Hemolytic activity of Serratia marcescens.
A cell-bound hemolytic activity was found in several strains of Serratia marcescens. One Serratia cell per ten erythrocytes was sufficient to cause complete lysis of human erythrocytes within 2 h in the liquid assay. The hemolytic activity resided in the membrane fraction and could be inactivated by incubating cells with proteases. The hemolytic activity was greatly enhanced in actively metabolizing Serratia cells and was partially controlled by the iron supply. Hemolysis was accompanied by degradation of erythrocyte membrane proteins (band 3 and 6, glycophorin) and was independent of the blood group. The exoprotease secreted by S. marcescens in large amounts was not involved in hemolysis. Comparison with various hemolytic strains of Escherichia coli showed that hemolysis of erythrocytes was more pronounced with S. marcescens than with E. coli. In contrast to hemolysis by E. coli, lysis of erythrocytes by S. marcescens was not enhanced by Ca2+ ions.


Acute and sub-chronic toxicity study of the ethanol extract from leaves of Aralia elata in rats.
Aralia elata Seem. (A. elata) is a well-known medicinal plant which has been used as a tonic, anti-arthritic and anti-diabetic agent in traditional Chinese medicine. This investigation aimed to evaluate the potential toxicological properties of the ethanol extract from leaves of A. elata, namely ethanol leaves extract (ELE), in rats by acute and sub-chronic toxicity studies. In the acute toxicity study, rats were orally administrated with ELE at doses of 1.00, 2.15, 4.64, and 10.00 g/kg to determine the oral medial lethal dose (LD50). Abnormal behavior, toxic symptom, and death were observed for 14 consecutive days. In the sub-chronic toxicity study, rats were orally administrated with ELE at doses of 0, 60, 180, and 540 mg/kg for 12 weeks and followed-up a 4-week recovery period. At the end of the treatment and recovery periods, the rats were sacrificed for hematological, biochemical, and histopathology analyses. The acute toxicity study showed that oral administration of ELE induced the incidence of adverse effects. The death rate also increased in a dose-dependent manner. The LD50 value was 3.16 g/kg for female rats, and 5.84 g/kg for male rats, respectively. The sub-chronic toxicity study showed that daily oral administration of ELE induced no significant difference in food consumption. However, the body weight of male rats in high dose group increased slowly compared with the control group during the recovery period. The hematological and biochemical analysis showed that compared with the control group, HGB and MCV levels were significantly increased in ELE treatment groups at the end of the treatment period, while TP and GLB levels were significantly decreased at the end of the recovery period. The absolute and relative weight of thymus, brain and adrenal gland showed a significant difference in low or high dose group at the end of the treatment period, although no histological changes were observed in various organs. The results of this study provided evidence that oral administration of ELE at dose of 540 mg/kg is safe in rats and may not exert severe toxic effects.


Effect of alpha-adrenergic receptor stimulation on ventricular electrical properties in the normal canine heart.
We examined the effects of alpha-adrenergic stimulation on ventricular excitability, refractoriness, and vulnerability to fibrillation. Methoxamine or phenylephrine was infused in five dogs each before and after aortic arch and carotid sinus baroreceptor denervation, in doses which increased mean arterial blood pressure by 20 to 30 mm Hg. Methoxamine or phenylephrine caused an increase in the ventricular fibrillation threshold (VFT) (from 27% to 41%) and in the repetitive extrasystole threshold (RET) (from 28% to 39%). This effect was abolished by baroreceptor denervation. Neither drug altered mid-diastolic threshold or effective refractory period duration either before or after denervation. We conclude that alpha-receptor activation exerts no direct effect on ventricular excitability or refractoriness in the normal intact heart.


Spatial averaging effects of hydrophone on field characterization of planar transducer using Fresnel approximation.
The purpose of this work was to improve the existing models that allow spatial averaging effects of piezoelectric hydrophones to be accounted for. The model derived in the present study is valid for a planar source and was verified using transducers operating at 5 and 20MHz. It is based on Fresnel approximation and enables corrections for both on-axis and off-axis measurements. A single-integral approximate formula for the axial acoustic pressure was derived, and the validity of the Fresnel approximation in the near field of the planar transducer was examined. The numerical results obtained using 5 and 20MHz planar transmitters with an effective diameter of 12.7mm showed that the derived model could account for spatial averaging effects to within 0.2% with Beissner's exact integral (Beissner, 1981), for k(a+b)2≫π (where k is the circular wavenumber, and a and b are the effective radii of the transmitter and hydrophone, respectively). The field distributions along the acoustic axis and the beam directivity patterns are also included in the model. The spatial averaging effects of the hydrophone were generally observed to cause underestimation of the absolute pressure amplitudes of the acoustic beam, and overestimation of the cross-sectional size of the beam directivity pattern. However, the cross-sectional size of the directivity pattern was also found to be underestimated in the "far zone" (beyond Y0=a(2)/λ) of the transmitter. The results of this study indicate that the spatial averaging effect on the beam directivity pattern is negligible for π(γ(2)+4γ)s≪1 (where γ=b/a, and s is the normalized distance to the planar transducer).


A simple technique for decompression of distended gallbladder during laparoscopic cholecystectomy.
During laparoscopic cholecystectomy, distended gallbladder can create exposure difficulties, that precludes adequate visualization, thus rendering laparoscopic dissection impossible and even unsafe. To overcome this problems, we devised a simple technique for the decompression of distended gallbladders.


Transplacental pharmacokinetics and teratogenicity of a single dose of retinol (vitamin A) during organogenesis in the mouse.
Pregnant mice received 10 or 100 mg retinol/kg body wt. by gavage on day 11 of gestation (plug day = day 0). One group of animals was used for a pharmacokinetic study. At various times after dosing, plasma and tissue samples were collected and analyzed by HPLC for retinyl esters, retinol, 13-cis- and all-trans-retinoic acid and 13-cis-4-oxo and all-trans-4-oxoretinoic acid. In the other group the fetuses were removed on day 18 and examined for malformations. After 10 mg/kg retinol, no teratogenic effect was observed. The pharmacokinetic investigation revealed a moderate increase of retinyl esters, retinol and all-trans-retinoic acid in plasma, embryonic tissue, placenta, yolk sac membranes and extraembryonic fluid. A high incidence of severe fetal malformations occurred after 100 mg/kg retinol. These malformations included limb defects (81% of fetuses) and cleft palate (55% of fetuses) which are characteristically found after administration of a single teratogenic dose of an active retinoid on day 11 of gestation. The concentration-time profile of retinoids after 100 mg/kg on day 11 showed a pronounced increase of retinyl esters and retinol in all compartments including the embryo and a massive generation of the polar metabolites all-trans-retinoic acid and all-trans-4-oxoretinoic acid. These polar metabolites were found in the embryo with peak concentrations of 327 +/- 115 and 143 +/- 20.7 ng/g (mean +/- SE) wet tissue, respectively. It is likely that all-trans-retinoic acid and all-trans-4-oxoretinoic acid, both well-known teratogens, largely contributed to the teratogenic outcome. The in-vivo oxidation of retinol may be an important factor in the teratogenic activity of high doses of vitamin A.


An open call for contributions to a special issue of Biophysical Reviews highlighting the research themes of VII Congress of Russian Biophysicists 2023.
We announce a call for contributions to a Special Issue of Biophysical Reviews associated with the VII Congress of Russian Biophysicists (to be held in Krasnodar, Russia, 17-23 April 2023). The Congress is the main biophysical meeting held within Russia and is organized every four years. The Congress will focus on both the physical principles and mechanisms of biological processes occurring at different levels of structural organization, from molecular to cellular to organism and to population levels. The Special Issue will accept reviews on topics from molecular biophysics, structure and dynamics of biopolymers, biophysics of the cell, energy transformation mechanisms, biophotonics, ecological biophysics, and medical biophysics, following the sections of the Congress. The VII Congress of Russian Biophysicists is supported by International Union of Pure and Applied Biophysics (IUPAB). Here we describe main topics and sections of the coming event, the paper types for the journal issue, and the key deadline dates.


Function and regulation of the Spt-Ada-Gcn5-Acetyltransferase (SAGA) deubiquitinase module.
The Spt-Ada-Gcn5 Acetyltransferase (SAGA) chromatin modifying complex is a critical regulator of gene expression and is highly conserved across species. Subunits of SAGA arrange into discrete modules with lysine aceyltransferase and deubiquitinase activities housed separately. Mutation of the SAGA deubiquitinase module can lead to substantial biological misfunction and diseases such as cancer, neurodegeneration, and blindness. Here, we review the structure and functions of the SAGA deubiquitinase module and regulatory mechanisms acting to control these.


The atypical subthalamic nucleus--an anatomical variant relevant for stereotactic targeting.
The improvement of PD motor symptoms by DBS of the STN depends on exact targeting. A combination of MRI and multitrajectory microrecordings was used for localization of the STN in a group of 228 consecutive PD patients. In 1% of our cases, the STN was consistently shifted in the anterior (3.3 ± 0.8mm) and medial (3.0 ± 0.9 mm) direction within the target plane, compared to controls. Adjustment of the original target coordinates after intraoperative reevaluation of the MRI and confirmation by typical subthalamic neuronal recordings along the deviant trajectory allowed the implantation of clinically effective electrodes in all cases. The relative improvement of the motor UPDRS at 6-months follow-up in patients with an atypical and typical STN was comparable. An atypical position of the STN does not need to complicate DBS surgery, if detected by a combination of MRI-based targeting and electrophysiological guidance.


The serine proteases dipeptidyl-peptidase 4 and urokinase are key molecules in human and mouse scar formation.
Despite recent advances in understanding skin scarring, mechanisms triggering hypertrophic scar formation are still poorly understood. In the present study, we investigate mature human hypertrophic scars and developing scars in mice at single cell resolution. Compared to normal skin, we find significant differences in gene expression in most cell types present in scar tissue. Fibroblasts show the most prominent alterations in gene expression, displaying a distinct fibrotic signature. By comparing genes upregulated in murine fibroblasts during scar development with genes highly expressed in mature human hypertrophic scars, we identify a group of serine proteases, tentatively involved in scar formation. Two of them, dipeptidyl-peptidase 4 (DPP4) and urokinase (PLAU), are further analyzed in functional assays, revealing a role in TGFβ1-mediated myofibroblast differentiation and over-production of components of the extracellular matrix in vitro. Topical treatment with inhibitors of DPP4 and PLAU during scar formation in vivo shows anti-fibrotic activity and improvement of scar quality, most prominently after application of the PLAU inhibitor BC-11. In this study, we delineate the genetic landscape of hypertrophic scars and present insights into mechanisms involved in hypertrophic scar formation. Our data suggest the use of serine protease inhibitors for the treatment of skin fibrosis.


