies and liver disease among hemophiliacs.
Hepatic histologic materials (biopsy or autopsy) and associated clinical data from 155 hemophiliacs were collected by an ad hoc hemophilia study group and analyzed retrospectively in an effort to determine the spectrum of liver disease in this population and to examine the relationship between the severity of liver disease and treatment history. Clinical information on the frequency of complications from 126 biopsies in 115 hemophilic patients provided a unique opportunity to assess the safety of liver biopsy in such patients. The incidence of cirrhosis (15%) and chronic active hepatitis (7%) was lower than previously reported. The frequency of severe liver disease (chronic active hepatitis or cirrhosis) in patients receiving large pooled concentrates was no greater than in patients treated principally with cryoprecipitate or plasma. The risks of liver biopsy in this setting are relatively high: clinically significant hemorrhage followed 12.5% of the procedures.


Deterministic dynamics of neural activity during absence seizures in rats.
The study of brain electrical activities in terms of deterministic nonlinear dynamics has recently received much attention. Forbidden ordinal patterns (FOP) is a recently proposed method to investigate the determinism of a dynamical system through the analysis of intrinsic ordinal properties of a nonstationary time series. The advantages of this method in comparison to others include simplicity and low complexity in computation without further model assumptions. In this paper, the FOP of the EEG series of genetic absence epilepsy rats from Strasbourg was examined to demonstrate evidence of deterministic dynamics during epileptic states. Experiments showed that the number of FOP of the EEG series grew significantly from an interictal to an ictal state via a preictal state. These findings indicated that the deterministic dynamics of neural networks increased significantly in the transition from the interictal to the ictal states and also suggested that the FOP measures of the EEG series could be considered as a predictor of absence seizures.


Craniofacial modifications in children with habitual snoring and obstructive sleep apnoea: a case-control study.
Habitual snoring and obstructive sleep apnoea in children, which are frequently associated with adenotonsillar hypertrophy, may begin early in life and in relation with orocraniofacial features. The aim of this study was to detect the presence of early bone craniofacial modifications in young children with a long history of habitual snoring. Twenty-six habitually snoring children (mean age 4.6 yrs) were studied by nocturnal portable recording or diurnal polysomnography, cephalometry and orthodontic evaluation. A comparison of cephalometric findings was made between the studied group and 26 age-matched children (mean age 5.1 yrs) with no history of snoring or respiratory problems during sleep. The cephalometric analyses showed a significant increase in craniomandibular intermaxillar, lower and upper goniac angles with a retroposition and posterior rotation of the mandible (high angle face) and a reduction in the rhinopharynx space caused by higher thickness of adenoids in habitually snoring children compared with controls. Cross-bites and labial incompetence as well as daytime symptoms and familiarity for habitual snoring were found in most of the studied group of snorers compared with controls. The results indicate that upper airway obstruction during sleep is associated with mild but significant cephalometric and craniofacial modifications in children complaining of habitual snoring. Whether this skeletal conformation is genetically determined or influenced by the early onset of habitual snoring remains to be assessed.


Electrical stimulation inhibits Val-boroPro-induced pyroptosis in THP-1 macrophages via sirtuin3 activation to promote autophagy and inhibit ROS generation.
The incidence of atherosclerosis (AS), a major contributor to cardiovascular disease, is steadily rising along with an increasingly older population worldwide. Pyroptosis, a form of inflammatory programmed cell death, determines the release of pro-inflammatory mediators by endothelial cells, smooth muscle cells, and atheroma-associated macrophages and foam cells, thereby playing a critical role in AS progression. Canonical pyroptosis is mediated by inflammasome formation, activation of caspase-1, and maturation and release of proinflammatory cytokines. Electrical stimulation (ES) is a noninvasive, safe therapy that has been shown to alleviate symptoms in several health conditions. Here, we investigated the anti-inflammatory and anti-pyroptotic effects of ES in human THP-1 macrophages treated with the dipeptidyl peptidase inhibitor Val-boroPro (VbP). We found that ES downregulated NOD-like receptor family protein 3 (NLRP3) inflammasome, ASC, and caspase-1 expression and abrogated the release of Interleukin-1β (IL-1β) and Interleukin-18 (IL-18), indicating effective pyroptosis inhibition. These changes were paralleled by a reduction in reactive oxygen species (ROS) production, reversal of VbP-induced sirtuin3 (Sirt3) downregulation, deacetylation of ATG5, and induction of autophagy. These findings suggest that ES may be a viable strategy to counteract pyroptosis-mediated inflammation in AS by raising Sirt3 to promote autophagy and inhibit ROS generation.


Dose, duration and strain of bacillus Calmette-Guerin in the treatment of nonmuscle invasive bladder cancer: Meta-analysis of randomized clinical trials.
Intravesical bacillus Calmette-Guerin (BCG) instillation is widely used as an adjuvant therapy after transurethral resection of bladder tumor (TURBT) in patients with intermediate- and high-risk nonmuscle invasive bladder cancer (NMIBC). However, the effective dose, duration, and strain of BCG have not yet been clearly determined. We aimed to elucidate the relationship between dose, duration, and strain of BCG and clinical outcomes in NMIBC patients treated with TURBT. We conducted a literature search in Embase, Scopus, and PubMed databases for all relevant articles published up to October 2016 in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. The relative risks of clinical outcomes, including recurrence, progression, cancer-specific mortality, and all-cause mortality according to dose (standard vs low), duration (induction vs maintenance), and strain of BCG were presented as the pooled risk ratio (RR) and 95% confidence interval (CI). Nineteen studies meeting the inclusion criteria were finally selected in this meta-analysis. The risk of recurrence was significantly highly observed in case of low-dose BCG (RR, 1.17; 95% CI 1.06-1.30) and induction BCG (RR, 1.33; 95% CI 1.17-1.50) only group without heterogeneity among the included studies. Although there were no significant differences between dose or duration and other clinical outcomes. On direct comparison in each study comparing BCG strains, the Tice stain showed a relatively high probability of recurrence compared with the Connaught (RR, 1.29; 95% CI 1.01-1.64) and RIVM (RR, 2.04, 95% CI 1.28-3.25) strains. Funnel plot testing revealed no significant publication bias. The use of standard dose and maintenance BCG instillation may be effective to reduce recurrence rate after TURBT for NMIBC. Further large scale, well-designed, and prospective studies, with stratification of the patients into risk group at randomization, will be required to determine the optimal guideline of BCG use to improve clinical outcomes in NMIBC.


Pain management documenting the decision making process.
From patient admission to discharge, pain is a critical symptom of concern to the nurse case manager. This descriptive study examined nurses' decision-making regarding pain management as documented in clinical records of patients after orthopedic surgery. Using a Nurses' Pain Management Audit Tool, data analysis revealed that during the first 24 hours after emergence from the Post-Anesthesia Care Unit, these patients received less than 50% of the narcotic doses available for their pain relief. Nurses documented less than 25% of the "ideal occurrences" possible for pain assessment, as described in the Agency for Health Care Policy and Research Guidelines. Incomplete databases for guiding patient outcomes of effective pain management were perpetuated by insufficient documentation. Nurse case managers could stimulate increased commitment and quality improvement in pain management as a crucial aspect of patient care.


Social adaptation status of Syrian refugee physicians living in Turkey.
Since the beginning of the civil war in Syria, over 3.5 million Syrians have fled to Turkey. Considering the massive burden of healthcare service needs of this population, the Turkish government has launched an initiative as employing Syrian doctors to provide health services to their citizens in Refugee Health Centres. In this study, we aimed to explore the social adaptation status of Syrian physicians living in Turkey using a structured questionnaire and the Social Adaptation Self Evaluation Scale (SASS). Between November 2016 and April 2018, 799 physicians who participated in "Syrian Physicians' Adaptation Training" were enrolled in the study and underwent a structured questionnaire that questioned socio-demographic data and the SASS. The participants were divided into two groups as having poor and normal/high SASS scores. The binary SASS groups were compared with some demographic data. The median SASS score of the respondents was found as 43 (min. 10, max. 60, IQR 10) which can be accepted as normal. In the binary grouping, it was seen that 107 (13.39%) participants had poor social adaptation, whereas 692 (86.61%) participants had normal or high social adaptation scores. The physicians who were certain about not going back to Syria had significantly higher SASS scores. The social adaptation scores of the Syrian physicians were considerably high. The adaptation status was found to be associated with some characteristics like living in Turkey for a long time and having pre-knowledge about the Turkish healthcare system.


