Hypocalcemia in Trauma is Determined by the Number of Units Transfused, Not Whole Blood Versus Component Therapy.
Blood component resuscitation is associated with hypocalcemia (HC) (iCal <0.9 mmol/L) that contributes to coagulopathy and death in trauma patients. It is unknown whether or not whole blood (WB) resuscitation helps mitigate the risk of HC in trauma patients. We hypothesized that calcium homeostasis is maintained and mortality improved in patients who only receive WB. This is a retrospective review of all adult trauma patients who received WB from July 2018 to December 2020. Variables included transfusions, ionized calcium levels, and calcium replacement. Patients were characterized as follows based on blood products received: WB or WB with other blood components. Groups were compared with respect to HC, correction of HC, 24 h, and inpatient mortality. Two hundred twenty-three patients received WB and met the inclusion criteria. 107 (48%) received WB only. HC occurred in 13% of patients who received more than one WB unit compared to 29% of WB and other blood component patients (P = 0.02). WB patients received less calcium replacement (median 250 mg versus 2000 mg, P < 0.01). HC and total units transfused within 4 h were associated with mortality in the adjusted model. HC significantly increased after 5 units of blood products were transfused, regardless of product type. WB was not protective against HC. HC and failure to correct HC are significant risk factors for mortality in trauma. Resuscitations with WB only and WB in combination with other blood components are associated with HC especially when more than 5 units of any blood product are transfused. Calcium supplementation should be prioritized in any large volume transfusion, regardless of blood product type.


Small vesicovaginal fistula.
A simple method of curettage of the fistulous tract, using an ordinary metal screw, has been successful in the cure of certain types of vesicovaginal fistulas. This technique applies to small, high, usually postoperative vesicovaginal fistulas in which the tissue appears normal and in which there is good blood supply and no evidence of scarring or inflammatory reaction. By curetting and removing the epithelium of the fistulous tract, the tissues will follow their normal tendency toward healing and a good chance of closure of the fistula is thereby present. The main virtues of this procedure are its simplicity, the minimal risk involved, the short hospitalization time, and the fact that there is no delay in the performance of the standard type of excisional operation in case of failure. Three cases are reported.


Recognition of the 'calcium paradox' and the effects of verapamil and gallopamil in human adenoidal mast cells.
Human mast cells from adenoids show when resuspended in medium containing 10(-3) M CaCl2 after their temporary exposure to Ca2+-free saline for about 20 min an irreversible reduction of responsiveness to a variety of stimuli: The histamine release induced by concanavalin A or ionophore A 23187 is only 30-50% of the one obtained in cells which were kept in 10(-3) M Ca2+ throughout the experiment. This phenomenon called 'calcium paradox' can be almost entirely avoided if the cells are temporarily exposed to 10(-4) M Ca2+ instead of Ca2+-free saline. Number yields, average histamine contents of mast cells and the rate of the spontaneous histamine release are not affected by the transitory lack of Ca2+, nor is the histamine release enhancing effect of adenosine. At 10(-3) M Ca2+ concentration the calcium antagonists verapamil or gallopamil cause a significant inhibition of the Con A-induced histamine release only at concentrations much higher (10(-4) M than those effective in smooth muscle preparations. The actions of both calcium antagonists were not affected by the presence of added extracellular adenosine.


Multi-slice tomographic diagnosis of isolated right aortic arch in an elderly patient.
Occasional report of asyntomatic right aortic arch in a 90-year-old man with any congenital defect associated.


Running, esophageal acid reflux, and atrial fibrillation: a chain of events linked by evidence from separate medical literatures.
Using a previously described approach to generating novel medical hypotheses, this paper shows how two separate medical literatures taken together can suggest new information not apparent in either literature alone. Many studies have demonstrated that aerobic exercise in healthy people can induce esophageal acidic reflux that increases with the duration and intensity of exercise. Separately, independently of exercise, it has been shown that, in patients with gastroesophageal reflux, esophageal acid exposure can lead to atrial fibrillation (AF) and to other heart dysrhythmias. The two arguments together suggest that a regimen of excessive exercise may be conducive to AF mediated by acid reflux, an implicit, but unpublished, hypothesis. Proton pump inhibitors are widely used to treat gastroesophageal reflux. Remarkably, several small clinical trials of these drugs have been shown also to reduce symptoms and frequency of AF episodes in patients with comorbid acid reflux. Plausible mechanisms have been suggested. These small-scale tests in a highly restricted population may be of particular interest in the light of a possible exercise-reflux-AF causal chain of events in a broader population of athletes. Because the minimum degree of esophageal acidity exposure required to induce AF is unknown, further tests of proton pump inhibitors for that purpose are therefore merited without regard to any known prior reflux in a population of runners with lone AF. The prospect of reducing AF burden with a relatively benign agent is attractive in view of the limited options for effective treatment otherwise available. The study of arrhythmia and esophageal reflux in athletes may offer insights on the origin and natural history of lone atrial fibrillation.


Erratum: Cissus quadrangularis inhibits IL-1β induced inflammatory responses on chondrocytes and alleviates bone deterioration in osteotomized rats via p38 MAPK signaling [Corrigendum].
[This corrects the article on p. 2927 in vol. 9.].


Evaluation of entomopathogenic bacteria against Aedes polynesiensis, the vector of lymphatic filariasis in French Polynesia.
Thirteen strains among 3 species of entomopathogenic bacteria were tested against 3 medically important mosquito species in French Polynesia. Two strains of Bacillus thuringiensis were highly toxic to Aedes polynesiensis, Aedes aegypti, and Culex quinquefasciatus. Six of 7 strains of Bacillus sphaericus tested were highly toxic to Cx. quinquefasciatus but not to the Aedes spp. Clostridium bifermentans serovar. malaysia was more toxic to Ae. polynesiensis than to the other 2 species. Entomopathogenic bacteria merit field testing for larval mosquito control in French Polynesia.


Exome analysis of the evolutionary path of hepatocellular adenoma-carcinoma transition, vascular invasion and brain dissemination.
Hepatocellular adenoma (HCA) is a rare benign liver tumor, predominantly seen in young women. Its major complications are malignant transformation, spontaneous hemorrhage, and rupture. We describe a case of a young female with no underlying liver disease who presented with acute abdominal pain and was found to have a 17cm heterogeneous mass in the left lobe of the liver. She underwent left hepatectomy and pathology revealed a 14cm moderately differentiated hepatocellular carcinoma (HCC) arising in a shell of a HCA. At that time, vascular invasion was already present. She rapidly developed recurrent multifocal hepatic lesions and subsequent spread to the brain, leading to her death 18months after surgery. To investigate the underlying genetic events occurring during hepatocellular adenoma-carcinoma transition and extra-hepatic dissemination, we performed whole exome sequencing of DNA isolated from peripheral blood leucocytes, HCA, HCC, tumor thrombus and brain metastasis. Our data show a step-wise addition of somatic mutations and copy number variations with disease progression, suggesting a linear tumor evolution, which is supported by clonality analysis. Specifically, using a model based clustering of somatic mutations, one single founding clone arising in the HCA, which included catenin beta 1 (CTNNB1) and IL6ST driver mutations, was identified and displayed an increasing clonality rate in HCC, tumor thrombus and brain metastasis. Our data highlight the feasibility of performing whole exome capture, sequencing and analysis using formalin-fixed paraffin-embedded (FFPE) samples, and we describe the first genomic longitudinal study of hepatocellular adenoma-carcinoma transition, vascular invasion and brain metastasis with detailed clinicopathologic annotation.


Pitfalls in the use of brain slices.
In vitro brain slices are the preparation of choice for the detailed examination of local circuit properties in mammalian brain. However it is the investigator's responsibility to verify that the circuits under investigation are indeed confined within the boundaries of the functional region of the slice used. The medium in which the slice is maintained is under the full control of the investigator. This places the burden on the investigator to ensure that: (1) the properties of the medium are fully under control; (2) the effects of the medium on the slice are known; (3) the conditions under which the slice is being maintained bear some reasonable relation to those it enjoys (or endures) in vivo. Generalizations to in vivo conditions must be made with caution. If at all possible, similar studies (perhaps less extensive, due to the greater technical difficulties) should be done in vivo to provide a basis for comparison. Investigators using drugs should be aware of, and respect, the basic pharmacological principles cited in the text. In particular, the substantial freedom the investigator has in defining the extracellular medium should not be abused.


How Has Statistical Testing in Orthopedics Changed Over Time? An Assessment of High Impact Journals Over 25 Years.
It is important for physicians to be familiar with statistical techniques commonly used in published medical research. Statistical errors in medical literature are common, and there is a reported lack of understanding regarding statistical knowledge necessary for data interpretation and journal reading. As study design has become increasingly complex, peer-reviewed literature poorly addresses and explains the most common statistical methods utilized across leading orthopedic journals. Articles from 5 leading general and subspecialty orthopedic journals were compiled from 3 distinct time periods. After exclusions were applied, 9521 remained, and a random 5% sampling of these articles, balanced across journals and years, was conducted yielding 437 articles after additional exclusions. Information regarding the number of statistical tests used, power/sample size calculation, type of statistical tests used, level of evidence (LOE), study type, and study design was collected. The mean number of statistical tests across all 5 orthopedic journals increased from 1.39 to 2.29 by 2018 (p = 0.007). The percentage of articles that reported power/sample size analyses was not found to differ by year, but the value has increased from 2.6% in 1994 to 21.6% in 2018 (p = 0.081). The most commonly used statistical test was the t-test which was present in 20.5% of articles, followed by chi-square test (13%), Mann-Whitney analysis (12.6%) and analysis of variance (ANOVA, 9.6%). The mean number of tests was generally greater in articles from higher impact factor journals (p = 0.013). Studies with a LOE of I used the highest mean number of statistical tests (3.23) compared to studies with lower LOE ratings (range 1.66-2.69, p < 0.001). Randomized control trials used the highest mean number of statistical test (3.31), while case series used the lowest mean number of tests (1.57, p < 0.001). The mean number of statistical tests used per article has increased over the past 25 years with the t-test, chi-square test, Mann-Whitney analysis, and ANOVA being the most used statistical tests in leading orthopedic journals. Despite an increase in statistical tests it should be noted that there was a paucity in advance statistical testing within the orthopedic literature. This study displays important trends in data analysis and can serve as a guide to help clinicians and trainees better understand the statistics used in literature as well as identifying deficits within the literature that should be addressed to help progress the field of orthopedics.


