Tissue perfusion pressure enables continuous hemodynamic evaluation and risk prediction in the intensive care unit.
Treatment of circulatory shock in critically ill patients requires management of blood pressure using invasive monitoring, but uncertainty remains as to optimal individual blood pressure targets. Critical closing pressure, which refers to the arterial pressure when blood flow stops, can provide a fundamental measure of vascular tone in response to disease and therapy, but it has not previously been possible to measure this parameter routinely in clinical care. Here we describe a method to continuously measure critical closing pressure in the systemic circulation using readily available blood pressure monitors and then show that tissue perfusion pressure (TPP), defined as the difference between mean arterial pressure and critical closing pressure, provides unique information compared to other hemodynamic parameters. Using analyses of 5,988 admissions to a modern cardiac intensive care unit, and externally validated with 864 admissions to another institution, we show that TPP can predict the risk of mortality, length of hospital stay and peak blood lactate levels. These results indicate that TPP may provide an additional target for blood pressure optimization in patients with circulatory shock.


Carbon-13 and proton magnetic resonance of mouse muscle.
It is shown that roughly 4 mmol carbon atoms/g mouse muscle can give rise to a "high resolution" 13C NMR spectrum. From the 13C spectrum, it is estimated that the protons from mobile organic molecules or molecular segments amount to 6-8%of total nonrigid protons (organic plus water) in muscle. Their spin-spin relaxation times (T2) are of the order of 0.4-2 ms. At 37 degrees C, the proton spin-echo decay of mouse muscle changes rapidly with time after death, while that of mouse brain does not.


High systemic immune-inflammation index is a predictor of poor prognosis in patients with nonsmall cell lung cancer and bone metastasis.
This study aimed to evaluate whether systemic immune inflammation (SII) is correlated with overall survival (OS) in patients with nonsmall cell lung cancer (NSCLC) and bone metastasis. This was a retrospective analysis of the value of pretreatment SII in patients with NSCLC and bone metastasis. Two hundred and thirty-four patients with pathologically confirmed NSCLC and bone metastasis treated at Harbin between January 2008 and May 2010 were included. Baseline clinical characteristics and pretreatment SII were collected for further analysis. Receiver operating characteristic curve analysis was used to calculate the optimal cutoff value for SII. Survival analysis was performed using the Kaplan-Meier method. Factors associated with OS were identified by univariate and multivariate analyses. The optimal cutoff value for pretreatment SII was 618.3 × 109/L. Pretreatment SII ≥618.3 × 109/L was more commonly seen in patients with a greater number of distant metastases (<2 vs. ≥2, 56.4% vs. 70.0%, P = 0.033). Univariate analysis showed that sex, tumor histology, Eastern Cooperative Oncology Group-Performance Status (ECOG-PS) score, pretreatment SII, and systemic chemotherapy were associated with OS (P < 0.05). Multivariate analysis showed that sex (hazard ratio [HR] = 1.349, 95% confidence interval [CI] = 1.029-1.708, P = 0.030), ECOG-PS (HR = 1.674, 95% CI = 1.256-2.232, P < 0.001), SII (HR = 1.456, 95% CI = 1.100-1.927, P = 0.009), and systemic chemotherapy (HR = 0.596, 95% CI = 0.437-0.813, P = 0.001) were independent prognostic factors. Subgroup analyses found that SII was prognostic for patients with the following characteristics: age <65 years (P = 0.002), female (P = 0.021), nonsmoker (P = 0.010), histology of adenocarcinoma (P = 0.022), ECOG-PS <2 (P = 0.013), two or more distant metastases (P = 0.004), and two or more bone metastases (P = 0.009). Pretreatment SII may be a prognostic biomarker for NSCLC and bone metastasis.


Kinetics of cell spreading on protein precoated substrata: a study of interfacial aspects.
In this paper, interfacial aspects of spreading and adhesion of human skin fibroblasts on solid substrata after protein precoating have been studied. Three solid substrata were used with different surface free energy (gamma s): Tissue Culture Polystyrene (TCPS) with gamma s = 70 erg.cm-2, Polyvinylfluoride (PVF) with gamma s = 56 erg.cm-2 and Fluoroethylenepropylene (FEP) copolymer with gamma s = 18 erg.cm-2. The substrata were precoated with fetal calf serum, bovine fibronectin or bovine serum albumin. Cell spreading was evaluated by means of light microscopy and scanning electron microscopy (SEM). Adhesion sites were studied by transmission electron microscopy (TEM). In general, spreading was lowest on FEP and highest on TCPS. Although protein precoating markedly increased cell spreading, the relative order in which the cells spread on the protein precoated substrata remained identical to that on the bare substrata. Analysis of the kinetics of spreading demonstrated that spreading was fastest on the high-energy substratum and slowest on the low-energy substratum. In the presence of all three types of protein precoating, the average distance between a cell and a substratum after spreading was smaller (20-50 nm) than without a coating (greater than 100 nm).


Effect of probucol on serum lipids, atherosclerosis and toxicology in fat-fed LDL receptor deficient mice.
Although numerous transgenic mouse models for atherosclerosis have been developed recently, little is known about their response to hypolipidaemic or anti-atherosclerotic agents. We investigated the effect of the known hypocholesterolaemic and anti-atherosclerotic drug probucol on serum lipids, lipoproteins and atherosclerosis in fat-fed low density lipoprotein (LDL) receptor deficient mice. Probucol at doses of 0.2 and 1% in the diet which are similar to those used in the mouse by other investigators reduced serum cholesterol by 26 and 37%, respectively. Probucol also reduced serum triglyceride levels by 33 and 47% at doses of 0.2 and 1%, respectively. The decrease in serum cholesterol and triglycerides was mainly due to a decrease of these lipids in VLDL and or chylomicrons. Despite these potentially beneficial changes in serum lipids atherosclerotic lesion areas in the aortic root were unchanged in the probucol treated mice. After 12 weeks treatment most of the mice receiving probucol had swollen feet and tails due to oedema. Histological examination of the base of the hearts from the probucol treated mice revealed lipid droplets within the reticuloendothelial and other interstitial cells. There was also an interstitial subacute inflammatory cell infiltration associated with the lipid deposition. The oedema induced by probucol could be the result of cardiac insufficiency due to interstitial lipidosis and inflammation in the base of the heart together with the extensive atherosclerotic lesions in the aortic sinus.


Anti-immunoglobulin antibodies. VI. Age-dependent isotype and auto anti-immunoglobulin variation during secondary immune response in 129 mice.
The secondary and tertiary immune responses to TNP-KLH and the autoanti-immunoglobulin response were studied in 1-, 3- and 6-month-old 129/J and 129/Sv mice. A profound inability of aging 129/Sv mice (lifespan: 9 months) to produce gamma 2a anti-TNP antibodies relative to their normal counterparts was observed. However, this markedly low response could not be related to clearance of antibody by RFs since all 129 mice studied produced significant amounts of RFs after immunization with this T-dependent antigen. Furthermore, the results of the plaque forming cell assays indicated that young (1 month old) 129/Sv mice have an accelerated immune response while older mice produce significantly low direct and indirect responses compared to the control groups. The data suggest a fundamental dysfunction of B and/or T cells in 129/Sv mice and that spontaneous production of RFs in older mice may affect the ability of B and T cells to cooperate in a secondary response.


Author Correction: Faithful animal modelling of human glioma by using primary initiating cells and its implications for radiosensitization therapy.
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.


Preferential nuclear location of a transgene does not depend on its transcriptional activity during early mouse development.
Changes in chromatin structure play an important role in regulation of the HSP70.1 gene during mouse preimplantation development. Using in situ PCR we have now examined whether the spatial organization of an HSP70.1 luciferase transgene within the nucleus is also a factor in regulating its expression. The transgene showed a preferential localization towards the nuclear periphery throughout preimplantation development. This preferential location was independent of the level of constitutive activity of the transgene and did not change when transgene expression was induced through core histone hyperacetylation at the eight-cell stage or by heat shock in blastocysts. In contrast, at the two-cell stage, when embryos are unable to continue development after heat shock, thermal stress provoked a significant disruption of the nuclear location of the transgene. These results do not agree with a recent model of embryonic genome activation in mice which hypothesizes that directed, active movement of DNA within the nucleus is a determinant factor in establishing early patterns of gene expression. Instead, they are consistent with models proposing that chromatin segments are restricted to nuclear subregions, but that they remain free to undergo substantial Brownian motion.


Effectiveness of recombinant human follicle-stimulating hormone (r-hFSH): recombinant human luteinizing hormone versus r-hFSH alone in assisted reproductive technology treatment cycles among women aged 35-40 years: A German database study.
This non-interventional study compared the effectiveness of recombinant human follicle-stimulating hormone (r-hFSH) and recombinant human luteinizing hormone (r-hLH) (2:1 ratio) versus r-hFSH alone for ovarian stimulation (OS) during assisted reproductive technology treatment in women aged 35-40 years, using real-world data from the Deutsches IVF-Register (D·I·R). Numerically higher clinical pregnancy (29.8% [95% CI 28.2, 31.6] vs. 27.8% [26.5, 29.2]) and live birth (20.3% [18.7, 21.8] vs. 18.0% [16.6, 19.4]) rates were observed with r-hFSH:r-hLH versus r-hFSH alone. The treatment effect was consistently higher for r-hFSH:r-hLH compared with r-hFSH alone in terms of clinical pregnancy (relative risk [RR] 1.16 [1.05, 1.26]) and live birth (RR 1.16 [1.02, 1.31]) in a post-hoc analysis of women with 5-14 oocytes retrieved (used as a surrogate for normal ovarian reserve), highlighting the potential benefits of r-hFSH:r-hLH for OS in women aged 35-40 years with normal ovarian reserve.


Middle ear adenoma diagnosed by recurrent facial paralysis.
Middle ear adenoma is a rare disease derived from the middle ear mucosa. It is usually lack specific findings and easily mistaken for other conditions, delaying a correct diagnosis. In particular, few cases with facial nerve paralysis have been reported. We describe a case of middle ear adenoma that caused hearing loss and recurrent facial paralysis in a 29-year-old woman. In an attempt to treat the facial nerve paralysis, we performed tympanomastoidectomy and facial nerve decompression. By pathological examination, we finally diagnosed it middle ear adenoma with neuroendocrine differentiation. Retrospectively, if we meet the antibiotic resistant mass in the middle ear, we should suspect the tumor. One year after surgery, the adenoma has not recurred but long-term observation is required.


