Pivotal role of superoxides generated in the mitochondrial respiratory chain in peroxynitrite-dependent activation of phospholipase A2.
Exposure of PC12 cells to reagent peroxynitrite promotes the release of arachidonic acid (AA) mediated by activation of phospholipase A(2) [Guidarelli, Palomba and Cantoni (2000) Br. J. Pharmacol. 129, 1539-1542]. We now present experimental evidence consistent with the notion that this response is not directly triggered by peroxynitrite but, rather, by reactive oxygen species generated at the level of complex III of the mitochondrial respiratory chain. In particular, superoxide (and not hydrogen peroxide) has a pivotal role in peroxynitrite-dependent activation of phospholipase A(2). This observation was confirmed by results showing that superoxide, or peroxynitrite, promotes release of AA in isolated mitochondria. Consistently, the release of AA elicited by either peroxynitrite or A23187 in intact cells was shown to be calcium-dependent and differentially affected by phospholipase A(2) inhibitors with different levels of specificity. In particular, the effects of peroxynitrite, unlike those of A23187, were both sensitive to low concentrations of two general phospholipase A(2) inhibitors and insensitive to arachidonyltrifluoromethyl ketone, which shows some selectivity towards cytosolic phospholipase A(2). In addition, peroxynitrite and A23187 synergistically enhanced the release of AA. Collectively, the above results demonstrate that peroxynitrite causes inhibition of complex III, followed by enforced formation of superoxides that stimulate the activity of a calcium-dependent PLA(2) isoform, probably localized in the mitochondria.


Arbovirus investigations in Argentina, 1977-1980. I. Historical aspects and description of study sites.
This is the introductory paper to a series on the ecology of arboviruses in Argentina. Epizootics of equine encephalitis have occurred since at least 1908, principally in the Pampa and Espinal biogeographic zones, with significant economic losses; human cases of encephalitis have been rare or absent. Both western equine and eastern equine encephalitis viruses have been isolated from horses during these epizootics, but the mosquitoes responsible for transmission have not been identified. A number of isolations of Venezuelan equine encephalitis (VEE) virus were reported between 1936 and 1958 in Argentina, but the validity of these findings has been seriously questioned. Nevertheless, serological evidence exists for human infections with a member of the VEE virus complex. Serological surveys conducted in the 1960s indicate a high prevalence of infection of humans and domestic animals with St. Louis encephalitis (SLE), and 2 SLE virus strains have been isolated from rodents. Human disease, however, has rarely been associated with SLE infection. Only 7 isolations of other arboviruses have been described (3 of Maguari, 1 of Aura, 2 of Una, and 1 of an untyped Bunyamwera group virus). In 1977, we began longitudinal field studies in Santa Fe Province, the epicenter of previous equine epizootics, and in 1980 we extended these studies to Chaco and Corrientes provinces. The study sites are described in this paper.


Effect of temperature on the CO2 splitting rate in a DBD microreactor.
A novel plate-to-plate dielectric barrier discharge microreactor (micro DBD) has been demonstrated in CO2 splitting. In this design, the ground electrode has a cooling microchannel to maintain the electrode temperature in the 263-298 K range during plasma operation. A small gap size between the electrodes of 0.50 mm allowed efficient heat transfer from the surrounding plasma to the ground electrode surface to compensate for heat released in the reaction zone and maintain a constant temperature. The effect of temperature on CO2 conversion and energy efficiency was studied at a voltage of 6-9 kV, a frequency of 60 kHz and a constant CO2 flow rate of 20 ml min-1. The CO2 decomposition rate first increased and then decreased as the electrode temperature decreased from 298 to 263 K with a maximum rate observed at 273 K. Operation at lower temperatures enhanced the vibrational dissociation of the CO2 molecule as opposed to electronic excitation which is the main mechanism at room temperature in conventional DBD reactors, however it also reduced the rate of elementary reaction steps. The counterplay between these two effects leads to a maximum in the reaction rate. The power consumption monotonously increased as the temperature decreased. The effective capacitance of the reactor increased by 1.5 times at 263 K as compared to that at 298 K changing the electric field distribution inside the plasma zone.


Spore Germination Requires Ferrichrome Biosynthesis and the Siderophore Transporter Str1 in Schizosaccharomyces pombe.
Spore germination is a process whereby spores exit dormancy to become competent for mitotic cell division. In Schizosaccharomyces pombe, one critical step of germination is the formation of a germ tube that hatches out the spore wall in a stage called outgrowth. Here, we show that iron deficiency blocks the outgrowth of germinating spores. The siderophore synthetase Sib1 and the ornithine N5-oxygenase Sib2 participate in ferrichrome biosynthesis, whereas Str1 functions as a ferrichrome transporter. Expression profiles of sib1+ , sib2+ , and str1+ transcripts reveal that they are induced shortly after induction of germination and their expression remains upregulated throughout the germination program under low-iron conditions. sib1Δ sib2Δ mutant spores are unable to form a germ tube under iron-poor conditions. Supplementation with exogenous ferrichrome suppresses this phenotype when str1+ is present. Str1 localizes at the contour of swollen spores 4 hr after induction of germination. At the onset of outgrowth, localization of Str1 changes and it moves away from the mother spore to primarily localize at the periphery of the new daughter cell. Two conserved Tyr residues (Tyr553 and Tyr567) are predicted to be located in the last extracellular loop region of Str1. Results show that these amino acid residues are critical to ensure timely completion of the outgrowth phase of spores in response to exogenous ferrichrome. Taken together, the results reveal the essential requirement of ferrichrome biosynthesis to promote outgrowth, as well as the necessity to take up ferrichrome from an external source via Str1 when ferrichrome biosynthesis is blocked.


Childhood locus of control and self-esteem, education, psychological distress and physical exercise as predictors of adult obesity.
To investigate to what extent locus of control, self-esteem, psychological distress, physical exercise, as well as socio-demographic factors are associated with obesity in 42-year-old adults in a longitudinal birth cohort study. The sample consisted of 5645 participants born in Great Britain in 1970 and followed up at 10, 34 and 42 years with data on body mass index measured at 34 and 42 years. There was an increase of adult obesity from 15.5% at age 34 to 21.2% at 42 years. Locus of control and self-esteem measured at age 10 years, psychological distress and educational qualifications assessed at age 34, and current occupational levels and physical exercise were all significantly associated with adult obesity at age 42. The associations remained significant after controlling for birth weight and gestation, maternal and paternal BMI, childhood BMI, and intelligence. Childhood locus of control and self-esteem, educational qualifications, psychological distress and physical exercise were all significantly and independently associated with adult obesity.


Functionality of soymilk powder and its components in fresh soy bread.
The physicochemical changes upon addition of soymilk powder (SMP) to soy bread were investigated. Two-pound loaves of soy bread were produced with components (soluble fiber [SF], insoluble fiber [ISF], soy protein) that mimic those levels contributed by SMP. Soy flour and soy flour/SMP soy breads served as controls. The following were determined for all breads produced: physical properties (loaf volume, crust, and crumb color); chemical compositions (SF and ISF contents, protein and ash contents); and physicochemical properties (water activity, total moisture content by thermogravimetric analysis [TGA], "freezable" water [FW], "unfreezable" water [UFW] content by DSC, stiffness at 25 degrees C by dynamic mechanical analysis [DMA], and firmness with Instron testing machine). SMP contained significant amounts of SF aside from the ISF fraction and mostly denatured soy protein. SMP addition to soy bread formulation significantly decreased loaf volume with respect to control soy bread, which can be attributed to the ISF and SPI contents of this ingredient. Other effects of SMP were found to be lighter and yellowish crumb color, darker crust color, and increase in firmness, as well as no change in moisture content, FW and UFW contents, water activity, and stiffness parameters.


High genetic diversity of paramyxoviruses infecting domestic cats in Western Brazil.
Feline morbillivirus was discovered in 2012 in cats from Hong Kong, and it was initially found to be associated with chronic kidney disease. Although subsequent molecular surveys showed a common occurrence in cat populations from distinct countries, there were controversial results regarding the relationship between viral shedding through urine and reduced kidney function. In this study, 276 domestic cats of diverse origins from Western Brazil had their urine evaluated for the presence of paramyxoviral RNA by reverse transcription seminested PCR and direct sequencing. Additionally, a selected Brazilian feline morbillivirus strain was isolated in Crandell Rees feline kidney cells, and a nearly complete genome sequence was obtained. To assess the kidney function of all cats, serum biochemistry screening and standard urinalysis were performed. Our results revealed a relatively high paramyxovirus-positive rate (34.7%) in the evaluated cats although there was not a statistical association between the shedding of viral RNA through urine and kidney disease. Direct sequencing of partial fragments of the L gene demonstrated high genetic diversity among strains detected in cats in this study, since both feline morbillivirus RNA and feline paramyxovirus RNA were frequently shed in urine. Phylogenetic reconstruction based on partial amino acid sequences of the L gene showed that Brazilian feline paramyxovirus strains were genetically diverse since they grouped into two distinct subclusters; one subcluster contained three strains identified in Germany, while the second contained Japanese strain 163, which was recently classified in the Jeilongvirus genus of the Paramyxoviridae family. In contrast, the Brazilian feline morbillivirus strain FeMV/BR_Boni, herein characterized by nearly complete genome sequencing, was classified in the Morbillivirus genus with other strains previously identified as genotype 1. In conclusion, urinary excretion of diverse paramyxoviral RNA is frequent in cats of different origins from Western Brazil, but viral infection is not related to altered kidney function.