Determinants of fetal macrosomia among live births in southern Ethiopia: a matched case-control study.
Fetal macrosomia defined as birth weight of 4000 g and above regardless of gestational age and associated with adverse maternal and fetal outcomes, especially among women in developing countries like Ethiopia. Despite the observed burden, there is limited evidence on determinants of fetal macrosomia. This study aimed to identify determinants of fetal macrosomia among live births at Wolaita Sodo town Southern Ethiopia. A facility-based matched case-control study design involved 360 singletons deliveries attended at hospitals in Wolaita Sodo town, southern Ethiopia, with 120 cases and 240 controls included. Cases and control were matched by maternal age. Cases were neonates with a birth weight of ≥ 4000, while controls were neonates with a birthweight between 2500gm and less than 4000gm. Data were collected by interviews, measuring, and reviewing mothers' medical documents. Conditional logistic regression analysis was carried to identify the independent predictor variables. Statistical significance was set using a p-value < 0.05 and 95% CI for AOR. Male neonates were four times more likely to be macrosomia than female neonates MAOR = 4.0 [95%CI; 2.25-7.11, p < 0.001]. Neonates born at gestational age ≥ 40 weeks were 4.33 times more likely to be macrosomia with MAOR = 4.33 [95%CI; 2.37-7.91, p < 0.001]. Neonates born from physically inactive mothers were 7.76 times more likely to be macrosomia with MAOR = 7.76 [95CI; 3.33-18.08, p < 0.001]. Neonates born from mothers who consumed fruits and dairy products in their diet frequently were 2 and 4.9 times more likely to be macrosomia MAOR = 2.03 [95%CI; 1.11-3.69, p = 0.021] and AOR = 4.91[95%CI; 2.36-10.23, p < 0.001] respectively. Mothers' physical exercise and consumption of fruit and dairy products were significant predictor variables for fetal macrosomia. Hence, health care providers may use these factors as a screening tool for the prediction, early diagnosis, and timely intervention of fetal macrosomia and its complications.


Impaired function of regulatory T cells in patients with psoriasis is mediated by phosphorylation of STAT3.
Psoriasis is a T cell-mediated chronic inflammatory skin disease. Regulatory T cells (Tregs) are crucial in suppressing immune response to maintain the immune balance. Wheras Tregs from psoriatic patients showed poorly activity in suppressing activation of responder T cells (Tresp), the mechanisms involved in this process are still unknown. In this study, we investigated the possible role of STAT3 pathway in the pathogenesis of dysfunctional Tregs in psoriasis. The suppressive function and the proliferative activity of Tregs were detected from psoriatic patients and normal healthy controls. Expression of phospho-STAT3 in psoriatic Tregs was evaluated by flow cytometry and immunofluorescence. Furthermore, Tregs were treated with Stattic V (STAT3 inhibitor) in order to investigate the role of STAT3 pathway in the function of Tregs. In addition, IL-6, IL-21 and IL-23 treatments were performed to identify the upstream molecules of STAT3 pathway in Tregs. Tregs from peripheral blood of psoriatic patients showed decreased suppressive function, together with phosphorylation of STAT3. In addition, Tregs isolated from psoriatic patients could produce IFN-γ, TNF-α and IL-17. In the co-culture system of Tregs and Tresp isolated from psoriatic patients, addition of STAT3 inhibitor partially restored the suppressive function of Tregs and restrained the expressions of IFN-γ, TNF-α and IL-17 in psoriatic patients. Moreover, we found that IL-6, IL-21 and IL-23 induced the phosphorylation of STAT3 in Tregs. Our findings suggest that psoriatic Tregs experience a predominant STAT3 phosphorylation by exposure to pro-inflammatory cytokines, leading to their impaired functions in suppressing Tresp activation.


Survival and growth of Virola surinamensis yearlings: Water augmentation in gap and understory.
Factors affecting seedling Virola surinamensis (Myristicaceae) survival and growth were investigated on Barro Colorado Island, Panama. Seedlings planted 3 months after germination were monitored in treefall gaps and understory using 2.25 ha irrigated and control plots through the first dry season. During the dry season, irrigated plants in gaps increased total leaf area significantly more than did irrigated plants in the shaded understory. Over the same dry season, control plants in gaps and in the shaded understory lost similar amounts of leaf area. Seedlings in understory were suppressed in stem height and biomass in both irrigated and control plots; these measures were greater in gaps and greatest in irrigated gaps (height). Roots were similar in length in all treatments, but greater in biomass in gaps than understory due to greater proliferation of secondary roots in control and irrigated gaps than in control and irrigated understory. This experiment demonstrates both water and light limitation during the first dry season after germination. V. surinamensis seedlings are capable of survival and modest growth of leaf area in the deep shade of the understory in moist locations; they are severely disadvantaged in shaded understory subject to drought, where most seeds fall and most seedlings establish. The broken canopy of a gap allows shoot and consequently root growth that permits seedlings to survive seasonal drought.


On the working stroke elicited by steps in length and temperature.
Muscle contraction is generally thought to involve tilting of the light chain region of the myosin head. This could account for 5-10 nm of axial displacement as it moves from nearly perpendicular to the filament axis (the state at the beginning of the working stroke) to the rigor conformation (at the end of the working stroke). According to the kinetic model of Huxley and Simmons, the extent that a cross-bridge progresses through the working stroke depends on the mechanical conditions. A large tilting occurs only when the fibre is allowed to shorten. Evidence for such tilting was provided by the changes in intensity of the third myosin meridional reflection (M3) following a step release. However, there is little change in the M3 intensity when a force increase is elicited by a 10 degrees C temperature jump, and these results were interpreted to indicate that tilting is not the structural transition responsible for force generation. Here we present a simulation of the changes in the intensity of the M3 reflection elicited by step changes in either length or temperature, based on the atomic model of the actin-myosin head complex. The results show that the same set of assumptions for the motions associated with the working stroke can predict the response to both kinds of perturbation. The main difference is due to the larger extent of the working stroke elicited by the length step.


UV-assisted ultrafast construction of robust Fe3O4/polydopamine/Ag Fenton-like catalysts for highly efficient micropollutant decomposition.
Fenton-like catalysts represent a family of promising materials to degrade micropollutants from contaminated water. However, the practical applications of Fenton-like catalysts are mainly limited by low catalytic degradation efficiency and stability. Herein, for the first time, rapid fabrication of Ag-decorated Fe3O4/polydopamine (FPA) microspheres was achieved via the help of UV irradiation, and the designed FPA microspheres were employed as Fenton-like catalysts to degrade micropollutants. Results showed that UV irradiation could activate the generation of the polydopamine shell and accelerate the Ag deposition, which played a crucial role in the rapid synthesis of highly active and stable FPA catalysts. Relative to reported catalysts, these FPA microspheres exhibited outstanding catalytic degradation performance, achieving 94.38% removal of tetracycline within 60 min. This work will provide a convenient strategy in the sustainable and efficient purification of wastewater to improve the quality of human life.


Follow-up Contemporary Commercial Music (CCM) Survey: who's teaching what in nonclassical music.
A previous study, published in the Journal of Voice in 2003, revealed that a majority of teachers of Music Theater (MT), a style of Contemporary Commercial Music (CCM), had little professional experience and little formal training in vocal pedagogy for this style. Those who did indicate that they had had training did not describe the training nor quantify it in any manner. To ascertain what type of training was available for CCM in general and MT, in particular, a follow-up study seemed warranted. A new questionnaire was developed which asked for further information from teachers of MT in several areas including performance experience, training methods, teaching philosophy, the use of terminology, knowledge of voice science and medicine, and other parameters. Responses were gathered from 145 singing teachers throughout the United States and several foreign countries. Statistical analysis obtained from the data may lead to both a better understanding of the kind of training available for teachers of CCM repertoire, and of its content and applicability.


Severe sepsis in women with group B Streptococcus in pregnancy: an exploratory UK national case-control study.
To estimate the incidence of severe maternal sepsis due to group B Streptococcus (GBS) in the UK, and to investigate the associated outcomes for mother and infant. National case-control study. All UK consultant-led maternity units. 30 women with confirmed or suspected severe GBS sepsis, and 757 control women. Disease incidence, additional maternal morbidity, critical care admission, length of stay, infant infection, mortality. The incidences of confirmed and presumed severe maternal GBS sepsis were 1.00 and 2.75 per 100,000 maternities, respectively, giving an overall incidence of 3.75 per 100,000. Compared with controls, severe GBS sepsis was associated with higher odds of additional maternal morbidity (OR 12.35, 95% CI 3.96 to 35.0), requiring level 2 (OR 39.3, 95% CI 16.0 to 99.3) or level 3 (OR 182, 95% CI 21.0 to 8701) care and longer hospital stay (median stay in cases and controls was 7 days (range 3-29 days) and 2 days (range 0-16 days), respectively, p<0.001). None of the women died. Severe maternal GBS sepsis was associated with higher odds of infant sepsis (OR 32.7, 95% CI 8.99 to 119.0); 79% of infants, however, did not develop sepsis. There were no associated stillbirths or neonatal deaths. Severe maternal GBS sepsis is a rare occurrence in the UK. It is associated with adverse maternal and neonatal outcomes.


Intramedullary Spinal Metastatic Renal Cell Carcinoma: Systematic Review of Disease Presentation, Treatment, and Prognosis with Case Illustration.
Renal cell carcinoma (RCC) metastases to the intramedullary spinal cord carry a grim prognosis. The purpose of this review is to provide the reader with a comprehensive and systematic review of the current literature, and to present an illustrative case that would aid in the future management of similar scenarios. A systematic review of the literature using the PubMed electronic database was made according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Only human clinical reports of intramedullary RCC metastasis were included. We also present an illustrative case that was treated at our institution. We identified 23 reports with a total of 31 patients. Of the tumors, 47% were located at the cervical level. Brain metastases were present in 41% of cases. Limb weakness (72%), urinary incontinence (41%), dysesthesia (47%), and localized spinal pain (38%) were the most frequently reported symptoms. Surgical resection alone was used in 34% of cases, followed by a combination of surgery and radiotherapy (31%), and radiotherapy alone (25%). Spinal metastases were detected an average of 32.1 months after the diagnosis of RCC, and mean patient survival after that was 8 months (range, 0-65 months). Reported survival after radiotherapy appeared to be the longest (11.2 months) compared with surgery (9.1 months) and combination therapy (5 months). Intramedullary spinal metastatic RCC is a rare entity with debilitating neurologic potential. Survival appears to be affected by the treatment method but is also likely influenced by the stage of discovery of the disease.