Admission temperature and hospital outcomes in extremely preterm infants.
To evaluate trends in admission temperature and its effect on mortality and short-term morbidities in extremely preterm infants. A regional cohort study of infants born at 23-28 weeks' gestation and admitted to the 10 neonatal intensive care units in New South Wales and the Australian Capital Territory between 1994 and 2012. Hypothermia was defined as skin temperature <36°C on admission to the neonatal intensive care unit. The primary outcome was hospital mortality. In total, 6267 infants were included. Mean admission temperatures improved significantly from 35.6°C in 1994 to 36.4°C in 2012 (R < 0.88). The incidence of hypothermia was 29.5 and 13.9% between 1994-2005 and 2006-2012, respectively. In comparison with normothermic infants, hypothermic infants had lower gestational age at birth (26 vs. 27 weeks) and lower birthweight (800 vs. 976 g). In-hospital mortality was higher in hypothermic infants (28.5 vs. 12.9%; odds ratio (OR) 2.69, 95% confidence interval (CI) 2.37-3.06). Severe intraventricular haemorrhage (12.1 vs. 8.5%, OR 1.48, 95% CI 1.25-1.75), necrotising enterocolitis (NEC) (11.0 vs. 7.5%; OR 1.54, 95% CI 1.29-1.83) and severe retinopathy of prematurity (16.5 vs. 8.9%; OR 2.02, 95% CI 1.70-2.39) were significantly higher in hypothermic infants. Multivariate regression analysis showed hypothermia was an independent risk factor for increased mortality (AOR (adjusted odds ratio ) 1.50, 95% CI 1.29-1.74, P < 0.001) and NEC (AOR 1.28, 95% CI 1.05-1.55, P = 0.01). Admission temperatures improved during the time period. Hypothermia at admission was associated with a significant increase in mortality and NEC.


Old targets, new strategy: Apigenin-7-O-β-d-(-6″-p-coumaroyl)-glucopyranoside prevents endothelial ferroptosis and alleviates intestinal ischemia-reperfusion injury through HO-1 and MAO-B inhibition.
With the increasing morbidity and mortality, intestinal ischemia/reperfusion injury (IIRI) has attracted more and more attention, but there is no efficient therapeutics at present. Apigenin-7-O-β-D-(-6″-p-coumaroyl)-glucopyranoside (APG) is a new flavonoid glycoside isolated from Clematis tangutica that has strong antioxidant abilities in previous studies. However, the pharmacodynamic function and mechanism of APG on IIRI remain unknown. This study aimed to investigate the effects of APG on IIRI both in vivo and in vitro and identify the potential molecular mechanism. We found that APG could significantly improve intestinal edema and increase Chiu's score. MST analysis suggested that APG could specifically bind to heme oxygenase 1 (HO-1) and monoamine oxidase b (MAO-B). Simultaneously, APG could attenuate ROS generation and Fe2+ accumulation, maintain mitochondria function thus inhibit ferroptosis with a dose-dependent manner. Moreover, we used siRNA silencing technology to confirm that knocking down both HO-1 and MAO-B had a positive effect on intestine. In addition, we found the HO-1 and MAO-B inhibitors also could reduce endothelial cell loss and protect vascular endothelial after reperfusion. We demonstrate that APG plays a protective role on decreasing activation of HO-1 and MAO-B, attenuating IIRI-induced ROS generation and Fe2+ accumulation, maintaining mitochondria function thus inhibiting ferroptosis.


Differentiating brain metastasis from glioblastoma by time-dependent diffusion MRI.
This study was designed to investigate the use of time-dependent diffusion magnetic resonance imaging (MRI) parameters in distinguishing between glioblastomas and brain metastases. A retrospective study was conducted involving 65 patients with glioblastomas and 27 patients with metastases using a diffusion-weighted imaging sequence with oscillating gradient spin-echo (OGSE, 50 Hz) and a conventional pulsed gradient spin-echo (PGSE, 0 Hz) sequence. In addition to apparent diffusion coefficient (ADC) maps from two sequences (ADC50Hz and ADC0Hz), we generated maps of the ADC change (cADC): ADC50Hz - ADC0Hz and the relative ADC change (rcADC): (ADC50Hz - ADC0Hz)/ ADC0Hz × 100 (%). The mean and the fifth and 95th percentile values of each parameter in enhancing and peritumoral regions were compared between glioblastomas and metastases. The area under the receiver operating characteristic curve (AUC) values of the best discriminating indices were compared. In enhancing regions, none of the indices of ADC0Hz and ADC50Hz showed significant differences between metastases and glioblastomas. The mean cADC and rcADC values of metastases were significantly higher than those of glioblastomas (0.24 ± 0.12 × 10-3mm2/s vs. 0.14 ± 0.03 × 10-3mm2/s and 23.3 ± 9.4% vs. 14.0 ± 4.7%; all p < 0.01). In peritumoral regions, no significant difference in all ADC indices was observed between metastases and glioblastomas. The AUC values for the mean cADC (0.877) and rcADC (0.819) values in enhancing regions were significantly higher than those for ADC0Hz5th (0.595; all p < 0.001). The time-dependent diffusion MRI parameters may be useful for differentiating brain metastases from glioblastomas.


Optimization of tocopherol concentration process from soybean oil deodorized distillate using response surface methodology.
Soybean oil deodorized distillate is a product derived from the refining process and it is rich in high value-added products. The recovery of these unsaponifiable fractions is of great commercial interest, because of the fact that in many cases, the "valuable products" have vitamin activities such as tocopherols (vitamin E), as well as anticarcinogenic properties such as sterols. Molecular distillation has large potential to be used in order to concentrate tocopherols, as it uses very low temperatures owing to the high vacuum and short operating time for separation, and also, it does not use solvents. Then, it can be used to separate and to purify thermosensitive material such as vitamins. In this work, the molecular distillation process was applied for tocopherol concentration, and the response surface methodology was used to optimize free fatty acids (FFA) elimination and tocopherol concentration in the residue and in the distillate streams, both of which are the products of the molecular distiller. The independent variables studied were feed flow rate (F) and evaporator temperature (T) because they are the very important process variables according to previous experience. The experimental range was 4-12 mL/min for F and 130-200 degrees C for T. It can be noted that feed flow rate and evaporator temperature are important operating variables in the FFA elimination. For decreasing the loss of FFA, in the residue stream, the operating range should be changed, increasing the evaporator temperature and decreasing the feed flow rate; D/F ratio increases, increasing evaporator temperature and decreasing feed flow rate. High concentration of tocopherols was obtained in the residue stream at low values of feed flow rate and high evaporator temperature. These results were obtained through experimental results based on experimental design.


B cell extracellular vesicles contain monomeric IgM that binds antigen and enters target cells.
The production and release of small phospholipid membrane vesicles, or extracellular vesicles (EVs), is a trait of most prokaryotic and eukaryotic cells. EVs display heterogeneity in content, size, biogenesis, activity, and function. B cells uniquely express immunoglobulin and produce EVs; however, the relationship between these entities has not been clarified. Here, we used several methodologies to isolate large (11,000 × g) and small (110,000 × g) EVs and evaluate their IgM content, characteristics and activity. We found that B cells from multiple cell lines and primary B cells produce EVs that display monomeric IgM on the surface and contain encapsulated monomeric IgM, which is independent of secreted pentameric IgM. Our data indicate EV IgM can bind antigen specifically, and EV IgM can be incorporated intracellularly into secondary cells. These results suggest immunological activities different from secreted pentameric IgM that may constitute a separate and distinct antibody distribution system.


N-acetylcysteine induced quenching of red fluorescent oligonucleotide-stabilized silver nanoclusters and the application in pharmaceutical detection.
In this work, we reported a new, simple and sensitive method for determination of N-acetylcysteine (NAC) based on quenching of the red fluorescence of oligonuleotide-protected silver nanoculsters (Ag NCs) with the quantum yield of 68.3±0.3%. This method was successfully used for the assay of NAC granules presenting a linear range from 100 nM to 1200 nM (LOD of 50 nM) with minimal interferences from potential coexisting substances. It is for the first time that quenching performance of the thiol-containing compound was found to follow a non-linear Stern-Volmer profile, indicative of a complicated quenching mechanism with static quenching dominating, in which DNA-template of Ag NCs was partly replaced by NAC, as elucidated by spectral investigations. This study extended the analytical application of silver nanoclusters as well as provided a more insightful understanding of the quenching mechanism of thiol-compounds on the fluorescence of Ag NCs.


Thrombin stimulates L-type calcium channels of guinea pig cardiomyocytes in cell-attached patches but not after intracellular dialysis.
The action of the blood clotting enzyme thrombin on single channel and whole cell Ca(2+)-currents was studied in isolated mammalian cardiac myocytes. Thrombin, at a concentration of 10(-8) mol/l, increased the Ca(2+)-channel activity in cell-attached patches. The mean open probability of the channel was enhanced, while the number of sweeps without openings, which reflects the availability of the channel, was significantly reduced. Neither the single channel conductance nor the activation curve were affected by thrombin. Thrombin was added to the bath solution, and its effect is therefore indirect and probably mediated via a second messenger. However, thrombin did not affect whole-cell Ca(2+)-currents, whereas a beta-adrenergic stimulation in the same cell increased the Ca(2+)-current. It is concluded that thrombin affects an intracellular mechanism for Ca2+ channel current regulation, which is still unknown and which is rapidly lost during conventional whole-cell Ca2+ current measurements.


Molecular characterization of thyroid toxicity: anchoring gene expression profiles to biochemical and pathologic end points.
Organic iodides have been shown to induce thyroid hypertrophy and increase alterations in colloid in rats, although the mechanism involved in this toxicity is unclear. To evaluate the effect that free iodide has on thyroid toxicity, we exposed rats for 2 weeks by daily gavage to sodium iodide (NaI). To compare the effects of compounds with alternative mechanisms (increased thyroid hormone metabolism and decreased thyroid hormone synthesis, respectively), we also examined phenobarbital (PB) and propylthiouracil (PTU) as model thyroid toxicants. Follicular cell hypertrophy and pale-staining colloid were present in thyroid glands from PB-treated rats, and more severe hypertrophy/colloid changes along with diffuse hyperplasia were present in thyroid glands from PTU-treated rats. In PB- and PTU-treated rats, thyroid-stimulating hormone (TSH) levels were significantly elevated, and both thyroxine and triiodothyronine hormone levels were significantly decreased. PB induced hepatic uridine diphosphate-glucuronyltransferase (UDPGT) activity almost 2-fold, whereas PTU reduced hepatic 5 -deiodinase I (5 -DI) activity to < 10% of control in support of previous reports regarding the mechanism of action of each chemical. NaI also significantly altered liver weights and UDPGT activity but did not affect thyroid hormone levels or thyroid pathology. Thyroid gene expression analyses using Affymetrix U34A GeneChips, a regularized t-test, and Gene Map Annotator and Pathway Profiler demonstrated significant changes in rhodopsin-like G-protein-coupled receptor transcripts from all chemicals tested. NaI demonstrated dose-dependent changes in multiple oxidative stress-related genes, as also determined by principal component and linear regression analyses. Differential transcript profiles, possibly relevant to rodent follicular cell tumor outcomes, were observed in rats exposed to PB and PTU, including genes involved in Wnt signaling and ribosomal protein expression.


