Cerebral microembolization after protected carotid artery stenting in surgical high-risk patients: results of a 2-year prospective study.
This was a prospective single-center study to assess and analyze cerebral embolization resulting from carotid artery stenting with neuroprotective filter devices in patients considered as poor surgical candidates for surgical carotid endarterectomy. Fifty-three consecutive patients with an internal carotid artery stenosis were treated by placement of carotid Wallstents with two different types of temporary distal filter protection devices: the Spider filter and the FilterWire. Diffusion-weighted magnetic resonance imaging (DWI) of the brain was obtained 24 hours before the procedure and within 5 to 30 hours after the procedure to detect ischemic brain lesions resulting from the procedure. Inclusion criteria were symptomatic (> or =70%) or asymptomatic (> or =80%) stenoses in surgical high-risk patients. Two (4%) regressive minor strokes occurred. Postprocedural DWI detected new focal ischemic lesions in 21 patients (40%). The average number of lesions was 5.9 per patient, and the mean lesion volume was 1 mL or less in 19 patients (90%). Small differences were found in the lesion distribution: homolateral anterior circulation in eight cases (15.1%), other vascular territories in seven cases (13.2%), and homolateral anterior circulation plus other vascular territories in six cases (11.3%). The microembolization risk seemed nonpredictable on the basis of clinical parameters and internal carotid artery lesion characteristics. An increased risk in the rate of ipsilateral hemispheric embolization has been observed in difficult carotid arch implantations (P = .04). The incidence of new focal ischemic lesions detected by DWI is higher than expected on the basis of previous reports. Embolization from the aortic arch or common carotid arteries could account for most of those events in patients considered as surgical high-risk patients. Although 90% of the events were clinically silent, this high rate of microembolization raises questions about the possible consequences on cerebral cognitive functions.


Fluphenazine decanoate, fluphenazine hydrochloride given orally, and placebo in remitted schizophrenics. I. Relapse rates after one year.
In a simple remitted, nonpsychotic schizophrenics, the relapse rate within one year was significantly higher for those patients taking placebo as opposed to those taking fluphenazine hydrochloride orally or fluphenazine decanoate. There were no differences in relapse rates between the two active drugs, but there were significantly more terminations due to toxicity from fluphenazine decanoate than from pluphenazine given orally, entirely due to the fact that in 35% of patients receiving fluphenazine decanoate, severe akinesia developed.


New insights into pathogenesis of IgA nephropathy.
IgA nephropathy (IgAN) is the usual form of glomerulonephritis worldwide; however, the pathogenesis remains complex and uncertain. The interactions of gene, immune and environment lead to the variability of IgAN clinical presentations. Except for gene, it is still a question that what kind of the external factors that may cause IgAN. We summarized exposome, microbiome and infectome may be involved in the pathogenesis of IgAN through literature. Based on the above discoveries, we proposed a hypothesis of the course of IgAN that gene determines the internal cause, while skin and mucosa inflammations are the conditions of inducing immune disorders, the low point of immune disorders and change of immune status caused by internal and external environment lead to the disease onset. Therefore, a more detailed clinical phemomics of IgAN was required to be collected for further study.


Detection of pathogenic leptospires in urine from naturally infected cattle by nested PCR.
A nested polymerase chain reaction (PCR) using primers from the LipL32 sequence of Leptospira spp. was used to detect shedding of pathogenic leptospires in urine from naturally infected cattle. Amplicons (497bp) were obtained from 21 pathogenic reference serovars belonging to four species (L. interrogans, L. borgpetersenii, L. santarosai, L. kirschneri). DNA was amplified from 26/30 urine samples taken from cattle with suspected leptospirosis and from leptospires cultivated from 10 of these samples. The limit of detection of DNA in the clinical samples was 200pg and the nested PCR detected all pathogenic reference serovars of Leptospira spp. tested. No PCR products were amplified using DNA from other common bacterial species from the bovine urogenital tract or urine, or from the non-pathogenic L. biflexa Andamana serovar. The nested PCR exhibited high specificity and sensitivity for detection of pathogenic serovars in urine from cattle.


Safety and efficacy of repeat radiosurgery for acromegaly: an International Multi-Institutional Study.
Surgical resection is the first line treatment for growth hormone (GH) secreting tumors. Stereotactic radiosurgery (SRS) is recommended for patients who do not achieve endocrine remission after resection. The purpose of this study was to evaluate safety and efficacy of repeat radiosurgery for acromegaly. Three hundred and ninety-eight patients with acromegaly treated with the Gamma Knife radiosurgery (Elekta AB, Stockholm) were identified from the International Gamma Knife Research Foundation database. Among these, 21 patients underwent repeated SRS with sufficient endocrine follow-up and 18 patients had sufficient imaging follow-up. Tumor control was defined as lack of adenoma progression on imaging. Endocrine remission was defined as a normal IGF-1 concentration while off medical therapy. Median time from initial SRS to repeat SRS was 5.0 years. The median imaging and endocrine follow-up duration after repeat SRS was 3.4 and 3.8 years, respectively. The median initial marginal dose was 17 Gy, and the median repeat marginal dose was 23 Gy. Of the 18 patients with adequate imaging follow up, 15 (83.3%) patients had tumor control and of 21 patients with endocrine follow-up, 9 (42.9%) patients had endocrine remission at last follow-up visit. Four patients (19.0%) developed new deficits after repeat radiosurgery. Of these, 3 patients had neurologic deficits and 1 patient had endocrine deficit. Repeat radiosurgery for persistent acromegaly offers a reasonable benefit to risk profile for this challenging patient cohort. Further studies are needed to identify patients best suited for this type of approach.


