Protective effect of tumor necrosis factor alpha antibody on experimental necrotizing enterocolitis in the rat.
Necrotizing enterocolitis (NEC) is a common and devastating disorder of premature infants. Elevated proinflammatory cytokines, especially tumor necrosis factor alpha (TNF-alpha), have been implicated in the pathogenesis of NEC. The aim of this study was to evaluate the effects of TNF-alpha on the inflammatory response in NEC by immunoneutralizing TNF-alpha with a selective antibody. Neonatal Sprague-Dawley rats were divided in 3 groups: group 1 (n = 20), a NEC-like enterocolitis was induced by formula feeding, asphyxia, and cold exposure; group 2 (n = 9), animals were treated like in group 1 and additionally received TNF-alpha antibody intraperitoneally; and group 3 (n = 17), animals were dam-fed (controls). Animals were killed in case of imminent death or after 96 hours. Specimens from small bowel were processed for blinded histologic (H&E) and immunhistologic (myeloperoxidase [MPO]) analysis. In group 1, animals developed severe NEC (mean NEC score, 3.28 +/- 0.32; mean MPO, 65.85 +/- 9.46). In group 2, animals developed mild NEC (mean NEC score, 1.72 +/- 0.41; mean MPO, 34.33 +/- 9.69; P < .05). In group 3, no NEC was induced (mean NEC score, 0.0 +/- 0; mean MPO, 6 +/- 1.32; P < .05). Tumor necrosis factor alpha antibody may have an attenuating effect on experimental NEC in rats.


Color-axis determination on the Farnsworth-Munsell 100-hue test.
Error scores on the Farnsworth-Munsell 100-hue test were partitioned into those representing red-green and those representing blue-yellow losses. Data from two groups of normal observers were used. One group showed results characteristic of published norms; one group showed superior performance. Both observers showed a correlation between red-green and blue-yellow scores indicative of a strong performance factor in this test. The difference between blue-yellow and red-green scores eliminates their correlated variance and allows evaluation of the axis. Both groups showed an increase in difference scores, with age indicating development of a blue-yellow axis. This increase was significant for the observers characteristic of the norms. We suggest cutoff scores to allow a decision as to whether a given patient shows a blue-yellow or red-green axis.


An unusual location of an esteochondroma.
An unusual hip tumor was seen in a 13-year-old youth following a brief history of discomfort. The osteochondroma was differentiated from dysplasia epiphysealis hemimelica by its location.


Cerebrospinal fluid shunts in pregnancy. Report of two cases and review of the literature.
With the introduction of silicone indwelling cerebrospinal fluid (CSF) shunts in the 1960s, the prognosis for children with hydrocephalus changed dramatically. These individuals are leading normal and productive lives today. Many women with CSF shunts are not entering the childbearing years. Previously, only 13 cases of pregnancy occurring in patients with CSF shunts have been reported. We present two cases here and review the complications and outcome of the other reported cases. Shunt malfunction appears to be common in pregnancy due to increased intraperitoneal pressure and the enlarging uterus. Rarely is surgical correction or premature delivery necessary. A successful pregnancy ending in the vaginal delivery of a term infant can be expected in the majority of these patients.


A Porous Nanostructured ZnO Layer for Ultraviolet Sensing with Quartz Crystal Microbalance Technique.
Porous films of metals and metal oxides have gained growing attention as potential materials for use in applications that require large, specific surface areas, such as sensors, supercapacitors, and batteries. In this study, a "black-metal"-like porous Zn-ZnO composite layer was grown by room temperature co-sputtering of Zn metal and ZnO:Ga (3 at/%) ceramic targets. Following deposition, a porous ZnO layer was obtained by a subsequent thermal annealing process at 400 °C in air. The morphology and structural properties of the obtained porous layered objects were analyzed. The porosity and chemical characteristics of the nanostructured ZnO layer obtained with the method herein described make it suitable to be used as a sensitivity-enhancing active layered element in quartz crystal microbalance (QCM)-based ultraviolet (UV) sensors. The prepared resonant ZnO/QCM sensors under UV radiation exhibited maximum shift up to 35 Hz for several "on-off" UV cycles, excellent response, and recovery times of 11 and 12 s, respectively.


Use of Monoclonal Antibodies in Pregnant Women Infected by COVID-19: A Case Series.
Monoclonal antibodies are designed to target specific proteins of COVID-19 and can be used as a treatment for people with mild to moderate infection and at a high risk of severe disease. Casirivimab/imdevimab, sotrovimab, and Bamlanivimab/etesevimab have been authorized for emergency use in the treatment of COVID-19. However, during pregnancy, these drugs have not been extensively studied. A total of 22 pregnant women with mild to moderate infection were treated with three different monoclonal antibodies, and efficacy and safety were evaluated in the first period and until six months of follow-up. No infusion/allergic reactions occurred. No fatal or adverse events were observed in the pregnant women or fetus. The time of negativization with sotrovimab was shorter in comparison to Imdevimav/casirivimab (p = 0.0187) and Bamlanivimab/etesevimab (p < 0.00001). The time of negativization with sotrovimab was earlier in comparison to Imdevimav/casirivimab (t-value: 2.92; p = 0.0052) in vaccinated patients and similar in comparison to Imdevimav/casirivimab (t-value: 1.48; p = 0.08). In unvaccinated patients, sotrovimab was faster to achieve negativization in comparison to Bamlanivimab/etesevimab (t-value: 10.75; p < 0.0005). Pregnant COVID-19 patients receiving sotrovimab obtained better clinical outcomes. Pregnancy or neonatal complications were not observed after monoclonal treatment, confirming the safety and tolerability of these drugs in pregnant women.


Electrophysiological and electron microscopic analysis of the vagus nerve of the pigeon, with particular reference to the cardiac innervation.
The compound action potential components and their associated fiber contingents were investigated in the pigeon vagus nerve with a view toward identifying the vagal cardioinhibitory fibers. In the cervical vagus, the compound action potential evoked by electrical stimulation included four major components that conducted at 17.0-30.0 (A-wave), 8.0-14.5 (B2-wave) and 0.8-2.0 (C-wave) m/sec. Cardiac slowing was not elicited until activation of the Bl-wave, and the bradycardic response was maximal when this component was maximized. Electron microscopic analysis of the cervical vagus revealed myelinated fibers 1.1-6.8 micron in diameter and unmyelinated fibers 0.3-1.4 micron in diameter. A contingent of myelinated fibers approximately 2-4 micron in diameter apparently generated the Bl-wave, while the prominent unmyelinated fiber contingent (37%) accounted for the C-wave. Analysis of various vagal branches indicated that approximatley 20% of the cervical vagal fibers exit the main trunk between cervical and mid-thoracic levels, but few of these are the larger myelinated fibers greater than 2 micron in diameter. The upper abdominal vagus consists largely of unmyelinated and small myelinated fibers, and consequently the vast majority of larger myelinated fibers found in the cervical vagus exit between mid-thoracic and upper abdominal levels, presumably in the cardiac branches. Direct examination of the cardiac branches confirmed this. Thus, it is concluded that the Bl-wave of the compound action potential is uniquely associated with cardiac slowing, that this component is generated by myelinated fibers ranging from 2 to 4 micron in diameter, and that almost all such fibers are destined for the cardiac branches of the vagus.


Central serotonin transporter availability measured with [123I]beta-CIT SPECT in relation to serotonin transporter genotype.
A functional polymorphism has been described in the promoter region of the gene (SLC6A4) coding for the serotonin transporter protein (SERT). This polymorphism has two common alleles, designated as long and short. Each allele has been linked with a number of human clinical phenotypes, including neuropsychiatric diseases associated with dysregulation of serotonin transmission. In vitro studies of nonneural cells have suggested that the long allele may have higher transcriptional activity than the short allele. However, the relevance of these findings for SERT levels in the brain remains unclear. The authors assessed genotypes at the SLC6A4 promoter polymorphism in 96 healthy European American subjects who underwent single photon emission computed tomography scanning with [123I]2beta-carbomethoxy-3beta-(4-iodophenyl) tropane ([123I]beta-CIT) for measurement of central SERT availability. A ratio of specific to nondisplaceable brain uptake (i.e., V3"=[brainstem-diencephalon-occipital]/occipital), a measure proportional to the binding potential (Bmax/KD), was derived. The results showed that the main effect of genotype was significant. Post hoc Tukey pairwise comparisons revealed that the short-short homozygotes had significantly greater SERT availability than the long-short heterozygotes. There was a nonsignificant tendency for the long-long homozygotes to have greater SERT availability than the heterozygotes, but no difference was observed between the long-long homozygotes and the short-short homozygotes. The effect of age was significant in the analysis of covariance model. These results do not suggest higher central SERT levels in association with the long allele in European American subjects but point to a more complex relationship between SLC6A4 genotype and protein availability.


Pleasure or pain? A profile of smokers in Northern England.
To construct a profile of smokers using multiple indices of physical, mental and social health. Cross-sectional study. The setting was Wigan and Bolton Health Authority, an urban district in the North West of England. A random sample of over 15000 adults from the Health Authority adult population completed a written questionnaire. Prevalence ratios were calculated for physical, mental and social health indicators for smokers compared with non-smokers, adjusted for borough, age and deprivation score of place of residence. Smokers were less likely to report their current health as good, and reported a significantly higher prevalence of arthritis, bronchitis, backache and respiratory symptoms. Smokers had more mobility problems and recent severe pain. Smokers had less healthy lifestyles across many behaviours (e.g. poorer diet, taking less regular exercise and more problem drinking). Depression and the proportion of people with a high psychiatric morbidity score were increased. More women smokers reported a lack of social support, and smokers more often reported financial difficulties. Differences were exaggerated by comparing heavy smokers with non-smokers. Independent of the level of deprivation of their area of residence, smokers have poorer physical, social and mental health, with a dose-response effect. Smoking creates considerable pain, but little evidence of pleasure.