Basal neutrophil-to-lymphocyte ratio is associated with overall survival in melanoma.
Several studies have reported that a high neutrophil-to-lymphocyte ratio (NLR) is associated with poor clinical outcomes in several cancers, but this ratio has not been thoroughly studied in melanoma except in stage IV. This is the first study on NLR in melanoma stages I-III. This was a retrospective study of 742 melanoma patients. The NLR was classified into NLR<2 and a NLR≥2 on the basis of a receiver operating characteristic curve. Associations of NLR with clinicopathological characteristics and survival were examined. The median patient age was 57 years (range: 15-91; Q1=46, Q3=70), and the median Breslow's thickness was 3.0 mm (range: 0.5-60; Q1=1.0, Q3=7). Clinical stage at presentation was as follows: (i) stage I in 27%; (ii) stage II in 33.2%; (iii) stage III in 36.5%; and (iv) stage IV in 3.3%. NLR≥2 was associated with lymph node metastasis (36.6 vs. 18.1%) and recurrence (28.2 vs. 22.1%). The 5-year overall survival (OS) was 63% for the NLR<2 group and 53% for the NLR≥2 group. Stage-by-stage analysis showed that the 5-year OS in the NLR≥2 group for stages I, II, III, and IV were 91, 60, 28, and 0%, respectively, whereas for the NLR<2 group the 5-year OS were 98, 68, 31, and 0%, respectively. Significant differences between NLR<2 and ≥2 occurred only in stage II (P=0.014). Univariate analysis showed that factors associated with decreased OS clinical stage were Breslow's thickness, ulceration, male sex, and NLR≥2. In the multivariate analysis, all of these factors were predictors of decreased survival. The NLR appears to be an accurate prognostic marker for decreased OS in patients with melanoma, especially in clinical stage II. NLR≥2 correlated with lymph node metastasis and recurrence.


Cardiologic aspects of aortic valve surgery--who? when? what?
The title invites a discussion of a patient (age, lesion, physical condition, compliance, and other organ pathology) with aortic valve disease in the context of proposed surgical management. It further seeks clarification on the timing of such surgical contribution and on which operation is optimal. Without reviewing all the vast and somewhat conflicting literature, these aspects are addressed by a clinical cardiologist based principally on his own experience. Among the principal conclusions are the following: a) Surgery can safely be delayed in hemodynamically significant congenital aortic stenosis in children or young adults provided that the patients are nearly asymptomatic and that submaximal or maximal stress testing shows minimal or no ST-T changes. b) Prognosis after successful valve surgery for critically tight aortic stenosis in middle-aged and elderly patients differs from that for aortic regurgitation in that left ventricular myocardial dysfunction, however severe, will always improve postoperatively in the former condition. There is, therefore, never a cardiac contraindication to surgical management of symptomatic patients with tight aortic stenosis. c) Certain features in cases of chronic severe aortic regurgitation, such as diminished ejection fraction, increased end-systolic left ventricular diameter, electrocardiographic repolarization abnormalities, marked cardiomegaly on radiologic examination, and NYHA class III or IV symptoms, reflect a higher operative mortality and poorer long-term prognosis. Nevertheless, none of these features, alone or combined, can to date justify a definite contraindication to surgery in a specific patient. d) There is little uniformity or agreement among surgeons, including their cardiologists if or when that is pertinent, on the type of operation for patients of any age requiring aortic valve surgery. For example, a patient aged 40 years and depending on the "whims and fancies" of a Department or indeed those of an individual surgeon, which include his own judgement of his technical ability, may be subjected to a repair, a Ross procedure, insertion of a homograft or replacement with one of a variety of bioprosthetic and mechanical valves. The reasons, logic or motives behind these different choices are sometimes difficult, certainly for this author, to comprehend. Hopefully, ongoing international experience and research endeavors will, at least partially, clarify the current confusion. There is presumably an "optimal" way to hold a golf club or to kick a football?! The skill and judgement of the operators will, inevitably and sometimes regrettably, always vary.


Mechanism and role of growth arrest in programmed (apoptotic) death of prostatic cancer cells induced by thapsigargin.
More than 95% of metastatic androgen independent prostatic cancer cells per day are in a proliferatively quiescent G0 state [Berges et al.: Clin Cancer Res 1:473-480, 1995] limiting their responsiveness to anti-proliferative chemotherapeutic agents. Novel therapeutics capable of activating the programmed (apoptotic) death pathway in these cells without requiring entrance into the proliferative cell cycle are urgently needed. Thapsigargin (TG) treatment of rapidly growing androgen independent prostatic cancer cells arrests such cells in G0 and induces their programmed death. This raises not only the issue of the mechanism for such growth arrest, but also whether this programmed death is simply a response of rapidly growing cells to growth arrest making cytotoxicity still dependent upon the initial rate of cell proliferation. To resolve the mechanism of TG induced growth arrest, rat AT3.1 prostatic cancer cells were analyzed for RNA and protein expression of the growth arrest gene, gadd153, intracellular free Ca2+ levels (Cai), and cell cycle distribution on exposure to TG alone and in combination with Ca2+ chelation induced by BAPTA-AM or BAPTA-AM/EGTA. To resolve whether growth arrest is required for TG cytotoxicity, primary cultures of proliferatively quiescent, human prostatic cancer cells were exposed to TG. Co-treatment of androgen independent AT-3 rat prostatic cancer cells with the Cai chelator BAPTA plus TG prevented growth arrest, as monitored by DNA flow cytometry, and failure to induce mRNA and protein for gadd153, demonstrating that growth arrest is due to Cai elevation, not depletion of intracellular Ca2+ pools. In addition, proliferatively quiescent G0 primary cultures of human prostatic cancer cells were resistant to anti-proliferative agents, but could be induced to undergo programmed death by TG as documented by morphological criteria and 14C-labeled DNA fragmentation assays. These results demonstrate that TG with its ability to elevate Cai induces proliferating prostate cancer cells to growth arrest. Such Cai dependent growth arrest is not required, however, since TG can induce the programmed death of proliferatively quiescent G0 prostatic cancer cells without requiring either growth arrest or progression through the proliferative cell cycle.


In vivo proton magnetic resonance spectroscopy of brain tumors.
The ability of magnetic resonance spectroscopy (MRS) to differentiate neoplastic brain cells and their metabolic and structural characteristics is evaluated. We examined 120 patients with brain tumors using a 1.5-tesla MRI unit and MRS. The peak areas of N-acetyl-aspartate (NAA), phosphocreatine-creatine (Pcr-Cr), choline-containing compounds (Cho), lactate, lipids, myoinositol, amino acids and the ratios of NAA/Pcr-Cr, NAA/Cho and Cho/Pcr-Cr were calculated by a standard integral algorithm. In normal brain tissue, the following metabolites were identified: NAA at 2.0 ppm, Pcr-Cr at 3.0 ppm and Cho at 3.2 ppm. The different concentrations of the metabolites examined and their role in the biochemical profile of different types of tumors are discussed. The confidence interval of the MRS versus pathology was between 0.9 and 0.954, while it was between 0.52 and 0.631 for MRI versus pathology. The Cho/Pcr-Cr ratio is a very important malignancy marker for histologic tumor grading of astrocytomas. The greater this ratio, the higher the grade of the astrocytoma. NAA/Pcr-Cr together with Cho/Pcr-Cr help specify the presence or absence of a neoplasm. Proton MRS is a useful and promising diagnostic modality not only in diagnosing but also in grading solid brain tumors.


Age and Outcome in Gastrointestinal Cancers: A Population-Based Evaluation of Oesophageal, Gastric and Colorectal Cancer.
With demographic changes and partial representativeness of randomized studies the question arises which results are achieved in the treatment of the elderly. The objective was to analyse population-based data on gastrointestinal cancers in terms of age. Analyses included data of the Munich Cancer Registry, i.e. 4,014, 10,127 and 42,809 invasive oesophageal, gastric and colorectal cancer patients, respectively, which were diagnosed between 1998 and 2014. Tumour characteristics and outcome were analysed by age groups and therapy. Overall survival was analysed using the Kaplan-Meier method, and relative survival was computed as estimation for cancer-specific survival. Additionally, conditional survival of patients surviving at least 6 or 12 months was analysed by age. 21, 44 and 38% of oesophageal, gastric and colorectal cancer patients, respectively, were aged >75 years. Of these, 15, 46 and 73% were surgically treated with curative intent, respectively, which is significantly less than in younger patients. The total 5-year relative survival was 24, 33 and 66%, respectively. The differences in median survival by age group were diminished by selecting those surviving at least 6 or 12 months and those with curatively intended treatment. An adequate patient selection for therapies of these gastrointestinal cancers was demonstrated at large. If the patients' general conditions allowed curatively intended treatment, it was applied and led to similar outcomes irrespective of age.


Generation of linear and nonlinear nonparaxial accelerating beams.
We study linear and nonlinear self-accelerating beams propagating along circular trajectories beyond the paraxial approximation. Such nonparaxial accelerating beams are exact solutions of the Helmholtz equation, preserving their shapes during propagation even under nonlinearity. We generate experimentally and observe directly these large-angle bending beams in colloidal suspensions of polystyrene nanoparticles.


Development of in House ELISAs to Detect Antibodies to SARS-CoV-2 in Infected and Vaccinated Humans by Using Recombinant S, S1 and RBD Proteins.
(1) Background: The aim of this study was to produce in-house ELISAs which can be used to determine SARS-CoV-2-specific antibody levels directed against the spike protein (S), the S1 subunit of S and the receptor binding domain (RBD) of S in SARS-CoV-2 vaccinated and infected humans. (2) Methods: Three in-house ELISAs were developed by using recombinant proteins of SARS-CoV-2, namely the S, S1 and RBD proteins. Specificity and sensitivity evaluations of these tests were performed using sera from SARS-CoV-2-infected (n = 70) and SARS-CoV-2-vaccinated (n = 222; CoronaVac vaccine) humans in Istanbul, Turkey. The analyses for the presence of SARS-CoV-2-specific antibodies were performed using the in-house ELISAs, a commercial ELISA (Abbott) and a commercial surrogate virus neutralization test (sVNT). We also analyzed archival human sera (n = 50) collected before the emergence of COVID-19 cases in Turkey. (3) Results: The sensitivity of the in-house S, S1 and RBD ELISAs was found to be 88.44, 90.17 and 95.38%, while the specificity was 72.27, 89.08 and 89.92%, respectively, when compared to the commercial SARS-CoV-2 antibody test kit. The area under curve (AUC) values were 0.777 for the in-house S ELISA, 0.926 for the S1 ELISA, and 0.959 for the RBD ELISA. The kappa values were 0.62, 0.79 and 0.86 for the S, S1 and RBD ELISAs, respectively. (4) Conclusions: The in-house S1 and RBD ELISAs developed in this study have acceptable performance characteristics in terms of sensitivity, specificity, AUC and kappa values. In particular, the RBD ELISA seems viable to determine SARS-CoV-2-specific antibody levels, both in infected and vaccinated people, and help mitigate SARS-CoV-2 outbreaks and spread.


