Transcriptional repression of p21 by EIF1AX promotes the proliferation of breast cancer cells.
Dysregulation of the cell cycle is associated with the progression of malignant cancer, but its precise functional contribution is unknown. The expression of EIF1AX in breast cancer tissues was detected by qRT-PCR and immunohistochemistry staining. Colony formation and tumour xenograft assays were used to examine the tumorigenesis-associated function of EIF1AX in vitro and in vivo. RNA-Seq analysis was used to select the downstream target genes of EIF1AX. Flow cytometry, ChIP and luciferase assays were used to investigate the molecular mechanisms by which EIF1AX regulates p21 in breast cancer cells. EIF1AX promoted breast cancer cell proliferation by promoting the G1/S cell cycle transition. A mechanistic investigation showed that EIF1AX inhibited the expression of p21, which is an essential cell cycle regulator. We identified that the transcriptional regulation of p21 by EIF1AX was p53-independent. Clinically, EIF1AX levels were significantly elevated in breast cancer tissues, and the high level of EIF1AX was associated with lower survival rates in breast cancer patients. Our results imply that EIF1AX may play a key role in the incidence and promotion of breast cancer and may, thus, serve as a valuable target for breast cancer therapy.


Atheroprotective effect of adjuvants in apolipoprotein E knockout mice.
Strategies aimed at treating atherosclerosis by immunization protocols are emerging. Such protocols commonly use adjuvants as non-specific stimulators of immune responses. However, adjuvants are known to modify various disease processes. The aim of this study was to determine whether adjuvants alter the development of atherosclerosis. We performed immunization protocols in apolipoprotein E knockout mice (E degrees ) following chronic administration schedules commonly employed in experimental atherosclerosis. Our results point out a dramatic effect of several adjuvants on the development of atherosclerosis; three of the four adjuvants tested reduced lesion size. The Alum adjuvant, which is the adjuvant currently used in most vaccination protocols in humans, displayed a strong atheroprotective effect. Mechanisms accounting for atheroprotective effect of Freund's adjuvants included their capacity to increase both Th2 responses and anti-MDA-LDL IgM titers, and/or to impose atheroprotective lipoprotein profiles. The present study indicates that adjuvants have potent atheromodulating capabilities, and thus, implies that the choice of adjuvant is crucial in long-term immunization protocols in experimental atherosclerosis.


Lateral soft-tissue release through a medial incision: Anatomic comparison of two techniques.
The distal soft tissue procedure is an integral part of hallux valgus surgery, providing soft tissue balance and alignment restoration of the first metatarsophalangeal joint. Various approaches have been established to this end. For techniques that do not include a separate dorsal incision, lateral release may be achieved via a transarticular approach or via a medial incision and a dorsal flap over the first metatarsal. Compared to the double-incision technique, these techniques are not only cosmetically superior and thus meet the demands of most surgeons and patients. Using six pairs of frozen cadaveric feet, lateral release was performed using one of the above techniques in a randomized manner with pair comparison. The specimens were then dissected and the completeness of the release as well as any damage to anatomic structures was documented. The transarticular technique enabled complete release of the metatarsal-sesamoid suspensory ligament (MSL) and the transverse and oblique head of the adductor hallucis muscle in five of six specimens. The comparative technique enabled the same in only two of six cases for the adductor hallucis muscle and in four cases for the MSL. The transarticular approach achieved complete release of the lateral joint capsule in three of six specimens, whereas the dorsal approach achieved no release in any specimen. Neither of the methods caused any macroscopic injury to the surfaces of the first metatarsophalangeal joint. The examined arteries, veins, and nerves remained intact in all specimens treated with the transarticular approach, but dorsal release resulted in one documented injury to the first dorsal metatarsal artery and its concomitant veins. Compared to release by dissection superficially to the extensor tendons, transarticular release provides a more complete lateral release and less injuries to neurovascular bundles. Further anatomic and clinical studies are needed, however, before conclusive recommendations can be made.


Lymph node metastases from head and neck squamous cell carcinoma: MR imaging with ultrasmall superparamagnetic iron oxide particles (Sinerem MR) -- results of a phase-III multicenter clinical trial.
The aim of this study was to compare the clinical usefulness of ultrasmall superparamagnetic iron oxide (USPIO) MR contrast media (Sinerem, Guerbet Laboratories, Aulnay-sous-Bois, France) with precontrast MRI in the diagnosis of metastatic lymph nodes in patients with head and neck squamous cell carcinoma, using histology as gold standard. Eighty-one previously untreated patients were enrolled in a multicenter phase-III clinical trial. All patients had a noncontrast MR, a Sinerem MR, and surgery within a period of 15 days. The MR exams were analyzed both on site and by two independent radiologists (centralized readers). Correlation between histology and imaging was done per lymph node groups, and per individual lymph nodes when the short axis was > or = 10 mm. For individual lymph nodes, Sinerem MR showed a high sensitivity (> or = 88%) and specificity (> or = 77%). For lymph node groups, the sensitivity was > or = 59% and specificity > or = 81%. False-positive results were partially due to inflammatory nodes; false-negative results from the presence of undetected micrometastases. Errors of interpretation were also related to motion and/or susceptibility artifacts and problems of zone assignment. Sinerem MR had a negative predictive value (NPV) > or = 90% and a positive predictive value (PPV) > or = 51%. The specificity and PPV of Sinerem MR were better than those of precontrast MR. Precontrast MR showed an unexpectedly high sensitivity and NPV which were not increased with Sinerem MR. The potential contribution of Sinerem MR still remains limited by technical problems regarding motion and susceptibility artifacts and spatial resolution. It is also noteworthy that logistical problems, which could reduce the practical value of Sinerem MR, will be minimized in the future since Sinerem MR alone performed as good as the combination of precontrast and Sinerem MR.


Combined vaccination by measles and hepatitis B vaccines: a new cause of Gianotti-Crosti syndrome.
An 11-month-old boy presented with Gianotti-Crosti syndrome. He had received measles and a third dose of hepatitis B vaccines 2 weeks before the onset of the eruption. There were no clinical symptoms of any viral infection at the presentation. Serological tests for common viral infections were negative. The combination of measles and hepatitis B vaccines was likely the relevant factor in the etiology.


Segmentation-Based Blood Flow Parameter Refinement in Cerebrovascular Structures Using 4-D Arterial Spin Labeling MRA.
Cerebrovascular diseases are one of the main global causes of death and disability in the adult population. The preferred imaging modality for the diagnostic routine is digital subtraction angiography, an invasive modality. Time-resolved three-dimensional arterial spin labeling magnetic resonance angiography (4D ASL MRA) is an alternative non-invasive modality, which captures morphological and blood flow data of the cerebrovascular system, with high spatial and temporal resolution. This work proposes advanced medical image processing methods that extract the anatomical and hemodynamic information contained in 4D ASL MRA datasets. A previously published segmentation method, which uses blood flow data to improve its accuracy, is extended to estimate blood flow parameters by fitting a mathematical model to the measured vascular signal. The estimated values are then refined using regression techniques within the cerebrovascular segmentation. The proposed method was evaluated using fifteen 4D ASL MRA phantoms, with ground-truth morphological and hemodynamic data, fifteen 4D ASL MRA datasets acquired from healthy volunteers, and two 4D ASL MRA datasets from patients with a stenosis. The proposed method reached an average Dice similarity coefficient of 0.957 and 0.938 in the phantom and real dataset segmentation evaluations, respectively. The estimated blood flow parameter values are more similar to the ground-truth values after the refinement step, when using phantoms. A qualitative analysis showed that the refined blood flow estimation is more realistic compared to the raw hemodynamic parameters. The proposed method can provide accurate segmentations and blood flow parameter estimations in the cerebrovascular system using 4D ASL MRA datasets. The information obtained with the proposed method can help clinicians and researchers to study the cerebrovascular system non-invasively.


Purification and characterization of the individual glutathione S-transferases from sheep liver.
The glutathione S-transferases (EC 126.96.36.199) have been purified to electrophoretic homogeneity from 105,000g supernatant of sheep liver homogenate by employing a combination of gel filtration on Sephadex G-150 and affinity chromatography on S-hexylglutathione-linked Sepharose-6B columns. Approximately 70% of the original glutathione S-transferase activity toward 1-chloro-2,4-dinitrobenzene and glutathione peroxidase activity toward cumene hydroperoxide could be recovered by this purification method. Of particular importance in developing this procedure was the fact that the enzyme preparation obtained after affinity column chromatography represented all the isozymes of sheep liver glutathione S-transferases. Further purification by CM-cellulose and DEAE-cellulose column chromatography resolved the glutathione S-transferases into seven distinct cationic isozymes designated C-1, C-2, C-3, C-4, C-5, C-6, and C-7 and five overlapping anionic transferases designated A-1, A-2, A-3, A-4, and A-5, respectively, in the order of their elution from the ion-exchange columns. The sodium dodecyl sulfate SDS-gel electrophoretic data on subunit composition revealed that cationic enzymes are composed of two subunits with an identical Mr of 24,000 whereas a predominant subunit with Mr of 26,000 was observed in all anionic isozyme peaks except A-1. Cationic isozymes accounted for approximately 98% of the total peroxidase activity associated with the glutathione S-transferase whereas only A-1 of the anionic isozymes displayed some peroxidase activity. Isozyme C-4 was found to be the most abundant glutathione S-transferase in the sheep liver. Characterization of the individual transferases by their specificity toward a number of selected substrates, subunit composition, and isoelectric points showed some similarities to those patterns for human liver glutathione S-transferases.


Proximal tibial morphology is associated with risk of trauma to the posteromedial structures during tibial bone resection reproducing the anatomical posterior tibial slope in bicruciate-retaining total knee arthroplasty.
A tibial cut with the native posterior tibial slope (PTS) is a theoretical prerequisite in bicruciate-retaining total knee arthroplasty (BCRTKA) to regain physiological knee kinematics. The present study reveals tibial morphological risk factors of trauma to the posteromedial structures of the knee during tibial bone resection in BCRTKA. Fifty patients undergoing BCRTKA for varus knee osteoarthritis were analyzed. A three-dimensional tibial bone model was reconstructed using a computed tomography-based preoperative planning system, and the coronal tibial slope (CTS) and medial PTS (MPTS) were measured. Then, we set the simulated tibial cutting plane neutral on the coronal plane, posteriorly inclined in accordance with the MPTS on the sagittal plane, and 9 mm below the surface of the subchondral cortical bone (i.e., 11 mm below the surface of the cartilage) of the lateral tibial plateau. The association between the tibial morphology and the distance from the simulated cutting plane to the semimembranosus (SM) insertion (Dsm) was analyzed. Of the 50 patients, 19 (38%) had negative Dsm values, indicating a cut into the SM (namely, below the posterior oblique ligament) insertion. The MPTS was negatively correlated with Dsm (r = -0.396, p = 0.004), whereas the CTS was positively correlated with Dsm (r = 0.619, p < 0.001). On multivariate linear regression analysis, the MPTS and CTS were independent predictors of Dsm. In the setting of tibial cuts reproducing the native MPTS in BCRTKA, patients with larger PTS and smaller CTS had more risk of trauma to the posteromedial structures.