Mutagenicity testing of quinine with submammalian and mammalian systems.
Quinine hydrochloride was assayed for genotoxic activity by using 4 different test systems with distinct genetic endpoints. No indications for point mutations were observed in the Ames system. In 3 cytogenetic tests performed on small rodents, Chinese hamsters showed no genotoxic activity, while inbred strains of mice revealed a dose dependent increase of SCEs, enhanced incidence of micronuclei and elevated chromatid breaks.


Wound infection following appendicectomy: the effect of extraperitoneal wound drainage and systemic antibiotic prophylaxis.
The value of extraperitoneal wound drainage and a 3-day course of prophylactic systemic cephaloridine used both separately and together have been assessed in a prospective controlled randomized trial involving 246 patients undergoing appendicectomy at the Leicester Royal Infirmary. Extraperitoneal wound drainage was shown to reduce significantly the incidence of postoperative wound infection in patients with a gangrenous or perforated appendix (P less than 0-025). Prophylactic cephaloridine significantly reduced the overall incidence of wound infection (P less than 0-02) and was also effective when the appendix was gangrenous or perforated (P less than 0-01). A highly significant reduction in wound infection was achieved when the appendix was gangrenous or perforated by the addition of wound drainage to the antibiotic regimen (P less than 0-001).


Anaphylaxis to succinylated gelatin in a patient with a meat allergy: galactose-α(1, 3)-galactose (α-gal) as antigenic determinant.
Specific immunoglobulin E (sIgE) antibodies towards the galactose-α(1,3)-galactose (α-gal) moieties may elicit life-threatening and fatal anaphylactic reactions. Patients sensitized to α-gal moieties from mammalian meat may also react towards mammalian gelatins and gelatin-containing drugs such as bovine gelatin-based colloid plasma substitute. The case of a 56 year old woman with a meat allergy who suffered anaphylaxis to succinylated gelatin is reported.


ATP and spontaneous calcium oscillations control neural stem cell fate determination in Huntington's disease: a novel approach for cell clock research.
Calcium, the most versatile second messenger, regulates essential biology including crucial cellular events in embryogenesis. We investigated impacts of calcium channels and purinoceptors on neuronal differentiation of normal mouse embryonic stem cells (ESCs), with outcomes being compared to those of in vitro models of Huntington's disease (HD). Intracellular calcium oscillations tracked via real-time fluorescence and luminescence microscopy revealed a significant correlation between calcium transient activity and rhythmic proneuronal transcription factor expression in ESCs stably expressing ASCL-1 or neurogenin-2 promoters fused to luciferase reporter genes. We uncovered that pharmacological manipulation of L-type voltage-gated calcium channels (VGCCs) and purinoceptors induced a two-step process of neuronal differentiation. Specifically, L-type calcium channel-mediated augmentation of spike-like calcium oscillations first promoted stable expression of ASCL-1 in differentiating ESCs, which following P2Y2 purinoceptor activation matured into GABAergic neurons. By contrast, there was neither spike-like calcium oscillations nor responsive P2Y2 receptors in HD-modeling stem cells in vitro. The data shed new light on mechanisms underlying neurogenesis of inhibitory neurons. Moreover, our approach may be tailored to identify pathogenic triggers of other developmental neurological disorders for devising targeted therapies.


Structures and photophysical properties of two luminescent bipyridine compounds: 2',6'-difluoro-6-[3-(pyridin-2-yloxy)phenyl]-2,3'-bipyridine and 2',6'-dimethoxy-6-[3-(pyridin-2-yloxy)phenyl]-2,3'-bipyridine.
The title compounds, C21H13F2N3O (1) and C23H19N3O3 (2), have been synthesized by typical cross-coupling reactions. Both compounds have been characterized by single-crystal X-ray diffraction. Bipyridine 1 exhibits a fully extended structure in which the terminal pyridine rings are oriented away from each other, while bipyridine 2 displays a bent structure in which terminal pyridine rings are oriented in the same direction. Several intermolecular interactions lead to the formation of two- and three-dimensional supramolecular networks in the crystal structures of 1 and 2, respectively. Compound 1 bears fluorine substituents and emits a strong fluorescence with λmax = 325 nm, while methoxy-substituted compound 2 displays red-shifted emissions with λmax = 366 nm. The emissions observed in both compounds originate from phenyl- and 2,3'-bipyridine-based π-π* transitions, according to theoretical calculations. Both compounds have high triplet energies (T1) ranging from 2.64 to 2.65 eV, which makes them potential host materials in organic light-emitting diodes (OLEDs).