The lived experience of family members of persons who compulsively hoard: a qualitative study.
The current study took an Interpretive Phenomenological Analysis approach to investigate the lived experiences of 12 family members of persons who hoard to better understand family members' cognitions, emotions, perceptions, experiences, and responses in their interactions with their loved ones who hoard. Five overarching themes for the participants' experiences of having a person who hoards in the family emerged: negative feelings toward the persons who hoard; lack of understanding of hoarding behavior; experiences of loss; internal barriers to seeking support; and internal conflicts. Clinical implications and recommendations for future research are discussed, including a proposed application of an ambiguous loss framework for understanding and working with the experiences of family members of persons who hoard.


The relationships between growth rate and mitochondrial metabolism varies over time.
Mitochondrial metabolism varies significantly between individuals of the same species and can influence animal performance, such as growth. However, growth rate is usually determined before the mitochondrial assay. The hypothesis that natural variation in mitochondrial metabolic traits is linked to differences in both previous and upcoming growth remains untested. Using biopsies to collect tissue in a non-lethal manner, we tested this hypothesis in a fish model (Dicentrarchus labrax) by monitoring individual growth rate, measuring mitochondrial metabolic traits in the red muscle, and monitoring the growth of the same individuals after the mitochondrial assay. Individual variation in growth rate was consistent before and after the mitochondrial assay; however, the mitochondrial traits that explained growth variation differed between the growth rates determined before and after the mitochondrial assay. While past growth was correlated with the activity of the cytochrome c oxidase, a measure of mitochondrial density, future growth was linked to mitochondrial proton leak respiration. This is the first report of temporal shift in the relationship between growth rate and mitochondrial metabolic traits, suggesting an among-individual variation in temporal changes in mitochondrial traits. Our results emphasize the need to evaluate whether mitochondrial metabolic traits of individuals can change over time.


Stroke mortality and trends from 1990 to 2006 in 39 countries from Europe and Central Asia: implications for control of high blood pressure.
The aim of the present study was to extend our understanding of international trends in stroke and major sequelae in Europe and countries peripheral to Europe by assessing: (1) current mortality rates, (2) the most recent 15-year prevalence trends, and (3) the relationship between systolic blood pressure in community surveys and national stroke mortality. Data were obtained from the World Health Organization (WHO www.who.int/whosis/database/mort/table.cfm), and represent national vital statistics as reported by 39 countries (European and Central Asian countries) using a standard format and population-based cardiovascular surveys. Total numbers of deaths by stroke (International Classification of Diseases 430-438, 444) and the age, sex-adjusted incidence rates were obtained and grouped according to three standard demographic categories: A, B, and C (WHO). A Bayesian linear mixed effect model was fitted to the annual mortality rates. Higher rates of stroke mortality were observed for B and C group countries as compared with those countries belonging to Group A (e.g. Bulgaria 273.9 and 281.1; Israel 37.7 and 45.4 per 100 000 men and women, respectively). Even though the mortality rates within the country groupings were relatively similar, countries with marked deviation from the average were observed, mainly in Groups B and C. Stroke mortality decreased sharply in Group A during the period of study; conversely it had increased substantially in Group B and to a lesser extent in Group C. For both sexes markedly higher rates were noted moving from west to east, with some exceptions. We have entered a period of rapidly increasing international inequality in stroke risk, where countries with low adult mortality in the latter 20th century extended their downward trend and countries with moderate as well as high mortality have on average seen unprecedented increases in death rates from stroke.


Magnesium intake and incidence of stroke: meta-analysis of cohort studies.
Prospective cohort studies are inconsistent regarding the association between magnesium intake and the risk of stroke. The objective was to perform a meta-analysis to summarise the relationship between magnesium intake and risk of stroke in observational studies. We searched the PubMed and EMBASE databases for studies conducted from 1966 through August 2011. Prospective studies that provided relative risk (RR) estimates with 95% confidence intervals (CIs) for the association between magnesium intake and the risk of total stroke incidence or mortality were included. Data were independently abstracted by two investigators using a standardised protocol. Study-specific risk estimates were combined by using a random effects model. A total of eight studies, with 8367 stroke cases among 304,551 participants, were included in the meta-analysis. The summary RR indicated a significant association between the highest magnesium intake and reduced risk of total stroke (summary RR: 0.89; 95% CI: 0.82, 0.97); our dose-response analysis showed a borderline inverse association between magnesium intake and total stroke risk (an increment of 100 mg day(-1); summary RR: 0.98; 95% CI: 0.95, 1.00). Subgroup analyses suggested a significant inverse association between highest magnesium intake and the risk of ischaemic stroke (summary RR: 0.88; 95% CI: 0.80, 0.98). The present meta-analysis of prospective cohorts suggests that higher magnesium intake is associated with reduced risk of total and ischaemic stroke. However, well-designed randomised controlled trials are needed to draw a definitive conclusion.


Bird migratory flyways influence the phylogeography of the invasive brine shrimp Artemia franciscana in its native American range.
Since Darwin's time, waterbirds have been considered an important vector for the dispersal of continental aquatic invertebrates. Bird movements have facilitated the worldwide invasion of the American brine shrimp Artemia franciscana, transporting cysts (diapausing eggs), and favouring rapid range expansions from introduction sites. Here we address the impact of bird migratory flyways on the population genetic structure and phylogeography of A. franciscana in its native range in the Americas. We examined sequence variation for two mitochondrial gene fragments (COI and 16S for a subset of the data) in a large set of population samples representing the entire native range of A. franciscana. Furthermore, we performed Mantel tests and redundancy analyses (RDA) to test the role of flyways, geography and human introductions on the phylogeography and population genetic structure at a continental scale. A. franciscana mitochondrial DNA was very diverse, with two main clades, largely corresponding to Pacific and Atlantic populations, mirroring American bird flyways. There was a high degree of regional endemism, with populations subdivided into at least 12 divergent, geographically restricted and largely allopatric mitochondrial lineages, and high levels of population structure (Φ ST of 0.92), indicating low ongoing gene flow. We found evidence of human-mediated introductions in nine out of 39 populations analysed. Once these populations were removed, Mantel tests revealed a strong association between genetic variation and geographic distance (i.e., isolation-by-distance pattern). RDA showed that shared bird flyways explained around 20% of the variance in genetic distance between populations and this was highly significant, once geographic distance was controlled for. The variance explained increased to 30% when the factor human introduction was included in the model. Our findings suggest that bird-mediated transport of brine shrimp propagules does not result in substantial ongoing gene flow; instead, it had a significant historical role on the current species phylogeography, facilitating the colonisation of new aquatic environments as they become available along their main migratory flyways.


Phase I and pharmacokinetic study of imatinib mesylate in patients with advanced malignancies and varying degrees of liver dysfunction: a study by the National Cancer Institute Organ Dysfunction Working Group.
To develop dosing guidelines and to evaluate the pharmacokinetics of imatinib in patients with liver dysfunction (LD). Patients (N = 89) with varying solid tumors and liver function were stratified into four groups according to serum total bilirubin and AST and were treated with escalating doses of imatinib. Plasma and urine were assayed for concentrations of imatinib and its active metabolite, CGP74588. In the mild LD group, dose-limiting toxicity, specifically nausea/vomiting and fatigue, occurred in two patients at the 600 mg/d dose level. In the moderate and severe LD groups, the maximal dose evaluated was 300 mg/d. Grade 3 to 4 toxicities consisted primarily of liver function test elevations (24%), nausea/vomiting (10%), fatigue (6%), and edema (5%). After the first imatinib dose, the mean (+/- SD) dose-normalized areas under the plasma concentration-time curve from time 0 to infinity (AUC(0-infinity)) were 162 +/- 155, 171 +/- 72, 182 +/- 157, and 185 +/- 172 (mug/mL x h)/mg for normal, mild, moderate, and severe LD groups, respectively. Renal excretion of imatinib was less than 10% of the total dose in all groups. Imatinib exposure (as measured by the dose-normalized AUC) did not differ between patients with normal liver function and those with LD. The maximal recommended dose of imatinib for patients with mild LD is 500 mg/d. Dosing guidelines for patients with moderate and severe LD remain undetermined.


A system for tracking braille readers using a Wii Remote and a refreshable braille display.
This article describes a cheap and easy-to-use finger-tracking system for studying braille reading. It provides improved spatial and temporal resolution over the current available solutions and can be used with either a refreshable braille display or braille-embossed paper. In conjunction with a refreshable braille display, the tracking system has the unique capacity to implement display-change paradigms derived from sighted reading research. This will allow researchers to probe skilled braille reading in significantly more depth than has heretofore been possible.


AIDS volunteers and their motivations: theoretical issues and practical concerns.
Volunteers and volunteer organizations are critical elements in society's response to the HIV epidemic. This article reviews a model of the volunteer process that draws on psychological theory and methodology and incorporates concerns of individual volunteers, volunteer organizations, and society at large. An inventory for assessing the motivations of AIDS volunteers is introduced. The findings from a survey of volunteers working in AIDS organizations around the United States speak to their motivations, their choices of volunteer roles, and their decisions about quitting or continuing service. Based on these findings, a detailed set of recommendations for effective volunteer recruitment, assignment, and retention is offered.


Ultra-small superparamagnetic iron oxides for metastatic lymph node detection: back on the block.
In the past 15 years, encouraging clinical results for the detection of small lymph node metastases was obtained by the use of Combidex-enhanced MRI (CEM, also known as magnetic resonance lymphography). Withdrawal of the European Medicines Agency approval application by the manufacturer made it impossible for patients to benefit from this agent; a loss, especially for men with prostate cancer. Current conventional imaging techniques are not as accurate as CEM is, thus a surgical diagnostic exploration (extended lymph node dissection) is still the preferred technique to evaluate the lymph nodes, resulting in peri- and postoperative complications. In 2013, the Radboud University Medical Center (Radboudumc) obtained all licenses and documentation for the production process of Combidex (ferumoxtran-10), and manufactured the contrast agent under supervision of the Department of Pharmacy. Since 2014, 310 men with prostate cancer have been examined with CEM in the Radboudumc. Within this cohort, seven minor possibly contrast-related adverse effects were observed after administration of Combidex. As the contrast agent is now back again in the Netherlands, this review highlights the working mechanism, previous results, observed side effects since the reintroduction, and the future perspectives for Combidex. WIREs Nanomed Nanobiotechnol 2018, 10:e1471. doi: 10.1002/wnan.1471 This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.


