Reasons for the Underutilization of Generic Drugs by US Ophthalmologists: A Survey.
Cross-sectional survey of 92 board-certified practicing Midwestern ophthalmologists to determine why prescribing habits favor brand-name drugs over generics and to identify approaches for increasing generic drug utilization. A survey was sent to members of state ophthalmology societies, private practice groups, and individual ophthalmologists to evaluate basic demographic/practice information, knowledge and opinions on generic drugs, frequency of drug representative visits, understanding of the Food and Drug Administration's process of evaluating generics, knowledge of patients' financial status and preferences, and action items that would increase generic utilization. Three factors increase the likelihood of ophthalmologists switching patients to generic drugs: increased knowledge of (1) generic options, (2) price differences between brand-names and generics, and ((3) patient preference for generics. The following four factors decrease the likelihood of ophthalmologists switching patients to generic drugs: (1) increased disease severity, (2) feeling that patient outcomes may be affected by choice of brand-name versus generic, (3) personal preference for taking a brand-name drug over a generic for their own hypothetical eye disease even if both were free, and (4) increased personal preference for taking a brand-name drug for their hypothetical eye disease. Ophthalmologists should continue to update themselves on generic medication options, become familiar with the price difference of generics versus brand-name drugs for commonly prescribed medications, and seek patients' opinions on generics and correct them when possible to increase generic utilization. In addition, studies evaluating the clinical equivalence of generic drugs relative to brand-name drugs should be performed and may help increase generic utilization.


Flexible Doppler ultrasound device for the monitoring of blood flow velocity.
Thrombosis and restenosis after vascular reconstruction procedures may cause complications such as stroke, but a clinical means to continuously monitor vascular conditions is lacking. Conventional ultrasound probes are rigid, particularly for postoperative patients with fragile skin. Techniques based on photoplethysmography or thermal analysis provide only relative changes in flow volume and have a shallow detection depth. Here, we introduce a flexible Doppler ultrasound device for the continuous monitoring of the absolute velocity of blood flow in deeply embedded arteries based on the Doppler effect. The device is thin (1 mm), lightweight (0.75 g), and skin conforming. When the dual-beam Doppler method is used, the influence of the Doppler angle on the velocity measurement is avoided. Experimental studies on ultrasound phantoms and human subjects demonstrate accurate measurement of the flow velocity. The wearable Doppler device has the potential to enhance the quality of care of patients after reconstruction surgery.


Docosahexaenoic acid biostatus is associated with event-related functional connectivity in cortical attention networks of typically developing children.
Although extant preclinical evidence suggests that the long-chain omega-3 fatty acid docosahexaenoic acid (DHA) is important for neurodevelopment, little is known about its role in human cortical structural and functional maturation. In the present cross-sectional study, we investigated the relationship between DHA biostatus and functional connectivity in cortical attention networks of typically developing children. Male children (aged 8-10 years, n = 36) were divided into 'low-DHA' (n = 18) and 'high-DHA' (n = 18) biostatus groups by a median split of erythrocyte DHA levels. Event-related functional connectivity during the performance of a sustained attention task (identical pairs continuous performance task (CPT-IP)) was conducted using functional magnetic resonance imaging. A voxelwise approach used the anterior cingulate cortex (ACC) as the seed-region. Erythrocyte DHA composition in the low-DHA group (2.6 ± 0.9%) was significantly lower than the high-DHA group (4.1 ± 1.1%, P ≤ 0.0001). Fish intake frequency was greater in the high-DHA group (P = 0.003) and was positively correlated with DHA levels among all subjects. The low-DHA group exhibited reduced functional connectivity between the ACC and the ventrolateral prefrontal cortex, insula, precuneus, superior parietal lobule, middle occipital gyrus, inferior temporal gyrus, and lingual gyrus compared with the high-DHA group (P < 0.05; corrected). The low-DHA group did not exhibit greater ACC functional connectivity with any region compared with the high-DHA group. On the CPT-IP task, the low-DHA group had slower reaction time (P = 0.03) which was inversely correlated with erythrocyte DHA among all subjects. These data suggest that low-DHA biostatus is associated with reduced event-related functional connectivity in cortical attention networks of typically developing children.


Biotic and abiotic factors affecting Brevicoryne brassicae (L.) (Hemiptera: Aphididae) and the associated hyperparasitoid Alloxysta fuscicornis Hartig (Hymenoptera: Figitidae) morphologies.
This study investigates the influence of biotic and abiotic factors associated with the morphological development of Brevicoryne brassicae (Linnaeus) and the associated hyperparasitoid Alloxysta fuscicornis (Hartig). The experiment involved the examination of whether aphid size was influenced by their vertical distribution and density on the host plant, as well as whether variations in hyperparasitoid size and symmetry were correlated with those of their aphid hosts. An aphid multivariate size index was obtained using principal component analysis, while symmetry was evaluated in terms of fluctuating asymmetry (FA). Samples were collected in 2007 on cabbage plants cultivated at an experimental farm located in Uberlândia, Minas Gerais, Brazil (18°56'54"S; 48°12'46"W). The results demonstrated that the size of B. brassicae was negatively associated with temperature, but not with its vertical distribution on the host plant. Temperature was also negatively correlated with hyperparasitoid size. During warmer periods, females produced large quantities of small-sized offspring, whereas an opposite pattern, i.e. the production of fewer offspring of larger size took place during colder periods. This type of adjustment involving trade-offs between physiological and morphological mechanisms, as well as individual interaction with abiotic environmental factors, such as temperature, can be considered an adaptive plastic response in order to increase the chances of survival at a given locality. The encountered relationship between aphid and hyperparasitoid sizes may be an after effect of their indirectly biotic interaction. Hyperparasitoid FA was dependent on the width of the mummified aphids. However, the hypothesis that temperature and vertical distribution on the host plant might influence FA was not confirmed.


Autonomic function in Kawasaki disease with myocardial infarction: usefulness of monitoring heart rate variability.
Despite anticoagulant therapy, many patients with Kawasaki disease and giant coronary artery aneurysm develop myocardial infarction. These patients have a high risk of sudden death, but the etiology is not clear. We studied autonomic function and the possibility of malignant ventricular arrhythmia through heart rate variability. We studied six Kawasaki disease patients with myocardial infarction and 16 normal controls. Heart rate variability was investigated using a 24 h electrocardiogram. We assessed the standard deviation from the mean of the normal R-R intervals (SDNN), the proportion of adjacent R-R intervals with a difference greater than 50 msec (pNN50) and the root-mean square of successive R-R differences as time-domain analysis (rMSSD). We assessed very low-frequency power, low-frequency power (LF), high-frequency power (HF) and the LF/HF ratio in frequency-domain analysis. There was no significant difference in SDNN, but there was a significant difference in pNN50 and rMSSD. Patients with Kawasaki disease showed lower HF and higher LF/HF than normal controls. Our findings suggest that patients with Kawasaki disease and myocardial infarction show decreased vagal activity, which could cause malignant arrhythmia.


Antimicrobial peptides conjugated with fatty acids on the side chain of D-amino acid promises antimicrobial potency against multidrug-resistant bacteria.
With the alarming burden of antibiotic resistance, antimicrobial peptides (AMPs) seem to be novel antimicrobial alternatives for infection treatment due to their rapid broad-spectrum antimicrobial activity and low tendency for bacterial resistance. To obtain promising AMPs, a series of new peptides were designed and synthesized by conjugating various lengths of fatty acid chains onto the side chain of the position 4 or 7 D-amino acid of Ano-D4,7 (analogue of anoplin with D-amino acid substitutions at positions 4 and 7). The new peptides exhibited excellent antimicrobial activity against a range of bacteria, especially multidrug-resistant bacteria in contrast to conventional antibiotics. Moreover, the new peptides conjugated with fatty acid chains ranging from 8 to 12 carbons in length presented preferable antimicrobial selectivity and anti-biofilm activity. Additionally, the new peptides also exerted high stability to trypsin, serum, salts and different pH environments. Most notably, the new peptides showed a low tendency to develop bacterial resistance and they displayed optimal antimicrobial activity against the obtained resistant strains. Furthermore, the results from the outer/inner membrane permeabilization and cytoplasmic membrane depolarization assays and flow cytometry and scanning electron microscopy analyses demonstrated that the new peptides exert antimicrobial effects by typical non-receptor-mediated membrane mechanisms, as well as intracellular targets characterized by gel retardation and reactive oxygen species (ROS) generation assays. Furthermore, the new peptides presented remarkable in vivo antimicrobial potency, anti-inflammatory activity, and endotoxin neutralization. Collectively, the conjugation of fatty acids to the side chains of D-amino acids is a potential strategy for designing hopeful antimicrobial alternatives to tackle the risk of bacterial resistance.


Publisher Correction: Present and future Köppen-Geiger climate classification maps at 1-km resolution.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Local depot methylprednisolone injection for painful anal Crohn's disease.
Treatment, by local depot methylprednisolone injection, of severe anal pain in Crohn's disease not associated with overt sepsis is reported. It has given dramatic relief in 5 patients, but has not been successful in 2 patients where anal disease was in continuity with severe rectal involvement. Treatment has been effective for greater than 1 yr, and no complication of the technique has been found on regular follow-up. When compared with previous attempts at treatment, the beneficial results attained with methylprednisolone injection suggest that the effect is more than a placebo response. Careful patient selection to exclude overt sepsis or severe rectal disease is recommended before proceeding to steroid injection.


Label-Free Fluorescent Kinase and Phosphatase Enzyme Assays with Supramolecular Host-Dye Pairs.
The combination of the macrocyclic hosts p-sulfonatocalix[4]arene and cucurbit[7]uril with the fluorescent dyes lucigenin and berberine affords two label-free enzyme assays for the detection of kinase and phosphatase activity by fluorescence monitoring. In contrast to established assays, no substrate labeling is required. Since phosphorylation is one of the most important regulatory mechanisms in biological signal transduction, the assays should be useful for identification of inhibitors and activators in high-throughput screening (HTS) format for drug discovery.


Incidence of delayed graft function in cadaveric kidney transplants in Brazil: a multicenter analysis.
To evaluate the frequency of delayed graft function (DGF) in kidney transplant centers in Brazil, we sent a questionnaire requesting information on the number of cadaveric donor kidney transplants performed during the years 2000, 2001, and 2002, the number of early nonfunctioning grafts, and the number of patients on dialysis during the first posttransplant week with subsequent recovery. Among all centers performing more than 50 kidney transplants during the last year of evaluation, 6, performing 612 cadaveric kidney transplants during the study period, replied to the questionnaire. Sixty procedures (9.7%) resulted in nonfunctioning grafts, while 312 (55.6%) patients required dialysis during the first Ptx week: 216 (53.9%) in 2000, 189 (62.3%) in 2001, and 216 (51.6%) in 2002. The frequency of DGF during the study period was higher than that noted by several previous foreign studies. To better evaluate the possible causes of this finding, a more extensive and focused study is warranted.