Optimization of artificial neural network models through genetic algorithms for surface ozone concentration forecasting.
This study proposes three methodologies to define artificial neural network models through genetic algorithms (GAs) to predict the next-day hourly average surface ozone (O(3)) concentrations. GAs were applied to define the activation function in hidden layer and the number of hidden neurons. Two of the methodologies define threshold models, which assume that the behaviour of the dependent variable (O(3) concentrations) changes when it enters in a different regime (two and four regimes were considered in this study). The change from one regime to another depends on a specific value (threshold value) of an explanatory variable (threshold variable), which is also defined by GAs. The predictor variables were the hourly average concentrations of carbon monoxide (CO), nitrogen oxide, nitrogen dioxide (NO(2)), and O(3) (recorded in the previous day at an urban site with traffic influence) and also meteorological data (hourly averages of temperature, solar radiation, relative humidity and wind speed). The study was performed for the period from May to August 2004. Several models were achieved and only the best model of each methodology was analysed. In threshold models, the variables selected by GAs to define the O(3) regimes were temperature, CO and NO(2) concentrations, due to their importance in O(3) chemistry in an urban atmosphere. In the prediction of O(3) concentrations, the threshold model that considers two regimes was the one that fitted the data most efficiently.


A novel plasma-sprayed Ti4O7/carbon nanotubes/Al2O3 coating with bifunctional microwave application.
High-performance microwave absorption coatings are critically required in the stealth defense system of military platforms. Regrettably, just optimizing the property but neglecting the application feasibility seriously inhibits its practical application in the field of microwave absorption. To face this challenge, the Ti4O7/carbon nanotubes (CNTs)/Al2O3 coatings were successfully fabricated by a plasma-sprayed method. For the different oxygen vacancy-induced Ti4O7 coatings, the enhanced ε' and ε'' values in the frequency of X-band is due to the synergistic manipulation of conductive path, defects and interfacial polarization. The optimal reflection loss of Ti4O7/CNTs/Al2O3 sample (0 wt% CNTs) is -55.7 dB (8.9 GHz of 2.41 mm), while the electromagnetic interference shielding effectiveness of Ti4O7/CNTs/Al2O3 sample (5 wt% CNTs) increases to 20.5 dB as the enhanced electrical conductivity. In special, the flexural strength of Ti4O7/CNTs/Al2O3 coatings first increases from 48.59 MPa (0 wt% CNTs) to 67.13 MPa (2.5 wt% CNTs) and then decreases to 38.31 MPa (5 wt% CNTs), demonstrating that an appropriate amount of CNTs evenly dispersed in the Ti4O7/Al2O3 ceramic matrix can effectively play the role of CNTs as the strengthening phase of the coatings. This research will provide a strategy by tailoring synergistic effect of dielectric loss and conduction loss for oxygen vacancy-mediated Ti4O7 material to broaden the application of absorbing or shielding ceramic coatings.


The residue from the acidic concentrated lithium bromide treated crop residue as biochar to remove Cr (VI).
In this work, the hydrolysis residue produced from the acidic concentrated lithium bromide hydrolysis (ALBH) of wheat straw, corn stover and elephant grass were characterized as biochar. The ALBH biochar as the black power had high content of carbon (49.65-55 wt%), specific surface areas (4.53-7.79 m2/g), porous structures (micropores, mesopores and macropores) and abundant oxygen functional groups (hydroxy, carbonyl, ester and ketone groups). These properties made ALBH biochar as a potential adsorbent for environmental remediation, with relatively high removal efficiency for a variety of heavy metal ions, especially hexavalent chromium (Cr(VI)). Therefore, ALBH technology may be an efficient strategy for synthesis of bio-char along with fermentable sugars, which met the concern of sustainability and green chemistry.


Immunization and atopy: possible implications of ethnicity.
The possible effects of immunization on subsequent development of asthma and atopy remains a matter of controversy. Although some studies have suggested that immunization might increase the risk for atopic disease, a number of studies have found no association or have even reported a protective effect for immunization against atopy. Recent studies have provided evidence that ethnicity might affect the susceptibility to the immunomodulatory effects of vaccination. In this review the association between immunization and atopy and the effect of ethnicity on this association are briefly outlined. The focus will be particularly on BCG vaccination.


Airway Impedance: A Novel Diagnostic Tool to Predict Extraesophageal Airway Inflammation.
To validate a novel biomarker, airway impedance for extraesophageal disease. We prospectively recruited patients with respiratory symptoms undergoing combined endoscopy and direct laryngoscopy for the evaluation of symptoms. The direct laryngoscopy was performed and videotaped for blinded scoring by 3 otolaryngologists and an impedance catheter was placed onto the posterior larynx to obtain measurements. Following this, an endoscopy was performed and impedance measurements and biopsies were taken at 3 esophageal heights. Impedance values were compared within and between patients. Eighty-eight patients were recruited, of which 73 had complete airway and endoscopic exams. There was no significant correlation between airway impedance values and mean reflux finding scores (r2 = 0.45, P = .07). There was no significant positive correlation between airway impedance and esophageal impedance values (r2 = 0.097-0.138, P > .2). Patients taking proton pump inhibitors had significantly lower mean airway impedance values (706 ± 450 Ω) than patients not taking them (1069 ± 809 Ω, P = .06). Patients who had evidence of aspiration on video fluoroscopic swallow studies had lower airway impedance (871 ± 615 Ω) than patients without aspiration (1247 ± 360 Ω, P = .008). Inhaled steroids did not impact airway impedance levels (P = .7). Airway impedance may be an important diagnostic tool to diagnose gastroesophageal reflux or aspiration, eliminating the subjectivity of airway appearance alone.


Cystathionine-gamma-lyase deficient mice are protected against the development of multiorgan failure and exhibit reduced inflammatory response during burn.
Considering the role of H2S in critical illness, the aim of this study was to compare the outcome of burn in wild-type mice and in mice deficient in CSE, one of the principal mammalian H2S-generating enzymes. Animals were subjected to scald burn. Outcome variables included indices of organ injury, clinical chemistry parameters and plasma levels of inflammatory mediators. Plasma levels of H2S significantly increased in response to burn in wild-type mice, but remained unchanged in CSE-/- mice. Expression of the three H2S-producing enzymes (CSE, CBS and 3-MST) in the lung and liver, and the capacity of tissue homogenates to produce H2S, however, was not affected by burn. In CSE deficient mice there was a significant amelioration of burn-induced accumulation of myeloperoxidase levels in heart, lung, liver and kidney and significantly lower degree of malon dialdehyde accumulation in the heart, lung and kidney than in wild-type mice. CSE deficient mice, compared to wild-type mice, showed a significant attenuation of the burn-induced elevation in circulating alkaline aminotransferase and blood urea nitrogen and creatinine levels, indicative of protective effects of CSE deficiency against burn-induced hepatic, and renal functional impairment. Multiple burn-induced inflammatory mediators (TNF-α, IL-1β, IL-4, IL-6, IL-10 and IL-12) were significantly lower in the plasma of CSE-/- animals after burn than in the plasma of wild-type controls subjected to burns. In conclusion, CSE deficiency improves organ function and attenuates the inflammatory response in a murine model of burn.


Histopathology of epi-LASIK in eyes with virgin corneas and eyes with previously altered corneas.
To perform a histological analysis of free epithelial flaps that were intentionally created with an Epi-K epikeratome (Moria S.A.) during epi-LASIK in eyes with virgin corneas and eyes with previous corneal surgery or keratoconus. Vissum-Instituto Oftalmológico de Alicante, Alicante, Spain. This prospective and consecutive case series comprised 18 free flaps obtained from 18 patients. Twelve patients had virgin corneas, and 6 had altered corneas from previous surgery, trauma, or keratoconus. The flaps were fixed in 4% buffered formaldehyde (pH 7) for posterior histopathological analysis. Serial cuts of each flap were performed, and the sheets were stained with hematoxylin-eosin and periodic acid-Schiff. The main outcome measure was the histopathology of the corneal flaps. All flaps from virgin corneas consisted entirely of epithelium without residual stromal tissue or Bowman's layer. Histopathological analysis of the flaps after epi-LASIK in patients with previously altered corneas showed varying levels of stroma in all cases. Epi-LASIK with the Epi-K epikeratome effectively cleaved the epithelium from Bowman's layer in healthy corneas; however, when the integrity of Bowman's layer is compromised, epi-LASIK should be avoided as stromal invasion will likely occur.


Dietary alfalfa hay or lipid-soluble alfalfa extract may improve broiler growth, but fiber presence may be detrimental during Eimeria vaccine challenge.
Lipid-soluble components in late-cutting alfalfa are linked to beneficial immune and microbiota responses in mouse challenge models; therefore, responses in a comparative poultry Eimeria challenge model were investigated. The study objective was to evaluate performance, immunity, and the cecal microbiota in broilers fed ground hay or lipid-soluble extract from late (fifth) cutting alfalfa during Eimeria challenge. At hatch, 432 Ross 708 broilers were placed in 24 floor pens (18 birds/pen) and assigned to 3 isocaloric/isonitrogenous dietary treatments consisting of control, 5% ground hay, or 0.25% lipid-soluble extract for a 42-d trial divided into 14 d starter, grower, and finisher periods. On d 14, 4 birds/treatment were euthanized to collect blood and cecal contents before half the remainder were inoculated with 10X Merck Coccivac-B52 (Kenilworth, NJ). Tissue samples were collected at 3, 7, 14, and 28 d postinoculation (pi; 4 birds/diet × Eimeria group) with body weight (BW) and feed intake (FI) recorded weekly. Immune populations within peripheral blood mononuclear cells were characterized by flow cytometry while cecal microbial communities were profiled by 16S rRNA gene amplicon sequencing. Data were normalized when appropriate and analyzed to evaluate the effects of diet, Eimeria challenge, and timepoint (SAS 9.4; P ≤ 0.05). Before challenge, dietary alfalfa hay or extract increased FI 6.9 to 8.0% and increased CD3+ T cells 19.3 to 24.9% compared to control-fed birds (P ≤ 0.007). Alfalfa did not significantly affect post-Eimeria performance, but Eimeria-challenged birds fed hay showed the greatest numeric reduction in final BW compared to their unchallenged counterparts (0.17 kg) vs. control and extract-fed birds (0.02-0.04 kg). Immune cell changes did not indicate recruitment from peripheral blood to local infection sites; however, alfalfa hay may have accelerated Bu-1+ B cell development by 7 d in unchallenged birds (P < 0.0001). During Eimeria-challenge, dietary alfalfa extract preserved alpha diversity measures related to species richness (P ≤ 0.007). Collectively, these results indicate potential benefits of feeding lipid-soluble extract from late cutting alfalfa to broilers during Eimeria challenge.