Mechanisms for linezolid-induced anemia and thrombocytopenia.
Linezolid has been associated with anemia and thrombocytopenia. Mechanisms for neither have been elucidated. To propose mechanisms for linezolid-induced anemia and thrombocytopenia. A 78-year-old white woman with Staphylococcus epidermidis endocarditis was treated with linezolid after developing resistance to multiple antibiotic regimens. After 7 days of linezolid therapy, she developed thrombocytopenia, while an anemia present since admission remained unchanged. A bone marrow biopsy was performed, primarily looking for a mechanism for the thrombocytopenia. Histopathology revealed adequate megakaryocytes, ringed sideroblasts, and vacuolated pronormoblasts. A course of immune globulin (IVIG) was administered, with slowing in the rate of decline in platelets. She died 24 hours after her last dose of IVIG of congestive heart failure. The presence of ringed sideroblasts and vacuolated pronormoblasts suggests that linezolid-induced anemia is secondary to a chloramphenicol-like suppression of erythropoiesis. The presence of adequate, normal-appearing megakaryocytes suggests immune-mediated thrombocytopenia, not marrow suppression. Although the response to IVIG is difficult to interpret because of the patient's death, there was a slowing in the rate of decline of the platelet count, further supporting immune-mediated thrombocytopenia. An objective causality assessment indicated that the adverse drug event was probably due to linezolid. There appear to be 2 distinct mechanisms for linezolid-induced cytopenias. While anemia is reversible and manageable with transfusions, thrombocytopenia can be a treatment-limiting toxicity. The ability to treat through an immune-mediated cytopenia with IVIG may be beneficial for critically ill patients with few therapeutic options.


[Neuropsychological aspects of oneiric activity: theoretical considerations suggested by clinical features].
Based on observations in five patients, we review the main theories concerning dreams and propose a comprehensive theory on their cognitive function. We classify dreams based on the role performed by them in inhibition, stimulation or creation of cognitive strategies around an emotional nucleus. These are stored in the memory bank and retrieved by an elicitation mechanism linking affective experiences on awareness and the strategies processed in previous dreams. We also propose that the changes in logical and emotional patterns in dreams are based on fronto-limbic dominance oscillations during each REM period. Preliminary observations we made show that awakening patients during most rapid frontal EEG activity REM sleep elicits more logical and less bizarre dreams. Contrariwise, when they are awakened during slower REM cortical EEG activity, mainly over the frontal lobes, their dreams are more bizarre and consequently less elaborated from a cognitive point of view.


Molecular remission at T cell level in patients with rheumatoid arthritis.
While numerous disease-modifying anti-rheumatic drugs (DMARDs) have brought about a dramatic paradigm shift in the management of rheumatoid arthritis (RA), unmet needs remain, such as the small proportion of patients who achieve drug-free status. The aim of this study was to explore key molecules for remission at the T cell level, which are known to be deeply involved in RA pathogenesis, and investigate the disease course of patients who achieved molecular remission (MR). We enrolled a total of 46 patients with RA and 10 healthy controls (HCs). We performed gene expression profiling and selected remission signature genes in CD4+ T cells and CD8+ T cells from patients with RA using machine learning methods. In addition, we investigated the benefits of achieving MR on disease control. We identified 9 and 23 genes that were associated with clinical remission in CD4+ and CD8+ T cells, respectively. Principal component analysis (PCA) demonstrated that their expression profiling was similar to those in HCs. For the remission signature genes in CD4+ T cells, the PCA result was reproduced using a validation cohort, indicating the robustness of these genes. A trend toward better disease control was observed during 12 months of follow-up in patients treated with tocilizumab in deep MR compared with those in non-deep MR, although the difference was not significant. The current study will promote our understanding of the molecular mechanisms necessary to achieve deep remission during the management of RA.


[Stress and progression in multiple sclerosis].
The hypothesis that stress might be connected to causation or exacerbation of multiple sclerosis has been under discussion for a long time. The current studies indicate that there is a coincidence between stress and disease progression. Besides the state of art in research different stress models will be introduced in the paper and the relations between disease, resources and coping will be discussed. Besides the influence of distressing life events on disease, the effect of illness-related characteristics on the coping behaviour will be considered in this regard. From the results of the presented studies and the described stress models it was concluded that the possibilities of stress avoiding intervention programs should be taken into account more strongly in the future.


PAI-1 and TAFI in inflammatory bowel disease: the yin and yang of the fibrinolytic system.
In both Crohn's disease and ulcerative colitis, the two major forms of inflammatory bowel disease (IBD), an increased risk of thrombotic events has been demonstrated. Pathogenesis of thrombosis is multifactorial as various primary coagulation system abnormalities other than acquired factors have been reported. The fibrinolytic system has been widely investigated in IBD. Most of the available data report an imbalance in fibrinolytic capacity with a tendency toward a hypofibrinolytic state. Plasma thrombin-activatable fibrinolysis inhibitor and plasminogen activator inhibitor-1 are fundamental inhibitors of the fibrinolytic process and are also considered to be acute-phase reactants. Recent studies have shown an imbalance of plasminogen activator inhibitor-1 and thrombin-activatable fibrinolysis inhibitor, suggesting that these molecules might contribute to thromboembolic events in both forms of IBD.


Food intake, growth rate, food conversion and food choice in broilers fed on diets high in rapeseed meal and pea meal, with observations on sensory evaluation of the resulting poultry meat.
1. Experiments were done to measure the effects of 100 and 200 g/kg of either pea meal or low glucosinolate, low erucic acid rapeseed meal on food intake and growth, food choice and meat organoleptic quality in broiler chickens. 2. The test diets were formulated to be iso-energetic and iso-nitrogenous with a soy-wheat control diet. In all diets, lysine was fixed at 11.0 g/kg and all other indispensable amino acids were present in excess of requirements. 3. Food intake was little affected by the inclusion of 100 g/kg of pea meal in the diet but 200 g/kg of peas caused a decrease. Rapeseed produced a decrease in food intake at both dietary concentrations. 4. Weight gain was similarly affected, but food conversion from d 0 to d 42 was little affected by the inclusion of either peas or rapeseed. 5. Absolute breast muscle weight was affected by diet but there was no significant difference in breast weight as a proportion of total body weight. 6. From d 7 onwards, selection against the pea-containing diet approached statistical significance. Between d 7 and d 14, birds ate almost twice as much of the control as of the pea-containing diet. Birds offered a rapeseed meal diet ate similar amounts of that and the control diet. 7. The breast meat from birds given 200 g rapeseed/kg was the only meat identified as different but no strong aversion was expressed by the tasting panel.


Interpleural morphine vs bupivacaine for postthoracotomy pain relief.
This prospective randomized double-blind trial was designed to compare the analgesic effects of interpleural bupivacaine and interpleural morphine for postthoracotomy pain management. Thirty-six American Society of Anesthesiologists class I and II patients undergoing an elective posterolateral thoracotomy were randomly divided into 2 groups of 18 each. Before chest closure, an interpleural catheter was inserted under direct vision. At the end of the operation and every 4 hours thereafter, they received either 0.25% bupivacaine with epinephrine or 0.2 mg x kg(-1) morphine sulfate interpleurally for 24 hours. The chest tubes were clamped during injection and for 15 min afterwards. Supplementary doses of intravenous morphine were given on request. The pain severity was evaluated at rest and on coughing before and 30 min after each interpleural injection, using an 11-point visual analog scale. Supplemental analgesic consumption and side effects were recorded. Both interpleural morphine and bupivacaine significantly reduced pain scores 30 min after each injection. However, pain scores and supplementary analgesic requirements were significantly lower in the interpleural morphine group. No serious side effects were detected in either group. Interpleural morphine provides better pain control than interpleural bupivacaine after a posterolateral thoracotomy.


Evaluation of a Multidrug Assay for Monitoring Adherence to a Regimen for HIV Preexposure Prophylaxis in a Clinical Study, HIV Prevention Trials Network 073.
Daily oral tenofovir disoproxil fumarate (TDF)-emtricitabine (FTC) is a safe and effective intervention for HIV preexposure prophylaxis (PrEP). We evaluated the performance of a qualitative assay that detects 20 antiretroviral (ARV) drugs (multidrug assay) in assessing recent PrEP exposure (detection limit, 2 to 20 ng/ml). Samples were obtained from 216 Black men who have sex with men (208 HIV-uninfected men and 8 seroconverters) who were enrolled in a study in the United States evaluating the acceptability of TDF-FTC PrEP (165 of the uninfected men and 5 of the seroconverters accepted PrEP). Samples from 163 of the 165 HIV-uninfected men who accepted PrEP and samples from all 8 seroconverters were also tested for tenofovir (TFV) and FTC using a quantitative assay (detection limit for both drugs, 0.31 ng/ml). HIV drug resistance was assessed in seroconverter samples. The multidrug assay detected TFV and/or FTC in 3 (1.4%) of the 208 uninfected men at enrollment, 84 (40.4%) of the 208 uninfected men at the last study visit, and 1 (12.5%) of the 8 seroconverters. No other ARV drugs were detected. The quantitative assay confirmed all positive results from the multidrug assay and detected TFV and/or FTC in 9 additional samples (TFV range, 0.65 to 16.5 ng/ml; FTC range, 0.33 to 14.6 ng/ml). Resistance mutations were detected in 4 of the 8 seroconverter samples. The multidrug assay had 100% sensitivity and specificity for detecting TFV and FTC at drug concentrations consistent with daily PrEP use. The quantitative assay detected TFV and FTC at lower levels, which also might have provided protection against HIV infection.


Fabrication and Investigation of Graphite-Flake-Composite-Based Non-Invasive Flex Multi-Functional Force, Acceleration, and Thermal Sensor.
This work examines the physics of a non-invasive multi-functional elastic thin-film graphite flake-isoprene sulfone composite sensor. The strain design and electrical characterization of the stretching force, acceleration, and temperature were performed. The rub-in technique was used to fabricate graphite flakes and isoprene sulfone into sensors, which were then analyzed for their morphology using methods such as SEM, AFM, X-ray diffraction, and Fourier transform infrared spectroscopy to examine the device's surface and structure. Sensor impedance was measured from DC to 200 kHz at up to 20 gf, 20 m/s2, and 26-60 °C. Sensor resistance and impedance to stretching force and acceleration at DC and 200 Hz rose 2.4- and 2.6-fold and 2.01- and 2.06-fold, respectively. Temperature-measuring devices demonstrated 2.65- and 2.8-fold decreases in resistance and impedance at DC and 200 kHz, respectively. First, altering the graphite flake composite particle spacing may modify electronic parameters in the suggested multi-functional sensors under stress and acceleration. Second, the temperature impacts particle and isoprene sulfone properties. Due to their fabrication using an inexpensive deposition technique, these devices are environmentally friendly, are simple to build, and may be used in university research in international poverty-line nations. In scientific laboratories, such devices can be used to teach students how various materials respond to varying environmental circumstances. They may also monitor individuals undergoing physiotherapy and vibrating surfaces in a controlled setting to prevent public health risks.


