[Histochemical mechanisms in etiology of pulmonary fibrosis after short-term exposure to a mixture of dust and quartz from copper mine].
The authors induced pulmonary silicosis in albino rats by the intratracheal method with 50 mg mixed middling slime from Panaguiriste and quartz dust, dissolved in I ml physiological solution. The animals received a single treatment and were killed on 90th day of the experiment. Some intime characteristics of collagen-forming mechanisms in lungs were followed up via routine histological, histochemical, enzymohistochemical/ acid phosphatase activity, beta-glucoronidase, AS-esterase and lipase/ and autoradiographic/H3 labelled proline/ methods. It was established, that under the effect of both dusts from Panaguiriste mines studied/ mixed dust and pure quartz dust/ considerable deviations developed in the structure of the lungs of the experimental animals in the enzyme activity of acid phosphatase and carbon esterase, accompanied by various forms of fibrosis in the organ, depending on the dust applied. The difference in the composition of both dusts quartz and mixed dust slime - had an effect on the degree of the deviations, but not on their character, manifested in: I. specific protective reaction of organism, with activation of the ferments from the group of carbon esterase in macrophagic elements of interstitium and around the silicotic alterations in the lungs of the experimental animals; 2. inhibition of the maturation of macrophages in silicotic foci and 3. acceleration of the proliferation of fibroblasts with intensification of collagen-formation, accompanied by an enhanced activity of the ferments from the group of carbon esterase and in the cytoplasm of fibroblasts. The authors draw the conclusion that the complex use of routine histological, histochemical and quantitative isotope methods enables the more significant determination of fibrinogenicity of quartz-containing dust even at the early terms of their exposure under experimental conditions.


Chemical venous thromboembolic prophylaxis is safe and effective for patients with traumatic brain injury when started 24 hours after the absence of hemorrhage progression on head CT.
Venous thromboembolism (VTE) continues to be an important complication for patients with trauma, including patients with intracranial hemorrhage. We implemented a protocol starting chemical prophylaxis 24 hours after the absence of progression of hemorrhage on computed tomography (CT) to increase consistency with the use of chemical venous thromboembolic prophylaxis in this population. The objective of this study was to review the protocol of VTE prophylaxis for patients with traumatic brain injury at our institution to determine whether it has been effective and safe in preventing VTE without increasing intracranial hemorrhage. A retrospective case series was conducted to study 205 patients with intracranial hemorrhage admitted to a Level I trauma center during a 24-month period. These patients were reviewed with respect to type of intracranial injury, need for surgery, injury severity, time to initiation of chemical prophylaxis, and progression of injury on brain CT. Patients with a hospital length of stay less than 3 days or nonstable CT were excluded in the analysis of administration of chemical prophylaxis. Time to chemical prophylaxis in relation to absence of progression on brain CT was examined as well as the subsequent risk of progression of hemorrhage and risk of VTE events. The overall rate of venous thromboembolism was compared with that of matched historical controls. All patients received mechanical prophylaxis in the form of sequential compression devices. One hundred sixty-two intracranial hemorrhages were identified in 122 patients who met the study's inclusion criteria. Of this group of patients who did not have progression of hemorrhage on follow-up CT, 76.2% received chemical prophylaxis during their hospitalization.No patients had progression of intracranial hemorrhage after initiation of chemical VTE prophylaxis, and no patients developed VTE. This represents a decrease of VTE from previous years. No other complications related to chemical VTE prophylaxis were identified. A protocol based on an early use of chemical venous thromboembolic prophylaxis after the absence of progression of tramatic intracranial hemorrhage does not result in increased progression of intracranial hemorrhage and reduced the rate of venous thromboembolic events at our institution.


Somatostatinoma syndrome: a challenging differential diagnosis among pancreatic tumors.
Among the neuroendocrine neoplasia, the pancreatic somatostatin-producing tumors are very rare. Usually functional, these tumors produce the somatostatinoma syndrome, which encompasses diabetes mellitus, diarrhea/steatorrhoea, and cholelithiasis. Other symptoms may include dyspepsia, weight loss, anemia, and hypochlorhydria. All theses symptoms are explained by the inhibitory actions of the somatostatin released by tumoral cells originated from pancreatic delta cells or endocrine cells of the digestive tract. The diagnosis is easy to overlook since these symptoms are commonly observed in other more common syndromes. Besides the clinical features, diagnosis is based on serum determination of somatostatin, and imaging exams, such as ultrasound, computer tomography and positron emission tomography. Pathologic examination is characterized by the positivity of immunohistochemical reaction for synaptophysin, chromogranin, and somatostatin. These tumors can be classified according to tumor size, mitotic index, neural or vascular invasion, and distant metastases. The authors describe the case of a 61-year-old female patient who sought medical care because of a 6-month history of watery diarrhea, weight loss, and depression. She was diagnosed with diabetes mellitus 3 years ago. Imaging examination revealed a tumoral mass of 4 cm in its longest axis in the topography of the head of the pancreas and calculous cholecistopathy. The patient's clinical status was unfavorable for a surgical approach. She died after 20 days of hospitalization. The definitive diagnosis was achieved with the autopsy findings, which disclosed a pancreatic somatostatinoma.


Automatically Generating Natural Language Descriptions of Images by a Deep Hierarchical Framework.
Automatically generating an accurate and meaningful description of an image is very challenging. However, the recent scheme of generating an image caption by maximizing the likelihood of target sentences lacks the capacity of recognizing the human-object interaction (HOI) and semantic relationship between HOIs and scenes, which are the essential parts of an image caption. This article proposes a novel two-phase framework to generate an image caption by addressing the above challenges: 1) a hybrid deep learning and 2) an image description generation. In the hybrid deep-learning phase, a novel factored three-way interaction machine was proposed to learn the relational features of the human-object pairs hierarchically. In this way, the image recognition problem is transformed into a latent structured labeling task. In the image description generation phase, a lexicalized probabilistic context-free tree growing scheme is innovatively integrated with a description generator to transform the descriptions generation task into a syntactic-tree generation process. Extensively comparing state-of-the-art image captioning methods on benchmark datasets, we demonstrated that our proposed framework outperformed the existing captioning methods in different ways, such as significantly improving the performance of the HOI and relationships between HOIs and scenes (RHIS) predictions, and quality of generated image captions in a semantically and structurally coherent manner.


Sexuality in multiple sclerosis.
Sexuality and partnership have an important influence on the quality of life of every person and also on people with chronic disorders such as multiple sclerosis. The findings in literature show high evidence that people with multiple sclerosis experience high levels of sexual dysfunction, most of them with hypoactive sexual behaviour often associated with dissatisfaction in relationship, and also the partners seem to show lower sexual and partnership satisfaction. The most common problems in women are lack of sexual interest and decreased libido, often with problems in orgasmic capacity, while men report erectile dysfunction and also lack of sexual interest. The impact of the level of disability and duration of the illness remains unclear. Positive familial support can often help the patient in coping with the illness, nonetheless problems with changing roles and multiple-sclerosis-minimizing can improve the need of contacts to outstanding persons.


Molecular dynamics study on the diffusion process of AuAgCuNiPd high-entropy alloy metallurgy induced by pulsed laser heating.
As novel alloy materials with outstanding mechanical properties, high-entropy alloys have a wide range of promising applications. By establishing individual Au, Ag, Cu, Ni, and Pd nanolaminates with face-centered-cubic lattice structure arrangements, molecular dynamics simulation is carried out to track the diffusion process of AuAgCuNiPd high-entropy alloy metallurgy, which is induced by pulsed laser heating. The temperature, potential energy, and kinetic energy are analyzed to evaluate the metallurgy. The snapshots and atomic fractions are presented to show the mass transfer between metallic nanolaminates. The diffusion process is firstly observed 0.3 ns after the central point for pulsed laser heating (absorbed laser energy density at 7 kJ cm-3 and pulse duration of 0.5 ns). Meanwhile, the degrees of atomic activity for Au, Ag, Cu, Ni, and Pd are assessed by calculating the mean square displacement and diffusion coefficient. Ni has a slightly larger diffusion coefficient than the other four metallic elements. Moreover, after the central point of laser irradiation, the kinetic energy of the system reduces, while the potential energy increases, which relates to the transition from nanolaminates to high-entropy alloys. A critical absorbed laser energy density of 6 kJ cm-3 with a relative error of 8.3% for the generation of AuAgCuNiPd high-entropy alloys is found. The order of constituent nanolaminates configured with the earlier initiation of diffusion between atoms in the neighboring nanolaminates speeds up the metallurgy.


Development of type 2 diabetes following intrauterine growth retardation in rats is associated with progressive epigenetic silencing of Pdx1.
Intrauterine growth retardation (IUGR) has been linked to the onset of diseases in adulthood, including type 2 diabetes, and has been proposed to result from altered gene regulation patterns due to epigenetic modifications of developmental genes. To determine whether epigenetic modifications may play a role in the development of adult diabetes following IUGR, we used a rodent model of IUGR that expresses lower levels of Pdx1, a pancreatic and duodenal homeobox 1 transcription factor critical for beta cell function and development, which develops diabetes in adulthood. We found that expression of Pdx1 was permanently reduced in IUGR beta cells and underwent epigenetic modifications throughout development. The fetal IUGR state was characterized by loss of USF-1 binding at the proximal promoter of Pdx1, recruitment of the histone deacetylase 1 (HDAC1) and the corepressor Sin3A, and deacetylation of histones H3 and H4. Following birth, histone 3 lysine 4 (H3K4) was demethylated and histone 3 lysine 9 (H3K9) was methylated. During the neonatal period, these epigenetic changes and the reduction in Pdx1 expression could be reversed by HDAC inhibition. After the onset of diabetes in adulthood, the CpG island in the proximal promoter was methylated, resulting in permanent silencing of the Pdx1 locus. These results provide insight into the development of type 2 diabetes following IUGR and we believe they are the first to describe the ontogeny of chromatin remodeling in vivo from the fetus to the onset of disease in adulthood.


Postmortem histologic evaluation of mandibular titanium and maxillary hydroxyapatite-coated implants from 1 patient.
Postmortem examination of human specimens is an extremely important aspect of evaluating the relative compatibility and long-term success of endosseous implant surfaces. The bone-implant interface of 5 commercially pure titanium screw-type mandibular implants after 85 months of service and 2 hydroxyapatite- (HA) coated maxillary implants after 38 months of service were examined. All implants were stable at the time of the patient's death. The mandibular implants had an average of 65% contact with bone and the maxillary implants had an average of 47% contact. The HA coating had separated from the maxillary implants in some areas and was free within surrounding connective tissue or surrounded by invaginating sulcular epithelium. The arrangement and pattern of bone contact appeared different between HA-coated and titanium implant surfaces.