Paediatric choroid plexus carcinoma: a retrospective case series from Karachi.
The objective of this study is to report clinical, radiological, and histopathological characteristics of three paediatric patients diagnosed as Choroid plexus carcinoma seen at our hospital, between 2015 and 2020. Three patients were diagnosed with choroid plexus carcinomas between 2015 and 2018. The mean age at diagnosis was 1.3 years (range 8 months to 1.5 years). All the three patients had subtotal resection and received adjuvant chemotherapy. One patient also received adjuvant radiotherapy. Despite these treatment measures, residual disease was noted in all three patients and two patients were subsequently treated on palliative care grounds. The average duration of follow-up after the first surgery for all three patients was approximately 33 months. Attaining satisfactory outcome in patients with CPC is challenging. Our case series reflects the difficulty in achieving gross total resection and ensuring that the disease does not recur.


[Therapy of esophageal stenoses in recessive epidermolysis bullosa dystrophica].
Stenosis or complete occlusion of the oesophagus are potentially life-threatening complications of recessive dystrophic epidermolysis bullosa. Consequences are malnutrition, growth retardation, aspiration, or cachexia. Total replacement of the oesophagus by colon interposition has been recommended in such patients. We report on successful conservative management. We applied recently developed knowledge concerning the defective collagenase involved in this disorder and oesophageal dilatation. Phenytoin has been shown to reduce the excessive production of collagenase and thereby to diminish blistering of skin and mucous membranes and stricture formation of the oesophagus. Stepwise dilatation of oesophageal strictures instead of bouginage represents a less traumatic way to restore the oesophageal lumen. The lumen can be maintained by soft nasogastric feeding tubes which may be removed later on after successful dilatation. Oesophageal passage has been maintained for up to 4 years. The management of these severe complications of recessive dystrophic epidermolysis bullosa requires interdisciplinary efforts of dermatologists, internists and otorhinolaryngologists.


Anti-müllerian hormone protein expression is reduced during the initial stages of follicle development in human polycystic ovaries.
Polycystic ovary syndrome, the most common cause of anovulatory infertility, is characterized by disordered folliculogenesis, notably increased progression from the primordial to the primary stages. This ovarian phenotype is similar to that observed in mice lacking anti-müllerian hormone (AMH). The objective of this study is to investigate whether AMH is involved in accelerating the transition of follicles from primordial to primary stages in polycystic ovaries. This study compares AMH expression in archive tissue from normal and polycystic ovaries. This is a laboratory-based study. Ovarian tissue from seven normoovulatory women and 16 women with polycystic ovaries (five of whom were anovulatory) was used in this study. Ovaries were classified by histology and with reference to menstrual cycle history and ultrasound. Presence and intensity of AMH expression in 1403 follicles was the main outcome measure. AMH was observed from the primordial stage onward. AMH immunostaining was observed in significantly fewer primordial (P = 0.007) and transitional follicles (P = 0.001) in ovaries from anovulatory women with polycystic ovaries compared with women with regular cycles and either normal or polycystic ovaries. AMH-negative follicles had fewer pregranulosa cells in the largest cross-section of the follicle at both the primordial (median, four and six for AMH-negative and -positive follicles, respectively; P < 0.0001) and transitional stages (median six and nine; P < 0.0007) in normal tissue, and fewer at the transitional stage (median, seven and 11; P < 0.0001) in tissue from anovulatory women with polycystic ovaries. This suggests that AMH expression is associated with granulosa cell mitosis. These findings indicate a relative deficiency of AMH in primordial and transitional follicles in ovaries from anovulatory women with polycystic ovaries. This may contribute to disordered early follicle development in polycystic ovary syndrome.


Care management for Type 2 diabetes in the United States: a systematic review and meta-analysis.
This systematic review and meta-analysis aims at assessing the composition and performance of care management models evaluated in the last decade and their impact on patient important outcomes. A comprehensive literature search of electronic bibliographic databases was performed to identify care management trials in type 2 diabetes. Random effects meta-analysis was used when feasible to pool outcome measures. Fifty-two studies were eligible. Most commonly reported were surrogate outcomes (such as HbA1c and LDL), followed by process measures (clinic visit or testing frequency). Less frequently reported were quality of life, patient satisfaction, self-care, and healthcare utilization. Most care management modalities were carved out from primary care. Meta-analysis demonstrated a statistically significant but trivial reduction of HbA1c (weighted difference in means -0.21%, 95% confidence interval -0.40 to -0.03, p < .03) and LDL-cholesterol (weighted difference in means -3.38 mg/dL, 95% confidence interval -6.27 to -0.49, p < .02). Most care management programs for patients with type 2 diabetes are 'carved-out', accomplish limited effects on metabolic outcomes, and have unknown effects on patient important outcomes. Comparative effectiveness research of different models of care management is needed to inform the design of medical homes for patients with chronic conditions.


Pseudotyped Viruses As a Molecular Tool to Monitor Humoral Immune Responses Against SARS-CoV-2 Via Neutralization Assay.
Pseudotyped viruses (PVs) are molecular tools that can be used to study host-virus interactions and to test the neutralizing ability of serum samples, in addition to their better-known use in gene therapy for the delivery of a gene of interest. PVs are replication defective because the viral genome is divided into different plasmids that are not incorporated into the PVs. This safe and versatile system allows the use of PVs in biosafety level 2 laboratories. Here, we present a general methodology to produce lentiviral PVs based on three plasmids as mentioned here: (1) the backbone plasmid carrying the reporter gene needed to monitor the infection; (2) the packaging plasmid carrying the genes for all the structural proteins needed to generate the PVs; (3) the envelope surface glycoprotein expression plasmid that determines virus tropism and mediates viral entry into the host cell. In this work, SARS-CoV-2 Spike is the envelope glycoprotein used for the production of non-replicative SARS-CoV-2 pseudotyped lentiviruses. Briefly, packaging cells (HEK293T) were co-transfected with the three different plasmids using standard methods. After 48 h, the supernatant containing the PVs was harvested, filtered, and stored at -80 °C. The infectivity of SARS-CoV-2 PVs was tested by studying the expression of the reporter gene (luciferase) in a target cell line 48 h after infection. The higher the value for relative luminescence units (RLUs), the higher the infection/transduction rate. Furthermore, the infectious PVs were added to the serially diluted serum samples to study the neutralization process of pseudoviruses' entry into target cells, measured as the reduction in RLU intensity: lower values corresponding to high neutralizing activity.


A sex difference in the seasonal variation of suicide rate: a single cycle for men, two cycles for women.
The marked seasonal fluctuation in suicide rates observed by Durkheim appears to be diminishing, and in some cases, to have vanished. In this study, suicide data in Britain from 1958 to 1974 were studied by auto-correlational methods. A cyclical variation was found for both men and women. Men showed a single twelve monthly cycle whereas women showed two cycles. No explanation for this difference is immediately apparent.