Mechanical properties of human enamel under compression: On the feature of calculations.
The paper is aimed at determination of the causes of shape effect in human tooth enamel under compression and correction of the relevant mechanical characteristics. For this purpose, six groups of samples with different ratios of the compression surface diagonal to the sample height, which consisted of 10 cuboid samples in each, were prepared from the backside of human enamel. The lateral deformation of a sample was calculated at the maximum compressive stress for correction of the mechanical characteristics. It is shown that the ratio between the lateral and axial deformations decreases with an increase in the ratio of the compression surface diagonal to the sample height. This is caused by the friction between the compression plates and the working surfaces of the enamel sample when the lateral deformation is suppressed. In addition, the slope of enamel sample by about 15° occurred during compression due to the inclination of rigid and low deformable enamel rods. The corrections of the elastic modulus and the compression strength taking into account the lateral deformation and the sample slope are carried out. The mechanical properties of enamel samples with the 2.1 aspect ratio are closer to the intrinsic properties of human enamel samples. The elastic modulus and the compression strength of human enamel under compression are 5.64 GPa and 363 MPa, respectively. The lateral deformation (~10%) may be considered as the critical parameter that indicates the strength of human enamel.


circFLT1 and lncCCPG1 Sponges miR-93 to Regulate the Proliferation and Differentiation of Adipocytes by Promoting lncSLC30A9 Expression.
Although many circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs) have been discovered in adipocytes, their precise functions and molecular mechanisms remain poorly understood. Based on existing circRNA and lncRNA sequencing data of bovine adipocytes, we screened for the differential expression of circFLT1 and lncCCPG1 in preadipocytes and adipocytes and further analyzed their function and regulation during adipogenesis. The overexpression of circFLT1 and lncCCPG1 together facilitated adipocyte differentiation and suppressed proliferation. Computationally, the RNA hybrid showed that circFLT1 and lncCCPG1 had multiple potential binding sites with miR-93. Additionally, luciferase reporting experiments verified that circFLT1 and lncCCPG1 may interact with miR-93. We also demonstrated that overexpressed miR-93 effectively suppresses the expression of lncSLC30A9. Signaling pathway enrichment analysis, luciferase activity assay, and expression analysis revealed that lncSLC30A9 inhibits proliferation by inhibiting the expression of AKT protein and promotes differentiation by recruiting the FOS protein to the promoter of peroxisome proliferator-activated receptor gamma (PPARG). In sum, our results elucidate the regulatory mechanisms of circFLT1 and lncCCPG1 as miR-93 sponges in bovine adipocytes.


A wintertime study of polycyclic aromatic hydrocarbons in PM(2.5) and PM(2.5-10) in Beijing: assessment of energy structure conversion.
Sixteen priority polycyclic aromatic (PAHs) in PM(2.5) and PM(2.5-10) samples collected from 20 sites in Beijing, China in December 2005 and January 2006 were analyzed to determine the composition, spatial distribution and sources. Total PAHs of PM(2.5) and PM(2.5-10) ranged from 5.2 to 1062.2 ng m(-3) and 7.6 to 759.7 ng m(-3), respectively, categorized as heavier pollution. Among five kind of functional zones involved, industrial center, commercial area and village were heavily polluted. The mean concentration of PAHs in PM(2.5) of 407 ng m(-3) was 1.67-fold of that in PM(2.5-10), which was relatively high compared to the previous studies (winter in 2001 and 2002). The most evident change was the increase of Flu, BbkF and InP, which are believed to be less harmful and related to the increasing use of clean energy. However, pollution distribution was spatially heterogeneous inside the city. The most polluted sites located in the southeast of the city. Unlike previous studies, fluoranthene was the most abundant component quantified, which could be associated with increasing use of natural gas as clean energy. Compositional analysis and principal component analysis (PCA) suggested that different kinds of combustion were the main source of the PAHs in PM, though contribution of coal was still evident.


Adrenal hematoma following falling in a 5-year-old boy.
There is scarcity of reports regarding adrenal hemorrhage secondary to blunt abdominal trauma, which is as a result of the location of the adrenal glands. Most adrenal injuries occur in the right gland solitary and they are not life-threatening. Hence, they can be treated with conservative actions. In this case report, we describe the history a 5-year-old child with the history of falling and was diagnosed with adrenal hemorrhage. He did not need any surgical procedures and the outcome of conservative treatment was satisfactory.


Giant left atrial myxoma mimicking severe mitral valve stenosis and severe pulmonary hypertension.
Myxoma is the most common primary tumor of the heart and can arise in any of the cardiac chambers. This paper reports A 50 -year-old woman without medical history and any cardiovascular risk factors was hospitalized for exertional dyspnea and palpitations from three months and signifiant weight loss. Transthoracic echocardiogram showed a giant left atrial myxoma mobile confined to the left atrium in systole, in diastole the tumor was seen prolapsing across the mitral valve into the left ventricle and partially obstructing it and causing severe functional mitral stenosis with a mean gradient of 21,3 mmHg. Severe pulmonary hypertension was confirmed by Doppler PAPs =137 mmHg. The patient was scheduled for cardiac surgery with good outcome.


Activated protein C mediates a healing phenotype in cultured tenocytes.
Tendon injuries cause considerable morbidity in the general adult population. The tenocytes within the tendon have the full capacity to heal the tendon intrinsically. Activated protein C (APC) plays an important role in coagulation and inflammation and more recently has been shown to promote cutaneous wound healing. In this study we examined whether APC can induce a wound healing phenotype in tenocytes. Sheep tenocytes were treated with APC, endothelial protein C receptor (EPCR) blocking antibody (RCR252) and/or EPCR small interfering (si)RNA. Cell proliferation and migration were measured by crystal violet assay and a scratch wounding assay, respectively. The expression of EPCR, matrix metalloproteinase (MMP)-2, type I collagen and MAP kinase activity were detected by real time PCR, zymography, immunofluorescence, immunohistochemistry and Western blotting. APC stimulated proliferation, MMP-2 activity and type I collagen deposition in a dose-dependent manner and promoted migration of cultured tenocytes. APC dose-dependently stimulated phosphorylated (P)-ERK2 and inhibited P-p38. Interestingly, tenocytes expressed EPCR protein, which was up-regulated by APC. When tenocytes were pre-treated with RCR252 or EPCR siRNA the effect of APC on proliferation, MMP-2 and type 1 collagen synthesis and MAP kinases was blocked. APC promotes the growth, MMP-2 activity, type I collagen deposition and migration of tenocytes. Furthermore, EPCR is expressed by tenocytes and mediates the actions of APC, at least partly by signalling through selective MAP kinases. These data implicate APC as a potential healing agent for injured tendons.


Chemical Composition of Cuticle and Barrier Properties to Transpiration in the Fruit of Clausena lansium (Lour.) Skeels.
The plant cuticle, as a lipid membrane covering aerial plant surfaces, functions primarily against uncontrolled water loss. Herein, the cuticle chemical composition and the transpiration of wampee fruit (Clausena lansium (Lour.) Skeels) at the green, turning, and yellow stages in cultivars of "Jixin" and "Tianhuangpi" were comprehensively studied. The coverage of wax and cutin monomers per unit of fruit surface area at the green stage was lower in "Jixin" than in "Tianhuangpi" and increased gradually during development. Cutin monomers accumulated ranging from 22.5 μg cm-2 (green) to 52.5 μg cm-2 (turning) in "Jixin" and from 36.5 μg cm-2 (green) to 81.7 μg cm-2 (yellow) in "Tianhuangpi." The total composition of waxes ranged between 6.0 μg cm-2 (green) and 11.1 μg cm-2 (turning) in "Jixin," while they increased from 7.4 μg cm-2 (green) to 16.7 μg cm-2 (yellow) in "Tianhuangpi." Cutin monomers were dominated by ω-, mid-dihydroxy fatty acids (over 40%), followed by multiple monomers of α,ω-dicarboxylic acids with or without added groups, α-monocarboxylic acids with or without ω- or mid-chain hydroxy or mid-epoxy groups, primary alcohols, and phenolics. The very-long-chain (VLC) aliphatic pattern of cuticular waxes was prominently composed of n-alkanes (ranging from 21.4% to 39.3% of total wax content), fatty acids, primary alcohols, and aldehydes. The cyclic waxes were dominated by triterpenoids (between 23.9 and 51.2%), sterols, and phenolics. Water loss in wampee fruit exhibited linear changes over time, indicating an overall monofunctional barrier to transpiration. Permeance for water in wampee fruit was higher at the green stage than at the yellow stage in both "Jixin" and "Tianhuangpi," which showed a negative correlation with the changes of VLC n-alkanes. The results showed the cuticular chemicals, including cutin monomers and waxes, in wampee fruit and further indicated the potential contributions of the cuticular chemical composition to the physiological functions in fruits.


Role of Schmallenberg virus infection in congenital malformations in ruminants in Scotland in spring 2017.
Scotland's Rural College (SRUC), together with the Moredun Research Institute, carries out surveillance for Schmallenberg virus (SBV) infection in cattle and sheep. This article reports findings relating to diagnoses of fetopathy associated with SBV infection and other congenital malformations in these species made between January 1 and May 5, 2017.


X-ray fluorescence with synchrotron radiation.
The use of synchrotron radiation for X-ray fluorescence has several advantages over the use of other conventional X-ray sources. The principles of synchrotron radiation and methods for applying synchrotron radiation to the X-ray fluorescence measurements of trace elements are discussed. The Brookhaven National Laboratory X-ray microprobe, facilities dedicated to X-ray fluorescence, and related analytical techniques are discussed. Some examples of trace element analyses in biological materials with synchrotron radiation are presented.