Optics in computing: introduction to the feature issue.
This issue of Applied Optics features 21 papers that describe the implementation of optics in computer systems and applications. This feature is the eighth in a series on the application of optics in the field of computing.


[Functional alterations of human platelets following 111In labeling with different ligands and incubation media].
We studied the effects of various 111In-water soluble chelates and incubation media on labeling efficiency of platelets and in vitro platelet aggregability. High labeling efficiency of platelets in ACD-saline was achieved with 111In-oxine sulfate, 111In-tropolone and 111In-MPO (2-mercaptopyridine-N-oxide). In the condition with 4.8 x 10(6)/mm3 platelets in ACD-plasma, 111In-oxine-sulfate had low labeling efficiency and inconsistent labeling, while 111In-tropolone and 111In-MPO had high labeling efficiency. In vitro platelet aggregability (ADP 2 microM) was reduced when platelets were labeled in the absence of plasma. However, there was no significant difference in platelet aggregability among 111In-platelets labeled by three different chelates. In conclusion, to maintain aggregation activity of the platelets with relatively high labeling efficiency, the best result was obtained by using MPO or tropolone chelate in plasma at 4.8 x 10(6)/microliters platelet concentration.


Can you have dementia with an MMSE score of 30?
To investigate the possibility that a patient with a diagnosis oF probable Alzheimer's disease (AD) can still obtain a score oF 30/30 on the Mini-Mental State Exam (MMSE). Chart review. Setting. The McGill University/Jewish General Hospital Memory Clinic. Participants were selected From the Memory Clinic's patient database. All underwent comprehensive evaluations, including relevant blood work and a computed tomographic scan or a magnetic resonance imaging scan oF the brain to rule out other causes oF dementia. All patients had one or more neuropsychological evaluation. Data oF all psychometric testing, including the MMSE, were gathered From these visits. Results. Eight patients were Found to meet the criteria oF AD although achieving a score oF 30/30 on the MMSE. Four oF 8 patients achieved this score although they were taking cholinesterase inhibitors. Although rare, it is possible to achieve a score oF 30/30 on the MMSE even iF a subject is suFFering From a dementing illness.


Draft Genome Sequence of a Mycobacterium africanum Clinical Isolate from Antioquia, Colombia.
Mycobacterium africanum is a member of the Mycobacterium tuberculosis complex. Most commonly found in West African countries, it has scarcely been described in South America. Here, we report the first genome sequence of a Colombian M. africanum clinical isolate. It is composed of 4,493,502 bp, with 4,069 genes.


Effective treatment of lymphomas of Burkitt's type and B-ALL in adults.
Malignant lymphomas, Burkitt's type, and B-ALL are rarely encountered in adult patients. Rapid initial responses are usually followed by early relapse and death. In a pilot study four adult patients, two presenting with B-ALL, were successfully treated with an aggressive protocol developed by the BFM study group for childhood lymphomas of B-type. Rapid clearance of tumor masses was achieved in all patients; no relapse occurred during an observation period ranging from 19-33 months of complete remission.


[Infectious diseases in migrants].
The current influx of refugees and the high rate of immigration increase the prevalence and impact of infectious diseases in Europe. Infections may be detected at first contact, as a result of systematic screening or as part of general medical care. Diagnosis and treatment require special expertise and, in some cases, special precautions. The spectrum of imported infections is determined by the countries of origins of the migrants and the circumstances associated with their escape to Germany. In this article, diagnosis and treatment of the most important infectious diseases will be presented. As far as infectious diseases are concerned, refugees and migrants are not a threat to the host population, but instead have to be perceived and cared for as a highly vulnerable group.


Cyclic nucleotide changes in murine lymphocytes following thymosin incubation in vitro.
Thymosin fraction 5 and a more purified acidic fraction of thymosin at a 100-fold lower concentration elevated cGMP levels, but not cAMP levels, in murine thymocytes. When both thymus and spleen lymphocytes were fractionated via a BSA gradient procedure, both cAMP and cGMP basal values varied depending on the density of the subpopulations. Thymosin Fr5 did not elevate cAMP in any thymus subpopulation of lymphocytes obtained from the BSA density gradients. The cGMP elevation due to thymosin Fr5 in thymocytes was maximal in the most buoyant thymocytes, and no elevation of cGMP was detected in nude mouse spleen lymphocytes. These results suggest that the cGMP elevation may be an early event in the thymosin-mediated differentiation of a more mature subpopulation of thymocytes. They also suggest that utilization of subpopulations may be necessary for the complete determination of the effects of agents on cyclic nucleotide values of lymphocytes.


Comparison of unilateral versus bilateral instrumented transforaminal lumbar interbody fusion in degenerative lumbar diseases.
Transforaminal lumbar interbody fusion (TLIF) has become a well-established technique that is traditionally performed with bilateral pedicle screw (PS) fixation. There are only a small number of case reports of unilateral instrumented TLIF. To our knowledge, there have been few well-designed studies comparing unilateral versus bilateral instrumentation with TLIF. To compare clinical and radiographic outcomes in a selected series of patients treated with unilateral versus bilateral PS instrumented TLIF. Prospective randomized study in one unit. A total of 80 patients were enrolled in this study. Thirty-seven patients (17 men and 20 women; average age 57.1 years) were randomized to the unilateral PS group and 43 patients (18 men and 25 women; average age 58.2 years) to the bilateral PS group. The demographic data collected from both groups were gender, age, preoperative index diagnosis, degenerated segment, and single/double level of fusion. Operative time, blood loss, hospital time, and implant costs were also evaluated. Postsurgical pain and functional results were analyzed by the visual analog scale (VAS), modified Prolo (mProlo) scores, and Oswestry Disability Index (ODI). Radiographic examinations were carried out to assess total fusion rates, screw failure, and general complications. Patients were randomized into the unilateral or bilateral PS instrumented TLIF group based on a computer-generated number list. Patients were asked to return to hospital for follow-up at 4 weeks, 3 months, 6 months, 12 months, and thereafter once a year after surgery. The mean follow-up was 25.3 months, with a range of 18 to 32 months. There were no significant differences between the two groups in terms of demographic data. The unilateral PS group had a significantly shorter operative time, less blood loss, and reduced implant costs compared with the bilateral PS group, although hospital time was the same for double-level cases. The average postoperative VAS, mProlo, and ODI scores improved significantly in both groups, with no significant difference between groups. The total fusion rate, screw failure, and general complication rate were not significantly different. Unilateral PS instrumented TLIF is a viable treatment option generating better results, especially in terms of operative time, blood loss, and hospital time for single-level disease and implant costs. No decrease in the fusion rate or increase in the complication rate was observed in this group. Further improved study design and a longer period of follow-up are needed to confirm this effect.


Induction of a polyubiquitin gene (ubi1) by potato phytoalexins and heat shock in Gibberella pulicaris.
Gibberella pulicaris, a causal agent of potato dry rot, infects potato tubers via wounds, where it is exposed to the phytoalexins rishitin and lubimin. Incubation of mycelium on agar supplemented with phytoalexins transiently induced the transcription of a polyubiquitin gene consisting of four ubiquitin units arranged head to tail; the fourth unit contains a 54-bp intron and an additional glutamine at the C-terminus of the encoded protein. Southern analysis of the G. pulicaris genome revealed one copy of the isolated polyubiquitin gene and one or two copies of other ubiquitin genes. Increased transcription of the gene was detectable above a threshold of 100 microg/ml of rishitin and at elevated temperatures, which indicates that exposure to phytoalexins causes a stress reaction of hyphal cells similar to that after heat shock.


A revised method for projecting two different movies to two groups of viewers without their noticing the duality.
The MORI technique reported in Mori (2003) has evolved into its second generation after the appearance of a new type of video projector with two advantages over the first generation. The new MORI technique uses a pair of DLP projectors instead of the LCD type. The improved technique does not require sideways framing of the movie for presentation as required formerly. Therefore, any ready-made movie clip can be used. Second, it utilizes a pair of circular polarizing filters instead of linear polarizers. Linear polarizing filters may leak the to-be-blocked light wave when they are tilted. Circular polarizing filters are less susceptible to that weakness. The effectiveness of the revised technique has been proved by several studies carried out in two separate laboratories in which undergraduates and preschoolers participated as eyewitnesses to observe simulated criminal events presented using this technique.


Lipoprotein lipase HindIII polymorphism influences HDL-cholesterol levels in statin-treated patients with coronary artery disease.
HDL-cholesterol (HDL-C) is a recognized athero-protective factor and low levels of HDL-C occur frequently in patients with coronary artery disease. Regulation of HDL-C level most probably results from the interaction of genes involved in lipoprotein metabolism and also from non-genetic factors. We studied associations and interactions among HindIII polymorphisms of the lipoprotein lipase gene LPL and selected non-genetic factors with respect to HDL-C levels in patients with coronary artery disease. 288 Slovak patients (35% women) with documented coronary artery disease, age (mean +/- SEM) 60 +/- 1 years and BMI 29 +/- 0.3 kg/m(2), were examined and genotyped for LPL HindIII (rs320) using a PCR/RFLP method. HDL-C levels were determined in a direct enzymatic assay. In the sample overall there were no significant differences across the LPL genotypes in adjusted HDL-C levels or in other lipids, although a trend toward higher HDL-C and lower triglycerides in H-H- homozygotes was observed. Multiple linear regression identified a significant interaction between LPL HindIII and statin treatment, which together with sex and diabetes explained 12.1% of HDL-C variance. Accordingly, in statin-treated patients we observed significant stepwise increments of the HDL-C level related to the increasing number of H- alleles (P = 0.04 for linear trend), whereas no such association was observed in patients without hypolipidemic treatment. H-H- homozygotes had a 16% (0.19 mmol/l) higher level of HDL-C than the H+H+ homozygotes (P = 0.06). HDL-C may be influenced by an interaction between statin treatment and LPL HindIII genotype. However, the effect of this interaction appears to be small when compared with the effect of non-genetic factors. This finding requires replication in a pharmacogenetic study.


The adenovirus E4orf4 protein induces growth arrest and mitotic catastrophe in H1299 human lung carcinoma cells.
The human adenovirus E4orf4 protein, when expressed alone, induces p53-independent death in a wide range of cancer cells. Earlier studies by our groups suggested that although in some cases cell death can be associated with some hallmarks of apoptosis, it is not always affected by caspase inhibitors. Thus it is unlikely that E4orf4-induced cell death occurs uniquely through apoptosis. In the present studies using H1299 human lung carcinoma cells as a model system we found that death is induced in the absence of activation of any of the caspases tested, accumulation of reactive oxygen species, or release of cytochrome c from mitochondria. E4orf4 caused a substantial change in cell morphology, including vigorous membrane blebbing, multiple nuclei in many cells and increased cell volume. Most of these characteristics are not typical of apoptosis, but they are of necrosis. FACS analysis and western blotting for cell cycle markers showed that E4orf4-expressing cells became arrested in G(2)/M and also accumulated high levels of cyclin E. The presence of significant numbers of tetraploid and polyploid cells and some cells with micronuclei suggested that E4orf4 appears to induce death in these cells through a process resulting from mitotic catastrophe.