Moderate mass loss enhances flight performance via altering flight kinematics and postures in a passerine bird.
Many birds experience fluctuations in body mass throughout the annual life cycle. The flight efficiency hypothesis posits that adaptive mass loss can enhance birds' flight ability. However, whether birds can increase additional wing loading following mass loss and how birds adjust flight kinematics and postures remain largely unexplored. We investigated physiological changes in body condition in breeding female Eurasian tree sparrows (Passer montanus) through a dietary restriction experiment and determined the changes in flight kinematics and postures. Body mass decreased significantly, but the external maximum load and mass-corrected total load increased significantly after three days of dietary restriction (DR3). After six days of dietary restriction (DR6), the hematocrit and both pectoralis and hepatic fat contents, the takeoff speed, theoretical maximum range speed and maximum power speed declined significantly. Notably, the load capacity and power margin remained unchanged relative to the control group. The wing stroke amplitude and relative downstroke duration were not affected by the interaction between diet restriction and extra load. The wing stroke amplitude significantly increased after DR6 treatment, while the relative downstroke duration significantly decreased. The stroke plane angle significantly increased after DR6 treatment only in the load-free condition. In addition, the sparrows adjusted their body angle and stroke plane angle in response to the extra load, but stroke amplitude and wingbeat frequency remained unchanged. Therefore, birds can maintain and even enhance their flight performance by adjusting flight kinematics and postures after a short-term mass loss.


Molecular pathways: YAP and TAZ take center stage in organ growth and tumorigenesis.
The evolution of a solid tumor is fueled by genetic aberrations. Yet, the tumor environment often dominates over the effects of genetics: normal tissues have powerful tumor-suppressive properties that constantly tame or eliminate cells carrying transforming mutations. Critical elements of such a suppressive microenvironment are structural characteristics of normal cells and tissues, such as cell polarity, attachment to the extracellular matrix (ECM), and epithelial organization. Once these tissue-level checkpoints have been overcome, tumor growth is enhanced by recruitment of stromal cells and remodeling of the ECM. Genetic inactivation in mouse models indicates the Hippo pathway as a fundamental inhibitor of organ growth during development and as a critical tumor suppressor in epithelial tissues, such as the liver, skin, and ovaries, and soft tissues. At the centerpiece of this pathway lie two related transcriptional coactivators, YAP and TAZ, that promote tissue proliferation and the self-renewal of normal and cancer stem cells, and incite metastasis. Strikingly, YAP and TAZ are controlled by the same architectural features that first inhibit and then foster cancer growth, such as ECM elasticity, cell shape, and epithelial-to-mesenchymal transition. These findings open unexpected opportunities for the development of new cancer therapeutics targeting key YAP/TAZ regulatory inputs such as Wnt signaling, cytoskeletal contractility, G-protein-coupled receptors, or YAP/TAZ-regulated transcription.


Balanced vs. slightly unbalanced selection.
Balanced selection, defined as that all parents have equal contributions to the next generation, is expected to minimize the loss of gene diversity and thereby to allow a steady increase of selection response even at very advanced generations. In this study, balanced selection was compared with two degrees of slightly unbalanced selection (equal contributions from most of the families) and with unrestricted selection (unequal contributions) in terms of the retrieved response and genetic diversity consumed (group coancestry) over 30 generations of selection. A simulation was used varying the heritability and considering two population sizes and two family sizes. Results showed that a slight unbalance can bring a favourable relation between retrieved response and genetic diversity when compared to balanced selection at low and moderate heritabilities, and when small families and population size were assumed. The implicit constraint of a constant number of contributing families imposed in balanced and slightly unbalanced selection reduced the likelihood of gene loss compared to unrestricted selection. I conclude that a slight unbalance often could be more favourable than complete balance regarding selection efficiency, and that gain retrieved per unit of group coancestry declined with further unbalance.


Genetic changes accompanying increased fitness in evolving populations of Escherichia coli.
Two populations of Escherichia coli, each initiated with a single clone containing a derivative of the plasmid pBR322, were maintained for long periods in glucose-limited continuous culture. In both populations, after an extensive number of generations had elapsed, clones were isolated in which the transposon Tn3 from the plasmid had integrated into the bacterial chromosome. In both cases examined, the transpositions were shown to increase relative fitness approximately 6-7%, in the environment in which the populations were maintained. The loci of integration were mapped to approximately 13.2 min (population 1) and approximately 32.8 min (population 2).


Curcumin loaded fibrinogen nanoparticles for cancer drug delivery.
In this work we prepared and evaluated the curcumin loaded fibrinogen nanoparticles (CRC-FNPs) as a novel drug delivery system for cancer therapy. These novel CRC-FNPs were prepared by a two-step co-acervation method using calcium chloride as the cross-linker. The prepared nanoparticles were characterized using dynamic light scattering (DLS), atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FT-IR), thermogravimetry (TG), differential thermal analysis (DTA) and X-ray diffraction (XRD) studies. DLS studies showed that the particle size of CRC-FNPs was in the range of 150-200 nm. The loading efficiency (LE) and in vitro drug release were studied using UV spectrophotometer. The LE was found to be 90%. The cytotoxicity was studied using L929 (mouse fibroblast), PC3 (prostate) and MCF7 (breast) cancer cell lines by MTT assay, which confirmed that CRC-FNPs were comparatively non toxic to L929 cell line while toxic to PC3 and MCF7 cancer cells. Cellular uptake of CRC-FNPs studied using L929, MCF-7 and PC3 cells monitored by fluorescent microscopy, demonstrated significant internalization and retention of nanoparticles inside the cells. The preferential accumulation of curcumin within the cancer cells were also confirmed by flowcytometry based uptake studies. The apoptosis assay showed increased apoptosis on MCF-7 compared to L929 cells. The blood compatibility of CRC-FNPs throws light on the fact that it is possible to administer the prepared nanoformulation intravenously. The results indicated that CRC-FNPs could be a promising therapeutic agent for cancer treatment.


Impact of quality mentorship on achievements of Shiraz Medical School in the 1970s and the role of professor Faramarz Ismail-Beigi.
Almost four decades ago, an eminent physician, outstanding mentor and scholar, Professor Faramarz Ismail-Beigi (b. 1941) was appointed Chair of the Department of Internal Medicine at Shiraz Medical School. Soon, this proved to be the beginning of a golden era in medical education at that center. Professor Ismail-Beigi invited outstanding teachers and physicians to collaborate with him. Their efforts during the next decade laid a strong and unique foundation for medical education based on quality mentorship and role-modeling. In this paper, we briefly highlight the importance of mentorship in medicine and medical education, followed by a glance at the academic life and career of Professor Ismail-Beigi and his role as a prominent mentor at the Shiraz School of Medicine.


Yoga Practice Improves Physiological and Biochemical Status at High Altitudes: A Prospective Case-control Study.
Context • High altitude (HA) is a psychophysiological stressor for natives of lower altitudes. Reducing the morbidity and optimizing the performance of individuals deployed in an HA region has been attempted and reported with varied results. Objective • The present study intended to explore the effects of comprehensive yogic practices on the health and performance of Indian soldiers deployed at HAs. Design • The research team designed a prospective, randomized, case-control study. The study was done at Karu, Leh, India, at an altitude of 3445 m. Participants • Fully acclimatized soldiers in the Indian army were randomly selected from those posted to HA regions (ie, altitudes >3000 m). Intervention • The soldiers were divided into 2 groups of equal size. The first group, the control group, carried out the routine activities for physical training in the Indian army. The second group, the intervention group practiced a comprehensive yoga package, including physical asanas, pranayama, and meditation, and did not perform the physical training that the first group did. Both groups were monitored during their activities. Outcome Measures • A wide and comprehensive range of anthropometrical, physiological, biochemical, and psychological parameters were measured: (1) height and weight; (2) body fat percentage (BFP); (3) heart rate (HR); (4) respiratory rate (RR); (5) systolic and diastolic blood pressure (DPB); (6) peripheral saturation of oxygen; (7) end tidal CO2 (EtCO2); (8) chest expansion; (9) pulmonary function; (10) physical work capacity (VO2Max); (11) hematological variables; (12) lipid profile; (13) serum urea; (14) creatinine; (15) liver enzymes; (16) blood glucose; and (17) anxiety scores. Measurements were made at baseline and postintervention. Results • Two-hundred soldiers took part in the study. The yoga group showed a significant improvement in health indices and performance as compared with the control group. They had lower weights, BFPs, RRs, DBPs, and anxiety scores. They also had a significantly higher EtCO2, forced vital capacity, forced expiratory volume in the first second (FEV1), and VO2Max. Also, the yoga group showed a significant reduction in serum cholesterol, low-density lipoprotein, triglycerides, and blood urea as compared with their preyoga levels and with the exercise group. Conclusions • Practice of yoga facilitates improvements in health and performance at HAs and is superior to routine training with physical exercises. Comprehensive yogic practices are an effective modality for improving health and performance at HAs.