Neurological and neurobehavioral development of the mutant 'twitcher' mouse.
The present study described the neurological and locomotor development of the mutant 'twitcher' mouse (B57BL/6J-twi), an enzymatically authentic model of globoid cell (Krabbe) leukodystrophy. Comparisons were made on a neurological developmental battery and a series of behavioral tests, including open field, rotorod, and hangtime performance. Homozygous affected (twi/twi), heterozygous carriers (+/twi) and homozygous normals (+/+) were compared. Neurological development was slowed in twi/twi with some subtler differences between +/twi and normals. Twi/twi reached all functional milestones except grasp. There was a rapid deterioration of motor indices after 20 days of age. However, most sensory markers were preserved. On hangtime, there were significant differences from normal for both twi/twi and +/twi at 15 days of age and across the 15-30 day developmental stage, with the +/twi males slightly more impaired. On the rotorod, all animals were equally unable to stay on the rod at 15 days of age and neither male nor female twi/twi showed significant development. Male +/twi lagged significantly behind male +/+. In the open field, all groups were equally inactive at 13-15 days and showed similar increases in activity, rearing, and grooming until weaning. All groups peaked immediately after weaning and declined thereafter, with twi/twi showing the lowest activity. The data were discussed in terms of the relationship between the human disease and the animal model.


Ecotoxicity assessment for environmental risk and consideration for assessing the impact of silver nanoparticles on soil earthworms.
Silver nanoparticles (AgNPs) are found in a range of commercial products due to their proven antibacterial properties. The unused silver nanoparticles (AgNPs) may make its way into the soil via biosolids that come from wastewater treatment or the effluent that comes from industrialisation processes, where it could be harmful to the organism that live in terrestrial ecosystems. In addition, silver ions are one of the most toxic forms of heavy metal released from dissolved silver nitrate (AgNO3) and AgNPs through dissolution or oxidation. The study examined the effect of engineered AgNPs, and AgNO3 on earthworms which are one of the most important bioindicator for determining toxicity in soil environment. Epigeic earthworm, Eudrilus eugeniae was exposed to soils spiked with equivalent concentrations of AgNPs or AgNO3 at 0, 10, 100, and 200 mg kg-1 in soil for 56 days of experiments. The survival and growth rate was recorded at 7th, 14th, 21st, 28th days and accumulation of Ag in earthworm tissue at 14th and 28th days, antioxidant enzymes at 28th days and reproduction at 56th days of experiment. Further, a short-term exposure of AgNPs and AgNO3 was conducted to observe avoidance behaviour after 48 h of exposure. The result indicated that survivability was relatively low on exposure of AgNO3 (83.3%) than AgNPs (86.7%) in 200 mg kg-1 spiked soils, besides the growth was inhibited in both AgNPs (3.68%) and AgNO3 (3.25%) at 28th days. The uptake of Ag from AgNO3 in the earthworm tissue was slightly higher than uptake of Ag from AgNPs and it showed concentration-dependent inhibitory effects on reproduction. In AgNO3 spiked soil, a high level of the Malondialdehyde (MDA) based lipid peroxidation and increased activity of antioxidant enzyme catalase (CAT) was observed than AgNPs spiked soil. Similarly, glutathione (GSH), a cofactor for GPx and GST enzymes, was lower in AgNO3-spiked soil than in AgNPs-spiked soil. In terms of avoidance behaviour, there was no discernible difference between the distribution of earthworms in AgNPs and AgNO3 after 48 h. The study found E. eugeniae exhibits concentration-dependent alterations in its competence to survive, antioxidant enzymes, and reproduction. AgNO3 was found to be more sensitive than AgNPs in the study. The research investigates the effect of AgNPs on earthworms in the soil ecosystem since this understanding is crucial for a comprehensive evaluation of AgNPs' environmental consequences.


Hepatoprotective agent tethered isoniazid for the treatment of drug-induced hepatotoxicity: Synthesis, biochemical and histopathological evaluation.
The aim of the study was to investigate the protective effect of isoniazid-curcumin conjugate (INH-CRM) in INH-induced hepatic injury by biochemical analysis and histology examination of liver in Wistar rats. The biochemical analysis included determination of the levels of plasma cholesterol, triglycerides (TG), albumin content, and lipid peroxidation (MDA). INH-CRM administration resulted in a significant decrease in plasma cholesterol, TG, and MDA levels in the liver tissue homogenate with an elevation in albumin level indicating its hepatoprotective activity. Histology of the liver further confirmed the reduction in hepatic injury. The hepatoprotective with INH-CRM can be attributed to the antioxidant activity of curcumin. The conjugate probably stabilizes the curcumin molecule, preventing its presystemic metabolism thereby enhancing its bioavailability and therefore, its hepatoprotective activity. Thus, the novel INH-CRM has the potential to alleviate INH-induced liver toxicity in antitubercular treatment.


High-contrast grating resonators for label-free detection of disease biomarkers.
A label-free optical biosensor is described that employs a silicon-based high-contrast grating (HCG) resonator with a spectral linewidth of ~500 pm that is sensitive to ligand-induced changes in surface properties. The device is used to generate thermodynamic and kinetic data on surface-attached antibodies with their respective antigens. The device can detect serum cardiac troponin I, a biomarker of cardiac disease to 100 pg/ml within 4 mins, which is faster, and as sensitive as current enzyme-linked immuno-assays for cTnI.


Association of diet quality with glycemia, insulinemia, and insulin resistance in families at high risk for type 2 diabetes mellitus in Europe: Feel4 Diabetes Study.
The aim of the present study was to investigate the association of diet quality with fasting glycemia, insulinemia, and insulin resistance in a cross-sectional sample of adults from families at high risk for type 2 diabetes mellitus (T2DM) from six European countries, taking into account their socioeconomic status (SES). Baseline data from non-diabetic adults from the Feel4 Diabetes study were used and diet was assessed by the Healthy Diet Score (HDS). Insulin resistance (IR) was determined by homeostasis model assessment of IR (HOMA-IR). Sociodemographic and lifestyle characteristics were assessed through standardized questionnaires. Multiple linear regressions were adjusted for many confounders, in the total sample and by SES category. In 1980 adults, the third tertile of diet quality was inversely associated with insulin levels (-1.48; 95% confidence interval [CI], -2.34 to 0.62), and HOMA-IR (-0.33; 95% CI, -0.57 to 0.09), yet with no statistically significant results for glucose levels. In the SES subgroup analysis, in the high SES group, both second and third diet score tertiles were inversely associated with insulin levels (-1.81; 95% CI, -2.66 to 0.95) and HOMA-IR values (-0.45; 95% CI -0.69 to 0.21), independent of age, sex, smoking and body mass index. No such associations were observed for glucose levels in the high SES group and for all indices in the low SES group. In adults from families at high risk for T2DM, higher diet quality was negatively associated with fasting insulin levels and IR, only in the high SES group and not in the low SES group. Future larger studies may be able to explore further this association, as well as the potential factors that mitigate its strength in the low SES groups.


Neuropeptide Y-like immunoreactivity in neurons of the human retina.
The distribution of neuropeptide Y-like immunoreactivity (NPY-LI) was investigated in wholemounts and in transverse sections of the human retina. NPY-LI was localized to the soma and axonal processes of large ganglion cells (GCs) and to the soma and dendritic arborization of amacrine cells (ACs). NPY-LI GCs were unevenly distributed across the retina, the highest density of 875 cells/mm2 was found in the fovea centralis and the lowest density of 15 cells/mm2 in the peripheral retina. The total number of NPY-LI GCs in the retina was estimated to be about 85,000. The soma sizes of NPY-LI GCs increased from 116 microns 2 +/- 23 (s.d.) in the retinal centre to 251 microns 2 +/- 57 in the retinal periphery. The soma size of NPY-LI ACs was in the range of 40 and 50 microns 2. In transverse sections NPY-LI was seen to be localized to the optic fibre layer, to the somata of GCs, to the scleral sublamina of the inner plexiform layer (AC dendrites) and to the innermost part of the inner nuclear layer (somata of ACs). The gradients of soma sizes and retinal distribution of NPY-LI GCs were taken as an indication that they correspond to the class of large to very large GCs, previously identified in the human retina by Golgi impregnation.


[Vladimir Zederbaum" (1883-1942): Physician, journalist, contributor to the Russian "Jewish, Encyclopedia". A research report].
Vol. 15 o f the "Jewish Encyclopedia" (St. Petersburg 1908-1913) contains an article on Freud, signed by Vladimir Zederbaum. The data for the article were provided by Max Eitingon. This paper addresses the question of whether Zederbaum himself was Eitingon's contact. Several archives produced a lot of information about Zederbaum's medical and journalistic activities in St. Petersburg. However, to date no connection between the two men could be established.


Nutritional modulation of gut microbiota - the impact on metabolic disease pathophysiology.
The obesity epidemic afflicts over one third of the United States population. With few therapies available to combat obesity, a greater understanding of the systemic causes of this and other metabolic disorders is needed to develop new, effective treatments. The mammalian intestinal microbiota contributes to metabolic processes in the host. This review summarizes the research demonstrating the interplay of diet, intestinal microbiota and host metabolism. We detail the effects of diet-induced modifications in microbial activity and resultant impact on (1) sensory perception of macronutrients and total energy intake; (2) nutrient absorption, transport and storage; (3) liver and biliary function; (4) immune-mediated signaling related to adipose inflammation; and (5) circadian rhythm. We also discuss therapeutic strategies aimed to modify host-microbe interactions, including prebiotics, probiotics and postbiotics, as well as fecal microbiota transplantation. Elucidating the role of gut microbes in shaping metabolic homeostasis or dysregulation provides greater insight into disease development and a promising avenue for improved treatment of metabolic dysfunction.


A review on the scope of remediating chlorinated paraffin contaminated water bodies and soils/sediments.
Chlorinated paraffins (CPs) involve a wide range of complex mixtures of chlorinated alkanes. The versatility of their physicochemical properties and their wide range of use has turned them into ubiquitous materials. This review covers the scope of remediating CP-contaminated water bodies and soil/sediments via thermal, photolytic, photocatalytic, nanoscale zero-valent iron (NZVI), microbial and plant-based remediation techniques. Thermal treatments above 800 °C can lead to almost 100 % degradation of CPs by forming chlorinated polyaromatic hydrocarbons and thus should be supported with appropriate pollution control measures leading to high operational and maintenance costs. The hydrophobic nature of CPs lowers their water solubility and reduces their subsequent photolytic degradation. However, photocatalysis can have considerably higher degradation efficiency and generates mineralized end products. The NZVI also showed promising CP removal efficiency, especially at lower pH, which is challenging to achieve during field application. CPs can also be bioremediated by introducing both naturally occurring bacteria and also by engineered bacterial strains which are capable of producing specific enzymes (like LinA2 and LinB) to catalyze CP degradation. Depending on the type of CP, bioremediation can even achieve a dechlorination efficiency of >90 %. Moreover, enhanced degradation rates can be achieved through biostimulation. Phytoremediation has also exhibited CP bioaccumulation and transformation tendencies, both at lab-scale and in field-scale studies. The future research scope can include developing more definitive analytical techniques, toxicity and risk assessment studies of CPs and their degradation products, and technoeconomic and environmental assessment of different remediation approaches.