BMX bicycles: accident comparison with other models.
A comparison has been made between BMX bicycle accidents and those occurring when children ride other types of bicycle. The injuries sustained are compared to see if the clinical impressions that BMX are more dangerous, and produce more facial injuries, are correct. This was found not to be true as half the children involved rode BMX bicycles, and the injuries sustained were similar to those occurring to non BMX riders. BMX riders had a lower proportion of serious injuries than riders of racing cycles. There were a large number of head injuries needing admission to hospital, but BMX riders had fewer head injuries than the other groups. The use of protective headgear was minimal. Facial injuries were evenly distributed between BMX and non BMX groups. The major cause of accidents to BMX riders was performing stunts but, overall, poor cycling technique associated with minimal cycling experience were the factors common to 50% of accidents.


Accelerating regular polygon beams.
Beams that possess high-intensity peaks that follow curved paths of propagation under linear diffraction have recently been shown to have a multitude of interesting uses. In this Letter, a family of phase-only masks is derived, and each mask gives rise to multiple accelerating intensity maxima. The curved paths of the peaks can be described by the vertices of a regular polygon that is centered on the optic axis and expands with propagation.


The pediatric obsessive-compulsive disorder treatment study: rationale, design, and methods.
Obsessive-compulsive disorder (OCD), which has a prevalence of 1 in 200 in children and adolescents, carries with it significant functional morbidity. A growing empirical literature supports the efficacy of short-term treatment with OCD-specific cognitive-behavior therapy (CBT) or medication management with a selective serotonin reuptake inhibitor. These and other studies also identify a substantial probability of partial response and, possibly, differences in durability when treatment is discontinued between medication and CBT. The Pediatric OCD Treatment Study is a multicenter, randomized, masked clinical trial designed to evaluate the relative benefit and durability of four treatments for children and adolescents with OCD: sertraline, CBT, combination of sertraline and CBT, and pill placebo. Stage 1 (12 weeks) is a balanced randomized comparison of these four treatments. Responders at the end of stage 1 advance to 4 months of open follow-up in their assigned arm during which all treatment is discontinued. At the end of stage 2 (if not before), nonresponders to any treatment at the end of stage 1, any patient relapsing in stage 2, and all stage 1 placebo patients receive open treatment that is tailored to the patient's needs. A volunteer sample of 120 subjects between the ages of 7 and 17 inclusive with a primary Diagnostic and Statistical Manual of Mental Disorders (fourth edition) diagnosis of OCD enters the study. All patients, regardless of responder status, return for all scheduled assessments. This report describes the design of the trial, the rationale for the design choices made, and the methods used to carry out the trial.


Prehabilitative high-intensity interval training and resistance exercise in patients prior allogeneic stem cell transplantation.
Physical capacity prior allogeneic stem cell transplantation (allo-HCT) has been shown as a relevant prognostic factor for survival after transplant. Therefore, we evaluated feasibility and preliminary efficacy of a high-intensity interval training (HIIT) and moderate to high-intensity resistance exercise (RE) to increase physical capacity in patient's prior allo-HCT. In this multicentre single arm pilot study, a supervised exercise program was performed twice weekly for 4-12 weeks prior allo-HCT, depending on the individual time remaining. Outcomes were feasibility (recruitment, adherence, safety), physical capacity (cardiorespiratory fitness [VO2peak], muscle strength) and patient reported outcomes (physical functioning, fatigue). Thirty patients were intended, 16 could be included, and 14 completed post intervention assessment (75% male, 55 ± 11 years). The study was stopped early due to a low recruitment rate. Nine patients (64%) reached the initial minimum planned number of eight exercise sessions. Individual adherence was high with 92% for HIIT and 85% for RE. 87% of all performed exercise sessions were completed without complaints and VO2peak increased significantly from 20.4 to 23.4 ml/kg/min. The low recruitment rate suggests that initiation of the intervention concept immediately before allo-HCT is feasible only in a small number of patients. In particular, the timeframe directly prior allo-HCT seems too short for exercise interventions, although the exercise program was designed to improve outcomes in a very short time frame. HIIT and RE were feasible, effective and well accepted by the included patients.


A systematic review on recurrent cardioinhibitory vasovagal syncope: Does pacing therapy break the fall?
Vasovagal reflex is the most common cause of syncope. Pacemaker with rate drop response (RDR) or closed-loop stimulation (CLS) anti-syncope algorithms have been studied in recurrent vasovagal syncope (VVS), with conflicting results. We aim to investigate the role of pacemaker therapy and anti-syncope pacing mode in cardioinhibitory recurrent VVS. MEDLINE, Cochrane Library and registered clinical trials were searched for single or double-blind randomized controlled trials on pacing as a treatment for recurrent VVS. Five studies were eligible, overall enrolling 228 patients. After pooling data from all trials, pacemaker therapy showed a 63% reduction in syncope recurrence compared to control [Risk Ratio (RR): 0.37; 95% CI: 0.14-0.98; I2 = 67%)]. Subgroup analyses suggested that the effect was greater in single-blind studies (RR: 0.07; 95% CI: 0.01-0.52, I2 = 0%). When comparing pacing algorithms, the results from RDR versus no pacing trials (n = 2) did not show a significant reduction in syncope recurrence (RR: 0.73; 95% CI: 0.25-2.16, I2 60 = 75%). In contrast, the data from the CLS versus standard pacing trials (n = 3) evidenced a statistically meaningful reduction in syncopal burden (RR: 0.18; 95% CI: 0.07-0.47, I2 = 0%). It is unclear whether pacemaker therapy reduces syncopal burden in cardioinhibitory recurrent VVS. However, our results suggest effectiveness of CLS pacing mode.


Kinetics of the Temperature-Dependent eaq - and ⋅OH Radical Reactions with Cr(III) Ions in Aqueous Solutions.
The reactivity of chromium(III) species with the major oxidizing and reducing radiolysis products of water was investigated in aqueous solutions at temperatures up to 150 °C. The reaction between the hydrated electron (eaq - ) and Cr(III) species showed a positive temperature dependence over this temperature range. The reaction was also studied in pH 2.5 and 3.5 solutions for the first time. This work also studied the reaction between acidic Cr(III) species and the hydroxyl radical (⋅OH). It was found that Cr3+ did not react significantly with the ⋅OH radical, but the first hydrolysis species, Cr(OH)2+ , did with a rate coefficient of k= (7.2±0.3)×108 M-1 s-1 at 25 °C. The oxidation of Cr(OH)2+ by the ⋅OH radical formed an absorbing product species that ultimately oxidized to give Cr(VI). These newly measured reaction rates allow for the development of improved models of aqueous chromium speciation for the effective remediation of liquid high-level nuclear waste via vitrification processes.


An Analysis of the Influence of Physical Activity Level on Total Knee Arthroplasty Expectations, Satisfaction, and Outcomes: Increased Revision in Active Patients at Five to Ten Years.
This article was updated on September 19, 2018, because of a previous error. On page 1546, in the section titled "Discussion," the sentence that had read "Although a significant improvement was found in the vast majority of the inactive group, surprisingly, a majority of the active group (72.7%) reported a decrease in their activity levels below their baseline at 5 to 10 years postoperatively." now reads "Although a significant improvement was found in the vast majority of the inactive group, surprisingly, a majority of the active group (72.7%) reported no change or a decrease in their activity levels below their baseline at 5 to 10 years postoperatively." Patients undergoing total knee arthroplasty expect pain relief, functional improvement, and a return to physical activity. The objective of this study was to determine the impact of patients' baseline physical activity level on preoperative expectations, postoperative satisfaction, and clinical outcomes in patients undergoing total knee arthroplasty. Using an institutional registry from 2007 to 2012, we retrospectively identified patients who underwent a unilateral primary total knee arthroplasty for osteoarthritis and completed a preoperative Lower Extremity Activity Scale (LEAS), a Hospital for Special Surgery Knee Replacement Expectations Survey (HSS-KRES), and a Knee injury and Osteoarthritis Outcome Score (KOOS) evaluation in addition to 2-year KOOS and satisfaction evaluations. Active patients were defined by an LEAS level of 13 to 18. Active patients (n = 1,008) were matched to inactive patients (n = 1,008) by age, sex, body mass index, and comorbidities. The cohorts were compared with regard to the association of expectations with KOOS and satisfaction, the change in LEAS level from baseline to 2 years, complications, and revision surgical procedures. Multivariable analyses identified predictors of satisfaction, KOOS, and revision surgical procedures. Significantly more active patients (68.2%) expected to be back to normal with regard to the ability to exercise and participate in sports compared with inactive patients (55.5%; p < 0.0001). Although overall satisfaction was equivalent, active patients were more commonly very satisfied with regard to the ability to do recreational activities (67.2% compared with 57.7%; p = 0.001). There were no associations between expectations and satisfaction or outcomes. Only the inactive patient group improved in activity level at 2 years. At 2 years, 69.5% of the inactive patients and 27.3% of the active patients improved upon their baseline activity levels (p < 0.0001). Complications rates were similar. The revision rate was higher for active patients (3.2%) compared with inactive patients (1.6%) at 5 to 10 years postoperatively (p = 0.019). At 2 years following total knee arthroplasty, inactive patients improved from baseline activity levels and active patients did not. Active patients had an elevated revision risk. Therefore, active patients should be carefully counseled regarding total knee arthroplasty to give them an understanding of its limitations and the potential risk of future revision. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.


Magnetic field-induced pair density wave state in the cuprate vortex halo.
High magnetic fields suppress cuprate superconductivity to reveal an unusual density wave (DW) state coexisting with unexplained quantum oscillations. Although routinely labeled a charge density wave (CDW), this DW state could actually be an electron-pair density wave (PDW). To search for evidence of a field-induced PDW, we visualized modulations in the density of electronic states N(r) within the halo surrounding Bi2Sr2CaCu2O8 vortex cores. We detected numerous phenomena predicted for a field-induced PDW, including two sets of particle-hole symmetric N(r) modulations with wave vectors QP and 2Q P , with the latter decaying twice as rapidly from the core as the former. These data imply that the primary field-induced state in underdoped superconducting cuprates is a PDW, with approximately eight CuO2 unit-cell periodicity and coexisting with its secondary CDWs.