Evaluation of bronchoscopic lung volume reduction coil treatment results in patients with severe emphysema.
Bronchoscopic lung volume reduction coil (BLVR-C) implantation is an alternative therapeutic approach that can be applied together with medical treatment for patients with severe emphysema. BLVR-C is both easier and safer in terms of complications than volume reduction surgery. This study aimed to evaluate medium-term outcomes following BLVR-C treatment. Forty patients who underwent BLVR-C between September 2013 and March 2014 were reviewed retrospectively. We compared changes between the baseline and 6-month post-procedural results with respect to pulmonary function tests, a 6-min walk test (6MWT), chronic obstructive pulmonary disease (COPD) assessment test (CAT), St. George's Respiratory Questionnaire (SGRQ), and pulmonary artery pressure (PAP) and arterial blood gas analyses. Secondary outcomes included procedure-related and follow-up complications. An average of 9.5 (range: 5-11) coils were placed per lung in an average procedural duration of 20.8 ± 7.0 min (range: 9-45) min. Six months after BLVR-C treatment, significant improvements were observed in patients' pulmonary function tests and quality of life. Changes were observed in the forced exhalation volume in 1 s (+150 mL), residual volume (-14.5%), 6MWT (+48 m), SGRQ (-10.5) and CAT Score (-7.5). Changes in the PAP and partial pressure of carbon dioxide values were not significant, and pneumothorax did not occur. In a 6-month follow-up, 11 cases of COPD exacerbation (41.4%), 7 cases of pneumonia (16.9%) and 1 death (2%) occurred. Treatment in 1 case was postponed because of hypotension and bradycardia during the process. BLVR-C treatment appears to be effective over the medium-term and safe for patients with severe emphysema.


Management of Thyroid Nodular Disease: Current Cytopathology Classifications and Genetic Testing.
Preoperative diagnosis and operative planning for patients with thyroid nodules has improved over the last decade. The Bethesda criteria for cytopathologic classification of thyroid nodule aspirate has enhanced communication between pathologists and clinicians. Multiple genetic tests, including molecular markers and the Afirma gene expression classifier, have been developed and validated. The tests, along with clinical and radiologic information, are most useful in the setting of indeterminate cytology. The development of an updated diagnostic and treatment algorithm incorporating all available tests will help standardize the management of patients with nodular thyroid disease and reduce variation and inefficiencies in care.


Overlapping gaze shifts reveal timing of an eye-head gate.
The ability to dissociate eye movements from head movements is essential to animals with foveas and fovea-like retinal specializations, as these species shift the eyes constantly, and moving the head with each gaze shift would be impractical and energetically wasteful. The processes by which the dissociation is effected remain unclear. We hypothesized that the dissociation is accomplished by means of a neural gate, which prevents a common gaze-shift command from reaching the neck circuitry when eye-only saccades are desired. We further hypothesized that such a gate would require a finite period to reset following opening to allow a combined eye-head saccade, and thus the probability of generating a head movement during a saccade would be augmented when a new visual target (the 'test' target) appeared during, or soon after, a combined eye-head saccade made to an earlier, 'conditioning' target. We tested human subjects using three different combinations of targets-a horizontal conditioning target followed by a horizontal test target (H/H condition), horizontal conditioning followed by vertical test (H/V), and vertical conditioning followed by horizontal test (V/H). We varied the delay between the onset of the conditioning head movement and the presentation of the test target, and determined the probability of generating a head movement to the test target as a function of target delay. As predicted, head movement probability was elevated significantly at the shortest target delays and declined thereafter. The half-life of the increase in probability averaged 740, 490, and 320 ms for the H/H, H/V, and V/H conditions, respectively. For the H/H condition, the augmentation appeared to outlast the duration of the conditioning head movement. Because the augmentation could outlast the conditioning head movement and did not depend on the head movements to the conditioning and test targets lying in the same directions, we could largely exclude the possibility that the augmentation arises from mechanical effects. These results support the existence of the hypothetical eye-head gate, and suggest ways that its constituent neurons might be identified using neurophysiological methods.


A case of neurofibrosarcoma associated with neurofibromatosis: light microscopic, ultrastructural, immunohistochemical and biochemical investigations.
A case of neurofibrosarcoma (NFS) with neurofibromatosis was studied by light microscopic, ultrastructural, immunohistochemical and biochemical methods. Histologically, spindle-shaped tumor cells with atypical hyperchromatic nuclei were arranged in a fascicular or sheet-like fashion. Electron microscopic examination revealed discontinuous basement membrane-like structures. Immunohistochemical study revealed S100 protein alpha chains in tumor cells. A biochemical analysis showed large amounts of gangliosides (sialic acid 13.5 micrograms/g wet tissue weight) in tumors. GM3 and GD3 were the major components; these results were compatible with the NFS ganglioside patterns found in our previous study. Results confirmed the diagnosis of NFS and indicate that NFS clearly has some neuroectodermal characteristics and that Schwann cells may possibly be related to its origin.


A label-free, G-quadruplex DNAzyme-based fluorescent probe for signal-amplified DNA detection and turn-on assay of endonuclease.
A novel G-quadruplex DNAzyme molecular beacon (G-DNAzymeMB) strategy is developed for assays of target DNA and restriction endonuclease. The detection system consists of G-DNAzymeMB strand and a blocker DNA by using the fluorescence of 2',7'-dichlorodihydrofluorescein diacetate (H(2)DCFDA) catalyzed by G-DNAzymeMB as a signal reporter. G-DNAzymeMB exhibits peroxidase activity in its free hairpin structure, and forms a catalytically inactive hybrid when hybridized with blocker DNA. Upon displacement of blocker DNA by target DNA or cleavage by restriction endonuclease, G-DNAzymeMB is released and two lateral portions of G-DNAzymeMB form a G-quadruplex structure, resulting in the recovery of catalytic activity which acts as a cofactor to catalyze H(2)O(2)-mediated oxidation of H(2)DCFDA. For DNA detection system, exonuclease III (Exo III)-catalyzed amplification strategy is introduced to improve the sensitivity and target DNA could be detected as low as 0.1 pM. With respect to restriction endonuclease detection system, 0.1 U/mL EcoRI endonuclease could be detected and this method could be easily transported to other restriction endonuclease analysis by simply changing the recognition sequence. These results demonstrate that the proposed G-DNAzymeMB strategy could be used as a label-free, simple, sensitive and cost-effective approach in analysis of target DNA and restriction endonuclease.


Problems faced by homeless men in obtaining health care.
The vast majority of homeless people in the UK are male. In addition to becoming susceptible to many illnesses and to alcohol abuse, homeless men face a number of problems in accessing health care. A transformation of the health services is required to meet the needs of this vulnerable group.


Effect of dietary fat on diethylnitrosamine induced hepatocarcinogenesis in Wistar rats.
In a diethylnitrosamine (DEN) induced hepatoma model, the effect of fish oil, a rich source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and ground nut oil, a rich source of oleic acid (OA) and linoleic acid (LA), was studied. Both 20% fish oil and ground nut oil inhibited DEN-induced hepatocarcinogenesis in rats. Contrary to general belief, an inverse correlation was observed between the development of neoplastic nodules and the amount of lipid peroxides formed in the high fat (20% fish oil and ground nut oil) diet groups, indicating that the higher the lipid peroxides formed, the lower the incidence of liver tumours in DEN-treated animals. Results of the analysis of liver fatty acid composition of the phospholipid fraction suggested that DEN and fish oil treatment can inhibit the activity of the delta-6 and 5-desaturases. It is concluded from the results of the present study that a 'high fat' diet and lipid peroxidation can modulate DEN-induced hepatocarcinogenesis in rats.


In-vivo characterisation of an implanted microphone and totally implantable active middle ear implant.
To objectively evaluate acoustic sensitivity of the implanted microphone, and maximum stable gain of a totally implantable active middle ear implant. Prospective, single centre evaluation. Fourteen adult patients. Microphone sensitivity is approx. 10 dB lower than an externally worn conventional hearing aid, at frequencies up to 4000 Hz, and substantially lower at higher frequencies. The masking level due to microphone noise, which determines the softest test tones that can be detected, is estimated at <20 to <30 dB HL up to 1000 Hz, and <40 dB HL at higher frequencies. Maximum stable effective gain is the maximum amplification achievable without causing feedback whistling. In sensorineural hearing loss (SNHL) cases, it is 30-40 dB at frequencies up to 2000 Hz, allowing to compensate for even the maximum recommended hearing loss (60-70 dB HL). In both SNHL and mixed hearing loss (MHL) cases, maximum stable effective gain is lower (+20 to -30 dB) around 3000-6000 Hz. Microphone sensitivity is high enough to achieve aided thresholds of 20-40 dB HL. A strong correlation between actuator coupling efficiency and maximum stable effective gain implies that any effort to improve actuator efficiency should also increase the available gain.


A prospective, randomized, placebo controlled, double blind study of silicone gel in prevention of hypertrophic scar at donor site of skin grafting.
Hypertrophic scarring at donor site of skin grafting is prevalent among Asians. The effectiveness of silicone gel in scar prevention may influence the surgeons and patients regarding its routine use during the postoperative period. To study the efficacy of silicone gel in prevention of hypertrophic scars at donor site of skin grafting. Prospective randomized placebo controlled double blind study. The study was conducted in the department of Plastic Surgery, Sri Venkateswara Institute of Medical Sciences (SVIMS) University, Tirupati, Andhra Pradesh, India from June 2007 to June 2009. Patients were recruited during follow-up in the OPD. The susceptibility to scar development varied among patients; therefore, donor site scars were divided into upper half and lower half. Two types of coded gel prepared by an independent pharmacist were used on either half. Thus, selection and assessment biases and confounders were eliminated. 100 scars in 50 patients were randomized into two arms, 50 control and 50 silicone gel. The median age was 25.5 years and there were 30 men (60%) and 20 women (40%). Thirty-seven patients (74%) had good compliance. The overall incidence of donor site hypertrophic scar was 94% (47 out of 50). At the second month postoperatively, the silicone gel scars were scored lower when compared with the control scars. The differences were statistically significant in all parameters, including pigmentation (P = 0.001), Vascularity (P = 0.010), pliability (P = 0.001), and height (P = 0.010). The effect of silicone gel in prevention of hypertrophic scar development in donor site scars is promising. Success of silicone gel in its prophylactic role will create its routine use in all types of surgery to minimize the formation of hypertrophic scars in the early postoperative period.