Rare glial tumors.
This chapter describes the epidemiology, pathology, molecular characteristics, clinical and neuroimaging features, treatment, outcome, and prognostic factors of the rare glial tumors. This category includes subependymal giant cell astrocytoma, pleomorphic xanthoastrocytoma, astroblastoma, chordoid glioma of the third ventricle, angiocentric glioma, ganglioglioma, desmoplastic infantile astrocytoma and ganglioma, dysembryoplastic neuroepithelial tumor, papillary glioneuronal tumor, and rosette-forming glioneuronal tumor of the fourth ventricle. Many of these tumors, in particular glioneuronal tumors, prevail in children and young adults, are characterized by pharmacoresistant seizures, and have an indolent course, and long survival following surgical resection. Radiotherapy and chemotherapy are reserved for recurrent and/or aggressive forms. New molecular alterations are increasingly recognized.


Accuracy and Prognostic Role of NCCT-ASPECTS Depend on Time from Acute Stroke Symptom-onset for both Human and Machine-learning Based Evaluation.
We hypothesize that the detectability of early ischemic changes on non-contrast computed tomography (NCCT) is limited in hyperacute stroke for both human and machine-learning based evaluation. In short onset-time-to-imaging (OTI), the CT angiography collateral status may identify fast stroke progressors better than early ischemic changes quantified by ASPECTS. In this retrospective, monocenter study, CT angiography collaterals (Tan score) and ASPECTS on acute and follow-up NCCT were evaluated by two raters. Additionally, a machine-learning algorithm evaluated the ASPECTS scale on the NCCT (e-ASPECTS). In this study 136 patients from 03/2015 to 12/2019 with occlusion of the main segment of the middle cerebral artery, with a defined symptom-onset-time and successful mechanical thrombectomy (MT) (modified treatment in cerebral infarction score mTICI = 2c or 3) were evaluated. Agreement between acute and follow-up ASPECTS were found to depend on OTI for both human (Intraclass correlation coefficient, ICC = 0.43 for OTI < 100 min, ICC = 0.57 for OTI 100-200 min, ICC = 0.81 for OTI ≥ 200 min) and machine-learning based ASPECTS evaluation (ICC = 0.24 for OTI < 100 min, ICC = 0.61 for OTI 100-200 min, ICC = 0.63 for OTI ≥ 200 min). The same applied to the interrater reliability. Collaterals were predictors of a favorable clinical outcome especially in hyperacute stroke with OTI < 100 min (collaterals: OR = 5.67 CI = 2.38-17.8, p < 0.001; ASPECTS: OR = 1.44, CI = 0.91-2.65, p = 0.15) while ASPECTS was in prolonged OTI ≥ 200 min (collaterals OR = 4.21,CI = 1.36-21.9, p = 0.03; ASPECTS: OR = 2.85, CI = 1.46-7.46, p = 0.01). The accuracy and reliability of NCCT-ASPECTS are time dependent for both human and machine-learning based evaluation, indicating reduced detectability of fast stroke progressors by NCCT. In hyperacute stroke, collateral status from CT-angiography may help for a better prognosis on clinical outcome and explain the occurrence of futile recanalization.


[Pseudoxanthoma elasticum-like disease with deficiency of vitamin K-dependent clotting factors and cutis laxa features].
Pseudoxanthoma elasticum (PXE)-like syndrome is characterized by the association of PXE and cutis laxa (CL) features with a deficiency of vitamin K-dependent clotting factors. It was first described in 1971 and was identified as a distinct genetic entity in 2007 with analysis of the GGCX (γ-glutamyl carboxylase) gene, which is involved in congenital deficiency in vitamin K-dependent clotting factors. Here we report a new case of this extremely rare syndrome. A 23-year-old female patient was seen for the emergence of loose and redundant skin following extensive weight loss. She also presented a deficiency of vitamin K-dependent clotting factors. Physical examination revealed excessive, leathery skin folds in the axillary and neck regions. A skin biopsy revealed polymorphous and fragmented elastic fibers in the reticular dermis. These were mineralized, as was demonstrated by Von Kossa staining. The clinical features of CL associated with the histopathological features of PXE and vitamin K-dependent clotting factor deficiency led us to a diagnosis of PXE-like syndrome. A molecular study of the GGCX gene showed compound heterozygosity. The GGCX gene is usually responsible for PXE-like syndrome. GGCX encodes a γ-glutamyl carboxylase necessary for activation of gla-proteins. Gla-proteins are involved both in coagulation factors in the liver and in the prevention of ectopic mineralization of soft tissues. Uncarboxylated forms of gla-proteins in fibroblast would thus enable mineralization and fragmentation of elastic fibers.


The role of offset stems in revision knee arthroplasty.
Revision total knee arthroplasty (TKA) represents a technically challenging procedure. The use of an offset stem extension can help in addressing some of the difficulties that can be encountered during surgery and, in particular, anatomical mismatch, malalignment, and gap balancing. Different offset stem extensions are available and can be classified according to four parameters: modularity, location of the offset, direction, and size of the displacement. Offset stem extensions can assist with implant alignment on the metaphysis if there is an offset diaphysis, can avoid medial-lateral or anterior-posterior component overhang, can reduce the incidence of coronal or sagittal malalignment, and can help in balancing the flexion and extension spaces by effectively translating the components. The aim of this study is to give an overview of the currently available evidence regarding the use of offset stem extensions in revision TKA as well as some useful surgical tips.


The efficacy of systemic antibiotics as an adjunct to surgical treatment of peri-implantitis: a systematic review.
Microbial biofilm accumulation is the main cause of peri-implantitis. The majority of surgical peri-implantitis treatment protocols suggests adjunctive use of systemic antibiotics to target specific putative bacteria. The aim of this systematic review was to critically evaluate the adjunctive use of systemically administered antibiotics in surgical treatment of peri-implantitis by reviewing previously published systematic reviews and primary studies. A systematic literature search was conducted in four electronic databases (MEDLINE, The Cochrane Library, EMBASE, and Web of Science) for randomised controlled trials, cohort studies, case-control studies, and systematic reviews reporting surgical treatment of peri-implantitis with and without adjunctive systemically administered antibiotic therapy. The included systematic reviews and primary studies were qualitatively assessed using AMSTAR and GRADE, respectively. No restrictions were set for date of publication, journal, or language. The literature search identified 681 papers. Only seven systematic reviews and two primary studies met the inclusion criteria. Four out of seven included systematic reviews concluded that no evidence exists for use of systemic antibiotics to improve the clinical outcomes in surgical treatment of peri-implantitis. One review did not estimate the level of evidence, one did not clearly state any beneficial effect, whereas one reported a limited adjunctive effect. Further, the two included primary studies did not show a long-term significant benefit of adjunctive use of systemically administrated antibiotics. However, one study reported a short-term adjunctive effect in patients with modified surface implants. Due to heterogeneity in study design, low number of included primary studies, and grade of bias, no meta-analysis was performed. The use of systemically administered antibiotics as an adjunct to surgical interventions of peri-implantitis cannot be justified as a part of a standard treatment protocol. A pervasive problem is the lack of uniform diagnosis criteria for peri-implantitis, deficient information about patient characteristics, absence of high quality long-term randomised controlled trials, and authors' declaration on conflict of interest.


O-Glycoside quercetin derivatives: Biological activities, mechanisms of action, and structure-activity relationship for drug design, a review.
Quercetin as a valuable natural flavonoid has shown extensive biological activities, including anticancer, antioxidant, antibacterial, antiinflammatory, anti-Alzheimer, antifungal, antiviral, antithalassemia, iron chelation, antiobesity, antidiabetic, antihypertension, and antiphospholipase A2 (PLA2) activities, by the modulation of various targets and signaling pathways that have attracted much attention. However, the low solubility and poor bioavailability of quercetin have limited its applications; therefore, the researchers have tried to design and synthesize many new derivatives of quercetin through different strategies to modify quercetin restrictions and improve its biological activities. This review categorized the O-glycoside derivatives of Quercetin into two main classes, 3-O-glycoside and other O-glycoside derivatives. Also, it studied biological activities, structure-activity relationship (SAR), and the action mechanism of O-glycoside quercetin derivatives. Overall, we summarized past and present research for discovering new potent lead compounds. HIGHLIGHTS: Quercetin is a natural flavonoid with a valuable scaffold. O-Glycoside quercetin derivatives represents broad-spectrum biological activities. The structure-activity relationship investigation is discussed after modifying the scaffold of quercetin. This review can help researchers to rationally design/develop various drugs.


New antiarrhythmic drugs.
While controversy still exists as to the precise indications for the treatment of all forms of ventricular arrhythmia, advances in the number and, more importantly, type of antiarrhythmic drugs can provide the clinician with a rational basis for selecting antiarrhythmic drug therapy. A host of new agents with different pharmacokinetic and electrophysiological actions are now available, and can be compared or contrasted to conventional antiarrhythmic agents such as quinidine, procainamide, disopyramide, lignocaine (lidocaine) and bretylium. This review summarises the electrophysiological, haemodynamic, pharmacokinetic, and efficacy and safety data of mexiletine, tocainide, flecainide, encainide, propafenone, amiodarone, sotalol, pirmenol, cibenzoline (cifenline) and ethmozine (moracizine, moricizine), and aims to provide a basis on which clinicians can compare and contrast these agents and form an algorithm for selection of antiarrhythmic drug therapy in the treatment of patients with ventricular arrhythmias.