A novel link between locus coeruleus activity and amyloid-related cognitive decline.
Recent work from Prokopiou, Engels-Domínguez et al. assessed locus coeruleus (LC) activity and its functional connectivity (FC) to forebrain regions during a novelty task in cognitively unimpaired adult individuals with varying degrees of amyloid deposition. Novelty increased LC activity and LC FC, but lower responses on these measures were associated with steeper cognitive decline in amyloid-positive individuals.


Molecular structure, spectroscopic studies and first-order molecular hyperpolarizabilities of p-amino acetanilide.
The infrared absorption, Raman spectra and SERS spectra of p-amino acetanilide have been analyzed with the aid of density functional theory calculations at B3LYP/6-311G(d,p) level. The electric dipole moment (mu) and the first hyperpolarizability (beta) values of the investigated molecule have been computed using ab initio quantum mechanical calculations. The calculation results also show that the synthesized molecule might have microscopic nonlinear optical (NLO) behavior with non-zero values. Computed geometries reveal that the PAA molecule is planar, while secondary amide group is twisted with respect to the phenyl ring is found, upon hydrogen bonding. The hyperconjugation of the C=O group with adjacent C-C bond and donor-acceptor interaction associated with the secondary amide have been investigated using computed geometry. The carbonyl stretching band position is found to be influenced by the tendency of phenyl ring to withdraw nitrogen lone pair, intermolecular hydrogen bonding, conjugation and hyperconjugation. The existence of intramolecular C=O...H hydrogen bonded have been investigated by means of the natural bonding orbital (NBO) analysis. The influence of the decrease of N-H and C=O bond orders and increase of C-N bond orders due to donor-acceptor interaction has been identified in the vibrational spectra. The SERS spectral analysis reveals that the large enhancement of in-plane bending, out of plane bending and ring breathing modes in the surface-enhanced Raman scattering spectrum indicates that the molecule is adsorbed on the silver surface in a 'atleast vertical' configuration, with the ring perpendicular to the silver surface.


Clinical zinc and copper deficiencies in cattle of western Sudan.
Clinical cases of both Zn and Cu deficiencies are reported in a cattle farm in Kordofan Region of the Sudan after drought. The animals showed general weakness, stunted growth, infertility, parakeratosis and achromotrichia. There was macrocytic hypochromic anaemia and low Cu and Zn concentrations in sera. The condition was more prevalent in zebu-Friesian crosses than the local breeds. Drought and marginal or low Cu and Zn content in pasture may be the predisposing factors.


Technical feasibility of transperineal MR-guided prostate interventions in a low-field open MRI unit: canine study.
Magnetic resonance imaging (MRI) provides superior visualization of the prostate, its substructure, surrounding tissues, and, most important, focal lesions or cancer. The purpose of our canine study was to demonstrate the feasibility of a low-field (0.35 T) transperineal system that enables precise MR image guidance of prostate interventions. The canines were placed in the right lateral decubitus position. Template reconstruction, trajectory planning, contouring were based on T2-weighted FSE images. For image guidance and target confirmation, fast gradient spoiled-echo (FSPGR) sequence was used. MR compatible coaxial needles were manually inserted through the perineum to the base of the prostate. After satisfactory position was confirmed, brachytherapy catheters were placed through the coaxial needles. The mean deviation of the needle displacements was 2.9 mm with a median value of 2.7 mm. 97% of the errors were less than 4.0 mm. The needle placement accuracy was modelled by the Rayleigh distribution with a sigma value of 2.3 mm. Visual confirmation of needle placements was demonstrated on pathology tissue slices. The time needed for each step was: anaesthesia - 15 min, setup and positioning - 15 min, initial imaging - 15 min, template registration, projection - 15 min, contouring, trajectory planning, insertion of 12 needles - 60 min Based on our canine experiences our method seems to be a promising approach for performing feasible, accurate, reliable and high-quality prostate MR guidance within a reasonable time span.


[Autoimmune pancreatitis associated with rheumatoid arthritis: successful combination therapy with steroids and methotrexate].
MEDICAL HISTORY AND CLINICAL FINDINGS: A 70-year-old female patient suffered from steatorrhea and upper abdominal discomfort for 8 weeks combined with new onset of arthralgia in both hands. Additionally she reported elevated fasting blood glucose levels. The physical examination was without pathological findings except for mild upper abdominal pressure pain. Imaging studies, including MRI and ultrasound examinations showed diffuse pancreatic enlargement without peripancreatic vessel involvement. Serological examinations showed elevated Cancer Associated Antigen 19 - 9 (1289 U/ml) and hyperglobulinemia with an IgG level of 170 mg/dl. The inflammatory markers were within normal ranges other than a slightly elevated erythrocyte sedimentation rate (35mm/1 h). Subsequent pancreatic biopsy showed lymphoplasmocellular, neutrophile and eosinophile granulocyte infiltration causing damage of the acinar pancreatic cells, typical for autoimmune pancreatitis (AIP). Magnetic resonance imaging (MRI) confirmed arthritis of both hands. Medical treatment was started with oral prednisolone (50 mg/day) for one week, tapered to 25 mg/day for another 2 weeks, followed by dose reductions of 5 mg/day every 2 weeks with a final maintenance dose of 5 mg/day for 8 months. After the first week of steroid therapy methotrexate (MTX) was started with an initial dose of 10 mg/week. Dose was raised until a final dosage of 30 mg/week. After 8 months without relapse, the maintenance therapy was reduced to 20 mg/week MTX and corticosteroids were stopped. With this treatment regimen the patient has showed complete remission of AIP and arthritis for 36 months. MTX may be successful as an initial basic treatment to reach better control of autoimmune-related extrapancreatic manifestations.


Metal Coated Polypropylene Separator with Enhanced Surface Wettability for High Capacity Lithium Metal Batteries.
Lithium metal batteries are among the strong contenders to meet the increasing energy demands of the modern world. Metallic lithium (Li) is light in weight, possesses very low standard negative electrochemical potential and offers an enhanced theoretical capacity (3860 mA h g-1). As a negative electrode Li paves way to explore variety of elements including oxygen, sulfur and various other complex oxides as potential positive electrodes with a promise of much higher energy densities than that of conventional positive electrodes. However, there are technical challenges in utilizing metallic lithium due to its higher reactivity towards liquid electrolytes and higher affinity to form Li dendrites, leading to serious safety concerns. Here, we report on preparation of niobium (Nb) metal-coated binder-free and highly hydrophilic polypropylene separator prepared via radio frequency (RF) magnetron sputtering. Thin layer of niobium metal (Nb) particles were deposited onto the polypropylene (PP) sheet for various time periods to achieve desired coating thickness. The as-prepared separator revealed excellent hydrophilic behaviour due to enhanced surface wettability. Symmetric cells display reduced interface resistance and uniform voltage profiles for 1000 cycles with reduced polarization at higher current densities suggesting smooth stripping and plating of Li and homogeneous current distribution at electrode/electrolyte interface under room temperature conditions. Nb nanolayer protected separator with LiNi0.33M0.33Co0.33O2 (LNMC) and composite sulfur cathodes revealed an enhanced cycling stability.


SOHO State of the Art Updates and Next Questions | New Pathways and New Targets in PTCL: Staying on Target.
While the peripheral T-cell lymphomas (PTCL) remain a therapeutic challenge, and increasingly account for a disproportionate number of lymphoma-related deaths, improved understanding of disease pathogenesis and classification, and the development of novel therapeutic agents over the past decade, all provide reasons for a more optimistic outlook in the next. Despite their genetic and molecular heterogeneity, many PTCL are dependent upon signaling input provided by antigen, costimulatory, and cytokine receptors. While gain-of-function alterations effecting these pathways are recurrently observed in many PTCL, more often than not, signaling remains ligand-and tumor microenvironment (TME)-dependent. Consequently, the TME and its constituents are increasingly recognized as "on target". Utilizing a "3 signal" model, we will review new-and old-therapeutic targets that are relevant for the more common nodal PTCL subtypes.


Continuous-Flow Pd-Catalyzed Carbonylation of Aryl Chlorides with Carbon Monoxide at Elevated Temperature and Pressure.
The development of a continuous-flow protocol for a palladium-catalyzed methoxycarbonylation of (hetero)aryl chlorides using carbon monoxide gas and methanol is described. (Hetero)aryl chlorides are the least expensive of the aryl halides, but are underutilized in carbonylation reactions due to their very poor reactivity. The described protocol exploits intensified conditions at elevated temperature and pressure, which are readily accessed within a continuous-flow environment, to provide moderate to excellent product yields (11 examples) in a short 16 min residence time. The continuous-flow protocol enables the safe and potentially scalable carbonylation of aryl chlorides using CO gas.


Prognostic score in liver cirrhosis developed using the Cox's proportional hazard regression model.
In order to assess the prognostic value of clinical and laboratory variables in liver cirrhosis, 36 of these variables were statistically analyzed in 151 patients followed up for 8 years. The 'survival time' was taken as the reference variable. In a first step we analyzed by log-rank test and by Cox's proportional hazard regression model the data of 98 patients (study group), obtaining 7 prognostically significant variables (age, leukocytes, calcium, potassium, globulins, cholesterol and previous diagnosis). From the regression coefficients of these variables, a risk score was obtained for each patient. To validate the prognostic value of this score, we computed it, using the same coefficients obtained in the study group, in 53 subsequently examined patients (control group) showing that the prognostic score allows the classification of these patients in 3 risk classes with different observed survival times.


Haemolysin secretion from E coli.
Haemolysin (HlyA) secretion from E coli is directed by a specific C-terminal targeting signal, located within the last 27-50 amino acids, with quite novel characteristics. The HlyA molecule is secreted directly to the medium without a periplasmic intermediate or detectable proteolytic processing. The C-terminal domain of HlyA can also be used to promote the secretion of several other E coli and mammalian proteins. HlyD and HlyB are essential for translocation of HlyA to the medium and we propose that these proteins form a transenvelope complex which initially binds the HlyA signal followed by transport of HlyA to the medium. HlyB is a member of a family of membrane proteins engaged in ATP dependent secretion mechanisms conserved in many organisms including man (P-glycoprotein and the CF protein). In this review we discuss the structure, function and regulation of the secretion mechanism.