Binding capacities of various analogues of S-adenosyl-L-homocysteine to protein methyltransferase II from human erythrocytes.
A series of analogues of S-adenosyl-L-homocysteine, modified mainly in the amino acid portion of the molecule, have been synthesized. All were found to be competitive inhibitors of protein methyltransferase II from human erythrocytes. S-adenosyl-L-homocysteine remains however by far the most effective inhibitor of the methylase.


An assessment of the mechanical properties of leaflets from four second-generation porcine bioprostheses with biaxial testing techniques.
The aim of this study was to determine whether second-generation porcine bioprostheses, glutaraldehyde fixed at pressures said to be less than 4 mm Hg, exhibit more natural leaflet material properties than earlier valves fixed at 80 to 100 mm Hg. Biaxial mechanical testing techniques were used to compare Carpentier-Edwards SAV, St. Jude Medical BioImplant, Hancock II, and Medtronic Intact bioprostheses (12 leaflets from four valves in each case) with fresh porcine aortic valves and high pressure-fixed Carpentier-Edwards 6625 bioprostheses (14 leaflets from five valves in each case). The circumferential extensibility of leaflets from Medtronic Intact bioprostheses and from fresh porcine aortic valves were not significantly different (p greater than 0.05), whereas leaflets from the other second-generation valves tested and from Carpentier-Edwards 6625 valves were highly inextensible in the circumferential direction. The radial material properties of leaflets from all bioprostheses differed from those of fresh porcine aortic valves, which were very extensible with a high pretransitional compliance. The radial extensibility and compliance of Hancock II, St. Jude Medical BioImplant, and Carpentier-Edwards 6625 leaflets were not significantly different (p greater than 0.05). In the radial direction, Carpentier-Edwards SAV and Medtronic Intact valve leaflets were substantially more extensible than Carpentier-Edwards 6625 leaflets (p less than 0.01), whereas Medtronic Intact leaflets were more compliant than all other bioprostheses. These data demonstrate (1) that second-generation porcine bioprosthetic valves do not necessarily exhibit more natural leaflet material properties than earlier high pressure-fixed xenografts and (2) that Medtronic Intact valve leaflets have material properties most closely approximating the fresh porcine aortic valve.


Probing conformational dynamics in biomolecules via chemical exchange saturation transfer: a primer.
Although Chemical Exchange Saturation Transfer (CEST) type NMR experiments have been used to study chemical exchange processes in molecules since the early 1960s, there has been renewed interest in the past several years in using this approach to study biomolecular conformational dynamics. The methodology is particularly powerful for the study of sparsely populated, transiently formed conformers that are recalcitrant to investigation using traditional biophysical tools, and it is complementary to relaxation dispersion and magnetization transfer experiments that have traditionally been used to study chemical exchange processes. Here we discuss the concepts behind the CEST experiment, focusing on practical aspects as well, we review some of the pulse sequences that have been developed to characterize protein and RNA conformational dynamics, and we discuss a number of examples where the CEST methodology has provided important insights into the role of dynamics in biomolecular function.


Risk of de novo proteinuria following hospitalization with acute kidney injury.
Acute Kidney Injury (AKI) incidence has continued to rise and is recognized as a major risk factor for kidney disease progression and cardiovascular complications. Early recognition of factors associated with post-AKI complications is fundamental to stratifying patients that could benefit from closer follow-up and management after an episode of AKI. Recent studies have shown that proteinuria is a prevalent sequela after AKI and a strong predictor of complications post-AKI. This study aims to evaluate the frequency and timing of the development of de-novo proteinuria after an AKI episode in patients with known kidney function and no prior history of proteinuria. We retrospectively analyzed data from adult AKI patients with pre- and post-kidney function information between Jan 2014 and March 2019. The presence of proteinuria determined before and after index AKI encounter was based on ICD-10 code and/or urine dipstick and UPCR during the follow-up period. Of 9697 admissions with AKI diagnoses between Jan 2014 and March 2019, 2120 eligible patients with at least one assessment of Scr and proteinuria before AKI index admission were included in the analysis. The median age was 64 (IQR 54-75) years, and 57% were male. 58% (n-1712) patients had stage 1 AKI, 19% (n = 567) stage 2 AKI, and 22% (n = 650) developed stage 3 AKI. De novo proteinúria was found in 62% (n = 472) of patients and was already present by 90 days post-AKI in 59% (209/354). After adjusting for age and comorbidities, severe AKI (stage 2/3 AKI) and diabetes, were independently associated with increased risk for De novo proteinuria. Severe AKI is an independent risk factor for subsequent de novo proteinuria post-hospitalization. Further prospective studies are needed to determine whether strategies to detect AKI patients at risk of proteinuria and early therapeutics to modify proteinuria can delay the progression of kidney disease.


Assessment of membrane protection by 31P-NMR effects of lidocaine on calcium-paradox in myocardium.
In studying calcium paradox, perfused rat hearts were used to investigate the myocardial protective effects of lidocaine. Intracellular contents of phosphates were measured using the 31P-NMR method. In hearts reexposed to calcium, following 3 minute calcium-free perfusion, a rapid contracture occurred, followed by rapid and complete disappearance of intracellular phosphates with no resumption of cardiac function. In hearts where lidocaine was administered from the onset of the calcium-free perfusion until 2 minutes following the onset of reexposure to calcium, both intracellular phosphates and cardiac contractility were maintained. Therefore, it can be said that cell membranes were protected by lidocaine.


Cross-reactions of bovine herpesvirus 1 antigens with those of other cattle herpesviruses.
Bovine embryonic kidney cells were infected with bovine herpesviruses (BHV1, 2, or 3), suid herpesvirus 1 (SHV1), or were sham-inoculated. When cytopathic effect was apparent, the cells were solubilized using Triton X-100 detergent. Resulting antigen preparations were tested by 2-dimensional immunoelectrophoresis using bovine fetal serum and antisera directed against BHV1, BHV2, BHV3, SHV1 or a restricted spectrum of BHV1 antigens. Interaction of BHV1 antiserum with BHV1 antigen preparations resulted in 11 precipitation arcs. The same antiserum produced 3 arcs with BHV2, none with BHV3, and 5 with SHV1. The interaction of BHV1 antigen preparations with BHV2, BHV3, or SHV1 antisera failed to produce demonstrable arcs. However, when heterologous antigen or antibody preparations were added to BHV1 homologous 2-dimensional immunoelectrophoresis tests, all 11 BVH1 arcs were modified by BHV1, 2 by BHV2, 4 by BHV3 and 4 by SHV1 preparations. Two antigens were common to the 4 herpesviruses. Antigen preparations were tested for their ability to inhibit virus neutralization by BHV1 antiserum; only the BHV1 preparation was active. Sera were tested for BHV1 neutralizing activity; only BHV1 antiserum and a serum specific for a restricted spectrum of BHV1 antigens were active. A glycoprotein antigen associated with BHV1 neutralization was identified which may be important in the protection of animals against disease.


Screening for Inhibitors of YAP Nuclear Localization Identifies Aurora Kinase A as a Modulator of Lung Fibrosis.
Idiopathic pulmonary fibrosis is a progressive lung disease with limited therapeutic options that is characterized by pathological fibroblast activation and aberrant lung remodeling with scar formation. YAP (Yes-associated protein) is a transcriptional coactivator that mediates mechanical and biochemical signals controlling fibroblast activation. We previously identified HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase inhibitors (statins) as YAP inhibitors based on a high-throughput small-molecule screen in primary human lung fibroblasts. Here we report that several Aurora kinase inhibitors were also identified from the top hits of this screen. MK-5108, a highly selective inhibitor for AURKA (Aurora kinase A), induced YAP phosphorylation and cytoplasmic retention and significantly reduced profibrotic gene expression in human lung fibroblasts. The inhibitory effect on YAP nuclear translocation and profibrotic gene expression is specific to inhibition of AURKA, but not Aurora kinase B or C, and is independent of the Hippo pathway kinases LATS1 and LATS2 (Large Tumor Suppressor 1 and 2). Further characterization of the effects of MK-5108 demonstrate that it inhibits YAP nuclear localization indirectly via effects on actin polymerization and TGFβ (Transforming Growth Factor β) signaling. In addition, MK-5108 treatment reduced lung collagen deposition in the bleomycin mouse model of pulmonary fibrosis. Our results reveal a novel role for AURKA in YAP-mediated profibrotic activity in fibroblasts and highlight the potential of small-molecule screens for YAP inhibitors for identification of novel agents with antifibrotic activity.


[Experience with open meniscus refixation. Results of follow-up in 17 cases].
Results of refixation in 17 cases of meniscus ruptures are presented. The operation was an open arthrotomy. The follow-up examination is described. There are found 7 very good, 7 good and 3 satisfactory results. These results allow the attempt to preserve meniscus under certain preconditions by means of suture.


Protective effects of acetyl-L-carnitine against serum and glucose deprivation-induced apoptosis in rat adipose-derived mesenchymal stem cells.
Low survival rate of grafted mesenchymal stem cells (MSC) in injured tissue is one of the major limitations of stem cell therapy. One of the most important factors that limits the MSCs survival rate and retention is ischemic stress, which can lead to damage to all components of the cell. In particular, it can damage mitochondria, that play an important role in apoptosis with releasing apoptotic factors. Therefore, we investigated the protective effects of Acetyl-L-carnitine (ALCAR) against serum and glucose deprivation (SGD) in adipose-derived mesenchymal stem cells (AD-MSCs). We measured cell viability, proliferation, and apoptosis in cells experiencing SGD stress for 8 h with exposure to varying concentrations of ALCAR. Results showed that ALCAR protects cells against SGD stress by reducing apoptosis. Its protective effects are associated with reductions in cleaved caspase-3 and attenuation of apoptosis. Result showed that ALCAR exhibits protective effects against SGD-induced damage to AD-MSCs by enhancing the expression of survival signals and by decreasing the expression of death signals.


Studies on human corneal ulcers treated with histoacrylic glue. Morphological studies of a successful and unsuccessful membrane.
Artificial epithelial corneal barriers of histoacrylic glue have been used since 1968. Experimental and clinical studies have since then indicated that the barrier protects the cornea from repopulation by polymorphonuclear leukocytes from the tears and thereby from tissue-destroying enzymes. Using light-, scanning electron- and transmission electron-microscopical techniques, the differences between a successful and an unsuccessful treatment of a corneal ulcer with histoacrylic glue have been investigated. The successful glue barrier is a continuous membrane tightly bound to the corneal stroma and preventing population of the stroma by polymorphonuclear leukocytes from the tear fluid.