A comparison of frequent and infrequent visitors to an urban emergency department.
Frequent visitors account for a high proportion of Emergency Department (ED) visits and costs. Some of these visits could be handled effectively in less expensive primary care settings. Effective interventions to redirect these patients to primary care depend on an in-depth understanding of frequent visitors and the reasons they seek care in the ED. The objective of this study was to explore the differences between frequent visitors and infrequent visitors who seek medical care in one urban ED, as a first step toward developing effective interventions to direct patients to effective sources of care. In structured interviews, we asked 69 frequent visitors and 99 infrequent visitors to an inner-city, adult ED about medical diagnoses, general health, depression, alcohol abuse, physical functioning, self-perceived social support, primary care and ED service use, payment method, satisfaction with their primary care physician, and demographic characteristics. Differences in responses between groups were compared using t-tests for continuous variables and chi-square for categorical variables. Frequent visitors were more likely than infrequent visitors to be insured by Medicaid (53% vs. 39%, respectively) and less likely to be uninsured (13% vs. 24%, respectively) or have private insurance (6% vs. 15%, respectively). They reported higher levels of stress, lower levels of social support, and worse general health status. They were much more likely to screen positive for depression (47% vs. 27%, respectively, p = 0.017). Frequent visitors were more likely to have a primary care physician (75% vs. 66%, respectively), and 45% of the frequent visitors had a primary care physician at the ED hospital compared to 23% of the infrequent visitors. These findings suggest the need to improve access to frequent visitors' primary care physicians, screen them for depression, and offer psychological and social services more aggressively. These findings may apply to other inner city EDs.


Occurrence of chiral organochlorine compounds in the environmental matrices from King George Island and Ardley Island, west Antarctica.
Chiral organochlorine compounds (OCs) were measured in various environmental matrices (air, soil and vegetation) from west Antarctica using high resolution gas chromatography coupled with high resolution mass spectrometry (HRGC/HRMS). They were generally detected at a global background level compared with the previous studies. α-HCH and PCB-183 was observed in all the matrices except PCB-183 in two soil samples, while PCB-95, -136, -149, -174, -176 and o,p'-DDT were detected in most air but only a few solid matrices. Enantiomeric fractions (EFs) indicated that nonracemic residues of chiral OCs occurred in all the matrices and a wide variation of the EF values was observed in the vegetation. There was significant discrepancy between the EF values of PCB-183 and the racemic values, indicating that stereoselective depletion of PCB-183 was probably associated with the water-air exchange. The EFs values of α-HCH were generally lower than the racemic values but no statistical difference was obtained in all the matrices except lichen, supporting the assumption that water-air exchange may make influence on long-range transport of α-HCH.


Alexithymia and metabolic syndrome: the mediating role of binge eating.
Alexithymia, a personality trait characterized by difficulties in emotional processing, has been associated with unhealthy behaviors and chronic medical conditions. This study aimed to further develop our understanding of this complex relationship by investigating whether alexithymia increases the risk of metabolic syndrome (MetS) in participants with obesity or overweight through the mediating role of binge eating (BE). A consecutive sample of 238 treatment-seeking patients with obesity or overweight were recruited. Alexithymia (TAS-20), binge eating symptoms (BES), body mass index (BMI), and depression and anxiety symptoms (HADS) were concurrently assessed. Almost half of the participants met the criteria for MetS (44.12%). Compared to patients without MetS, those with MetS were older, had a longer duration of overweight, and had a higher BMI (p < 0.01). Individual with MetS also had higher HADS, BES, and TAS-20 scores, particularly difficulty identifying and describing feelings. The structural equation modeling (SEM) analysis revealed that BES levels exerted a significant direct effect on MetS (p < 0.01), and that TAS-20 levels exerted a significant direct effect on BES (p < 0.01), anxiety (p < 0.001) and depression (p < 0.001). Moreover, psychological distress (anxiety, p = 0.01, and depression, p = .05) indirectly affected MetS through the mediating effect of BES, and TAS-20 (p = 0.01) indirectly affected MetS through the mediating effect of HADS and BES. Finally, age had a significant direct effect on MetS (p < 0.001). Our findings indicate that alexithymia is a concurrent causative factor to the development of MetS through the mediating role of BE and psychological distress. Level III, case-control analytic study.


Acute myocardial infarction treated with intracoronary streptokinase: a report of the Society for Cardiac Angiography.
The Society for Cardiac Angiography maintains a registry of intracoronary streptokinase therapy (IC-SK) in patients with acute myocardial infarction. Between July 1981 and August 1984, 1,029 patients were entered into the registry. The baseline and clinical characteristics of patients were determined, the early results of therapy were evaluated, and baseline characteristics of those in whom reperfusion was achieved were compared with those in whom it was not. Multivariate discriminant analysis was used to identify the predictors of reperfusion and hospital mortality. The overall rate of reperfusion was 71.2%. Reperfusion was positively associated with hypotension, absence of cardiogenic shock and early treatment. The hospital mortality rate for all patients was 8.2% and was higher for women and the elderly. The hospital mortality was significantly lower among patients in whom reperfusion was achieved compared with those in whom it was not (5.5% vs 14.7%, p less than 0.0001) and for several high-risk subgroups. Thus, coronary artery reperfusion induced by IC-SK significantly reduces hospital mortality in high-risk patients with acute myocardial infarction. High-risk patients in whom reperfusion fails with IC-SK therapy should be considered for early coronary angioplasty or coronary artery bypass surgery.


Human alveolar macrophage response to Mycobacterium tuberculosis: immune characteristics underlying large inter-individual variability.
Mycobacterium tuberculosis (M.tb), the causative bacterium of tuberculosis (TB), establishes residence and grows in human alveolar macrophages (AMs). Inter-individual variation in M.tb-human AM interactions can indicate TB risk and the efficacy of therapies and vaccines; however, we currently lack an understanding of the gene and protein expression programs that dictate this variation in the lungs. Herein, we systematically analyze interactions of a virulent M.tb strain H37Rv with freshly isolated human AMs from 28 healthy adult donors, measuring host RNA expression and secreted candidate proteins associated with TB pathogenesis over 72h. A large set of genes possessing highly variable inter-individual expression levels are differentially expressed in response to M.tb infection. Eigengene modules link M.tb growth rate with host transcriptional and protein profiles at 24 and 72h. Systems analysis of differential RNA and protein expression identifies a robust network with IL1B, STAT1, and IDO1 as hub genes associated with M.tb growth. RNA time profiles document stimulation towards an M1-type macrophage gene expression followed by emergence of an M2-type profile. Finally, we replicate these results in a cohort from a TB-endemic region, finding a substantial portion of significant differentially expressed genes overlapping between studies. We observe large inter-individual differences in bacterial uptake and growth, with tenfold variation in M.tb load by 72h.The fine-scale resolution of this work enables the identification of genes and gene networks associated with early M.tb growth dynamics in defined donor clusters, an important step in developing potential biological indicators of individual susceptibility to M.tb infection and response to therapies.


Comparative efficacy of intranasal and oral vaccines against Bordetella bronchiseptica in dogs.
In order to determine the comparative efficacy of vaccines administered intranasally or orally to protect puppies from disease subsequent to experimental infection with Bordetella bronchiseptica (Bb), a randomized controlled trial was performed using 48 approximately 8-week-old specific pathogen free, Bb naive Beagle puppies. Puppies were randomized into three groups and administered vaccines containing Bb intranasally or orally, or a placebo intranasally. Twenty-one days later, all dogs were challenge exposed via aerosol administration of Bb. Clinical signs, nasal bacterial shedding and immune responses were monitored for 28 days after challenge. Intranasally vaccinated puppies had significantly lower rates of coughing, nasal discharge, retching and sneezing (i.e. were less sick clinically) than control puppies. The distinction between the orally vaccinated puppies and the control puppies was less consistent. The orally vaccinated puppies had less coughing and less retching than the control puppies, but nasal discharge and sneezing did not differ from control animals. Orally vaccinated puppies had higher rates of coughing, nasal discharge, retching and sneezing than the intranasally vaccinated puppies. Although both intranasal and oral Bb vaccines stimulated immune responses associated with disease sparing following Bb infection, the intranasal route of delivery conferred superior clinical outcomes. The observed difference in clinical efficacy suggests the need to question the rationale for the use of currently available orally administered Bb vaccines.


Correlates of systemic disease in adult Henoch-Schönlein purpura: a retrospective study of direct immunofluorescence and skin lesion distribution in 87 patients at Mayo Clinic.
Detection of IgM in lesional skin of adult patients with Henoch-Schönlein purpura via direct immunofluorescence (DIF) has been associated with the presence of renal disease. We sought to examine whether DIF findings of skin biopsy specimens and distribution of skin lesions were associated with the presence of systemic disease, including renal, gastrointestinal tract, and joint involvement. We performed a retrospective review of adult patients with Henoch-Schönlein purpura seen at Mayo Clinic between 1992 and 2011. Of the 87 patients (mean age, 46.1 years), 51 (59%) were male. A total of 39 patients (45%) had renal disease; 32 (37%), gastrointestinal tract involvement; 39 (45%), joint involvement; and 65 (75%), some systemic involvement. In all, 61 patients (70%) had cutaneous lesions above the waist. The DIF findings showed the presence of IgA in all 87 patients (100%). In addition, findings were positive for IgM in 32 patients (37%); IgG in 3 patients (3%); C3 in 75 patients (87%); and fibrinogen in 78 patients (92%). IgM was not found to be significantly associated with renal disease (P = .10); however, absence of fibrinogen was correlated with presence of renal involvement (P = .04). No other correlations were detected between DIF findings and systemic disease. Lesions above the waist were not significantly associated with renal (P = .12) or any (P = .76) systemic involvement. This study is retrospective. Neither IgM in lesional skin nor distribution of skin lesions above the waist was a reliable indicator of renal or systemic disease in adults with Henoch-Schönlein purpura.


Thiirancarboxamides as inhibitors of papain.
Derivatives of the thiirancarboxylic acid building-block containing a peptide bond were synthesised and screened against the model cysteine protease papain. The most active of the series showed a second-order rate constant of inactivation comparable to that of the parent compound. The insertion of a peptide moiety seems to compensate the lack of a free carboxylate interacting with the histidinium ion at the enzyme's active site.


Initial cholesterol uptake by everted sacs of rat small intestine: kinetic and thermodynamic aspects.
The kinetics of initial cholesterol uptake by everted rat proximal and distal small intestinal sacs were evaluated in vitro. The mucosal incubation solution consisted of 0.05 mM cholesterol solubilized in 4.8 mM sodium taurocholate micellar solution at pH 7.4 Experiments were performed at temperatures from 26 to 38 C. The rate of cholesterol uptake followed a linear relationship when plotted against time indicating an apparent zero-order kinetics mechanism for initial uptake. An Arrhenius plot of the results of uptake versus temperature remained linear over the entire range of temperatures studied. The large free energy of activation (20 kcal/mole) suggests that an energy barrier for cholesterol uptake exists at the enterocyte luminal cell membrane and may be an important limiting step in cholesterol uptake. It is proposed that a transient association between cholesterol and a component of the enterocyte luminal cell membrane is formed during initial uptake of cholesterol. The transient association may be an activated complex formed with proteins present at or within the luminal enterocyte cell membrane.