Comprehending the allergen repertoire of shrimp for precision molecular diagnosis of shrimp allergy.
Clinical management of shrimp allergy is hampered by the lack of accurate tests. Molecular diagnosis has been shown to more accurately reflect the clinical reactivity but the full spectrum of shrimp allergens and their clinical relevance are yet to be established. We therefore sought to comprehend the allergen repertoire of shrimp, investigate and compare the sensitization pattern and diagnostic value of the allergens in allergic subjects of two distinct populations. Sera were collected from 85 subjects with challenge-proven or doctor-diagnosed shrimp allergy in Hong Kong and Thailand. The IgE-binding proteins of Penaeus monodon were probed by Western blotting and identified by mass spectrometry. Recombinant shrimp allergens were synthesized and analyzed for IgE sensitization by ELISA. Ten IgE-binding proteins were identified, and a comprehensive panel of 11 recombinant shrimp allergens was generated. The major shrimp allergens among Hong Kong subjects were troponin C (Pen m 6) and glycogen phosphorylase (Pen m 14, 47.1%), tropomyosin (Pen m 1, 41.2%) and sarcoplasmic-calcium binding protein (Pen m 4, 35.3%), while those among Thai subjects were Pen m 1 (68.8%), Pen m 6 (50.0%) and fatty acid-binding protein (Pen m 13, 37.5%). Component-based tests yielded significantly higher area under curve values (0.77-0.96) than shrimp extract-IgE test (0.70-0.75). Yet the best component test differed between populations; Pen m 1-IgE test added diagnostic value only in the Thai cohort, whereas sensitizations to other components were better predictors of shrimp allergy in Hong Kong patients. Pen m 14 was identified as a novel shrimp allergen predictive of challenge outcome. Molecular diagnosis better predicts shrimp allergy than conventional tests, but the relevant component is population dependent.


The prevalence and prognostic significance of right ventricular systolic dysfunction in nonischemic dilated cardiomyopathy.
Cardiovascular magnetic resonance is the gold-standard technique for the assessment of ventricular function. Although left ventricular volumes and ejection fraction are strong predictors of outcome in dilated cardiomyopathy (DCM), there are limited data regarding the prognostic significance of right ventricular (RV) systolic dysfunction (RVSD). We investigated whether cardiovascular magnetic resonance assessment of RV function has prognostic value in DCM. We prospectively studied 250 consecutive DCM patients with the use of cardiovascular magnetic resonance. RVSD, defined by RV ejection fraction≤45%, was present in 86 (34%) patients. During a median follow-up period of 6.8 years, there were 52 deaths, and 7 patients underwent cardiac transplantation. The primary end point of all-cause mortality or cardiac transplantation was reached by 42 of 86 patients with RVSD and 17 of 164 patients without RVSD (49% versus 10%; hazard ratio, 5.90; 95% confidence interval [CI], 3.35-10.37; P<0.001). On multivariable analysis, RVSD remained a significant independent predictor of the primary end point (hazard ratio, 3.90; 95% CI, 2.16-7.04; P<0.001), as well as secondary outcomes of cardiovascular mortality or cardiac transplantation (hazard ratio, 3.35; 95% CI, 1.76-6.39; P<0.001), and heart failure death, heart failure hospitalization, or cardiac transplantation (hazard ratio, 2.70; 95% CI, 1.32-5.51; P=0.006). Assessment of RVSD improved risk stratification for all-cause mortality or cardiac transplantation (net reclassification improvement, 0.31; 95% CI 0.10-0.53; P=0.001). RVSD is a powerful, independent predictor of transplant-free survival and adverse heart failure outcomes in DCM. Cardiovascular magnetic resonance assessment of RV function is important in the evaluation and risk stratification of DCM patients.


Intraoperative awake language mapping correlates to preoperative connectomics imaging: An instructive case.
Connectomics enables the study of structural-functional relationships in the brain, and machine learning technologies have enabled connectome maps to be developed for individual brain tumor patients. We report our experience using connectomics to plan and guide an awake craniotomy for a tumor impinging on the language area. Preoperative connectomics imaging demonstrated proximity of the tumor to parcellations of the language area. Intraoperative awake language mapping was performed, revealing speech arrest and paraphasic errors at areas of the tumor boundary correlating to functional regions that explained these findings. This instructive case highlights the potential benefits of implementing connectomics into neurosurgical planning.


Life history patterns of a livebearing fish in contrasting environments.
The population dynamics and energy allocations of the Gila topminnow, a small livebearing fish, were studied in two contrasting environments, a spring run of constant characteristics and a fluctuating desert wash. Topminnows grew and matured in two basic patterns. First, many fish in both areas matured the year after their birth. Second, spring fish born early in the breeding season grew rapidly, bred within five months, and died by eight months of age. Although spring fish assimilated more energy, wash fish actually expended more calories for growth and reproduction, partly because of lower maintenance costs. Reproductive effort of long-lived spring fish varied with age between 3.1 and 6.5%; whereas efforts of short-lived spring and wash fish increased steadily with age to 5.2 and 9.8%, respectively. Although spring fish produced eggs of higher energy content, females in both areas varied their investment per offspring, apparently tracking seasonal changes in the availability of food for fry. When long-lived spring fish experienced food shortage, they allocated less energy to both growth and reproduction; in contrast, wash and short-lived spring fish under similar conditions reduced only their growth allocation. The reproductive mass in spring fish appeared to be limited by food availability, incompletely filled the abdominal space, and reflected no tradeoff between fecundity and investment per offspring. Reproduction by wash fish appeared to be limited by body space and was characterized by a tradeoff between fecundity and egg size.


Intragenomic diversity of the V9 hypervariable domain in eukaryotes has little effect on metabarcoding.
Metabarcoding revolutionized our understanding of diversity and ecology of microorganisms in different habitats. However, it is also associated with several inherent biases, one of which is associated with intragenomic diversity of a molecular barcode. Here, we compare intragenomic variability of the V9 region of the 18S rRNA gene in 19 eukaryotic phyla abundant in marine plankton. The level of intragenomic variability is comparable across all the phyla, and in most genomes and transcriptomes one V9 sequence and one OTU is predominant. However, most of the variability observed at the barcode level is probably caused by sequencing errors and is mitigated by using a denoising tool, DADA2. The SWARM algorithm commonly used in metabarcoding studies is not optimal for collapsing genuine and erroneous sequences into a single OTU, leading to an overestimation of diversity in metabarcoding data. For an unknown reason, SWARM inflates diversity of eupelagonemids more than that of other eukaryotes.


Molecular compasses and gyroscopes. II. Synthesis and characterization of molecular rotors with axially substituted bis[2-(9-triptycyl)ethynyl]arenes.
We have developed a simple convergent procedure for the synthesis of molecular rotors consisting of a central aromatic group coupled with two axially positioned ethynyltriptycenes. Molecular rotors with 1,4-phenylene (1), 1,4'-1,1'-biphenylene (2), 9,10-anthracenylene (3), and 2,7-pyrenylene (4) groups were prepared by Pd(0)-catalyzed coupling of ethynyl triptycenes with the corresponding dibromoarenes. Although compounds 1-4 were not expected to have free rotation in the solid state, the rotational potentials of 1 and 3 were analyzed by semiempirical methods and the crystal packing of 1 was analyzed to design the structures most likely to yield a functional rotor in the solid state. Semiempirical PM3 calculations predict compounds 1, 2, and 4 to have frictionless internal rotation even at temperatures as low as 25 K, while compound 3 is expected to have a barrier of ca. 4 kcal/mol.


Hand hygiene compliance in transplant and other special patient groups: an observational study.
This study evaluates hand hygiene behavior of health care workers in a German university hospital stratified for treatment of special patient groups (eg, transplant patients). From 2008 to 2010, comprehensive education and training of all health care workers was implemented to improve hand hygiene compliance. Consumption rates of alcohol-based hand rub and gloves were collected and evaluated. Of the 5,647 opportunities of hand disinfection evaluated, 1,607 occurred during care for transplant patients. To our knowledge, this is the largest survey of hand hygiene compliance in special patient groups on intensive care units in a university hospital in Germany. Health care workers on surgical intensive care units showed lower hand hygiene compliance compared with health care workers on other types of intensive care units. Compliance toward hand hygiene was significantly higher on hemato-oncologic and pediatric wards. In general, hand disinfection was performed significantly more frequently after an intervention than before (P < .05, 95% confidence interval: 1.24-1.84). Overall, there was no significant difference in hand hygiene compliance when caring for transplant patients or other patients (odds ratio, 1.16; 95% confidence interval: 0.95-1.42). Nurse's and physician's hand hygiene compliance improved because of education. Hand hygiene compliance is not increased in the care for transplant patients (despite their predisposition for nosocomial infections) compared with other patients. Additional studies will be necessary to further investigate these findings.


Purification and immobilization of the soluble and insoluble portions of recombinant lipase by gram-positive enhancer matrix (GEM) particles.
Lipases are important enzyme for industries. In this work, the recombinant lipase with an AcmA tag working as purification and immobilization tag was expressed in Escherichia coli. Gram-positive enhancer matrix (GEM) particles work to purify and immobilize the recombinant lipase. GEM particles are produced by boiling the cells of Lactococcus lactis NZ9000 to remove the DNA and most proteins. GEM particles specifically bind protein with the AcmA tag in the C-terminal. The recombinant lipase was in two forms, the soluble part and the inclusion body. GEM particles could purify and immobilize the lipase from the soluble part in one step. After the inclusion body being dissolved by 8 M urea, the enzyme activity was recycled by the GEM particles. The GEM particles could immobilize over 75% of the enzyme activity. The lipase immobilized was a basophilla enzyme with the optimal temperature was 30 °C. The activity of the lipase immobilized was 47.1U/OD600 GEM particles at optimal conditions. The enzyme catalysis did not need the ions added to improve the activity. The GEM particles had excellent enzyme activity reusability.


Hydroxyamino acid specificity of smooth muscle myosin light chain kinase.
Synthetic peptides corresponding to the phosphorylation site in the myosin regulatory light chain from smooth muscle, Lys-Lys-Arg-Ala-Arg-Ala-Thr-Ser-Asn-Val-Phe-Ala ([Ala14,15]MLC(11-23] and containing a variety of hydroxyamino acid analogs at position 19, were tested as substrates for the smooth muscle myosin light chain kinase. Peptide analogs containing either D-serine or cis-hydroxyproline were not phosphorylated. The corresponding trans-hydroxyproline containing peptide was poorly phosphorylated with a Km of 2.3 microM and a Vmax of 3 X 10(-3) mumol.min-1.mg-1 compared to a Km of 12.5 microM and a Vmax of 1.43 mumol.min-1.mg-1 for the parent peptide. All three hydroxyamino acid analog peptides acted as relatively potent inhibitors of myosin light chain phosphorylation with Ki values in the range 7.5-10 microM, comparable to 7 microM for the parent peptide. Thus the failure of the hydroxyamino acid analog peptides to act as effective substrates was not the result of poor binding to the enzyme. In contrast, the same substitutions made in the peptide substrate for the cAMP-dependent protein kinase resulted in poor inhibitors. It is likely that the hydroxyl group of the substituting amino acids in the myosin light chain peptide analogs is not presented in the correct orientation in the active site for transfer of the phosphate group.