A Review of the Design and Implementation of a Hybrid Cardiac Rehabilitation Program: AN EXPANDING OPPORTUNITY FOR OPTIMIZING CARDIOVASCULAR CARE.
This review describes the considerations for the design and implementation of a hybrid cardiac rehabilitation (HYCR) program, a patient-individualized combination of facility-based cardiac rehabilitation (FBCR) with virtual cardiac rehabilitation (CR) and/or remote CR. To help meet the goal of the Millions Hearts Initiative to increase CR participation to 70% by 2022, a targeted review of the literature was conducted to identify studies pertinent to the practical design and implementation of an HYCR program. Areas focused upon included the current use of HYCR, exercise programming considerations (eligibility and safety, exercise prescription, and patient monitoring), program assessments and outcomes, patient education, step-by-step instructions for billing and insurance reimbursement, patient and provider engagement strategies, and special considerations. A FBCR is the first choice for patient participation in CR, as it is supported by an extensive evidence base demonstrating effectiveness in decreasing cardiac and overall mortality, as well as improving functional capacity and quality of life. However, to attain the CR participation rate goal of 70% set by the Million Hearts Initiative, CR programming will need to be expanded beyond the confines of FBCR. In particular, HYCR programs will be necessary to supplement FBCR and will be particularly useful for the many patients with geographic or work-related barriers to participation in an FBCR program. Research is ongoing and needed to develop optimal programming for HYCR.


Acute spasticity secondary to ischemic stroke involving superior frontal gyrus and anterior cingulate gyrus.
Spasticity is a velocity-dependent increase in muscle resistance associated with hypertonia after an acute stroke. Spasticity is expected to appear within a few weeks due to different mechanisms; we are reporting acute spasticity observed at the time of ischemic stroke involving the superior frontal gyrus and anterior cingulate gyrus. A healthy 64-year-old male patient suffered from subarachnoid hemorrhage secondary to aneurysmal rupture of the anterior communicating artery. He was referred to our center and treated with percutaneous transluminal coil embolization. In post-coiling, he developed acute left-sided weakness and spasticity. Magnetic resonance imaging brain showed an acute ischemic stroke involving the superior frontal gyrus and anterior cingulate gyrus. Patient follow-up showed improvement of weakness and spasticity. Therefore, acute spasticity can be related to a stroke involving the superior frontal gyrus and anterior cingulate gyrus.


The thiol methyltransferase activity of TMT1A (METTL7A) is conserved across species.
Although few resistance mechanisms for histone deacetylase inhibitors (HDACis) have been described, we recently demonstrated that TMT1A (formerly METTL7A) and TMT1B (formerly METTL7B) can mediate resistance to HDACis with a thiol as the zinc-binding group by methylating and inactivating the drug. TMT1A and TMT1B are poorly characterized, and their normal physiological role has yet to be determined. As animal model systems are often used to determine the physiological function of proteins, we investigated whether the ability of these methyltransferases to methylate thiol-based HDACis is conserved across different species. We found that TMT1A was conserved across rats, mice, chickens, and zebrafish, displaying 85.7%, 84.8%, 60.7% and 51.0% amino acid sequence identity, respectively, with human TMT1A. Because TMT1B was not found in the chicken or zebrafish, we focused our studies on the TMT1A homologs. HEK-293 cells were transfected to express mouse, rat, chicken, or zebrafish homologs of TMT1A and all conferred resistance to the thiol-based HDACIs NCH-51, KD-5170 and romidepsin compared to empty vector-transfected cells. Additionally, all homologs blunted the downstream effects of HDACi treatment such as increased p21 expression, increased acetylated histone H3, and cell cycle arrest. Increased levels of dimethylated romidepsin were also found in the culture medium of cells transfected to express any of the TMT1A homologs after a 24 h incubation with romidepsin compared to empty-vector transfected cells. Our results indicate that the ability of TMT1A to methylate molecules is conserved across species. Animal models may therefore be useful in elucidating the role of these enzymes in humans.


[Differential diagnosis of tuberculosis and other diseases affecting the middle lobe of the lung (lingular lobe)].
Based on data resulting from clinical, laboratory, bronchological and radiological correlations investigated in 102 patients with affections involving the median pulmonary lobe (the lingula), the author concluded that no characteristic symptoms can be evidenced, suggesting lesions of the anterior pulmonary areas. The major role in establishing the characteristics of the lesion in this area falls to the radio-bronchological investigation performed specifically for this. According to the radiological aspects the author identified 6 types of broncho-stenotic syndromes involving the median pulmonary lobe, but he stresses that in view of making an etiologic diagnosis the bronchologic investigation, and the cytohistologic study of bioptic material are of major importance. The use of immunologic test is also stressed, in the diagnosis of bronchopulmonary diseases. The author reveals that the diagnosis of "syndrome of the median lobe" cannot replace the exact diagnosis of the disease that should be made in accordance with the nomenclature of the disease and the precise indication of the nosologic form.


Evolutionary relationships can be more important than abiotic conditions in predicting the outcome of plant-plant interactions.
Positive and negative plant-plant interactions are major processes shaping plant communities. They are affected by environmental conditions and evolutionary relationships among the interacting plants. However, the generality of these factors as drivers of pairwise plant interactions and their combined effects remain virtually unknown. We conducted an observational study to assess how environmental conditions (altitude, temperature, irradiance and rainfall), the dispersal mechanism of beneficiary species and evolutionary relationships affected the co-occurrence of pairwise interactions in 11 Stipa tenacissima steppes located along an environmental gradient in Spain. We studied 197 pairwise plant-plant interactions involving the two major nurse plants (the resprouting shrub Quercus coccifera and the tussock grass S. tenacissima) found in these communities. The relative importance of the studied factors varied with the nurse species considered. None of the factors studied were good predictors of the co-ocurrence between S. tenacissima and its neighbours. However, both the dispersal mechanism of the beneficiary species and the phylogenetic distance between interacting species were crucial factors affecting the co-occurrence between Q. coccifera and its neighbours, while climatic conditions (irradiance) played a secondary role. Values of phylogenetic distance between 207-272.8 Myr led to competition, while values outside this range or fleshy-fruitness in the beneficiary species led to positive interactions. The low importance of environmental conditions as a general driver of pairwise interactions was caused by the species-specific response to changes in either rainfall or radiation. This result suggests that factors other than climatic conditions must be included in theoretical models aimed to generally predict the outcome of plant-plant interactions. Our study helps to improve current theory on plant-plant interactions and to understand how these interactions can respond to expected modifications in species composition and climate associated to ongoing global environmental change.


LINC00680 enhances hepatocellular carcinoma stemness behavior and chemoresistance by sponging miR-568 to upregulate AKT3.
Hepatocellular carcinoma (HCC) has an extremely poor prognosis due to the development of chemoresistance, coupled with inherently increased stemness properties. Long non-coding RNAs (LncRNAs) are key regulators for tumor cell stemness and chemosensitivity. Currently the relevance between LINC00680 and tumor progression was still largely unknown, with only one study showing its significance in glioblastoma. The study herein was aimed at identifying the role of LINC00680 in the regulation HCC stemness and chemosensitivity. QRT-PCR was used to detect the expression of LINC00680, miR-568 and AKT3 in tissue specimen and cell lines. Gain- or loss-of function assays were applied to access the function of LINC00680 in HCC cells, including cell proliferation and stemness properties. HCC stemness and chemosensitivity were determined by sphere formation, cell viability and colony formation. Luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays were performed to examine the interaction between LINC00680 and miR-568 as well as that between miR-568 and AKT3. A nude mouse xenograft model was established for the in vivo study. We found that LINC00680 was remarkably upregulated in HCC tissues. Patients with high level of LINC00680 had poorer prognosis. LINC00680 overexpression significantly enhanced HCC cell stemness and decreased in vitro and in vivo chemosensitivity to 5-fluorouracil (5-Fu), whereas LINC00680 knockdown led to opposite results. Mechanism study revealed that LINC00680 regulated HCC stemness and chemosensitivity through sponging miR-568, thereby expediting the expression of AKT3, which further activated its downstream signaling molecules, including mTOR, elF4EBP1, and p70S6K. LINC00680 promotes HCC stemness properties and decreases chemosensitivity through sponging miR-568 to activate AKT3, suggesting that LINC00680 might be a potentially important HCC diagnosis marker and therapeutic target.


Pregnancy managed by unfractionated heparin after mechanical aortic valve replacement.
Pregnancy after mechanical valve replacement involves high risk. Maternal valve thrombosis and hemorrhagic complications are associated with lethal outcomes; therefore, strict anticoagulant therapy is needed. Our patient was 26-year-old primiparous woman. She had undergone aortic valve replacement with a mechanical valve at 4 years of age and had used warfarin 3 mg per day since then. Because of her desire for a baby, she stopped warfarin and conceived spontaneously. She was referred to our hospital. After being informed of her choices, unfractionated heparin (UFH) administration was started. She experienced mild heart failure with sacroiliitis, bacteremia, and hematuria during pregnancy. She delivered her newborn at 37 weeks. Blood loss at delivery was 220 g. Administration of UFH was restarted 4 h after delivery and 3 mg of warfarin was administered from postpartum day (PPD) 6. Hemostatic suturing was required for vaginal bleeding on PPD7. A therapeutic dose of warfarin was achieved on PPD9. Although warfarin use is recommended as anticoagulant therapy for pregnant woman with mechanical valves, the safety and efficacy of UFH have not yet been clarified because of its limited use. More cases are needed to clarify this.