Distance from Dura mater to spinal cord at the thoracic vertebral level: An introductory study on local subdural geometry for thoracic epidural block.
To evaluate the anatomical safety margins in relation to thoracic epidural block by analysing magnetic resonance (MR) images. This retrospective study identified consecutive patients who underwent MR imaging of the thoracic vertebral spine. The distance from the dura mater to the spinal cord (DTC) was measured at different thoracic intervertebral levels using three different pathways as references: the 'U', 'L' and 'M' lines. A total of 346 patients provided MR images for analysis. The vertical DTC was the longest at the T5/6 intervertebral level (mean ± SD: 4.22 ± 1.43 mm) and the shortest at the T11/12 intervertebral level (mean ± SD: 2.51 ± 0.87 mm). The DTC was the longest on the 'L' line at the T1/2 and T5/6 intervertebral levels and on the 'U' line at the T10/11 intervertebral level. The difference in DTC between the 'U' and 'L' lines was the greatest at the T5/6 intervertebral level. Differences in the DTC were observed among the thoracic intervertebral levels. The variability of the safety margin according to the angle of needle insertion was the largest at the T5/6 intervertebral level.


Identification of 14-3-3γ as a Mieap-interacting protein and its role in mitochondrial quality control.
Mieap, a p53-inducible protein, controls mitochondrial integrity by inducing the accumulation of lysosomal proteins within mitochondria. This phenomenon is designated MALM, for Mieap-induced accumulation of lysosome-like organelles within mitochondria. To identify this novel Mieap-interacting protein(s), we performed a two-dimensional image-converted analysis of liquid chromatography and mass spectrometry (2DICAL) on the proteins immunoprecipitated by an anti-Mieap antibody. We indentified 14-3-3γ as one of the proteins that was included in the Mieap-binding protein complex when MALM was induced. The interaction between Mieap and 14-3-3γ was confirmed on the exogenous and endogenous proteins. Interestingly, 14-3-3γ was localized within mitochondria when MALM occurred. A 14-3-3γ deficiency did not affect the accumulation of Mieap and lysosomal proteins within mitochondria, but dramatically inhibited the elimination of oxidized mitochondrial proteins. These results suggest that 14-3-3γ plays a critical role in eliminating oxidized mitochondrial proteins during the MALM process by interacting with Mieap within mitochondria.


Stressors and Pain across the Late-Life Span: Findings from Two Parent Longitudinal Studies of Aging and Health.
The objective is to determine associations between stressors and pain across the late-life span. Multilevel linear modeling was applied separately to harmonized repeated measures data from the Longitudinal Late-Life Health study (LLLH; n = 342; 13-year interval) and the Health and Retirement Study (HRS; n = 2959; 8-year interval). In both the LLLH and HRS samples, independent of age, gender, and race, participants with higher average stressor levels experienced more numerous painful conditions and higher pain severity over the study intervals. In the HRS sample, they also experienced higher levels of pain interference. In general, participants' stressor levels did not influence rates of increase in their pain. Gender and race had few moderating effects on associations between stressors and pain. Stressors and pain are associated across the late-life span. Future research should focus on the mediating mechanisms that account for this association and the moderating factors that affect its strength.


Effects of folic acid on cardiac myocyte apoptosis in rats with streptozotocin-induced diabetes mellitus.
The effect of folic acid on cardiac myocyte apoptosis secondary to diabetes is unknown. Diabetic rats were divided into diabetic control (DC, n = 11), low-dose (LDF, 0.4 mg/kg/day, n = 12) and high-dose (HDF, 1.2 mg/kg/day, n = 12) folic acid groups. Non-diabetic rats (n = 11) were used as the normal control (NC). After 11 weeks of treatment, compared with the NC group, the DC group showed a reduced blood levels of reactive oxygen species (ROS, P < 0.01). The rate of cardiac myocyte apoptosis in the diabetic control group was also greater than in the non-diabetic control group (P < 0.01). In folic acid-treated rats, the blood levels of ROS was higher than in the diabetic control group (P < 0.05). There was a dose-dependent reduction in the rate of cardiac myocyte apoptosis in the folic acid groups (P < 0.01), and this was accompanied by an increased level of anti-apoptotic protein Bcl-2 and decreased level of pro-apoptotic protein Bax and Fas (P < 0.01). Dietary folic acid supplementation diminishes the cardiac myocyte apoptosis in streptozotocin-induced diabetes. The apoptosis suppression is accompanied by an increase in the expression of Bcl-2 and a decrease in Bax and Fas.


Outcomes After Elective Proximal Aortic Replacement: A Matched Comparison of Isolated Versus Multicomponent Operations.
Guidelines supporting the decision to replace the aorta in patients with chronic asymptomatic proximal aortic disease are limited by lack of data on operative risks and long-term effectiveness in relation to aortic size. Therefore, we assessed and compared outcomes of patients undergoing elective isolated proximal aortic replacement for this disease vs replacement during multicomponent operations. From January 2006 to January 2011, 1,889 patients underwent proximal aortic replacement (isolated, 212; multicomponent, 1,677) for chronic asymptomatic ascending and arch pathology. Mean age was 60 ± 14 years, and maximum proximal aortic diameter was 52 ± 10 mm (isolated) and 49 ± 10 mm (multicomponent; p = 0.0004). Propensity matching using 64 preoperative variables yielded 197 well-matched patient pairs. Patients were more likely to undergo isolated replacement if they had prior cardiac operations and a larger middescending aortic diameter (p < 0.0001). Multicomponent operations were more common among those with connective tissue disorder or porcelain aorta. Among propensity-matched patients, in-hospital mortality was 1 of 197 (0.5%) in the isolated group vs 8 of 197 (4.1%) in the multicomponent group. Occurrence of stroke, renal failure, and prolonged ventilation were similar. Median postoperative stay was 7.9 vs 8.1 days (p = 0.07). At 30 days, 1 year, and 4 years, survival was 97%, 93%, and 87%, and freedom from reintervention was 98%, 90%, and 89%, respectively, similar between groups. Elective ascending aortic replacement is safe and effective. Ascending aneurysms should be treated aggressively even when encountered in patients undergoing a multicomponent operation. An aggressive approach to replacement of the ascending aorta may be warranted given the increased risk of stroke during a subsequent reoperation.


Focal epilepsy caused by single cerebral cavernous malformation (CCM) is associated with regional and global resting state functional connectivity (FC) disruption.
Epilepsy, including the type with focal onset, is increasingly viewed as a disorder of the brain network. Here we employed the functional connectivity (FC) metrics estimated from the resting state functional MRI (rsfMRI) to investigate the changes of brain network associated with focal epilepsy caused by single cerebral cavernous malformation (CCM). Eight CCM subjects and 21 age and gender matched controls were enrolled in the study. Seven of 8 CCM subjects underwent surgical resection of the CCM and became seizure free and 4 of the surgical subjects underwent a repeat rsfMRI study. We showed that there was both regional and global disruption of the FC values among the CCM subjects including decreased in homotopic FC (HFC) and global FC (GFC) in the regions of interest (ROIs) where the CCMs were located. There was also the disruption of the default mode network (DMN) especially the FC between the middle prefrontal cortex (MPFC) and the right lateral parietal cortex (LPR) among these individuals. We observed the trend of alleviation of these disruptions after the individual has become seizure free from the surgical resection of the CCM. Using a voxel-based approach, we found the disruption of the HFC and GFC in the brain tissue immediately adjacent to the CCM and the severity of the disruption appeared inversely proportional to the distance of the brain tissue to the lesion. Our findings confirm the disruption of normal brain networks from focal epilepsy, a process that may be reversible with successful surgical treatments rendering patients seizure free. Some voxel-based metrics may help identify the epileptogenic zone and guide the surgical resection.


[Hypertension as a common element of renal transplantation with pressor kidney and posterior reversible encephalopathy syndrome].
Secondary arterial hypertension accounts for only 5-10% of cases of arterial hypertension, hence the importance of its clinical suspicion for diagnosis. One of the most common causes of secondary hypertension is renovascular hypertension, caused by renal hypoperfusion and activation of the renin-angiotensin-aldosterone system. In addition to arterial hypertension being one of the most prevalent cardiovascular risk factors in the population, its poor control can cause acute neurological disorders such as Posterior Reversible Leukoencephalopathy syndrome (PRES), being characteristic the appearance of visuals alterations. Next, we present the case of a kidney transplant patient with well-controlled arterial hypertension with worsening secondary to renal artery stenosis and development of PRES.


Chemistry of New Zealand Apiaceae: a rare phenylpropanoid and three new germacrane derivatives from Anisotome lyallii.
A phytochemical investigation of the New Zealand endemic Apiaceae species Anisotome lyallii Hook.f. yielded (+)-alpha-angeloyloxylatifolone (1), 6-O-angeloyl-8-O-tigloyl-6beta,8alpha,11-trihydroxygermacra-1(10)E,4E-diene (2), 6-O-tigloyl-8-O-tigloyl-6beta,8alpha,11-trihydroxygermacra-1(10)E,4E-diene (3) and 6-O-tigloyl-8-O-tigloyl-1alpha,6beta,8alpha,11-tetrahydroxygermacra-4E,10-(14)diene (4). The structures were elucidated by HR mass spectrometry and 1D- and 2D-NMR spectroscopy. A chemosystematic survey for compounds 1-3 in other New Zealand Apiaceae by HPLC-MS revealed that 1-3 were confined to A. haastii Cockayne & Laing and A. lyallii, and that some minor compounds in other species of Anisotome were isomers of 2 and 3.


Critical review of self-reported functional ankle instability measures.
Since functional ankle instability (FAI) lacks a "gold standard'' measure, a variety of self-reported ankle instability measures have been created. The purpose of this study was to determine which ankle instability measure identifies individuals who meet a minimum acceptable criterion for FAI. Participants volunteered from a large university population which included 242 participants (104 males, 138 females; 21.4 ± 1.4 years). The predictor variables were seven ankle instability questionnaires: Ankle Instability Instrument (AII), Ankle Joint Functional Assessment Tool (AJFAT), Chronic Ankle Instability Scale (CAIS), Cumberland Ankle Instability Tool (CAIT), Foot and Ankle Ability Measure (FAAM), Foot and Ankle Instability Questionnaire (FAIQ), and Foot and Ankle Outcome Score (FAOS). The outcome variable (MC_FAI) was created based on the minimum acceptable criteria for FAI. This was established as at least one ankle sprain and an episode of giving way. Data were modeled using chi-square and multinomial logistic regression. The regression model revealed all of the questionnaires were more useful at identifying participants who did not meet the minimum criteria for FAI (No MC_FAI = 95.7%, MC_FAI = 55.6%, overall = 84.6%). Based on the Wald criterion, the full model was reduced to the CAIT, AII, and FAAM. The reduced model revealed the CAIT (X(2) = 8.756, p = 0.003) and AII (X(2) = 31.992, p = 0.001) as the only variables that had a significant relationship with the outcome variable. The model illustrates no single measure was able to predict if individuals met the minimally accepted criteria for FAI. However, a significantly accurate prediction of ankle stability status was produced by combining the CAIT and AII. Based on the results we recommend that researchers and clinicians use both the CAIT and AII to determine ankle stability status.