Use of elderly tumor-free subjects as a "supercontrol" for cancer epidemiological studies: pros and cons.
Search for cancer-predisposing single-nucleotide gene polymorphisms is complicated due to weakness of expected associations. We introduced a novel design for molecular epidemiological study, which relies on selection of highly demonstrative cases and controls. It is assumed that patients with clinical features of hereditary predisposition (e.g., cancer bilaterality, or young onset, or presence of family history, etc.) are more likely to accumulate at-risk alleles than randomly recruited cases. Furthermore, subjects with characteristics of cancer tolerance, e.g., elderly tumor-free smokers, may serve as a "supercontrol" for the rapid assessment of polymorphic candidates. The utility of the "comparison of extremes" design has already been exemplified in a series of reports. However, the use of elderly subjects for cancer case-control studies may possess a bias; for example, factors contributing to cancer predisposition may nevertheless be advantageous for the overall longevity, as they could compensate age-related decline of tissue maintenance and renewal. For example, there is some evidence for a dual role of the apoptosis-deficient Pro/Pro genotype of p53 gene, which may simultaneously increase both cancer risk and survival. Comprehensive studies on distribution of cancer-related gene polymorphisms in elderly population remain to be done.


Visual exposure using single-handed magnet-driven intra-abdominal wireless camera in minimal access surgery: is better than 30 degrees endoscope.
The operative field of view in minimal access surgery is constrained by the location of the optical port, the direction of view of the endoscope, and the limited degrees of freedom of movement of rigid endoscopes through the access port. The aim of this study was to examine the feasibility of employing a special magnetic setup with a single external handle to fixate, drive, and orientate intra-abdominal wireless camera, and compare its visual exposure with that of a 30 degrees endoscope. A wireless magnet-driven camera setup was developed comprising a mini wireless camera with integrated white light-emitting diodes, a specially constructed base unit for orientation control and smooth sliding motion, and an external magnetic handle to fixate and drive the camera from the outer surface of the abdominal wall. In a laboratory-based experiment, ten subjects with no laparoscopic surgical experience were asked to identify 160 randomly distributed labels in a trainer box using both a 30 degrees endoscope and the wireless camera magnetic setup in a random order. Data were analyzed using Student's t-test. The mean (standard deviation) of the number of identified labels was higher using the wireless camera magnetic setup 74.8 (16.96) compared with 30 degrees endoscope 54.7 (12.18); p \ 0.001. However, the mean execution time was longer with the camera magnetic system 34.9 (4.4) min compared with the 30 degrees endoscope 24.1 (2.8) min; p \ 0.001. The use of the magnetic wireless camera setup with a single external handle is feasible and has demonstrated a wider visual exposure than the 30 degrees endoscope.


The Influence of Prenatal Fumonisin Exposure on Bone Properties, as well as OPG and RANKL Expression and Immunolocalization, in Newborn Offspring Is Sex and Dose Dependent.
The current study examined the effects of exposure of pregnant dams to fumonisins (FBs; FB1 and FB2), from the seventh day of pregnancy to parturition, on offspring bone metabolism and properties. The rats were randomly divided into three groups intoxicated with FBs at either 0, 60, or 90 mg/kg b.w. Body weight and bone length were affected by fumonisin exposure, irrespective of sex or dose, while the negative and harmful effects of maternal FBs' exposure on bone mechanical resistance were sex and dose dependent. The immunolocalization of osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-Β ligand (RANKL), in bone and articular cartilage, indicated that the observed bone effects resulted from the FB-induced alterations in bone metabolism, which were confirmed by the changes observed in the Western blot expression of OPG and RANKL. It was concluded that the negative effects of prenatal FB exposure on the general growth and morphometry of the offspring bones, as a result of the altered expression of proteins responsible for bone metabolism, were dose and sex dependent.


Relationship between aeroallergen sensitization pattern and clinical features in adult asthmatics.
Asthma can be classified into atopic and non-atopic phenotypes. However, limited data are available on the clinical implications of these two phenotypes in real life. This study aimed to examine the clinical features as well as control level and disease severity of asthmatic patients with their aeroallergen sensitivity profiles. Between 2013 and 2020, adult asthmatic patients who had been followed up regularly at our tertiary healthcare institution for at least one year were included in the study. We collected data retrospectively using manually filled patient files. The mean age of 382 asthmatic patients was 46.6 ± 30.0; 77.5% were women and 75.6% had at least one aeroallergen sensitivity. Polysensitized asthmatics had better asthma symptom control and milder asthma severity than monosensitized asthmatics. Asthma symptom control status was well controlled in 67.5% of the patients, and according to asthma severity, 51.3% of the patients were classified as having moderate asthma. There was a negative relation between age (OR:0.95, CI:0.92-0.98) and atopy presence. The presence of atopy was higher in moderate asthmatics than in mild asthmatics (OR:2.02, CI:1.01-4.09). Finally, there was a positive relationship between the percent predicted forced expiratory volume in first second (FEV1%) (OR:1.02, CI:1.009-1.048) and the presence of atopy. The presence of rhinitis (OR:0.44, CI:0.22-0.88) and per 1 unit increase of Tiffeneau index (FEV1/forced vital capacity) (OR:0.94, CI:0.90-0.99) had a negative association, whereas number of medication use for asthma symptoms (OR:1.68, CI:1.18-2.39) and presence of cardiovasculary disease (OR:2.64, CI:1.19-5.84) had a positive association with not well-controlled asthma symptom level. Aeroallergen sensitivity was associated with asthma severity. However, this was not the case with asthma control levels in this adult asthma cohort. Among the atopic asthmatics polysensitized asthmatics had better asthma symptom control level and milder asthma severity level.


Temperature-induced water stress in high-latitude forests in response to natural and anthropogenic warming.
The Arctic is particularly sensitive to climate change, but the independent effects of increasing atmospheric CO2 concentration (pCO2 ) and temperature on high-latitude forests are poorly understood. Here, we present a new, annually resolved record of stable carbon isotope (δ(13) C) data determined from Larix cajanderi tree cores collected from far northeastern Siberia in order to investigate the physiological response of these trees to regional warming. The tree-ring record, which extends from 1912 through 1961 (50 years), targets early twentieth-century warming (ETCW), a natural warming event in the 1920s to 1940s that was limited to Northern hemisphere high latitudes. Our data show that net carbon isotope fractionation (Δ(13) C), decreased by 1.7‰ across the ETCW, which is consistent with increased water stress in response to climate warming and dryer soils. To investigate whether this signal is present across the northern boreal forest, we compiled published carbon isotope data from 14 high-latitude sites within Europe, Asia, and North America. The resulting dataset covered the entire twentieth century and spanned both natural ETCW and anthropogenic Late Twentieth-Century Warming (~0.7 °C per decade). After correcting for a ~1‰ increase in Δ(13) C in response to twentieth century pCO2 rise, a significant negative relationship (r = -0.53, P < 0.0001) between the average, annual Δ(13) C values and regional annual temperature anomalies is observed, suggesting a strong control of temperature on the Δ(13) C value of trees growing at high latitudes. We calculate a 17% increase in intrinsic water-use efficiency within these forests across the twentieth century, of which approximately half is attributed to a decrease in stomatal conductance in order to conserve water in response to drying conditions, with the other half being attributed to increasing pCO2 . We conclude that annual tree-ring records from northern high-latitude forests record the effects of climate warming and pCO2 rise across the twentieth century.


Cell clones and segmentation in leech development.
Cell lineage tracer dyes rhodamine-D-peptide and fluorescein-D-peptide were used to study the development of segmentation in embryos of the leech Helobdella triserialis. The earliest overt manifestation of segmentation is in the mesodermal cell layer of the germinal bands, where a repeating pattern of nearly isomorphic mesoblast clusters is seen at an early stage of development. With joint use of both lineage tracers, it is shown that each mesoblast cluster is a clone derived from a single primary mesoblast, as well as being the precursor to an adult mesodermal hemisegment. Not all of the primary mesoblasts give rise to hemisegments, however. Cell clones derived from the first primary mesoblasts produced contribute to the nonmetameric prostomial region, whereas the last primary mesoblasts produced appear to be supernumerary.


Heroin-related deaths in New South Wales, Australia, 1992-1996.
The coronial files of all heroin-related fatalities that occurred in New South Wales (NSW) over the period 1992-1996 were inspected. There were 953 heroin-related fatalities in NSW over the study period. There was a substantial, statistically significant increase in heroin-related fatalities over the study period, from 152 deaths in 1992 to 226 during 1996. The mean age of cases was 31.0 years, 85% were male, and 85% were classified as dependent on heroin at the time of death. There was a significant increase in the age of cases over the study period and the proportion of cases that were employed. Fatalities predominantly occurred in home settings (61%). No intervention occurred in 79% of cases. Fifty deaths (5%) occurred in the month following release from prison, 16 of which occurred the first 24 hours after release. Morphine concentrations rose from 0.24 mg/l in 1992 to 0.38 mg/l in 1996. Seventy six percent of cases involved heroin in combination with other drugs: alcohol (46%), benzodiazepines (27%), antidepressants (7%) and cocaine (7%). In only 24% of cases was morphine the sole drug detected. Males were significantly more likely to have alcohol detected at autopsy (49 vs. 24%), while females were more likely to have benzodiazepines detected (41 vs. 17%). The median blood morphine concentration among cases in which alcohol was detected was significantly lower than other cases (0.27 vs. 0.39 mg/l). It is concluded that heroin-related deaths continued to rise throughout the study period, and that deaths were predominantly among older, untreated males. Despite the rise in blood morphine concentrations, polydrug use remained the predominant toxicological pattern.