Assessment of proportional growth of very low birth weight infants fed banked human milk.
Twenty appropriate (mean +/- S.D., gestational age (AGA): 29.9 +/- 1.5 weeks) and 15 small (GA: 34.6 +/- 2.4 weeks) for gestational age (SGA) very low birth weight infants fed banked mature human milk were studied until term for anthropometric parameters: midarm (MAC), chest (CC), head (HC) circumferences, triceps (TSKF) and subscapular (SSKF) skinfold thickness recorded at 15 and 60 s, dynamic skinfold (delta % SKF), muscle (AMA) and fat (AFA) areas, weight and length. In AGA infants, all the parameters at term were significantly lower in extrauterine (EUL) that in intrauterine life (IUL). At term the relative proportion of AFA to total arm area was increased in EUL compared to IUL both in AGA (25.87 +/- 3.8 vs. 23.26 +/- 1.27% respectively, P less than 0.01) and in SGA infants (21.89 +/- 4.63 vs. 18.81 +/- 3.9 respectively, P less than 0.05). SGA infants showed a similar growth in EUL compared to IUL, and a significantly lower AMA and AFA than in AGA infants in EUL. Although HC was in both infants below the 10th centile at term, the ratio weight/HC2 suggests a relative preservation of head growth in EUL compared to IUL (AGA: 20.72 less than 0.87 vs. 22.65 +/- 1.46 respectively, P less than 0.001; SGA; 20.82 +/- 1.16 vs. 21.62 +/- 1.86 respectively, NS). Delta %SKF were negatively correlated with post-conceptional age suggesting a loss of extracellular water in AGA (delta %TSKF: r = -0.287, P less than 0.02) and in SGA infants (delta %TSKF: r = -0.301, P less than 0.02; delta %SSKF: r = -0.316, P less than 0.02). An intrauterine model of discrimination between AGA and SGA infants does not apply to EUL. An equation was established in SGA infants with the best discriminant parameters giving a predictive post-conceptional age: post-conceptual age (PCA) (weeks) = 0.276 HC (cm) + 0.723 CC (cm) - 0.122 MAC (cm) + 0.5 TSKF (mm) + 10.173, (r = 0.867, P less than 0.001) allowing a clear discrimination between AGA and SGA infants. These results suggest that infants show quite different growth patterns between IUL and EUL both for AGA and SGA infants.


Phylogenetic study of bisexual Artemia using random amplified polymorphic DNA.
Study of polymorphisms in the eukaryotic genome is an important way to discover the evolutionary relationships between species. Artemia (Crustacea, Anostraca) offers a very interesting model for evolutionary studies. In fact the genus, distributed all over the world in hundreds of known biotopes, comprises both bisexual sibling species and parthenogenetic populations easily available from the Artemia Reference Center of Ghent. In spite of great interest in it and its extensive use in aquaculture, little is known about relationships between the different species and intraspecific populations. Recently it has been demonstrated that polymorphisms in genomic fingerprints generated by arbitrarily primed polymerase chain reaction (PCR) can distinguish between strains in many organisms. We have used this technique to estimate the phylogenetic relationships existing between 14 populations living in the American continent, in the Mediterranean area, and in China. The principal coordinate analysis (PCO) obtained from 86 random amplified polymorphic DNA (RAPD) markers indicates that the populations analyzed can be divided into homogeneous clusters representing the four known bisexual species--the American A. franciscana and A. persimilis, the Mediterranean A. salina, and the A. species from China.


A synthetic peptide to the predicted 6.9K translation product of the HindIII-H/EcoRI-D region of the AcNPV genome induces antibodies to the basic DNA-binding protein.
The sequence of the HindIII-H/EcoRI-D region of the AcNPV genome revealed a 55 codon methionine-initiated open reading frame (Wilson, M.E., Mainprize, T.H., Friesen, P.D. and Miller, L.K., 1987, J. Virol. 61, 661-666). This open reading frame predicts a 6.9K translation product with an amino acid composition nearly identical to the basic virion DNA-binding protein. A synthetic peptide was prepared to a region of the predicted 6.9K protein and used to induce antibodies in rabbits. Western blots of viral proteins, infected cell-specific proteins (24 h p.i.), and basic chromatin-associated proteins (24 h p.i.) were probed with anti-6.9K antisera. In all immunoblots, the anti-6.9K antisera were specific for the basic DNA-binding protein. This investigation provides further evidence that the basic DNA-binding protein of the virion is a viral-encoded gene transcribed from the HindIII-H/EcoRI-D region of the genome.


Epidermal growth factor receptor (EGF-R) in Dupuytren's disease.
The aim of this paper was to examine participation of the epidermal growth factor receptor (EGF-R) signal pathway in the pathogenesis of Dupuytren's disease. The study showed changes in the ratio of membrane EGF-R to its intracellular level during the different clinical stages of Dupuytren's contracture progression. Our observations of a high ratio of surface to intracellular EGF-R in the palmar aponeurosis of patients with second degree of Dupuytren's disease (Iselin's classification), which was significantly higher than this ratio in control palmar fascia (P=0.022), would suggest that EGF-R has a role in the involutional phase of the disease.


Volvulus of the colon.
We have reviewed the records of 48 patients who had colonic volvulus. Volvulus occurred in the sigmoid colon in 27 (56%) and in the right colon in 19 (40%). Volvulus elsewhere in the colon is rare, requiring unusual anatomic circumstances of a long mesentery and a mobile colon. The clinical history is characterized by a long history of bowel dysfunction followed by an episode of acute intestinal obstruction. The patient is often aged and is plagued by mental disorders and a number of degenerative diseases. Distention of the abdomen is the most significant finding, and tenderness may indicate peritonitis due to ischemic changes in the bowel. Three-positional films of the abdomen are most valuable, showing great distention of the colon and air-fluid levels in the bowel with regularity. Barium-enema studies will more accurately reveal the site and nature of obstruction. The barium-enema examination must be done carefully. It is omitted when peritonitis is present. Operative treatment is necessary for volvulus of the right colon. Non-operative reduction is effective for nonstrangulating volvulus of the sigmoid colon as an emergency procedure. Sigmoidoscopic examination and insertion of a long rubber tube will give dramatic relief to a substantial number of patients. Operative intervention is necessary when conservative measures fail. When gangrene is found at operation, exteriorization resection of the colon may be life-saving. Elective resections are recommended for patients who are in otherwise good health in order to prevent recurrences. The mortality rate in this series of 48 cases was 12.5 per cent. Cecal volvulus was present in each of the six patients who died. Sepsis and cardiopulmonary diseases were common in patients who died.


A case study of the Tenwek hospital community health programme in Kenya.
Tenwek mission hospital, situated in the west-central highlands of Kenya, initiated a community health programme in 1984. This paper describes the major features of the programme and assesses the impact on a number of health and family planning practices after 3 years of implementation. Comparison of the results in the programme areas with the baseline survey and with control areas show significant changes in several indicators. It is concluded that Tenwek hospital demonstrated the impact a hospital can have on health of communities by effectively moving into community-based health care.


Detection of a suppressive immunoregulatory factor (IRF) in the sera of sarcoma patients by enzyme-linked immunoassay (ELISA) and correlation with clinical course.
Immunoregulatory factor (IRF) is a 70,000 molecular weight glycoprotein produced by human tumors that suppresses lymphocyte function including mitogen-stimulated tritiated leucine (3H-leu) and tritiated thymidine (3H-Tdr) uptake, in vitro immunoglobulin synthesis, induction of allospecific cell-mediated cytotoxicity, and proliferation of T-cell growth factor-dependent lymphocyte cultures. Antisera to IRF were produced by immunization of goats and rabbits with IRF purified by diethylaminoethyl (DEAE)-anion exchange and affinity chromatography. Antisera specificity was demonstrated by binding to IRF but not control muscle extract in an ELISA test and by specific removal of IRF activity by antibody coupled to acrylamide beads. Using these antisera, a double antibody-binding assay was developed to measure circulating levels of IRF and to determine its relationship to tumor growth and relevance for monitoring the clinical course of cancer patients. Quantitative autologous as well as allogeneic binding of sarcoma patients' sera to anti-IRF antibody was demonstrated. Of five tumor extracts tested, two had immunosuppressive activity, and IRF was detected in the preoperative sera of both patients. These extracts were not suppressive and IRF was not detected in the preoperative sera of these patients. In a double-blind study, analysis of serial serum samples from 26 sarcoma patients, 11 normal volunteers, and eight noncancer patients, demonstrated four patterns of circulating IRF: sustained high levels, increasing levels, decreasing levels, and no detectable IRF. Seven of 14 patients who eventually developed metastatic disease demonstrated sustained high or increasing levels of IRF. Eleven of 12 patients clinically free of tumor for five years or more, ten of 11 normal volunteers, and eight of eight noncancer patients had either a pattern of decreasing levels or no detectable IRF. Circulating IRF levels are correlated with the presence of tumor and may be useful in monitoring the clinical course of cancer patients.


Cloning and expression of two anti-lipopolysaccharide factors in Eriocheir hepuensis under Vibrio alginolyticus-induced stress.
Anti-lipopolysaccharide factors (ALFs) are small basic proteins that exhibit broad-spectrum antiviral properties and antibacterial activity. In this research, we cloned and studied two Eriocheir hepuensis ALFs, EhALF2 and EhALF3. The results showed that the open reading frame lengths of EhALF2 and EhALF3 were 363 and 372 bp, encoding 120 and 123 amino acids, respectively. Their sequences both contained an Lipopolysaccharide-binding (LPS) domain and were highly similarity to other crab ALFs. qRT-PCR showed that EhALF2 and EhALF3 were detected in nine examined tissues and were expressed the highest in the haemocytes. After challenge with Vibrio alginolyticus, in the hepatopancreas, the expression levels of EhALF2 and EhALF3 reached the highest levels at 48 and 3 h, respectively. In the heart, the expression levels of the two genes were highest at 12 h. These results indicate that EhALF2 and EhALF3 could participate in the resistance of E. hepuensis to V. alginolyticus stress within a short time. They have potential applications in the study of environmental stress markers and disease-resistance factors in E. hepuensis.


Virtual facebow technique.
This article describes a virtual technique for transferring the location of a digitized cast from the patient to a virtual articulator (virtual facebow transfer). Using a virtual procedure, the maxillary digital cast is transferred to a virtual articulator by means of reverse engineering devices. The following devices necessary to carry out this protocol are available in many contemporary practices: an intraoral scanner, a digital camera, and specific software. Results prove the viability of integrating different tools and software and of completely integrating this procedure into a dental digital workflow.