Distraction as a simple and effective method to reduce pain during local anesthesia: A randomized controlled trial.
The administration of local anesthetics is considered the most unpleasant part of office-based surgery. Many procedural and pharmacological strategies have been developed to minimize pain. In children and adolescents, distraction has been demonstrated to be an effective way of minimizing pain during local anesthesia. We present a randomized controlled trial of the effect of distraction on pain during local anesthesia in adults. We have included 115 patients undergoing small office-based surgery to either the face, wrist, or hand. We randomized these patients between two groups: a control group and an intervention group. The intervention group watched a distractive video during the administration of the local anesthetic; for the rest the surgical procedures were performed in an equal fashion in both groups. Preoperative anxiety was scored from 0 to 10 and pain experienced during the injection of local anesthetic was measured on the visual analogue scale of pain (VAS), ranging from 0 to 10. Patient satisfaction was measured on the Patient Satisfaction Questionnaire (PSQ-18), ranging from 18 to 90. Patients had an equal anticipated pain score in control and intervention group. In the intervention group, a reduction of pain scores of 1 point was observed (p = 0.01). There was no difference in patient satisfaction scores between both groups. In this study, we demonstrate the pain minimizing effect of distraction during the administration of local anesthesia. Less experienced pain did not result in improved patient satisfaction in our study. We encourage physicians to seek ways to actively distract patients during unpleasant procedures.


Physical Activity Patterns Among Adolescents in Latin America and the Caribbean Region.
Physical activity implies different patterns, but many studies have focused on physical inactivity and sedentary behaviors. This study aimed to estimate the prevalence of different physical activity patterns among adolescents in Latin America and the Caribbean region. Pooled analysis of the most updated data of the Global School-based Student Health surveys. Age-standardized prevalence of 4 outcomes was estimated using information from the last 7 days: physical inactivity (0 d of at least 60 min/d), insufficient physical activity (<5 d of at least 60 min/d), commuting physical activity (≥5 d of walking or biking to school), and sedentary behavior (≥3 h/d of sitting time). A total of 132,071 records (33 countries) were analyzed, mean age 14.6 years, 51.2% girls. Pooled age-standardized prevalence of physical inactivity was 22.3%, greater among girls (25.4%) than boys (19.1%); insufficient physical activity was present in 67.7%, greater in girls (73.6%) than boys (61.5%); commuting physical activity was seen in 43.7%, similar between girls (43.3%) and boys (44.1%); and sedentary behavior was present in 43.4%, greater among girls (45.4%) than boys (41.3%). In Latin America and the Caribbean region, almost two-thirds of adolescents are insufficiently physically active, ≥40% are sedentary, and ≥20% are physically inactive, and these behaviors are more frequent among girls than boys.


Long-term clinical outcomes following treatment of childhood craniopharyngioma.
To review our institution's experience with treatment of craniopharyngioma in children, and to report long-term treatment outcomes stratified by treatment era to assess whether modern treatment techniques result in improvements in local control and survival. We retrospectively reviewed the records of 100 children who underwent surgery for craniopharygioma at Children's Hospital Boston (CHB) from August 1976 to March 2003. Of these, 79 children (median age 8.5 years) had initial treatment at CHB and sufficient follow-up data to be included in this analysis. We report their treatment course, recurrence rates, and treatment-related morbidity. We compared the results in two different treatment eras based on changes in surgical approach at CHB. Thirty-six patients underwent initial treatment with surgery alone; 63% treated prior to 1988 recurred and 36% treated after 1988 recurred. Recurrence rates following combined modality therapy (CMT) with limited surgery followed by radiation were 21 and 5% in the pre- and post-1988 eras, respectively. Accounting for treatment era, patients treated with surgery alone were 7.7 times as likely to recur as those treated with CMT (95%CI: 2.0, 28.7). In the Cox regression model, there was no significant difference in local control or overall survival based on treatment era; initial treatment remained the only statistically significant variable (P = 0.02). Advancements in treatment techniques have improved local control in children diagnosed with craniopharyngioma. The excellent survival rates necessitate long-term patient follow-up to identify and manage any treatment-related effects, including second tumors, vascular abnormalities, and endocrinopathies.


Facilitated recycling pathway for RNA polymerase III.
We show that the high in vitro transcription efficiency of yeast RNA pol III is mainly due to rapid recycling. Kinetic analysis shows that RNA polymerase recycling on preassembled tDNA.TFIIIC.TFIIIB complexes is much faster than the initial transcription cycle. High efficiency of RNA pol III recycling is favored at high UTP concentrations and requires termination at the natural termination signal. Runoff transcription does not allow efficient recycling. The reinitiation process shows increased resistance to heparin as compared with the primary initiation cycle, as if RNA polymerase was not released after termination. Indeed, template competition assays show that RNA pol III is committed to reinitiate on the same gene. A model is proposed where the polymerase molecule is directly transferred from the termination site to the promoter.


Anti-Stokes Yb3+ emission--valuable structure information in spectra of rare earth compounds measured with FT-Raman spectrometers.
Raman spectroscopy is a powerful and simple method which proved to be very useful in studies of solids. The most widely used Raman spectrometers are FT-Raman instruments with YAG:Nd(3+) laser as an excitation source. However, in the case of samples containing rare earth elements, the quality of FT-Raman spectra is often low due to strong fluorescence effects. We show that, in such cases, anti-Stokes part of the Raman spectra often contains strong, well resolved bands identified as multiphonon-assisted emission bands of Yb(3+) present as an impurity. We show on several examples that analysis of these bands may provide useful structure information, similar to that obtained by "Eu structure probe" method in optical spectroscopy. The Yb(3+) emission can be also measured using standard luminescence detection systems. However, the application of FT-Raman system allows one to obtain good quality spectra in a much cheaper, easier and faster way (in times as short as a few seconds). Moreover, high-sensitivity of FT-Raman spectrometers allows to detect even very small amounts of Yb(3+) impurity.