Separation and quantification of 15 carotenoids by reversed phase high performance liquid chromatography coupled to diode array detection with isosbestic wavelength approach.
The manuscript presents the development of a new reverse phase high performance liquid chromatography (RP-HPLC) photo diode array detection method allowing the separation and quantification of 15 carotenoids (adonirubin, adonixanthin, astaxanthin, astaxanthin dimethyl disuccinate, asteroidenone, beta-apo-8'-carotenal, beta-apo-8'-carotenoic acid ethyl ester, beta-carotene, canthaxanthin, capsanthin, citranaxanthin, echinenone, lutein, lycopene, and zeaxanthin), 10 of which are feed additives authorised within the European Union. The developed method allows for the reliable determination of the total carotenoid content in one run using the corresponding E-isomer as calibration standard while taking into account the E/Z-isomers composition. This is a key criterion for the application of the method, since for most of the analytes included in this study analytical standards are only available for the E-isomers. This goal was achieved by applying the isosbestic concept, in order to identify specific wavelengths, at which the absorption coefficients are identical for all stereoisomers concerned. The second target referred to the optimisation of the LC conditions. By means of an experimental design, an optimised RP-HPLC method was developed allowing for a sufficient chromatographic separation of all carotenoids. The selected method uses a Suplex pKb-100 HPLC column and applying a gradient with a mixture of acetonitrile, tert-butyl-methyl ether and water as mobile phases. The limits of detection and limits of quantification ranged from 0.06 mg L(-1) to 0.14 mg L(-1) and from 0.20 mg L(-1) to 0.48 mg L(-1), respectively.


Wolman's disease: ultrastructural evidence of lipid accumulation in central and peripheral nervous systems.
We report the first case of Wolman's disease in which the fine structure of either the peripheral or the central nervous system has been examined. We confirm ultrastructurally the presence of lipid within endothelial and pericytic cells. Several cell types previously believed to be uninvolved in this storage process demonstrate lipid inclusions characteristic of Wolman's disease: perineural, endoneurial and Schwann cells of peripheral nerve, and oligodendrocytes and astrocytes of the central nervous system.


Interactions among unrelated species: Granivorous rodents, a parasitic fungus, and a shared prey species.
Granivorous rodents and a parasitic fungus in the Sonoran Desert utilize a common prey species, Erodium cicutarium, a desert annual plant. Experimental removal of rodents from field exclosures resulted in significantly higher densities of E. cicutarium. Fungal infection was significantly higher in the absence of rodents, suggesting that, while they do not interact directly, rodents and the fungus affect each other's densities by their use of a common prey species.


Evolving roles of CD38 metabolism in solid tumour microenvironment.
Given that plenty of clinical findings and reviews have already explained in detail on the progression of CD38 in multiple myeloma and haematological system tumours, here we no longer give unnecessary discussion on the above progression. Though therapeutic antibodies have been regarded as a greatest breakthrough in multiple myeloma immunotherapies due to the durable anti-tumour responses in the clinic, but the role of CD38 in the immunologic regulation and evasion of non-hematopoietic solid tumours are just initiated and controversial. Therefore, we will focus on the bio-function of CD38 enzymatic substrates or metabolites in the variety of non-hematopoietic malignancies and the potential therapeutic value of targeting the CD38-NAD+ or CD38-cADPR/ADPR signal axis. Though limited, we review some ongoing researches and clinical trials on therapeutic approaches in solid tumour as well.


Predicting late symptoms of head and neck cancer treatment using LSTM and patient reported outcomes.
Patient-Reported Outcome (PRO) surveys are used to monitor patients' symptoms during and after cancer treatment. Acute symptoms refer to those experienced during treatment and late symptoms refer to those experienced after treatment. While most patients experience severe symptoms during treatment, these usually subside in the late stage. However, for some patients, late toxicities persist negatively affecting the patient's quality of life (QoL). In the case of head and neck cancer patients, PRO surveys are recorded every week during the patient's visit to the clinic and at different follow-up times after the treatment has concluded. In this paper, we model the PRO data as a time-series and apply Long-Short Term Memory (LSTM) neural networks for predicting symptom severity in the late stage. The PRO data used in this project corresponds to MD Anderson Symptom Inventory (MDASI) questionnaires collected from head and neck cancer patients treated at the MD Anderson Cancer Center. We show that the LSTM model is effective in predicting symptom ratings under the RMSE and NRMSE metrics. Our experiments show that the LSTM model also outperforms other machine learning models and time-series prediction models for these data.


[Dependence of the expression of the biological features of Vibrio cholerae on the conditions of their cultivation].
The biological activity of toxigenic and non-toxigenic V. cholerae supernatants was found to depend on the cultivation medium. The use of iron-free tryptone medium made it possible to obtain supernatants of toxigenic V. cholerae with haemolytic activity and destructive action on passaged cell cultures. In the experimental infection of suckling rabbits the influence of the cultivation conditions of V. cholerae on the character and expression of their pathogenic properties was determined. The dissemination of V. cholerae into the internal organs of rabbits after their infection with both toxigenic and non-toxigenic strains correlated neither with the cultivation conditions of these strains, nor with the character of changes in the intestine of the infected animals.


Clinical significance of coronary flow velocity measurement using transthoracic Doppler echocardiography for unstable angina: a two-case report.
Clinical significance of coronary flow velocity measurement by transthoracic Doppler echocardiography in 2 patients with unstable angina (UA) was reported. No significant abnormality was observed on electrocardiography. Coronary flow sequence of the left anterior descending coronary artery (LAD) was detected in diastole. Peak diastolic flow velocity was 11.1 cm/s in case 1 and 10.1 cm/s in case 2. On the basis of these data, emergency coronary angiography was performed in both cases. Severe stenosis was observed at the proximal portion of LAD; consequently, emergency coronary angioplasty was performed. Coronary flow velocity measurement is useful as a diagnostic strategy in UA.


Differentiating among children with PDD-NOS, ADHD, and those with a combined diagnosis on the basis of WISC-III profiles.
Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS) and Attention Deficit/Hyperactivity Disorder (ADHD) have partly overlapping symptoms. It can also be debated whether a third diagnostic category exists: children with a combined diagnosis. In this study an attempt was made to distinguish among the three groups on the basis of intelligence (WISC-III) profiles. It was found that the PDD-NOS group had higher verbal and performance IQ's, as well as higher WISC-III index scores than the ADHD group. Subtests Block Design and Mazes discriminated best. It was concluded that based on intelligence scores, only PDD-NOS and ADHD emerged as distinct categories, whereas the combined diagnosis did not. Future research on the distinctiveness of these diagnostic groups, however, should include variables other than IQ.


Swimming as a measure of motor impairment after ethanol and pentobarbital in rats.
Ethanol and pentobarbital produced dose-dependent increases in time required by rats to swim a straight alley to an escape ladder.


The characteristics of upper airway edema in hereditary and acquired angioedema with C1-inhibitor deficiency.
Angioedemas localized in the upper airway are potentially life threatening, and without proper treatment, they may lead to death by suffocation. Upper airway edemas (UAE) in bradykinin-mediated angioedemas can even be the first symptoms of the disease. Our survey was performed with a retrospective long-term follow-up method from the medical history of 197 hereditary (C1-INH-HAE) and 20 acquired C1-inhibitor deficiency (C1-INH-AAE), 3 factor XII and 3 plasminogen gene mutation (FXII-HAE, PLG-HAE) patients treated at our center between 1990 and 2020. The UAE group included edemas localized to the mesopharynx, hypopharynx, and larynx, as narrowing of these anatomical regions can lead to suffocation. 98/197 C1-INH-HAE (47 families) and 13/20 C1-INH-AAE, 1/3 PLG-HAE, 1/3 FXII-HAE patients had experienced UAE at least once according to their medical history. In case of C1-INH-HAE patients, in 6/47 families who had undiagnosed ancestors had 13 members who died of suffocation. After the diagnosis, 1-1 member of two families died of UAE. 44/64 C1-INH-HAE patients did not smoke, 20/64 did. The occurrence of UAE was significantly higher in smoker patients. We analyzed 7607 HAE attacks of 56/98 patients. Out of all attacks, the incidence of UAE in the C1-INH-HAE group was 4%, and 9.5% in the C1-INH-AAE group, respectively. Early diagnosis is key in bradykinin-mediated angioedemas cases, since the patient must be provided with adequate treatment; and also it is essential to inform patients about the importance of avoiding the trigger factors and the early symptoms of UAE, as these measures could significantly decrease the incidence of lethal UAEs.


MicroRNAs as the pivotal regulators of cisplatin resistance in osteosarcoma.
Osteosarcoma (OS) is an aggressive bone tumor that originates from mesenchymal cells. It is considered as the eighth most frequent childhood cancer that mainly affects the tibia and femur among the teenagers and young adults. OS can be usually diagnosed by a combination of MRI and surgical biopsy. The intra-arterial cisplatin (CDDP) and Adriamycin is one of the methods of choices for the OS treatment. CDDP induces tumor cell death by disturbing the DNA replication. Although, CDDP has a critical role in improving the clinical complication in OS patients, a high ratio of CDDP resistance is observed among these patients. Prolonged CDDP administrations have also serious side effects in normal tissues and organs. Therefore, the molecular mechanisms of CDDP resistance should be clarified to define the novel therapeutic modalities in OS. Multidrug resistance (MDR) can be caused by various cellular and molecular processes such as drug efflux, detoxification, and signaling pathways. MicroRNAs (miRNAs) are the key regulators of CDDP response by the post transcriptional regulation of target genes involved in MDR. In the present review we have discussed all of the miRNAs associated with CDDP response in OS cells. It was observed that the majority of reported miRNAs increased CDDP sensitivity in OS cells through the regulation of signaling pathways, apoptosis, transporters, and autophagy. This review highlights the miRNAs as reliable non-invasive markers for the prediction of CDDP response in OS patients.


[Vertebroplasty--state of the art].
Percutaneous vertebroplasty (PVP) using PMMA (polymethyl methacrylate) was first described in 1987 by Gallibert and Deramond for the treatment of vertebral body instability in patients with aggressive forms of vertebral hemangioma. Other types of painful osteolytic bone lesions, such as osteoporotic vertebral fractures and vertebral metastasis are in the meantime more commonly treated using this method. Within the last few years, this technique has become widely accepted and it is proposed for osteolytic bone lesions in areas that are more difficult to approach surgically, e.g., the pelvis and sacrum. Rapid pain relief and resulting stability have conferred an important role upon osteoplasty especially in palliative tumor-treatment for patients with shortened expected life spans. In addition, combined treatment of painful osteolytic metastases with image-guided thermoablation and percutaneous cement injection has been shown to be a safe palliative modality in the therapy of nonresectable tumors.