Nonalcoholic fatty liver disease and sarcopenia: pathophysiological connections and therapeutic implications.
Nonalcoholic fatty liver disease (NAFLD) is currently one of the most common liver diseases worldwide. Recent data suggest that loss of skeletal muscle mass and function (i.e. sarcopenia) is highly prevalent and frequently overlooked in NAFLD patients. Experimental and clinical data suggest that the relationship between NAFLD and sarcopenia is pathophysiologically complex and bi-directional and there is a growing interest in unveiling how sarcopenia could influence NAFLD development and progression. PubMed/MEDLINE was searched for articles related to concomitant occurrence of NAFLD and sarcopenia between January 2013 and April 2020. Areas covered in this review include: (1) updated sarcopenia diagnosis strategy, (2) discussion of current data on pathophysiological connections between NAFLD and sarcopenia, and (3) analysis of current and future therapeutic implications of this knowledge. Clinical studies describe a consistent association between NAFLD and sarcopenia, although a cause-effect relation remains to be determined. Active implementation of current diagnosis algorithms and optimized treatment can prevent sarcopenia related complications in subjects with NAFLD. Pathogenic pathways implicated in this relation are multiple and complex, a better understanding of them can provide novel biomarkers and targeted therapies that will hopefully have an important impact in NAFLD management.


Sex differences in the pathophysiology, treatment, and outcomes in IHD.
Heart disease is the number one killer of women. Although there are many similarities between men and women, the evolving understanding of ischemic heart disease in women allow us to emphasize the important differences that need to be recognized. These differences, including symptoms at presentation, importance of particular risk factors, pathophysiology of disease, and treatments/outcomes, will be discussed in this review.


Three-dimensional magnetic resonance spectroscopic imaging of brain and prostate cancer.
Clinical applications of magnetic resonance spectroscopic imaging (MRSI) for the study of brain and prostate cancer have expanded significantly over the past 10 years. Proton MRSI studies of the brain and prostate have demonstrated the feasibility of noninvasively assessing human cancers based on metabolite levels before and after therapy in a clinically reasonable amount of time. MRSI provides a unique biochemical "window" to study cellular metabolism noninvasively. MRSI studies have demonstrated dramatic spectral differences between normal brain tissue (low choline and high N-acetyl aspartate, NAA) and prostate (low choline and high citrate) compared to brain (low NAA, high choline) and prostate (low citrate, high choline) tumors. The presence of edema and necrosis in both the prostate and brain was reflected by a reduction of the intensity of all resonances due to reduced cell density. MRSI was able to discriminate necrosis (absence of all metabolites, except lipids and lactate) from viable normal tissue and cancer following therapy. The results of current MRSI studies also provide evidence that the magnitude of metabolic changes in regions of cancer before therapy as well as the magnitude and time course of metabolic changes after therapy can improve our understanding of cancer aggressiveness and mechanisms of therapeutic response. Clinically, combined MRI/MRSI has already demonstrated the potential for improved diagnosis, staging and treatment planning of brain and prostate cancer. Additionally, studies are under way to determine the accuracy of anatomic and metabolic parameters in providing an objective quantitative basis for assessing disease progression and response to therapy.


Polarized helper-T-cell responses against Leishmania major in the absence of B cells.
B-cell-to-T-cell signaling can shape helper T (Th) cell responses. During infection with Leishmania major, Th response is critical in determining the outcome of disease. Resistance depends on the generation of a protective Th1 response, while susceptibility is mediated by the generation of a Th2 response. In this study, we determined whether B cells are required for the development of polarized Th1 and Th2 responses during infection with L. major. Mice lacking B cells due to disruption of the immunoglobulin M locus (microMT) were infected with L. major, and disease progression and Th cell development were assessed. On the genetically resistant C57BL background, both wild-type and microMT mice controlled the infection and mounted a Th1 response. On the genetically susceptible BALB/c background, both wild-type and microMT mice were susceptible to infection and generated Th2 responses. Thus, during L. major infection, neither direct antigen presentation or costimulation by B cells nor antibody-mediated effector functions are essential for the development of polarized Th responses.


Relationship Between Residents' Physiological Stress and Faculty Leadership Skills in a Department of Surgery.
Leadership skills of team leaders can impact the functioning of their teams. It is unknown whether attending surgeons' leadership skills impact residents' physiological stress. This study sought to (1) assess the relationship between attending surgeons' leadership skills and residents' physiological stress and (2) to characterize lifestyle behaviors associated with resident physiological stress. We hypothesized that strong attending leadership skills would be associated with low resident physiological stress. This prospective observational cohort study was conducted at a single urban, academic medical center in the US, over 12 months. Residents were enrolled during their rotation of 1 to 2 months on the Trauma and ICU services. The primary predictor was the attending surgeons' leadership skills that were measured using a weekly survey filled out by residents, using the Surgeons' Leadership Inventory (SLI). The SLI uses a 4-point Likert scale to measure surgeons' leadership skills across eight domains. The primary outcome was residents' physiological stress, which was measured by their Heart Rate Variability (HRV). We recorded the residents' HRV with a WHOOP strap that was continuously worn on the wrist or the bicep. We used multivariate repeated measures gamma regression to assess the relationship between attending leadership skills and residents' physiological stress, adjusting for hours of sleep, age, and service. Sixteen residents were enrolled over 12 months. The median attending surgeons' leadership score was 3.8 (IQR: 3.2-4.0). The median residents' percent of maximal HRV was 70.8% (IQR: 56.7-83.7). Repeated measure gamma regression model demonstrated a minimal nonsignificant increase of 1.6 % (95% CI: -5.6, 8.9; p-value = 0.65) in the percent of maximal HRV (less resident physiological stress) for every unit increase in leadership score. There was an increase of 2.9% (95% CI= 1.6, 4.2; p-value < 0.001) in the percent of maximal HRV per hour increase in sleep and a significant decrease of 10.9% (95% CI= -16.8, -5.2; < 0.001) in the percent of HRV when working in the ICU compared to the Trauma service. This study revealed that more residents' sleep was associated with lower physiological stress. Attending surgeons' leadership skills were not associated with residents' physiological stress.


DNA electroporation prime and protein boost strategy enhances humoral immunity of tuberculosis DNA vaccines in mice and non-human primates.
DNA vaccines have shown to induce strong immune response in small animals; however, its capacity of inducing robust antigen-specific immune responses in large animals is limited. In the present study, in vivo electroporation (EP) was applied and the effect of EP on humoral immune response against tuberculosis (TB) induced by DNA vaccination was tested in mice and rhesus macaques. Mice injected with 10 microg DNA encoding Ag85A and ESAT-6 followed by EP showed a reproducible humoral immunity which was equal to that obtained by using 100 microg DNA without EP. Boosting the DNA/EP treated animals with corresponding recombinant protein (50 microg of either Ag85A or ESAT-6) without adding adjuvant gave more than a 7-8-fold increase in the antibody titre but only 3-4-fold increase was found in the mice receiving 100 microg DNA without EP followed by protein boost. In concordance with the results obtained in mice, the monkeys received less DNA achieved equal high antibody responses to those induced by high dosage of DNA. Boosting the the DNA/EP treated monkeys with TB protein (500 microg of either Ag85A or ESAT-6) improved the humoral response by 7-8-fold increase in antibody titre, indicating electroporation's ability to compensate lower DNA concentration and enhance humoral immunity of TB DNA vaccines in mice and non-human primates.


Logistic distributed activation energy model--Part 1: Derivation and numerical parametric study.
A new distributed activation energy model is presented using the logistic distribution to mathematically represent the pyrolysis kinetics of complex solid fuels. A numerical parametric study of the logistic distributed activation energy model is conducted to evaluate the influences of the model parameters on the numerical results of the model. The parameters studied include the heating rate, reaction order, frequency factor, mean of the logistic activation energy distribution, standard deviation of the logistic activation energy distribution. The parametric study addresses the dependence on the forms of the calculated α-T and dα/dT-T curves (α: reaction conversion, T: temperature). The study results would be very helpful to the application of the logistic distributed activation energy model, which is the main subject of the next part of this series.


Persistent damage induces mitochondrial DNA degradation.
Considerable progress has been made recently toward understanding the processes of mitochondrial DNA (mtDNA) damage and repair. However, a paucity of information still exists regarding the physiological effects of persistent mtDNA damage. This is due, in part, to experimental difficulties associated with targeting mtDNA for damage, while sparing nuclear DNA. Here, we characterize two systems designed for targeted mtDNA damage based on the inducible (Tet-ON) mitochondrial expression of the bacterial enzyme, exonuclease III, and the human enzyme, uracil-N-glyosylase containing the Y147A mutation. In both systems, damage was accompanied by degradation of mtDNA, which was detectable by 6h after induction of mutant uracil-N-glycosylase and by 12h after induction of exoIII. Unexpectedly, increases in the steady-state levels of single-strand lesions, which led to degradation, were small in absolute terms indicating that both abasic sites and single-strand gaps may be poorly tolerated in mtDNA. mtDNA degradation was accompanied by the loss of expression of mtDNA-encoded COX2. After withdrawal of the inducer, recovery from mtDNA depletion occurred faster in the system expressing exonuclease III, but in both systems reduced mtDNA levels persisted longer than 144h after doxycycline withdrawal. mtDNA degradation was followed by reduction and loss of respiration, decreased membrane potential, reduced cell viability, reduced intrinsic reactive oxygen species production, slowed proliferation, and changes in mitochondrial morphology (fragmentation of the mitochondrial network, rounding and "foaming" of the mitochondria). The mutagenic effects of abasic sites in mtDNA were low, which indicates that damaged mtDNA molecules may be degraded if not rapidly repaired. This study establishes, for the first time, that mtDNA degradation can be a direct and immediate consequence of persistent mtDNA damage and that increased ROS production is not an invariant consequence of mtDNA damage.


Milestones in chloroplast genetic engineering: an environmentally friendly era in biotechnology.
Chloroplast genomes defied the laws of Mendelian inheritance at the dawn of plant genetics, and continue to defy the mainstream approach to biotechnology, leading the field in an environmentally friendly direction. Recent success in engineering the chloroplast genome for resistance to herbicides, insects, disease and drought, and for production of biopharmaceuticals, has opened the door to a new era in biotechnology. The successful engineering of tomato chromoplasts for high-level transgene expression in fruits, coupled to hyper-expression of vaccine antigens, and the use of plant-derived antibiotic-free selectable markers, augur well for oral delivery of edible vaccines and biopharmaceuticals that are currently beyond the reach of those who need them most.