Behavioral reactivity to a noradrenergic challenge after chronic oral methylphenidate (ritalin) in rats.
Methylphenidate (Ritalin) is routinely used for the treatment of attention-deficit/hyperactivity disorder (ADHD). It is a psychomotor stimulant with pharmacodynamics similar to those established for cocaine and amphetamine with primary activation of the noradrenergic and dopaminergic systems. Long-term exposure to psychostimulants including methylphenidate (MPD) is believed to result in enduring functional changes along both these pathways and various behaviors mediated by these systems may be affected. In the present experiment, the effects of intermittent oral administration of methylphenidate (10 mg/kg) to rats over a 4-week period were subsequently (after a drug washout interval) assessed in three animal models sensitive to noradrenergic manipulation: the elevated plus-maze, predator odor avoidance, and social interaction tests. The behaviors of methylphenidate-experienced animals were compared with untreated controls. Thirty minutes prior to testing, half the animals with each of these histories received an injection of yohimbine hydrochloride (2.0 mg/kg), an alpha2-adrenoreceptor blocker intended to evoke noradrenergic system activation, while the remainder received a saline injection. Yohimbine was expected to reduce both exploration of novel stimuli and interaction with conspecifics, and it was predicted that methylphenidate would potentiate these effects. Relative to saline-tested controls, rats that received both the methylphenidate treatment and the yohimbine challenge exhibited the least exploration in the predator odor test and the lowest duration of interaction with an unfamiliar conspecific partner in the social interaction test. The behavior patterns observed in this group of rats suggest heightened emotionality and defensiveness that are typically seen when rats are administered drugs known to be anxiogenic in human subjects. In the plus-maze, exploratory locomotor activities remained unaltered by either drug while yohimbine decreased risk-assessment behaviors, an effect that remained uninfluenced by methylphenidate pretreatment.


Evaluating medical students' knowledge of patient-reported outcomes and the impact of curriculum intervention in consecutive cohorts.
Patient-reported outcomes (PROs) collection and utilization improves patient-provider communication, symptom reporting, and patient satisfaction. Despite their significance, the science and utility of PROs are not part of required curriculum in medical education. The authors describe the results of a survey distributed to medical students evaluating their experience, knowledge, and perceptions of PROs, report on outcomes of the impact of formal PRO education on medical student knowledge, and describe strategies to foster the spread of PRO education into other programs. The authors developed and distributed a 20-question web-based survey distributed to medical students at two U.S. medical schools to evaluate students' experience, knowledge, and perceptions of PROs. To compare medical students' knowledge in their pre-clinical years (M1-M2) to those in their clinical years (M3-M4), the authors calculated odds ratios and determined significance determined using chi-squared tests. To determine the utility of formal education on medical students' knowledge of PROs, the authors invited 4th year medical students at a single institution to participate in a survey before and two weeks after receiving formal PRO education as part of the medical school curriculum, spanning three years. 137 (15%) medical students responded to the initial survey. Respondents' knowledge of PROs was low and did not differ when comparing pre-clinical to clinical years in school. Less than 10% had received education on PROs and only 16% felt prepared to use PROs in patient care. Respondents demonstrated positive attitudes towards PROs, with 84% expressing interest in learning about PROs. In the second phase education cohort of 231 (77% response rate) 4th -year medical students over three years, formal education improved correct response rates to PRO questions. After education, 90% (121/134) agreed PROs are an important component of high-quality care. This study identifies a gap in knowledge about PROs among medical students irrespective of year in training. It also shows that structured education may help fill the PRO knowledge gap, potentially providing future clinicians with the skills to implement PROs into clinical practice, aligning with the broader shift towards patient-centric evidence-based healthcare practices.


When can categorical variables be treated as continuous? A comparison of robust continuous and categorical SEM estimation methods under suboptimal conditions.
A simulation study compared the performance of robust normal theory maximum likelihood (ML) and robust categorical least squares (cat-LS) methodology for estimating confirmatory factor analysis models with ordinal variables. Data were generated from 2 models with 2-7 categories, 4 sample sizes, 2 latent distributions, and 5 patterns of category thresholds. Results revealed that factor loadings and robust standard errors were generally most accurately estimated using cat-LS, especially with fewer than 5 categories; however, factor correlations and model fit were assessed equally well with ML. Cat-LS was found to be more sensitive to sample size and to violations of the assumption of normality of the underlying continuous variables. Normal theory ML was found to be more sensitive to asymmetric category thresholds and was especially biased when estimating large factor loadings. Accordingly, we recommend cat-LS for data sets containing variables with fewer than 5 categories and ML when there are 5 or more categories, sample size is small, and category thresholds are approximately symmetric. With 6-7 categories, results were similar across methods for many conditions; in these cases, either method is acceptable.


Ketoprofen pharmacokinetics, efficacy, and tolerability in pediatric patients.
The NSAID ketoprofen is used widely in the management of inflammatory and musculoskeletal conditions, pain, and fever in children and adults. Pharmacokinetic studies show that drug exposure after a single intravenous dose is similar in children and adults (after dose normalization), and thus similar mg/kg bodyweight dosing may be used in children and adults. Ketoprofen crosses the blood-brain barrier and therefore has the potential to cause central analgesic effects. Ketoprofen has been investigated in children for the treatment of pain and fever, peri- and postoperative pain, and inflammatory pain conditions. The results of four clinical trials in febrile conditions with the oral syrup formulation indicate that ketoprofen is as effective as acetaminophen (paracetamol) and ibuprofen, allowing children to rapidly return to daily activities with improvements in sleep quality and appetite. Studies of ketoprofen in the management of postoperative pain indicate that ketoprofen is a highly effective analgesic when administered perioperatively for a variety of surgical types, by a variety of routes, and whether given preoperatively or postoperatively. For adenoidectomy, intravenous ketoprofen provided superior postoperative analgesic efficacy compared with placebo. Analgesic efficacy was similar with intravenous, intramuscular, or rectal routes of administration, but oral administration just before surgery was inferior to intravenous administration in this setting. In patients undergoing a tonsillectomy, intravenous ketoprofen was superior to intravenous tramadol in terms of the need for postoperative rescue analgesia, but did not remove the need for rescue opioid therapy in these patients. Intravenous ketoprofen had superior postoperative analgesic efficacy to placebo when given as an adjuvant to epidural sufentanil analgesia after major surgery. Oral ketoprofen has shown efficacy in the treatment of juvenile rheumatoid arthritis. Ketoprofen is generally well tolerated in pediatric patients. Most of the adverse events reported are mild and transient, and are similar to those observed with other NSAIDs. Long-term tolerability has not yet been fully established in children, but data from three studies in >900 children indicate that oral ketoprofen is well tolerated when administered for up to 3 weeks after surgery. In conclusion, ketoprofen is effective and well tolerated in children for the control of post-surgical pain and for the control of pain and fever in inflammatory conditions.


Air transported pediatric rescue extracorporeal membrane oxygenation: a single institutional review.
Pediatric extracorporeal membrane oxygenation (ECMO) programs are sophisticated endeavors usually found only in high-volume cardiac surgical programs. Worldwide, many cardiology programs do not have on-site pediatric cardiac surgery expertise. Our single-center experience shows that an organized multidisciplinary rescue-ECMO program, in collaboration with an accepting facility, can achieve survival rates comparable to modern era on-site ECMO. A retrospective review was conducted of all patients initiated on rescue-ECMO from 2004 to 2009 in a single academic pediatric hospital without a pediatric cardiac surgery program. All aspects of ECMO were formalized using Failure Mode Effects Analysis. Eight patients were initially cannulated for ECMO at our institution. Six were subsequently transported by air to the receiving facility 1,305 km away. Extracorporeal membrane oxygenation was initiated in 0.2% of our Pediatric Intensive Care Unit admissions and in 0.52% of all our pediatric cardiac patients. Mean age was 4.0 years (7 weeks to 15 years). Indications for ECMO initiations were cardiogenic shock (n = 5) and acute respiratory distress syndrome (n = 3). Six had veno-arterial- and two had veno-veno ECMO. Two patients were not transported (one death and one weaned locally). Six patients were successfully transported within 2 to 24 hours, with a survival to hospital discharge rate of 67% (four of six). Median total time on ECMO was 5.5 days. Complication rate was 50% (4/8). Our rescue-ECMO survival results were comparable to that of current published results from established pediatric ECMO programs. Air transport of ECMO patients can be performed safely using an organized multidisciplinary team approach.


Postprandial hypotension in clinical geriatric patients and healthy elderly: prevalence related to patient selection and diagnostic criteria.
The aims of this study were to find out whether Postprandial hypotension (PPH) occurs more frequently in patients admitted to a geriatric ward than in healthy elderly individuals, what the optimal interval between blood pressure measurements is in order to diagnose PPH and how often it is associated with symptoms.The result of this study indicates that PPH is present in a high number of frail elderly, but also in a few healthy older persons. Measuring blood pressure at least every 10 minutes for 60 minutes after breakfast will adequately diagnose PPH, defined as >20 mmHg systolic fall, in most patients. However with definition of PPH as >30 mmHg systolic fall, measuring blood pressure every 10 minutes will miss PPH in one of three patients. With the latter definition of PPH the presence of postprandial complaints is not associated with the existence of PPH.


Electron binding energies of hydrated H3O+ and OH-: photoelectron spectroscopy of aqueous acid and base solutions combined with electronic structure calculations.
The electronic structure of hydrated H3O+ and OH- is probed in a water jet by photoelectron spectroscopy employing 100 eV photons. The first ionization potential for OH- at 9.2 eV and the second ionization potential for H3O+ at 20 eV are resolved, corresponding to the removal of an electron from the 2ppi highest occupied molecular orbital and from the 1e orbital, respectively. These assignments are supported by present computational results based on a combination of molecular dynamics and ab initio calculations.