Correction to: BCG revaccination of health workers in Brazil to improve innate immune responses against COVID-19: A structured summary of a study protocol for a randomised controlled trial.
An amendment to this paper has been published and can be accessed via the original article.


Prolactin and growth hormone releasing activity of [D-Met2, Pro5]-enkephalinamide in the rat after systemic administration.
The growth hormone (GH) and prolactin releasing (PRL) activity of [D-Met2, Pro5]-enkephalinamide (EKNH2). an opioid peptide analog with higher opiate agonist activity that morphine, was compared in the unanesthetized male rat to those of equimolar doses of morphine upon systemic injection. EKNH2 proved to be a higher PRL, but not GH, releaser than the opiate alkaloid.


Diagnostic imaging techniques in lung carcinoma.
For the early detection of lung cancer at a stage when it is localized and hence resectable, persons in a high-risk group should be screened periodically with sputum cytologic studies and chest radiographs. For determination of the intrathoracic extent of a lesion, posteroanterior and lateral chest radiographs should be followed by computerized tomography to evaluate the hila, mediastinum, pleura, and chest wall. Computerized tomographic examination of the chest should be extended to include the upper abdomen. The adrenal glands can be evaluated by such examination, but adequate examination of the liver requires both precontrast and postcontrast computerized tomography scans. The radiologic workup for assessing distant metastases to the liver, brain, or bone should be performed only when clinical and biochemical findings suggest such metastases. For detection of recurrent carcinoma following treatment, computerized tomograms of the chest are more sensitive than routine radiographs. Magnetic resonance imaging may prove useful in the future for initial staging and for differentiating posttreatment fibrosis from recurrent bronchogenic carcinoma.


Different nanostructures caused by competition of intra- and inter-β-sheet interactions in hierarchical self-assembly of short peptides.
To understand how molecular interactions lead to the self-assembly of twisted, helical and flat nanoribbons, we have compared the hierarchical self-assembly processes of three selected octapeptides with the same amino acid composition but different sequences by both experiments and molecular dynamics (MD) simulations. KE-F8 (NH2-KEFFFFKE-CONH2) and EK-F8 (NH2-KEFFFFEK-CONH2) have the same distribution of hydrophobic residues and only differ by swapping the positive and negative charged residues at their C-terminals, while KFE-8 (NH2-KFEFKFEF-CONH2) differs from KE-F8 and EK-F8 by having all hydrophobic and charged residues evenly distributed. MD simulations indicated that the competition between electrostatic and hydrophobic interactions at the molecular level results in different initial packing modes: KE-F8 monomers form completely matched anti-parallel β-sheets, EK-F8 monomers align with one residue shifting, and KFE-8 monomers pack β-sheets with two heterogeneous surfaces, consistent with previously suggested models. Driven by inter-strand and inter-sheet interactions, further growth of these molecular templates leads to larger oligomers with different twisting and stacking degrees, which are structurally consistent with the experimentally observed self-assembled morphologies. Further MD simulations showed that the competition between intra-β-sheet and inter-β-sheet interactions is responsible for the different twisting and stacking degrees of β-sheets and the subsequent formation of different nanostructures (twisted ribbons for KE-F8, helical ribbons/tubes for EK-F8 and flat ribbons for KFE-8). This study thus provided an important mechanistic insight into the fine tuning of molecular packing and interactions via peptide sequence variation leading to controllable self-assembly of twisted, helical and flat nanostructures.


Conservative management equally effective to new suture anchor technique for acute mallet finger deformity: A prospective randomized clinical trial.
Prospective randomized controlled trial. This study was designed to compare our new suture anchor technique with conservative management in acute Wehbe-Schneider type I A-B and II A-B mallet fingers. Twenty nine patients who presented to our clinic between 2013 and 2015 were randomized for surgical or conservative treatment. Wehbe-Schneider subtype C fractures were excluded. Fourteen were treated with surgery, and 15 were treated with conservative treatment. Primary outcomes were visual analog scale score, active distal interphalangeal (DIP) joint flexion, return to work, extension deficit and DIP joint degeneration. Follow-up time was 12 months. The mean visual analog scale was 2.0, and return to work was on average in 63.2 days in the surgical group and 1.47 and 53.7 days in the conservative group. Extension deficit was 8.1° in the surgical group and 6.1° in the conservative group. The mean DIP flexion at final follow-up was 54.5° (40-65) in the surgery group and 58.3° (45-70) in the conservative group. DIP joint degeneration was observed with X-rays in 4 patients in surgical group, and none of the patients in the conservative group had DIP degeneration at 1 year after treatment. The therapeutic effectiveness of suture anchor technique was not statistically different from conservative treatment. Subluxation seen after fixation treatment with suture anchors may be due to inadequate anchor fixation. DIP joint degeneration was seen significantly more in the surgical group. Our study suggests that the new suture anchor technique is not superior to conservative treatment. Ib.


Transcriptional control of the Saccharomyces cerevisiae ADH1 gene by autonomously replicating sequence binding factor 1.
Autonomously replicating sequence (ARS)-binding factor 1 (ABF1) is a multifunctional protein involved in transcriptional activation and repression, as well as DNA replication, in yeast. The ADH1 gene, encoding alcohol dehydrogenase 1, contains two ABF1 consensus binding sites in the promoter and the coding regions. To examine the effect of ABF1 on expression of the ADH1 gene, we constructed an ADH1-lacZ fusion plasmid. Both ABF1 binding sites appeared to be transcriptional activators because deletions and mutations of these sites decreased transcriptional activity. The ABF1 binding sites also acted in an orientation-independent manner when a synthetic ABF1 binding site was inserted into the yeast CYC1 gene lacking its transcriptional activation region. A gel mobility shift assay showed that ABF1 bound in vitro to both ABF1 binding sites in the promoter and coding regions. In a glycerol medium the degree of activation by ABF1 was higher than in a glucose medium. The expression of ADH1 was activated synergistically by both ABF1 binding sites. These observations suggest that ABF1 transactivates the ADH1 gene through its binding sequences in both the promoter and coding regions.


Proteomic analysis of Cryptostegia grandiflora latex, purification, characterization, and biological activity of two osmotin isoforms.
Although latex fluids are found in >20,000 plant species, the biochemical composition and biological function of their proteins are still poorly explored. Thus, this work aimed to conduct a proteomic analysis of Cryptostegia grandiflora latex (CgLP) for subsequent purification and characterization of an antifungal protein. After 2D-SDS-PAGE and mass spectrometry, 27 proteins were identified in CgLP, including a polygalacturonase inhibitor, cysteine peptidases, pathogenesis-related proteins (PR-4), and osmotins. Then, two osmotin isoforms (CgOsm) were purified, and a unique N-terminal sequence was determined (1ATFDIRSNCPYTVWAAAVPGGGRRLDRGQTWTINVAPGTA40). The PCR products revealed a cDNA sequence of 609 nucleotides for CgOsm, which encoded a polypeptide with 203 amino acid residues. The structure of CgOsm has features of typical osmotin or thaumatin-like proteins (TLPs), such as 16 conserved Cys residues, REDDD and FF motifs, an acidic cleft, and three main domains. Atomic force microscopy (AFM) and bioinformatics suggested that CgOsm is associated with three chain units. This result was interesting since the literature describes osmotins and TLPs as monomers. AFM also showed that Fusarium falciforme spores treated with CgOsm were drastically damaged. Therefore, it is speculated that CgOsm forms pores in the membrane of these cells, causing the leakage of cytoplasmic content.


[Limited surgery for early gastric cancer].
The prognosis of the resected "early gastric cancer" is very good, especially in mucosal cancer. In Japan, the surgery for the gastric cancer generally is subtotal gastrectomy combined with R2-lymph nodal dissection. But, some cases are free of lymph nodal metastasis, and might be cured without its dissection. We analyzed resected specimens of early gastric cancer pathologically, and assessed what cancers we could do the limited operation without impairing curability. Lymph nodal metastasis of the mucosal cancer developed 2.1% of all 291 mucosal cancers, and of the submucosal cancer, 15.7% of 229 cases. Lymph vessel permeation depicted 5.2% and 82.1%, respectively. As for the mucosal cancer, less than 10 mm in maximum diameter, there were no lymph vessel permeations nor lymph nodal metastasis. In these cases, the limited operation, especially the local resection and the endoscopic resection could be available without any fear of cancer residue. In contrast, the submucosal cancer was not considered the candidate of the limited surgery.


Iranian mother's perspectives about aspects and determinants of disrespect and abuse during labor and delivery: a qualitative study.
Respectful maternity care (RMC) is a crucial strategy in improving postpartum experiences of mothers. This study aimed to explain women's perception of determining aspects and determinants of disrespect and abuse (D&A) during childbirth. This study was carried out from October 2019 to February 2020 in Tabriz-Iran. A total of 12 postpartum women were enrolled in this qualitative study by purposive sampling. The data were collected through in-depth semi structured interviews and simultaneously analyzed with a conventional content analysis approach. Thirty eight sub-themes and 11 main themes extracted from data analysis. The main themes included: "physical abuse," "psychological violence," "discrimination," "violation of privacy," "unmet needs and preferences," "nonparticipation in decision-making," "abandonment of women," "Lack of sympathy," "shortage of human and non-human resources," "unpleasant psychological atmosphere of the ward" and "facilitators of D&A." The results of our study indicated the importance of sympathy with mothers and professional ethics. Moreover, healthcare providers, administrators, and policy-makers should design patient-centered interventions in order to secure the material, psychological, and legal needs of women to receive respectful maternity care.


Biphasic effect of insulin on beta cell apoptosis depending on glucose deprivation.
Insulin resistant states are associated with an increase in the beta cell mass and also high levels of circulating insulin. Ultimately the beta cells undergo a failure that leads to diabetes. At this stage, a question arises if those persistent high levels of circulating insulin may contribute to beta cell damage. To address this important issue, we submitted beta cells to a prolonged effect of increasing concentrations of insulin. We observed that a prolonged effect of high levels of insulin on the presence of serum (15-24h) in glucose-deprived beta cells induced apoptosis. This apoptotic effect was both dose- and cycloheximide-dependent.