90Y-ibritumomab Tiuxetan in B-cell Non-Hodgkin Lymphomas: Real-world Data From the United Arab Emirates.
B-cell non-Hodgkin lymphomas (NHLs) are significant contributors to cancer-related mortality. In this single-arm, retrospective cohort study, we aimed to examine the outcomes of a radioimmunotherapeutic modality, 90Y-labeled ibritumomab tiuxetan (90YIT) in B-cell NHLs. We conducted this study based on data from the United Arab Emirates lymphoma registry. All patients with NHL subjected to 90YIT were eligible for inclusion. The country of research lacked a national autologous stem cell transplantation (ASCT) center, but many ASCT-eligible patients received 90YIT. We investigated overall survival (OS) and event-free survival (EFS), as well as safety outcomes. Between 2004 and 2008, 54 of 111 patients with B-cell NHL received radioimmunotherapy. The therapy was applied as first-line treatment in 18 cases (33.3%) and second- or later-line treatment in 36 cases (66.7%). All patients were evaluable for response. The first-line group consisted mainly of follicular lymphoma cases, and 3 of 18 patients died (16.7%) during the follow-up (range, 22-67 months). Median OS was not reached. No progression occurred after treatment (median EFS, 36.5 months [Q1-Q3 range, 30.5-44 months]). The second- or later-line group consisted mainly of diffuse large B-cell lymphoma cases, and 3 of 36 patients died (8.3%) during the follow-up (range, 4-68 months). Median OS was not reached. One case of progression was registered (median EFS: 33 months [Q1-Q3 range, 30.5-44 months]). 90YIT had acceptable short- and long-term safety profiles. The findings suggest that patients with NHL may benefit from 90YIT as salvage treatment if ASCT is not available; however, this should be validated in randomized studies.


Measuring angiogenesis in mice.
Angiogenesis is the formation of new blood vessels from pre-existing vessels. This process is essential during embryonic development, wound healing, and regeneration as well as during several pathological conditions such as cancer. In this chapter, we describe an assay to measure angiogenesis in vivo in mice - the subcutaneous sponge assay.


Isolated distal DVT in trauma: A study of the management of isolated distal deep vein thrombosis acquired as an inpatient in trauma patients.
Isolated distal deep vein thromboses (IDDVT) are common complications of trauma inpatient admission, however their management is controversial. We aimed to analyse outcomes in patients admitted to a level three tertiary referral centre who received therapeutic anticoagulation compared to those that did not. We hypothesised that therapeutic anticoagulation would be safe and effective in trauma inpatients who develop IDDVT. We performed a review of the electronic case notes of all patients with venous thromboembolism listed as a complication whilst admitted as an inpatient under the trauma unit at a tertiary institution over a 4-year period, from October 2014 to October 2018. Demographic data was collected, as well as data regarding management, major bleeding and progression of thrombosis to proximal DVT or PE. 91 IDDVT in trauma inpatients were identified. 33 patients received therapeutic anticoagulation within seven days of their diagnosis. No major bleeding was observed in this group, while one episode of thrombus progression was observed. 58 patients were not given therapeutic anticoagulation within seven days of IDDVT diagnosis. There were seven episodes of thrombus progression in this group on median day 5 post diagnosis, while no major bleeding was observed. Only approximately 1/3rd of patients with IDDVT after trauma received therapeutic anticoagulation, and in these selected cases it appears safe. Those who did not receive therapeutic anticoagulation had a significant rate of thrombosis extension into the proximal system and pulmonary embolus. Further studies on correctly identifying who can be safely anticoagulated are required and for those who cannot be, these data show more aggressive surveillance and prophylaxis needs to be considered.


The immunobiology of autoimmune encephalitides.
Autoimmune encephalitides, with an estimated incidence of 1.5 per million population per year, although described only 15 years ago, have already had a remarkable impact in neurology and paved the field to autoimmune neuropsychiatry. Many patients traditionally presented with aberrant behavior, especially of acute or subacute onset, and treated with anti-psychotic therapies, turn out to have a CNS autoimmune disease with pathogenic autoantibodies against synaptic antigens responding to immunotherapies. The review describes the clinical spectrum of these disorders, and the pathogenetic role of key autoantibodies directed against: a) cell surface synaptic antigens and receptors, including NMDAR, GABAa, GABAb, AMPA and glycine receptors; b) channels such as AQP4 water-permeable channel or voltage-gated potassium channels; c) proteins that stabilize voltage-gated potassium channel complex into the membrane, like the LGI1 and CASPR2; and d) enzymes that catalyze the formation of neurotransmitters such as Glutamic Acid Decarboxylase (GAD). These antibodies, effectively target excitatory or inhibitory synapses in the limbic system, basal ganglia or brainstem altering synaptic function and resulting in uncontrolled neurological excitability disorder clinically manifested with psychosis, agitation, behavioral alterations, depression, sleep disturbances, seizure-like phenomena, movement disorders such as ataxia, chorea and dystonia, memory changes or coma. Some of the identified triggering factors include: viruses, especially herpes simplex, accounting for the majority of relapses occurring after viral encephalitis, which respond to immunotherapy rather than antiviral agents; tumors especially teratoma, SCLC and thymomas; and biological cancer therapies (immune-check-point inhibitors). As anti-synaptic antibodies persist after viral infections or tumor removal, augmentation of autoreactive B cells which release autoantigens to draining lymph nodes, molecular mimicry and infection-induced bystander immune activation products play a role in autoimmunization process or perpetuating autoimmune neuroinflammation. The review stresses the importance of early detection, clinical recognition, proper antibody testing and early therapy initiation as these disorders, regardless of a known or not trigger, are potentially treatable responding to systemic immunotherapy with intravenous steroids, IVIg, rituximab or even bortezomid.