Auricular surface morphology and surface area does not influence subchondral bone density distribution in the dysfunctional sacroiliac joint.
The subchondral lamella of the sacroiliac auricular surface is morphologically inconsistent. Its morpho-mechanical relationship with dysfunction (SIJD) remains unstudied. Here, the iliac and sacral subchondral bone mineralization is compared between morphological subtypes and in large and small surfaces, in SIJD joints and controls. CT datasets from 29 patients with bilateral or unilateral SIJD were subjected to CT-osteoabsorptiometry. Surface areas and posterior angles were calculated and surfaces were classified by size: small (<15 cm3 ) and large (≥15 cm3 ), and morphological types: 1 (>160°), 2 (130°-160°), and 3 (<130°). Mineralization patterns were identified: two marginal (M1 and M2) and two non-marginal (N1 and N2). Each sacral and iliac surface was subsequently classified. Dysfunctional cohort area averaged 15.0 ± 2.4 cm2 (males 16.2 ± 2.5 cm2 , females 13.7 ± 1.6 cm2 ). No age correlations with surface area were found nor mean Hounsfield Unit differences when comparing sizes, sexes or morphology-type. Controls and dysfunctional cohort comparison revealed differences in female sacra (p = 0.02) and small sacra (p = 0.03). There was low-conformity in marginal and non-marginal patterns, 26% for contralateral non-dysfunctional joints, and 46% for dysfunctional joints. The majority of painful joints was of type 2 morphology (59%), equally distributed between small (49%) and large joints (51%). Larger joints had the highest frequency of dysfunctional joints (72%). Auricular surface morphology seems to have little impact on pain-related subchondral lamella adaptation in SIJD. Larger joints may be predisposed to the onset of pain due to the weakening of the extracapsular structures. Dysfunctional joints reflect common conformity patterns of sacral-apex mineralization with corresponding superior corner iliac mineralization.


Selection of Biodegrading Phytosterol Strains.
The phytosterol-biotransforming strains can be selected from Mycobacterium sp. using a high concentration of β-sitosterol. The selection is made by culturing the strains in a medium enriched with 14 g/L of β-sitosterol as the unique source of carbon. During 2 months, the bacterial cultures are transferred successively. The extraction of the biotransformation products is made with methanol and ethyl acetate. The qualitative and quantitative analyses are made by means of thin-layer chromatography, gas-liquid chromatography (GLC), and GLC-mass spectrometry. Under these conditions, it is observed that after seven transfers, the strains Mycobacterium sp. MB-3683 and Mycobacterium fortuitum B-11045 increase their biotransformation capacity from 20% to 64% and from 34% to 55%, respectively. The products in the highest proportion identified for each trial are androstenedione and androstadienedione. The results suggest that the high substrate concentration could be a selective mechanism to obtain strains more efficient in the biotransformation of β-sitosterol into steroidal bases.


High-titer production of monomeric hydroxyvalerates from levulinic acid in Pseudomonas putida.
Hydroxyacids represent an important class of compounds that see application in the production of polyesters, biodegradable plastics and antibiotics, and that serve as useful chiral synthetic building blocks for other fine chemicals and pharmaceuticals. An economical, high-titer method for the production of 4-hydroxyvalerate (4HV) and 3-hydroxyvalerate (3HV) from the inexpensive and renewable carbon source levulinic acid was developed. These hydroxyvalerates were produced by periodically feeding levulinate to Pseudomonas putida KT2440 expressing a recombinant thioesterase II (tesB) gene from Escherichia coli K12. The titer of 4HV in shake flask culture reached 13.9+/-1.2 g L(-1) from P. putida tesB(+) cultured at 32 degrees C in LB medium periodically supplemented with glucose and levulinate. The highest 3HV titer obtained was 5.3+/-0.1 g L(-1) in M9 minimal medium supplemented with glucose and levulinate.


Thermally induced stress in a nanoconfined gas medium.
Molecular dynamics simulations of static argon gas at three different levels of rarefaction are conducted for a channel of 5.4 nm height to investigate the simultaneous effect of the wall force field and the gas temperature on the stress distribution along the channel height. Using the interactive thermal wall model, different temperatures are applied on the channel walls to be able to investigate the effect of the wall temperature and the induced heat flux through the gas medium on the stress distribution. Considering the monoatomic neutral argon gas, the kinetic, particle-particle virial, and surface-particle virial are considered for computing the stress distribution along the channel height. The normal stress components in the bulk gas region are distributed isotropically regardless of the gas density, temperature, and induced heat flux through the domain, while an anisotropy is observed due to the presence of the surface-particle virial. As the gas becomes hotter, the velocity of the gas atoms increases, and thus the kinetic stress component also increases. Besides, the gas density in the wall force field region reduces which eventually attenuates the surface-particle and particle-particle virial stress within 1 nm from each wall. This effect was also observed as the gas becomes cooler. It is shown that the combination of gas density, wall temperature, and induced heat flux are the main parameters which determine the distribution of stress within the gas medium especially in the wall force field region where repulsive and attractive interactions exist.


Comparative studies of various run buffers for chiral capillary electrophoresis using chiral crown ether as a chiral selector.
In the capillary electrophoretic separation of primary amine enantiomers using (+)-(18-crown-6)-tetracarboxylic acid (18C6H4) as a chiral selector, the presence of run buffer constituents such as tris(hydroxymethyl)aminomethane (Tris) or Na+ competing with analytes for 18C6H4, diminishes the effectiveness of 18C6H4. In order to determine appropriate buffer systems for 18C6H4, various run buffer cationic components including Tris, 1,3-bis[tris(hydroxymethyl)methylamino]propane, bis(2-hydroxyethyl)iminotris(hydroxymethyl)methane, triethanolamine, tetramethylammonium, and Na+ were compared. Quantitative studies of the effects of the competitive constituents were carried out by measuring the electrophoretic mobilities of histidine as a function of the 18C6H4 concentration. We also derived a simple equation to estimate the optimal chiral selector concentration for a maximum mobility difference in the presence of a competitive inhibitor.


[Case of pulmonary tuberculosis with both a solitary nodule and enlarged lymph nodes showing intense uptake on 18f-fluoro-deoxy glucose positron emission tomography (18FDG-PET) requiring differentiation from lung cancer].
A 63-year-old man was admitted to our hospital for the evaluation of an abnormal nodule in lung. Chest CT demonstrated a smooth nodular shadow in the left S6 and enlarged left hilar and mediastinal lymph nodes. Local uptake in these nodes was demonstrated on 18FDG-PET. Although bronchoscopic study was performed, definitive diagnosis had not yet been determined. After one year, the nodular shadow increased in its size. To confirm the diagnosis, VATS was performed. The histological findings showed a caseating epithelioid-cell granuloma and culture of the specimen was positive for Mycobacterium tuberculosis. This case suggested the difficulty in distinguishing lung cancer from solitary tuberculous nodules by using 18FDG.


The effect of a distribution of separations upon intramolecular distances in biopolymers, as determined by radiationless energy transfer.
In a fluorescent donor group and a nonfluorescent acceptor group are incorporated into a biopolymer, so that radiationless energy transfer occurs between the two groups, the apparent separation of the groups, as determined by energy transfer, will be influenced by the existence of a distribution of separations. This might arise from the presence of significant localized flexibility at the sites of attachment of the two groups, or from internal flexibility involving the biopolymer itself. If a Gaussian form is assumed for the distribution of separations of the donor and acceptor groups, the efficiency of transfer is dependent upon the width of the distribution, as well as the average distance between the groups. Significant differences may thereby arise between the true average separation and the separation computed from transfer efficiencies by the usual procedures. The deviations are different for transfer efficiencies computed from quantum yields and from decay times. They become more important with increasing width of the distribution of separations and increasing efficiency of transfer. In general, if a distribution of separations is present, the average separation is most reliably computed by procedures which take into account the effects of this distribution.


Age-period-cohort analysis of cervical cancer incidence in Hong Kong from 1972 to 2001 using maximum likelihood and Bayesian methods.
To examine the secular effects of opportunistic screening for cervical cancer in a rich, developed community where most other such populations have long adopted organised screening. The analysis was based on 15 140 cases of invasive cervical cancer from 1972 to 2001. The effects of chronological age, time period, and birth cohort were decomposed using both maximum likelihood and Bayesian methods. The overall age adjusted incidence decreased from 24.9 in 1972-74 to 9.5 per 100,000 in 1999-2001, in a log-linear fashion, yielding an average annual reduction of 4.0% (p<0.001) during the 30 year period. There were two second order and thus identifiable changes: (1) around the mid-1920s cohort curve representing an age-period interaction masquerading as a cohort change that denotes the first availability of Pap testing during the 1960s concentrated among women in their 40s; (2) a hook around the calendar years 1982-83 when cervical cytology became a standard screening test for pregnant women. Hong Kong's cervical cancer rates have declined since Pap tests first became available in the 1960s, most probably because of increasing population coverage over time and in successive generations in a haphazard fashion and punctuated by the systematic introduction of routine cytology as part of antenatal care in the 1980s.


Pertussis toxin reverses the inhibition of insulin secretion caused by [Arg8]vasopressin in rat pancreatic islets.
When rat pancreatic islets were incubated with 10(-8) M arginine vasopressin in the presence of 15 mM glucose there was a pronounced inhibition of insulin release in comparison with controls. This inhibitory effect appeared to be specific for vasopressin since it was antagonised by vasopressin antibody. Moreover, pertussis toxin (100 ng/ml) reversed the inhibition of insulin release due to vasopressin, indicating the possible involvement of a guanyl-nucleotide regulatory protein in the inhibitory effect. Nevertheless, 10(-8) M vasopressin increased islet concentrations of cyclic AMP even under conditions where insulin release was decreased.


Characterization and classification of fluorescent pseudomonads isolated from tap water and surface water.
A total of 665 fluorescent pseudomonads, isolated from surface water and from different types of tap water, were classified into 22 groups defined by the results of the following 5 tests: hydrolysis of casein or gelatin, production of N2 from NO3-, and growth on sucrose, ethanol and D-sorbitol, respectively. Differences in colonial morphology and in the degree of proteolysis revealed that these groups were inhomogeneous. A more detailed subdivision was achieved by adding the following characters: growth on L-arabinose, D-mannitol, mesoinositol, and adonitol, respectively, and hydrolysis of Tween-80. Repeating the tests for hydrolyzing enzymes, denitrification, and growth on the carbohydrates and alcohols with strains stored in the laboratory for 1 to 3 years revealed that most characters, except hydrolysis of Tween-80, denitrification, and growth on sucrose, were very stable. Forty-five biotypes of the fluorescent pseudomonads were defined, based on the results of the repeated tests and the results of tests on nine aromatic compounds. The observed changes of some characters in a number of isolates did not diminish the value of this classification, but indicated that close relationships exist between many biotypes. About half of the biotypes described in this paper are similar to those defined by Stanier, Palleroni and Doudoroff (1966) and by Doudoroff and Palleroni (1974a), confirming the wide-spread occurrence of well-definable biotypes of fluorescent pseudomonads. Representatives of some biotypes were most frequently isolated from surface water and from tap water prepared from surface water. Tap water prepared from anaerobic or aerobic ground water contained representatives of biotypes which were typical of these water types. Some pseudomonads were found to grow especially in filters. The observed relationships between origin of the fluorescent pseudomonads and their classification into biotypes as defined in this paper supported the presented classification.