Clinical validation of a non-invasive electrodermal biofeedback device useful for reducing chronic perceived pain and systemic inflammation.
This study was performed to evaluate the potential clinical usefulness of a new non-invasive electrodermal biofeedback device in reducing perceived pain levels and chronic systemic inflammation. This multicenter study was designed and coordinated by BioTekna, included 20 general practice medical centers, took place between June 2010 and January 2011, and was validated clinically at the National and Kapodistrian University of Athens, Greece. The study participants were 1015 Caucasian men (401) and women (614), while the placebo-treated controls were 950 Caucasian men (500) and women (450). Patients were aged between 30 and 86 years (average age about 50 years) and all suffered from chronic pain and other medically unexplained symptoms (MUS). The RegMatEx electrodermal biofeedback device (brand BioTekna - Biomedical Technologies, Marcon, Venice, Italy) was used to evaluate the clinical efficacy of electrodermal biofeedback in reducing the level of pain perceived by decreasing the chronic systemic inflammation of the subjects. All subjects received 6 × 30 min sessions of electrodermal or placebo biofeedback given twice a week over 3 weeks. Perceived pain was evaluated using the Numeric Rating Scale (NRS) for pain, while systemic inflammation was examined with measurements of morning circulating C-reactive protein (CRP) concentrations. Perceived pain in the treatment group was significantly lessened in the NRS scale (p < 005), while circulating CRP concentrations were also decreased (p < 0.05). Parallel placebo studies showed no changes in perceived pain or morning serum CRP concentrations. Use of the electrodermal biofeedback RegMatEx device was associated with reduced pain perception and decreased chronic systemic inflammation, with stability over time. This did not occur in the placebo-treated group. The symptomatology of the treated patients significantly improved in terms of pain relief as shown on the NRS scale, and this was accompanied by reported improvements in mobility, mood, and quality of life. The RegMatEx electrodermal biofeedback procedure is a non-invasive and easy to use therapeutic method, free of side effects, with high patient acceptability, excellent efficacy, and duration of effect, and, hence, a valuable tool in the treatment of chronic pain and inflammation.


Effects of an autonomy-supportive exercise instructing style on exercise motivation, psychological well-being, and exercise attendance in middle-age women.
The present study evaluated the effectiveness of an autonomy-supportive intervention based on self-determination theory in influencing perceptions of autonomy support, basic psychological needs, behavioral regulations, subjective vitality, and exercise behavior. 35 female exercise participants age 30 to 58 years who enrolled to an 8-week exercise program attended 24 exercise classes that were taught using either an autonomy-supportive (n = 19) or a lack of autonomy support (n = 16) instructing style. The experimental group reported an increase in perceived autonomy support, the fulfillment of the needs for autonomy and competence, identified regulation, intrinsic motivation, and subjective vitality. They also reported higher attendance rates during the program and greater participation to moderate and/or mild nonstructured exercise during 5 weeks after the end of the program. The control group reported a decrease in perceived autonomy support, the needs for autonomy and competence, intrinsic motivation, and subjective vitality. The results supported tenets of self-determination theory and highlighted the motivational and psychological benefits of an autonomy-supportive exercise instructing style among middle-age women.


The random measurement of the transverse diameter of the fetal heart: a potential source of error.
In a recent report it was suggested that the transverse diameter of the fetal heart measured randomly during the cardiac cycle from the real-time image was useful in predicting congenital heart disease (Jeanty P, Romero R, Cantraine F, et al: Fetal cardiac dimensions: a potential tool for the diagnosis of congenital heart disease. J Ultrasound Med 3:359, 1984). Comparing the above approach with M-mode measurements at end-diastole and end-systole suggests that random measurement of the transverse diameter is not appropriate for fetal cardiovascular evaluation because it could predict over 40 per cent of normal fetuses to have an "abnormally" increased cardiac dimension.


Pharmacokinetics of haloalkylamines: cyclization and distribution in blood in vitro and in vivo.
The cyclization of N-(5-chloropentyl)-N-methylaminoaceto-2,6-xylidide hydrochloride (RAD 150) and N-(5-bromopentyl)-N-methylamino-aceto-2,6-xylide hydrobromide (RAD 154) in red blood cells of rats and rabbits was examined under in vitro and in vivo conditions. The rate of cyclization was much slower in plasma and blood than in a buffer solution, probably due to influence of protein binding of the compounds. The tertiary amines disappeared rapidly from the blood cells in vitro and in vivo and the piperidinium derivative (RAD 179) formed from the haloalkylamines disappeared almost as rapidly as the tertiary amines from the plasma in vivo. In contrast, the efflux of RAD 179 formed in the blood cells was slow (T 1/2 for rabbit erythrocytes: 9 h in vitro; 8 h in vivo) following a 1st order reaction. RAD 179 itself was only to a small extent taken up in the blood cells.


The structure of trp pseudorepressor at 1.65A shows why indole propionate acts as a trp 'inducer'.
The trp repressor is a small dimeric regulatory protein which controls the expression of three operons in Escherichia coli. The inactive aporepressor protein must bind two molecules of L-tryptophan to form the active repressor. If desamino analogues of L-tryptophan such as indole propionate (IPA) are substituted for L-tryptophan, an inactive pseudorepressor is formed. Because the desamino analogues thus cause derepression of operons under control of the trp repressor, they appear to be 'inducers'. We have determined the crystal structure of the pseudorepressor and refined it to 1.65 A. The molecular structure was compared to that of the nearly isomorphous orthorhombic form of the repressor. Surprisingly, the indole ring of IPA is in the same position as the indole ring of L-tryptophan in the repressor, but is 'flipped over'. As a result, the carboxyl group of IPA is oriented toward the DNA-binding surface of the protein and is in a position where it sterically and electrostatically repels the phosphate backbone of both operator and non-operator DNA. This explains why IPA acts as an apparent trp inducer.


Bacterial, short-chain fatty acid and gas profiles of partially hydrolyzed guar gum in vitro fermentation by human fecal microbiota.
Carbohydrates with different structures have metabolic differences in the human body, as well as individual differences. The present study aimed to investigate the effects of bacterial, short-chain fatty acids (SCFAs) and gas profiles of partially hydrolyzed guar gum (PHGG) on the fecal microbiota of 41 Chinese individuals by simulated fermentation in vitro. Results showed that PHGG stimulated the growth of Bifidobacterium and Faecalibacterium, inhibited the growth of Escherichia-Shigella, Klebsiella, and Dorea, and induced the production of fermentation gases (CO2, and H2) and SCFAs (acetic acid, butyric acid). Furthermore, Bifidobacterium was significantly increased in the young female and the old male-originated samples, while Klebsiella was significantly decreased in the old female ones after PHGG intervention, and there were also certain differences in gases and SCFAs among different population samples. These findings indicate that PHGG can modulate gut microbiota and metabolism well, whereas its use varies in different populations.


Weighing up beta-cell mass in mice and humans: self-renewal, progenitors or stem cells?
Understanding how beta-cells maintain themselves in the adult pancreas is important for prioritizing strategies aimed at ameliorating or ideally curing different forms of diabetes. There has been much debate over whether beta-cell proliferation, as a means of self-renewal, predominates over the existence and differentiation of a pancreatic stem cell or progenitor cell population. This article describes the two opposing positions based largely on research in laboratory rodents and its extrapolation to humans.


Quality of medical care and excess mortality in psychiatric patients--a nationwide register-based study in Sweden.
To assess overall and cause-specific mortality and the quality of somatic care among psychiatric patients. A register-based cohort study. All individuals aged 20-79 years in Sweden in 2005. In total 6 294 339 individuals. The individuals were followed for mortality in 2006 and 2007, generating 72 187 deaths. Psychiatric patients were grouped according to their diagnosis in the National Patient Register. Mortality risk of psychiatric patients was compared with that of non-psychiatric patients. Estimates of RR of mortality were calculated as incidence rate ratios (IRRs) with 95% CIs using Poisson regression analysis. Psychiatric patients were compared with non-psychiatric patients for three healthcare quality indicators: the proportion of avoidable hospitalisations, case death rate after myocardial infarction and statin use among diabetic patients. Compared with individuals with no episodes of treatment for mental disorder, psychiatric patients had a substantially increased risk of all studied causes of death as well as death from conditions considered amenable to intervention by the health service, that is, avoidable mortality. The highest mortality was found among those with another mental disorder, predominantly substance abuse (for women, an IRR of 4.7 (95% CI 4.3 to 5.0) and for men, an IRR of 4.8 (95% CI 4.6 to 5.0)). The analysis of quality of somatic care revealed lower levels of healthcare quality for psychiatric patients, signalling failures in public health and medical care. This study shows a marked increase in excess mortality, suggesting a lower quality of somatic healthcare in psychiatric patients.


Crystal structure of a papain-fold protein without the catalytic residue: a novel member in the cysteine proteinase family.
A 31kDa cysteine protease, SPE31, was isolated from the seeds of a legume plant, Pachyrizhus erosus. The protein was purified, crystallized and the 3D structure solved using molecular replacement. The cDNA was obtained by RT PCR followed by amplification using mRNA isolated from the seeds of the legume plant as a template. Analysis of the cDNA sequence and the 3D structure indicated the protein to belong to the papain family. Detailed analysis of the structure revealed an unusual replacement of the conserved catalytic Cys with Gly. Replacement of another conserved residue Ala/Gly by a Phe sterically blocks the access of the substrate to the active site. A polyethyleneglycol molecule and a natural peptide fragment were bound to the surface of the active site. Asn159 was found to be glycosylated. The SPE31 cDNA sequence shares several features with P34, a protein found in soybeans, that is implicated in plant defense mechanisms as an elicitor receptor binding to syringolide. P34 has also been shown to interact with vegetative storage proteins and NADH-dependent hydroxypyruvate reductase. These roles suggest that SPE31 and P34 form a unique subfamily within the papain family. The crystal structure of SPE31 complexed with a natural peptide ligand reveals a unique active site architecture. In addition, the clear evidence of glycosylated Asn159 provides useful information towards understanding the functional mechanism of SPE31/P34.


KRAB zinc finger protein diversification drives mammalian interindividual methylation variability.
Most transposable elements (TEs) in the mouse genome are heavily modified by DNA methylation and repressive histone modifications. However, a subset of TEs exhibit variable methylation levels in genetically identical individuals, and this is associated with epigenetically conferred phenotypic differences, environmental adaptability, and transgenerational epigenetic inheritance. The evolutionary origins and molecular mechanisms underlying interindividual epigenetic variability remain unknown. Using a repertoire of murine variably methylated intracisternal A-particle (VM-IAP) epialleles as a model, we demonstrate that variable DNA methylation states at TEs are highly susceptible to genetic background effects. Taking a classical genetics approach coupled with genome-wide analysis, we harness these effects and identify a cluster of KRAB zinc finger protein (KZFP) genes that modifies VM-IAPs in trans in a sequence-specific manner. Deletion of the cluster results in decreased DNA methylation levels and altered histone modifications at the targeted VM-IAPs. In some cases, these effects are accompanied by dysregulation of neighboring genes. We find that VM-IAPs cluster together phylogenetically and that this is linked to differential KZFP binding, suggestive of an ongoing evolutionary arms race between TEs and this large family of epigenetic regulators. These findings indicate that KZFP divergence and concomitant evolution of DNA binding capabilities are mechanistically linked to methylation variability in mammals, with implications for phenotypic variation and putative paradigms of mammalian epigenetic inheritance.