Efficacy of coumaphos crumbles and naftalofos boluses against nematodes of cattle.
Coumaphos crumbles (0.32%) administered to cattle at the dose level of 2 mg of active ingredient per kilogram of body weight each day for 6 days reduced fecal egg counts by 98.4%. The compound was highly efficacious in removing adult worms of the genera Haemonchus, Ostertagia, Trichostrongylus, Cooperia, Oesophagostomum, and Trichuris, removing 99.8, 86.7, 95.9, 99.8, 74.8, and 90.9% of the worms, respectively. The overall efficacy of coumaphos crumbles against the adult forms of the 6 genera was 91.3%. Naftalofos boluses administered to cattle at the dose level of 50 mg of active ingredient per kilogram of body weight reduced fecal egg counts by 83.5%. The efficacies against adult nematodes were as follows: Haemonchus, 99.8%; Ostertagia, 86.9%; Trichostrongylus, 74.0%; Cooperia, 71.9%; Oesophagostomum, 40.1%; and Trichuris, 87.9%. The overall efficacy of naftalofos boluses against the nematodes was 76.8%.


Design and Synthesis of Bicyclo[4.3.0]nonene Nucleoside Analogues.
Nucleoside analogues are effective antiviral agents, and the continuous emergence of pathogenic viruses demands the development of novel and structurally diverse analogues. Here, we present the design and synthesis of novel nucleoside analogues with a carbobicyclic core, which mimics the conformation of natural ribonucleosides. Employing a divergent synthetic route featuring an intermolecular Diels-Alder reaction, we successfully synthesized carbobicyclic nucleoside analogues with high antiviral efficacy against respiratory syncytial virus.


Measurements at calving for straightbred and crossbred cows of diverse types.
Reproductive and calving records of 611 cows from F1 and F2 generations from a diallel mating system with Angus, Brahman, Hereford, Holstein and Jersey were examined. The inter se matings were by artificial insemination, and each cow had three or four parturitions. Dependent variables included weight, hip weight at first calving, age at first calving, gestation length and calving interval. Brahmans were the heaviest, tallest and oldest purebred at first calving. Crossbred Brahman females tended to be older than other crosses at first calving. Purebred Brahmans and one-half Brahman crosses also had the longest gestation lengths and calving intervals. First-gestation (F1) crossbred cows were 18 kg heavier (P less than .05), 2.0 cm taller (P less than .01) and 35 d younger (P less than .05) at first calving than contemporary straightbreds. Average maternal heterosis for height at calving was significant (1.4 cm; P less than .05); however, estimates of specific and average maternal heterosis for measurements taken at first calving were generally nonsignificant. Estimates of specific and average individual and maternal heterosis were generally small and nonsignificant for gestation length and calving interval.


Polymer-brush-afforded SPIO Nanoparticles Show a Unique Biodistribution and MR Imaging Contrast in Mouse Organs.
To investigate the biodistribution and retention properties of the new super paramagnetic iron oxide (new SPIO: mean hydrodynamic diameter, 100 nm) nanoparticles, which have concentrated polymer brushes in the outer shell and are difficult for phagocytes to absorb, and to compare the new SPIO with clinically approved SPIO (Resovist: mean hydrodynamic diameter, 57 nm). 16 male C57BL/6N mice were divided in two groups according to the administered SPIO (n = 8 for each group; intravenous injection does, 0.1 ml). In vivo magnetic resonance imaging (MRI) was performed before and one hour, one day, one week and four weeks after SPIO administration by two dimensional-the fast low angle shot (2D-FLASH) sequence at 11.7T. Ex vivo high-resolution images of fixed organs were also obtained by (2D-FLASH). After the ex vivo MRI, organs were sectioned and evaluated histologically to confirm the biodistribution of each particle precisely. The new SPIO was taken up in small amounts by liver Kupffer cells and showed a unique in vivo MRI contrast pattern in the kidneys, where the signal intensity decreased substantially in the boundaries between cortex and outer medulla and between outer and inner medulla. We found many round dark spots in the cortex by ex vivo MRI in both groups. Resovist could be detected almost in the cortex. The shapes of the dark spots were similar to those observed in the new SPIO group. Transmission electron microscopy revealed that Resovist and the new SPIO accumulated in different cells of glomeruli, that is, endothelial and mesangial cells, respectively. The new SPIO was taken up in small amounts by liver tissue and showed a unique MRI contrast pattern in the kidney. The SPIO were found in the mesangial cells of renal corpuscles. Our results indicate that the new SPIO may be potentially be used as a new contrast agent for evaluation of kidney function as well as immunune function.


Whole-Genome Sequence of Sphingomonas sp. Strain FARSPH, a Novel Sf9 Insect Cell Culture Contaminant.
Here, we report the whole-genome sequence of Sphingomonas sp. strain FARSPH, isolated from an insect cell line as a contaminant. FARSPH shared high identity with Sphingomonas melonis and Sphingomonas aquatilis strains. Due to this finding, we recommend taking this genus into consideration for cell culture quality control.


Portacaths are safe for long-term regular blood transfusion in children with sickle cell anaemia.
Peripheral venous access in children with sickle cell anaemia (SCA) requiring regular blood transfusions can become difficult over time. Previous reports have suggested the use of totally implantable venous access devices, Portacaths (PAC) in this patient group are associated with unacceptable high rates of complications. We present our experience in seven children with SCA over a 9-year period. Seven devices were placed for a total of 9754 PAC days during the study period. The median age at insertion was 6.3 years (range 3-15 years). The rate of PAC associated infection was 0.2 per 1000 PAC days. There were no episodes of thrombosis. The median length of time in situ during the study period was 3.7 years (range 1.3-7.5 years). Our experience highlights the safe and reliable use of PAC in children with SCA requiring regular blood transfusions when venous access has become a major problem.


Mycophenolic acid differentially impacts B cell function depending on the stage of differentiation.
Production of pathogenic Abs contributes to disease progression in many autoimmune disorders. The immunosuppressant agent mycophenolic acid (MPA) has shown clinical efficacy for patients with autoimmunity. The goal of these studies was to elucidate the mechanisms of action of MPA on B cells isolated from healthy individuals and autoimmune patients. In this study, we show that MPA significantly inhibited both proliferation and differentiation of primary human B cells stimulated under various conditions. Importantly, MPA did not globally suppress B cell responsiveness or simply induce cell death, but rather selectively inhibited early activation events and arrested cells in the G0/G1 phase of the cell cycle. Furthermore, MPA blocked expansion of both naive and memory B cells and prevented plasma cell (PC) differentiation and Ab production from healthy controls and individuals with rheumatoid arthritis. Finally, whereas MPA potently suppressed Ig secretion from activated primary B cells, terminally differentiated PCs were not susceptible to inhibition by MPA. The target of MPA, IMPDH2, was found to be downregulated in PCs, likely explaining the resistance of these cells to MPA. These results suggest that MPA provides benefit in settings of autoimmunity by directly preventing activation and PC differentiation of B cells; however, MPA is unlikely to impact autoantibody production by preexisting, long-lived PCs.