A Comparison of Physical Activity Mobile Apps With and Without Existing Web-Based Social Networking Platforms: Systematic Review.
Physical activity mobile apps present a unique medium to disseminate scalable interventions to increase levels of physical activity. However, the effectiveness of mobile apps has previously been limited by low levels of engagement. Existing Web-based social networking platforms (eg, Facebook and Twitter) afford high levels of popularity, reach, and sustain engagement and, thus, may present an innovative strategy to enhance the engagement, and ultimately the effectiveness of mobile apps. This study aimed to comparatively examine the effectiveness of, and engagement with, interventions that incorporate physical activity mobile apps in conjunction with and without existing Web-based social networking platforms (eg, Facebook and Twitter). A systematic review was conducted by following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Guidelines. A systematic search of the following databases was conducted: Medline, PsycINFO, Web of Science, Scopus, CINAHL, ProQuest, SPORTDiscus, EMBASE, and Cochrane. According to the comparative objective of this review, 2 independent literature searches were conducted. The first incorporated terms related to apps and physical activity; the second also incorporated terms related to Web-based social networking. The results of the two searches were synthesized and compared narratively. A total of 15 studies were identified, 10 incorporated a physical activity app alone and 5 incorporated an app in conjunction with an existing Web-based social networking platform. Overall, 10 of the 15 interventions were effective in improving one or more physical activity behaviors. Specifically, improvements in physical activity behaviors were reported in 7 of the 10 interventions incorporating physical activity apps alone and in 3 of the 5 interventions incorporating physical activity apps in conjunction with existing Web-based social networking platforms. Interventions incorporating physical activity apps alone demonstrated a decline in app engagement. In contrast, the physical activity apps in conjunction with existing Web-based social networking platforms showed increased and sustained intervention engagement. The interventions incorporating physical activity apps in conjunction with and without existing Web-based social networking platforms demonstrated effectiveness in improving physical activity behaviors. Notably, however, the interventions that incorporated existing Web-based social networking platforms achieved higher levels of engagement than those that did not. This review provides preliminary evidence that existing Web-based social networking platforms may be fundamental to increase engagement with physical activity interventions.


[Using thromboelastography to measure coagulation following massive blood loss].
Thromboelastography is becoming increasingly important for diagnosing coagulation disorders in patients with massive blood loss. This whole-blood measurement provides information about the speed of clot formation, clot strength, and degree of fibrinolysis. The result can be used as a basis for making a faster and better choice of a suitable blood product for the patient with severe blood loss. This technique can be carried out simply and quickly as a rapid test ('point-of-care test') or in a central laboratory. Use of thromboelastography in patients undergoing cardiac surgery results in reduced use of blood products and is proven to be cost effective. A reduction in the use of blood products was also seen in trauma patients and patients undergoing liver transplantation when this technique was used. Studies on other groups of patients with massive blood loss are being conducted at the moment.


Advanced knowledge of three important classes of grape phenolics: anthocyanins, stilbenes and flavonols.
Grape is qualitatively and quantitatively very rich in polyphenols. In particular, anthocyanins, flavonols and stilbene derivatives play very important roles in plant metabolism, thanks to their peculiar characteristics. Anthocyanins are responsible for the color of red grapes and wines and confer organoleptic characteristics on the wine. They are used for chemotaxonomic studies and to evaluate the polyphenolic ripening stage of grape. They are natural colorants, have antioxidant, antimicrobial and anticarcinogenic activity, exert protective effects on the human cardiovascular system, and are used in the food and pharmaceutical industries. Stilbenes are vine phytoalexins present in grape berries and associated with the beneficial effects of drinking wine. The principal stilbene, resveratrol, is characterized by anticancer, antioxidant, anti-inflammatory and cardioprotective activity. Resveratrol dimers and oligomers also occur in grape, and are synthetized by the vine as active defenses against exogenous attack, or produced by extracellular enzymes released from pathogens in an attempt to eliminate undesirable toxic compounds. Flavonols are a ubiquitous class of flavonoids with photo-protection and copigmentation (together with anthocyanins) functions. The lack of expression of the enzyme flavonoid 3',5'-hydroxylase in white grapes restricts the presence of these compounds to quercetin, kaempferol and isorhamnetin derivatives, whereas red grapes usually also contain myricetin, laricitrin and syringetin derivatives. In the last ten years, the technological development of analytical instrumentation, particularly mass spectrometry, has led to great improvements and further knowledge of the chemistry of these compounds. In this review, the biosynthesis and biological role of these grape polyphenols are briefly introduced, together with the latest knowledge of their chemistry.


Cervical neoplasia and repeated positivity of human papillomavirus infection in human immunodeficiency virus-seropositive and -seronegative women.
Increased risk for cervical intraepithelial neoplasia (CIN) in human immunodeficiency virus (HIV)-infected women may be explained by repeated positivity of human papillomavirus (HPV) infection facilitated by HIV infection and related immunosuppression. As part of a longitudinal study with semiannual examinations, 268 women in Baltimore, Maryland (of whom 184 were HIV+), provided 1,426 cervicovaginal lavage specimens tested for HPV DNA by a polymerase chain reaction-based assay between 1992 and 1998. HPV positivity and time to HPV clearance according to HIV serostatus and CD4+ cell count were compared using models for correlated binary data and survival analysis. Of the 187 participants who had at least one positive measurement, the probability of subsequent HPV positivity among HIV- women and HIV+ women with CD4+ > or =200 and <200 cells/microl was 47.5%, 78.7%, and 92.9% (p < 0.001). Within-women HPV results were correlated (i.e., clustered) in each group (p < 0.01). Compared with HIV-participants, the relative incidence of HPV clearance was 0.29 and 0.10 among HIV+ women with CD4+ > or =200 and <200 cells/microl (p < 0.001). At the end of follow-up, 11 women had biopsy-confirmed CIN. The association of HIV and CIN (p = 0.014) was fully explained by repeated HPV positivity induced by HIV infection (p = 0.648). Reversal of immunosuppression following potent antiretroviral therapy must be expected to have a dramatic impact on HIV-related CIN.


Structural requirements for the binding of benzodiazepines to their peripheral-type sites.
The DS19 Friend erythroleukemia cells possess peripheral-type benzodiazepine recognition sites that are similar to those characterized in other tissues and cells. These sites recognize only specific and well-defined ligand structures. In order for the benzodiazepines to bind to these sites, an alkyl group of 3 carbons or less is required at position 1, together with a carbonyl group at position 2. In addition, the binding affinity is enhanced by 4'-halogen or 4'-methoxy substituents, and by 7- or 2'-halogens. However, the affinity is decreased by substitutions at position 3 or 4. Central-type benzodiazepine binding in brain, on the other hand, is not affected by 1-alkyl groups and is inhibited by 4'-substitutions. Furthermore, unlike the peripheral-type site, the brain receptor is stereo-selective. These results demonstrate that the two binding sites are fundamentally different in their recognition of benzodiazepine ligands.


Influence of magnetite and its weathering originated maghemite and hematite minerals on sedimentation and transport of nanoplastics in the aqueous and subsurface environments.
Persistent nanoplastics (NPs) and their interaction with ubiquitous iron oxide minerals (IOMs) require a detailed understanding to dictate NPs fate and transport in aqueous and subsurface environments. Current study emphasizes on understanding nanoplastics (NPs) interaction with magnetite, and its weathering-originated mineral colloids, i.e., maghemite and hematite under varying environmental conditions (pH, humic acid and ionic strength). Results showed that the higher surface hydroxyl group, smaller particle size, and positive surface charge of magnetite led to maximum NPs sorption (805.8 mg/g) in comparison to maghemite (602 mg/g) and hematite (384.3 mg/g). Charge distribution and sedimentation kinetic studies in bimodal systems showed enhanced coagulation in magnetite-NPs system. FTIR and XPS analysis of NPs-IOMs reaction precipitate revealed the vital role of surface functionality in their interaction. Column experiments revealed higher NPs retention in IOMs-coated quartz sand than bare quartz sand. Further, in river water (RW), magnetite-coated sand has shown maximum NPs retention (>80 %) than maghemite (62 %) and hematite (52 %), suggesting limited NPs mobility in the presence of magnetite in subsurface conditions. These findings elucidated the dependence of NPs on IOMs in freshwater systems and illustrated IOMs impact on NPs mobility in the subsurface porous environment.


Experience with the modified Blalock-Taussig operation using polytetrafluoroethylene (Impra) grafts.
Between June 1978 and January 1982, 115 patients underwent 122 subclavian artery-pulmonary artery shunts using polytetrafluoroethylene (PTFE Impra) grafts. Forty-six of the patients had a ductus dependent pulmonary circulation, the patency of which was maintained by an infusion of prostaglandin E2 in 29 cases. There were nine hospital deaths, four of which were related to shunt failure. Five patients underwent a second shunt procedure within one week of the first. There were two cases of late graft occlusion. Twelve shunts were considered to have failed. The actuarial estimate of shunt patency was 90% (+/- 3%) at two years for all patients and 74% (+/- 10%) for neonates. There was no statistically significant difference in two year shunt patency between 4 mm grafts (88 +/- 5%) and 6 mm grafts (96 +/- 3%). The modified Blalock shunt using a PTFE graft is an effective pulmonary-systemic shunt with a good short term patency.


[Acute kidney insufficiency in patients treated with fumaric acid esters for psoriasis].
We describe four female patients with psoriasis treated with fumaric acid esters. In two patients acute renal failure developed during this therapy. Histological investigation of renal biopsy in one patient was compatible with the diagnosis of acute tubular necrosis; her renal function was reversible after cessation of the medication. The histological diagnosis of the other patient was tubulo-interstitial nephritis, possibly as a reaction to acute tubular necrosis. The recovery of her renal function was incomplete after 9 months.


Intraspecific differences in the immunochemical reactivity and neutralization of venom from Argentinean Bothrops (Rhinocerophis) alternatus by specific experimental antivenoms.
The venoms of Bothrops (Rhinocerophis) alternatus (B.a.) from different regions of Argentina have shown biochemical, toxicological and immunological variations. Considering these variations, we produced nine experimental antisera (rabbit, IgG) against venoms from snakes of nine different regions and a pool of venom, comprised of equal amounts of venoms from each region. The immunologic studies (ELISA, Westernblot) showed significant cross reactivity among all regional antivenoms with all regional venoms, with no significant differences regarding the specificity of the immunogens used for the production of antivenom. Neutralization of hemorrhage was variable (although all the antivenoms neutralized this activity in all venoms) and the neutralization of coagulant and phospholipase activities were evident in all cases. Some antivenoms neutralized toxic activities that were absent or very low in the venoms used as immunogen, on other non-homologous venoms (e.g. thrombin like activity). Despite the different toxic potencies of regional venoms, antivenoms developed using venoms of snakes from a particular region showed high immunochemical reactivity and cross-neutralizing capacity on snake venoms from different and distant regions, in occasions over those of the homologous antivenoms. These findings could be used to improve the generation of pools of venoms for the production of antivenoms.