Prediction of the maximal voluntary ventilation in healthy adult Chinese subjects.
The aim of the present study was to investigate the relationship between the FEV(1) and maximal voluntary ventilation (MVV) in healthy adult Chinese subjects, and to determine the validity of existing prediction equations of MVV for use in the Chinese population. Ninety-five healthy subjects (48 male and 47 female) stratified into five age groups (from 20 to 70 years) for both sexes were recruited from the general population. The FEV(1) and MVV of these subjects were measured with a clinical spirometer. The MVV was determined using the closed-circuit technique. The MVV was assessed for 12 s and values were calculated to obtain L/min. Multiple regression analysis was used to develop equations to predict MVV with age, height, FEV(1) as well as with FEV(1) alone as predictor variables. One-sample t-tests were used to compare the actual values of MVV for the subjects with their predicted values using equations from previous studies of MVV in healthy subjects. Using FEV(1) only, the following predictive equation was obtained: MVV = FEV(1) x 45.12 - 15.85 (adjusted r(2) = 0.792). Predicted MVV values using previously cited equations, including MVV = FEV(1) x 35 or 40, were all significantly different from the actual MVV values of these subjects. The relationship between MVV and FEV(1) among healthy adult Chinese subjects is described. Previously cited equations describing the relationship between FEV(1) and MVV cannot be applied to healthy adult Chinese subjects.


Peptides derived from HIV-1, HIV-2, Ebola virus, SARS coronavirus and coronavirus 229E exhibit high affinity binding to the formyl peptide receptor.
Peptides derived from the membrane proximal region of fusion proteins of human immunodeficiency viruses 1 and 2, Coronavirus 229 E, severe acute respiratory syndrome coronavirus and Ebola virus were all potent antagonists of the formyl peptide receptor expressed in Chinese hamster ovary cells. Binding of viral peptides was affected by the naturally occurring polymorphisms at residues 190 and 192, which are located at second extracellular loop-transmembrane helix 5 interface. Substitution of R190 with W190 enhanced the affinity for a severe acute respiratory syndrome coronavirus peptide 6 fold but reduced the affinity for N-formyl-Nle-Leu-Phe by 2.5 fold. A 12 mer peptide derived from coronavirus 229E (ETYIKPWWVWL) was the most potent antagonist of the formyl peptide receptor W190 with a K(i) of 230 nM. Fluorescently labeled ETYIKPWWVWL was effectively internalized by all three variants with EC(50) of approximately 25 nM. An HKU-1 coronavirus peptide, MYVKWPWYVWL, was a potent antagonist but N-formyl-MYVKWPWYVWL was a potent agonist. ETYIKPWWVWL did not stimulate GTPgammaS binding but inhibited the stimulation by formyl-NleLeuPhe. It also blocked beta arrestin translocation and receptor downregulation induced by formyl-Nle-Leu-Phe. This indicates that formyl peptide receptor may be important in viral infections and that variations in its sequence among individuals may affect their likelihood of viral and bacterial infections.


Past, present, and future developments in enantioselective analysis using capillary electromigration techniques.
Enantioseparation of chiral products has become increasingly important in a large diversity of academic and industrial applications. The separation of chiral compounds is inherently challenging and thus requires a suitable analytical technique that can achieve high resolution and sensitivity. In this context, CE has shown remarkable results so far. Chiral CE offers an orthogonal enantioselectivity and is typically considered less costly than chromatographic techniques, since only minute amounts of chiral selectors are needed. Several CE approaches have been developed for chiral analysis, including chiral EKC and chiral CEC. Enantioseparations by EKC benefit from the wide variety of possible pseudostationary phases that can be employed. Chiral CEC, on the other hand, combines chromatographic separation principles with the bulk fluid movement of CE, benefitting from reduced band broadening as compared to pressure-driven systems. Although UV detection is conventionally used for these approaches, MS can also be considered. CE-MS represents a promising alternative due to the increased sensitivity and selectivity, enabling the chiral analysis of complex samples. The potential contamination of the MS ion source in EKC-MS can be overcome using partial-filling and counter-migration techniques. However, chiral analysis using monolithic and open-tubular CEC-MS awaits additional method validation and a dedicated commercial interface. Further efforts in chiral CE are expected toward the improvement of existing techniques, the development of novel pseudostationary phases, and establishing the use of chiral ionic liquids, molecular imprinted polymers, and metal-organic frameworks. These developments will certainly foster the adoption of CE(-MS) as a well-established technique in routine chiral analysis.


Impact of point vacancy defects on vibrational behaviour of three-walled carbon nanotubes.
Through experimental observations and reports, various challenges have been identified in carbon nanotubes (CNT), including Stone Wales (SW) flaws and position flaws. Among these imperfections, point vacancies are the most prevalent in the CNT lattice. However, there is currently no established method for detecting these issues, and the influence of these flaws on the vibrational properties of three-walled carbon nanotubes (TWCNTs) remains uncertain. This research paper introduces a novel approach that utilizes vibrational analysis to detect flaws in TWCNTs. By conducting the first investigation into the impact of point vacancies on the vibrational modal frequencies of TWCNTs, our study bridges these knowledge gaps. This study examines the impact of defect quantity on various types of TWCNTs and investigates the vibrational properties of TWCNTs with point vacancies using a molecular structural mechanics technique. A total of 432 TWCNT models were simulated using molecular structural mechanics (MSM), and their modes were identified through finite element (FE) analysis. The fundamental vibration's natural frequency in TWCNTs with defects was then determined. The findings indicate that the depth of the mode shape is influenced by the TWCNTs' diameter, the extent of point vacancy defects, and the boundary condition. It was observed that as the number of vacancy defects increases from 0 to 4%, the natural frequency decreases. The study also establishes the order of TWCNTs with the highest natural vibrational frequency at 0%-point vacancy and [Formula: see text] a given attached mass, which follows the sequence of chiral, armchair, and zigzag TWCNTs.


New Perspectives for Prosthetic Valve Endocarditis: Impact of Molecular Imaging by FISHseq Diagnostics.
The microbial etiology of prosthetic valve infective endocarditis (PVE) can be difficult to identify. Our aim was to investigate the benefit of molecular imaging technique fluorescence in situ hybridization (FISH) combined with 16S rRNA-gene polymerase chain reaction (PCR) and sequencing (FISHseq) for the analysis of infected prosthetic heart valves. We retrospectively evaluated the diagnostic outcome of 113 prosthetic valves from 105 patients with suspected PVE, treated in 2003-2013 in the Department of Cardiac Surgery, Charité University Medicine Berlin. Each prosthetic valve underwent cultural diagnostics and was routinely examined by FISH combined with 16S rRNA gene PCR and sequencing. We compared classical microbiological culture outcomes (blood and valve cultures) with FISHseq results and evaluated the diagnostic impact of the molecular imaging technique. Conventional microbiological diagnostic alone turned out to be insufficient, as 67% of preoperative blood cultures were noninformative (negative, inconclusive, or not obtained) and 67% of valve cultures remained negative. FISHseq improved the conventional cultural diagnostic methods in PVE in 30% of the cases and increased diagnostic accuracy. Of the valve culture-negative PVE cases, FISHseq succeeded in identifying the causative pathogen in 35%. FISHseq improves PVE diagnostics, complementing conventional cultural methods. In addition to species identification, FISH provides information about the severity of PVE and state of the pathogens (eg, stage of biofilm formation, activity, and localization on and within the prosthetic material). As a molecular imaging technique, FISHseq enables the unambiguous discrimination of skin flora as contaminant or infectious agent.


High resolution computed tomography of the vertebrae yields accurate information on trabecular distances if processed by 3D fuzzy segmentation approaches.
The structure of trabecular bone represents an aspect of bone properties that affects vertebral bone strength independently of bone mineral density [M. Kleerekoper, A. Villanueva, J. Stanciu, D. Rao, and A. Parfitt. The role of three-dimensional trabecular microstructure in the pathogenesis of vertebral compression fractures. Calcif. Tissue Int., 37:594-597, Dec 1985; E. Seeman and P. Delmas. Bone quality-the material and structural basis of bone strength and fragility. N. Engl. J. Med., 354:2250-2261, May 2006.]. Using the mathematical concept of fuzzy distance transformation (FDT), we evaluated the accuracy of measurements of trabecular distance (Tb.Di(f)) which can be determined for vertebrae in vivo using high resolution computed tomography (HRCT). In a first step extrema voxels with a very high likelihood of representing bone or marrow are identified. A probability level of being a bone voxel is assigned to all other voxel. This probability is based on the FDT of the voxel's gray-level, preprint submitted to Elsevier June 10, 2008; revised July 15, 2008 i.e. the shortest gray-value weighted distance to the marrow background. Next, the resulting bone structure is skeletonized. The space between the ridges of the skeleton is filled with the largest possible spheres. The average over the radii of the spheres defines Tb.Di(f), a measure of trabecular distance. 14 whole vertebrae embedded in polymethyl methylacrylate were scanned by HRCT (voxel size 156 x 156 x 400 mum(3)) inside an anthropomorphic abdomen phantom. Scans obtained on Scanco Xtreme CT (XCT, voxel size 82(3) microm(3)) without the phantom were used as reference. Tb.Di(f) calculated on XCT data were almost identical to trabecular distance values (1/Tb.N*) determined with the manufacturer's standard software (r(2)=0.98). Tb.Di(f) values obtained with HRCT correlated strongly with Tb.Di(f) values obtained by XCT (r(2)=0.89). Over the range from 400 to 1400 microm trabecular distance could be estimated with a residual error of 78 microm. The FDT based variable Tb.Di(f) provides 3D estimates of trabecular distances with residual errors of less than 100 microm using a HRCT protocol which also can be employed in vivo for assessing vertebral microarchitecture.


Capillary electrophoresis of proteins 1999-2001.
This review article with 223 references describes recent developments in capillary electrophoresis (CE) of proteins and covers papers published during last two years, from the previous review (V. Dolnik, Electrophoresis 1999, 20, 3106-3115) through Spring 2001. It describes the topics related to CE of proteins including modeling of the electrophoretic properties of proteins, sample pretreatment, wall coatings, improving selectivity, detection, special electrophoretic techniques, and applications.