Effects of invertebrate iridescent virus 6 in Phyllophaga vandinei and its potential as a biocontrol delivery system.
Invertebrate iridescent virus 6 (IIV6) was determined to cause infection in Phyllophaga vandinei Smyth (Coleoptera: Scarabaeidae) through a range of modes of transmissions. This is the first evidence of IIV6 infection in P. vandinei that caused both patent and sub-lethal infections in larvae and adults. Mortality rates were determined to be ~30% when virus inoculum was injected into larvae or adults. Adults injected with virus showed dramatically altered behavior; injected beetles were not observed feeding or mating compared with adults injected with buffer or adults that were not injected. Tissue collected from infected adults resulted in infection when injected into healthy adults, as confirmed with PCR. PCR also confirmed that frass of infected larvae and adults contained virus, and when reconstituted frass from infected individuals was injected into healthy adults or larvae they become infected. Healthy adults could be infected by coming into contact with soil or plant material that had been exposed to infected adults as much as two weeks prior to introduction of nonvirus exposed adults. Although relatively low mortality resulted when adults or larvae were injected with the virus, the demonstration of horizontal transmission, potentially through frass of infected individuals, identifies a mode of transmission that may be exploited as a potential management tool to reduce P. vandinei.


Standardization of Spirometry 2019 Update. An Official American Thoracic Society and European Respiratory Society Technical Statement.
Background: Spirometry is the most common pulmonary function test. It is widely used in the assessment of lung function to provide objective information used in the diagnosis of lung diseases and monitoring lung health. In 2005, the American Thoracic Society and the European Respiratory Society jointly adopted technical standards for conducting spirometry. Improvements in instrumentation and computational capabilities, together with new research studies and enhanced quality assurance approaches, have led to the need to update the 2005 technical standards for spirometry to take full advantage of current technical capabilities.Methods: This spirometry technical standards document was developed by an international joint task force, appointed by the American Thoracic Society and the European Respiratory Society, with expertise in conducting and analyzing pulmonary function tests, laboratory quality assurance, and developing international standards. A comprehensive review of published evidence was performed. A patient survey was developed to capture patients' experiences.Results: Revisions to the 2005 technical standards for spirometry were made, including the addition of factors that were not previously considered. Evidence to support the revisions was cited when applicable. The experience and expertise of task force members were used to develop recommended best practices.Conclusions: Standards and consensus recommendations are presented for manufacturers, clinicians, operators, and researchers with the aims of increasing the accuracy, precision, and quality of spirometric measurements and improving the patient experience. A comprehensive guide to aid in the implementation of these standards was developed as an online supplement.


Interplay between Oral Hypoglycemic Medication Adherence and Quality of Life among Elderly Type 2 Diabetes Mellitus Patients.
Adherence to medications is an important factor that contributes to therapeutic success. With the current increase in the elderly population, information relating to adherence to treatment and quality of life (QoL) of diabetic elderly patients will help the healthcare provider to improve their treatment. Thus, this study aims to determine the factors affecting adherence to medications and the consequence of non adherence to QoL. This was a cross-sectional study using validated Morisky Medication Adherence Scale (MMAS) Questionnaire. This study was conducted to assess the level of adherence on oral hypoglycemic medications (OHM) and quality of life of the Type 2 diabetes mellitus (T2DM) elderly patients in an urban health centre in Malaysia. A retrospective medication record review was also conducted to collect and confirm data on patients' demographics, diagnosis, treatments, and outcomes. One hundred and seventy nine patients were recruited in this study. Median adherence score was 7.75 (IQR 6.50- 8.00). Good adherer was observed in 48.00% of the participants. A Chi-square test indicated significant correlation between adherence and HbA1c (p= 0.010). The mean elderly diabetes mellitus Problem Areas in Diabetes (PAID) score was 6.30 ±SD 8.50. A significant inversed association was observed between PAID score and the level of adherence (r = - 0.175, p< 0.05). A highly significant difference in the low adherence group (p = 0.002). PAID score significantly correlated with age (years), female gender and HbA1c (p <0.05). A negative association between HbA1c levels and adherence was identified where a 1% increase in HbA1c was associated with a 30% decrease in the likelihood of being adherent. A medication adherence rate of 48% was obtained among elderly T2DM patients treated in the primary care clinic. This study showed that HbA1c is a relevant tool to assess patient glycemic control and adherence. Sociodemographic characteristics were not statistically significantly associated with adherence. We reported a negative correlation between adherence and T2DM related emotional distress. The identified factors that relieve emotional distress of the elderly T2DM patients are similar with the western countries.


Hepatitis C virus maintains infectivity for weeks after drying on inanimate surfaces at room temperature: implications for risks of transmission.
Healthcare workers may come into contact with fomites that contain infectious hepatitis C virus (HCV) during preparation of plasma or following placement or removal of venous lines. Similarly, injection drugs users may come into contact with fomites. Hypothesizing that prolonged viability of HCV in fomites may contribute significantly to incidence, we determined the longevity of virus infectivity and the effectiveness of antiseptics. We determined the volume of drops misplaced during transfer of serum or plasma. Aliquots equivalent to the maximum drop volume of plasma spiked with the 2a HCV reporter virus were loaded into 24-well plates. Plates were stored uncovered at 3 temperatures: 4°C, 22°C, and 37°C for up to 6 weeks before viral infectivity was determined in a microculture assay. The mean volume of an accidental drop was 29 µL (min-max of 20-33 µL). At storage temperatures 4°C and 22°C, we recovered viable HCV from the low-titer spots for up to 6 weeks of storage. The rank order of HCV virucidal activity of commonly used antiseptics was bleach (1:10) > cavicide (1:10) > ethanol (70%). The hypothesis of potential transmission from fomites was supported by the experimental results. The anti-HCV activity of commercial antiseptics varied.


Maturation of frataxin within mammalian and yeast mitochondria: one-step processing by matrix processing peptidase.
Friedreich's ataxia is a neurodegenerative disease caused by mutations in the nuclear gene encoding frataxin (FRDA). FRDA is synthesized with an N-terminal signal sequence, which is removed after import into mitochondria. We have shown that FRDA was imported efficiently into isolated mammalian or yeast mitochondria. In both cases, the processing cleavage that removed the N-terminal signal sequence occurred in a single step on import, generating mature products of identical mobility. The processing cleavage could be reconstituted by incubating the FRDA preprotein with rat or yeast matrix processing peptidase (MPP) expressed in Escherichia coli. We used these assays to evaluate the import and processing of an altered form of FRDA containing the disease-causing I154F mutation. No effects on import or maturation of this mutated FRDA were observed. Likewise, no effects were observed on import and maturation of the yeast frataxin homolog (Yfh1p) carrying a homologous I130F mutation. These results argue against the possibility that the I154F mutation interferes with FRDA function via effects on maturation. Other mutations can be screened for effects on FRDA biogenesis as described here, by evaluating import into isolated mitochondria and by testing maturation with purified MPP.


Ultrasound findings of ruptured Peyronie's plaque: Case report and review of the literature.
We present here a rare case of rupture of tunica albuginea and corpus cavernosum, in the site of a Peyronie's plaque, which happened in a 61- year-old man during a vacuum cleaner masturbation. Ultrasound study showed an irregular hyperechoic defect at the cavernosal rupture site in correspondence of the Peyronie's plaque. The hematoma was evacuated, partially plaque excised, and the tear repaired. Ultrasonography is an ideal technique for evaluating patients with penile trauma and can be routinely used in an emergency. It is a non-invasive method that gives faster results than cavernosography and Magnetic Resonance Imaging.


[Use of beta adrenergic blockaders in the prevention of vitreous body prolapse in cataract extraction].
To prevent vitreous body prolapse in cataract extraction, intraocular pressure is reduced by means of beta-adrenoblockers instillation (timolol 0.5% solution) in the evening and 2 hours before surgery in the morning. Intraocular pressure was followed up in 59 patients with senile and 12 with complicated cataract subjected to cataract cryoextraction by the same surgeon. The pressure decreased by 5.6 +/- 1.3 mm Hg. Prolapse of the vitreous body occurred in 1 case.


Recent advances in sequence assembly: principles and applications.
The application of advanced sequencing technologies and the rapid growth of various sequence data have led to increasing interest in DNA sequence assembly. However, repeats and polymorphism occur frequently in genomes, and each of these has different impacts on assembly. Further, many new applications for sequencing, such as metagenomics regarding multiple species, have emerged in recent years. These not only give rise to higher complexity but also prevent short-read assembly in an efficient way. This article reviews the theoretical foundations that underlie current mapping-based assembly and de novo-based assembly, and highlights the key issues and feasible solutions that need to be considered. It focuses on how individual processes, such as optimal k-mer determination and error correction in assembly, rely on intelligent strategies or high-performance computation. We also survey primary algorithms/software and offer a discussion on the emerging challenges in assembly.


Care transitions for frail, older people from acute hospital wards within an integrated healthcare system in England: a qualitative case study.
Frail older people experience frequent care transitions and an integrated healthcare system could reduce barriers to transitions between different settings. The study aimed to investigate care transitions of frail older people from acute hospital wards to community healthcare or community hospital wards, within a system that had vertically integrated acute hospital and community healthcare services. The research design was a multimethod, qualitative case study of one healthcare system in England; four acute hospital wards and two community hospital wards were studied in depth. The data were collected through: interviews with key staff (n = 17); focus groups (n = 9) with ward staff (n = 36); interviews with frail older people (n = 4). The data were analysed using the framework approach. THREE THEMES ARE PRESENTED: Care transitions within a vertically integrated healthcare system, Interprofessional communication and relationships; Patient and family involvement in care transitions. A vertically integrated healthcare system supported care transitions from acute hospital wards through removal of organisational boundaries. However, boundaries between staff in different settings remained a barrier to transitions, as did capacity issues in community healthcare and social care. Staff in acute and community settings need opportunities to gain better understanding of each other's roles and build relationships and trust.