Contemporary antimicrobial susceptibility patterns of bacterial pathogens commonly associated with febrile patients with neutropenia.
One of the most challenging problems in antimicrobial chemotherapy is the effective empirical treatment of infection in patients with neutropenia. The rates of occurrence for pathogens have significantly changed (from predominance of gram-negative to gram-positive organisms) under selective pressure of broad-spectrum antimicrobial therapy or prophylaxis, and novel resistance mechanisms have emerged. To address the need for appropriate monotherapy or combination regimens for patients with neutropenia, physicians must prescribe agents with a spectrum of antimicrobial activity to inhibit the major, prevalent pathogens encountered in bloodstream infection and pneumonia; in addition, these selected agents must be active against recently described resistant organisms. Data from the SENTRY Antimicrobial Surveillance Program indicate that several broad-spectrum agents remain highly active and can be used alone or in combinations. In most cases, the newer compounds with increased activity and spectrum against gram-positive cocci (i.e., carbapenems, cefepime, levofloxacin, and trovafloxacin) offer a greater inhibitory potential for empirical therapy among patients with neutropenia and severe infections.


Effects of chlorophyll a, chlorophyll b, and xanthophylls on the in vitro assembly kinetics of the major light-harvesting chlorophyll a/b complex, LHCIIb.
The major light-harvesting chlorophyll a/b complex (LHCIIb) of photosystem II in higher plants can be reconstituted with pigments in lipid-detergent micelles. The pigment-protein complexes formed are functional in that they perform efficient internal energy transfer from chlorophyll b to chlorophyll a. LHCIIb formation in vitro, can be monitored by the appearance of energy transfer from chlorophyll b to chlorophyll a in time-resolved fluorescence measurements. LHCIIb is found to form in two apparent kinetic steps with time constants of about 30 and 200 seconds. Here we report on the dependence of the LHCIIb formation kinetics on the composition of the pigment mixture used in the reconstitution. Both kinetic steps slow down when the concentration of either chlorophylls or carotenoids is reduced. This suggests that the slower 200 seconds formation of functional LHCIIb still includes binding of both chlorophylls and carotenoids. LHCIIb formation is accelerated when the chlorophylls in the reconstitution mixture consist predominantly of chlorophyll a although the complexes formed are thermally less stable than those reconstituted with a chlorophyll a:b ratio < or = 1. This indicates that although chlorophyll a binding is more dominant in the observed rate of LHCIIb formation, the occupation of (some) chlorophyll binding sites with chlorophyll b is essential for complex stability. The accelerating effect of various carotenoids (lutein, zeaxanthin, violaxanthin, neoxanthin) on LHCIIb formation correlates with their affinity to two lutein-specific binding sites. We conclude that the occupation of these two carotenoid binding sites but not of the third (neoxanthin-specific) binding site is an essential step in the assembly of LHCIIb in vitro.


Randomised, controlled trial of effectiveness of ampicillin in mild acute respiratory infections in Indonesian children.
The recommended treatment for mild acute respiratory infections (ARI) in children is supportive care only, but many physicians, especially in developing countries, continue to prescribe antibiotic treatment because they believe it prevents progression to more severe ARI. To find out whether ampicillin treatment conferred any benefit over supportive care alone, a randomised, controlled trial was carried out among 889 children (under 5 years) with mild ARI in Indonesia. 447 were randomly allocated ampicillin (25-30 mg/kg body weight three times daily for 5 days) plus supportive care (continued breastfeeding, clearing of the nose, and paracetamol to control fever); 442 were allocated supportive care only. The treatment groups were almost identical after randomisation in terms of age, sex, level of parental education, history of measles immunisation, and fever. After 1 week the percentages cured were nearly identical (204 [46%] ampicillin; 209 [47%] control), as were the percentages of cases progressing to moderate ARI (56 [13%] vs 53 [12%]). The effect of treatment was not modified by age, sex, measles immunisation status, or the educational level of the parents. At the 2-week follow-up, the percentages cured were 62% (277) in the ampicillin group and 58% (256) in the control group; 14% of both groups had progressed to moderate ARI; and 24% (107) and 28% (123), respectively, still had mild ARI. None of the differences in outcome between the ampicillin and control groups was statistically significant. Thus, ampicillin plus supportive care offers no benefit over supportive care alone for treatment of mild ARI in young Indonesian children.


[At the crossover of adolescent and alcohol].
These last ten years, we observed an increased number of alcohol abuse among young adolescents in Swiss Hospitals. The Pediatric Department of Geneva has established a brief intervention program for adolescents brought to the emergency unit for acute alcohol intoxication (one night at the emergency unit followed by an ambulatory consultation within ten days). In these consultations, we evaluate their psychosocial situation and risk behaviors. If necessary these adolescents are referred to psychiatric or addiction units for special care. Adolescents were informed about the risks of alcohol abuse (secondary prevention) and the parents were counseled in their educational function. This program seems to answer to a real need since 88% of adolescents came to the followup evaluation. The parents also felt reassured by this interventional program.


A SHORT INTERNODES (SHI) family transcription factor gene regulates awn elongation and pistil morphology in barley.
The awn, an apical extension from the lemma of the spikelet, plays important roles in seed dispersal, burial, and photosynthesis. Barley typically has long awns, but short-awn variants exist. The short awn 2 (lks2) gene, which produces awns about 50% shorter than normal, is a natural variant that is restricted to Eastern Asia. Positional cloning revealed that Lks2 encodes a SHI-family transcription factor. Allelism tests showed that lks2 is allelic to unbranched style 4 (ubs4) and breviaristatum-d (ari-d), for which the phenotypes are very short awn and sparse stigma hairs. The gene identity was validated by 25 mutant alleles with lesions in the Lks2 gene. Of these, 17 affected either or both conserved regions: the zinc-binding RING-finger motif and the IGGH domain. Lks2 is highly expressed in awns and pistils. Histological observations of longitudinal awn sections showed that the lks2 short-awn phenotype resulted from reduced cell number. Natural variants of lks2 were classified into three types, but all shared a single-nucleotide polymorphism (SNP) that causes a proline-to-leucine change at position 245 in the IGGH domain. All three lks2 natural variants were regarded as weak alleles because their awn and pistil phenotypes are mild compared with those of the 25 mutant alleles. Natural variants of lks2 found in the east of China and the Himalayas had considerably different sequences in the regions flanking the critical SNP, suggesting independent origins. The available results suggest that the lks2 allele might have a selective advantage in the adaptation of barley to high-precipitation areas of Eastern Asia.


Living off a fish: a trade-off between parasites and the immune system.
Research in fish immune system and parasite invasion mechanisms has advanced the knowledge of the mechanisms whereby parasites evade or cope with fish immune response. The main mechanisms of immune evasion employed by fish parasites are reviewed and considered under ten headings. 1) Parasite isolation: parasites develop in immuno-privileged host tissues, such as brain, gonads, or eyes, where host barriers prevent or limit the immune response. 2) Host isolation: the host cellular immune response isolates and encapsulates the parasites in a dormant stage without killing them. 3) Intracellular disguise: typical of intracellular microsporidians, coccidians and some myxosporeans. 4) Parasite migration, behavioural and environmental strategies: parasites migrate to host sites the immune response has not yet reached or where it is not strong enough to kill them, or they accommodate their life cycles to the season or the age in which the host immune system is down-regulated. 5) Antigen-based strategies such as mimicry or masking, variation and sharing of parasite antigens. 6) Anti-immune mechanisms: these allow parasites to resist innate humoral factors, to neutralize host antibodies or to scavenge reactive oxygen species within macrophages. 7) Immunodepression: parasites either suppress the fish immune systems by reducing the proliferative capacity of lymphocytes or the phagocytic activity of macrophages, or they induce apoptosis of host leucocytes. 8) Immunomodulation: parasites secrete or excrete substances which modulate the secretion of host immune factors, such as cytokines, to their own benefit. 9) Fast development: parasites proliferate faster than the ability of the host to mount a defence response. 10) Exploitation of the host immune reaction. Knowledge of the evasion strategies adopted by parasites will help us to understand host-parasite interactions and may therefore help in the discovery of novel immunotherapeutic agents or targeted vaccines, and permit the selection of host-resistant strains.


Why do chitons curl into a ball?
Many animals with external armour, such as hedgehogs, isopods and trilobites, curl into a protective ball when disturbed. However, in situations where predators would engulf an exposed animal whole, regardless of position, conglobation may provide limited added defence and the benefits were previously unclear. We show that polyplacophoran molluscs (chitons) are three times less likely to spend time curled into a ball in the presence of a predator. When the cue of a potential predator is present, animals instead spend significantly more time in active, high risk, high reward behaviours such as arching, balancing on the head and tail ends of their girdle and pushing the soft foot up into an exposed position. Arching increases vulnerability, but also can increase the likelihood of rapidly encountering new substratum that would allow the animal to right itself. In some other animals, the ability to roll into a ball is associated with rolling away from danger. Curling into a ball would improve mobility, to be rolled on to a safer position, but reattachment is the higher priority for chitons in the face of danger.


Systematic Review and Meta-Analysis to Estimate a Reference Range for Circulating Ionized Magnesium Concentrations in Adult Populations.
There is a lack of consensus on a reference range for ionized magnesium (iMg2+) in blood as a measure of the status of circulating iMg2+ for the screening of populations. We estimated the reference range of iMg2+ levels for healthy adult populations and the ranges for populations with cardiovascular disease (CVD), type 2 diabetes, hypertension, and renal disease. We also estimated 95% ranges for circulating magnesium (Mg) in healthy and those with cardiometabolic diseases. We searched Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Embase through 24 July, 2020 to identify articles. We included English, peer-reviewed, randomized controlled trials, prospective and retrospective cohort studies, case-control studies, and cross-sectional studies that measured iMg2+ in blood or circulating Mg at baseline. The protocol was registered on PROSPERO (CRD42020216100). Estimated ranges were calculated by employing a frequentist random-effects model using extracted (or calculated) means and SDs from each included study. We determined the 95% confidence interval of the pooled mean. A total of 95 articles were included with 53 studies having data for healthy participants and 42 studies having data for participants with cardiometabolic diseases. The estimated reference range for iMg2+ for healthy populations was 0.40-0.68 mmol/L, 0.38-0.64 mmol/L for CVD, 0.34-0.66 mmol/L for type 2 diabetes, 0.39-1.04 mmol/L for hypertension, and 0.40-0.76 mmol/L for renal disease. For circulating Mg, the estimated range was 0.72-1.0 mmol/L for healthy adults, 0.56-1.05 mmol/L for CVD, 0.58-1.14 mmol/L for type 2 diabetes, 0.60-1.08 mmol/L for hypertension, and 0.59-1.26 mmol/L for renal disease. Estimated reference ranges for cardiometabolic disease states for both iMg2+ and circulating Mg were broad and overlapped with the estimated range for healthy populations (0.40-0.68 mmol/L). Further studies should evaluate whether iMg2+ can be used as a biomarker of cardiometabolic disease.