Malignant thymoma. A complicated triad of SVC syndrome, cardiac tamponade, and DIC.
A patient presented with multisystem disease due to a very aggressive malignant thymoma. The case was complicated by the triad of cardiac tamponade, superior vena cava (SVC) syndrome, and disseminated intravascular coagulation (DIC). A review of the English literature reveals this to be a unique constellation of clinical symptoms and that DIC was heretofore unreported.


Cardiac Pacing in Sub-Saharan Africa: JACC International.
Many parts of the developing world, especially Sub-Saharan Africa, completely lack access to cardiac pacing. The authors initiated a multinational program to implement cardiac pacing in 14 countries in Sub-Saharan Africa (1996 to 2018), aiming to eventually build self-sustainable capacity in each country. This was based on an "on-site training" approach of performing procedures locally and educating local health care teams to work within resource-limited settings, with prospective evaluation of the program. In 64 missions, a total of 542 permanent pacemakers were implanted. In 11 of these countries, the first pacemaker implant in the country was through the mission. More than one-half of those initially listed as suitable died before the mission(s) arrived. The proportion of implantations that were completely handled by local teams increased from 3% in 1996 to 98% in 2018. These findings demonstrate the feasibility and effectiveness of a proctorship-based approach to the development of local cardiac pacing capabilities in Sub-Saharan African nations.


Engineering an Escherichia coli platform to synthesize designer biodiesels.
Biodiesels, fatty acid esters (FAEs), can be synthesized by condensation of fatty acid acyl CoAs and alcohols via a wax ester synthase in living cells. Biodiesels have advantageous characteristics over petrodiesels such as biodegradability, a higher flash point, and less emission. Controlling fatty acid and alcohol moieties are critical to produce designer biodiesels with desirable physiochemical properties (e.g., high cetane number, low kinematic viscosity, high oxidative stability, and low cloud point). Here, we developed a flexible framework to engineer Escherichia coli cell factories to synthesize designer biodiesels directly from fermentable sugars. In this framework, we designed each FAE pathway as a biodiesel exchangeable production module consisting of acyl CoA, alcohol, and wax ester synthase submodules. By inserting the FAE modules in an engineered E. coli modular chassis cell, we generated E. coli cell factories to produce targeted biodiesels (e.g., fatty acid ethyl (FAEE) and isobutyl (FAIbE) esters) with tunable and controllable short-chain alcohol moieties. The engineered E. coli chassis carrying the FAIbE production module produced 54mg/L FAIbEs with high specificity, accounting for>90% of the total synthesized FAEs and ∼4.7 fold increase in FAIbE production compared to the wildtype. Fed-batch cultures further improved FAIbE production up to 165mg/L. By mixing ethanol and isobutanol submodules, we demonstrated controllable production of mixed FAEEs and FAIbEs. We envision the developed framework offers a flexible, alternative route to engineer designer biodiesels with tunable and controllable properties using biomass-derived fermentable sugars.


The role of colour Doppler ultrasonography in detecting prostate cancer.
To determine the usefulness of colour Doppler ultrasonography (CDUS) in detecting prostate cancer, by comparing CDUS with grey-scale transrectal ultrasonography (TRUS) and magnetic resonance imaging (MRI). In all, 278 patients who underwent prostate biopsies because of an abnormal digital rectal examination, elevated prostate specific antigen levels, and/or abnormal TRUS between May 1998 and November 1999 were evaluated. The diagnostic accuracies of TRUS, CDUS, MRI and combinations of these imaging techniques in detecting prostate cancer were compared, based on the biopsy results. Carcinoma was detected in 233 of 1696 specimens, and 87 patients were diagnosed with prostate cancer. For each detected cancer site, the sensitivity of CDUS was lower than those of other imaging techniques, but CDUS had high a specificity and positive predictive value. The combination of grey-scale TRUS and CDUS or MRI improved the sensitivity and negative predictive value. The specificity and positive predictive value of the combination of grey-scale TRUS and MRI were less than those for grey-scale TRUS alone, while those for the combination of grey-scale TRUS and CDUS were higher than those for grey-scale TRUS alone. Five tumours were isoechoic but seen as hypervascular lesions with CDUS. CDUS provides information useful for detecting prostate cancer when used in combination with grey-scale TRUS, and should be included in the routine examination for prostate cancer.


EGR1 mediates METTL3/m6A/CHI3L1 to promote osteoclastogenesis in osteoporosis.
To investigate EGR1-mediated METTL3/m6A/CHI3L1 axis in osteoporosis. Ovariectomy (OVX) was performed on mice to induce osteoporosis, followed by μ-CT scanning of femurs, histological staining, immunohistochemistry analysis of MMP9 and NFATc1, and ELISA of serum BGP, ALP, Ca, and CTXI. The isolated mouse bone marrow mononuclear macrophages (BMMs) were differentiated into osteoclasts under cytokine stimulation. TRAP staining was performed to quantify osteoclasts. The levels of Nfatc1, c-Fos, Acp5, and Ctsk in osteoclasts, m6A level, and the relationships among EGR1, METTL3, and CHI3L1 were analyzed. The EGR1/METTL3/CHI3L1 levels and m6A level were upregulated in osteoporotic mice and the derived BMMs. EGR1 was a transcription factor of METTL3. METTL3 promoted the post-transcriptional regulation of CHI3L1 by increasing m6A methylation. EGR1 downregulation reduced BMMs-differentiated osteoclasts and alleviated OVX-induced osteoporosis by regulating the METTL3/m6A/CHI3L1 axis. EGR1 promotes METTL3 transcription and increases m6A-modified CHI3L1 level, thereby stimulating osteoclast differentiation and osteoporosis development.


[What role can the psychologist have in patient education in nephrology? An out-center example].
This article presents the experience of a psychologist in the development of a multidisciplinary and collective Therapeutic Patient Education program for dialysis patients in out-center (self-dialysis). The role of the psychologist is situated at different levels: construction of the program, animation and co-animation of interventions and evaluation of the program.


Formation of Hassall's corpuscles in vitro by the thymic epithelial cell line IT-26R21 of the rat.
In the monolayer of an established epithelial cell line from the rat thymus, IT-26R21, characteristic cell aggregates quite similar to Hassall's corpuscles were formed. These aggregates were examined by light and electron microscopy, and immunohistochemically. Their interpretation as Hassall's corpuscles is based n the following observations: (1) The aggregates are formed in the monolayer of cells that greatly resemble medullary epithelial cells of the thymus. (2) They consist of flattened epithelial cells in a concentric pattern with one or ore degenerating cells in the center. (3) Loss of microvilli suggests that these cells are keratinizing. (4) The aggregates show strongly positive reactions in immunofluorescent staining with antikeratin and antiprekeratin. When Hassall's corpuscles increase in size, cellular proliferation is somewhat suppressed. Both in vivo and in vitro, they may be interpreted as an expression of a changing growth pattern in confined spaces and thus seem to have little immunological function.


Signal recognition particle contains a 7S RNA essential for protein translocation across the endoplasmic reticulum.
In addition to its previously characterized, six different polypeptide components, signal recognition protein--which functions in protein translocation across and integration into the endoplasmic reticulum membrane--contains a 7S RNA molecule. The RNA is closely identified with the small cytoplasmic 7SL RNA and is required for both structural and functional properties of signal recognition protein--which we therefore rename signal recognition particle.


The effect of previous cold storage on the subsequent recovery of infective third stage nematode larvae from sheep faeces.
An investigation undertaken to determine the effect of previous cold storage on the recovery of third stage larvae of gastrointestinal nematodes of sheep, showed that increasing periods of exposure of faeces to 4 degrees C resulted in decreasing numbers of larvae subsequently recovered from them. Differences in the abilities of the eggs of the various genera, to survive such treatment, were found to lead to significant changes in the percentage generic compositions of their third stage larvae--in some cases following the prior refrigeration of faecal samples for as little as 24 h. These results suggest that where larval cultures are intended to provide estimates of the proportions of the various worm eggs in the faeces of sheep harboring mixed gastrointestinal nematode burdens, they should be performed only on freshly collected samples.


Is age a barrier to pancreaticoduodenectomy? An Italian dual-institution study.
The aim of this study is to evaluate the role of age after pancreaticoduodenectomy. This is a retrospective study of 223 patients who underwent pancreaticoduodenectomy for periampullary diseases. Three age groups of patients were compared: ≤70 years of age (group A); between 71 and 79 years of age (group B) and 80 years of age or older (group C). The primary endpoint was the postoperative mortality rate. Secondary endpoints were the overall postoperative morbidity, postoperative pancreatic fistula, postoperative pancreatic haemorrhage, bile leakage, delayed gastric emptying rates, the length of hospital stay, intensive care unit stay, the type of discharge from hospital, reoperation rate and overall survival. Uni-multivariate analyses and Kaplan-Meier curve were carried out. At univariate analysis, only the type of discharge from hospital showed that group B and C patients required a period of rehabilitation more frequently than group A (P = 0.047 and P < 0.001, respectively). Multivariate analysis confirmed that age was not related to postoperative mortality (P = 0.258), morbidity (P = 0.912) and overall survival (P = 0.658), but it was related to type of discharge (P < 0.001). The present study seems to suggest that a pancreaticoduodenectomy is a feasible and safe procedure, even in elderly and very elderly patients even if the latter require a longer period of rehabilitation.


Distribution of three non-essential trace metals (Cadmium, Mercury and Lead) in the organs of fish from Aiba Reservoir, Iwo, Nigeria.
The distribution of non-essential trace elements in some vital organs of 11 fish species from Aiba Reservoir, Iwo, Nigeria was assessed between November 2010 and June 2011. The fish species belong to seven families; family Mormyridae, family Cyprinidae, family Hepsetidae and family Channidae each with one species; family Bagridae and family Clariidae each with two species; and family Cichlidae with three species. All families, except Clariidae and Channidae, are common in the daily catch from the reservoir. Atomic absorption spectrophotometry was used to determine the levels of cadmium, mercury and lead in fish organs. The concentration of toxic trace metals in fish ranged from 0.001 to 0.100 ppm (Cd), 0.000-0.067 ppm (Hg) and 0.001-0.125 ppm (Pb) dry weight. This study shows similarity (p > 0.05) in the distribution of Cd, Hg and Pb among fish species; and a non-uniform distribution of toxic trace metals within fish organs with Kidney > Liver > Gill ≥ Intestine ≥ Muscle. Canonical variate analysis shows clear discrimination of Clarias macromystax and Channa obscura for gill trace metal levels of Cd, Hg and Pb while Labeo senegalensis and Oreochromis niloticus were discriminated for liver trace metal values of Cd and Pb only when compared to other fish species studied. The discrimination of some fish species based on trace metals in the gills and liver suggests different regulatory strategies for trace metal accumulation. Variation due to comparison among different fish species from the same water body suggests that accumulation may be species dependent. Differential accumulation of toxic trace metals in fish organs makes them good bioindicators of freshwater contamination.