Fructans Exacerbate Symptoms in a Subset of Children With Irritable Bowel Syndrome.
Dietary fructans exacerbate symptoms in some, but not all, adults with irritable bowel syndrome (IBS). We sought to determine whether fructans worsen symptoms in children with IBS and whether clinical and psychosocial factors, and/or gas production, can identify those who are fructan sensitive. We performed a double-blind placebo-controlled (maltodextrin) cross-over trial of 23 children with IBS, based on pediatric Rome III criteria, from September 2014 through December 2016. At baseline, participants completed 1-week pain and stool diaries and a 3-day food record and psychosocial factors (depression, anxiety, and somatization) were measured. Subjects were randomly assigned to groups that were provided meals for 72 hours containing either fructans or maltodextrin (0.5 g/kg; maximum, 19 g). Following a washout period of 10 days or more, the subjects received the meal they were not given during the first study period (crossed over). Gastrointestinal symptoms and breath hydrogen and methane production were captured during each meal period. Fructan sensitivity was defined as an increase of 30% or more in abdominal pain frequency following fructan ingestion. Subjects had more mean episodes of abdominal pain/day during the fructan-containing diet (3.4 ± 2.6) vs the maltodextrin-containing diet (2.4 ± 1.7) (P < .01), along with more severe bloating (P < .05) and flatulence (P = .01). Hydrogen (but not methane) production was greater while subjects were on the fructan-containing diet (617 ± 305 ppm∗h) than the maltodextrin-containing diet (136 ± 78 ppm*h) (P < .001). Eighteen subjects (78.2%) had more frequent abdominal pain while on the fructan-containing diet and 12 (52.2%) qualified as fructan sensitive. We found no difference between fructan-sensitive and fructan-insensitive subjects in baseline abdominal pain or bowel movement characteristics, dietary intake, psychosocial parameters, IBS subtype, or gas production. In a randomized controlled trial of children with IBS, we found fructans to exacerbate several symptoms. However, fructan sensitivity cannot be identified based on baseline gastrointestinal symptoms, dietary intake, psychosocial factors, or gas production. Clinicaltrials.gov no: NCT02842281.


Hydrodynamics of micropipette aspiration.
The dynamics of human neutrophils during micropipette aspiration are frequently analyzed by approximating these cells as simple slippery droplets of viscous fluid. Here, we present computations that reveal the detailed predictions of the simplest and most idealized case of such a scheme; namely, the case where the fluid of the droplet is homogeneous and Newtonian, and the surface tension of the droplet is constant. We have investigated the behavior of this model as a function of surface tension, droplet radius, viscosity, aspiration pressure, and pipette radius. In addition, we have tabulated a dimensionless factor, M, which can be utilized to calculate the apparent viscosity of the slippery droplet. Computations were carried out using a low Reynolds number hydrodynamics transport code based on the finite-element method. Although idealized and simplistic, we find that the slippery droplet model predicts many observed features of neutrophil aspiration. However, there are certain features that are not observed in neutrophils. In particular, the model predicts dilation of the membrane past the point of being continuous, as well as a reentrant jet at high aspiration pressures.


SAGIT®: clinician-reported outcome instrument for managing acromegaly in clinical practice--development and results from a pilot study.
The SAGIT instrument is a comprehensive clinician-reported outcome instrument assessing key features of acromegaly: signs and symptoms, associated comorbidities; growth hormone levels; insulin-like growth factor-1 levels; and tumor profile. The SAGIT instrument has been designed to assist endocrinologists managing acromegaly in practice. Here, we report on pre-testing (to assess ease of understanding and acceptability) and a pilot study (to assess relevance, ease of use, and utility in real-life conditions) (NCT02231593). For pre-testing, 11 endocrinologists completed the SAGIT instrument using patient medical records and were also interviewed. They subsequently completed a PRAgmatic Content and face validity Test (PRAC-Test(©)) to report their experiences using SAGIT, and feedback was used to revise the instrument. In the pilot study, nine endocrinologists completed the SAGIT instrument in real-time with patients belonging to three different categories (stable/controlled, active/uncontrolled acromegaly, treatment-naïve), while four completed the instrument based on medical-record review. All participants then completed the PRAC-Test(©) and their feedback was used to update the instrument. The SAGIT instrument was well accepted by endocrinologists, with most indicating that it was concise, practical, easy to understand, useful for assessing treatment response, and valuable as a component of the patient's medical record. The pilot study confirmed the instrument's acceptability, utility, and ease of use, and indicated its potential for distinguishing acromegaly clinical stages. The SAGIT instrument is promising as a tool for use by endocrinologists in everyday practice to assess the status and evolution of disease in patients with acromegaly and to guide treatment decision-making.


The importance of clinical suspicion in the diagnosis of a successfully managed case with De Bakey Type 1 acute aortic dissection: A case report.
Type 1 aortic dissection is a catastrophic clinical entity originating from the ascending aorta. Clinical suspicion in patients with epigastric pain, chest pain and gastrointestinal symptoms might be life saving. Aortic dissection and acute mesenteric ischemia might be confusing in diagnosis of patients with epigastric pain, chest pain, gastrointestinal symptoms and high white blood cell count and D-dimer. In this case report of a patient who was admitted to the emergency room with a presentation resembling acute mesenteric ischemia, this diagnosis was excluded within the first 24 hours as a result of clinical suspicion. In this case report, the successful management in diagnosis and treatment of a 30-year-old male patient with type 1 aortic dissection is discussed in light of the literature.


Toll-like receptor 10 expression in chicken, cattle, pig, dog, and rat lungs.
Toll-like receptors (TLRs) are conserved immune receptors that play critical roles in innate immunity and are known as "gate keepers" of immune system. TLR10 is identified as type 1 plasma membrane protein but the identity of its ligand remains unclear. Till date, no data are available on tissue and cell specific expression of TLR10 in normal and inflamed lungs of domestic animal species, and rat, which is commonly used as a model to study human diseases. We characterized a commercially available TLR10 antibody for use in cattle, pig, dog, chicken, and rat. Western blotting of total lung protein extracts from cattle, dog, pig and chicken showed a band of 85-100kDa, which is similar to the molecular weight of TLR10. The immuno-histochemical and immuno-electron microscopic data show TLR10 expression in vascular endothelium and smooth muscles in lungs of control and inflamed animals. Further, we found that expression of TLR10 in bovine neutrophils is altered upon treatment with Escherichia coli lipopolysaccharide. These data show TLR10 expression in the lungs of these mammalian species and that activation of bovine neutrophils alters the expression of TLR10.


Lead stimulates intercellular signalling between hepatocytes and Kupffer cells.
The role of intercellular signalling between liver cells in lead (Pb)(1)-induced liver toxicity was investigated in cocultures of freshly isolated and cultured rat hepatocytes and Kupffer cells. The Kupffer cells (seeded onto culture dish inserts), the hepatocytes or the two in cocultures were exposed to Pb acetate (2-50 microM) in combination with lipopolysaccharide (0.1-1000 ng/ml). In hepatocyte cultures, the combined Pb/lipopolysaccharide treatment induced no significant increase in the release of the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) whereas in Kupffer cell cultures and in cocultures, at low lipopolysaccharide levels (0.1 and 1 ng/ml), TNF-alpha release was synergistically increased (up to 30-fold) when compared to lipopolysaccharide exposure alone. This stimulation of Kupffer cell-derived TNF-alpha release was specific for Pb or not detectable with mercury and cadmium. As a response to the Pb/lipopolysaccharide induced release of TNF-alpha, the cocultured hepatocytes increased their nitric oxide (NO) content sixfold when compared with lipopolysaccharide alone and downregulated the negatively regulated acute phase protein albumin. This downregulation was also detectable without lipopolysaccharide and without TNF-alpha release, indicating that Pb induces additional thus far unidentified Kupffer cell-derived factors, which interact with the cocultured hepatocytes. At the time of TNF-alpha release, the viability of the hepatocytes and the Kupffer cells was not affected. However, after a 48-h treatment period, Pb induced a Kupffer cell specific toxicity without affecting the hepatocytes. Loss of hepatocyte viability after lipopolysaccharide/Pb stimulation was only detectable in the presence of cocultured Kupffer cells together with human-derived granulocytes. It is concluded that Pb stimulates intercellular signalling between Kupffer cells and hepatocytes which is synergistically enhanced in the presence of low lipopolysaccharide levels. The released Kupffer cell-derived signals (e.g. cytokines) promotes most likely proteolytic hepatocyte killing in combination with a direct cellular interaction between the granulocytes and the hepatocytes.


Practicality of non-invasive glucagon-loaded dissolving microneedle for life-saving treatment of severe hypoglycemia in a diabetic rat model.
The development of dissolving microneedles (DMNs) has brought light to the transdermal delivery of biomolecules that are released into the skin through the rapid dissolution of the matrix material to enter the systemic circulation and exert therapeutic effects. Herein, we aimed to prepare, characterize, and analyze the effectiveness of a glucagon-loaded DMN system that rapidly increases blood sugar levels in rats with diabetic hypoglycemia. The stability and content of biological drugs following DMNs preparation was assessed using circular dichroism and bicinchoninic acid kit for protein determination kits(BCA kits). The maximum drug loading capacity of DMNs was approximately 140 μg in each patch, and the microneedles could be stored for up to 14 days under dry storage conditions. In vitro skin permeation studies were conducted using a Franz diffusion cell apparatus for glucagon-loaded DMNs. To investigate the efficacy of transdermal drug delivery, drug-laden DMNs were administered to rats with hypoglycemic diabetes. Compared to subcutaneous injections, microneedle drug release demonstrated comparable efficacy in raising blood glucose levels in vivo. Therefore, this study demonstrated that glucagon-loaded DMNs may be a promising approach for efficient transdermal drug delivery as an alternative to subcutaneous injection for the treatment of severe hypoglycemia in patients with diabetes.


Computer Tomography (CT)-based Screening of Hospitalized Patients with Moderate to Severe Chronic Obstructive Pulmonary Disease Complicated by Bronchiectasis Phenotype During Acute Exacerbation: A Clinical Analysis.
In the past, many experts considered chronic obstructive pulmonary disease (COPD) and bronchiectasis to be separate, chronic respiratory diseases. Nonetheless, the widespread use of high-resolution lung computed tomography (CT) has led to the discovery that these diseases can occur alone or together. The current study aimed to compare the effects of nutritional status on the clinical outcomes in moderate to severe COPD patients with bronchiectasis. This study identifies the nutritional risk in hospitalized patients with moderate to severe COPD complicated by bronchiectasis phenotype during acute exacerbation screened using computer tomography (CT). Also, determines its correlation with disease progression. NRS 2002 (Nutrition Risk Screening Evaluation Tool) was used to determine and evaluate the nutritional risk status in 182 hospitalized patients with moderate to severe COPD complicated by bronchiectasis phenotype during an acute exacerbation. Selected patients were divided into the nutritional risk (NR) group and the non-nutritional risk (NNR) group according to their nutritional status determined by NRS 2002. The body mass index (BMI), serum albumin (ALB), pre albumin (PAB), lymphocyte count (TLC), FEV1/FVC, FEV1% predicted, PEF% predicted, blood gas analysis, number of acute exacerbations in the past year, number of respiratory failure cases, number of anti-infection days, and length of hospitalization of the two groups were observed. The hospitalized patients in acute exacerbation of moderate to severe COPD complicated by bronchiectasis phenotype had a nutritional risk of 62.64%. BMI, ALB, PAB, TLC, FEV1% predicted, FEV1/FVC, PEF% predicted, blood gas analysis, number of acute exacerbations in the past year, number of respiratory failure cases, number of anti-infection days, and length of hospitalization were statistically significantly different between the NR group and NNR group (P<0.05). Hospitalized patients with moderate to severe COPD complicated by bronchiectasis phenotype during acute exacerbation are often associated with nutritional risk. An increase in nutritional risk reduces the level of pulmonary function of the patient and elevates the risk for repeated acute exacerbations, which predispose the patient to respiratory failure, thereby increasing the length of hospitalization. Therefore, the nutritional risk status of COPD patients with bronchiectasis was closely related to the occurrence, development, and prognosis of the disease.