Stop signs in hippocampal insulin signaling: the role of insulin resistance in structural, functional and behavioral deficits.
In peripheral tissues insulin activates signaling cascades to facilitate glucose uptake from the blood into tissues like liver, muscle and fat. While insulin appears to play a minor role in the regulation of glucose uptake in the central nervous system (CNS), insulin is known to play a major role in regulating synaptic plasticity in brain regions like the hippocampus. The concept that insulin regulates hippocampal neuroplasticity is further supported from animal models of type 2 diabetes (T2DM) and Alzheimer's disease (AD). The goal of this review is to provide an overview of these studies, as well as the studies that have examined whether deficits in hippocampal insulin signaling are amenable to intervention strategies.


Limitations of oxygen transport to the cell.
Perhaps the major points to be made from this review are the following: 1. Transport of O2 from the environment to the mitochondrion is accomplished in a well-described but not yet well-understood sequence of diffusive and convective steps that are highly interactive and thus integrative in their outcome. 2. Thus, under conditions of O2-supply limitation of VO2max in strenuous exercise in health, all transport steps affect the value of VO2max reached, but the sensitivity of VO2max (to changes in any step) is not the same for each step, and moreover, will vary with the quantitative conditions. It is time to abandon the very concept of a single limiting factor to VO2max. 3. O2 supply limitation of VO2 is seen under two very different conditions that in fact are at the opposite ends of the spectrum of metabolic scope: VO2max in strenuous exercise in health and basal VO2 in severe disease. Analysis of the latter using lessons learned from the former may be valuable. 4. We are currently greatly limited in our understanding of supply limitation in disease, mostly because of unavailability of methods to assess organ-specific cellular metabolism and its relation to O2 supply in patients, essentially noninvasively--a research direction that needs much support.


Visits at the primary clinic do not reduce ketoacidosis rates at presentation in type 1 diabetes mellitus.
The rate of diabetic ketoacidosis at time of diagnosis of type 1 diabetes remains high. We examined whether visits to a primary care clinic up to a month prior to diagnosis of new onset diabetes affected ketoacidosis rates. Retrospective chart review of children who were diagnosed with type 1 diabetes from January 1, 2010, to December 31, 2014. Data collection included demographics, age at diagnosis, number of visits to the primary care clinic during the month prior the diagnosis, relevance to diabetes and outcome of those visits and the presence of ketoacidosis at diagnosis. We examined the relationship between the rate of ketoacidosis at diagnosis and the number of visits in the clinic, and to the demographic characteristics. Of 159 patients, 115 visited their clinic in the month prior to diagnosis of type 1 diabetes. The rate of ketoacidosis at diagnosis was similar between those who visited the clinic and those who did not (37.4% compared to 38.6%). There was no difference in ketoacidosis rates between the different ethnic and socio-economic groups. Medical encounters in the month prior to diagnosis of type 1 diabetes did not reduce ketoacidosis rates in children.


Retracted: A Study of Athlete Pose Estimation Techniques in Sports Game Videos Combining Multiresidual Module Convolutional Neural Networks.
[This retracts the article DOI: 10.1155/2021/4367875.].


Primary Ewing's Sarcoma of Body of Mandible, Multimodal Treatment with Excellent Spontaneous Bone Regeneration: a Case Report.
Ewing's sarcoma is an invariable manifestation in facial bones. Primary lesions in head and neck region had come up with better prognosis compared to other primary sites; hence, management of such jaw lesions is a challenge particularly in pediatric patients during first decade of life as functional impairment and facial disfigurement may affect the quality of life. Here, we are discussing a unique case of primary lesion of horizontal region of mandible with special focus on use of radiation therapy, radiation dose-related effects and spontaneous bone regeneration.


Primary malignant melanoma of the esophagus: a rare and aggressive disease.
Primary malignant melanoma of the esophagus is an uncommon tumor, with approximately 300 cases having been reported thus far. The purpose of this study was to describe a case of a 60 year-old man with a 10 month history of progressive dysphagia and thoracic pain, the investigations of which led to a diagnosis of primary malignant melanoma of the esophagus. The patient underwent a transhiatal esophagectomy with subcarinal lymphadenectomy, and isoperistaltic gastric tube replacement of the esophagus. Nine months after surgery, he developed ischemic colitis, and metastasis in the mesentery was diagnosed. His disease progressed and he died one year after the esophagectomy. A review of the literature was performed.


YAP/STAT3 inhibited CD8+ T cells activity in the breast cancer immune microenvironment by inducing M2 polarization of tumor-associated macrophages.
Breast cancer (BC) is the leading cause of cancer-related death among women. One of the hallmarks of cancer is sustained angiogenesis. YAP/STAT3 may promote angiogenesis and driving BC progression. This study aimed to investigate how YAP/STAT3 affects the immune microenvironment in BC and understand the underlying mechanism. To establish a tumor-associated macrophages (TAMs) model, macrophages were cultured in the 4T1 cell culture medium. A BC mouse model was created by injecting 4T1 cells. The expression of YAP, STAT3, p-STAT3, VEGF, VEGFR-2, and PD-L1 was analyzed using immunofluorescence, western blotting, and quantitative real-time PCR. Flow cytometry was used to identify M1 and M2 macrophages, CD4+ T, CD8+ T, and Treg cells. Levels of iNOS, IL-12, IL-10, TGF-β, Arg-1, and CCL-22 were measured using enzyme-linked immunosorbent assay. Co-IP was used to verify whether YAP binds to STAT3. Hematoxylin-eosin staining was used to observe tumor morphology. Cell counting kit-8 was selected to detect T-cell proliferation. YAP, STAT3, P-STAT3, VEGF, VEGFR-2, and PD-L1 were highly expressed in BC tissues. The M2/M1 macrophages ratio increased in the TAMs group compared with the control group. Inhibiting of YAP and STAT3 decreased the M2/M1 macrophages ratio. YAP was found to bind with STAT3. T-cell proliferation was enhanced after YAP inhibition, and overexpression of STAT3 reversed the regulation of YAP on T-cell proliferation. In animal studies, inhibiting YAP inhibited tumor weight and volume development. After YAP inhibition, inflammatory infiltration, M2/M1 macrophage ratio, and Treg cell ratio declined, while CD8+ and CD4+ T-cell ratio increased. In conclusion, this study suggested inhibition of YAP/STAT3 reversed M2 polarization of TAMs and suppressed CD8+ T-cell activity in the BC immune microenvironment. These findings open up new avenues for the development of innovative therapies in the treatment of BC.


Feasibility and Added Value of Fetal DTI Tractography in the Evaluation of an Isolated Short Corpus Callosum: Preliminary Results.
Prognosis of isolated short corpus callosum is challenging. Our aim was to assess whether fetal DTI tractography can distinguish callosal dysplasia from variants of normal callosal development in fetuses with an isolated short corpus callosum. This was a retrospective study of 37 cases referred for fetal DTI at 30.4 weeks (range, 25-34 weeks) because of an isolated short corpus callosum less than the 5th percentile by sonography at 26 weeks (range, 22-31 weeks). Tractography quality, the presence of Probst bundles, dysmorphic frontal horns, callosal length (internal cranial occipitofrontal dimension/length of the corpus callosum ratio), and callosal thickness were assessed. Cytogenetic data and neurodevelopmental follow-up were systematically reviewed. Thirty-three of 37 fetal DTIs distinguished the 2 groups: those with Probst bundles (Probst bundles+) in 13/33 cases (40%) and without Probst bundles (Probst bundles-) in 20/33 cases (60%). Internal cranial occipitofrontal dimension/length of the corpus callosum was significantly higher in Probst bundles+ than in Probst bundles-, with a threshold value determined at 3.75 for a sensitivity of 92% (95% CI, 77%-100%) and specificity of 85% (95% CI, 63%-100%). Callosal lipomas (4/4) were all in the Probst bundles- group. More genetic anomalies were found in the Probst bundles+ than in Probst bundles- group (23% versus 10%, P = .08). Fetal DTI, combined with anatomic, cytogenetic, and clinical characteristics could suggest the possibility of classifying an isolated short corpus callosum as callosal dysplasia and a variant of normal callosal development.


Pathogenesis of Burkitt's lymphoma in children.
The reason that the classical African type of Burkitt's lymphoma often occurs in children is still not well understood. Several data published during the last months have, however shed some light on this phenomenon.


Safety and feasibility of laparoscopic colo-rectal surgery for cancer at a tertiary center in a developing country: Egypt as an example.
Laparoscopic colectomy has been shown to have significant short- and long-term benefits compared to open approach. The incorporation of laparoscopy in developing countries is challenging, due to the high costs of equipment and lack of expertise. The aim of this study was to evaluate the safety and feasibility of laparoscopic colorectal surgery for cancer that could be performed in developing countries under different circumstances in developed countries. Thirty-seven patients (23 males and 14 females) with colorectal cancer with a median age of 46 years (39-72) have been enrolled for laparoscopic colo-rectal surgery in a tertiary center in Egypt (South Egypt Cancer Institute) with the trend of reuse of some disposable laparoscopic instruments. The median operative time was 130 min (95-195 min). The median estimated blood loss was 70 ml (30-90 ml). No major intra-operative complications have been encountered. Two cases (5.5%) have been converted because of local advancement (one case) and bleeding with unavailability of vessel sealing device at that time (one case). The median time for passing flatus after surgery was 36 h (12-72 h). The median hospital stay was 4.8 days (4-7 days). The peri-operative period passed without events. Pathologic outcome revealed that the median number of retrieved lymph nodes was 14 (range 9-23 lymph node) and all cases had free surgical margin. Laparoscopic colorectal surgery for cancer in developing countries could be safe and feasible. Safe reuse of disposable expensive parts of some laparoscopic instruments could help in propagation of this technique in developing countries.


Plastic rain-Atmospheric microplastics deposition in urban and peri-urban areas of Patna City, Bihar, India: Distribution, characteristics, transport, and source analysis.
Evidence of atmospheric microplastics (MPs) deposition in India is scarce though reports of MPs pollution in other environmental media exist. Henceforth, this study for the first time examines and compares the abundance, characteristics, transport, and source analysis of atmospheric MPs in the urban and peri-urban areas of Patna city, Bihar, India. Wet atmospheric fallout samples were collected and analyzed for MPs deposition rate. The results showed that the mean MPs concentrations at each site were 1959.6 ± 205 (urban) and 1320.4 ± 126 (peri-urban) MPs/m2/day. The deposited MPs were mainly transparent fibers and fragments with a mean size of 347.9 ± 189.2 µm. Polyethylene terephthalate and polypropylene were the most abundant polymer found at both sites. Morphological characteristics revealed surface degradation and deposition of metal contaminants on the identified MPs. Meteorological parameters (wind direction and rainfall intensity) were significantly associated with the distribution of atmospheric MPs in the study area. The cluster mean backward trajectory suggested vehicular emissions, construction activities, and waste mismanagement as the potential sources of MPs. Findings of the present work necessitates future studies in gaining a deeper understanding of the fate, movement, and potential health hazards associated with atmospheric MPs.