An epidemic of allergic contact dermatitis caused by a new allergen, caprylhydroxamic acid, in moisturizers.
In 2016, dermatologists in Finland suspected contact allergy in several patients using moisturizers under the trade name Apobase®. Following a formulation change, Phenostat™, which is a mixture of phenoxyethanol, caprylhydroxamic acid, and methylpropanediol, was used as a preservative in Apobase® moisturizers in Finland. To confirm the suspected contact allergy to Apobase® cream, oily cream, and/or lotion, and to identify the specific contact allergen and define its optimal patch test concentration. Thirty-nine patients with suspected contact allergy to Apobase® creams or lotion were patch tested in four Finnish dermatological clinics. The patch tests included old and new Apobase® formulas and their preservative agents: phenoxyethanol, methylpropanediol, and dilution series of Phenostat™ and caprylhydroxamic acid or its potassium salt. The patch tests showed positive reactions to the new Apobase® formulas, Phenostat™, and caprylhydroxamic acid or its potassium salt, but not to the old Apobase® formulas, methylpropanediol, or phenoxyethanol. We found a new contact allergen, caprylhydroxyamic acid, which caused an epidemic of allergic contact dermatitis in patients using moisturizers containing this preservative. Whether the sensitizing capacity of caprylhydroxamic acid depends on the other chemicals used in Apobase® moisturizers needs further investigation.


PCR methodology as a valuable tool for identification of endodontic pathogens.
This paper reviews the principles of polymerase chain reaction (PCR) methodology, its application in identification of endodontic pathogens and the perspectives regarding the knowledge to be reached with the use of this highly sensitive, specific and accurate methodology as a microbial identification test. Studies published in the medical, dental and biological literature. Evaluation of published epidemiological studies examining the endodontic microbiota through PCR methodology. PCR technology has enabled the detection of bacterial species that are difficult or even impossible to culture as well as cultivable bacterial strains showing a phenotypically divergent or convergent behaviour. Moreover, PCR is more rapid, much more sensitive, and more accurate when compared with culture. Its use in endodontics to investigate the microbiota associated with infected root canals has expanded the knowledge on the bacteria involved in the pathogenesis of periradicular diseases. For instance, Tannerella forsythensis (formerly Bacteroides forsythus), Treponema denticola, other Treponema species, Dialister pneumosintes, and Prevotella tannerae were detected in infected root canals for the first time and in high prevalence when using PCR analysis. The diversity of endodontic microbiota has been demonstrated by studies using PCR amplification, cloning and sequencing of the PCR products. Moreover, other fastidious bacterial species, such as Porphyromonas endodontalis, Porphyromonas gingivalis and some Eubacterium spp., have been reported in endodontic infections at a higher prevalence than those reported by culture procedures.


The Glasgow Coma Scale: time for change.
To summarize and evaluate evidence on the psychometric properties of the Glasgow Coma Scale (GCS). This instrument attempts to capture the phenomenon of consciousness with three gross indicators of nervous system function. Although the GCS does capture consciousness to a limited extent and has pragmatic utility for practitioners, it suffers serious limitations for clinical monitoring and prediction and is being eclipsed by a variety of other instruments. In spite of its acknowledged shortcomings and the emergence of parallel instruments with greater reliability and validity, the GCS continues to enjoy a privileged, but unwarranted, position in clinical and investigational contexts.


Glutaconate CoA-transferase from Acidaminococcus fermentans: the crystal structure reveals homology with other CoA-transferases.
Coenzyme A-transferases are a family of enzymes with a diverse substrate specificity and subunit composition. Members of this group of enzymes are found in anaerobic fermenting bacteria, aerobic bacteria and in the mitochondria of humans and other mammals, but so far none have been crystallized. A defect in the human gene encoding succinyl-CoA: 3-oxoacid CoA-transferase causes a metabolic disease which leads to severe ketoacidosis, thus reflecting the importance of this family of enzymes. All CoA-transferases share a common mechanism in which the CoA moiety is transferred from a donor (e.g. acetyl CoA) to an acceptor, (R)-2-hydroxyglutarate, whereby acetate is formed. The transfer has been described by a ping-pong mechanism in which CoA is bound to the active-site residue of the enzyme as a covalent thiol ester intermediate. We describe here the crystal structure of glutaconate CoA-transferase (GCT) from the strictly anaerobic bacterium Acidaminococcus fermentans. This enzyme activates (R)-2-hydroxyglutarate to (R)-2-hydroxyglutaryl-CoA in the pathway of glutamate fermentation. We initiated this project to gain further insight into the function of this enzyme and the structural basis for the characteristics of CoA-transferases. The crystal structure of GCT was solved by multiple isomorphous replacement to 2.55 A resolution. The enzyme is a heterooctamer and its overall arrangement of subunits can be regarded as an (AB)4tetramer obeying 222 symmetry. Both subunits A and B belong to the open alpha/beta-protein class and can be described as a four-layered alpha/alpha/beta/alpha type with a novel composition and connectivity of the secondary structure elements. The core of subunit A consists of seven alpha/beta repeats resulting in an all parallel central beta sheet, against which helices pack from both sides. In contrast, the centre of subunit B is formed by a ninefold mixed beta sheet. In both subunits the helical C terminus is folded back onto the N-terminal domain to form the third layer of helices. The active site of GCT is located at the interface of subunits A and B and is formed by loops of both subunits. The funnel-shaped opening to the active site has a depth and diameter of about 20 A with the catalytic residue, Glu54 of subunit B, at the bottom. The active-site glutamate residue is stabilized by hydrogen bonds. Despite very low amino acid sequence similarity, subunits A and B reveal a similar overall fold. Large parts of their structures can be spatially superimposed, suggesting that both subunits have evolved from a common ancestor.