Acculturation, sociodemographic and lifestyle factors associated with compliance with physical activity recommendations in the Mexican-American Mano A Mano cohort.
Being physically active is important for health, and few Mexican-Americans meet national US physical activity recommendations. The aim of this study was to investigate sociodemographic, acculturation and lifestyle factors that were associated with meeting physical activity recommendations in this group. A cross-sectional analysis of a large population-based cohort study in southern Texas, USA. Between 2001 and 2011, 21 551 adult members of the Mexican-American Mano A Mano cohort completed baseline questionnaires on physical activity and other lifestyle factors. Meeting US physical activity recommendations was defined as participating in 150 min of moderate, or 75 min of vigorous, activity per week. Factors contributing to the likelihood of meeting physical activity recommendations were examined by sex and country of birth in multivariate logistic regression models. Less than half of all men and less than a quarter of all women met US physical activity recommendations. Having some college education, greater acculturation and current alcohol use were each associated with greater odds of meeting physical activity recommendations in all groups except US-born men. Higher body mass index was associated with lower odds of meeting recommendations in US-born and Mexico-born women. Results demonstrate that factors associated with meeting physical activity recommendations differ by sex and country of birth. Tailored interventions to increase Mexican-Americans' activity levels to achieve health benefits should consider education, acculturation and alcohol use.


Atrial fibrillation among adults with heart failure in sub-Saharan Africa - prevalence, incidence and all-cause mortality: a systematic review and meta-analysis protocol.
Heart failure (HF) remains a major non-communicable disease in sub-Saharan Africa (SSA) associated with high rates of readmission, mortality and loss of economic productivity as it affects mostly young and economically active adults. Atrial fibrillation (AFib) is a major determinant of mortality among patients with HF in SSA. Meanwhile, the use of anti-arrhythmic medications in the region remains unacceptably low. This review aims to evaluate the prevalence and incidence of AFib in adult patients with HF in SSA, and the all-cause mortality rate among patients with HF and AFib. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols 2015 statement was used to prepare this protocol. All eligible studies from database inception to December, 31 2018 in MEDLINE, Embase, Google Scholar, Web of science and Africa-specific databases (AFROLIB, African Index Medicus and African Journals Online) will be included without language restrictions. The process of study screening, selection, data extraction and assessment of risk of bias will be conducted independently by two reviewers. Disagreements will be arbitrated by a third reviewer. Study-specific estimates will be pooled using random-effect meta-analysis and summary measures obtained will be presented in forest plots. The χ2 test on Cochrane's Q and the I2 statistics will be used to assess and quantify heterogeneity, respectively. The Egger's test and funnel plots will be used to assess publication bias. Since our review will be based on already published data, an ethical approval is not required. The findings of this review will be presented in conferences and peer-reviewed journals and shared on social media such as Researchgate, Facebook, WhatsApp and Twitter. CRD42018087564.


Luteinizing hormone and cortisol responses to naloxone in normal weight women with bulimia.
The present study was undertaken in order to establish whether alterations in the endogenous opioid control of luteinizing hormone (LH) and ACTH/cortisol secretion occur in bulimic women with normal body weight and normal menstrual cycles. For this purpose, the capability of the opioid antagonist naloxone (4 mg injected as an intravenous bolus at time 0, plus 10 mg infused over 2 hr) to increase the circulating levels of LH and cortisol was tested in nine bulimic women and in nine age- and weight-matched normal controls. All women were tested on the 22nd day of a normal menstrual cycle. Two days later, a control test with normal saline (NaCl 0.9%) instead of naloxone was performed. The basal levels of LH and cortisol were similar in the bulimic and normal subjects and were not modified by the administration of normal saline. In contrast, the administration of naloxone significantly increased plasma LH and cortisol levels in all subjects, with peak LH responses at 30 min and peak cortisol responses at 60 min. The naloxone-induced LH and cortisol increases were significantly higher in the bulimic women than in the normal controls. These data indicate the presence of an increased opioid inhibitory tone in the control of LH and ACTH/cortisol secretion in normal weight bulimic women with normal menstrual cycles.


[IMRT and head and neck tumors: does differential fractionation have a role?].
For head and neck cancer, intensity-modulated radiation therapy (IMRT) provides benefits in terms of coverage of the target tumour volume and reduction of the dose to organs at risk. Altered fractionation called SMART (simultaneous modulated accelerated radiation therapy) or SIB (simultaneous integrated boost), equivalent to the "concomitant boost" of conventional techniques, provides additional theoretical gain in the therapeutic index and simplifies the practical implementation of the treatment. The impact on tumour control and acute and late toxicities is encouraging but needs to be confirmed by prospective clinical studies with sufficient follow-up. A lot of different protocols have been tested without really bringing out a "gold standard". However, the current results tend to suggest a SIB/SMART-IMRT moderately accelerated without combined chemotherapy for limited stages (I and II), and SIB-IMRT slightly accelerated with induction and/or concomitant chemotherapy for more advanced stages (III and IV).


Intraoperative optical pachymetry in photorefractive keratectomy.
To study the effect of variables on the accuracy and reliability of the optical pachymeter built into the WaveLight EX500 excimer laser during photorefractive keratectomy (PRK). John A. Moran Eye Center, University of Utah, Salt Lake City, USA. Retrospective case series. A chart review of 352 eyes (181 patients) that had excimer laser PRK was performed. Programmed excimer laser residual stromal bed (RSB) measurements, optical pachymeter measurements after ablation, and Scheimpflug pachymetry measurements (Pentacam) at the 1-year follow-up were compared. Variables included ablation time, preoperative spherical equivalent (SE), 1-year SE, mitomycin-C use, operating room temperature and humidity, and programmed monovision. The mean programmed RSB was 27 μm greater than the optical pachymetry post-ablation measurement (P < .001). Of patients with a 1-year follow-up, the 1-year Scheimpflug pachymetry RSB was 24 μm greater than the optical pachymetry post-ablation RSB (P < .001). Comparison of the programmed RSB with the optical pachymetry post-ablation RSB showed that the preoperative SE and ablation time had a Pearson correlation coefficient of -0.36 and 0.30, respectively (P < .001). There was no correlation between operating room temperature, humidity, or programmed monovision with these differences. The RSB post-ablation values measured by optical pachymetry during PRK were significantly lower than the programmed excimer laser RSB value and 1-year Scheimpflug pachymetry RSB value. Intraoperative pachymetry during PRK underpredicted the actual long-term RSB thickness. The greater temporary drying effect associated with increased ablation time in higher myopic corrections might have caused this error.


A comparative examination of the health status of earthquake-affected and non-earthquake-affected adolescents in Yushu.
Yushu, Qinghai Province, which is located in the remote Tibetan Plateau in western China, was struck by a disastrous earthquake in 2010. This study aimed to compare the health status of adolescents who had (Exp-Group) and had not (Non-Group) experienced the Yushu earthquake, 7 years after it occurred; additionally, group-specific predictors of health status were identified. A cross-sectional study was adopted among students from two junior schools in Yushu, whereby two groups were compared. Descriptive statistics, t-tests, Wilcoxon rank-sum tests, Kruskal-Wallis H tests, and stepwise linear regression were used to analyze data. Exp-Group scored higher than Non-Group on Physiological Component Summary (PCS) but not on Mental Component Summary (MCS). Among Exp-Group participants, lower PCS scores were predicted for "house damaged," "injured," "family member injured," and "family member or friend dead." Lower MCS scores were predicted by "family member or friend dead." Among Non-Group participants, PCS scores were predicted by "residence" and "family member or friend dead." Lower MCS scores were predicted by "not living with parents." Lower PCS and MCS scores of Exp-Group adolescents mainly contributed to earthquake-related injuries, while lower PCS and MCS scores of Non-Group are related to poor living conditions and the fact of the left-behind child.


The renal urate transporter SLC17A1 locus: confirmation of association with gout.
Two major gout-causing genes have been identified, the urate transport genes SLC2A9 and ABCG2. Variation within the SLC17A1 locus, which encodes sodium-dependent phosphate transporter 1, a renal transporter of uric acid, has also been associated with serum urate concentration. However, evidence for association with gout is equivocal. We investigated the association of the SLC17A1 locus with gout in New Zealand sample sets. Five variants (rs1165196, rs1183201, rs9358890, rs3799344, rs12664474) were genotyped across a New Zealand sample set totaling 971 cases and 1,742 controls. Cases were ascertained according to American Rheumatism Association criteria. Two population groups were studied: Caucasian and Polynesian. At rs1183201 (SLC17A1), evidence for association with gout was observed in both the Caucasian (odds ratio (OR) = 0.67, P = 3.0 × 10-6) and Polynesian (OR = 0.74, P = 3.0 × 10-3) groups. Meta-analysis confirmed association of rs1183201 with gout at a genome-wide level of significance (OR = 0.70, P = 3.0 × 10-8). Haplotype analysis suggested the presence of a common protective haplotype. We confirm the SLC17A1 locus as the third associated with gout at a genome-wide level of significance.


The flavonoid, fisetin, inhibits UV radiation-induced oxidative stress and the activation of NF-kappaB and MAPK signaling in human lens epithelial cells.
Ultraviolet (UV) radiation-induced oxidative stress plays a significant role in the progression of cataracts. This study investigated the photoprotective effect of fisetin on UV radiation-induced oxidative stress in human lens epithelial cells and the possible molecular mechanism involved. SRA01/04 cells exposed to different doses of ultraviolet B (UVB) were cultured with various concentrations of fisetin and subsequently monitored for cell viability by the 4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT) assay. The effect of fisetin on the generation of reactive oxygen species (ROS) of SRA01/04 cells was determined by flow cytometry. Translocation of nuclear factor kappa-B (NF-kappaB) was examined by immunocytochemistry. Expression of NF-kappaB/P65, inhibiter kappa B (IkappaB), and mitogen activated protein kinase (MAPK) proteins were measured by western blot. Treatment of SRA01/04 cells with fisetin inhibited UVB-induced cell death and the generation of ROS. Fisetin inhibited UVB-induced activation and translocation of NF-kappaB/p65, which was mediated through an inhibition of the degradation and activation of IkappaB. Fisetin also inhibited UVB-induced phosphorylation of the p38 and c-Jun N-terminal kinase (JNK) proteins of the MAPK family at various time points studied. The flavonoid, fisetin, could be useful in attenuation of UV radiation-induced oxidative stress and the activation of NF-kappaB and MAPK signaling in human lens epithelial cells, which suggests that fisetin has a potential protective effect against cataractogenesis.