Astrocytes, the rising stars of the glioblastoma microenvironment.
Glioblastoma (GBM) is an aggressive primary tumor, causing thousands of deaths worldwide every year. The mean survival of patients with GBM remains below 20 months despite current available therapies. GBM cells' interactions with their stromal counterparts are crucial for tumor development. Astrocytes are glial cells that comprise ~50% of all brain cells and are therefore likely to establish direct contact with GBM cells. As other tumor cell types can hijack fibroblasts or immune cells to facilitate tumor growth, GBM cells can actually activate astrocytes, namely, the tumor associated astrocytes (TAAs), to promote GBM invasion in the healthy tissue. TAAs have thus been shown to be involved in GBM cells growth and limited response to radiation or chemotherapy (i.e., Temozolomide). Nevertheless, even though the interest in the cancer research community is increasing, the role of TAAs during GBM development is still overlooked. Yet, obtaining an in-depth understanding of the mechanisms by which TAAs influence GBM progression might lead to the development of new therapeutic strategies. This article therefore reports the different levels of GBM progression at which TAAs have been recently described to be involved in, including tumor cells' proliferation/invasion and resistance to therapies, especially through the activity of extracellular vesicles.


An accelerator for neural networks with pulse-coded model neurons.
The labeling of features by synchronization of spikes seems to be a very efficient encoding scheme for a visual system. Simulation of a vision system with millions of pulse-coded model neurons, however, is almost impossible on the base of available processors including parallel processors and neurocomputers. A "one-to-one" silicon implementation of pulse-coded model neurons suffers from communication problems and low flexibility. On the other hand, acceleration of the simulation algorithm of pulse-coded leaky integrator neurons has proved to be straightforward, flexible, and very efficient. Thus we decided to develop an accelerator for a special version of the French and Stein neurons with modulatory inputs which are advantageous for simulation of synchronization mechanisms. Moreover, our accelerator also provides a Hebbian-like learning rule and supports adaptivity. Up to 128 K neurons with a total number of 16 M freely allocatable synapses are simulated within one system. The size of networks, however, is not at all limited by these numbers as the system may be arbitrarily expanded. Simulation speed obviously depends on the number of interconnections and on the average activity within the network. In the case of locally interconnected networks for simulation of vision mechanisms there is only a very low percentage of simultaneously active neurons: stimuli are not simultaneously presented in all orientations and at all positions of the visual field. In these cases our accelerator provides close to real-time behavior if one second of a biological neuron is simulated by 1000 time slots.


Identification and regulation of plasma membrane sulfate transporters in Chlamydomonas.
Chlamydomonas (Chlamydomonas reinhardtii) exhibits several responses following exposure to sulfur (S)-deprivation conditions, including an increased efficiency of import and assimilation of the sulfate anion (SO(4)(2-)). Aspects of SO(4)(2-) transport during S-replete and S-depleted conditions were previously studied, although the transporters had not been functionally identified. We employed a reverse genetics approach to identify putative SO(4)(2-) transporters, examine their regulation, establish their biogenesis and subcellular locations, and explore their functionality. Upon S starvation of wild-type Chlamydomonas cells, the accumulation of transcripts encoding the putative SO(4)(2-) transporters SLT1 (for SAC1-like transporter 1), SLT2, and SULTR2 markedly increased, suggesting that these proteins function in high-affinity SO(4)(2-) transport. The Chlamydomonas sac1 and snrk2.1 mutants (defective for acclimation to S deprivation) exhibited much less of an increase in the levels of SLT1, SLT2, and SULTR2 transcripts and their encoded proteins in response to S deprivation compared with wild-type cells. All three transporters were localized to the plasma membrane, and their rates of turnover were significantly impacted by S availability; the turnover of SLT1 and SLT2 was proteasome dependent, while that of SULTR2 was proteasome independent. Finally, mutants identified for each of the S-deprivation-responsive transporters were used to establish their critical role in the transport of SO(4)(2-) into S-deprived cells.


Clinical utility of texture analysis of 18F-FDG PET/CT in patients with Stage I lung cancer treated with stereotactic body radiotherapy.
We evaluated the reproducibility and predictive value of texture parameters and existing parameters of 18F-FDG PET/CT images in Stage I non-small-cell lung cancer (NSCLC) patients treated with stereotactic body radiotherapy (SBRT). Twenty-six patients with Stage I NSCLC (T1-2N0M0) were retrospectively analyzed. All of the patients underwent an 18F-FDG PET/CT scan before treatment and were treated with SBRT. Each tumor was delineated using PET Edge (MIM Software Inc., Cleveland, OH), and texture parameters were calculated using open-source code CGITA. From 18F-FDG PET/CT images, three conventional parameters, including maximum standardized uptake value (SUV), metabolic tumor volume (MTV) and total lesion glycolysis (TLG), and four texture parameters, including entropy and dissimilarity (derived from a co-occurrence matrix) and high-intensity large-area emphasis (HILAE) and zone percentage (derived from a size-zone matrix) were analyzed. Reproducibility was evaluated using two independent delineations conducted by two observers. The ability to predict local control (LC), progression-free survival (PFS) and overall survival (OS) was tested for each parameter. All of the seven parameters except zone percentage showed good reproducibility, with intraclass correlation coefficient values >0.8. In univariate analysis, only HILAE was a significant predictor for LC. Histology, dose fractionation, and maximum SUV were associated with PFS, and histology and dose fractionation were associated with OS. We showed that texture parameters derived from 18F-FDG PET/CT were reproducible and potentially beneficial for predicting LC in Stage I lung cancer patients treated with SBRT.


A genetic screen for regulators of muscle morphogenesis in Drosophila.
The mechanisms that determine the final topology of skeletal muscles remain largely unknown. We have been developing Drosophila body wall musculature as a model to identify and characterize the pathways that control muscle size, shape, and orientation during embryogenesis. Our working model argues muscle morphogenesis is regulated by (1) extracellular guidance cues that direct muscle cells toward muscle attachment sites, and (2) contact-dependent interactions between muscles and tendon cells. While we have identified several pathways that regulate muscle morphogenesis, our understanding is far from complete. Here, we report the results of a recent EMS-based forward genetic screen that identified a myriad of loci not previously associated with muscle morphogenesis. We recovered new alleles of known muscle morphogenesis genes, including back seat driver, kon-tiki, thisbe, and tumbleweed, arguing our screen had the depth and precision to uncover myogenic genes. We also identified new alleles of spalt-major, barren, and patched that presumably disrupt independent muscle morphogenesis pathways. Equally as important, our screen shows that at least 11 morphogenetic loci remain to be mapped and characterized. Our screen has developed exciting new tools to study muscle morphogenesis, which may provide future insights into the mechanisms that regulate skeletal muscle topology.


Mollugin from Rubea cordifolia suppresses receptor activator of nuclear factor-κB ligand-induced osteoclastogenesis and bone resorbing activity in vitro and prevents lipopolysaccharide-induced bone loss in vivo.
Osteopenic diseases, such as osteoporosis, are characterized by progressive and excessive bone resorption mediated by enhanced receptor activator of nuclear factor-κB ligand (RANKL) signaling. Therefore, downregulation of RANKL downstream signals may be a valuable approach for the treatment of bone loss-associated disorders. In this study, we investigated the effects of the naphthohydroquinone mollugin on osteoclastogenesis and its function in vitro and in vivo. Mollugin efficiently suppressed RANKL-induced osteoclast differentiation of bone marrow macrophages (BMMs) and bone resorbing activity of mature osteoclasts by inhibiting RANKL-induced c-Fos and NFATc1 expression. Mollugin reduced the phosphorylation of signaling pathways activated in the early stages of osteoclast differentiation, including the MAP kinase, Akt, and GSK3β and inhibited the expression of different genes associated with osteoclastogenesis, such as OSCAR, TRAP, DC-STAMP, OC-STAMP, integrin αν, integrin β3, cathepsin K, and ICAM-1. Furthermore, mice treated with mollugin showed significant restoration of lipopolysaccharide (LPS)-induced bone loss as indicated by micro-CT and histological analysis of femurs. Consequently, these results suggested that mollugin could be a novel therapeutic candidate for bone loss-associated disorders including osteoporosis, rheumatoid arthritis, and periodontitis.


Facial profile and maxillary arch dimensions in unilateral cleft lip and palate children in the mixed dentition stage.
The aim of this study was to evaluate the vertical and sagittal facial profile and maxillary arch width, depth, and length of patients with unilateral cleft lip and palate (UCLP) and to compare them with healthy noncleft children in the mixed dentition stage (7-13 years). This study is conducted at Hospital Universiti Sains Malaysia. UCLP group comprised 48 patients with nonsyndromic UCLP who have had the lip and palate repaired, whereas the control group comprised 48 healthy noncleft cases. The lateral cephalometrics measurements were used to determine the vertical height, sagittal depth of the face, and cranial base length and angle. Maxillary arch dimensions were measured on the study cast including arch width, depth, and length. Vertical facial height and sagittal depth measurements showed a significant decrease (P < 0.05) in the mean growth pattern in UCLP group. The anterior cranial base length (S-N) was shorter in UCLP children (P < 0.001), while Ba-N length had no significant difference (P = 0.639). Nasion-Sella Tursica-Basion angle was significantly higher in the UCLP group (P = 0.016). Dental arch width with reference to canine-to-canine and first premolar-to- first premolar distance was significantly larger in control (P = 0.001). Mean vertical and sagittal facial dimensions in the UCLP children who do not undergo orthodontic treatment are significantly lesser in all directions of growth than healthy noncleft children. The maxillary dental arch had a normal depth but constricted in width and arch length.