Study on the cost attributable to central venous catheter-related bloodstream infection and its influencing factors in a tertiary hospital in China.
Central venous catheters (CVC) have been widely used for patients with severe conditions. However, they increase the risk of catheter-related bloodstream infection (CRBSI), which is associated with high economic burden. Until now, no study has focused on the cost attributable to CRBSI in China, and data on its economic burden are unavailable. The aim of this study was to assess the cost attributable to CRBSI and its influencing factors. A retrospective matched case-control study and multivariate analysis were conducted in a tertiary hospital, with 94 patients (age ≥ 18 years old) from January 2011 to November 2015. Patients with CRBSI were matched to those without CRBSI by age, principal diagnosis, and history of surgery. The difference in cost between the case group and control group during the hospitalization was calculated as the cost attributable to CRBSI, which included the total cost and five specific cost categories: drug, diagnostic imaging, laboratory testing, health care technical services, and medical material. The relation between the total cost attributable to CRBSI and its influencing factors such as demographic characteristics, diagnosis and treatment, and pathogenic microorganism, was analysed with a general linear model (GLM). The total cost attributable to CRBSI was $3528.6, and the costs of specific categories including drugs, diagnostic imaging, laboratory testing, health care technical services, and medical material, were $2556.4, $112.1, $321.7, $268.7, $276.5, respectively. GLM analysis indicated that the total cost was associated with the intensive care unit (ICU), pathogenic microorganism, age, and catheter number, according to the sequence of standardized estimate (β). ICU contributed the most to the model R-square. Central venous catheter-related bloodstream infection represents a great economic burden for patients. More attentions should be paid to further prevent and control this infection in China.


Editorial for Special Issue "Advances in the Pathogenesis and Treatment of Immune-Mediated Inflammatory Diseases".
This Special Issue focuses on the rapidly evolving field of immune-mediated inflammatory diseases (IMIDs) and the achievements that were made over the last 10 years [...].


Potential human health risk by metal(loid)s, 234,238U and 210Po due to consumption of fish from the "Luis L. Leon" Reservoir (Northern México).
Concentrations of As, Cu, Fe, Hg, Pb and Zn and activity concentrations from 234,238U and 210Po in water, fillet, liver and gills were determined in three stocked fish species from the Luis L. Leon reservoir, located in Northern Mexico. The considered species were Lepomis cyanellus, Cyprinus carpio and Ictalurus furcatus. 238U and 234U activity concentration (AC) in fillet samples showed values of 0.007-0.014 and 0.01-0.02 Bq∙kg-1 wet weight (ww), respectively. Liver samples for L. cyanellus, C. carpio and I. furcatus present 210Po AC of 1.16-3.26, 0.70-1.13 and 0.93-1.37 Bq∙kg-1 ww. Arsenic, mercury and lead concentration intervals in fillet samples were 0.13-0.39, 0.005-0.126 and 0.009-0.08 mg∙kg-1 ww, respectively, while in gill samples they were 0.11-0.43, 0.002-0.039 and 0.02-0.26 mg∙kg-1 ww. The elemental Bioaccumulation Factor (BAF) for fish tissues with respect to their concentrations in water was determined. L. cyanellus showed the highest BAF values for As and total U, being BAFAs = 37 and 40 L∙kg-1 in fillet and gills, respectively, and BAFU total = 1.5 L∙kg-1 in fillet. I. furcatus showed the highest BAF values for Hg and Pb, being BAFHg = 40 and 13 L∙kg-1 in fillet and gills, and BAFPb = 6.5 and 22 L∙kg-1 in fillet and gills, respectively. Some metal(loid) concentrations are slightly higher than European regulations for fish fillets. The difference in concentrations of metal(loid)s in fillet among the studied species is probably due to their differences in diet and habitat.


[Not Available].
A good way to promote breastfeeding is to implement the Ten Steps to Successful Breastfeeding of UNICEF. However, this is not an easy task and there are many difficulties prior to success. Based on our experience on the subject, supported by our recent accreditation as a Baby-friendly hospital, we have analyzed various doubts and problems that we think are important in order to enhance breastfeeding in a hospital setting: how to begin, how to train the health personnel and keep them updated, when and how to supplement breastfeeding, how to promote the activity of support groups, how to improve the support to the mother after discharge, how much time may be necessary, etc. Furthermore, we comment on factors that we consider important and that may be essential for success.