Cellular reactions of O6-methylguanine, a product of some alkylating carcinogens.
Cultures of a purine-requiring mutant of Chinese hamster ovary cells (CHO-104b), randomly bred hamster embryo cells, or Escherichia coli B(s-1) were treated with non-toxic doses of (3)H-labelled O(6)-methylguanine. DNA and RNA were isolated and subjected to enzymic digestion to nucleosides at pH8. The products of digestion were analysed by ion-exchange chromatography on columns of Dowex 50 (NH(4) (+) form) at pH8.9. No (3)H-labelled O(6)-methylguanosine was detected in nucleic acid digests. (3)H-labelled O(6)-methylguanine was O-demethylated yielding [(3)H]guanine in CHO-104b cells. Radioactivity in nucleic acid digests was associated with thymidine, guanosine, deoxyguanosine and an unidentified early-eluting product. Reports of similar unidentified products from nucleic acids labelled with various agents are discussed.


Histone deacetylase inhibitors modulate miRNA and mRNA expression, block metaphase, and induce apoptosis in inflammatory breast cancer cells.
To develop new therapies for inflammatory breast cancer (IBC) we have compared the effects of two hydroxamic acid-based histone deacetylase (HDAC) inhibitors, CG-1521 and Trichostatin A (TSA) on the biology of two IBC cell lines: SUM149PT and SUM190PT. CG-1521 and TSA induce dose (0-10 µM) and time-dependent (0-96 h) increases in the proportion of cells undergoing cell cycle arrest and apoptosis in the presence or absence of 17β-estradiol. In SUM 149PT cells, both CG-1521 and TSA increase the levels of acetylated α-tubulin; however the morphological effects are different: CG-1521 blocks mitotic spindle formation and prevents abscission during cytokinesis while TSA results in an increase in cell size. In SUM190PT cells CG-1521 does not cause an increase in acetylated-α-tubulin and even though TSA significantly increases the levels of acetylated tubulin, neither inhibitor alters the morphology of the cells. Microarray analysis demonstrates that CG-1521 modulates the expression of 876 mRNAs and 63 miRNAs in SUM149PT cells, and 1227 mRNAs and 35 miRNAs in SUM190PT cells. Only 9% of the genes are commonly modulated in both cell lines, suggesting that CG-1521 and TSA target different biological processes in the two cell lines most likely though the inhibition of different HDACs in these cell lines. Gene ontology (GO) analysis reveals that CG-1521 affects the expression of mRNAs that encode proteins associated with the spindle assembly checkpoint, chromosome segregation, and microtubule-based processes in both cell lines and has cell-type specific effects on lipid biosynthesis, response to DNA damage, and cell death.


Assessing the impact of autologous neutralizing antibodies on viral rebound in postnatally SHIV-infected ART-treated infant rhesus macaques.
While the benefits of early antiretroviral therapy (ART) initiation in perinatally infected infants are well documented, early ART initiation is not always possible in postnatal pediatric HIV infections, which account for the majority of pediatric HIV cases worldwide. The timing of onset of ART initiation is likely to affect the size of the latent viral reservoir established, as well as the development of adaptive immune responses, such as the generation of neutralizing antibody responses against the virus. How these parameters impact the ability of infants to control viremia and the time to viral rebound after ART interruption is unclear. To gain insight into the dynamics, we utilized mathematical models to investigate the effect of time of ART initiation via latent reservoir size and autologous virus neutralizing antibody responses in delaying viral rebound when treatment is interrupted. We used an infant nonhuman primate Simian/Human Immunodeficiency Virus (SHIV) infection model that mimics breast milk HIV transmission in human infants. Infant Rhesus macaques (RMs) were orally challenged with SHIV.C.CH505 375H dCT and either given ART at 4-7 days post-infection (early ART condition), at 2 weeks post-infection (intermediate ART condition), or at 8 weeks post-infection (late ART condition). These infants were then monitored for up to 60 months post-infection with serial viral load and immune measurements. We develop a stochastic mathematical model to investigate the joint effect of latent reservoir size, the autologous neutralizing antibody potency, and CD4+ T cell levels on the time to viral rebound and control of post-rebound viral loads. We find that the latent reservoir size is an important determinant in explaining time to viral rebound by affecting the growth rate of the virus. The presence of neutralizing antibodies also can delay rebound, but we find this effect for high potency antibody responses only.


Applying a health system perspective to the evolving Farmácia Popular medicines access programme in Brazil.
The Farmácia Popular Program (FPP) launched a subsidy system in Brazil, but in coexistence with the ongoing regular governmental access to medicines (Unified Health System (SUS) dispensings) mechanisms, causing overlaps in terms of financing and target population. This characteristic is quite different from most countries with medicines cost-sharing schemes. This paper aims to analyse the FPP under a health systems perspective considering the different health system levels. We analysed the findings from the study 'Impact of consecutive subsidies policies on access to and use of medicines in Brazil - ISAUM-Br', designed with the objective of describing and evaluating the impact of the government medicines subsidy policies implemented between 2004 and 2011. Patient share of copayment increased with the implementation of the intervention, which decreased the reference price and decreased with SNP (Saúde Não Tem Preço; zero copayment for patients). There was an increased number of FPP dispensations over time, but SUS dispensings remained the most important source for medicines, especially for hypertension and diabetes. FPP allowed the establishment of a well-designed pharmaceutical information system in the country. Despite the improvement on control mechanism, fraud remained a problem. There were important effects on the pharmaceutical market and sales of generic medicines. FPP has proven to be a very important policy for promoting access to medicines for hypertension and diabetes in Brazil. Examining this policy with a health system perspective has allowed us to highlight many of its important consequences, including for the first time a broad and consistent information system on access to medicines in the country.


Effects of growth-inhibitory concentrations of copper on alginate biosynthesis in highly mucoid Pseudomonas aeruginosa.
Alginate production and degree of polymerization were affected when the highly mucoid Pseudomonas aeruginosa 8821M was grown with growth-inhibitory concentrations of Cu2+ (supplied as CuCl2; 1-5 mM). The inhibition of alginate biosynthesis was consistent with the decreased activity in Cu2+-stressed cells of phosphomannose isomerase/GDP-mannose pyrophosphorylase (encoded by algA), phosphomannomutase (encoded by algC) and GDP-mannose dehydrogenase (encoded by algD). However, in cells grown with concentrations of CuCl2 below 2 mM, the steady-state mRNA levels from algA, algC, algD and from the regulatory gene algR1 increased moderately. This observation is consistent with the suggested linkage between the control of alginate gene expression and the global regulation involved in the oxidative stress response. At highly inhibitory concentrations the levels of the four alginate gene transcripts decreased from maximal values. The bell-shaped curves, representing the effect of Cu2+ concentration on mRNA levels from the four alginate genes, exhibited similar patterns but did not concur. The decrease of the specific activity of enzymes necessary for GDP-mannuronic acid synthesis in Cu2+-grown cells was correlated with changes in gene expression, with the inhibitory effect of Cu2+ on enzyme activities and with Cu2+-induced oxidative inactivation of enzymes, especially the particularly sensitive phosphomannose isomerase activity.


Characterological depression in patients with narcissistic personality disorder.
Background: Depressive symptoms often occur in patients with personality disorders. Along the lines of the precious concepts of reactive and melancholic forms of depression, two different patterns of depressive symptoms can be identified. Reactive forms of depression is considered to be related to dysfunction of emotional regulation and social functioning, and to personality disorders. This study aimed at exploring the pattern of depressive symptoms in patients with Narcissistic Personality Disorder (NPD) compared to a group of depressed patients without Personality Disorder (PD). The Newcastle Diagnostic Depression Scale (NDDS) is a clinical instrument designed to differentiate reactive depression from melancholic depression. Method: The study investigated patterns of depressive symptoms in 117 out-patients, divided into two groups. One group containing 56 patients with depressive symptoms by no PD and the other group comprised of 61 patients with depressive symptoms and NPD. The participants were interviewed using the Newcastle Diagnostic Depression Scale. Results: There was a significant difference between the groups, as the NPD group suffered from reactive forms of depression. The NPD group showed a pattern of depressive symptoms characterized by fluctuation of the depressive state, without time demarcation of depressive episode, ruminations preoccupied with hostility and accusatory feelings towards other, but not self-accusatory feelings, fluctuation suicidal ideation triggered by external events accompanied by parasuicidal behavior, lack of neuro-vegetative symptoms such as insomnia with early wakening, loss of appetite and weight loss. The No PD group showed the opposite pattern. Conclusion: Based on these results NDDS is considered to be an applicable instrument for identifying personality pathology in patients with depressive symptoms, by recognizing the specific pattern. This is thought to be important for adequate treatment planning.