Prevention of diabetic glomerulopathy in streptozotocin diabetic rats by insulin treatment. Kidney size and glomerular volume.
Kidney weight and glomerular volume have been studied in groups of insulin-treated streptozotocin diabetic rats maintained at high, or nearly normal plasma glucose levels. Kidney weight and glomerular volume in these groups were compared to a non-diabetic control group. --Rats with nearly normal plasma glucose levels (95 +/- 35 to 182 +/- 20 mg/100 ml) had the same kidney weight as the non-diabetic controls, 1.04 +/- 0.14 and 1.07 +/- 0.09 g, respectively. In the rats with constant high plasma glucose (338 +/- 71 to 555 +/- 86 mg/100 ml) kidney weight was significantly increased, 1.73 +/- 0.20 g, compared to each of the two other groups. Glomerular volume was 0.559 millimicron3 in the diabetic animals with nearly normal plasma glucose, a value very close to that of the non-diabetic controls, 0.587 milimicron3. In animals with high plasma glucose concentrations glomerular volume was 0.775 millimicron3, 2 p less than 0.03 compared with both other groups. --The study indicates that good diabetic control for 6 months prevents the development of large kidneys and large glomeruli in dibatic rats.


Unique mechanical properties of nanostructured transparent MgAl2O4 ceramics.
Nanoindentation tests were performed on nanostructured transparent magnesium aluminate (MgAl2O4) ceramics to determine their mechanical properties. These tests were carried out on samples at different applied loads ranging from 300 to 9,000 μN. The elastic recovery for nanostructured transparent MgAl2O4 ceramics at different applied loads was derived from the force-depth data. The results reveal a remarkable enhancement in plastic deformation as the applied load increases from 300 to 9,000 μN. After the nanoindetation tests, scanning probe microscope images show no cracking in nanostructured transparent MgAl2O4 ceramics, which confirms the absence of any cracks and fractures around the indentation. Interestingly, the flow of the material along the edges of indent impressions is clearly presented, which is attributed to the dislocation introduced. High-resolution transmission electron microscopy observation indicates the presence of dislocations along the grain boundary, suggesting that the generation and interaction of dislocations play an important role in the plastic deformation of nanostructured transparent ceramics. Finally, the experimentally measured hardness and Young's modulus, as derived from the load-displacement data, are as high as 31.7 and 314 GPa, respectively.


Severe autonomic failure in moderate to severe aortic stenosis: prevalence and association with hemodynamics and biomarkers.
Severe autonomic failure (SAF) refers to combined abnormalities in reflex and tonic autonomic function. SAF indicates increased risk of death in post-infarction and heart failure patients, but has not been studied in aortic stenosis (AS). Here, we investigated SAF in patients with AS and tested its correlation with hemodynamic and biochemical markers. We prospectively enrolled 174 patients with moderate to severe AS in sinus rhythm (age 76 ± 9 years; mean aortic valve area 0.9 ± 0.3 cm(2)). Heart rate turbulence (as marker of autonomic reflex activity) and deceleration capacity (as marker of autonomic tonic activity) were calculated from 24-h Holter recordings. According to the previously published technology, SAF was considered present if both factors were abnormal. 44 (25.3%) of the 174 patients had signs of SAF. Patients with SAF had lower left ventricular ejection fraction (LVEF: 48.1 vs. 54.8%; p = 0.002), lower mean aortic gradients (28 vs. 34 mmHg, p = 0.019), higher systolic pulmonary artery pressures (46.8 vs. 40.9 mmHg, p = 0.028), higher levels of brain natriuretic peptide (905 vs. 407 ng/l; p = 0.003) and higher levels of high sensitive troponin I (0.65 vs. 0.24 μg/l; p = 0.013). Impaired LVEF (≤50%) was the only independent factor associated with SAF, but only explained autonomic abnormalities in less than half of the patients. In patients with moderate to severe AS prevalence of SAF is high. SAF correlates with hemodynamic and biochemical markers indicating increased risk. Future studies should evaluate the prognostic value of SAF in patients with AS.


Early gut microbiota in very low and extremely low birth weight preterm infants with feeding intolerance: a prospective case-control study.
The potential role of the gut microbiota in the pathogenesis of feeding intolerance (FI) remains unclear. Understanding the role of the gut microbiota could provide a new avenue for microbiota-targeted therapeutics. This study aimed to explore the associations between aberrant gut microbiota and FI in very low or extremely low birth weight (VLBW/ELBW) preterm infants. In this observational case-control study, VLBW/ELBW infants were divided into two groups: FI group and feeding tolerance (FT) group. 16S rRNA gene sequencing was performed to analyze the gut microbial diversity and composition of the infants. The differences in the gut microbiota of the two groups were compared. In total, 165 stool samples were obtained from 44 infants, among which, 31 developed FI and 13 served as controls. Alpha diversity was the highest in the meconium samples of the two groups. LEfSe analysis revealed that the abundances of Peptostreptococcaceae, Clostridiales and Clostridia in the FT group were significantly higher than in the FI group. At the phylum level, the FI group was dominated by Proteobacteria, and the FT group was dominated by Firmicutes. The meconium samples of the FI group had higher proportions of γ-proteobacteria and Escherichia-Shigella and a lower proportion of Bacteroides compared with the FT group. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that aberrant gut bacteria in the FI group were strongly associated with dysregulation of C5-Branched-dibasic-acid-metabolism, protein kinases, and sporulation. These findings reveal candidate microbial markers to prevent FI. Increased relative abundances of γ-proteobacteria and Escherichia-Shigella and decreased abundance of Bacteroides in meconium were associated with an increased risk of FI, while Peptostreptococcaceae, Clostridiales and Clostridia reduced the risk of FI in VLBW/ELBW infants.


In situ hybridization to detect and localize signature cytokines of T-helper (Th) 1 and Th2 immune responses in chicken tissues.
The avian immune system has been shown to possess a repertoire of cytokines directing T-helper (Th) 1 and Th2 types of immune responses similar to that in mammals. The objective of this study was to establish in situ hybridization (ISH) for the localization of mRNA of selected signal cytokines, chicken interferon-γ (ChIFN-γ), chicken interleukin (ChIL)-4 and ChIL-13 in fixed tissues. RNA probes were generated to hybridize to 488, 318, and 417bp of the respective target mRNA. Probe concentrations ranging from 100ng/ml to 400ng/ml were shown to be suitable to label cells that expressed these cytokines. The specificity of every probe was verified using the respective sense probe. ChIFN-γ, ChIL-4 and ChIL-13 positive cells were observed in the lymphocytic infiltrations of liver and in the periarteriolar lymphatic sheaths of spleen collected from specific-pathogen-free chickens. ISH of these cytokines in a severely inflamed liver due to infiltration with the parasite Histomonas meleagridis revealed the expression of both ChIFN-γ and ChIL-13 mRNA in the mononuclear infiltrates. In conclusion, ChIFN-γ, ChIL-4 and ChIL-13 mRNA were efficiently localized by ISH, which supplies a valid technique to characterize immune responses in fixed tissues.


Purification and characterization of an Mr 87,000 protein kinase C substrate from rat brain.
We (Kligman, D., and Patel, J. (1986) J. Neurochem. 47, 298-303) and others have previously identified a major protein kinase C substrate of apparent molecular weight 87,000 (Mr 87,000). To gain insight into the function of this potentially important phosphoprotein, we have undertaken its purification and characterization from rat brain. We now report a purification scheme involving heat treatment, ammonium sulfate precipitation, anion ion-exchange and reversed-phase chromatography. This procedure gave a Mr 87,000 that was homogeneous (based on silver staining), 1,600-fold enriched relative to heat-treated material and at a yield of approximately 58 micrograms/kg wet weight. We also report the amino acid composition to be high in acidic residues and in alanine and show the protein to be phosphorylated on serine residues with a stoichiometry of 2 mol of phosphate/mol of substrate. The subcellular distribution indicates Mr 87,000 is present in two forms, membrane-bound and soluble. The membrane-bound Mr 87,000 represents 45% of the total phosphoprotein content and is enriched in microsomal and synaptic membranes. Ontogenic study has revealed this protein to be developmentally regulated, with the highest concentrations of Mr 87,000 found in prenatal animals. The availability of a purification procedure should greatly facilitate further structural characterization and elucidation of the function of Mr 87,000.


Short text topic modelling approaches in the context of big data: taxonomy, survey, and analysis.
Social media platforms such as (Twitter, Facebook, and Weibo) are being increasingly embraced by individuals, groups, and organizations as a valuable source of information. This social media generated information comes in the form of tweets or posts, and normally characterized as short text, huge, sparse, and low density. Since many real-world applications need semantic interpretation of such short texts, research in Short Text Topic Modeling (STTM) has recently gained a lot of interest to reveal unique and cohesive latent topics. This article examines the current state of the art in STTM algorithms. It presents a comprehensive survey and taxonomy of STTM algorithms for short text topic modelling. The article also includes a qualitative and quantitative study of the STTM algorithms, as well as analyses of the various strengths and drawbacks of STTM techniques. Moreover, a comparative analysis of the topic quality and performance of representative STTM models is presented. The performance evaluation is conducted on two real-world Twitter datasets: the Real-World Pandemic Twitter (RW-Pand-Twitter) dataset and Real-world Cyberbullying Twitter (RW-CB-Twitter) dataset in terms of several metrics such as topic coherence, purity, NMI, and accuracy. Finally, the open challenges and future research directions in this promising field are discussed to highlight the trends of research in STTM. The work presented in this paper is useful for researchers interested in learning state-of-the-art short text topic modelling and researchers focusing on developing new algorithms for short text topic modelling.


Phenotypic plasticity and population differentiation in seeds and seedlings of the grass Anthoxanthum odoratum.
Seeds of Anthoxanthum odoratum were transplanted reciprocally between a xeric and a mesic field population that were genetically differentiated in adult traits. In one experiment seeds were reciprocally buried in bags in the soil, in a second experiment seeds were reciprocally sown in small plots. For most traits, site effects were much larger than seed-source effects. Germination, emergence, mortality of buried seed and recruitment were significantly higher at the xeric site than at the mesic site, irrespective of population of origin. Seed dormancy, was significantly higher for seed originating from the mesic than from the xeric population. Seedling recruits originating from the xeric population tended to be larger at both sites. Fecundity of seedling recruits depended on the environment; fecundities of plants growing in the xeric site had more than double the fecundity of plants growing in the mesic site. Phenotypic plasticity rather than population differences determined variation in performance in the seed and seedling stages.