Evaluating modulators of "Regulator of G-protein Signaling" (RGS) proteins.
"Regulator of G-protein Signaling" (RGS) proteins constitute a class of intracellular signaling regulators that accelerate GTP hydrolysis by heterotrimeric Gα subunits. In recent years, RGS proteins have emerged as potential drug targets for modulation by small molecules. Described in this unit are high-throughput screening procedures for identifying modulators of RGS protein-mediated GTPase acceleration (GAP activity), for assessment of RGS domain/Gα interactions (most avid in vitro when Gα is bound by aluminum tetrafluoride), and for validation of candidate GAP-modulatory molecules with the single-turnover GTP hydrolysis assay.


Cellular biosensing system for discovery of protein synthesis inhibitors with an electrochemical phosphate modulator to regulate the acid phosphatase gene expression of Saccharomyces cerevisiae.
A cellular biosensing system for screening protein synthesis inhibitors has been developed by linking an electrochemical phosphate modulator and matrix-immobilized yeast cells with an optical sensing device. To screen the protein synthesis inhibitors, yeast phosphatase gene regulating system has been employed by linking an electrochemical phosphate modulator. Since the yeast phosphatase gene coding gammaAPase is expressed, when the phosphate concentration in solution is lowered below the threshold, the gammaAPase production is triggered by lowering the phosphate concentration with the electrochemical phosphate modulator, and monitored continuously with the photometric device. The electrochemical phosphate modulator was assembled with matrix-immobilized yeast cells. The module could insert to ordinal cuvette to monitor the induced gammaAPase activity in an ordinal photometer. Using the system, induction profile of protein synthesis was easily observed and was affected remarkably by various protein synthesis inhibitors. This seems promising that the system can be applied for first screening process of de novo protein inhibitors. The cellular biosensing system seems promising in screening protein synthesis inhibitors.


Like Versus Unlike: Closure of a Moderate-sized Circular Tissue Defect Following Wide Local Excision of Primary Cutaneous Squamous Cell Carcinoma of Face by Rhombic Transposition Flap with Modification.
Closure of a circular tissue defect in the head-neck-face region is challenging because most transposition flaps are rhombic or triangular. For a tension-less closure, both rhombic transposition flap and the circular tissue defect need to be engineered maintaining strict geometric calculations. The present illustration demonstrates a modified rhombic transposition flap with greater freedom in rotation and mobility for closing a moderate-sized circular defect resulting from wide local excision of cutaneous squamous cell carcinoma in the mid-face. The circular shape of the primary tissue defect did not need to be altered. The authors revisited an earlier published technique in the process, adding their own modification to the rhombic transposition flap.


Combined transcranial Direct Current Stimulation and robot-assisted arm training in patients with stroke: a systematic review.
Upper limb motor deficits in patients with severe stroke often remain unresolved over time. Combining transcranial Direct Current Stimulation with robotic therapy is an innovative neurorehabilitation approach that holds promise to improve upper limb impairment after stroke. To investigate the effects of robotic training in combination with transcranial Direct Current Stimulation for treating poststroke upper limb impairment. PubMed, MEDLINE, Cochrane Library, and EMBASE electronic databases were searched using keywords, MeSH terms, and strings: "Stroke"[MeSH] AND ("Upper Extremity"[MeSH] OR "upper limb") AND ("Transcranial Direct Current Stimulation" [MeSH] OR "tDCS") AND ("robotics" OR "robotic therapy"). Full-text articles published in English up to October 2020 were included. Each was rated for quality according to the Physiotherapy Database (PEDro) score: eight out of eleven scored more than 8 points; their results were considered reliable for this review. Of the total of 171 publications retrieved, 11 met the inclusion criteria. The results of studies that examined the same outcome measures were pooled to draw conclusions on the effectiveness of transcranial Direct Current Stimulation and robot-assisted training in corticomotor excitability, upper limb kinematics, muscle strength and tone, function, disability, and quality of life after stroke. To date, there is insufficient evidence to support the hypothesis that transcranial Direct Current Stimulation enhances the effects of robot-assisted arm training in poststroke patients. Further studies with more accurate, comparable and standardized methodology are needed in order to better define the effects of robotic training in combination with transcranial Direct Current Stimulation on poststroke upper limb impairment. Therefore, given the scarce resources available to rehabilitation researches, other, more promising approaches should be given attention.


An evaluation of milk temperature measurement for detecting oestrus in dairy cattle. II. Variations in body and milk temperature associated with oestrus.
Vaginal and milk temperatures were measured at each milking in 15 post-partum Friesian cows showing recurrent oestrous cycles for a total of 33 oestruses. A significant increase (P less than 0.001) in both vaginal and milk temperature of 0.29 +/- 0.05 degrees C was shown between the milking prior to oestrus and the milking when oestrus occurred. Cows were divided into 3 groups: showing either a definite temperature rise (27% of cases), a limited temperature rise (60%) or no temperature change (13%) associated with oestrus. Various methods of analysis were investigated to determine the usefulness of the milk temperature data for oestrus prediction. The optimum compromise of high oestrus detection rate (73.3 +/- 16%) and lowest percentage of false positives (10.8 +/- 3.0%) was based on a temperature rise on the day of oestrus of greater than or equal to 0.2 degrees C over the corresponding mean temperature of the preceding three days. These rates suggest the measurement of milk temperature is less useful for oestrus prediction than some earlier reports have indicated.


Thoracic empyema due to nontuberculous mycobacteria in an immunocompetent patient without pulmonary disease: a case report.
Pleural involvement by non-tuberculous mycobacteria (NTM), especially NTM empyema in the immunocompetent patient without pulmonary diseases is a rare disease. It is difficult to diagnose with only a few cases of immunodeficient patients in the literature. We describe a 63-year-old male with empyema due to NTM and highlight the challenges of diagnosis. Non-tuberculous mycobacterial infection should be considered as a cause of pleuritis or empyema without pulmonary disease, however it is a real diagnostic dilemma.


Effect of Qingyangshen glycosides on social defeat mice model.
Qingyangshen (Cynanchum otophyllum C.K.Schneid.PI.Wilson.) is the folk medicine of Yunnan which is renowned for its use in the management of neuropsychiatric diseases. The isolated glycosides from Qingyangshen have demonstrated relief in the social defeat stress, however, mechanism of action has not yet been elucidated. This study is aimed to elucidate the effect of Qingyangshen glycosides (QYS) on chronic social defeat stress (CSDS)-induced depression-like symptoms and the related mechanism. In mice, CSDS model was developed, and the effect of QYS was evaluated by observing the behavioral performance of these mice exposed to tasks related to depression-like activities. Moreover, microscopic pathological examinutesation was also done. Furthermore, the protein expressions related to social defeat stress were also determined to elucidate the possible underlying mechanism. Our results indicated that QYS treatment reversed the CSDS-induced depressive-like behaviors as measured by the increased sucrose preference, open field activity, and social interactions among mice. The reversal of the morphological changes in the hippocampus of the CSDS mice was also noted. Additionally, QYS treatment also upregulated the silent mating type information regulation 2 homolog 1 (SIRT1), peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), fibronectin III domain containing protein 5 (FNDC5), brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase B (TrkB), and mitogen-activated protein kinase (MAPK) proteins. Our study indicated that QYS had a good anti-social defeat stress effect on CSDS-induced depression in mice, mainly through SIRT1/PGC-1α/FNDC5/BDNF-TrkB signaling pathway activation.


Molecular analysis of a public cross-neutralizing antibody response to SARS-CoV-2.
As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concerns (VOCs) continue to emerge, cross-neutralizing antibody responses become key toward next-generation design of a more universal COVID-19 vaccine. By analyzing published data from the literature, we report here that the combination of germline genes IGHV2-5/IGLV2-14 represents a public antibody response to the receptor-binding domain (RBD) that potently cross-neutralizes a broad range of VOCs, including Omicron and its sub-lineages. Detailed molecular analysis shows that the complementarity-determining region H3 sequences of IGHV2-5/IGLV2-14-encoded RBD antibodies have a preferred length of 11 amino acids and a conserved HxIxxI motif. In addition, these antibodies have a strong allelic preference due to an allelic polymorphism at amino acid residue 54 of IGHV2-5, which is located at the paratope. These findings have important implications for understanding cross-neutralizing antibody responses to SARS-CoV-2 and its heterogenicity at the population level as well as the development of a universal COVID-19 vaccine.


Genome Sequences of Multiresistant Staphylococcus capitis Pulsotype NRCS-A and Methicillin-Susceptible S. capitis Pulsotype NRCS-C.
Here, we report the draft genome sequences of methicillin-susceptible Staphylococcus captis pulsotype NCRS-C (CR02 strain) and multiresistant Staphylococcus captis pulsotype NCRS-A (CR07 strain).


Prediction of Pb speciation in concentrated and dilute nutrient solutions.
Despite the presence of numerous studies in the literature examining the phytotoxicity of Pb, there is a lack of precise quantitative data on limiting concentrations of Pb for plant growth. Using the PhreeqcI chemical equilibrium model, simulations were conducted to examine the speciation of Pb in concentrated and dilute nutrient solutions. Due to the higher P concentration of Hoagland's solution (1000microM), precipitation of chloropyromorphite (Pb5(PO4)3Cl) was predicted to occur at lower pH values, and at lower Pb concentrations, than for a dilute nutrient solution (2microM P). Although nutrient solutions prepared in the glasshouse were supersaturated (and Pb concentrations were substantially higher than predicted by modeling), they confirmed the importance of the P concentration in influencing the precipitation of Pb. Given the low solubility of Pb-phosphates, nutrient solutions with low P concentrations should be utilized, and plant growth should be related to measured Pb concentrations rather than to the quantity of Pb initially added.