Regional distribution of alpha-adrenoceptor subtypes in the female rabbit urethra.
The aim of the present investigation was to study the regional distribution of alpha-adrenoceptor subtypes in the female rabbit bladder base and urethra, using radioligand binding and mechanical activity studies. The binding studies performed on membranes prepared from the bladder base, and the proximal and distal part of the urethra, revealed that the number of alpha 1-adrenoceptors did not significantly differ between the three regions, whereas the number of alpha 2-adrenoceptors increased distally. The mechanical activity studies showed that noradrenaline and clonidine, but not phenylephrine, were more potent in the distal than the proximal part of the urethra. It is suggested that in the female rabbit urethra the lower EC50-value found for noradrenaline and clonidine in the distal as compared to the proximal part of the urethra, at least in part, is attributable to a higher number of postjunctional alpha 2-adrenoceptors in the distal than in the proximal urethra.


Nationwide Outcome of Tailored Surgery for Symptomatic Chronic Pancreatitis based on Pancreatic Morphology: Validation of the International guidelines.
To determine the nationwide use and outcome of tailored surgical treatment for symptomatic chronic pancreatitis (CP) as advised by recent guidelines. Randomized trials have shown that surgery is superior to endoscopy in patients with symptomatic CP, although endoscopy remains popular Recent guidelines advice to "tailor surgery" based on pancreatic morphology meaning that the least extensive procedure should be selected based on pancreatic morphology. However, nationwide, and multicenter studies On tailored surgery for symptomatic CP are lacking. Nationwide multicenter retrospective analysis of consecutive patients undergoing surgical treatment for symptomatic CP in all seven Dutch university medical centers (2010-2020). Outcomes included volume trend, major complications, 90-day mortality, postoperative opioid use and clinically relevant pain relief. Surgical treatment was tailored based on the size of the main pancreatic duct and pancreatic head (e.g. surgical drainage for a dilated pancreatic duct, and normal size pancreatic head). Overall, 381 patients underwent surgery for CP: 127 surgical drainage procedures ( 33%; mostly extended lateral pancreaticojejunostomy), 129 duodenum-preserving pancreatic head resections (DPPHR, 34%, mostly Frey), and 125 formal pancreatic resections (33%, mostly distal pancreatectomy). The annual surgical volume increased slightly (Pearson r=0.744). Mortality (90-day) occurred in 6 patients (2%), and was non-significantly lower after surgical drainage (0%, 3%, 2%; P=0.139). Major complications (12%, 24%, 26%; P=0.012), postoperative pancreatic fistula grade B/C (0%, 3%, 22%; P=0.038), surgical reintervention (4%, 16%, 12%; P=0.006), and endocrine insufficiency ( 14%, 21%, 43%; P<0.001) occurred less often after surgical drainage. After a median follow-up of 11 months [IQR 3-23] good rates of clinically relevant pain relief ( 83%, 69%, 80%; P=0.082) were observed and 81% of opioid users had stopped using (83%, 78%, 84%, P=0.496). The use of surgery for symptomatic CP increased over the study period. Drainage procedures were associated with the best safety profile and excellent functional outcome, highlighting the importance of tailoring surgery based on pancreatic morphology.


A comprehensive and practical approach to the management of idiopathic pulmonary fibrosis.
Introduction: Idiopathic pulmonary fibrosis (IPF) is a debilitating, progressive, and fatal fibrotic pulmonary disease with a prognosis comparable to that of lung cancer. IPF management is a complex process that involves pharmacological and nonpharmacological interventions, extensive patient education, and addressing patient needs that change through the course of the illness. Areas covered: This review summarizes the key aspects of a multifaceted, multidisciplinary, individualized approach to IPF care that incorporates available treatment options, strategies to improve compliance with antifibrotic therapies, pulmonary rehabilitation, and the integration of palliative care for symptom management. Aspects of care discussed include the use of antifibrotic therapy and nonpharmacological treatments, targeted education and psychosocial support, evaluation and management of comorbidities, and early integration of palliative care. Expert opinion: By incorporating this comprehensive approach to disease management, physicians can address most aspects of care for a patient with IPF to optimize survival and quality of life.


Human dietary change.
The transition from hunting and gathering to agriculture and animal husbandry in the Near East and Mediterranean Region began some 12,000 years ago. The ecological changes associated with this change are known to have been related to higher levels of stress from undernutrition and infectious disease. Certain pathologies found in human skeletal remains from this time are indicative of anaemia and osteoporosis, although it is not clear whether they had clear nutritional aetiologies. In this paper, dietary changes associated with changes in subsistence practices in this region are described. In addition, quantitative modelling of possible patterns of dietary and nutrient intakes of adult males before, and soon after, the establishment of agrarian economies is used to examine the proposition that the skeletal pathologies porotic hyperostosis, cribra orbitalia and porotic hyperostosis may have been due to nutritional deficiencies. The results suggest that protein deficiency was only likely if subjects were suffering from chronic energy deficiency (CED) and their diet contained no meat. Dietary calcium deficiency was possible after the transition to cultivation and animal husbandry, in the presence of moderate or severe CED. Anaemias, although present after the transition, were unlikely to have had dietary aetiologies, regardless of the severity of CED.


Pigment Degradation in Oil Paint Induced by Indoor Climate: Comparison of Visual and Computational Backscattered Electron Images.
For the first time the degradation of lead white pigment in mature oil paint has been used as an internal marker for the degree of saponification and hence chemical degradation of oil paint. Computational image analysis of the backscattered electron images quantified the degree of the intact lead white pigment versus the nonpigmented and lead-rich areas (degraded lead white) in the paint layers. This new methodology was applied to a series of paint samples taken from four painted wall hangings (dated 1778), which makes it possible to study the influence of indoor climate on chemical degradation of aged oil paintings. The visual interpretation and computational image analysis of the backscattered electron images revealed clear trends. The highest degree of lead white degradation in the room was found in samples from the north wall close to the windows, whereas degradation diminished further away from the window. Lead white from the south wall was less degraded, but showed a similar trend as in the paintings on the north wall. These results imply a strong relationship between chemical degradation of paint and location of the paint in the room.


Histopathological changes in lungs of patients with fatal COVID 19 infection: A series of 15 cases.
The predominant pathology noted in the lungs of patients dying of COVID-19 is reported to be diffuse alveolar damage (DAD). Other studies have identified microthrombi to be a prominent finding of lung injury in patients affected by COVID-19. We describe the lung histopathological findings in fifteen cases of COVID-19 who died from the disease with the aim of reporting the microscopic changes in the lungs of patients dying from this disease. Lung tissues from fifteen consecutive autopsy cases of COVID-19 were studied for gross and microscopic features. The case history of the deaths was noted, and the information was analyzed. The lung damage seen was graded on a semiquantitative scale on the basis of the percentage of tissue involved. Gross examination of the lungs showed multiple foci of consolidation mainly in the lower lobes of the lungs as the most commonly encountered finding. The other significant pattern was congested and edematous lungs with areas of consolidation. Microscopic assessment of lung sections showed 8 out of the 15 cases showing changes of the exudative phase of diffuse alveolar damage, whereas two cases were in the proliferative phase. Hyaline membranes were one of the common findings along with intra-alveolar edema and interstitial edema. Four cases showed changes in organizing phase. Other findings were microthrombi formation, fungal abscesses, dilated and collapsed alveoli, intra-alveolar hemorrhage, and acute neutrophilic pneumonia. DADand interstitial pneumonitis were the most striking features in our autopsy study. Features of different phases of diffuse alveolar damage were seen to coexist in the same patient indicating the temporal heterogeneity of the ongoing lung injury in these patients.