Changing Trends of Invasive Pneumococcal Disease in the Era of Conjugate Pneumococcal Vaccination in Olmsted County: A Population-Based Study.
To estimate the incidence of invasive pneumococcal disease (IPD) in the pre-13-valent pneumococcal conjugate vaccine (pre-PCV13; 7-valent pneumococcal conjugate vaccine era, 2002-2010) and post-PCV13 (2011-2018) time periods. Using the Rochester Epidemiology Project, we conducted a population-based cohort study of all IPD cases in Olmsted County, Minnesota, from January 1, 2002, to December 31, 2018. Overall, 187 cases of IPD were identified. The incidence of IPD decreased significantly from 11.1 (95% CI, 9.1 to 13.2) to 5.6 (95% CI, 4.3 to 6.9) per 100,000 person-years when the pre- and post-PCV13 periods (2002-2010 vs 2011-2018) were compared (P<.001). Of the 187 patients with IPD, 112 (59.9%) had previously received at least 1 dose of pneumococcal vaccine. Among the IPD cases in the post-PCV13 period, there was an increase in non-PCV13 serotypes, mainly 11A (from 1.0% [1 of 105] to 6.2% [4 of 64]) and 33F (from 2.9% [3 of 105] to 15.6% [10 of 64]), while PCV13/non-7-valent pneumococcal conjugate vaccine serotypes declined from 38.1% (40 of 105) to 15.6% (10 of 64). At 30 days after an IPD diagnosis, the survival rate was 88.8% (95% CI, 84.4% to 93.4%). A marked decline in IPD incidence occurred during the post-PCV13 era. Because of the observed increase in non-PCV13 serotypes, coupled with multiple factors that impact the epidemiology of IPD, ongoing surveillance of patients with IPD, particularly due to non-PCV13 serotypes, is warranted.


Service quality for Type 2 diabetes in Australia: the patient perspective.
To assess the service quality of care as perceived by people with Type 2 diabetes mellitus. A cross-sectional survey using a self-administered questionnaire was carried out among members of Diabetes Australia-Queensland with Type 2 diabetes. For 12 aspects of service quality derived from a literature review and focus group research, patients scored the relative importance of the aspects and their perception of quality of received care. A measure of service quality was derived by combining the relative importance and actual performance. A total of 603 people with Type 2 diabetes participated. Of the 12 aspects of care, communication, availability of support group, safety and prevention had the highest scores for importance; support group and basic amenities had the highest average performance values; but the highest service quality values were for support group, basic amenities, dignity and confidentiality. Younger participants had lower service quality scores (P = 0.001) and participants with good control of their diabetes had higher scores (P < 0.001). Compared with the reference population, our sample had 8.7% fewer people under 65 years old. From the perspective of people with Type 2 diabetes, there is a notable gap between their expectations and what they have actually received in most aspects of provided care. In addition, overall service quality and six aspects of service quality (choice of care provider, accessibility, prevention, continuity, timeliness and safety) were identified to be of inadequate quality. Hence, this study demonstrates a significant opportunity to improve quality of healthcare services.


Orforglipron (LY3502970), a novel, oral non-peptide glucagon-like peptide-1 receptor agonist: A Phase 1a, blinded, placebo-controlled, randomized, single- and multiple-ascending-dose study in healthy participants.
To evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple doses of orforglipron (LY3502970), an oral, non-peptide glucagon-like peptide-1 receptor agonist (GLP-1RA) in healthy participants. This was a double-blind, placebo-controlled, Phase 1 study. Overtly healthy adults aged 18 to 65 years with body mass index of 20 to 40 kg/m2 and glycated haemoglobin concentration of 47.5 mmol/mol (<6.5%) were eligible. In Part A, participants received single-dose orforglipron, with four cohorts receiving escalating doses (0.3-6 mg). In Part B, participants received 4 weeks of daily repeated oral orforglipron with doses escalating weekly to four different final target doses (2-24 mg). Ninety-two participants enrolled and received at least one study drug dose (32 in Part A [mean age 43.4 years] and 60 in Part B [mean age 42.5 years]). The most common adverse events were gastrointestinal tract-related. Pharmacokinetics were approximately dose proportional, and the mean t1/2 was 24.6 to 35.3 hours after a single dose (0.3-6 mg). On Day 28, the mean t1/2 was 48.1 to 67.5 hours across the dose range (2-24 mg). Substantial reductions in body weight of up to 5.4 kg were observed after 4 weeks in orforglipron-treated participants, compared to a reduction of 2.4 kg with placebo (P < 0.05). Orforglipron decreased fasting glucose levels across Days 1 to 28, and gastric emptying was delayed on Day 28. Orforglipron's long half-life (25-68 hours) allows once-daily oral dosing, without water and food restrictions. Orforglipron had a pharmacodynamic and safety profile similar to that of injectable GLP-1RAs, which supports continued clinical development.


Effect of charge regulation on steric mass-action equilibrium for the ion-exchange adsorption of proteins.
A thermodynamic formalism is developed for incorporating the effects of charge regulation on the ion-exchange adsorption of proteins under mass-overloaded conditions as described by the steric mass-action (SMA) isotherm. To accomplish this, the pH titration behavior of a protein and the associated adsorption equilibrium of the various charged forms of a protein are incorporated into a model which also accounts for the steric hindrance of salt counterions caused by protein adsorption. For the case where the protein is dilute, the new model reduces to the protein adsorption model described recently by the authors which accounts for charge regulation. Similarly, the new model reduces to the steric mass-action isotherm developed by Brooks and Cramer which applies to mass-overloaded conditions for the case where charge regulation is ignored so that the protein has a fixed charge. Calculations using the new model were found to agree with experimental data for the adsorption of bovine serum albumin (BSA) on an anion-exchange column packing when using reasonable physical properties. The new model was also used to develop an improved theoretical criterion for determining the conditions required for an adsorbed species to displace a protein in displacement chromatography when the pH is near the protein pI.


Morning floral heat as a reward to the pollinators of the Oncocyclus irises.
Relationships between flowering plants and their pollinators are usually affected by the amount of reward, mainly pollen or nectar, offered to pollinators by flowers, with these amounts usually positively correlated with floral display. The large Oncocyclus iris flowers, despite being the largest flowers in the East Mediterranean flora, are nectarless and have hidden pollen. No pollinators visit the flowers during daytime, and these flowers are pollinated only by night-sheltering solitary male bees. These iris flowers are partially or fully dark-colored, suggesting that they gather heat by absorbing solar radiation. Here we test the hypothesis that the dark-colored flowers of the Oncocyclus irises offer heat reward to their male solitary bee pollinators. Floral temperature was higher by 2.5 degrees C than ambient air after sunrise. Solitary male bees emerged earlier after sheltering in Oncocyclus flowers than from other experimental shelter types. Pollination tunnels facing east towards the rising sun hosted more male bees than other aspects. We suggest that floral heat reward can explain the evolution of dark floral colors in Oncocyclus irises, mediated by the pollinators' behavior.


Immunoglobulin G-positive in B-cell cross-match decreases kidney allograft survival.
We retrospectively studied all 1149 transplants performed at our center between 1993 and 2003 to determine the incidence and clinical effect of pretransplant B-positive cross-match on kidney graft survival. The patients were divided in two groups: B-negative (n = 1102) and B-positive in current sera (n = 47; 4.1%). AB-positive test was more frequent among regrafted patients (14% vs 3%; P = .00). Demographic data were not different between the groups. The overall rate of graft loss was similar (26% vs 24%, respectively; P = .86). However, early nonsurgical graft losses were more frequent among B-positive patients (46% vs 20%, respectively; P = .04). IgM was the most frequent immunoglobulin in the B-positive group (76% IgM and 24% IgG). There was no significant difference between B-negative and B-positive groups in the 1-, 5-, and 10-year graft survival rates (87% vs 83%, 73% vs 78%, 64% vs 66%, respectively; P = .87). The graft survival was significantly reduced comparing an IgG anti-B cell to the B-negative group (P = .03) as well as IgG compared to IgM (P = .004). In conclusion, only B-positive cross-match due to IgG decreased graft survival. Even though it is an uncommon situation (0.9%), this study stressed the clinical value of the B-cell cross-match as a tool to identify patients with a higher immunological risk.


Synthesis, Structure, and Characterization of Tris(1-ethyl-4-isopropyl-imidazolyl-κN)phosphine Nickel(II) Complexes.
In this work we report the synthesis of five new nickel(II) complexes all coordinated to the tripodal ligand tris(1-ethyl-4- i Pr-imidazolyl)phosphine (TlEt4iPrIP). They are [Ni(T1Et4iPrIP)(CH3CN)2(OTf)](OTf) (1), [Ni(T1Et4iPrIP)(OTf)2] (2), [Ni(T1Et4iPrIP)(H2O)(OTf)](OTf) (3), [Ni(T1Et4iPrIP)Cl](OTf) (4), and [Ni(T1Et4iPrIP)Cl2] (5). The complexes serve as bioinorganic structural model complexes for histidine-coordinated nickel proteins. The X-ray structures have been determine for all complexes which feature coordination numbers 4-6. We investigated the spectroscopic interconversions for these compound in dichloromethane solution and demonstrate interconversion between 1-3 and conversion of 2 to 4. Complex 5 can be spectroscopically converted to the cation of 4 by dissolving it in dichloromethane. Fits of variable temperature magnetic susceptibility data yielded the following parameters: g = 1.944, D = -0.327 cm-1, E/D = 3.706 for 1; g = 2.280, D = -0.365 cm-1, E/D = 22.178 for 2; g = 2.000, D = -7.402 cm-1, E/D = -0.272 for 3; g = 2.176, D = -0.128 cm-1, E/D = -0.783 for 4; g = 2.258, D = 14.288 cm-1, E/D = 0.095 for 5. DFT structure optimizations afforded HOMO and LUMO energies indicating that complex 1 is the most stable.


Humanistic approaches to the understanding and treatment of anorexia nervosa.
Research and treatment approaches to anorexia nervosa are primarily based on behaviourist psychology. This review summarizes some attempts to understand the causes and consequent treatments of the condition from the viewpoints of psychoanalytically informed, family, existential and feminist psychology. These perspectives, which focus on the individual experience of the anorexic, leave many questions unanswered, but provide fresh frameworks from which to investigate and treat the condition.