Creating a cultural analysis tool for the implementation of Ontario's civil mental health laws.
Ethno-racial people with mental health disabilities experience multiple inequities and differential outcomes when interacting with Ontario's civil mental health laws. Given the increasing multi-racial population in Ontario, there is a need to develop mechanisms to address these intersecting issues. Other countries that have created evaluative tools for mental health legislation include the United Kingdom and Australia. Australia's Rights Analysis Tool, the United Kingdom's Race Equality Impact Assessment, the Scottish Recovery Tool, and the World Health Organization's Mental Health and Human Rights checklist are examples of evaluative tools developed for mental health legislation. Such a tool does not exist in Canada, let alone in Ontario specifically. Thus, this study developed a Cultural Analysis Tool (CAT) consisting of specific and meaningful thematic questions that can be used by practitioners when addressing issues of culture and equity for ethno-racial people with mental health disabilities interacting with Ontario's civil mental health laws. It is hoped that the CAT, and the research underlying its development, will enable practitioners to critically question whether cultural and intersecting concerns are being appropriately addressed within an ethno-racial client's case and, furthermore, how equitable outcomes can be achieved. This article describes and analyzes the methodology, research and qualitative data used to develop the CAT. It then presents and examines the CAT itself. The qualitative data was drawn from thirty-five semi-structured interviews with seven members of each of the following groups: (1) ethno-racial people with mental health disabilities including in-patients and ex-patients, (2) lawyers who practice in the area of mental health law, (3) health care professionals including psychiatrists, nurses and social workers, (4) service providers such as front-line case workers at mental health agencies and (5) adjudicators, government advisors and academics. After an analysis of these data, the CAT's questions were refined through an expert review (involving the qualitative technique of member-checking) using three focus groups comprised of ethno-racial people with mental health disabilities, mental health lawyers and service providers and health care professionals.


Mouse Model for Efficient Simultaneous Targeting of Glycolysis, Glutaminolysis, and De Novo Synthesis of Fatty Acids in Colon Cancer.
Colon cancer is a highly anabolic entity with upregulation of glycolysis, glutaminolysis, and de novo synthesis of fatty acids, which also induces a hypercatabolic state in the patient. The blockade of either cancer anabolism or host catabolism has been previously proven to be a successful anticancer experimental treatment. However, it is still unclear whether the simultaneous blockade of both metabolic counterparts can limit malignant survival and the energetic consequences of such an approach. In this chapter, by using the CT26.WT murine colon adenocarcinoma cell line as a model of study, we provide a method to simultaneously perform a pharmacological blockade of tumor anabolism and host catabolism, as a feasible therapeutic approach to treat cancer, and to limit its energetic supply.


Immunolocalization of the vascular endothelial growth factor receptor-2 in the subepicardial mesenchyme of hamster embryos: identification of the coronary vessel precursors.
The earliest evidence of the development of the cardiac vessels in mammals is the emergence of subepicardial blood islands, which are thought to originate from mesenchymal progenitors. In order to identify these progenitor cells, we have studied the immunohistochemical localization in the heart of Syrian hamster embryos of the type 2 vascular endothelial growth factor receptor, the earliest molecule known to be expressed in the vasculogenic cell lineage. Only a few immunoreactive subepicardial mesenchymal cells were present by 10 days post coitum. By 11 days post coitum, the subepicardial mesenchymal cells became abundant at the dorsal part of the ventricle, the atrioventricular and the conoventricular grooves. About 20% of cells were labelled with the antibody. Immunoreactive cells were isolated or formed pairs, short cords, rounded clusters or ring-like structures at the subepicardium or, occasionally, within the ventricular myocardium. Other labelled cells were simultaneously cytokeratin immunoreactive. By 12 days post coitum, most immunoreactive mesenchymal cells have been replaced by a capillary network. We propose that an active process of vascular differentiation occurs between 10 and 12 days post coitum in the subepicardium of this species, and it might be a suitable model for the study of vasculogenetic mechanisms.


Early recovery following traumatic brain injury and alcohol withdrawal management.
To compare recovery experienced during inpatient rehabilitation among individuals with traumatic brain injury (TBI) based on whether their acute care included the Clinical Institute Withdrawal Assessment for Alcohol (CIWA) protocol. Participants included 234 individuals with TBI who completed inpatient rehabilitation at a TBI Model Systems site. Of these, 67 patients were treated using the CIWA protocol (TBI + CIWA); 167 patients were treated for TBI alone (TBI only). Demographic, injury, and treatment variables between the 2 groups were compared. A repeated-measures analysis of variance (ANOVA) compared Disability Rating Scale (DRS) scores between the groups at admission and discharge from inpatient rehabilitation. The 2 groups did not significantly differ on DRS scores at admission to inpatient rehabilitation: TBI + CIWA, M = 9.6 (SD = 3.5) vs. TBI only, M = 10.1 (SD = 4.2). There was a significant difference in DRS scores at discharge, with the TBI + CIWA group having lower scores: TBI + CIWA, M = 6.4 (SD = 1.9) vs. TBI only, M = 7.0 (SD = 2.2). A repeated-measures ANOVA of DRS scores from admission to discharge revealed a significant between-subjects effect based on patients' Mississippi categorization of posttraumatic amnesia (PTA) duration (p < .001) and age (p = .016) but not based on their CIWA status (p = .068). A post hoc comparison including age as a covariate revealed a significant difference based on CIWA status (p = .013) within the "moderate" injury group at discharge, with the TBI + CIWA group having lower discharge DRS scores. Given the significant symptom overlap between alcohol withdrawal and PTA, it is likely that these 2 delirium presentations are confounded during the initial recovery from TBI, leading to "overestimation" of injury severity-particularly among individuals with moderate TBI. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


Menstrual hygiene management practices and menstrual distress among adolescent secondary school girls: a questionnaire-based study in Nigeria.
Menstruation is a common and normal experience during the reproductive age of adolescent females and if not well managed might expose the female to menstrual distress. To determine the menstrual hygiene management practices and menstrual distress among adolescent secondary school girls. Six hundred participants randomly drawn participated in the study. A structured questionnaire which had two inventories was used to collect data. The first inventory was a self-developed Menstrual Hygiene Management Practices Questionnaire (MHMPQ) (r = 0.71) and the second one was a modified 11-item Menstrual Distress Scale (MDS) (r = 0.74). Data were analyzed using descriptive and inferential statistics. Results showed that menstrual hygiene management practices of the girls were poor and they were very highly distressed. Statistically significant differences were observed in menstrual hygiene management practices among the girls with regard to age, location of residence and occupation of mother and on menstrual distress in relation to occupation of father (p < 0.05). Significant positive relationship between menstrual hygiene management practices and menstrual distress was observed. The findings accentuate the need for a caring atmosphere for menstrual sanitation both at home and in school.


Mix-and-extrude: high-viscosity sample injection towards time-resolved protein crystallography.
Time-resolved crystallography enables the visualization of protein molecular motion during a reaction. Although light is often used to initiate reactions in time-resolved crystallography, only a small number of proteins can be activated by light. However, many biological reactions can be triggered by the interaction between proteins and ligands. The sample delivery method presented here uses a mix-and-extrude approach based on 3D-printed microchannels in conjunction with a micronozzle. The diffusive mixing enables the study of the dynamics of samples in viscous media. The device design allows mixing of the ligands and protein crystals in 2 to 20 s. The device characterization using a model system (fluorescence quenching of iq-mEmerald proteins by copper ions) demonstrated that ligand and protein crystals, each within lipidic cubic phase, can be mixed efficiently. The potential of this approach for time-resolved membrane protein crystallography to support the development of new drugs is discussed.


Differential expression of immediate early genes in the hippocampus and spinal cord.
We have demonstrated that immediate early genes can be differentially activated within the central nervous system. We examined the effects of tetanic stimulation in the hippocampus and of noxious sensory stimulation of the spinal cord on the expression of eight immediate early genes. Induction of long-term potentiation (LTP) in the dentate gyrus resulted in an increase in mRNA and protein for NGFI-A (also termed Zif/268, Egr-1, or Krox 24), and less consistently for jun-B mRNA. No increase was seen for c-fos, NGFI-B, c-jun, jun-D, SRF, or PC4 mRNAs. Blockade of the NMDA receptor prevented the induction of both LTP and NGFI-A mRNA in the dentate gyrus. However, commissural stimulation, which prevented the induction of LTP, resulted in bilateral activation of all the genes examined, including NGFI-A. No change was seen in animals trained in a water maze. These results suggest that no simple relationship exists between LTP, spatial learning, and immediate early gene induction. Stimulation of sensory fibers resulted in an increase in mRNA for NGFI-A, c-fos, SRF, NGFI-B, and c-jun in spinal cord neurons. Blockade of the NMDA receptor had no effect on immediate early gene induction in the spinal cord.


Strongyloides stercoralis hyperinfection in a patient with the acquired immune deficiency syndrome.
Severe infections with Strongyloides stercoralis occur in immunocompromised patients. Strongyloides hyperinfection syndrome complicated by gram-negative bacteremia and meningitis in a bisexual man with the acquired immune deficiency syndrome (AIDS) is described. Increased awareness of this infection, which may also be sexually transmitted, is recommended when caring for patients with AIDS who are homosexual, or have resided in areas endemic for strongyloidiasis. Multiple stool examinations should be performed routinely for such patients. Examination of sputum for the parasite is recommended if pneumonia is present. Prompt diagnosis and therapy are essential for prevention of fatal dissemination.