Maintenance of genetic variation in phenotypic plasticity: the role of environmental variation.
We study genetic variation in phenotypic plasticity maintained by a balance between mutation and weak stabilizing selection. We consider linear reaction norms allowing for spatial and/or temporal variation in the environments of development and selection. We show that the overall genetic variation maintained does not depend on whether the trait is plastic or not. The genetic variances in height and slope of a linear reaction norm, and their covariance, are predicted to decrease with the variation in the environment. Non-pleiotropic loci influencing either height or slope are expected to decrease the genetic variance in slope relative to that in height. Decrease in the ratio of genetic variance in slope to genetic variance in height with increasing variation in the environment presents a test for the presence of loci that only influence the slope, and not the height. We use data on Drosophila to test the theory. In seven of eight pair-wise comparisons genetic variation in reaction norm is higher in a less variable environment than in a more variable environment, which is in accord with the model's predictions.


The Compatibility of Chlorhexidine and a Skin Care Product Line: A Real-World Analysis of Hospital-Acquired Infection Rates.
Chlorhexidine gluconate (CHG) use helps reduce hospital-acquired infections (HAIs). Chlorhexidine gluconate effectiveness can be reduced by use of skin care products. Although laboratory work can be performed to prove compatibility, such work has limitations. The purpose of this study was to compare HAI rates when CHG antiseptic wipes were used in conjunction with a silicone- and micronutrient-based skin care product line (SMSP) and when CHG wipes were used without the SMSP. Using commercial distribution data, 17 hospitals that purchased both CHG wipes and SMSP were identified. Hospital-acquired infection rates from this group were compared with HAI rates from 18 hospitals that used CHG wipes, but not SMSP. Hospital-acquired infection information was obtained from the Leapfrog Group (www.hospitalsafetyscore.org/). Four infection rates were compared: (1) infection in the blood during an intensive care unit stay, (2) infection in the urinary tract during an intensive care unit stay, (3) surgical site infection after colon surgery, and (4) average infection rate from 1 to 3. There was no significant difference between the infection rates of the two groups (Ps ranged from .285 to .983). There was also no statistically significant association between hospital grade and product use (P = .194). When considering publicly available data on HAI, there was no measurable difference in HAI rates between facilities that use CHG wipes with or without an SMSP. The SMSP does not impact the efficacy of CHG wipes.


Glucocorticoid effects on insulin- and IGF-I-regulated muscle protein metabolism during aging.
This study was performed to assess the effect of glucocorticoids (dexamethasone) on insulin- and IGF-I-regulated muscle protein metabolism in adult and old rats. Muscle atrophy occurred more rapidly in old rats, and recovery of muscle mass was impaired when compared with adults. Muscle wasting resulted mainly from increased protein breakdown in adult rat but from depressed protein synthesis in the aged animal. Glucocorticoid treatment significantly decreased the stimulatory effect of insulin and IGF-I on muscle protein synthesis in adult rats by 25.9 and 58.1% respectively. In old rats, this effect was even greater, being 49.3 and 100% respectively. With regard to muscle proteolysis, glucocorticoids blunted the anti-proteolytic action of insulin and IGF-I in both age groups. During the recovery period, adult rats reversed the glucocorticoid-induced resistance of muscle protein metabolism within 3 days, at which time old rats still exhibited the decrease in insulin-regulated proteolysis. In conclusion, the higher sensitivity of old rat muscle to glucocorticoids may in part result from the greater modification of the effects of insulin and IGF-I on muscle protein metabolism. These responses to glucocorticoids in old rats may be associated with the emergence of muscle atrophy with advancing age.


Implications of MicroRNAs in the Treatment of Gefitinib-Resistant Non-Small Cell Lung Cancer.
Non-small cell lung cancer (NSCLC) represents about 85% of the reported cases of lung cancer. Acquired resistance to targeted therapy with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, is not uncommon. It is thus vital to explore novel strategies to restore sensitivity to gefitinib. Provided that microRNAs (miRNAs) negatively regulate their gene targets at the transcriptional level, it is speculated that miRNA mimetics may reduce the expression, activity and signal transduction of EGFR so that sensitization of tumour sites to gefitinib-induced cytotoxicity can be achieved. Indeed, a growing body of evidence has shown that the manipulation of endogenous levels of miRNA not only attenuates the EGFR/PI3K/Akt phosphorylation cascade, but also restores apoptotic cell death in in vitro models of experimentally-induced gefitinib resistance and provoked tumour regression/shrinkage in xenograft models. These data are in concordant with the clinical data showing that the differential expression profiles of miRNA in tumour tissues and blood associate strongly with drug response and overall survival. Furthermore, another line of studies indicate that the chemopreventive effects of a variety of natural compounds may involve miRNAs. The present review aims to discuss the therapeutic capacity of miRNAs in relation to recent discoveries on EGFR-TKI resistance, including chronic drug exposure and mutations.


The PPARalpha-PGC-1alpha Axis Controls Cardiac Energy Metabolism in Healthy and Diseased Myocardium.
The mammalian myocardium is an omnivorous organ that relies on multiple substrates in order to fulfill its tremendous energy demands. Cardiac energy metabolism preference is regulated at several critical points, including at the level of gene transcription. Emerging evidence indicates that the nuclear receptor PPARalpha and its cardiac-enriched coactivator protein, PGC-1alpha, play important roles in the transcriptional control of myocardial energy metabolism. The PPARalpha-PGC-1alpha complex controls the expression of genes encoding enzymes involved in cardiac fatty acid and glucose metabolism as well as mitochondrial biogenesis. Also, evidence has emerged that the activity of the PPARalpha-PGC-1alpha complex is perturbed in several pathophysiologic conditions and that altered activity of this pathway may play a role in cardiomyopathic remodeling. In this review, we detail the current understanding of the effects of the PPARalpha-PGC-1alpha axis in regulating mitochondrial energy metabolism and cardiac function in response to physiologic and pathophysiologic stimuli.


Accumulation of d-glucose from pentoses by metabolically engineered Escherichia coli.
Escherichia coli that is unable to metabolize d-glucose (with knockouts in ptsG, manZ, and glk) accumulates a small amount of d-glucose (yield of about 0.01 g/g) during growth on the pentoses d-xylose or l-arabinose as a sole carbon source. Additional knockouts in the zwf and pfkA genes, encoding, respectively, d-glucose-6-phosphate 1-dehydrogenase and 6-phosphofructokinase I (E. coli MEC143), increased accumulation to greater than 1 g/liter d-glucose and 100 mg/liter d-mannose from 5 g/liter d-xylose or l-arabinose. Knockouts of other genes associated with interconversions of d-glucose-phosphates demonstrate that d-glucose is formed primarily by the dephosphorylation of d-glucose-6-phosphate. Under controlled batch conditions with 20 g/liter d-xylose, MEC143 generated 4.4 g/liter d-glucose and 0.6 g/liter d-mannose. The results establish a direct link between pentoses and hexoses and provide a novel strategy to increase carbon backbone length from five to six carbons by directing flux through the pentose phosphate pathway.


Managing adverse effects of glaucoma medications.
Glaucoma is a chronic, progressive disease in which retinal ganglion cells disappear and subsequent, gradual reductions in the visual field ensues. Glaucoma eye drops have hypotensive effects and like all other medications are associated with adverse effects. Adverse reactions may either result from the main agent or from preservatives used in the drug vehicle. The preservative benzalkonium chloride, is one such compound that causes frequent adverse reactions such as superficial punctate keratitis, corneal erosion, conjunctival allergy, and conjunctival injection. Adverse reactions related to main hypotensive agents have been divided into those affecting the eye and those affecting the entire body. In particular, β-blockers frequently cause systematic adverse reactions, including bradycardia, decrease in blood pressure, irregular pulse and asthma attacks. Prostaglandin analogs have distinctive local adverse reactions, including eyelash bristling/lengthening, eyelid pigmentation, iris pigmentation, and upper eyelid deepening. No systemic adverse reactions have been linked to prostaglandin analog eye drop usage. These adverse reactions may be minimized when they are detected early and prevented by reducing the number of different eye drops used (via fixed combination eye drops), reducing the number of times eye drops are administered, using benzalkonium chloride-free eye drops, using lower concentration eye drops, and providing proper drop instillation training. Additionally, a one-time topical medication can be given to patients to allow observation of any adverse reactions, thereafter the preparation of a topical medication with the fewest known adverse reactions can be prescribed. This does require precise patient monitoring and inquiries about patient symptoms following medication use.


Induction of transcription of "immediate early genes" by low-dose ionizing radiation.
The induction of transcription of specific genes after exposure to ionizing radiation has previously been reported after lethal doses of radiation (2-50 Gy). Little attention has been focused on expression of "immediate early genes" after low doses of ionizing radiation, where cell viability remains high. This dose range (0.25-2.0 Gy) is above the diagnostic dose level but at or below the doses typical for a single exposure in fractionated radiotherapy treatment of cancer. In this study, it was observed that doses in the range of 0.25-2.0 Gy induced different amounts of the mRNAs of the proto-oncogenes c-fos, c-jun, c-myc and c-Ha-ras at a given dose and time in Epstein-Barr virus-transformed human lymphoblastoid 244B cells. A maximum response was seen after a dose of 0.5 Gy for all but c-fos, which showed a maximum response after exposure to 0.25 Gy. Time-course studies demonstrated that, for all four proto-oncogenes, the induction was transient, reaching a maximum at 1 h and declining to the constitutive level at 4 h after irradiation. Using second-messenger specific inhibitors, the signaling pathways involved in the induction of these proto-oncogenes was also investigated. The results showed that all four of the proto-oncogenes induced after 0.5 Gy shared a common pathway of tyrosine kinase activation. Other signaling pathways included protein kinase C, reactive oxygen intermediates and calcium-dependent kinases; these were found to be differentially involved in the induction of transcription of the individual proto-oncogenes. In summary, this study suggests that low-dose ionizing radiation (0.25-2.0 Gy) can modulate expression of immediate early genes. Secondly, the activation of immediate early genes after low-dose exposure involves multiple second-messenger signaling pathways. Third, the magnitude of involvement of the different signaling pathways after low-dose radiation is different for each proto-oncogene expressed.


Securing passenger aircraft from the threat of man-portable air defense systems (MANPADS).
In this article, we develop a model for the expected maximum hit probability of an attack on a commercial aircraft using MANPADS, as a function of the (random) location of the attacker. We also explore the sensitivity of the expected maximum hit probability to the parameters of the model, including both attacker parameters (such as weapon characteristics) and defender parameters (such as the size of the secure region around the airport). We conclude that having a large secure region around an airport offers some protection against MANPADS, and that installing onboard countermeasures reduces the success probability of a MANPADS attack.