Flow cytometric analysis of intracellular CD68 molecule expression in normal and malignant haemopoiesis.
CD68 molecules are heavily glycosylated lysosomal membrane constituents of unknown function with strong expression in monocytes and macrophages. Using flow cytometry, we quantified expression levels of CD68 molecules in normal and malignant haemopoietic cells. CD68 molecules are intensely expressed in the cytoplasm and weakly on the surface of mature CD14+ monocytes. CD68 expression seems to start very early during granulomonopoietic differentiation. Virtually all myeloperoxidase (MPO)+ bone marrow cells coexpress CD68 and similar proportions of CD34+ progenitor cells weakly express CD68 or MPO molecules. During further differentiation, CD68 expression is strongly up-regulated in early MPO+ precursor cells which lack lactoferrin (LF) and CD14 molecules. Compared to these, more mature MPO+LF+ bone marrow and peripheral blood granulocytes express considerable lower levels of CD68. In-line with this broad expression, all investigated acute myeloid leukaemia (AML) cases, classified as FAB M1-M5, were CD68 positive, and compared to normal CD34+ bone marrow cells. CD34+ AML blast cells expressed increased levels. CD68 expression is, however, not restricted to cells of myeloid origin, because a subset (40 +/- 15%, n = 6) of CD19+ peripheral blood B-lymphocytes and 50% of B-ALL are also weakly positive. In contrast, normal CD3+ lymphocytes lack (< 3%, n = 6) CD68 and only low proportions (6 +/- 3%, n = 6) of CD56+ NK cells are CD68+. Also, all investigated T-ALL cases (n = 6) lacked CD68.


Intestinal basement membrane of Ascaris suum. Characterization of carbohydrate units.
Characterization of glycopeptides obtained on alkaline hydrolysis and on extensive collagenase and pronase digestion of the intestinal basement membrane showed the existence of two distinctly different carbohydrate units. One of these is a disaccharide, composed of glucose and galactose, linked to hydroxylysine. It was shown to be identical to the unit (2-O-D-glucopyranosyl-O-D-galactopyranosylhydroxylyasine) present in vertebrate basement membranes, as determined from stability to alkaline hydrolysis, retention time on amino acid analyzer, chemical composition, graded acid hydrolysis, methylation analysis, and periodate oxidation. Direct quantitation after alkaline hydrolysis showed the presence of 9.71 disaccharide units/1000 amino acid residues, indicating that 89% of the hydroxylysine residues of the intestinal membrane are glycosylated. The other unit, consisting of the remaining monosaccharides of the membrane, was separated from the disaccharide unit by gel filtration and ion exchange chromatography of collagenase/pronase digests. Chemical analyses and molecular weight determination by thin layer gel filtration chromatography of purified glycopeptides indicated that this unit is an oligosaccharide which is composed of fucose, galactose, mannose, galactosamine, and glucosamine in a mole ratio of 1:1:1:1:2, respectively. The amount of this unit was calculated to be 2.6 units/1000 amino acid residues.


Improved image quality with simultaneously reduced radiation exposure: Knowledge-based iterative model reconstruction algorithms for coronary CT angiography in a clinical setting.
The aim of this study was to assess the potential for radiation dose reduction using knowledge-based iterative model reconstruction (K-IMR) algorithms in combination with ultra-low dose body mass index (BMI)-adapted protocols in coronary CT angiography (coronary CTA). Forty patients undergoing clinically indicated coronary CTA were randomly assigned to two groups with BMI-adapted (I: <25.0 kg/m2, II: <28.0 kg/m2, III: <30.0 kg/m2, IV: ≥30.0 kg/m2) low dose (LD, I: 100kVp/75 mAs, II: 100kVp/100 mAs, III: 100kVp/150 mAs, IV: 120kVp/150 mAs, n = 20) or ultra-low dose (ULD, I: 100kVp/50 mAs, II: 100kVp/75 mAs, III: 100kVp/100 mAs, IV: 120kVp/100 mAs, n = 20) protocols. Prospectively-triggered coronary CTA was performed using a 256-MDCT with the lowest reasonable scan length. Images were generated with filtered back projection (FBP), a noise-reducing hybrid iterative algorithm (iD, levels 2/5) and K-IMR using cardiac routine (CR) and cardiac sharp settings, levels 1-3. Groups were comparable regarding anthropometric parameters, heart rate, and scan length. The use of ULD protocols resulted in a significant reduction of radiation exposure (0.7 (0.6-0.9) mSv vs. 1.1 (0.9-1.7) mSv; p < 0.02). Image quality was significantly better in the ULD group using K-IMR CR 1 compared to FBP, iD 2 and iD 5 in the LD group, resulting in fewer non-diagnostic coronary segments (2.4% vs. 11.6%, 9.2% and 6.1%; p < 0.05). The combination of K-IMR with BMI-adapted ULD protocols results in significant radiation dose savings while simultaneously improving image quality compared to LD protocols with FBP or hybrid iterative algorithms. Therefore, K-IMR allows for coronary CTA examinations with high diagnostic value and very low radiation exposure in clinical routine.


A cardiovascular role for fractalkine and its cognate receptor, CX3CR1, in the rat nucleus of the solitary tract.
The nucleus of the solitary tract (NTS), an integral vasomotor region located in the hindbrain, is important for cardiovascular homeostasis. Fractalkine (FKN) and its cognate receptor, CX3CR1, are constitutively expressed in the normal rat brain. The physiological significance of this cytokine and its receptor are not well established. In this study, we sought to identify the expression of FKN and CX3CR1 in subnuclei of the NTS and to elucidate their functional relevance. Using immunohistochemistry, we found expression of FKN and CX3CR1 throughout the entire rostro-caudal axis of the NTS in normal adult male Sprague-Dawley rats. When FKN was unilaterally microinjected directly into the commissural and sub-postremal, but not rostral, NTS, blood pressure and heart rate were significantly decreased when compared with saline controls. The FKN-induced depressor and bradycardic responses were inhibited by pretreatment with a phosphoinositide 3-kinase inhibitor, LY294002. These data suggest that the cytokine, FKN, and its receptor, CX3CR1, may modulate cardiovascular responses in the NTS of normal healthy rats via the phosphoinositide 3-kinase intracellular signaling pathway.


S119N Mutation of the E3 Ubiquitin Ligase SPOP Suppresses SLC7A1 Degradation to Regulate Hepatoblastoma Progression.
A previous study on hepatoblastoma revealed novel mutations and cancer genes in the Wnt pathway and ubiquitin ligase complex, including the tumor suppressor speckle-type BTB/POZ (SPOP). Moreover, the SPOP gene affected cell growth, and its S119N mutation was identified as a loss-of-function mutation in hepatoblastoma. This study aimed to explore more functions and the potential mechanism of SPOP and its S119N mutation. The in vitro effects of SPOP on cell proliferation, invasion, apoptosis, and in vivo tumor growth were investigated by western blot analysis, Cell Counting Kit-8, colony formation assay, flow cytometry, and xenograft animal experiments. The substrate of SPOP was discovered by a protein quantification assay and quantitative ubiquitination modification assay. The present study further proved that SPOP functioned as an anti-oncogene through the phosphatidylinositol 3-kinase/Akt signaling pathway to affect various malignant biological behaviors of hepatoblastoma both in vitro and in vivo. Furthermore, experimental results also suggested that solute carrier family 7 member 1 (SLC7A1) might be a substrate of SPOP and influence cell phenotype by regulating arginine metabolism. In conclusion, these findings demonstrated the function of SPOP and revealed a potential substrate related to hepatoblastoma tumorigenesis, which might thus provide a novel therapeutic target for hepatoblastoma.


Q fever endocarditis: a case report and review of the literature.
The case of a 31-year-old man from Alberta diagnosed with Q fever endocarditis is presented. To the authors' knowledge, this is the first case of Q fever endocarditis diagnosed in the province of Alberta. The patient had undergone open valvulotomy for congenital aortic stenosis as an infant. He presented with congestive heart failure secondary to severe aortic regurgitation and underwent mechanical aortic valve replacement. Early failure of the mechanical prosthesis and numerous laboratory abnormalities prompted an investigation for endocarditis, which was initially negative. Markedly positive serology eventually established the diagnosis of chronic Q fever. The patient subsequently underwent a second aortic valve replacement following initiation of appropriate antimicrobials directed against Coxiella burnetii. The present report reviews the clinical presentation and diagnosis of Q fever endocarditis. It highlights the insidious and nonspecific nature of the presenting symptoms, and emphasizes the use of serology for diagnosis. Increased awareness and earlier diagnosis can significantly decrease the morbidity and mortality associated with this disease.


Particle Swarm Optimization for Single Objective Continuous Space Problems: A Review.
This paper reviews recent studies on the Particle Swarm Optimization (PSO) algorithm. The review has been focused on high impact recent articles that have analyzed and/or modified PSO algorithms. This paper also presents some potential areas for future study.


Phase space electroencephalography (EEG): a new mode of intraoperative EEG analysis.
Intraoperative monitoring of electroencephalography (EEG) data can help assess brain integrity and/or depth of anesthesia. We demonstrate a computer generated technique which provides a visually robust display of EEG data plotted as 'phase space trajectories' and a mathematically derived parameter ('dimensionality') which may correlate with depth of anesthesia. Application of nonlinear mathematical analysis, used to describe complex dynamical systems, can characterize 'phase space' EEG patterns by identifying attractors (geometrical patterns in phase space corresponding to specific ordered EEG data subjects) and by quantifying the degree of order and chaos (calculation of dimensionality). Dimensionality calculations describe the degree of complexity in a signal and may generate a clinically useful univariate EEG descriptor of anesthetic depth. In this paper we describe and demonstrate phase space trajectories generated for sine waves, mixtures of sine waves, and white noise (random chaotic events). We also present EEG phase space trajectories and dimensionality calculations from a patient undergoing surgery and general anesthesia in 3 recognizable states: awake, anesthetized, and burst suppression. Phase space trajectories of the three states are visually distinguishable, and dimensionality calculations indicate that EEG progresses from 'chaos' (awake) to progressively more 'ordered' attractors (anesthetized and burst suppression).


Effect of vitamin A on plasminogen activator synthesis by chick embryo fibroblasts.
Low concentrations of Vitamin A stimulated plasminogen activator synthesis (PA) in chick embryo fibroblasts (CEF). It caused a dose dependent and reversible increase in PA synthesis in both normal CEF and CEF infected with a temperature sensitive mutant of Rous Sarcoma virus (RSV-Ts68). Both induction and deinduction of PA could be inhibited by Actinomycin D. Vitamin A also accentuated the morphological changes associated with transformation in the Rous Sarcoma virus infected cells. The effects of Vitamin A on PA synthesis were essentially similar to those of the known tumour promoter, phorbol myristate acetate (PMA). Both Vitamin A and PMA were found to act synergistically with sarcoma gene expression as far as PA synthesis was concerned.