Involvement in bullying and suicide-related behavior at 11 years: a prospective birth cohort study.
To study the prospective link between involvement in bullying (bully, victim, bully/victim), and subsequent suicide ideation and suicidal/self-injurious behavior, in preadolescent children in the United Kingdom. A total of 6,043 children in the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort were assessed to ascertain involvement in bullying between 4 and 10 years and suicide related behavior at 11.7 years. Peer victimization (victim, bully/victim) was significantly associated with suicide ideation and suicidal/self-injurious behavior after adjusting for confounders. Bully/victims were at heightened risk for suicide ideation (odds ratio [OR]; 95% confidence interval [CI]): child report at 8 years (OR = 2.84; CI = 1.81-4.45); child report at 10 years (OR = 3.20; CI = 2.07-4.95); mother report (OR = 2.71; CI = 1.81-4.05); teacher report (OR = 2.79; CI = 1.62-4.81), as were chronic victims: child report (OR = 3.26; CI = 2.24-4.75); mother report (OR = 2.49; CI = 1.64-3.79); teacher report (OR = 5.99; CI = 2.79-12.88). Similarly, bully/victims were at heightened risk for suicidal/self-injurious behavior: child report at 8 years (OR = 2.67; CI = 1.66-4.29); child report at 10 years (OR = 3.34; CI = 2.17-5.15); mother report (OR = 2.09; CI = CI = 1.36-3.20); teacher report (OR = 2.44, CI = 1.39-4.30); as were chronic victims: child report (OR = 4.10; CI = 2.76-6.08); mother report (OR = 1.91; 1.22-2.99); teacher report (OR = 3.26; CI = 1.38-7.68). Pure bullies had increased risk of suicide ideation according to child report at age 8 years (OR = 3.60; CI = 1.46-8.84), suicidal/self-injurious behavior according to child report at age 8 years (OR = 3.02; CI = 1.14-8.02), and teacher report (OR = 1.84; CI = 1.09-3.10). Children involved in bullying, in any role, and especially bully/victims and chronic victims, are at increased risk for suicide ideation and suicidal/self-injurious behavior in preadolescence.


The Brighton Collaboration standardized template for collection of key information for benefit-risk assessment of viral vector vaccines.
Many of the vaccines under development for COVID-19 involve the use of viral vectors. The Brighton Collaboration Benefit-Risk Assessment of Vaccines by Technology (BRAVATO, formerly the Viral Vector Vaccine Safety Working Group, V3SWG) working group has prepared a standardized template to describe the key considerations for the benefit-risk assessment of viral vector vaccines. This will facilitate key stakeholders to anticipate potential safety issues and interpret or assess safety data. This would also help improve communication and public acceptance of licensed viral vector vaccines.


RANKL targeted peptides inhibit osteoclastogenesis and attenuate adjuvant induced arthritis by inhibiting NF-κB activation and down regulating inflammatory cytokines.
Peptides designed from osteoprotegerin (OPG) have previously been shown to inhibit receptor activator of NF-κB ligand (RANKL) and prevent bone loss without significantly inhibiting inflammation. The objective of this study was to develop a novel peptide with dual inhibitory activity against bone loss and inflammation using site-directed mutagenesis. Out of the three putative sites (i.e., Tyr70-Asp78, Tyr82-Glu96, and Leu113-Arg122) available on OPG for RANKL binding, Leu113-Arg122 was used as a template for peptide synthesis. Peptide mutants of the template sequence (112YLEIEFCLKHR122) were synthesized and initially screened for their inhibitory effect on RANK-RANKL binding by competitive ELISA. The most active peptide was further evaluated in vitro for RANKL induced osteoclastogenesis in mouse macrophage cells, and in vivo for Freund's complete adjuvant induced arthritis (AIA) in Lewis rats. The efficacy of the candidate peptide was compared with that of the standard drug celecoxib. The peptide YR-11 (YLEIEFSLKHR), obtained by direct substitution of cysteine with a serine residue in the template sequence, significantly (p<0.05) inhibited RANK-RANKL binding, and RANKL induced TRAP activity and formation of multinucleated osteoclasts without any cytotoxicity. Administration of YR-11 peptide at the dose of 30mg/kg (i.p.) ameliorated both bone loss and inflammation in AIA rats. To elucidate the mechanism for inhibition of inflammation in arthritic rats, serum and tissue cytokines (TNF-α, IL-1β, and IL-6) were analyzed by ELISA and RT-PCR methods. Results confirmed that YR-11 peptide inhibited pro-inflammatory cytokines in the sera and hind paw tissues of AIA rats through its suppressive effect on RANKL induced nuclear translocation of NF-κB. The results obtained in this study substantiate the therapeutic benefit of this novel peptide in the prevention of bone loss and inflammation in rheumatoid arthritis with reduced side effects.


The role of nitric oxide, endothelin, and prostaglandins in the transition of the pulmonary circulation.
This review emphasizes the importance of three endothelial-derived products in regulating fetal and transitional pulmonary vascular tone. Although the pathophysiologic events that culminate in PPHN are poorly understood, it is likely that endothelial cell dysfunction, with an alteration in the normal "balance" of endothelial-derived mediators, is a contributing factor. In addition to the three vasoactive mediators described herein, several other neurohumoral agents influence fetal and transitional pulmonary vascular tone. In addition, structural changes in the pulmonary circulation, with abnormal proliferation of smooth muscle and extracellular matrix components, also contribute to failure of normal postnatal adaptation. Continued research is necessary to better define the complex interactions that result in the normal transition from the fetal to the postnatal state. Continued advances in the understanding of the normal transition will allow a more rational approach to management of the failed transition reflected in the disease state, PPHN.


Analysis of short-chain bioactive peptides by unified chromatography-electrospray ionization mass spectrometry. Part II. Comparison to reversed-phase ultra-high performance liquid chromatography.
In the first part of this study, a unified chromatography (UC) analysis method, which is similar to supercritical fluid chromatography (SFC) but with wide mobile phase gradients of pressurized CO2 and solvent, was developed to analyse short-chain peptides, with UV and mass spectrometry (MS) detection. In this second part, the method is compared to a reference reversed-phase ultra-high-performance liquid chromatography (RP-UHPLC) method, based on the analysis of 43 peptides, including 10 linear peptides and 33 cyclic ones. First, the orthogonality between the two methods was examined, based on the retention patterns. As the UC method was developed on a polar stationary phase (Ascentis Express OH5), the elution orders and selectivities were expected to be significantly different from RPLC on a non-polar stationary phase (ACQUITY CSH C18). Secondly, the success rate of the methods was examined, based on successful retention / elution of the peptides and the absence of observed co-elutions between the main peak and impurities. A successful analysis was obtained for 81% of the peptides in UC and 67% in RPLC. Thirdly, the performance of the methods for the intended application of impurity profiling of peptide drug candidates was assessed, based on the comparison of peak purities, the number of impurities detected and the thorough examination of impurity profiles. Excellent complementarity of the two methods for the specific task of impurity profiling, and for the separation of isomeric species was observed, with only one isomeric pair in this set remaining unresolved. The method sensitivity was however better with RPLC than UC. Finally, the operational costs in terms of solvent cost per analysis were the same between the two methods.


Eustachian Tube Balloon Dilation: A Comprehensive Analysis of Adverse Events.
Eustachian tube balloon dilation (ETBD) has been Food and Drug Administration (FDA) approved for refractory Eustachian tube dysfunction since 2016. While ETBD is generally seen as safe, the complication profile has not been well defined. The objective of this study was to utilize the FDA manufacturer and user facility device experience (MAUDE) database to better assess adverse events (AE) related to ETBD. This is a study of a multiinstitutional database maintained by the U.S. FDA. A database analysis was performed via the collaboration of multiple clinicians at tertiary referral centers. The FDA MAUDE database was queried for all medical device reports (MDR) related to ETBD devices from January 2012 to November 2022. Eighty-eight unique MDR were identified, 16 of which met inclusion criteria. Three MDRs were classified as device-related (18.8%); none resulted in an AE. Thirteen MDRs (81.3%) were patient-related; all were classified as AEs. The most common AE was postoperative subcutaneous emphysema (n = 6, 46.2%). Of the patients with subcutaneous emphysema, there was a wide range of severity. The most severe AE (n = 1, 6.3%) was postoperative stroke secondary to carotid artery dissection. Though ETBD is generally seen as a safe procedure, there have been several concerning AEs reported to date. Increased awareness of ETBD complications can serve as a primer for improved patient education and counseling during the informed consent process and aid surgeons in clinical decision-making. Future studies with standardized reporting protocols are warranted to create a central registry for ETBD.


Carbohydrate polymers as constituents of exopolymer substances in seawater, their complexing properties towards copper ions, surface and catalytic activity determined by electrochemical methods.
The goal of this study was to investigate to which extent polysaccharides (PS) contribute to the complexing capacity for copper ion (LT), to determine their property of surface activity and evaluate their capability to cause the catalytic hydrogen evolution wave (peak "H") due to their adsorption and the catalytic groups in their structure. Complexing capacities and apparent stability constants (Kapp) were measured electrochemically for model polysaccharides (PS): carrageenans (κ-, ι- and λ-), chondroitin sulfate, dextran, dextran sulfate, Na-alginate and humic material. Cu-complexing capacities were determined for Na-alginate (logKapp=8.32) and chondroitin sulphate (logKapp=8.14). PS adsorb on different surfaces due to their amphyphylic properties and on that way they could increase the interaction of copper ions with these surfaces by forming the surface complexes with Cu ions.


Pretreatment with dual antiplatelet therapy in patients with ST-elevation myocardial infarction.
The optimal time to administer P2Y12 inhibitors in patients with ST-elevation myocardial infarction (STEMI) remains to be defined. We sought to assess whether a pretreatment strategy was associated with improved coronary reperfusion and clinical outcomes. Consecutive patients from the Melbourne Interventional Group registry (2005-2014) who presented with STEMI and underwent primary PCI were included. Those who received any P2Y12 inhibitor prior to arrival in the cardiac catheterisation laboratory were included in the pretreatment group. The primary endpoints were the proportion of patients with initial TIMI flow grade <3 and in-hospital bleeding. The secondary endpoints were 12-month mortality and major adverse cardiovascular events (MACE). Of the 2,807 patients included, 892(31.8%) received pretreatment. Clopidogrel was the most common P2Y12 inhibitor used (79.6%). Pretreatment was associated with less thromboaspiration and GPIIb/IIIa inhibitor use (both P < 0.01). Pretreatment was not associated with lower rates of TIMI flow <3 on initial angiogram (78.0% vs. 80.7%, P = 0.18) nor with increased in-hospital bleeding (3.6% vs. 3.9%, P = 0.67). Pretreatment was associated with lower 12-month mortality (4.7% vs. 7.0%, P = 0.02) but similar MACE rate (13.0% vs. 14.1%, P = 0.43). Multivariate analysis revealed pretreatment was not an independent predictor of 12-month mortality (OR 0.79; 95% CI 0.5-1.3, P = 0.32). Pretreatment with a P2Y12 inhibitor in patients with STEMI was not routine practice in our Australian cohort and was not associated with improved coronary reperfusion or clinical outcomes. Larger studies are required to definitively ascertain the risk/benefit ratio of dual antiplatelet therapy pretreatment in STEMI.