Antitubercular activity of the semi-polar extractives of Uvaria rufa.
To investigate the inhibitory activity of the chloroform extract, petroleum ether and chloroform sub-extracts, lead-acetate treated chloroform extract, fractions and secondary metabolites of Uvaria rufa (U. rufa) against Mycobacterium tuberculosis (M. tuberculosis) H(37)Rv. The antituberculosis susceptibility assay was carried out using the colorimetric Microplate Alamar blue assay (MABA). In addition, the cytotoxicity of the most active fraction was evaluated using the VERO cell toxicity assay. The in vitro inhibitory activity against M. tuberculosis H(37)Rv increased as purification progressed to fractionation (MIC up to 23 μg/mL). The chloroform extract and its sub-extracts showed moderate toxicity while the most active fraction from chloroform sub-extract exhibited no cytotoxicity against VERO cells. Meanwhile, the lead acetate-treated crude chloroform extract and its fractions showed complete inhibitions (100%) with MIC values up to 8 μg/mL. Phytochemical screening of the most active fraction showed, in general, the presence of terpenoids, steroids and phenolic compounds. Evaluation of the antimycobacterial activity of known secondary metabolites isolated showed no promising inhibitory activity against the test organism. The present results demonstrate the potential of U. rufa as a phytomedicinal source of compounds that may exhibit promising antituberculosis activity. In addition, elimination of polar pigments revealed enhanced inhibition against M. tuberculosis H(37)Rv. While several compounds known for this plant did not show antimycobacterial activity, the obtained results are considered sufficient reason for further study to isolate the metabolites from U. rufa responsible for the antitubercular activity.


Viscoelastic properties of middle ear effusions from pediatric otitis media with effusion and their relation to gross appearance.
The viscosity and the elasticity were measured in 146 individual middle ear effusions (MEEs) from 93 children with otitis media with effusion (OME). The effusions were classified into serous or mucoid type by their macroscopic appearance. The distribution of elasticity showed two peaks, corresponding to the peaks of serous and mucoid types of effusions. There were a small number of effusions in the intermediate range of elasticity, where the effusions were most effectively transported by the cilia. These findings suggests that the MEEs of pediatric OME are accumulations of rheologically suboptimal fluid in the middle ear cavity.


Photophysical Characterization and Biointeractions of NIR Squaraine Dyes for in Vitro and in Vivo Bioimaging.
The increasing demand for reliable near-infrared (NIR) probes exhibiting enduring fluorescence in living systems and facile compatibility with biomolecules such as peptides, antibodies or proteins is driven by the increasing use of NIR imaging in clinical diagnostics. To address this demand, a series of carboxy-functionalized unsymmetrical squaraine dyes (SQ-27, SQ-212, and SQ-215) along with non-carboxy-functionalized SQ-218 absorbing and emitting in the NIR wavelength range were designed and synthesized followed by photophysical characterization. This study focused on the impact of structural variations in the alkyl chain length, carboxy functionality positioning, and spacer chain length on dye aggregation and interaction with bovine serum albumin (BSA) as a model protein. In phosphate buffer (PB), the absorption intensity of the dyes markedly decreased accompanied by pronounced shoulders indicative of dye aggregation, and complete fluorescence quenching was seen in contrast to organic solvents. However, in the presence of BSA in PB, there was a enhancement in absorption intensity while regaining the fluorescence coupled with a remarkable increase in the intensity with increasing BSA concentrations, signifying the impact of dye-BSA interactions on preventing aggregation. Further analysis of Job's plot unveiled a 2:1 interaction ratio between BSA and all dyes, while the binding studies revealed a robust binding affinity (Ka) in the order of 107/mol. SQ-212 and SQ-215 were further tested for their in vitro and in vivo imaging capabilities. Notably, SQ-212 demonstrated nonpermeability to cells, while SQ-215 exhibited easy penetration and prominent cytoplasmic localization in in vitro studies. Injection of the dyes into laboratory mice showcased their efficacy in visualization, displaying stable and intense fluorescence in tissues without toxicity, organ damage, or behavioral changes. Thus, SQ-212 and SQ-215 are promising candidates for imaging applications, holding potential for noninvasive cellular and diagnostic imaging as well as biomarker detection when coupled with specific vectors in living systems.


Touchscreen typing pattern analysis for remote detection of the depressive tendency.
Depressive disorder (DD) is a mental illness affecting more than 300 million people worldwide, whereas social stigma and subtle, variant symptoms impede diagnosis. Psychomotor retardation is a common component of DD with a negative impact on motor function, usually reflected on patients' routine activities, including, nowadays, their interaction with mobile devices. Therefore, such interactions constitute an enticing source of information towards unsupervised screening for DD symptoms in daily life. In this vein, this paper proposes a machine learning-based method for discriminating between subjects with depressive tendency and healthy controls, as denoted by self-reported Patient Health Questionnaire-9 (PHQ-9) compound scores, based on typing patterns captured in-the-wild. The latter consisted of keystroke timing sequences and typing metadata, passively collected during natural typing on touchscreen smartphones by 11/14 subjects with/without depressive tendency. Statistical features were extracted and tested in univariate and multivariate classification pipelines to reach a decision on subjects' status. The best-performing pipeline achieved an AUC = 0.89 (0.72-1.00; 95% Confidence Interval) and 0.82/0.86 sensitivity/specificity, with the outputted probabilities significantly correlating (>0.60) with the respective PHQ-9 scores. This work adds to the findings of previous research associating typing patterns with psycho-motor impairment and contributes to the development of an unobtrusive, high-frequency monitoring of depressive tendency in everyday living.