Coastal bays and coral cays: Multi-element study of Chelonia mydas forage in the Great Barrier Reef (2015-2017).
There is increasing interest in understanding potential impacts of complex pollutant profiles to long-lived species such as the green sea turtle (Chelonia mydas), a threatened megaherbivore resident in north Australia. Dietary ingestion may be a key exposure route for metals in these animals and marine plants can accumulate metals at higher concentrations than the surrounding environment. We investigated concentrations of 19 metals and metalloids in C. mydas forage samples collected from a group of offshore coral cays and two coastal bays over a period of 2-3 years. Although no samples exceeded sediment quality guidelines, coastal forage Co, Fe, and V concentrations were up to 2-fold higher, and offshore forage Sr concentrations were ~3-fold higher, than global seagrass means. Principal Component Analysis differentiated coastal bay from coral cay forage according to patterns consistent with underlying terrigenous-type or marine carbonate-type sediment geochemistry, such that coastal bay forage was higher in Fe, Co, Mn, Cu, and Mo (and others) but forage from coral cays was higher in Sr and U. Forage from the two coastal bays was differentiated according to temporal variation in metal profiles, which may be associated with a more episodic sediment disturbance regime in one of the bays. For all study locations, some forage metal concentrations were higher than previously reported in the global literature. Our results suggest that forage metal profiles may be influenced by the presence of some metals in insoluble forms or bound to ultra-fine sediment particles adhered to forage surfaces. Metal concentrations in Great Barrier Reef forage may be present at levels higher than expected from the global seagrass literature and appear strongly influenced by underlying sediment geochemistry.


Phosphatase PTEN in neuronal injury and brain disorders.
The phosphatase and tensin homologue PTEN was originally identified as a tumor suppressor. In the CNS, mutation or inactivation of PTEN is best known for playing a tumorigenic role in the molecular pathogenesis of glioblastoma. However, recent studies show that PTEN is associated with several brain diseases other than cancer, suggesting a broader role of PTEN in CNS pathophysiology. Here, we review the evidence for the crucial involvement of PTEN in neuronal injury as well as in neurological and psychiatric disorders, and discuss the potential of PTEN as a molecular target for the development of a novel CNS therapeutic strategy.


Relationship between TH1/TH2 cytokines and immune tolerance in liver transplantation in rats.
To explore the relationship between Th1/Th2 cytokine expressions and immune tolerance in rat liver transplantation. Recipients were divided into three groups (each group = 12 rats). The allograft group underwent orthotopic liver transplantation from male Wistar-to-Sprague-Dawley (SD) rats. The isograft group of SD-to-SD liver transplantation was complemented with a control group of normal male SD rats that had sham operations. We evaluated the 2-week survival rates histological changes, as well as serum and mRNA expression levels of Th1/Th2 cytokines: interferon-gamma (IFN-gamma) and interleukin-10 (IL-10). The 1-week survival in the isograft and allograft groups were 100% and 41.67%, respectively. The 2-week survival rates were 75% and 8.33% (P < .05). Light microscopic inspection revealed severe acute rejection in the allograft but not the isograft group in the first week postoperation. This observation was verified by the cellular morphology under transmission electron microscopy. Serum IFN-gamma (Th1 cytokine) levels (pg/mL) determined by enzyme-linked immunosorbent assay in the allograft, isograft, and control groups were 386.67 +/- 14.36, 159.83 +/- 16.53, and 87.83 +/- 8.67, respectively; for IL-10 (Th2 cytokine), they were 126.33 +/- 13.10, 288.33 +/- 17.10, and 70.50 +/- 7.23, respectively (P < .05, allograft vs isograft). The semiquantitative reverse-transcriptase polymerase chain reaction assay showed that expression of IFN-gamma and IL-10 mRNA was similar to that of serum levels. IFN-gamma mRNA was more highly expressed in the allograft group and IL-10 mRNA, in the isograft group (P < .05). The dynamic equilibrium of Th1/Th2 cytokines is critically involved in immune tolerance. The deviation of Th1 to Th2 may be one mechanism of immune tolerance.


Effect of sodium orthovanadate on the hepatobiliary clearance of rose bengal in streptozotocin-induced diabetic rats.
Sodium orthovanadate is known to promote glucose uptake in muscle and adipose tissues and has been suggested as a possible oral hypoglycemic agent. In addition, insulin-dependent diabetes has been shown to alter the hepatobiliary clearance of several drugs in rats. This study has determined whether orthovanadate, like insulin, can reverse diabetes-induced changes in the biliary excretion of endogenous bile acids and in the hepatobiliary clearance of rose bengal. Six groups of male Sprague-Dawley rats were used; normal, insulin-treated normal, vanadate-treated normal, diabetic, insulin-treated diabetic, and vanadate-treated diabetic. Diabetes was induced by injection of streptozotocin (45 mg/kg, i.v.). One week later, insulin (2-4 U/day, s.c.) and sodium orthovanadate (877 +/- 82 mumol/kg/day, p.o.) treatments were initiated. After 4 weeks, the clearance and biliary excretion of rose bengal (60 mumol/kg, i.v.) were determined for 3 hr. Bile flow rate, rose bengal excretion, and excretion of endogenous bile acids were unchanged in the two treated normal groups and in the insulin-treated diabetic rats. These parameters were increased in untreated diabetic and vanadate-treated diabetic rats as compared with normal. Pharmacokinetic analyses indicated that total and biliary clearances of rose bengal were increased in diabetic rats and that orthovanadate did not reverse these changes. However, liver weight and serum glucose concentrations were reduced by orthovanadate treatment. These data indicate that the oral insulinomimetic chemical sodium orthovanadate effectively reversed some, but not all, of the diabetes-induced alterations of hepatic function.


Climate, race, and the cost of capital in the municipal bond market.
Both climate risk and race are factors that may affect municipal bond yields, yet each has received relatively limited empirical research attention. We analyzed > 712,000 municipal bonds representing nearly 2 trillion USD in par outstanding, focusing on credit spread or the difference between a debt issuer's interest cost to borrow and a benchmark "risk-free" municipal rate. The relationship between credit spread and physical climate risk is significant and slightly positive, yet the coefficient indicates no meaningful spread penalty for increased physical climate risk. We also find that racial composition (the percent of a community that is Black) explains a statistically significant and meaningful portion of municipal credit spreads, even after controlling for a variety of variables in domains such as geographic location of issuer, bond structure (e.g., bond maturity), credit rating, and non-race economic variables (e.g., per capita income). Assuming 4 trillion USD in annual outstanding par across the entire municipal market, and weighting each issuer by its percent Black, an estimated 19 basis point (bp) penalty for Black Americans sums to approximately 900 million USD annually in aggregate. Our combined findings indicate a systemic mispricing of risk in the municipal bond market, where race impacts the cost of capital, and climate does not.


High-capacity CoP-Mn3P nanoclusters heterostructures derived by Co2MnO4 as advanced electrodes for supercapacitors.
Although transition metal oxides (TMOs) have attracted enormous attention owing to their high performance in supercapacitors, it still remains challenging issues in terms of the poor electrical conductivity, sluggish redox kinetics and insufficient electrochemical active sites. Herein, the high-capacity CoP-Mn3P nanoclusters featuring the heterogeneous interfaces have been successfully synthesized through hydrothermal method followed by annealing. The heterojunction formed between CoP and Mn3P redistributes the charge at the interface between them, generating the built-in electric field to accelerate electron transfer, and thus the conductivity of the electrode is enhanced. Moreover, the unique morphology of nanoclusters composed of flake structures is beneficial to provide more electrochemical active sites. Consequently, the resultant CoP-Mn3P nanoclusters electrode delivers an exceptional gravimetric specific capacity (2714 F g-1 at 1 A g-1) as well as a long cycle lifespan (83.1% of capacitance retention after 10,000 cycles). An asymmetric supercapacitor (ASC) device assembling with employing CoP/Mn3P electrode presents an ultrahigh energy density value of 46.4 Wh kg-1 at a power density of 800.0 W kg-1 and a super capacitance retention of 86.2% after 30,000 cycles. This work paves an effective way for the investigation on the charge transfer kinetics of electrode materials.


Effect of the passive films on CaCO3 scale depositing on Q235 steel: Electrochemical and surface investigation.
The deposition of the CaCO3 scale in circulating cooling water is a common and serious concern in the industry, which hinders the heat transfer, reduces water flow and blocks membrane filters. This paper aims at studying the effect of the γ-Fe2O3, Fe2(MoO4)3·γ-Fe2O3 and FePO4·γ-Fe2O3 passive films on CaCO3 scale deposition on Q235 steel by electrochemical methods, including linear sweep voltammetry (LSV), chronoamperometry and electrochemical impedance spectroscopy (EIS) tests. The scale and corrosion inhibition performance of the passive films was evaluated by the residual current density (ir) and charge transfer resistance (Rct) values. Electrochemical results suggested that the passive films could inhibit corrosion and reduce the CaCO3 scale deposition on Q235 steel and the FePO4·γ-Fe2O3 complex passive film showed the best anti-scaling effect. Scanning electron microscope (SEM) and X-ray diffractometer (XRD) tests showed that the passive films could lead to a decrease in the proportion of aragonite to calcite under cathodic water reduction conditions and the composition of the FePO4·γ-Fe2O3 complex passive film could deform the CaCO3 crystal.


Two models of job stress and depressive symptoms. Results from a population-based study.
Evidence indicates that an adverse psychosocial work environment contributes to the explanation of depressive symptoms. Research was mainly informed by two theoretical models, the demand-control and the effort-reward imbalance model. Yet, a comparative analysis of the two models, using original scales, has not yet been conducted in an unselected working population. A total of 1,811 working men and women from the baseline screening of an epidemiological cohort study were interviewed (job stress, depressive symptoms [CES-D], health behaviours, medical history, socio-demographic characteristics). Logistic regression models were calculated to estimate associations between depressive symptoms, the two job stress models and relevant covariates. Analyses showed significantly increased multivariate odds ratio (OR) of job strain and effort-reward imbalance. When the two models were mutually adjusted control [OR, 95% CI=1.9, 1.3-2.7], effort-reward imbalance [OR, 95% CI=3.4, 2.1-5.1] and overcommitment OR, 95% CI=3.9, 2.7-5.8] were independently associated with depressive symptoms Additional tests of interaction between the models revealed relatively highest level of depressive symptoms in employees who simultaneously reported low control and high overcommitment. Components of an adverse psychosocial work environment are associated with depressive symptoms in an unselected working population. Policy implications of accumulated evidence on this relation should be addressed.