Early therapeutic monitoring of β-lactams and associated therapy outcomes in critically ill patients.
In the ICU, early and appropriate antimicrobial therapy is important to lower infection-related mortality. Assess whether achieving early β-lactam free concentration above the MIC 100% of the time (fT>MIC) is associated with positive outcomes in the ICU. This retrospective study was conducted in ICU patients admitted to UF Health Shands Hospital between 2016 and 2018. Adult patients who received β-lactam therapy and had drug concentration measured were included. Data collected included demographics, β-lactam regimens and concentrations, sources of infection, cultures and susceptibilities, mortality, length of stay, resistance acquisition for 30 days and clinical outcome at end of therapy. Multiple regression and time-to-event (TTE) analyses were performed. Two-hundred and six patients were included. Clinical cure occurred in 71%, microbial eradication occurred in 58% and new resistance to the β-lactam received developed in 8% of patients. Hospital and 30 day mortalities were 17% and 14%, respectively. fT>MIC and fT>4×MIC were associated with clinical cure (P = 0.0303), microbial eradication (P = 0.0476) and suppression of resistance (P = 0.0043). Delay in measuring β-lactam concentration was associated with clinical failure (P = 0.0072), longer ICU stay (P < 0.0001) and higher mortality (P = 0.0387). In the TTE analysis, patients with 100% fT>MIC had a significantly shorter ICU stay (P = 0.0297). Patients who had clinical cure and microbial eradication had drug concentrations measured earlier (P = 0.0025 and 0.0254, respectively). This study highlights the importance of early measurement of β-lactam concentration and confirms the association between fT>MIC and clinical cure, microbial eradication and emergence of resistance.


A novel label-free optical cysteine sensor based on the competitive oxidation reaction catalyzed by G-quadruplex halves.
A sensitive and selective colorimetric detection method for Cysteine (Cys) was established in this paper. The detection mechanism is based on the oxidation of Cys by H2O2, which prevents the catalysis of the 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS)-H2O2 reaction by G-quadruplex halves. With the addition of Cys, the amount of the blue-green-colored free-radical cation (ABTS(·+)) was reduced. The absorbance of ABTS(+) at 421nm weakened as the color of the solution changed from blue-green to colorless. The concentration of Cys can be determined by monitoring this competitive reaction with the naked eye or using a UV-vis spectrometer. The calibration curve showed that the net absorption value at 421nm linearly increased over the Cys concentration range of 0.005-100μM with a detection limit of 5nM. Furthermore, amino acids other than Cys cannot mediate the color change under the identical conditions because of the absence of thiol groups, thereby suggesting the selectivity towards Cys of the proposed method. The optical sensor is high selective, which is important for the determination of Cys in serum samples. The assay shows great potential for its practical application as a disease-associated indicator which could satisfy the need for amino acid determination in fields such as food processing, biochemistry, pharmaceuticals, and clinical analysis.


Maxillary antrum hypoplasia. Report of a case.
Hypoplasia of the maxillary antrum is a rarely encountered condition. Antral hypoplasia has been misdiagnosed as sinusitis, chronic sinus infection, and neoplasm. Antral hypoplasia can be associated with difficult and unnecessary surgical explorations. A case of unilateral maxillary antrum hypoplasia is reported. Associated anatomical anomalies and a review of literature is described.


Associations of polymorphisms in non-HLA loci with autoantibodies at the diagnosis of type 1 diabetes: INS and IKZF4 associate with insulin autoantibodies.
More than 50 loci outside the human leukocyte antigen (HLA) region have been confirmed to affect type 1 diabetes (T1D) risk but their effect on β-cell autoimmunity is poorly defined. We analyzed the association of 35 single nucleotide polymorphism (SNP) markers previously associated with T1D with the presence of disease-predictive autoantibodies at the time of T1D diagnosis. The study cohort comprised 1554 children diagnosed with T1D before the age of 15 yr. The associations between various genotypes and positivity for antibodies against islet cells [islet cell antibodies (ICA)], insulin [insulin autoantibodies (IAA)], glutamic acid decarboxylase (GADA), islet antigen 2 (IA2A), and zinc transporter 8 (ZnT8A) were analyzed. INS gene polymorphism rs689 and IKZF4 polymorphism (rs1701704) were strongly associated with IAA positivity at the time of T1D diagnosis (p = 0.000004 and 0.00044, respectively). The presence of the T1D-risk conferring INS AA genotype was associated with IAA. In contrast, the presence of the susceptible C allele of the IKZF4 marker was inversely associated with IAA. The INS and IKZF4 polymorphisms were not significantly associated with ICA, GADA, IA2A, or ZnT8A positivity. Both INS and IKZF4 polymorphisms modified the probability of IAA positivity at time of T1D onset but the inverse association of IKZF4 risk allele with IAA suggests that the IKZF4 polymorphism is involved in a pathway of β-cell autoimmunity alternate to the route characterized by IAA and development of T1D in early childhood. The IKZF4 gene encodes Eos, which is implicated to play an important role in Treg programming where this gene might exert its influence on T1D risk.


Generation of three induced pluripotent stem cell lines from a patient with Usher syndrome caused by biallelic c.949C > A and c.1256G > T mutations in the USH2A gene.
Mutations in the USH2A gene are the most common cause of Usher syndrome and autosomal recessive non-syndromic retinitis pigmentosa. Here, we describe the generation of three induced pluripotent stem cell lines from dermal fibroblasts derived from a patient carrying biallelic c.949C > A and c.1256G > T variants in the USH2A gene, using episomal reprogramming plasmids expressing OCT4, SOX2, KLF4, MYCL, LIN28, mir302/367 and shRNA targeting TP53. All three lines expressed pluripotency markers, displayed unaltered karyotypes as well as trilineage differentiation potential, and were negative for reprogramming episomes and mycoplasma.


Effects of Low-Dose Unfractionated Heparin Pretreatment on Early Brain Injury after Subarachnoid Hemorrhage in Mice.
Heparin is a pleiotropic drug that antagonizes many pathophysiological mechanisms. In this study, we evaluated whether heparin prevents early brain injury (EBI) after subarachnoid hemorrhage (SAH) in mice. SAH was induced by endovascular perforation in mice randomly assigned to sham-operated (n = 8), SAH + vehicle (n = 12), SAH + 10 U heparin pretreatment (n = 11), and SAH + 30 U heparin pretreatment (n = 14) groups. At 24 h post-SAH, severity of SAH, neurological scores, and brain water content were evaluated. Low-dose heparin pretreatment improved neurobehavioral function, and decreased brain edema in the ipsilateral cerebral hemisphere to the perforation side. High-dose heparin had a tendency for increased SAH, which obscured the neuroprotective effects by heparin. Low-dose heparin pretreatment may decrease the development of post-SAH EBI.


Quantum channel correction outperforming direct transmission.
Long-distance optical quantum channels are necessarily lossy, leading to errors in transmitted quantum information, entanglement degradation and, ultimately, poor protocol performance. Quantum states carrying information in the channel can be probabilistically amplified to compensate for loss, but are destroyed when amplification fails. Quantum correction of the channel itself is therefore required, but break-even performance-where arbitrary states can be better transmitted through a corrected channel than an uncorrected one-has so far remained out of reach. Here we perform distillation by heralded amplification to improve a noisy entanglement channel. We subsequently employ entanglement swapping to demonstrate that arbitrary quantum information transmission is unconditionally improved-i.e., without relying on postselection or post-processing of data-compared to the uncorrected channel. In this way, it represents realization of a genuine quantum relay. Our channel correction for single-mode quantum states will find use in quantum repeater, communication and metrology applications.


Periodic metabolic systems: oscillations in multiple-loop negative feedback biochemical control networks.
For a general multiple loop feedback inhibition system in which the end product can inhibit any or all of the intermediate reactions it is shown that biologically significant behaviour is always confined to a bounded region of reaction space containing a unique equilibrium. By explicit construction of a Liapunov function for the general n dimensional differential equation it is shown that some values of reaction parameters cause the concentration vector to approach the equilibrium asymptotically for all physically realizable initial conditions. As the parameter values change, periodic solutions can appear within the bounded region. Some information about these periodic solutions can be obtained from the Hopf bifurcation theorem. Alternatively, if specific parameter values are known a numerical method can be used to find periodic solutions and determine their stability by locating a zero of the displacement map. The single loop Goodwin oscillator is analysed in detail. The methods are then used to treat an oscillator with two feedback loops and it is found that oscillations are possible even if both Hill coefficients are equal to one.


Adherence by orthopaedic surgeons to AHPRA and Australian Orthopaedic Association advertising guidelines.
To examine adherence to Australian Health Practitioner Regulation Agency (AHPRA) and Australian Orthopaedic Association (AOA) advertising guidelines by AOA members. Cross-sectional survey, Australia. Two samples of AOA member orthopaedic surgeons: 81 randomly selected from a list of AOA members with publicly available contact details (AOA random sample); and a sample obtained by searching with Google for "orthopaedic surgeon" and the name of the major city in each of the eight Australian states and territories in turn; the top eight results for each search were considered for inclusion (AOA Google sample). Non-compliance of advertising material, by surgeon sample, with the AHPRA and AOA guidelines; associations between non-compliance and sample, state, location (metropolitan, regional), and subspecialty. Of the 81 surgeons in the AOA random sample, 52 (64%) were non-compliant with at least one aspect of the AHPRA guidelines, and 53 (65%) were non-compliant with at least one aspect of the AOA guidelines. Of the 59 surgeons in the AOA Google sample, 48 were non-compliant with the AHPRA guidelines (81%) and 46 with the AOA guidelines (78%). Incidence of non-compliance with the AHPRA guidelines was influenced by sample source (AOA Google v AOA random: incidence rate ratio [IRR], 1.37; 95% CI, 1.01-1.87), but not non-compliance with the AOA guidelines (IRR, 1.09; 95% CI, 0.77-1.55). A large proportion of AOA members who advertise online do not comply with AHPRA and AOA advertising guidelines.