[Freezing effects on the in vitro development of mice preantral follicles].
Comparison of in vitro development, survival and oocyte maturation rates of mice preantral follicles frozen by various methods. Cryopreservation of the germinal cells using the slow freezing method for entire ovary (Ova Cong) or isolated preantral follicles (Iso Cong) and vitrification in a closed system of isolated preantral follicles (Iso Vitr). Non-freezing follicles were considered as the control group. The four groups were simultaneous cultured for 12 days in a microdrop system. At each day of the culture, mean diameter was measured and at the end of the culture, follicular survival and mature oocyte rates were compared. Iso Cong and Ova Cong follicles achieved a smaller diameter (423.0 ± 47.1 μm et 450.3 ± 15.7 μm, respectively) than control group (680.7 ± 12.3 μm) at the 12th day of culture. At the end of the culture 6.21 % of Iso Cong follicles, 53.41 % of Ova Cong follicles and 83,77 % of Control follicles were alive. Mature oocyte rates were similar for the cryopreserved groups, 44.4 % for Iso Cong group and 44.7 % for Ova Cong group, but smaller than the Control group with 90 % of mature oocytes. Only 1/171 of the Iso Vitr follicles survived to the culture. This study shows that mice's ovarian follicles can grow in vitro after cryopreservation but their diameter, survival and oocytes maturation rates are smaller than in the control group.


Developmental aspects of experimental myopia in chicks: susceptibility, recovery and relation to emmetropization.
Chicks deprived of form-vision in the lateral part of their visual fields become severely myopic largely because of elongation of the vitreous chamber. The myopia mostly affects the visually deprived nasal retina; the nondeprived temporal retina is unaffected. These changes occur most rapidly early in life, being evident then after only 3 days of visual restriction. The susceptibility declines with age, being proportional to the rate of increase of axial length. Recovery from this myopia occurs if the visual restriction is removed during the first 6 weeks of life, as a result of the cessation of elongation of the vitreous chamber. The rate of recovery is directly related to the degree of myopia and inversely related to age. The pattern of changes in refractive status and variability argue for the probable existence of an active mechanism regulating eye growth in a manner dependent on refractive error, thereby producing emmetropization.


The effects of practice with MP3 players on driving performance.
This study examined the effects of repeated iPod interactions on driver performance to determine if performance decrements decreased with practice. Nineteen younger drivers (mean age=19.4, range 18-22) participated in a seven session study in the University of Calgary Driving Simulator (UCDS). Drivers encountered a number of critical events on the roadways while interacting with an iPod including a pedestrian entering the roadway, a vehicle pullout, and a lead vehicle braking. Measures of hazard response, vehicle control, eye movements, and secondary task performance were analyzed. Increases in perception response time (PRT) and collisions were found while drivers were performing the difficult iPod tasks, which involved finding a specific song within the song titles menu. Over the course of the six experimental sessions, driving performance improved in all conditions. Difficult iPod interactions significantly increased the amount of visual attention directed into the vehicle above that of the baseline condition. With practice, slowed responses to driving hazards while interacting with the iPod declined somewhat, but a decrement still remained relative to the baseline condition. The multivariate results suggest that access to difficult iPod tasks while vehicles are in motion should be curtailed.


Inhibition of immunotoxicity of Pb2+-induced RAW264.7 macrophages by selenium species in selenium-enriched rice.
Previous studies have revealed that Selenium-enriched rice protein hydrolysates (SPHs) could alleviate Pb2+-induced apoptosis in RAW264.7 macrophages. The purpose of the current study was to detect the effect of different selenium (Se) species on immunotoxicity of the Pb2+-induced RAW264.7 macrophages and explore the potential immunomodulatory mechanism. Herein, SPHs, an isolated SPHs fraction (SPHs-2), selenomethionine (SeMet), selenite (SeIV) were used to investigate their inhibitory effect and the impacts on the expression of cytokines and related protein kinases in immunomodulatory pathways. The results showed that, compared with Pb2+-only group, Se-containing components significantly enhanced the cell viability and effectively decrease nitric oxide (NO) content in Pb2+-induced RAW264.7 cells. Furthermore, compared with other Se species, SPHs-2 markedly decreased the secretion levels of pro-inflammatory cytokines TNF-α, NF-κB, IL-1β, MyD88, IL-6 and IL-8. Western blot results demonstrated that SPHs-2 effectively downregulated the expressions of IκB, IKKα, p38, and Erk1/2, and also successfully blocked the phosphorylation of these protein kinases. Our findings suggested that SPHs-2 effectively attenuate inflammatory response and inhibit the immunotoxicity of Pb2+ on RAW264.7 macrophages via regulating NF-κB/MAPK signaling pathways.


Association of variants in estrogen-related pathway genes with prostate cancer risk.
Through mediation of estrogen receptors, estradiol has been shown to have both carcinogenic and anti-carcinogenic effects on the prostate. We performed a population-based case-control study to investigate variants in estrogen-related genes ESR1, ESR2, CYP19A1, CYP1A1, and CYP1B1 and the potential association with risk of prostate cancer (PCa). We evaluated PCa risk conferred by 73 single nucleotide polymorphisms in 1,304 incident PCa cases and 1,266 age-matched controls. Analysis included stratification by clinical features and assessment of environmental modifiers. There was evidence of altered risk of developing PCa for variants in ESR1, CYP1A1, and CYP1B1, however, only CYP1B1 rs1056836 retained significance after adjustment for multiple comparisons. An association with risk for more aggressive PCa was observed for variants in ESR1, ESR2, and CYP19A1, but none was significant after adjustment for multiple comparisons. There was no effect modification by obesity. Germline genetic variation of these estrogen pathway genes may contribute to risk of PCa. Additional studies to validate these results and examine the functional consequence of validated variants are warranted.


Organizational Change Strategies to Support High-Quality Behavioral Health Care for LGBTQ Individuals.
There is growing recognition of the need to provide high quality behavioral health care for Lesbian, Gay, Bisexual, Transgender, and Queer/Questioning (LGBTQ) individuals. Research suggests that the LGBTQ community experiences high levels of psychological distress, psychological trauma, and other mental health symptoms as a result of minority stress. Despite these findings, the LGBTQ community continues to face barriers when seeking affirming behavioral health treatment. Using an established framework, this commentary highlights one behavioral health managed care organization's (BHMCO) work towards organizational change in the hopes of creating an affirming and inclusive environment for individuals influenced by the BHMCO (e.g., staff, members, behavioral health providers). In this commentary, we: (1) discuss the importance and role of insurers in promoting strategies to increase and deliver high quality care for LBGTQ individuals, (2) outline the steps our organization took to implement changes, (3) highlight the lessons learned throughout this process, and (4) provide recommendations for future efforts.


Poly(epsilon-caprolactone) nanocomposite scaffolds for tissue engineering: a brief overview.
Polycaprolactone is a bioresorbable polymer that has been extensively used in the biomaterials field and a number of drug-delivery systems. The superior rheological and viscoelastic properties of this polymer render it easy to manufacture and manipulate into a large range of medical devices and implants. The advantage of polycaprolactone over its aliphatic counterparts is that it has a long-term degradation period, which provides a good platform for the design and fabrication of implants that require long-term degradation kinetics for example in bone tissue engineering. The incorporation of nanofillers or blending of polycaprolactone with other polymers has yielded a class of hybrid materials with significantly improved physical and chemical properties such as strength, porosity, microstructure, controllable degradation rates, and bioactivity that are important for tissue engineering. This overview highlights the interesting advancements in polycaprolactone polymeric systems that relate to biological and tissue engineering applications, including aspects of technology in fabricating the scaffolds.


Phosphorus and Silicon-Based Macromolecules as Degradable Biomedical Polymers.
Synthetic polymers are indispensable in biomedical applications because they can be fabricated with consistent and reproducible properties, facile scalability, and customizable functionality to perform diverse tasks. However, currently available synthetic polymers have limitations, most notably when timely biodegradation is required. Despite there being, in principle, an entire periodic table to choose from, with the obvious exception of silicones, nearly all known synthetic polymers are combinations of carbon, nitrogen, and oxygen in the main chain. Expanding this to main-group heteroatoms can open the way to novel material properties. Herein the authors report on research to incorporate the chemically versatile and abundant silicon and phosphorus into polymers to induce cleavability into the polymer main chain. Less stable polymers, which degrade in a timely manner in mild biological environments, have considerable potential in biomedical applications. Herein the basic chemistry behind these materials is described and some recent studies into their medical applications are highlighted.


Predicting global and topic-specific certainty beliefs: domain-specificity and the role of the academic environment.
Epistemological beliefs are subjective theories of the structure and acquisition of knowledge. The instruments used to measure epistemological beliefs in educational psychology (see Duell & Schommer-Aikins, 2001) typically consist of questionnaires tapping general, decontextualized beliefs about knowledge or knowledge acquisition in a specific field or in general. Using specific theories as stimuli, we determine the degree of topic-specificity of certainty beliefs as well as the association between certainty beliefs and the learning environment. Participants were 662 upper secondary school students (Study 1) and 211 college students (Study 2). A global instrument and a topic-specific instrument were used to collect responses to up to 10 stimulus theories. Factor analysis, multiple regression analysis and multi-level modelling were carried out. Students' topic-specific certainty beliefs varied markedly across the stimulus theories. Furthermore, students in different academic environments differed more strongly on global certainty beliefs than on topic-specific certainty beliefs, and global certainty beliefs were only loosely connected to topic-specific certainty beliefs. Researchers should critically assess the validity of decontextualized global questionnaires for assessing certainty beliefs. If possible, global measures should be complemented by topic-specific measures.


The quantitative analysis of polymorphism on human chromosomes 1, 9, 16, and Y. III. Study of relationships of C segments' lengths in individual karyotypes.
The correlation relationship of the lengths of C segments on chromosomes 1, 9, 16, and Y was studied in a group of normal boys and girls (50 boys and 50 girls). No correlation was found between the C segment lengths, either on homologs or on chromosomes of various pairs. This confirms the idea of random combinations of the said chromosomes with C segments of different lengths in an individual karyotype.


Aryl hydrocarbon receptor (AHR): Towards understanding intestinal microbial ligands including vitamin B12 and folic acid as natural antagonists.
AHR has been identified as ligand-modulated transcription factor and environmental sensor. However, explanation of its multiple agonistic and antagonistic ligands is far from complete. Studies of AHR's role in host-microbiome interaction are currently a fruitful area of research. Microbial products and virulence factors have been identified as AHR agonists. In steady state they are involved in safeguarding intestinal barrier integrity. When virulence factors from pathogenic bacteria are identified by AHR of intestinal immune cells, anti-microbial defense mechanisms are activated by generating reactive oxygen species (ROS) in intestinal epithelial cells and recruited immune cells. ROS production has to be strictly controlled, and anti-inflammatory responses have to be initiated timely in the resolution phase of inflammation to avoid tissue damage and chronic inflammatory responses. Surprisingly, bacteria-generated vitamin B12/cobalamin and vitamin B9/folic acid have been identified as natural AHR antagonists, stimulating the interest of biochemists. Hints for AHR-cobalamin antagonism are pointing to cobalamin-dependent enzymes leading to alterations of TCA cycle intermediates, and TCDD-mediated loss of serum cobalamin. Although we are still at the beginning to understand mechanisms, it is likely that scientific efforts are on a rewarding path to understand novel AHR functions.