The effects of frequency lowering on speech perception in noise with adult hearing-aid users.
Frequency lowering (FL) strategies move high frequency sound into a lower frequency range. This study determined if speech perception differences are observed between some of the different frequency lowering strategies that are available. A cross-sectional, repeated-measures design was used to compare three hearing aids that used wide-dynamic range compression (WDRC) and either non-linear frequency compression (NFC), linear frequency transposition (LFT), or frequency translation (FT). The hearing aids were matched to prescriptive real ear targets for WDRC. The settings for each FL strategy were adjusted to provide audibility for a 6300 Hz filtered speech signal. Sentence recognition in noise, subjective measures of sound quality, and a modified version of the speech intelligibility index (SII) were measured. Ten adults between the ages of 63 to 82 years with bilateral, high frequency hearing loss. LFT and FT led to poorer sentence recognition compared to WDRC for most individuals. No difference in sentence recognition occurred with and without NFC. The quality questionnaire and SII showed few differences between conditions. Under similar fitting and testing conditions of this study, FL techniques may not provide speech understanding benefit in certain background noise situations.


[Prokaryotic expression and purification of human immunodeficiency virus p24 antigen].
To express and purify the HIV p24 gene in E. coli cells, and identify p24 antigen activity. The full length gene fragment of HIV p24 was amplified by PCR and inserted into the pRSET vector in order to construct the pRSET-p24 recombined vector. After transforming into E. coil, the purified p24 protein was prepared by metal-ligand affinity chromatography (IMAC). The accuracy of inserted gene and activity, specificity of HIV p24 proteins were detected by two enzymes digestion technology, SDS-PAGE, Western Blot (WB) and ELISA. The length of the HIV p24 gene fragment was 690 bp after digesting the recombinant plasmid T-p24 and pRSET-p24 with BamH I and Hind III. The expressed proteins had a single expected band of about 24 x 10(3) in SDS-PAGE. The specificity and activity of p24 protein were tested by WB and ELISA. The HIV p24 sequence from HIV-1 gene plasmid hasbeen expressed in E. coil. This protein possessed good specificity and activity.


Surgical resident technical skill self-evaluation: increased precision with training progression.
Surgical resident ability to accurately evaluate one's own skill level is an important part of educational growth. We aimed to determine if differences exist between self and observer technical skill evaluation of surgical residents performing a single procedure. We prospectively enrolled 14 categorical general surgery residents (six post-graduate year [PGY] 1-2, three PGY 3, and five PGY 4-5). Over a 6-month period, following each laparoscopic cholecystectomy, residents and seven faculty each completed the Objective Structured Assessment of Technical Skills (OSATS). Spearman's coefficient was calculated for three groups: senior (PGY 4-5), PGY3, and junior (PGY 1-2). Rho (ρ) values greater than 0.8 were considered well correlated. Of the 125 paired assessments (resident-faculty each evaluating the same case), 58 were completed for senior residents, 54 for PGY3 residents, and 13 for junior residents. Using the mean from all OSATS categories, trainee self-evaluations correlated well to faculty (senior ρ 0.97, PGY3 ρ 0.9, junior ρ 0.9). When specific OSATS categories were analyzed, junior residents exhibited poor correlation in categories of respect for tissue (ρ -0.5), instrument handling (ρ 0.71), operative flow (ρ 0.41), use of assistants (ρ 0.05), procedural knowledge (ρ 0.32), and overall comfort with the procedure (ρ 0.73). PGY3 residents lacked correlation in two OSATS categories, operative flow (ρ 0.7) and procedural knowledge (ρ 0.2). Senior resident self-evaluations exhibited strong correlations to observers in all areas. Surgical residents improve technical skill self-awareness with progressive training. Less-experienced trainees have a tendency to over-or-underestimate technical skill.


Micro-contextual identification of archaeological lipid biomarkers using resin-impregnated sediment slabs.
Characterizing organic matter preserved in archaeological sediment is crucial to behavioral and paleoenvironmental investigations. This task becomes particularly challenging when considering microstratigraphic complexity. Most of the current analytical methods rely on loose sediment samples lacking spatial and temporal resolution at a microstratigraphic scale, adding uncertainty to the results. Here, we explore the potential of targeted molecular and isotopic biomarker analysis on polyester resin-impregnated sediment slabs from archaeological micromorphology, a technique that provides microstratigraphic control. We performed gas chromatography-mass spectrometry (GC-MS) and gas chromatography-isotope ratio mass spectromety (GC-IRMS) analyses on a set of samples including drill dust from resin-impregnated experimental and archaeological samples, loose samples from the same locations and resin control samples to assess the degree of interference of polyester resin in the GC-MS and Carbon-IRMS signals of different lipid fractions (n-alkanes, aromatics, n-ketones, alcohols, fatty acids and other high polarity lipids). The results show that biomarkers within the n-alkane, aromatic, n-ketone, and alcohol fractions can be identified. Further work is needed to expand the range of identifiable lipid biomarkers. This study represents the first micro-contextual approach to archaeological lipid biomarkers and contributes to the advance of archaeological science by adding a new method to obtain behavioral or paleoenvironmental proxies.


Functionalization of LC molecular films with nanocrystalline cellulose: A study of the self-assembly processes and molecular stability.
The bottom-up approach in designing and synthesis of materials using nanoparticles of different size-, shape- or chemical composition is an extreme challenge. However, in this way, new task-specific or general use nanocomposites can be obtained. This work presents, the investigations of the preparation procedures and molecular stability of Langmuir films based on cellulose nanocrystals (CNC) and different liquid crystals. The CNC-based nanocomposite with the 5CB, 5OCB, 5FCB, and 5PCH liquid crystals, have been obtained by the modified Langmuir technique. The investigations of the Langmuir monolayers gives an excellent model system for studying intermolecular interactions at the interface, which allows analyzing the ordering, sorption, desorption, association and phase separation phenomena determining physical and chemical properties of studied systems. The process of self-assembly and molecular organization on the air-liquid interphase was studied for different compositions of LC/CNC films. The compressibility profiles and the mean molecular area have been calculated. The stability of prepared monolayers has been studied to investigate the sorption and desorption processes. The morphology of the prepared systems was determined by Brewster Angle Microscopy (BAM), and the influence of the CNC on LC organization in molecular monolayers on the air-liquid interphase has been studied.


High cervical spinal cord compression by an enterogenous cyst. Case report.
A case of enterogenous cyst causing compression of the spinal cord at C-1 is presented. The clinical course and radiological and histological findings are discussed.


Deep phenol peeling and fat injection: treatment option for perioral wrinkles in a scleroderma patient.
Scleroderma is characterized by abnormal growth of connective tissue, often manifested with hard and tight skin. The viscous properties of the skin are impaired, and the main histologic changes include a thicker dermis, absence of pilosebaceous units, and a decreased space between collagen bundles. Often these patients have wound healing problems. The objective was to demonstrate a case of scleroderma that had deep phenol perioral peeling and fat injection into the lips. According to our bibliographic search, this is the first report in the English literature of using these modalities in scleroderma patients. A 64-year-old woman suffering from scleroderma for more than 20 years came for improvement of her perioral appearance. We decided to manage her deep perioral wrinkles by deep peeling using the Baker formula and concomitantly to use autologous fat injection to augment her thin lips. The healing of our patient after these two interventions was uneventful, and satisfactory results have been obtained. Based on our experience, this intervention may be suggested for patients suffering from scleroderma after a detailed explanation of the possible wound healing difficulties is provided to the patients.


Temperature Sensitivity of Microbial Litter Decomposition in Freshwaters: Role of Leaf Litter Quality and Environmental Characteristics.
Ongoing global warming is expected to alter temperature-dependent processes. Nevertheless, how co-occurring local drivers will influence temperature sensitivity of plant litter decomposition in lotic ecosystems remains uncertain. Here, we examined the temperature sensitivity of microbial-mediated decomposition, microbial respiration, fungal biomass and leaf nutrients of two plant species varying in litter quality. We also assessed whether the type of microbial community and stream water characteristics influence such responses to temperature. We incubated alder (Alnus glutinosa) and eucalypt (Eucalyptus globulus) litter discs in three streams differing in autumn-winter water temperature (range 4.6-8.9 °C). Simultaneously, in laboratory microcosms, litter discs microbially conditioned in these streams were incubated at 5, 10 and 15 °C with water from the conditioning stream and with a water control from an additional stream. Both in the field and in the laboratory, higher temperatures enhanced litter decomposition rates, except for eucalypt in the field. Leaf quality modified the response of decomposition to temperature in the field, with eucalypt leaf litter showing a lower increase, whereas it did not in the laboratory. The origin of microbial community only affected the decomposition rates in the laboratory, but it did not modify the response to temperature. Water quality only defined the phosphorus content of the leaf litter or the fungal biomass, but it did not modify the response to temperature. Our results suggest that the acceleration in decomposition by global warming will be shaped by local factors, mainly by leaf litter quality, in headwater streams.


Environmental tobacco smoke and asthma exacerbations and severity: the difference between measured and reported exposure.
To assess the impact of measured versus reported environmental tobacco smoke (ETS) exposure on asthma severity and exacerbations in an urban paediatric population. We analysed cross-sectional data from the Chicago Initiative to Raise Asthma Health Equity study that followed a cohort of 561 children aged 8-14 with physician-diagnosed asthma between 2003 and 2005. Participant sociodemographic data and asthma symptoms were gathered by parental survey; exposures to ETS were determined by salivary cotinine levels and parent report. Multivariable negative binomial and ordered logistic regressions were used to assess associations between ETS and asthma outcomes. Among 466 children included in our analysis, 58% had moderate or severe persistent asthma; 32% had >2 exacerbations requiring a hospitalisation or an emergency room visit or same day care in the previous year. Half of caregivers reported that at least one household member smoked. In multivariable analyses, salivary cotinine was significantly associated with frequently reported exacerbations in the previous year (adjusted incidence rate ratio=1.39, 95% CI 1.09 to 1.79), but not significantly associated with asthma severity. Reported household smoking was not significantly associated with either asthma severity or frequency of exacerbations. Salivary cotinine was more predictive of asthma exacerbation frequency but caregiver- reported household smoking was not. Use of a nicotine biomarker may be important in both the clinical and research settings to accurately identify an important risk factor for asthma exacerbations.


[Statistical investigations of nosological parameters (sex distribution, diagnosis, age of onset) in 120 pairs of endogenous psychotic parent-child and sibling relationships (author's transl)].
120 pairs of parent-child and sibling relationships with endogenous psychoses--registered through 60 schizophrenic and manic-depressive probands each--are statistically investigated with regard to the nosologically and biologically relevant parameters of sex distribution, diagnosis and age of onset.