Studies on the participation of the dopaminergic system in the central effects of chelidonine.
Chelidonine administered to rats in doses of 25, 50, 100 and 200 mg/kg ip exerted an inhibitory effect on the dopaminergic structures in the rat. It was shown that chelidonine decreased amphetamine- and apomorphine-induced hyperactivity and inhibited amphetamine and apomorphine sterotype. Besides, chelidonine significantly inhibited the yawning and penile erection produced by apomorphine. However, chelidonine potentiated also catalepsy caused by haloperidol. In doses of 100 and 200 mg/kg ip chelidonine depressed the whole brain dopamine (DA) concentrations and enhanced DA utilization.


Type 2 diabetes mellitus: the grand overview.
Type 2 diabetes currently accounts for over 100 billion dollars in annual healthcare expenditure in the United States and 28% of the national (Medicare) healthcare budget for elderly Americans. In our inner-city hospital, 20% of all 950 beds are occupied by patients with diabetes; and 28-38% of patients receiving cardiac care in Coronary Care Units, catheterization laboratories or cardiovascular surgery, have diabetes as an underlying disorder. Both computer modelling and controlled clinical trials suggest that intensive therapy of diabetes can reduce significantly the morbidity and costs associated with this increasingly common disorder. Early detection of carbohydrate intolerance holds great promise for preventing the onset, progression and complications of Type 2 diabetes. To date our efforts have been futile, with 20% of newly diagnosed Type 2 diabetic patients already complicated by retinopathy and 14% complicated by peripheral vascular disease. It is now clear that high-risk individuals can be identified, and intervention trials are underway to test the hypothesis that Type 2 diabetes (and its attendant cardiovascular risks) can be prevented. The Study to Prevent Non-Insulin-Dependent Diabetes Mellitus (STOP NIDDM) in Canada and Europe has randomized 1200 individuals with impaired glucose tolerance (IGT) into a three-year trial to prevent disease progression. The Diabetes Prevention Program (DPP) in the US has randomized almost 3000 individuals with IGT into a six-year, three-arm study testing the efficacy of intensive lifestyle and pharmacological therapy in disease progression. Together, these studies should provide a public health model for the recognition of high-risk individuals and interventions to stem the epidemic of Type 2 diabetes. For those patients suffering with Type 2 diabetes already, pancreas transplantation remains an extreme intervention with the potential for 'curing' diabetes. Although applied usually to patients with Type 1 diabetes, experience is accumulating of transplantation in Type 2 diabetic patients with end-stage renal disease. Outcomes for these individuals are as good as for Type 1 diabetes. Islet-cell transplants, in fact, have been more successful in Type 2 diabetes compared with Type 1. Improved islet-cell availability, better immunosuppression, and the possibility of antigen masking make this technology a major hope for the future.


Evidence for natural vertical transmission of chikungunya viruses in field populations of Aedes aegypti in Delhi and Haryana states in India-a preliminary report.
Aedes aegypti and Aedes albopictus are principal vectors for the transmission of chikungunya virus (CHIKV). India is a hub for both dengue and chikungunya infections and there are several reports of co-infection of dengue and chikungunya virus in the clinical scenario. The present pilot entomological survey was conducted to evaluate vertical transmission of CHIKV in Aedes field populations. Aedes immature (larvae and pupae) collection was done in 2012, over a period of six months from selected sites in Delhi and Haryana, India. The immatures collected were reared for adult emergence and species identification was done. A. aegypti male and female mosquitoes were separated and pooled collection spot-wise, RNA extracted and RT PCR performed to test for the presence of CHIKV in the pools. Container index (CI) and minimum infection rate (MIR) were estimated. From study areas that tested positive for CHIKV, adult collections were made and females upon feeding on uninfected blood in laboratory were allowed to lay eggs. The progeny that emerged from these field-collected mothers were tested for CHIKV presence. Our pilot survey showed the existence of A. aegypti population even during peak summer season in a few foci which eventually helped the mosquitoes to tide over adverse environmental conditions and with the start of rainfall, the population exploded within a short period of time. Immatures collected from field and progeny of adults collected from the field were CHIKV positive demonstrating the presence of vertical transmission of chikungunya virus in field population of A. aegypti. The present study further demonstrates the importance of identifying permanent breeding sites for proper Aedes species control.


Effects of menstrual cycle on cardiac autonomic innervation as assessed by heart rate variability.
The aim of the study was to investigate the effects of menstrual cycle on cardiac autonomic function parameters in young healthy women by means of heart rate variability (HRV). Forty-three nonobese regularly cycling women (age 29 +/- 6, range 20-38) were enrolled. Recordings for HRV analysis were obtained during the two phases of the menstrual cycle when the estrogen and progesterone levels peaked (follicular phase 11 +/- 1 days and luteal phase 21 +/- 1 days from the start of bleeding). Power spectral analysis of HRV was performed to calculate the low frequency peak (LF, 0.04-0.15 Hz), high frequency peak (HF, 0.15-0.40 Hz), LF in normalized unit (LF nU), HF in normalized unit (HF nU), and LF/HF ratio during the two phases of menstrual cycle. The heart rates, LF and HF, were similar in both phases (P > 0.05). A significant increase was noted in the LF NU in the luteal phase compared to follicular phase of the menstrual cycle (P = 0.014), whereas a tendency for increased HF NU was observed in the follicular phase (P = 0.053). Furthermore, LF/HF ratio was significantly higher in the luteal phase compared to follicular phase (2.1 +/- 1.5 vs 1.6 +/- 0.9, P = 0.002), suggesting increased sympathetic activity in the luteal phase. We concluded that regulation of autonomic tone is modified during menstrual cycle. The alteration in the balance of ovarian hormones might be responsible for these changes in the cardiac autonomic innervation.


An effective and chemotherapy-free strategy of all-trans retinoic acid and arsenic trioxide for acute promyelocytic leukemia in all risk groups (APL15 trial).
The combination of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has been demonstrated to have comparable effectiveness or better to ATRA and chemotherapy (CHT) in non-high-risk acute promyelocytic leukemia (APL). However, the efficacy of ATRA-ATO compared to ATRA-ATO plus CHT in high-risk APL remains unknown. Here we performed a randomized multi-center non-inferiority phase III study to compare the efficacy of ATRA-ATO and ATRA-ATO plus CHT in newly diagnosed all-risk APL to address this question. Patients were assigned to receive ATRA-ATO for induction, consolidation, and maintenance or ATRA-ATO plus CHT for induction followed by three cycles of consolidation therapy, and maintenance therapy with ATRA-ATO. In the non-CHT group, hydroxyurea was used to control leukocytosis. A total of 128 patients were treated. The complete remission rate was 97% in both groups. The 2-year disease-free, event-free survival rates in the non-CHT group and CHT group in all-risk patients were 98% vs 97%, and 95% vs 92%, respectively (P = 0.62 and P = 0.39, respectively). And they were 94% vs 87%, and 85% vs 78% in the high-risk patients (P = 0.52 and P = 0.44, respectively). This study demonstrated that ATRA-ATO had the same efficacy as the ATRA-ATO plus CHT in the treatment of patients with all-risk APL.


Comparison of Different Extraction Methods for Analysis of 10 Organochlorine Pesticides: Application of MAE-SPE Method in Soil from Beijing.
Four commonly applied extraction techniques for organochlorine pesticides, microwave-assisted extraction (MAE), accelerated solvent extraction (ASE), quick, easy, cheap, effective, rugged, and safe (QuEChERS) extraction and ultrasonic solvent extraction, were applied on soil samples in order to evaluate their performances. The extracts were analyzed by GC-ECD and confirmed by GC-MS/MS. The MAE and QuEChERS extraction methods generally yielded higher results compared to the ultrasonication and ASE methods, while the lowest recovery (56.8 %) for o,p'-DDD was obtained using the QuEChERS method. The MAE method was further applied to six different soils from Beijing. In the soil samples only α-endosulfan and β-endosulfan were not detected. The ratios of α-HCH/γ-HCH and α-HCH/β-HCH indicated HCH residues likely originated from historical use of HCHs, and that technical HCHs were not likely being currently applied in Beijing.


Assessing the polyamine metabolism of Plasmodium falciparum as chemotherapeutic target.
More than 30 years ago the potent ornithine decarboxylase inhibitor difluoromethylornithine (DFMO) was designed as new anticancer drug. Its efficacy was not as expected since the polyamine metabolism in mammalian cells seemed to be far more complex. However when DFMO was applied to African trypanosomes its effect on this protozoan parasite was highly convincing. Thenceforward many researchers tested DFMO and also other polyamine synthesis inhibitors against different parasites among them the causative agent of malaria Plasmodium. This review recapitulates the different attempts to interfere chemically with the plasmodial polyamine metabolism, the impact on the disease as well as its biochemical and molecular background. It will show that this fast proliferating organism depends for growth on high amounts of polyamines and that Plasmodium has its own and unique polyamine synthesis, differing highly from the mammalian one mainly in the arrangement of the key enzymes, S-adenosylmethionine decarboxylase and ornithine decarboxylase (AdoMetDC/ODC), on a bifunctional protein.


Reply to Winston and Peters' "On the presentation and interpretation of international homicide data...".
The rationale not previously given for handling a data entry for the USA in a prior paper is carefully described, which makes clear the criticism leveled is not appropriate. Further, brief murder data were presented to illustrate "Brimelow's theory of emotional conditioning," which suggests a strong taboo against consideration of any genetic contribution to differences among races.


The Role of Scientific Communication Skills in Trainees' Intention to Pursue Biomedical Research Careers: A Social Cognitive Analysis.
Scientific communication (SciComm) skills are indispensable for success in biomedical research, but many trainees may not have fully considered the necessity of regular writing and speaking for research career progression. Our purpose was to investigate the relationship between SciComm skill acquisition and research trainees' intentions to remain in research careers. We used social cognitive career theory (SCCT) to test a model of the relationship of SciComm skills to SciComm-related cognitive variables in explaining career intentions. A sample of 510 graduate students and postdoctoral fellows at major academic health science centers in the Texas Medical Center, Houston, Texas, were surveyed online. Results suggested that interest in performing SciComm tasks, SciComm outcome expectations (SCOEs), and SciComm productivity predicted intention to remain in a research career, while SciComm self-efficacy did not directly predict career intention. SCOEs also predicted interest in performing SciComm tasks. As in other SCCT studies, SciComm self-efficacy predicted SCOEs. We conclude that social cognitive factors of SciComm skill acquisition and SciComm productivity significantly predict biomedical trainees' intentions to pursue research careers whether within or outside academia. While further studies are needed, these findings may lead to evidence-based interventions to help trainees remain in their chosen career paths.