Selecting the target and the message for a stroke public education campaign: a local survey conducted by neurologists.
In order to determine the baseline knowledge of stroke among population (terminology, signs and symptoms, risk factors (RF) and attitude) to select the best target and message, prior to educational campaigns, a structured interview using close-ended questions was conducted by neurologists among 1000 users of several Primary Health Centers around our Hospital, randomly sampled. In our population 10.1% totally ignores the disease; of the remainder, 50% has a good knowledge of signs and symptoms and 37% of RF. To be a woman, (OR: 1.7; 95% CI: 1.2-2.5), the university education (OR: 6.6; 95% CI: 3.0-14.7), the age between 45 and 65 years (OR: 2.5; 95% CI: 1.3-5.0) and to have an afflicted relative (OR: 1.4; 95% CI: 1.001-2.0) are associated with a better stroke knowledge. If symptoms are transient, there is a trend to contact primary physicians (43.5%). Less than a quarter of our population have a good knowledge of the disease. Stroke is considered an emergency unlike TIA. The benefits of public education and the best message for each target population are discussed.


Myasthenia in patients with dermatomyositis: clinical, electrophysiological and ultrastructural studies.
In 4 patients with clinical signs of dermatomyositis, confirmed by electromyography and muscle biopsy, a form of muscle fatigue was detected which was expressed clinically by predominantly proximal motor deficit, with phonation and deglutition disturbances, slightly influenced by prostigmine. In all patients, stimulation of the ulnar nerve at 3--10 Hz induced a decrement of muscle-evoked potentials in abductor digiti minimi and at 15--50 Hz an increment at the end of the trains (1.2 sec in duration) of repetitive stimulation (preceded in two cases by a decrement in the response to the fifth stimulus in the train). Stimulation at 30 Hz for 10 sec resulted in a transient facilitation, followed (at 3 Hz stimulation) by postactivation exhaustion which disappeared after 5--15 min. The post-tetanic facilitation, the incremental response and the myasthenic symptoms reverted to normal under treatment with corticosteroids, an immunosuppressor agent and guanidine hydrochloride. A mixed, pre- and postsynaptic mechanism is presumed to underlie the muscle fatigue in our patients. Electron microscopy of muscle biopsies disclosed zones of necrosis and, in incipient stages, large agglomerations of glycogen that had disorganized the structure of myofibrils. The end-plates in the biopsies were larger than normal and the cholinesterase reaction was hyperactive. Serum immunoelectrophoretic and electrophoretic data--increase of IgG and IgM, decrease of IgA and hypergammaglobulinaemia -- point to a possible autoimmune mechanism of the neuromuscular disorders in our patients.


Immunochemical and physicochemical characterization of commercial Alternaria extracts: a model for standardization of mold allergen extracts.
To develop a model for mold allergen extract standardization, we studied eight commercial Alternaria extracts from various suppliers by a variety of immunochemical and physicochemical techniques, including measurement of Alt-I, a purified allergenic fraction of Alternaria. Wide variations were noted in the allergenic and antigenic potencies of these extracts. Estimates of Alt-I content measured by Alt-I RAST inhibition and by radioimmunoassay correlated significantly (p less than 0.05), but Alt-I activity by either method could not be correlated with allergenic potency as measured by RAST inhibiton using solid-phase Alternaria. Each test extract produced unique and differing patterns of Coomassie blue-stained bands in isoelectrofocusing gels and in crossed immunoelectrophoresis gels using rabbit antibodies to Alternaria. The optimal method for mold allergen standardization involves a combination of RAST inhibiton, isoelectrofocusing, and crossed immunoelectrophoresis techniques, and, if possible, quantitation of individual allergens.


Illustrated and annotated checklist of Brazilian gall morphotypes.
The analysis on nine inventories on the richness and diversity of galling herbivores in Brazil accounted for 806 gall systems occurring in 443 host-plant species from 74 plant families. This checklist of the Brazilian gall morphotypes proposes seven standardized morphotypes and five additional shapes that group the majority of the three-dimensional shapes reported in literature. Criteria are proposed to standardize the terminology, and a critical analysis is provided aiming to avoid possible inconsistencies in order to generate easily comparable data in future inventories. The morphotypes are herein catalogued in alphabetical order, accompanied by a conceptual definition, an illustration, and examples that best represent the shape. It is proposed that the inventories should present at least the (1) host-plant species, (2) galling herbivore species or its identification to the lowest possible taxonomic level, (3) host-plant galled organ and gall position, (4) gall morphotype, (5) gall color and registration of indumentum when present, (6) gall phenological and developmental data, (7) association with other trophic levels, and (8) additional information, such as dimension, and number of chamber(s).


Synthesis of Arylazide- and Diazirine-Containing CrAsH-EDT2 Photoaffinity Probes.
Two photo-crosslinking biarsenical (CrAsH-EDT2 )-modified probes were synthesized that are expected to be useful tools for tetracysteine-labeled proteins to facilitate the co-affinity purification of their DNA binding sequences and interacting proteins. In addition, improvements for the synthesis of CrAsH-EDT2 and N(1) -(4-azido-2-nitrophenyl)hexane-1,6-diamine are reported. Both photoprobes effectively entered HeLa cells (and the nucleus) and were dependent on the tetracysteine motif in recombinant DMRT1 (doublesex and Mab3-related transcription factor) to induce fluorescence, suggesting that their crosslinking abilities can be exploited for the identification of nucleic acids and proteins associated with a protein of interest.


Radionuclide scanning in parathyroid diseases.
New radionuclide agents and scanning procedures have markedly improved preoperative parathyroid gland localization. The aim of this review was to evaluate the results of parathyroid scanning and to clarify its current place in the clinical management of parathyroid diseases. The literature describing the different radioisotopes and available scanning techniques was analysed and their clinical outcome in various parathyroid diseases was evaluated. Using 99mTc-radiolabelled sestamibi or other 9mTc-labelled cationic complexes, parathyroid scintigraphy detects 87 per cent of solitary adenomas (n=894), 55 per cent of abnormal glands in patients with multiglandular disease (n=303) and 75 per cent of persistent or recurrent lesions in patients with previous neck surgery (n=240). If necessary, three-dimensional imaging techniques can clarify the spatial localization of an ectopic uptake focus. The positive predictive value of the available scanning procedures is over 95 per cent, but false-positive uptake may be encountered. Radionuclide parathyroid gland scanning with 99mTc-labelled cationic complexes is the initial non-invasive method of choice for preoperative parathyroid gland localization in patients at special risk and/or with previous neck exploration. While scanning has also been proposed to facilitate parathyroidectomy, there is no objective evidence to support its routine use before a first-time surgical procedure.


[Asymmetric chlorobenzoic acid N,N-dialkylamides having phytotoxic activity].
In continuation of research on phytotoxic substances with selective activity, pre- and post-emergence tests against some weed species were made using a series of 3-chlorobenzamides substituted on the amide nitrogen with a sec.butyl or a 1-methylbutyl group, the second alkyl substituent being linear, branched, saturated or unsaturated. Asymmetric 3-chlorobenzamides with a tert.butyl in place of sec.butyl or with an 1-ethylpropyl in place of 1-methylbutyl and with a second alkyl residue of different nature and with variable weight, were prepared and tested for the purposes of comparison. The results show that amides with excellent phytotoxicity and selectivity of action are obtained if a sec.butyl, 1-methylbutyl or 1-ethylpropyl group is retained and the second substituent on the amide nitrogen is suitably varied. The results give further information on the importance of the steric characteristics of the substituents on nitrogen in the phytotoxic N,N-dialkylamides.


Briefing paper: xylitol, caries and plaque.
Xylitol is a naturally occurring sweetener. Beyond being non-cariogenic, it exhibits both passive and active anti-caries properties and is used in confectionery and oral care products.


The discriminative properties of the D1 dopamine agonist dihydrexidine in the rat.
The objective of this study was to train rats to discriminate the interoceptive stimuli produced by a selective dopamine D1 agonist. Fourteen male Sprague-Dawley rats acquired the discrimination of the fully effective, high potency, D1 agonist dihydrexidine (DHX) within 20 sessions using a training dose of 3.0 mg/kg. DHX (0.75-4.5 mg/kg) dose-dependently increased DHX-appropriate responding with an ED50 = 1.44 mg/kg. The selective D1 agonist SKF 38398 (2.0-8.0 mg/kg) dose-responsively generalized with an ED50 = 3.54 mg/kg; significantly less potent than DHX. The selective D1 antagonist SCH 23390 (0.06-0.12 mg/kg) dose-responsively decreased DHX-appropriate discriminative performance. These data would indicate that DHX is a selective D1 agonist that may allow for testing of the selectivity of other putative D1 agonists in this experimental procedure. Administration of non-selective dopaminergically active drugs, including apomorphine, amphetamine and cocaine, were each shown to produce intermediate DHX-appropriate discriminative performance.


Structural colour of unary and binary colloidal crystals probed by scanning transmission X-ray microscopy and optical microscopy.
Colloidal crystals composed of micro- or nano- colloids have been investigated in various fields such as photonics due to their unique optical properties. Binary colloidal crystals have an outstanding potential for fine-tuning material properties by changing the components, concentration, or size of colloids. Because of their tunable optical, electrical, magnetic, and mechanical properties, those materials attracted great attention. However, it has been hard to elucidate internal structures without fluorescent labelling or cross-sectioning. Here, we demonstrate the structural analysis of not only unary but also binary colloidal crystals using scanning transmission x-ray microscopy and compare the results with colloidal structures and optical properties observed by optical microscopy. Based on the comparison of images obtained by these two methods, the domains of colloidal crystals consisting of different structures and colours were directly identified without any additional sample preparation. Therefore, it was possible to investigate the structural colours of local domains of unary and binary colloidal crystals such as the face centred cubic (FCC) structure with different orientations, that is FCC (111) and FCC (001), and hexagonal close-packed structure, HCP (0001).


Cytogenetic and molecular studies in primary myelofibrosis.
Cytogenetic and molecular data of three patients affected by primary myelofibrosis with myeloid metaplasia (PMMM) evolving to blastic crisis are reported. The cytogenetic findings were uncommon. The first patient (female) showed an idic(X)(q13) as the sole alteration in chronic phase, with an additional r(7) in 67% of the cells of the blast crisis; the other two patients showed, in blast crisis, a partial trisomy of the long arm of chromosome 1, without translocation, as a unique structural abnormality. These findings confirm the presence of nonrandom, although nonspecific, alterations in PMMM that, in our cases, seem to be related to the multistep progression of the neoplastic process. Molecular investigations have been applied to study the genomic organization and the level of expression of genes such as bcr and calcyclin and c-fms protooncogene possibly involved in the molecular mechanisms underlying cell proliferation in hematopoietic cells. The data obtained are discussed with respect to the myeloproliferative disorder.