Distribution of the histamine H(2) receptor in monkey brain and its mRNA localization in monkey and human brain.
The distribution of histamine H(2) receptor mRNA was determined by in situ hybridization histochemistry in human and monkey brain. In the case of monkey brain, we combined this technique with receptor ligand autoradiography to compare the distribution of mRNA and receptor binding sites. [(125)I]Iodoaminopotentidine ([(125)I]-APT), a reversible, high specific activity antagonist with high affinity and selectivity for the H(2) receptor, was used for receptor autoradiography. Radiolabeled oligonucleotides derived from the human mRNA sequence encoding this receptor were used as hybridization probes. The highest density of the H(2) receptor mRNA in human and monkey brain was found in caudate and putamen nuclei and external layers of cerebral cortex. Moderate levels were seen in the hippocampal formation and lower densities in the dentate nucleus of cerebellum. Areas such as globus pallidus, amygdaloid complex, cerebellar cortex, and substantia nigra were devoid of hybridization signal. The distribution of H(2) receptor mRNA in monkey brain is generally in good agreement with that of the corresponding binding sites: prominent in caudate, putamen, accumbens nuclei, and cortical areas. The hippocampus showed lower densities of receptors and low levels were detected in the globus pallidus pars lateralis. No binding sites were seen in amygdaloid complex and substantia nigra. The distribution of histaminergic innervation is in good correlation with the areas of high density for H(2) receptors: caudate, putamen, and external layers of cerebral cortex in monkey and human brain. The presence of mRNA in caudate and putamen nuclei, together with its absence from substantia nigra, suggests that the H(2) receptors found in the striatum are synthesized by intrinsic cells and not by nigral dopaminergic cells. These striatal H(2) receptors may be located on short circuit striatal interneurons or somatodendritically on striatal projection neurons which project to the globus pallidus pars lateralis. In conclusion, the present results, which constitute, to our knowledge, the first report of the regional distribution of mRNA encoding H(2) receptors detected by in situ hybridization, define the sites of synthesis of H(2) receptors and are the basis for future, more detailed studies that should result in a better understanding of H(2) receptor function.


Dietary rice improves growth performance, mucosal enzyme activities and plasma urea nitrogen in weaning piglets.
In this study, we evaluated the nutritional functions of rice for weaning piglets. Sixteen weaning piglets with an average initial weight of 7.2 kg were divided into two groups. One group was fed a corn-soybean meal based diet, and the other was fed a rice-soybean meal based diet, containing 50% corn and rice, respectively. A 2 weeks growth trial was conducted and growth performance, intestinal mucosal enzyme activities and plasma urea nitrogen were measured. The average daily gain in rice-fed piglets was significantly higher than that in corn-fed piglets and the average daily feed intake tended to be higher in rice-fed piglets than in corn-fed piglets. Maltase and aminopeptidase activities (mol/g tissue) in the jejunum in rice-fed piglets were significantly higher than those in corn-fed piglets, although these enzyme activities were not different in the duodenum. Sucrase and dipeptidyl peptidase IV activities in the two groups were not different in either the duodenum or jejunum. Although the feed (nitrogen) intake was higher in rice-fed piglets, the plasma urea nitrogen in rice-fed piglets was significantly lower (P = 0.006) than that in corn-fed piglets. These results indicate that rice is a good alternative feedstuff for the diet of weaning piglets.


Catalytic chemical amide synthesis at room temperature: one more step toward peptide synthesis.
An efficient method has been developed for direct amide bond synthesis between carboxylic acids and amines via (2-(thiophen-2-ylmethyl)phenyl)boronic acid as a highly active bench-stable catalyst. This catalyst was found to be very effective at room temperature for a large range of substrates with slightly higher temperatures required for challenging ones. This methodology can be applied to aliphatic, α-hydroxyl, aromatic, and heteroaromatic acids as well as primary, secondary, heterocyclic, and even functionalized amines. Notably, N-Boc-protected amino acids were successfully coupled in good yields with very little racemization. An example of catalytic dipeptide synthesis is reported.


Klumpfuss is involved in the determination of sensory organ precursors in Drosophila.
The neural precursor cells (sensory organ precursor cell (SOP)) of the external sense organs of Drosophila melanogaster arise from proneural clusters, which are defined through the expression pattern of proneural genes such as the genes of the achaete-scute complex (AS-C). The activities of these genes enable each cell within a cluster to become the SOP. A selection process mediated by the Notch signalling pathway and Extramacrochaetae selects a defined number of cells within the proneural cluster to realise the SOP fate, while it redirects the rest to the epidermoblast fate. Here we report a new function required for SOP determination mediated by the zinc finger transcription factor Klumpfuss (Klu). Klu participates in a novel mechanism that appears to regulate the expression as well as the activity of the proneural proteins. Our analysis indicates that Klu is a repressor of transcription, which acts via a double-negative loop to promote SOP formation: it suppresses the expression of an unidentified antagonist of proneural activity. We present a detailed structure function analysis that identifies functionally important domains within Klu.


A "whole-blood" technique for the quantitation of canine "T-lymphocyte" progenitors using a semisolid culture system.
A whole blood technique is described for the growth of concanavalin A (Con A) stimulated canine lymphocyte colonies in semisolid medium. By eliminating the routine Ficoll-Paque (F-P) gradient lymphocyte isolation, this method avoids potential problems of growth modulation due to elimination of non-lymphoid accessory cells and the influences on colony formation associated with the selective effects of F-P on lymphocyte subpopulations. Thus, the technique more closely approximates the in vivo milieu. The whole-blood method also produces higher cloning efficiencies than methods using gradient isolation of lymphocytes. Studies over a wide range of blood concentration produced a linear response of in vitro colony formation although extrapolation of the cell-dose colony-response curve did not intersect zero. Mitogen titration data indicates that a relatively large dose of Con A is required for whole blood colony formation compared to the standard F-P method. The colonies ultrastructurally were composed of lymphoblastic and lymphocytic elements which were negative for non-specific esterase activity. Characterization of cells retrieved from the colonies using rosetting techniques indicates a high percentage of the colony cells relative to canine peripheral blood cells form rosettes with human erythrocytes.


Large-scale mGluR5 network abnormalities linked to epilepsy duration in focal cortical dysplasia.
To determine the extent of metabotropic glutamate receptor type 5 (mGluR5) network abnormalities associated with focal cortical dysplasia (FCD), we performed graph theoretical analysis of [11C]ABP688 PET binding potentials (BPND), which allows for quantification of mGluR5 availability. Undirected graphs were constructed for the entire cortex in 17 FCD patients and 33 healthy controls using inter-regional similarity of [11C]ABP688 BPND. We assessed group differences in network integration between healthy controls and the ipsilateral and contralateral hemispheres of FCD patients. Compared to healthy controls, FCD patients showed reduced network efficiency and reduced small-world connectivity. The mGluR5 network of FCD patients was also less resilient to targeted removal of high centrality nodes, suggesting a less integrated network organization. In highly efficient hub nodes of FCD patients, we observed a significant negative correlation between local efficiency and duration of epilepsy only in the contralateral hemisphere, suggesting that some nodes may be more vulnerable to persistent epileptic activity. Our study provides the first in vivo evidence for a widespread reduction in cortical mGluR5 network integration in FCD patients. In addition, we find that ongoing epileptic activity may alter chemoarchitectural brain organization resulting in reduced efficiency in distant regions that are essential for network integration.


Lifestyle modification increases circulating adiponectin concentrations but does not change vaspin concentrations.
The objective of the study was to evaluate the effects of a 10-month lifestyle intervention on the components of the metabolic syndrome (MetSyn) in Koreans with MetSyn as well as on blood concentrations of adiponectin and vaspin. One hundred thirty-eight patients with MetSyn, recruited from a community health care center, were consecutively enrolled in the study; 12 patients dropped of the intervention, leaving 126 subjects (76 men and 50 women; age, 65.3 ± 9.0 years). All participants followed a 10-month lifestyle modification interventional program, including dietary counseling, advice on increasing physical activity, and recommendations to stop or limit smoking and alcohol drinking. Anthropometric and biochemical parameters related to the components of the MetSyn, including blood concentrations of adiponectin and vaspin, were assessed pre- and postintervention. At baseline, adiponectin concentrations were moderately negatively correlated to insulin concentrations and insulin resistance evaluated by the homeostasis model assessment. In response to lifestyle modification, statistically significant changes were found in systolic and diastolic blood pressure, total cholesterol, triglyceride, and insulin concentrations, as well as in homeostasis model assessment of insulin resistance. Adiponectin concentrations postintervention, compared with the preintervention levels, increased (7.2 ± 4.0 vs 6.8 ± 3.9 μg/mL, respectively; P < .05), whereas vaspin concentrations remained unchanged (0.25 ± 0.19 vs 0.26 ± 0.20 ng/mL, respectively; P = .64). A 10-month lifestyle modification program in Korean patients with MetSyn led to favorable changes in metabolic parameters and adiponectin but not vaspin concentrations.


[Study of the conditions for mass transfer in the nystatin biosynthetic process].
The kinetics of the biomass growth, nystatin production and carbohydrate consumption in cultures of act. noursei in 180 liter fermenters was studied. Under conditions of intensive agitation (Klas greater than 6) dependence of the specific productivity on the specific rates of growth and carbohydrate consumption was found. No such dependence between the above parameters were observed under conditions of poor agitation (Klas smaller than 3.5). It was shown that at the beginning of the cultivation process the coefficient of oxygen transfer Kla rapidly decreased. Later the value of Kla decreased slightly. Dependence of the maximum activity of the culture fluid on the average coefficient of masstransfer with respect to oxygen was observed.


Serological anthrax surveillance in wild boar (Sus scrofa) in Ukraine.
Anthrax, caused by Bacillus anthracis, is an acute disease affecting wildlife, livestock, and humans worldwide, although its impact on these populations is underappreciated. In Ukraine, surveillance is passive, and anthrax is often detected in livestock. However, wildlife is not subject to surveillance, although anthrax deaths (such as in wild boar, Sus scrofa) have been documented. The wild boar is a plentiful and widespread species in Ukraine and is frequently hunted. We initiated a screening study testing Ukrainian wild boar blood samples for antibodies to B. anthracis. We mapped results relative to known livestock anthrax hotspots. We discovered evidence of exposure in wild boar up to 35 km from livestock anthrax hotspots and over 400 km from previous anthrax reports in boars. We make recommendations about using wildlife species as biosentinels for anthrax in Ukraine.