Prediction of coronary artery disease severity in patients referred for coronary angiography.
Diagnostic coronary angiography is often followed by coronary stenting. Therapy with aspirin and clopidogrel is currently the standard treatment for patients undergoing coronary stenting. Clopidogrel loading is usually given prior to the procedure. Some pretreated patients, however, are found to have triple-vessel disease (3VD) or left main disease (LMD) that requires referral for coronary artery bypass graft (CABG) surgery. Surgery in patients pretreated with clopidogrel may be complicated by excessive bleeding or delayed to avoid that risk. A risk factor-based formula may predict the likelihood that patients referred for coronary angiography will have 3VD or LMD. Consecutive patients (n = 2,180) referred for coronary angiography constitute the training subset (n = 1,296) used to build the model, and the validation subset (n = 884) used to test the model. Logistic regression models selected five variables showing strong associations with the presence of 3VD or LMD: age, gender, diabetes, hypercholesterolemia, and prior myocardial infarction (MI). A formula based on these variables and on the training subset was constructed to calculate the probability of 3VD or LMD. Applying this model to the validation subset predicted 3VD or LMD with 79% sensitivity, 53% specificity, 45% positive predictive value, and 83% negative predictive value. This simple formula based on five clinical variables is helpful in predicting the likelihood that patients, referred for coronary angiography, will have 3VD or LMD. Use of this formula can help decide in which patients clopidogrel loading prior to angiography should be avoided.


Correction: Phage Display of the Serpin Alpha-1 Proteinase Inhibitor Randomized at Consecutive Residues in the Reactive Centre Loop and Biopanned with or without Thrombin.
[This corrects the article DOI: 10.1371/journal.pone.0084491.].


Saccades in children.
Saccades are necessary for optimal vision. Little is known about saccades in children. We recorded saccades using an infrared eye tracker in 39 children, aged 8-19 years. Participants made saccades to visual targets that stepped 10 degrees or 15 degrees horizontally and 5 degrees or 10 degrees vertically at unpredictable time intervals. Saccadic latency decreased significantly with increasing age, while saccadic gain and peak velocity did not vary with age. Saccadic gains and peak velocities in children are similar to reported adult values. This implies maturity of the neural circuits responsible for making saccades accurate and fast. Saccade latency decreases as the brain matures.


Design and characterization of antitumor drug paclitaxel-loaded chitosan nanoparticles by W/O emulsions.
Chitosan nanoparticles and paclitaxel loaded chitosan nanoparticles were prepared by emulsification-crosslinking method in a W/O emulsion system, using glutaraldehyde as crosslinking agent. The mean diameter of chitosan nanoparticles decreased with increase of pH value of the reaction system from 4.5 to 6.5, and increased when the pH exceeded 6.5. Ultraviolet spectrum analysis showed that the largest loading efficiency and encapsulation efficiency could be 8.55% and 94.01%, respectively. In vitro drug release profile was also determined by ultraviolet spectrometry. MTT assays revealed that the blank chitosan nanoparticles had almost none toxicity, and cell culture was carried out accordingly.


Placebo effect model in asthma clinical studies: longitudinal meta-analysis of forced expiratory volume in 1 second.
Our objective was to describe the time course of the placebo effect in asthma and quantitatively investigate the affective factors of the placebo effect for the placebo response simulation during the asthma clinical study design. We conducted a systemic search of public data sources for the study-level forced expiratory volume in 1 second (FEV(1)) to build the placebo effect model for studies by oral or inhaled administrations simultaneously. The administration routes, types of inhalation device, mean patient age, mean male proportion, baseline FEV(1), disease severity, year of publication, inhaled corticosteroid status during the treatment, and dropout rate were tested as covariates. There are 34 literature sources containing 178 mean values for FEV(1) presenting the individual observations from about 3,703 patients. The exponential models adequately described the time course of placebo effect with the typical value of the maximum placebo effect (P(max)) of 0.060 L. Dropout rate incorporated in the residual error model and the disease severity (mild to moderate and moderate to severe) at baseline were covariates that remained in the final model. The placebo effect is adequately described by an exponential model over time. By incorporating the dropout rate in the residual error model, the estimation precision was improved. The model could predict the placebo response profile in mild to severe asthmatic patients for the asthma clinical study design and could also be a structure model of the placebo effect for the pure drug effect evaluation in the asthma clinical trials.


Use of liquid chromatography in the synthesis of isoluminol-labeled medroxyprogesterone acetate and zeranol.
A high-performance liquid chromatographic (HPLC) method for monitoring the syntheses of two isoluminol-labelled drugs, medroxyprogesterone acetate (MPA) and zeranol, has been developed. MPA and the ketone derivative of zeranol, zearalanone, were conjugated to N-(4-aminobutyl)-N-ethylisoluminol through the carboxymethyloxime derivative of the drug by using the N-succinimide ester as an intermediary. Reaction mixtures were sampled periodically and chromatographed directly by HPLC on a silica gel column, by using isocratic elution with mixtures of hexane-ethanol-acetic acid in several different proportions. The degree of reaction completion was determined by comparison of the peak area of the initial reactant to that present at sampling time. MPA oxime production was found to be complete after 15 min; 97.0% of the oxime was converted to succinimide ester in 24 h; 99.0% of the available ester reacted within 2.5 h to form the final labelled product. Zearalanone oxime production was found to be complete after 2 h; 93.3% of the oxime was converted to the activated ester within 24 h; 89.6% of available ester had reacted in 30 min to form the final labelled product. The chromatography can be performed in real time, permitting modification in the conditions of the reaction while in progress.


A fluorescent analog of colcemid, N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-colcemid, as a probe for the colcemid-binding sites of tubulin and microtubules.
The synthesis and biological testing of the fluorescent analog of colcemid, N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-colcemid (NBD-colcemid), are here described. NBD-colcemid exhibited a visible absorption maximum at 465 nm and fluoresced in the range of 520-540 nm, highly in environments of low polarity, whereas only slightly in aqueous solution. The addition of NBD-colcemid to bovine brain tubulin was accompanied by a striking enhancement of fluorescence. The fluorescent titration study suggested a stoichiometric binding of NBD-colcemid to tubulin. Assembled microtubules were directly visualized after mixing with NBD-colcemid using a fluorescence microscope. NBD-colcemid reversibly disrupted the metaphase spindles of sea urchin eggs as well as unlabeled colcemid. However, even when the birefringence of spindles was mostly lost, self-quenching properties of the NBD fluorescence allowed tubulin and its oligomers aggregated in higher concentrations in eggs to be visualized under a fluorescence microscope. The results suggest a wide applicability of NBD-colcemid as a fluorescent probe for studying the interactions of colcemid with tubulin and microtubules, as well as for localizing other colcemid-binding structures within cells.


Surgical repair of the kidney after blunt lesions of intermediate degree using a Vicryl mesh: an experimental study.
Twelve experimentally induced blunt renal lesions in pigs were treated either with an alloplastic renal capsule made of semi-elastic Vicryl mesh or with homologous pig fibrin adhesive or with through-and-through chromic catgut sutures as controls. The Vicryl mesh capsule was made by the Ethnor Company (Paris, France) to our specifications. The postoperative isotope nephrograms, which were repeated until the Vicryl had been fully resorbed, showed good renal function in every case. However, when compared to the controls, the kidneys which had been repaired with Vicryl mesh contained considerably less scar tissue at the site of parenchymal rupture and showed neither perirenal fibrosis nor atrophy of the parenchyma in the vicinity of the capsule. Our preliminary results seem to confirm that simple and rapid surgical treatment of moderately severe blunt renal lesions is possible using the alloplastic Vicryl mesh capsule. The method may also be suitable for reconstruction of the parenchyma following multiple nephrotomies, such as for removal of staghorn calculus, and experimental investigations are under way to clarify this point.


Corrigendum to "Design, molecular docking, and molecular dynamics of thiourea-iron (III) metal complexes as NUDT5 inhibitors for breast cancer treatment" [Heliyon 8 (9) (2022) e10694].
[This corrects the article DOI: 10.1016/j.heliyon.2022.e10694.].


High-throughput LPS profiling as a tool for revealing of bacteriophage infection strategies.
O-antigens of Gram-negative bacteria modulate the interactions of bacterial cells with diverse external factors, including the components of the immune system and bacteriophages. Some phages need to acquire specific adhesins to overcome the O-antigen layer. For other phages, O-antigen is required for phage infection. In this case, interaction of phage receptor binding proteins coupled with enzymatic degradation or modification of the O-antigen is followed by phage infection. Identification of the strategies used by newly isolated phages may be of importance in their consideration for various applications. Here we describe an approach based on screening for host LPS alterations caused by selection by bacteriophages. We describe an optimized LPS profiling procedure that is simple, rapid and suitable for mass screening of mutants. We demonstrate that the phage infection strategies identified using a set of engineered E. coli 4 s mutants with impaired or altered LPS synthesis are in good agreement with the results of simpler tests based on LPS profiling of phage-resistant spontaneous mutants.


Dr House, TV, and reality...
Medical practice in the media is usually far from reality. Thus, the viewer may be led astray. The world-famous fictional Dr House has to face a difficult diagnosis every week. His practice does not seem to reflect reality. The aim of this study was to assess the diagnosis strategy involved in this television program. An observer has previewed the 2011 season. The episode running time, the patient's age and sex, the list of all investigations and interventions, the final diagnosis, and the patient's outcome were collected. Number and proportion of French viewers for each episode were recorded. We analyzed 18 episodes. The median running time was 42.5 (42.1-43.2) minutes. Main patient characters were 12 men (66%) and 6 women (33%); the average age was 31 (22-38) years. There were 225 investigations or interventions reported, averaging 14 (9-15) per episode, representing one examination every 3.1 (2.9-4.8) minutes. The most frequently prescribed investigations were magnetic resonance imaging (MRI; 13; 72%), blood sample (11; 61%), and biopsy (10; 56%). The most frequent interventions were surgery, anti-infectious treatments, and steroid treatments (9 each; 50%). Two patients (11%) died. The median number of spectators was 8.4 (8.1-8.7) million, corresponding to 33% (33%-34%) of the French national audience. The population and the examination strategies used by Dr House were unrealistic. Because of this distortion, patients may not understand, nor accept the delay, the investigation choices, the intervention costs, risks, nor failures of a daily medical practice. Physicians should be aware of this "information bias."