A graphic representation of protein sequence and predicting the subcellular locations of prokaryotic proteins.
Zp curve, a three-dimensional space curve representation of protein primary sequence based on the hydrophobicity and charged properties of amino acid residues along the primary sequence is suggested. Relying on the Zp parameters extracted from the three components of the Zp curve and the Bayes discriminant algorithm, the subcellular locations of prokaryotic proteins were predicted. Consequently, an accuracy of 81.5% in the cross-validation test has been achieved using 13 parameters extracted from the curve for the database of 997 prokaryotic proteins. The result is slightly better than that of using the neural network method (80.9%) based on the amino acid composition for the same database. By jointing the amino acid composition and the Zp parameters, the overall predictive accuracy 89.6% can be achieved. It is about 3% higher than that of the Bayes discriminant algorithm based merely on the amino acid composition for the same database. The prediction is also performed with a larger dataset derived from the version 39 SWISS-PROT databank and two datasets with different sequence similarity. Even for the dataset of non-sequence similarity, the improvement can be of 4.4% in the cross-validation test. The results indicate that the Zp parameters are effective in representing the information within a protein primary sequence. The method of extracting information from the primary structure may be useful for other areas of protein studies.


Nurses' clinical competency and its correlates: before and during the COVID-19 outbreak.
Clinical competency is the ability to integrate knowledge, skills, attitudes and values into a clinical situation and it is very important in nursing education, clinical settings, nursing management, and crises. This study aimed to investigate nurses' professional competence and its correlates before and during the COVID-19 pandemic. We conducted this cross-sectional study before and during the COVID-19 outbreak and recruited all nurses working in hospitals affiliated to Rafsanjan University of Medical Sciences, southern Iran, so we included 260 and 246 nurses in the study before and during the COVID-19 epidemic, respectively. Competency Inventory for Registered Nurses (CIRN) was used to collect data. After inputting the data into SPSS24, we analysed them using descriptive statistics, chi-square and multivariate logistic tests. A significant level of 0.05 was considered. The mean clinical competency scores of nurses were 156.97 ± 31.40 and 161.97 ± 31.36 before and during the COVID-19 epidemic, respectively. The total clinical competency score before the COVID-19 epidemic was not significantly different from that during the COVID-19 epidemic. Interpersonal relationships (p = 0.03) and desire for research/critical thinking (p = 0.01) were significantly lower before the COVID-19 outbreak than during the COVID-19 outbreak. Only shift type had an association with clinical competency before the COVID-19 outbreak, while work experience had an association with clinical competency during the COVID-19 epidemic. The clinical competency among nurses was moderate before and during the COVID-19 epidemic. Paying attention to the clinical competence of nurses can improve the care conditions of patients, and nursing managers should improve the clinical competence of nurses in different situations and crises. Therefore, we suggest further studies identifying factors improving the professional competency among nurses.


Albumin's role in steroid hormone action and the origins of vertebrates: is albumin an essential protein?
Albumin, the major serum protein, binds a wide variety of lipophilic compounds including steroids, other lipophilic hormones and phytochemicals that bind to hormone receptors. Albumin has a low affinity for these lipophilic compounds. However, due to albumin's high concentration in serum, albumin is a major carrier of steroids and lipophilic hormones and regulator of their access to their receptors. Moreover, albumin functions as a sink for phytochemicals, which prevents their binding to hormone receptors and other cellular proteins, protecting animals from disruptive phytochemical-mediated endocrine effects. We propose that these properties of albumin were important in protochordates and vertebrates about 550 to 520 million years ago, just before and during the Cambrian. At that time, animal body sizes and exposure to phytochemicals in food were increasing, and animals in which albumin expression was high had a selective advantage in surviving and reproducing in the presence of toxic phytochemicals. This hypothesis that albumin has essential function(s) in mammalian endocrine physiology can be tested by comparing the effects of phytochemicals in Nagase rats that have 1/1000 the normal albumin concentration or in mice in which the albumin gene is knocked out with those in normal rats and mice.


Parameters affecting pleural drainage and management strategy after Fontan operation.
Prolonged pleural drainage is a common complication after undergoing the Fontan procedure. Although various protocols have been described, there is no definitive consensus for how to treat this complication. Our primary aim was to determine the effect of the management strategy protocol on the duration of drainage and length of hospital stay. Our secondary aim was to determine the parameters affecting the need for prolonged drainage after the Fontan procedure. Ninety-two consecutive patients who underwent the Fontan procedure were retrospectively analyzed. A protocol-based postoperative management strategy was adopted in July 2018. Group 1 (n = 48) consisted of patients that underwent the procedure before the protocol was implemented. Group 2 (n = 44) consisted of patients that underwent the procedure after the protocol was implemented. The mean age was 5 years (interquartile range [IQR], 4.0-6.9); the mean body weight was 17.3 kg (IQR, 15.1-21.8). Statistically significant differences were found between the groups in terms of total drainage, duration of pleural drainage, prolonged drainage, and length of hospital stays (LOHS) (P = .05, P = .04, P = .04, P = .04, respectively). The multivariate analysis results showed that the application of the protocol was the only factor impacting prolonged drainage (OR, 2.46, 95% CI lower-upper: 1.03-5.86, P = .04). Standardization and strict application of the medical treatment within a specific protocol without being affected by doctor-, nurse-, or patient-based factors increases the success rate of this procedure. After implementing the changes in the medical management strategy, total drainage and duration of pleural drainage and LOHS decreased, and the costs associated with these factors also decreased.


Inefficient replication reduces RecA-mediated repair of UV-damaged plasmids introduced into competent Escherichia coli.
Transformation of Escherichia coli with purified plasmids containing DNA damage is frequently used as a tool to characterize repair pathways that operate on chromosomes. In this study, we used an assay that allowed us to quantify plasmid survival and to compare how efficiently various repair pathways operate on plasmid DNA introduced into cells relative to their efficiency on chromosomal DNA. We observed distinct differences between the mechanisms operating on the transforming plasmid DNA and the chromosome. An average of one UV-induced lesion was sufficient to inactivate ColE1-based plasmids introduced into nucleotide excision repair mutants, suggesting an essential role for repair on newly introduced plasmid DNA. By contrast, the absence of RecA, RecF, RecBC, RecG, or RuvAB had a minimal effect on the survival of the transforming plasmid DNA containing UV-induced damage. Neither the presence of an endogenous homologous plasmid nor the induction of the SOS response enhanced the survival of transforming plasmids. Using two-dimensional agarose-gel analysis, both replication- and RecA-dependent structures that were observed on established, endogenous plasmids following UV-irradiation, failed to form on UV-irradiated plasmids introduced into E. coli. We interpret these observations to suggest that the lack of RecA-mediated survival is likely to be due to inefficient replication that occurs when plasmids are initially introduced into cells, rather than to the plasmid's size, the absence of homologous sequences, or levels of recA expression.


Potential mobility assessment of metals in salt marsh sediments from San Antonio Bay.
The BCR method was applied on sediments from the salt marsh of San Antonio Bay (SAB). It presents several channels among which the Encerrado is the most important and is impacted by abandoned mining wastes. The pseudototal concentrations of metals measured within this channel were relatively higher than in outer sites, and according to the Igeo index, its contamination level was low. The metal distribution in the different phases of sediment particles showed that the residual component, considered the safest from the environmental point of view, accounted for most of the Fe, Cd, Cu, and Zn contents. Conversely, Pb was mainly in the non-residual component as part of the reducible fraction, thus constituting the main environmental hazard among the studied elements. The predominance of residual and reducible fractions indicated a historic contamination of metal such as Pb, Cu, and Zn from the mining wastes. The low exchangeable and oxidizable fractions would indicate no actual input of metals.


A novel anti-CCN1 monoclonal antibody suppresses Rac-dependent cytoskeletal reorganization and migratory activities in breast cancer cells.
CCN1, a secreted matrix-associated molecule, is involved in multiple cellular processes. Accumulating evidence supports that CCN1 plays an important role in tumorigenesis and progression of breast cancer. In this study, we have developed a novel CCN1 function-blocking monoclonal antibody (mAb), designated YM1B. YM1B binds to human CCN1 with high specificity, recognizing the native CCN1 structure with undisturbed disulfide linkages. Our analyses have mapped the YM1B recognition region to domain IV of CCN1, likely in proximity to the DM site. In breast cancer cells, CCN1 can induce actin reorganization, formation of lamellipodia, and cell migration/invasion through the αV integrins/Rac1/ERK signaling axis; these CCN1-dependent activities can be effectively suppressed by YM1B. Our results also suggest that YM1B may exert its CCN1-blocking effect by perturbing the interaction of CCN1 with vitronectin and fibronectin, which are ligands of αV integrins and instrumental for integrin activation. This CCN1-specific mAb may open a new potential avenue for therapeutic intervention of breast cancer progression.


Auxin effects on ion transport in Chara corallina.
The plant hormone auxin has been widely studied with regard to synthesis, transport, signaling and functions among the land plants while there is still a lack of knowledge about the possible role for auxin regulation mechanisms in algae with "plant-like" structures. Here we use the alga Chara corallina as a model to study aspects of auxin signaling. In this respect we measured auxin on membrane potential changes and different ion fluxes (K(+), H(+)) through the plasma membrane. Results showed that auxin, mainly IAA, could hyperpolarize the membrane potential of C. corallina internodal cells. Ion flux measurements showed that the auxin-induced membrane potential change may be based on the change of K(+) permeability and/or channel activity rather than through the activation of proton pumps as known in land plants.


Controlled cell death by magnetic hyperthermia: effects of exposure time, field amplitude, and nanoparticle concentration.
To investigate the effects of alternating magnetic fields (AMF) on the death rate of dendritic cells (DCs) loaded with magnetic nanoparticles (MNPs) as heating agents. AMF exposure time and amplitude as well as the MNPs concentration were screened to assess the best conditions for a controlled field-induced cell death. Human-monocyte-derived DCs were co-incubated with dextran-coated MNPs. The cells were exposed to AMF (f = 260 kHz; 0 < H(0) < 12.7 kA/m) for intervals from 5 to 15 min. Morphology changes were assessed by scanning electron microscopy. Cell viability was measured by Trypan blue and fluorescence-activated cell sorting (FACS) using Annexin-propidium iodide markers. We were able to control the DCs viability by a proper choice AMF amplitude and exposure time, depending on the amount of MNPs uploaded. About 20% of cells showed Annexin-negative/PI-positive staining after 5-10 min of AMF exposure. Controlled cell death of MNP-loaded DCs can be obtained by adequate tuning of the physical AMF parameters and MNPs concentration. Necrotic-like populations were observed after exposure times as short as 10 min, suggesting a fast underlying mechanism for cell death. Power absorption by the MNPs might locally disrupt endosomic membranes, thus provoking irreversible cell damage.