[Effects of apomorphine and haloperidol on experimental hepatocarcinogenesis].
The modifying effect of apomorphine and haloperidol - agonist and antagonist of dopamine receptors, respectively - on the development of N-nitrosodiethylamine (NDEA) - induced hepatic tumors was studied in 60 noninbred albino male rats. The study was concerned with an evaluation of the effect of the drugs on tumor frequency as well as on the neoplastic transformation of such cell elements as hepatocytes, cholangiolar epithelium and endothelium. It was found that apomorphine significantly inhibited the carcinogenic effect of NDEA and neoplastic transformation of hepatocytes. Haloperidol revealed a tendency of stimulating NDEA effect on cholangiolar epithelium. The results are discussed in the context of the considerable importance of the functional condition of the presynaptic receptors of catecholaminergic systems in the mechanism of carcinogenic chemical action.


Effectiveness of Injectable Extended-Release Naltrexone vs Daily Buprenorphine-Naloxone for Opioid Dependence: A Randomized Clinical Noninferiority Trial.
To date, extended-release naltrexone hydrochloride has not previously been compared directly with opioid medication treatment (OMT), currently the most commonly prescribed treatment for opioid dependence. To determine whether treatment with extended-release naltrexone will be as effective as daily buprenorphine hydrochloride with naloxone hydrochloride in maintaining abstinence from heroin and other illicit substances in newly detoxified individuals. A 12-week, multicenter, outpatient, open-label randomized clinical trial was conducted at 5 urban addiction clinics in Norway between November 1, 2012, and December 23, 2015; the last follow-up was performed on October 23, 2015. A total of 232 adult opioid-dependent (per DSM-IV criteria) individuals were recruited from outpatient addiction clinics and detoxification units and assessed for eligibility. Intention-to-treat analyses of efficacy end points were performed with all randomized participants. Randomization to either daily oral flexible dose buprenorphine-naloxone, 4 to 24 mg/d, or extended-release naltrexone hydrochloride, 380 mg, administered intramuscularly every fourth week for 12 weeks. Primary end points (protocol) were the randomized clinical trial completion rate, the proportion of opioid-negative urine drug tests, and number of days of use of heroin and other illicit opioids. Secondary end points included number of days of use of other illicit substances. Safety was assessed by adverse event reporting. Of 159 participants, mean (SD) age was 36 (8.6) years and 44 (27.7%) were women. Eighty individuals were randomized to extended-release naltrexone and 79 to buprenorphine-naloxone; 105 (66.0%) completed the trial. Retention in the extended-release naltrexone group was noninferior to the buprenorphine-naloxone group (difference, -0.1; with 95% CI, -0.2 to 0.1; P = .04), with mean (SD) time of 69.3 (25.9) and 63.7 (29.9) days, correspondingly (P = .33, log-rank test). Treatment with extended-release naltrexone showed noninferiority to buprenorphine-naloxone on group proportion of total number of opioid-negative urine drug tests (mean [SD], 0.9 [0.3] and 0.8 [0.4], respectively, difference, 0.1 with 95% CI, -0.04 to 0.2; P < .001) and use of heroin (mean difference, -3.2 with 95% CI, -4.9 to -1.5; P < .001) and other illicit opioids (mean difference, -2.7 with 95% CI, -4.6 to -0.9; P < .001). Superiority analysis showed significantly lower use of heroin and other illicit opioids in the extended-release naltrexone group. No significant differences were found between the treatment groups regarding most other illicit substance use. Extended-release naltrexone was as effective as buprenorphine-naloxone in maintaining short-term abstinence from heroin and other illicit substances and should be considered as a treatment option for opioid-dependent individuals. clinicaltrials.gov Identifier: NCT01717963.


Newly identified biomarkers for detecting circulating tumor cells in lung adenocarcinoma.
Circulating tumor cells (CTCs) have been implicated in cancer prognosis and follow up. Detection of CTCs was considered significant in cancer evaluation. However, due to the heterogeneity and rareness of CTCs, detecting them with a single maker is usually challenged with low specificity and sensitivity. Previous studies concerning CTCs detection in lung cancer mainly focused on non-small cell lung carcinoma. Currently, there is no report yet describing the CTC detection with multiple markers in lung adenocarcinoma. In this study, by employing quantitative real-time PCR, we identified four candidate genes (mRNA) that were significantly elevated in peripheral blood mononuclear cells and biopsy tissue samples from patients with lung adenocarcinoma: cytokeratin 7 (CK7), Ca(2+)-activated chloride channel-2 (CLCA2), hyaluronan-mediated motility receptor (HMMR), and human telomerase catalytic subunit (hTERT). Then, the four markers were used for CTC detection; namely, positive detection was defined if at least one of the four markers was elevated. The positive CTC detection rate was 74.0% in patients with lung adenocarcinoma while 2.2% for healthy controls, 6.3% for benign lung disease, and 48.0% for non-adenocarcinoma non-small cell lung carcinoma. Furthermore, in a three-year follow-up study, patients with an increase in the detection markers of CTCs (CK7, CLCA2, HMMR or hTERT) on day 90 after first detection had shorter survival time compared to those with a decrease. These results demonstrate that the combination of the four markers with specificity and sensitivity is of great value in lung adenocarcinoma prognosis and follow up.


Synthesis and Evaluation of Novel Radioligands Based on 3-[5-(Pyridin-2-yl)-2H-tetrazol-2-yl]benzonitrile for Positron Emission Tomography Imaging of Metabotropic Glutamate Receptor Subtype 5.
We found out 3-[5-(pyridin-2-yl)-2H-tetrazol-2-yl]benzonitrile analogues as the candidate for positron emission tomography (PET) imaging agents of metabotropic glutamate receptor subtype 5 (mGluR5). Among these compounds, 3-methyl-5-(5-(pyridin-2-yl)-2H-tetrazol-2-yl)benzonitrile (10) exhibited high binding affinity (Ki = 9.4 nM) and moderate lipophilicity (cLogD, 2.4). Subsequently, [(11)C]10 was radiosynthesized at 25 ± 14% radiochemical yield (n = 11) via C-[(11)C]methylation of the arylstannyl precursor 15 with [(11)C]methyl iodide. In vitro autoradiography and PET assessments using [(11)C]10 showed high specific binding in the striatum and hippocampus, two brain regions enriched with mGluR5. Moreover, test-retest PET studies with [(11)C]10 indicated high reliability to quantify mGluR5 density, such as the intraclass correlation coefficient (0.90) and Pearson r (0.91) in the striatum of rat brain. We demonstrated that [(11)C]10 is a useful PET ligand for imaging and quantitative analysis of mGluR5. Furthermore, [(11)C]10 might be modified using its skeleton as a lead compound.