Components of Out-of-Pocket Expenditure and Their Relative Contribution to Economic Burden of Diseases in India.
High out-of-pocket expenditure (OOPE) on health in India may limit achieving universal health coverage. A clear insight on the components of health expenditure may be necessary to make allocative decisions to reduce OOPE, and such details by sociodemographic group and state have not been studied in India. To analyze the relative contribution of drugs, diagnostic tests, doctor and surgeon fees, and expenditure on other medical services and nonmedical health-related services, such as transport, lodging, and food, by sociodemographic characteristics of patients, geography, and type of illness. A population-based cross-sectional health consumption survey conducted by the National Sample Survey Organisation in 2018 was analyzed in this cross-sectional study. Respondents who provided complete information on costs of medicine, doctors, diagnostics tests, other medical costs, and nonmedical costs were selected. Data were analyzed from August through September 2021. Mean and median share of components (ie, medicine, diagnostic tests, doctor fees, other medical costs, and nonmedical costs) in total health care expenditure and income were calculated. Bivariate survey-weighted mean (with 95% CI) and median (IQR) expenditures were calculated for each component across sociodemographic characteristics. The proportion of total expenditure and income contributed by each cost was calculated for each individual. Mean and median were then used to summarize such proportions at the population level. The association between state net domestic product per capita and component share of each health care service was graphically explored. Health expenditure details were analyzed for 43 781 individuals for inpatient costs (27 272 [64.3%] women; 26 830 individuals aged 25-64 years [59.9%]) and 8914 individuals for outpatient costs (4176 [48.2%] women; 4901 individuals aged 25-64 years [54.2%]); most individuals were rural residents (24 106 inpatients [67.0]; 4591 outpatients [63.9%]). Medicines accounted for a mean of 29.1% (95% CI, 28.9%-29.2%) of OOPE among inpatients and 60.3% (95% CI, 59.7%-60.9%) of OOPE among outpatients. Doctor consultation charges were a mean of 15.3% (95% CI, 15.1%-15.4%) of OOPE among inpatients and 12.4% (95% CI, 12.1%-12.6%) of OOPE among outpatients. Diagnostic tests accounted for a mean of 12.3% (95% CI, 12.2%-12.4%) of OOPE for inpatient and 9.2% (95% CI, 8.9%-9.5%) of OOPE for outpatient services. Nonmedical costs accounted for a mean of 23.6% (95% CI, 23.3%-23.8%) of OOPE among inpatients and 14.6% (95% CI, 14.1%-15.1%) of OOPE among outpatients. Mean share of OOPE from doctor consultations and diagnostic test charges increased with socioeconomic status. For example, for the lowest vs highest monthly per capita income quintile among inpatients, doctor consultations accounted for 11.5% (95% CI, 11.1%-11.8%) vs 21.2% (95% CI, 20.8%-21.6%), and diagnostic test charges accounted for 10.9% (95% CI, 10.6%-11.1%) vs 14.3% (95% CI, 14.0%-14.5%). The proportion of mean annual health expenditure from mean annual income was $299 of $1918 (15.6%) for inpatient and $391 of $1788 (21.9%) for outpatient services. This study found that nonmedical costs were significant, share of total health care OOPE from doctor consultation and diagnostic test charges increased with socioeconomic status, and annual cost as a proportion of annual income was lower for inpatient than outpatient services.


Age-dependent changes in adenosine A1 receptor distribution and density within the nucleus tractus solitarii of normotensive and hypertensive rats.
This study shows the distribution and density of adenosine A1 receptor (A1R) within the nucleus tractus solitarii (NTS) of Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) from birth to adulthood (1, 15, 30 and 90 days old). The NTS shows heterogeneous distribution of A1R in dorsomedial/dorsolateral, subpostremal and medial/intermediate subnuclei. A1R decrease from rostral to caudal within dorsomedial/dorsolateral subnucleus in 15-, 30- and 90-day-old WKY and SHR. A1R increase from rostral to caudal subpostremal subnucleus in 30- and 90-day-old WKY, and in 15-, 30- and 90-day-old SHR. Furthermore, A1Rs are increased in SHR as compared with WKY within dorsomedial/dorsolateral in 30- and 90-day-old and within subpostremal of 15-, 30- and 90-day-old rats. Finally, A1Rs increase from 1- to 30-day-old rats. Medial/intermediate did not show any changes in A1R from rostral to caudal levels, age or strain. In summary, our result highlights the importance of A1 adenosine system regarding the neural control of blood pressure and the development of hypertension.


Blood mercury concentrations following methyl mercury exposure in adult and infant monkeys.
Female monkeys (Macaca fascicularis) were dosed chronically with the equivalent of 10, 25, or 50 micrograms/kg/day methyl mercury until at least 90% of estimated blood equilibrium was reached and were then bred to untreated males. Infants were dosed with the same dose their mothers had received. An additional group of infants was dosed with 50 micrograms/kg/day beginning at birth. Infants exposed in utero were born with higher (1.7x) mercury levels than their mothers, but blood mercury levels of the offspring decreased to less than one-half that of the mothers. The steady-state blood levels of the group exposed postnatally were not different from steady-state levels of the group exposed in utero plus postnatally. When dosing was discontinued, the rate coefficient of elimination from blood did not differ between the adults (mothers) and the in utero plus postnatally exposed group, while that of the group exposed postnatally only was lower. There was no indication of a relationship in the rate of elimination for mother-infant pairs. These results suggest that the kinetics of methyl mercury in blood are complicated and may depend on the age of the individual when exposure begins.


Patient safety in the rehabilitation of the adult with an amputation.
This article reviews and summarizes the literature on patient safety issues in the rehabilitation of adults with an amputation. Safety issues in the following areas are discussed; the prosthesis, falls, wound care, pain, and treatment of complex patients. Specific recommendations for further research and implementation strategies to prevent injury and improve safety are also provided. Communication between interdisciplinary team members and patient and caregiver education are crucial to executing a safe treatment plan. The multidisciplinary rehabilitation team members should feel comfortable discussing safety issues with patients and be able to recommend preventive approaches to patients as appropriate.


Sensitivity analysis of influence factors on multi-zone indoor airflow CFD simulation.
Computational fluid dynamics (CFD) is a powerful tool for performing indoor airflow analysis. The simulation results are usually validated with measurement results for accuracy in reflecting reality. When conducting CFD for simulating air flow in a multiple-zone indoor environment with different boundary conditions in different regions, the validation of the CFD model becomes sophisticated. To improve the accuracy of the simulation, boundary conditions need to be adjusted based on how significant the influence factors are affecting the multi-zone CFD model, which few studies have been conducted on. The objective of this study is to investigate the impact of influence factors on temperature and carbon dioxide concentration distribution of a validated CFD model of a typical office floor using ANSYS Fluent. This study provides insights on how to fine-tune a complex model to reflect the actual air flow and how the air quality and human comfort in different zones on the same floor could be affected by influence factors. The influence factors investigated are: (1) size of door gaps, (2) solar radiation and (3) number and orientation of occupants. The velocity variations caused by different door gap sizes were studied for improving multi-zone simulation accuracy by adjusting door gap sizes. To study the significant impact of solar heat on multi-zone environment, the sensitivity of different regions of the office floor to solar heat amount and distribution was analyzed by conducting solar analysis under different weather conditions. Impact of occupants on temperature and carbon dioxide concentration distributions in multi-zone environment were investigated by considering different numbers and facing directions of occupants in different regions of the office floor. In addition, this study demonstrates how to modify the influence factors efficiently using building information modeling (BIM).


Reproductive life events in the population living in the vicinity of a nuclear waste reprocessing plant.
There is concern about the health of populations living close to nuclear waste reprocessing plants. A comparative study was conducted on reproductive life events in the general population living near the nuclear waste reprocessing plant in Beaumont-Hague, France and a reference area in Brittany. Women were randomly selected and retrospectively questioned on reproductive life events occurring between 1985 and 2000. The monthly probability of pregnancy (assessed by time to pregnancy for pregnancy attempts leading or not to a live birth), occurrence of involuntary infertility, miscarriage and birth weight were compared between both areas using regression models with random effect. Compared with the reference area (326 couples) and after adjustment for sociodemographic and behavioural factors, couples from Beaumont-Hague (857 couples) had an estimated hazard ratio of pregnancy of 1.19 (95% CI 0.89 to 1.58). The prevalence ratio of 12-month involuntary infertility was 0.99 (95% CI 0.64 to 1.55) and the odds ratio of miscarriage was 0.86 (95% CI 0.85 to 1.33) for Beaumont-Hague, compared with the reference area. Mean birth weight was similar in both areas (95% CI of difference -85 g to 53 g). No increased risk of adverse reproductive life events was highlighted in the population living in the vicinity of the French nuclear waste reprocessing plant, compared with the reference area. Reproductive health is unlikely to be strongly altered in the general population of Beaumont-Hague.


Evaluation of microRNAs-208 and 133a/b as differential biomarkers of acute cardiac and skeletal muscle toxicity in rats.
Conventional circulating biomarkers of cardiac and skeletal muscle (SKM) toxicity lack specificity and/or have a short half-life. MicroRNAs (miRNAs) are currently being assessed as biomarkers of tissue injury based on their long half-life in blood and selective expression in certain tissues. To assess the utility of miRNAs as biomarkers of cardiac and SKM injury, male Sprague-Dawley rats received a single dose of isoproterenol (ISO); metaproterenol (MET); allylamine (AAM); mitoxantrone (MIT); acetaminophen (APAP) or vehicle. Blood and tissues were collected from rats in each group at 4, 24 and 48h. ISO, MET, and AAM induced cardiac and SKM lesions and APAP induced liver specific lesions. There was no evidence of tissue injury with MIT by histopathology. Serum levels of candidate miRNAs were compared to conventional serum biomarkers of SKM/cardiac toxicity. Increases in heart specific miR-208 only occurred in rats with cardiac lesions alone and were increased for a longer duration than cardiac troponin and FABP3 (cardiac biomarkers). ISO, MET and AAM induced increases in MyL3 and skeletal muscle troponin (sTnl) (SKM biomarkers). MIT induced large increases in sTnl indicative of SKM toxicity, but sTnl levels were also increased in APAP-treated rats that lacked SKM toxicity. Serum levels of miR-133a/b (enriched in cardiac and SKM) increased following ISO, MET, AAM and MIT treatments but were absent in APAP-treated rats. Our results suggest that miR-133a/b are sensitive and specific markers of SKM and cardiac toxicity and that miR-208 used in combination with miR-133a/b can be used to differentiate cardiac from SKM toxicity.