Oscillatory IL-2 stimulus reveals pertinent signaling timescales of T cell responsiveness.
Cell response to extracellular ligand is affected not only by ligand availability, but also by pre-existing cell-to-cell variability that enables a range of responses within a cell population. We developed a computational model that incorporates cell heterogeneity in order to investigate Jurkat T cell response to time dependent extracellular IL-2 stimulation. Our model predicted preferred timing of IL-2 oscillatory input for maximizing downstream intracellular STAT5 nuclear translocation. The modeled cytokine exposure was replicated experimentally through the use of a microfluidic platform that enabled the parallelized capture of dynamic single cell response to precisely delivered pulses of IL-2 stimulus. The in vitro results demonstrate that single cell response profiles vary with pulsatile IL-2 input at pre-equilibrium levels. These observations confirmed our model predictions that Jurkat cells have a preferred range of extracellular IL-2 fluctuations, in which downstream response is rapidly initiated. Further investigation into this filtering behavior could increase our understanding of how pre-existing cellular states within immune cell populations enable a systems response within a preferred range of ligand fluctuations, and whether the observed cytokine range corresponds to in vivo conditions.


Aire-ing self antigen variability and tolerance.
Positional cloning of the underlying genes for the rare syndrome autoimmune polyendocrinopathy candidadiasis extrodermal dystrophy (APECED) opened a new venue of research on the role of central tolerance in autoimmunity. The associated autoimmune regulator gene (AIRE), was found to be expressed in medullary thymus epithelial cells (mTEC) in both man and mice, and to control promiscuous expression of sets of self antigens. The lack of AIRE in both mice and man led to the development of a quite specific, but also an inter-individual variable, set of autoimmune and infectious diseases. An article in this issue of the European Journal of Immunology demonstrates that several autoantigens controlled by AIRE are variably expressed in different human individuals. Most importantly it is shown that carriers of the type 1 diabetes (T1D) associated locus IDDM2 show lower expression of insulin in mTEC, as controlled by AIRE. The genetic variability of autoantigen expression in the thymus thus seems to determine the variable predisposition to autoimmunity.


Adherence to the Dutch Breast Cancer Guidelines for Surveillance in Breast Cancer Survivors: Real-World Data from a Pooled Multicenter Analysis.
Regular follow-up after treatment for breast cancer is crucial to detect potential recurrences and second contralateral breast cancer in an early stage. However, information about follow-up patterns in the Netherlands is scarce. Details concerning diagnostic procedures and policlinic visits in the first 5 years following a breast cancer diagnosis were gathered between 2009 and 2019 for 9916 patients from 4 large Dutch hospitals. This information was used to analyze the adherence of breast cancer surveillance to guidelines in the Netherlands. Multivariable logistic regression was used to relate the average number of a patient's imaging procedures to their demographics, tumor-treatment characteristics, and individual locoregional recurrence risk (LRR), estimated by a risk-prediction tool, called INFLUENCE. The average number of policlinic contacts per patient decreased from 4.4 in the first to 2.0 in the fifth follow-up year. In each of the 5 follow-up years, the share of patients without imaging procedures was relatively high, ranging between 31.4% and 33.6%. Observed guidelines deviations were highly significant (P < .001). A higher age, lower UICC stage, and having undergone radio- or chemotherapy were significantly associated with a higher chance of receiving an imaging procedure. The estimated average LRR-risk was 3.5% in patients without any follow-up imaging compared with 2.3% in patients with the recommended number of 5 imagings. Compared to guidelines, more policlinic visits were made, although at inadequate intervals, and fewer imaging procedures were performed. The frequency of imaging procedures did not correlate with the patients' individual risk profiles for LRR.


Identification of a genetic signature of activated signal transducer and activator of transcription 3 in human tumors.
Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that is activated in diverse human tumors and may play a direct role in malignant transformation. However, the full complement of target genes that STAT3 regulates to promote oncogenesis is not known. We created a system to express a constitutively active form of STAT3, STAT3-C, in mouse fibroblasts and used it to identify STAT3 targets. We showed that a subset of these targets, which include transcription factors regulating cell growth, survival, and differentiation, are coexpressed in a range of human tumors. Using immunohistochemical staining of tissue microarrays, we showed that these targets are enriched in breast and prostate tumors harboring activated STAT3. Finally, we showed that STAT3 is required for the expression of these genes in a breast cancer cell line. Taken together, these results identify a cohort of STAT3 targets that may mediate its role in oncogenesis.


Accurate mass screening and identification of emerging contaminants in environmental samples by liquid chromatography-hybrid linear ion trap Orbitrap mass spectrometry.
The European Reach legislation will possibly drive producers to develop newly designed chemicals that will be less persistent, bioaccumulative or toxic. If this innovation leads to an increased use of more hydrophilic chemicals it may result in higher mobilities of chemicals in the aqueous environment. As a result, the drinking water companies may face stronger demands on removal processes as the hydrophilic compounds inherently are more difficult to remove. Monitoring efforts will also experience a shift in focus to more water-soluble compounds. Screening source waters on the presence of (emerging) contaminants is an essential step in the control of the water cycle from source to tap water. In this article, some of our experiences are presented with the hybrid linear ion trap (LTQ) FT Orbitrap mass spectrometer, in the area of chemical water analysis. A two-pronged strategy in mass spectrometric research was employed: (i) exploring effluent, surface, ground- and drinking-water samples searching for accurate masses corresponding to target compounds (and their product ions) known from, e.g. priority lists or the scientific literature and (ii) full-scan screening of water samples in search of 'unknown' or unexpected masses, followed by MS(n) experiments to elucidate the structure of the unknowns. Applications of both approaches to emerging water contaminants are presented and discussed. Results are presented for target analysis search for pharmaceuticals, benzotriazoles, illicit drugs and for the identification of unknown compounds in a groundwater sample and in a polar extract of a landfill soil sample (a toxicity identification evaluation bioassay sample). The applications of accurate mass screening and identification described in this article demonstrate that the LC-LTQ FT Orbitrap MS is well equipped to meet the challenges posed by newly emerging polar contaminants.


[CT imaging features of pulmonary involvement in connective tissue disorders].
Connective tissue disorders correspond to a heterogeneous group of inflammatory diseases characterized by abnormal immune system activity leading to connective tissue alterations in multiple parts of the body. In adults, connective tissue disorders include rheumatoid arthritis, progressive systemic sclerosis, Sjögren syndrome, systemic lupus erythematosus, dermatomyositis and polymyositis, ankylosing spondylitis, and mixed connective tissue disease. Broncho-pulmonary involvement may be variable with involvement of all anatomical components of the lung. Involvement of other intrathoracic structures (pleura, respiratory muscles, heart, rib cage) is frequent. The most specific manifestations include interstitial lung diseases and pulmonary hypertension. During follow-up, progressive respiratory diseases may occur due to the treatment, infections, pulmonary embolism or neoplasms.


PI 3-kinase/Rac1 and ERK1/2 regulate FGF-2-mediated cell proliferation through phosphorylation of p27 at Ser10 by KIS and at Thr187 by Cdc25A/Cdk2.
To determine the mechanism of p27 phosphorylation through common and differential pathways triggered by FGF-2 in corneal endothelial cells (CECs). A GTP pull-down assay was performed to identify Rac1-GTP. Expression and activation of protein were analyzed by immunoblotting. Cell proliferation was measured by an MTT assay. Transfection of CECs with kinase-interacting stathmin (KIS) siRNA was performed. FGF-2 activated Rac1 through Akt, and Rac1 inhibitor greatly inhibited the FGF-2-stimulated cell proliferation. Rac1 inhibitor reduced p27 phosphorylation at both serine 10 (Ser10) and threonine 187 (Thr187). ERK1/2 was also involved in FGF-2-stimulated CEC proliferation and phosphorylation of p27 at Ser10 and Thr187 in parallel to phosphatidylinositol (PI) 3-kinase. In both PI 3-kinase/Rac1 and ERK1/2 pathways, Ser10 of p27 is phosphorylated by KIS, confirmed by siRNA to KIS, which subsequently hampered the FGF-2-stimulated cell proliferation, while Thr187 of p27 was phosphorylated through Cdk2 activated by Cdc25A. Cdc25A inhibitor blocked activation of Cdk2, phosphorylation of p27 at Thr187, and cell proliferation. FGF-2 induced both KIS and Cdc25A during the G1 phase; the maximum KIS expression was observed 4 hours after FGF-2 stimulation, while the maximum Cdc25A expression was observed at 12 hours. Blockade of ERK1/2 and Rac1 greatly reduced KIS and Cdc25A expression. Results suggest that FGF-2 uses both PI 3-kinase/Rac1 and ERK pathways for cell proliferation; two signals employ common pathways for phosphorylating p27 according to the sites (KIS for Ser10 and Cdc25A/Cdk2 for Thr187) with their characteristic kinetics (early G1 for Ser10 and late G1 for Thr187).


Monte Carlo studies on the interfacial properties and interfacial structures of ternary symmetric blends with gradient copolymers.
Using Monte Carlo simulation methods, the effects of the comonomer sequence distribution on the interfacial properties (including interfacial tension, interfacial thickness, saturated interfacial area per copolymer, and bending modulus) and interfacial structures (including chain conformations and comonomer distributions of the simulated copolymers at the interfaces) of a ternary symmetric blend containing two immiscible homopolymers and one gradient copolymer are investigated. We find that copolymers with a larger composition gradient width have a broader comonomer distribution along the interface normal, and hence more pronouncedly enlarge the interfacial thickness and reduce the interfacial tension. Furthermore, the counteraction effect, which arises from the tendency of heterogeneous segments in gradient copolymers to phase separate and enter their miscible phases to reduce the local enthalpy, decreases the stretching of copolymers along the interface normal direction. As a result, copolymers with a larger width of gradient composition can occupy a larger interfacial area and form softer monolayers at saturation and are more efficient in facilitating the formation of bicontinuous microemulsions. Additionally, chain length ratio, segregation strength, and interactions between homopolymers and copolymers can alter the interfacial character of gradient copolymers. There exists a strong coupling between the comonomer sequence distribution, chain conformation, and interfacial properties. Especially, bending modulus is mainly determined by the complicated interplay of interfacial copolymer density and interfacial chain conformation.