An esophageal mass with coexistent Mycobacterium chelonae and Candida albicans infections in an immunocompetent adult.
Mycobacteria chelonae was originally included in group IV of Runyon's classification of atypical mycobacteria. This rapidly growing environmental organism often caused infections in immunocompromised hosts. Candida albicans is a ubiquitous micro-organism and frequently isolated from the gastrointestinal tract. These two micro-organisms seldom cause esophageal diseases in healthy humans. We report a case of a fruit farmer with a submucosa tumor of distal esophagus caused by coexistence of M. chelonae and C. albicans infections, which was successfully treated by surgical resection and following antimicrobial regimens postoperatively.


Evaluation of lamina cribrosa thickness and depth in ocular hypertension.
To investigate the differences in thickness and depth of the lamina cribrosa (LC) between ocular hypertension (OH) patients and normal control subjects, using enhanced depth imaging (EDI) spectral-domain optical coherence tomography (SD-OCT). EDI-OCT data were obtained from the subjects in a cross-sectional analysis of data from a retrospective study. After IOP correction according to central corneal thickness (CCT), we divided the OH patients into two groups based on the corrected IOP (cIOP)--OH with lower IOP (OH-L; cIOP < 23 mmHg) and OH with higher IOP (OH-H; cIOP ≥ 23 mmHg). Comparisons of LC thickness and depth among three groups were performed. Seventy-four OH patients and 45 normal control subjects were included in the analysis. Among the 74 OH patients, 41 were included in the OH-L group and 33 were included in the OH-H group. LC thickness was thicker in the OH-H group compared to normal controls both in superior (P = 0.02) and inferior (P = 0.01) portions. However, no difference was found in LC depth among the three groups in any portion (P = 0.36; P = 0.44; P = 0.31, respectively). OH patients may have a thicker LC than normal control subjects, especially in OH with definite high IOP.


Successful use of recombinant factor VIIa for hemostasis during total knee replacement in a severe hemophiliac with high-titer factor VIII inhibitor.
A 32-year-old male patient with severe factor VIII (FVIII) deficiency had developed a high-titer FVIII inhibitor at age 13. Recurrent hemarthroses caused bony destruction in both knees, significantly impairing his ability to walk. Knee examination revealed 20 degrees of varus, destruction of the medial joint line, and flexion contracture. Total knee arthroplasty was performed using recombinant factor VIIa (rFVIIa, NovoSeven) for hemostatic control. rFVIIa (85 microg/kg given intravenously over 3-5 minutes) was given just prior to surgery. The dose was repeated every 2 hours during and for the first 48 hours after surgery. When the tourniquet was removed, rFVIIa had not been infused for 1.5 hours, and significant hemorrhage was noted. The hemorrhage responded promptly to rFVIIa infusion. The infusion interval was extended to every 4 hours for an additional 48 hours, and subsequent doses were given every 6 hours until the patient returned to the clinic 2 days postdischarge. Hemoglobin levels dropped from 16.9 gm/dL on admission to 9.1 gm/dL at discharge. After 2 months, the patient returned to work. We recommend that tourniquet release be performed immediately after rFVIIa administration and that aggressive physical therapy be considered in the early postoperative period when rFVIIa infusions are frequent.


Evaluating intra-abdominal pressures in a porcine model of acute lung injury by using a wireless motility capsule.
Intra-vesical pressure measurement as the reference standard for assessing intra-abdominal pressures is mainly indirect and discontinuous. We therefore evaluated a motility capsule for continuous intra-abdominal pressure measurement in an animal model with a high probability for capillary leakage and intestinal edema. Motility capsules were inserted into the stomachs of 8 anesthetized and ventilated pigs. Stomach pH, pressure, and temperature data were wirelessly transmitted to a recorder attached to each animal's abdomen. Intra-gastric pressures measured by the capsule were compared to intra-vesical pressures measured by a pressure transducer system. The intra-abdominal pressures ranged from 3 to 15 mmHg (7.8 ± 2.4 mmHg [mean ± SD]) measured via the bladder. The capsule pressure recordings ranged from 1 to 3 mmHg (1.7 ± 0.5 mmHg [mean ± SD]). Bland-Altman analysis revealed an unacceptable bias between the 2 methods. The test bias was 6.2 (± 1.4) mmHg and the limits of agreement were from 3.3 to 8.9 mmHg. Pressures in the stomach as measured by motility capsule underestimated the intra-vesical pressures. Discrepancies between gastric and intra-vesical pressures could be caused by gastric dilatation or different position of the 2 devices to the zero reference point.


Metagenome-Assembled Genome of a Putative Methanogenic Methanosarcina sp. Strain Enriched from Terrestrial High-CO2 Subsurface Sediments.
A metagenome-assembled genome (MAG), named Methanosarcina sp. strain ERenArc_MAG2, was obtained from a 3-month-old H2/CO2 atmosphere enrichment culture, originally inoculated with 60-m deep drill core sediment collected from the tectonic Eger Rift terrestrial subsurface. Annotation of the recovered draft genome revealed putative archaeal methanogenesis genes in the deep biosphere.


A Retrospective Survey of Rodent-borne Viruses in Rural Populations of Brazilian Amazon.
The Amazon tropical rainforest has the most dense and diverse ecosystem worldwide. A few studies have addressed rodent-borne diseases as potential hazards to humans in this region. A retrospective survey was conducted using enzyme-linked immunosorbent assay for detecting mammarenavirus and orthohantavirus antibodies in 206 samples collected from rural settlers of the Brazilian Western Amazonian region. Six (2.91%) individuals in the age group of 16 to 36 years were found to possess antibodies against mammarenavirus. Evidence of previous exposure to mammarenavirus in the rural population points to its silent circulation in this region.


[The small RNP acceptor of glucocorticoids bound to chromatin in liver cell nuclei].
The buoyant density in the CsCl gradient of the small nuclear RNP tightly bound to chromatin has been studied. It was shown that the buoyant density of alpha-RNP is characteristic for ribonucleoproteins (p = 1.36-1.50 g/cm3). The alpha-particles are of extraordinary stability. These RNP were shown to remain stable under drastic conditions (high ionic strength, SDS, 6 M urea) and resist unfixed caesium chloride density centrifugation. The alpha-RNA hybridizes with total rat liver DNA at C0t1/2 = 10(3). The oligonucleotide analysis of the alpha-RNA shows that the alpha-RNA is heterogeneous.


Cumulative cisplatin dose is not associated with event-free or overall survival in children with newly diagnosed average-risk medulloblastoma treated with cisplatin based adjuvant chemotherapy: report from the Children's Oncology Group.
Survival rates for children with medulloblastoma have risen over the past decade, in part due to the addition of cisplatin-containing adjuvant chemotherapy. Total dose of cisplatin required for optimal treatment is unknown. The purpose of this study was to evaluate the survival outcomes based on cumulative cisplatin doses (CCD) in children with newly diagnosed average-risk medulloblastoma. CCD data were reviewed for 363 patients in a prospective study evaluating patients between 3 and 21 years with a newly diagnosed average-risk medulloblastoma and treated with craniospinal radiation and post-radiation cisplatin based adjuvant chemotherapy. Eight-year event-free survival (EFS) and overall survival (OS) estimates were 78.2 ± 2.6% and 83.9 ± 2.4%, respectively. Only 73 patients received the protocol specified CCD of 600 mg/m(2), primarily due to mandated cisplatin toxicity-related dose reductions. The median CCD given to those without relapse or death on treatment was 487.5 mg/m(2). CCD, as a time-dependent covariate, was not associated with EFS (P = 0.54) or OS (P = 0.11). The 343 patients who completed chemotherapy failure-free were categorized into four groups according to CCD (n = 10; 75-150 mg/m(2)), (n = 26; 151-300 mg/m(2)), (n = 113; 301-450 mg/m(2)), and (n = 194; 451-600 mg/m(2)). There were no statistically significant differences in distributions of EFS (P = 0.53) or OS (P = 0.49) among these four groups. CCD is not associated with EFS or OS suggesting that lower doses of cisplatin may be incorporated into future medulloblastoma trials, thereby limiting its toxicity profile without affecting survival. If ototoxicity is encountered, more stringent cisplatin dose modification/cessation rules seem warranted.


A pH-dependent cluster of charges in a conserved cryptic pocket on flaviviral envelopes.
Flaviviruses are enveloped viruses which include human pathogens that are predominantly transmitted by mosquitoes and ticks. Some, such as dengue virus, exhibit the phenomenon of antibody-dependent enhancement (ADE) of disease, making vaccine-based routes of fighting infections problematic. The pH-dependent conformational change of the envelope (E) protein required for fusion between the viral and endosomal membranes is an attractive point of inhibition by antivirals as it has the potential to diminish the effects of ADE. We examined six flaviviruses by employing large-scale molecular dynamics (MD) simulations of raft systems that represent a substantial portion of the flaviviral envelope. We utilised a benzene-mapping approach that led to a discovery of shared hotspots and conserved cryptic sites. A cryptic pocket previously shown to bind a detergent molecule exhibited strain-specific characteristics. An alternative conserved cryptic site at the E protein domain interfaces showed a consistent dynamic behaviour across flaviviruses and contained a conserved cluster of ionisable residues. Constant-pH simulations revealed cluster and domain-interface disruption under low pH conditions. Based on this, we propose a cluster-dependent mechanism that addresses inconsistencies in the histidine-switch hypothesis and highlights the role of cluster protonation in orchestrating the domain dissociation pivotal for the formation of the fusogenic trimer.


Isatin: A Scaffold with Immense Biodiversity.
Isatin is an endogenous and a significant category of fused heterocyclic components and has widely been a part of several potential biologically useful synthetics. Since its discovery, tons of research work has been conducted with respect to the synthesis, chemical properties, and biological and industrial applications. It contains an indole nucleus having both lactam and keto moiety, which, while being a part of a molecular framework, exerted several biological effects, viz.; anti-microbial, anti-tubercular, anticonvulsant, anti-cancer, etc. Isatin derivatives are synthetically significant substrates, which can be utilized for the synthesis of huge diversified chemical entities of which few members emerged as drugs. The reason for this review is to provide extensive information pertaining to the chemistry and its significance in altering several pathological states of isatin and its derivatives. A Structure-Activity Relationship study thus developed through a gamut of scientific information indicates the importance of mostly electron-withdrawing groups, halogens, nitro, alkoxy, and, to a minor extent, groups with positive inductive effects, such as methyl at position 1, 5, 6 and 7 of isatin in alleviating several clinical conditions. It is also observed from the survey that the presence of two oxo groups at positions 2 and 3 sometimes becomes insignificant as a fusion with a heterocycle at these positions resulted in a biologically relevant compound.