Seasonal reversal of competitive advantage between two spider species.
To test for inter- and intraspecific competition between two common orb-weaving spiders, Metepeira grinnelli and Cyclosa turbinata, I conducted separate field experiments in the spring and summer. During the spring experiment, the prey-consumption rate of Metepeira was reduced at higher inter- and intraspecific densities, but Cyclosa was only affected by intraspecific density. During the summer experiment, Metepeira prey-consumption was not affected by inter- or intraspecific densities, while Cyclosa was affected by both inter- and intraspecific densities. In addition to competition for food, during the spring experiment Cyclosa was observed displacing Metepeira but not vice versa, whereas during the summer experiment Metepeira displaced Cyclosa but not vice versa. The seasonal reversal in the competitive advantage between the species was linked to their asynchronous phenologies; in the spring most Cyclosa were larger than Metepeira, whereas in the summer most Metepeira were larger than Cyclosa. I suggest that in this system, temporal variability in the competitive abilities may promote species coexistence.


Stability-based biomarker selection.
Biomarker identification, i.e., finding those variables that indicate true differences between two or more populations, is an ever more important topic in the omics sciences. In most cases, the number of variables far exceeds the number of samples, making biomarker identification extremely difficult. We present a strategy based on the stability of putative biomarkers under perturbation of the data, and show that in several cases important gains can be achieved. The strategy is very general and can be applied with all common biomarker identification methods; it also has the advantage that it does not rely on error estimates from crossvalidation, that in this setting tend to be highly variable.


Synchronous conjugation of i-motif DNA and therapeutic siRNA on the vertexes of tetrahedral DNA nanocages for efficient gene silence.
The functionality of DNA biomacromolecules has been widely excavated, as therapeutic drugs, carriers, and functionalized modification derivatives. In this study, we developed a series of DNA tetrahedron nanocages (Td), via synchronous conjugating different numbers of i-(X) and therapeutic siRNA on four vertexes of tetrahedral DNA nanocage (aX-Td@bsiRNA, a+b = 4). This i-motif-conjugated Td exhibited good endosomal escape behaviours in A549 tumor cells, and the escape efficiency was affected by the number of i-motif. Furthermore, the downregulating mRNA and protein expression level of epidermal growth factor receptor (EGFR) caused by this siRNA embedded Td were verified in A549 cells. The tumor growth inhibition efficiency of the 2X-Td@2siRNA treated group in tumor-bearing mice was significantly higher than that of non-i-motif-conjugated Td@2siRNA (3.14-fold) and free siRNA (3.63-fold). These results demonstrate a general strategy for endowing DNA nanostructures with endosomal escape behaviours to achieve effective in vivo gene delivery and therapy.


Search for the origin of multiple sclerosis by first identifying the vector.
By intensive study of environmental conditions during the final stages in an active cluster area, an attempt is made to crack the enigmatic deadlock concerning the origin and etiological cause of Multiple Sclerosis (MS). Previous investigations of other cluster areas have emphasized the probability that the outbreaks of MS were most likely caused by an unknown exogenous environmental agent, but unfortunately, the studies were conducted several years after the epidemics had occurred, making it virtually impossible to observe changing environmental conditions. This study attempts to overcome such defects, and in the process identifies not only the probable exogenous viral agent(s), but the here-to-fore unknown avian vectors as well.


Photodegradation of metoprolol in the presence of aquatic fulvic acids. Kinetic studies, degradation pathways and role of singlet oxygen, OH radicals and fulvic acids triplet states.
Metoprolol is a pharmaceutical used for the treatment of cardiovascular diseases and disorders, whose frequent detection in surface waters raises concern. Indirect photodegradation is an important degradation pathway in waters and dissolved organic matter has a major role as photosensitizer. In this study, metoprolol photodegradation, in the absence and in the presence of fulvic acids extracted from the Vouga River (Portugal) (VRFA), was assessed under simulated sunlight. While metoprolol direct photodegradation was deniable, indirect photolysis occurred under the presence of VRFA. It followed a pseudo-first order kinetics and after 72 h of irradiation there was a decrease of metoprolol concentration of ∼80 %. The OH radical (OH) was verified to be the main reactive species (RS) responsible for the photosensitized degradation of metoprolol, but other RS are also involved, probably triplet excited states of FA (3FA*) and singlet oxygen (1O2), as demonstrated by the higher inhibition of the photodegradation in presence of sodium azide than in presence of 2-propanol. Based on a previous identification of photoproducts, tentative degradation mechanisms were here proposed. Photoproducts analysis after 24 h irradiation in the absence and presence of scavengers, shown that different RS are involved in the formation of different products/intermediates.


A review of 79 cases of eclampsia at University Teaching Hospital, Lusaka.
Seventy-nine cases of eclampsia (incidence 0.22%) are reviewed. The corrected maternal and perinatal mortality rates were 12.6% and 28.3%. Maternal and perinatal mortality were directly related to number of fits, severity of eclampsia, delay in onset of treatment, and duration of labour. Whereas the maternal mortality was 23 per cent in patients delivered vaginally and 8.6 per cent in patients delivered by caesarean section, the perinatal mortality was almost the same in both types of delivery.


Nursing grand rounds: promoting excellence in nursing.
Nursing grand rounds (NGR) provide staff nurses a forum to share clinical expertise and the best of nursing practice at their institutions in a setting that recognizes their unique contributions to the nursing profession. This article will describe how NGR were developed, facilitated, and implemented by the Department of Nursing Practice, Education, and Research at an academic healthcare facility.


The effects of antihistamine on the duration of the febrile seizure: A single center study with a systematic review and meta-analysis.
Several studies have investigated the potential effects of antihistamines on febrile seizure. However, these findings are inconsistent across the studies. A retrospective observational study was conducted on a total of 434 consecutive patients aged between 6 months and 5 years with the diagnosis of febrile seizure. Patients with chronic medical conditions were excluded. Multivariable generalized linear models were conducted to ascertain the effects of antihistamine use on duration of febrile seizure. Also, we conducted a systematic review and meta-analyses of the medical literatures to calculate the pooled estimates using random effects models. The adjusted mean duration of febrile seizure in the antihistamine group was 4.9 min shorter than that in the non-user group (95% confidence interval (CI), 0.4-9.5). The risk of duration in febrile seizure >5 min among antihistamine users was also 0.83 times that among the non-users (95%CI, 0.58-1.19), whereas the risk of duration in febrile seizure >10 min among first-generation antihistamine users was 1.21 times that among non-users (95%CI, 0.69-2.13). According to the systematic review of the literature, 8 observational studies were included in the meta-analyses. Comparing to non-users, the antihistamine users had prolonged duration of febrile seizure by 1.07 min (95%CI, -1.13 to 3.27), elevated risk of duration in febrile seizure >5 min (Risk ratio, 1.16; 95%CI, 0.90-1.49), and similar duration from fever to febrile seizure onset (pooled mean difference, -0.01 h; -1.43 to 1.41), but these estimates were imprecise. Similar results were obtained when we stratified the data by types of antihistamine (first vs. second generation). Our study may indicate the effects of antihistamine on prolonging febrile seizure duration, but they are still controversial given the limited evidence, highly heterogeneous results, and concerns of the internal and external validities.


Vitamin D deficiency and associated factors in south Korean childbearing women: a cross-sectional study.
Adequate levels of vitamin D are important for women of childbearing age as vitamin D helps maintain the pregnancy and ensures proper maternal and fetal bone metabolism and fetal skeletal development. However, vitamin D deficiency is a health problem prevalent in women of all ages, worldwide. This study aimed to determine the current status of serum vitamin D levels and the risk factors for vitamin D deficiency among South Korean nurses of childbearing age. Serum levels of 25-hydroxyvitamin D (25[OH]D) were measured in 1594 registered nurses aged 20 to 45 years who are participants in an ongoing prospective cohort study of the Korean Nurses' Health Study initiated in 2013. The participants completed surveys about demographic and occupational characteristics and physical and psychological health. We examined associations with vitamin D deficiency through multivariable logistic regression analysis. The average blood 25(OH) D concentration of the participants was 12.92 ng/mL (4.0-63.4 ng/mL), while the prevalence of vitamin D deficiency (< 20 ng/mL) was 89% (1419/1594). Multivariable logistic regression showed that significant risk factors for vitamin D deficiency included month of sampling (there was a lower level of vitamin D deficiency in winter than in spring, summer, or fall), age (women in their 20s had a lower vitamin D level than those in their 30s and 40s), and stress symptoms. Vitamin D levels were not associated with body mass index, physical activity, and depressive symptoms. This study showed a high prevalence of vitamin D deficiency in Korean female nurses. Serum levels of vitamin D were associated with age and season. Vitamin D deficiency should be recognized as one of the primary health concerns among young women. More proactive actions, such as vitamin D supplements and food fortification, are needed to improve vitamin D deficiency in high-risk groups.


Composition dependence of vesicle morphology and mixing properties in a bacterial model membrane system.
We have determined the mixing properties and lamellar organization of bacterial membrane mimetics composed of 1-palmitoyl-2-oleoyl-phosphatidylethanolamine (POPE) and -phosphatidylglycerol (POPG) at various molar ratios applying differential scanning calorimetry, small and wide-angle X-ray scattering, as well as optical phase contrast microscopy. Combining the experimental thermodynamic data with a simulation of the liquidus and solidus lines, we were able to construct a phase diagram. Using this approach, we find that the lipids mix in all phases non-ideally in the thermodynamic sense. As expected, pure POPE assembles into multilamellar and pure POPG into unilamellar vesicles, respectively, which are stable within the studied temperature range. In contrast, mixtures of the two components form oligolamellar vesicles consisting of about three to five bilayers. The layers within these oligolamellar liposomes are positionally correlated within the gel phase, but become uncorrelated within the fluid phase exhibiting freely fluctuating bilayers, while the vesicles as a whole remain intact and do not break up into unilamellar forms. X-ray, as well as DSC data, respectively, reveal a miscibility gap due to a lateral phase segregation at POPG concentrations above about 70 mol%, similar to previously reported data on mixtures composed of disaturated PEs and PGs. Hence, the existence of a region of immiscibility is a general feature of PE/PG mixtures and the mixing properties are dominated by PE/PG headgroup interactions, but are largely independent of the composition of the hydrocarbon chains. This is in accordance with a recent theoretical prediction.