Alteration of the expression of sirtuins and var genes by heat shock in the malaria parasite Plasmodium falciparum.
In Plasmodium falciparum the monoallelic expression of var virulence genes is regulated through epigenetic mechanisms. A study in the Gambia showed that an increase in var genes commonly expressed in patients with severe malaria is associated with fever and high blood lactate. A strong association was demonstrated between the upregulation of PfSir2A and group B var genes. A subsequent study in Kenya extended this association to show a link between elevated expression of PfSir2A and overall var transcript levels. We investigate here the link between heat shock and/or lactate levels on sirtuin and var gene expression levels in vitro. In vitro experiments were conducted using laboratory and recently-laboratory-adapted Kenyan isolates of P. falciparum. To investigate a potential cause-and-effect relationship between host stress factors and parasite gene expression, qPCR was used to measure the expression of sirtuins and var genes after highly synchronous cultured parasites had been exposed to 2 h or 6 h of heat shock at 40 °C or elevated lactate. Heat shock was shown to increase the expression ofPfSir2B in the trophozoites, whereas exposure to lactate was not. After the ring stages were exposed to heat shock and lactate, there was no alteration in the expression of sirtuins and severe-disease-associated upsA and upsB var genes. The association between high blood lactate and sirtuin/var gene expression that was previously observed in vivo appears to be coincidental rather than causative. This study demonstrates that heat stress in a laboratory and recently-laboratory-adapted isolates of P. falciparum results in a small increase in PfSir2B transcripts in the trophozoite stages only. This finding adds to our understanding of how patient factors can influence the outcome of Plasmodium falciparum infections.


Role of educational intervention in the management of comorbid depression and hypertension.
To assess the effect of health education on blood pressure control and depression symptoms, we conducted a prospective study in 272 patients with essential hypertension. Depression symptoms were assessed by the Zung Self-rating Depression Scale (SDS). There was no significant difference in the level of hypertension and SDS scores between the educational (n = 138) and control (n = 134) group before the study (p > 0.05). After 12 months of follow-up, the body mass index (BMI) was reduced in the educational group (23.6 +/- 2.6 vs 21.4 +/- 2.2 kg/m2, p < 0.01), but it remained unchanged in the control group. The average systolic and diastolic blood pressure were reduced in both groups, but the amplitude of systolic blood pressure reduction in the educational group was greater than that of the control group (7.9 +/- 2.3 vs 4.2 +/- 2.0 mmHg, p < 0.01). The incidence of depression (10.9% vs 10.4%) and the average SDS scores (32.4 +/- 6.7 vs 33.2 +/- 6.9) were similar between the two groups (p > 0.05). However, in the depressed patients who received hypertension education, the average systolic (160.2 +/- 12.4 mmHg) and diastolic (89.8 +/- 7.3 mmHg) blood pressure was significantly lower than that of the control group (169.1 +/- 16.8 and 96.8 +/- 13.0 mmHg, respectively, p < 0.01). We conclude that hypertension education does not reduce the incidence or symptoms of depression, but it may facilitate blood pressure management in patients with clinical depression.


Protein lipid interaction in bile: effects of biliary proteins on the stability of cholesterol-lecithin vesicles.
The nucleation of cholesterol crystals is an obligatory precursor to cholesterol gallstone formation. Nucleation, in turn, is believed to be preceded by aggregation and fusion of cholesterol-rich vesicles. We have investigated the effects of two putative pro-nucleating proteins, a concanavalin A-binding protein fraction and a calcium-binding protein, on the stability of sonicated small unilamellar cholesterol-lecithin vesicles. Vesicle aggregation is followed by monitoring absorbance, and upon addition of the concanavalin A-binding protein fraction the absorbance of a vesicle dispersion increases continuously with time. Vesicle fusion is probed by a fluorescence contents-mixing assay. Vesicles apparently fuse slowly after the addition of the concanavalin A-binding protein, although inner filter effects confound the quantitative measurement of fusion rates. The rates of change of absorbance and fluorescence increase with the concentration of the protein, and the second-order dimerization rate constant increases with both the protein concentration and the cholesterol content of the vesicles. On the other hand, the calcium-binding protein has no effect on the stability of the vesicle dispersion. This protein may therefore affect cholesterol crystal formation not by promoting the nucleation process, but by enhancing crystal growth and packaging. Our results demonstrate that biliary proteins can destabilize lipid vesicles and that different proteins play different roles in the mechanism of cholesterol gallstone formation.


Evidence of cellular immune activation in children with opsoclonus-myoclonus: cerebrospinal fluid neopterin.
To evaluate cellular immune activation in opsoclonus-myoclonus syndrome, we measured the inflammatory marker neopterin in the cerebrospinal fluid of 16 children with opsoclonus-myoclonus and neuroblastoma, 24 children with opsoclonus-myoclonus but no tumor, and 19 age-matched controls. The mean concentration in opsoclonus-myoclonus was 2.3-fold higher than in controls (P = .008). Neopterin was greatly elevated in four of the most neurologically severe cases, up to 8.3-fold above the highest control level. Thirteen of the 40 children with opsoclonus-myoclonus but no controls had a neopterin concentration >2 SD above the control mean (P = .005). In this high neopterin subgroup, neurologic severity was significantly greater and the duration of neurologic symptoms was less. In 16 children re-examined on immunotherapy, including adrenocorticotropic hormone (ACTH) combination therapy, treatment was associated with a significant reduction in both neopterin and neurologic severity. Neopterin did not differ significantly between the tumor and non-tumor opsoclonus-myoclonus etiologies. No abnormalities of tetrahydrobiopterin were found. Although cerebrospinal fluid neopterin lacked the sensitivity to be a biomarker of disease activity in opsoclonus-myoclonus, elevated concentrations do support a role for T-cell activation and cell-mediated immunity in its pathophysiology.


Development of thin-film photo-bioreactor and its application to outdoor culture of microalgae.
Photosynthetic microalgae have received much attention as a microbial source of diverse useful biomaterials through CO(2) fixation and various types of photo-bioreactors have been developed for efficient microalgal cultivation. Herein, we developed a novel thin-film photo-bioreactor, which was made of cast polypropylene film, considering outdoor mass cultivation. To develop optimal design of photo-bioreactor, we tested performance of three shapes of thin-film photo-bioreactors (flat, horizontal and vertical tubular shapes) and various parts in the bioreactor. Collectively, vertical tubular bioreactor with H/D ratio 6:1 and cylindrical stainless steel spargers showed the most outstanding performance. Furthermore, the photo-bioreactor was successfully applied to the cultivation of other microalgae such as Chlamydomonas reinhardtii and Chlorella vulgaris. The scalability of photo-bioreactor was confirmed by gradually increasing culture volume from 4 to 25 L and the biomass productivity of each reactor was quite consistent (0.05-0.07 g/L/day) during the cultivation of H. pluvialis under indoor and outdoor conditions. Especially, we also achieved dry cell weight of 4.64 g/L and astaxanthin yield of 218.16 mg/L through long-term cultivation (100 days) under outdoor condition in 15 L photo-bioreactor using Haematococcus pluvialis, which means that the astaxanthin yield from outdoor cultivation is equal or superior to that obtained from controlled indoor condition. Therefore, these results indicate that we can apply this approach to development of optimal photo-bioreactor for the large-scale culture of microalgae and production of useful biomaterials under outdoor condition.


Pediatric surgeons' attitudes toward regionalization of neonatal surgical care.
Research has suggested that high-risk pediatric surgical patients have better outcomes when treated in resource-rich children's environments. Surgical neonates are a particularly high-risk population and some suggest that regionalization might be a strategy to improve clinical outcomes in neonatal surgical patients. We conducted a national survey of pediatric surgeons in the United States to explore their attitudes toward regionalization of neonatal surgical care. Members of the American Pediatric Surgical Association were asked to participate in an anonymous online survey to assess both attitudes toward regionalization, as well as perceptions of the importance of various resources in providing optimal care for surgical neonates. Overall, 56.2% of participants favored regionalization. Surgeons whose practice was part of a training program tended to favor regionalization more, as did those from larger group practices and those who practiced at free-standing children's hospital. In addition, surgeons from larger groups and those involved with training programs more strongly favored the premise that a higher level of resource commitment should be available to treat surgical neonates. The impact of any national strategy to improve neonatal surgical outcomes will be large and multi-faceted. While the majority of pediatric surgeons favor regionalization, our findings demonstrate variation in this view and highlight the necessity for surgeon involvement and education that will be critical in this effort.