Research on the correlation of urine calcium integrin binding protein-1 and pro-BNP with ischemic heart failure.
To investigate the correlation between the levels of urine calcium integrin binding protein-1 (CIB1) and serum precursor N-terminal brain natriuretic peptide (pro-BNP) and ischemic heart failure. 30 patients diagnosed as acute ischemic heart failure for the first time in our hospital from January to August 2016 were continuously selected as the observation group 1, 30 patients with chronic stable ischemic heart failure as the observation group 2, and 30 healthy volunteers as the control group. Urine CIB1 level was detected via enzyme linked immunosorbent assay (ELISA) and serum pro-BNP level was detected via radioimmunoassay. The linear correlation between the CIB1 and pro-BNP levels in observation group 1 was observed, and the diagnostic value of CIB1 and pro-BNP levels for chronic stable ischemic heart failure were analyzed using the receiver operating characteristic (ROC) curve. CIB1 and pro-BNP levels in the observation group 1 were significantly higher than those in the observation group 2. These levels were significantly lower in the control group (p < 0.05). In the observation group 1, CIB1 and pro-BNP levels were positively correlated (p < 0.05). The diagnostic accuracy of CIB1 for chronic stable ischemic heart failure in the observation group 2 (area under the curve, AUC) was 0.854, the sensitivity was 86.6% and the specificity was 82.5%, respectively. The diagnostic accuracy of pro-BNP was 0.823, the sensitivity was 83.5% and the specificity was 85.9%, respectively. There is a significant correlation between the urine CIB1 and serum pro-BNP levels in patients with acute ischemic heart failure. In patients with chronic stable ischemic heart failure, the diagnostic value of urine CIB1 outperforms that of serum pro-BNP, which still needs further study.


Rh immunization in Manitoba: progress in prevention and management.
For two decades the perinatal mortality caused by erythroblastosis has been decreasing in Manitoba. The improved management of Rh-immunized pregnancies has lowered the death rate among affected infants from 10.8% to 3.4%, while the prevention of Rh immunization has reduced its incidence from 9.1 to 2.2 per 1000 total births. In its first 6 years and 8 months Manitoba's antenatal prophylaxis program, in which immunoglobulin is administered to Rh-negative women at 28 weeks' gestation, reduced the incidence of Rh immunization during pregnancy by 93%. In combination with post-abortion and postpartum prophylaxis the antenatal treatment has provided a protection rate of 98.6% among primigravidas at risk. Further improvements are expected.


Modeling the Concentration of Volatile and Semivolatile Contaminants in Direct Contact Membrane Distillation (DCMD) Product Water.
Direct contact membrane distillation (DCMD) is an emerging water treatment technology that has high salt rejection; however, its commercialization potential for applications such as seawater desalination or industrial wastewater reuse may be limited by low rejection of volatile and semivolatile contaminants. In this manuscript, a contaminant concentration (CC) model describing the transport of volatile and semivolatile contaminants for DCMD systems was developed and validated using data from the bench-scale DCMD treatment of synthetic wastewaters. The DCMD tests showed that the more volatile contaminants (methyl-tert-butyl ether, acetone, pentanone, butanol, and hexanol) accumulated in the permeate collection stream at greater concentrations than in the feed stream. The validated CC model (average normalized root mean squared error ≤11.3%) was then used to evaluate the product water quality from the large-scale DCMD treatment of oil and gas produced waters. The modeled product water contaminant concentrations exceeded the Environmental Protection Agency limits for discharging to publicly owned treatment works. This indicated that DCMD treatment of produced waters may require additional processing to meet discharge requirements.


Maternal sensitivity predicts language gain in preschool children who are deaf and hard of hearing.
The link between maternal sensitivity and child language gain was assessed in a prospective study of hearing mothers and their deaf and hard-of-hearing (D/HH) children. Maternal sensitivity in dyadic interaction was assessed when children were approximately 2 years old, and expressive language gain was assessed at 2 to 3 years using the Minnesota Child Development Inventory. Sensitivity made significant, positive, and unique predictions of expressive language gain when the effects of maternal education, degree of child hearing loss, dyadic mode of communication, and time between assessments were controlled. Findings indicate the value of affective measures of interaction in predicting language gain.


[A critical interpretation of aesthetical approach to nursing].
The purpose of the study was to interpretate Caper's view of the aesthetical approach to nursing, to discover problems of her arguments, and to ultimately expand the horizon of the aesthetical thinking of nursing. By means of the critical interpretation of Caper's paper, problems of her arguments were discovered. This then was suggested was the proper way of the aesthetical approach to nursing. Carper's arguments of aesthetics were seen to be confused, regarding the pattern of the nursing art and the relationship between aesthetical knowing and practical art, and to have no the nursing's perspective as moral art. The proper paradigm for the distinct thinking of the nursing aesthetics could be offered here through applying some aesthetical theories as follows; a mode of aesthetical knowing could be characterized as emphatical awareness in relationship between nurse and client, and a practical art of nursing understood as moral art in sense of the expression of the human dignity. This study suggested fundamental theme for the proper aesthetical approach to nursing in view of the aesthetical knowing and the practical art. The horizon of the aesthetical thinking in nursing can be expended through the inquiry into aesthetical theories which offer theoretical the base for nursing as an art.


Licochalcone D Induces ROS-Dependent Apoptosis in Gefitinib-Sensitive or Resistant Lung Cancer Cells by Targeting EGFR and MET.
Licochalcone D (LCD), a flavonoid isolated from a Chinese medicinal plant Glycyrrhizainflata, has a variety of pharmacological activities. However, the anti-cancer effects of LCD on non-small cell lung cancer (NSCLC) have not been investigated yet. The amplification of MET (hepatocyte growth factor receptor) compensates for the inhibition of epidermal growth factor receptor (EGFR) activity due to tyrosine kinase inhibitor (TKI), leading to TKI resistance. Therefore, EGFR and MET can be attractive targets for lung cancer. We investigated the anti-proliferative and apoptotic effects of LCD in lung cancer cells HCC827 (gefitinib-sensitive) and HCC827GR (gefitinib-resistant) through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, pull-down/kinase assay, cell cycle analysis, Annexin-V/7-ADD staining, reactive oxygen species (ROS) assay, mitochondrial membrane potential (MMP) assay, multi-caspase assay, and Western blot analysis. The results showed that LCD inhibited phosphorylation and the kinase activity of EGFR and MET. In addition, the predicted pose of LCD was competitively located at the ATP binding site. LCD suppressed lung cancer cells growth by blocking cell cycle progression at the G2/M transition and inducing apoptosis. LCD also induced caspases activation and poly (ADP-ribose) polymerase (PARP) cleavage, thus displaying features of apoptotic signals. These results provide evidence that LCD has anti-tumor effects by inhibiting EGFR and MET activities and inducing ROS-dependent apoptosis in NSCLC, suggesting that LCD has the potential to treat lung cancer.


Incarcerated foramen of Bochdalek hernia during pregnancy. A case report.
Symptomatic diaphragmatic hernia during pregnancy is a rare but potentially dangerous occurrence. A delay in diagnosis and treatment may be fatal to both the woman and the fetus. A case occurred of incarceration of the colon through a foramen of Bochdalek hernia; the diagnosis was made postpartum, with a successful maternal outcome. The failure of conservative measures to adequately diagnose and treat commonly voiced gastrointestinal complaints may lead to a delay in recognizing serious pathology.


Effects of repeated annual influenza vaccination on antibody responses against unchanged vaccine antigens in elderly frail institutionalized volunteers.
Concern about the possibility that annually repeated influenza immunizationmayinduce a lower antibody response than first vaccination. To ascertain the cumulative effects of yearly vaccination on serological response to unaltered vaccine antigens in the elderly. The haemagglutination-inhibiting (HI) antibody response was examined in 158 elderly institutionalized frail volunteers subdivided in 3 groups according to the sequential winters in which each subject received a trivalent inactivated influenza vaccine. The study, conducted over 5 consecutive winters (from 1998/99 to 2002/03), reports the antibody response only for sequential years (2 or 3) in which the vaccine strain examined was not altered. Significant increases in the values of HI antibody titres were observed after vaccination in each year examined against the different influenza vaccine strains used, except against B antigen in the second of the 3 winters studied (1999/00). The antibody responses found were not always adequate, i.e. at levels above the currently requested values for commercial vaccines (post-vaccination seroprotection rate >/=1:40, increases in geometric mean titres >/=2, positive responses >/=30% compared with pre-vaccination), probably because of old age (mean age >/=81 years) and the presence of underlying diseases in a high percentage of volunteers (>/=86%). The most frequent chronic diseases found werecardiovascular diseases (48%), endocrine disorders (19%), functional disability (10%) and pulmonary diseases (4%). The post-vaccination values observed in the sequential years were in general similar for A/H3N2 and A/H1N1 vaccine strains. A decrease, however, for some parameters at statistically significant levels, was observed against B antigen following repeated vaccine administrations. Our data seem to support the possibility of a slight impairment of HI antibody response against unaltered influenza vaccine antigens, especially for influenza strains that have circulated for prolonged periods of time. Indeed a tendency to a lower response was found only against B/Beijing antigen, introduced in the vaccine composition in the winter 1995/96, but not against the A/H3N2 and A/H1N1 vaccine strains, which weremore frequently changed.


COVID-19 PANDEMIC AND ITS POTENTIAL IMPACT ON SEXUAL AND REPRODUCTIVE HEALTH INDICATORS IN NIGERIA.
The impact of the novel corona virus disease (COVID-19) pandemic cuts across all sectors and has brought to the fore the true realities and status of health systems globally, revealing the gaps and cracks even in seemingly perfect health systems. The fragile and weak health system in the country is also riddled with a lot of sub-optimal health indicators including reproductive health. It is important to anticipate and look out for these effects in order to plan for and ensure early detection and necessary intervention to mitigate such. This paper discusses the potential effect of COVID-19 on reproductive health indicators in Nigeria. The reproductive health indices of a population have far and wide reaching impact on the health status of the population. However, reproductive health indicators are usually among the worst hit during health emergencies or disasters as seen in the Ebola pandemic in sub-Saharan Africa. Interventions must be put in place so that the pandemic does not set Nigeria back from the marginal gains made in reproductive health over the years.


Acute acalculous cholecystitis in a child with systemic lupus erythematosus.
A 10-year-old boy with systemic lupus erythematosus (SLE) developed abrupt right upper quadrant pain and vomiting during the course of his active disease. Antiphospholipid antibody was negative and the C3 level was low. Abdominal sonography showed cholecystitis with sludge balls in the gallbladder. He was treated by high-dose prednisolone with ceftriaxone and metronidazole IV for 3 days but due to poor response, cholecystectomy was performed and no stone was identified. Histopathologic examination showed vasculitis in the medium-sized arteries of the gallbladder wall. He was doing well at the 9-month follow-up after the operation. This report describes the first pediatric case of SLE with acalculous cholecystitis caused by vasculitis of the gallbladder.