Studies on the formation and state of determination of the trunk organizer in the newt,Cynops pyrrhogaster.
The exact localization of the presumptive trunk organizer was determined by means of vital staining at the initiation of gastrulation (0 h embryo) and subsequently in 6, 9, 12 and 24 h embryos.The progressive changes in the self-differentiation and inductive capacity of the trunk organizer were studied in isolation cultures (sitting drop) and in sandwich cultures with competent gastrula ectoderm. In the 0 and 6 h embryo cultures the excised trunk organizer predominantly formed atypical ectoderm. A dramatic change in differentiation and inductive capacity occurred in the 9 h embryo. The positive cases - 83% of the isolation and 50% of the sandwich cultures - mainly formed notochord and somites, accompanied by spinal cord and hindbrain in the sandwich cultures. Although no further change in self-differentiation occurred from that time onwards, a gradual increase in inductive capacity was recognized.


The Oldham Notebooks: an analysis of the development of IVF 1969-1978. I. Introduction, materials and methods.
In this introductory paper, we describe the primary source material studied in this Symposium, namely a set of 21 notebooks and 571 pages of loose sheets and scraps of paper, which, on cross-referencing, have allowed us to reconstruct the sequence, timing and numbers of the laparoscopic cycles planned, attempted and undertaken between 9 January 1969 and 1 August 1978 by Robert Edwards, Patrick Steptoe and Jean Purdy in Oldham, UK, as well as to identify most of the patients involved. In addition, we describe the background to the five papers that follow, and the secondary sources and recorded interviews, which have provided useful ancillary material.


Effect of lamotrigine on the electrically-evoked release of endogenous amino acids from slices of dorsal horn of the rat spinal cord.
The novel anti-epileptic, lamotrigine (LTG) has been shown to exhibit antinociceptive effects in the rat. In the present study, the effect of LTG on the electrically-evoked release of endogenous amino acids from rat isolated spinal dorsal horn slices with intact dorsal roots has been examined and compared with those of morphine in the same preparation. LTG (0.1-300 microM) inhibited the release of aspartate, glutamate and GABA in a concentration-dependent manner. The lowest concentrations of morphine (0.001-0.01 microM) enhanced the stimulated release of aspartate and glutamate while the higher concentrations inhibited their release. Stimulated GABA release was reduced in a concentration-dependent manner. The anticonvulsant was more potent at inhibiting the release of glutamate (IC50 = 20 microM) than that of GABA (IC50 = 44 microM) supporting the previous suggestion that lamotrigine is a selective inhibitor of glutamate release. This suggests that the reduction in glutamate release could be one of the mechanisms by which lamotrigine exerts its antinociceptive effect.


Genetic analysis of abiotic stress tolerance in crops.
Abiotic stress tolerance is complex, but as phenotyping technologies improve, components that contribute to abiotic stress tolerance can be quantified with increasing ease. In parallel with these phenomics advances, genetic approaches with more complex genomes are becoming increasingly tractable as genomic information in non-model crops increases and even whole crop genomes can be re-sequenced. Thus, genetic approaches to elucidating the molecular basis to abiotic stress tolerance in crops are becoming more easily achievable.


Global degranulation of rat mast cells stimulated with DNP-polystyrene.
Mediator release was studied in rat peritoneal mast cells sensitized with a mouse monoclonal anti-DNP IgE antibody, and stimulated with DNP-ornithine covalently attached to radio-derivatized polystyrene petri dishes. Cells releasing serotonin at maximal rates were investigated by transmission electron microscopy. Generalized exocytosis of granules could be observed, suggesting non-directional release of mediators, and non-compartmentalized action of second messengers in mast cells stimulated with polystyrene-bound DNP. Stimulation of sensitized mast cells by DNP covalently bound to the rigid polystyrene surface is consistent with extrinsic mechanisms proposed for Fc(epsilon)RI receptor action, and suggests that internalization of Fc(epsilon)RI is not needed for triggering cell degranulation.


Exploratory study of the typology of various grades of mature skin.
Post-menopausal skin aging has intrinsic as well as extrinsic origins, and this process induces important disparities of appearance and feeling within an age range. The objective of this study was to identify 3 grades of maturity of the facial skin of menopausal women. One hundred and fifty women aged between 50 and 80 (63 ± 7 years) were enrolled. The investigations combined clinical scoring, biometrological measurements (corneometry, cutometry, digital photography, and 3D analysis by fringe projection), and questionnaires. Images elaborated from photographs and 3D views were scored by 2 investigators to classify the subjects according to 3 grades of skin maturity. STEPDISC statistical analysis revealed that the most relevant variables to differentiate the maturity grades were elastosis, wrinkles on the cheeks, wrinkles on the upper lip, roughness, spots, and elasticity. The age does not reveal the degree of maturity of mature skin. Three grades of skin maturity in menopausal women, based on clinical and physiological patterns, have been differentiated in this study. Cosmetic treatments specifically adapted to the needs of menopausal women can therefore be developed.


The kinetics and capacity of repair of sublethal damage in mouse lip mucosa during fractionated irradiations.
The kinetics and capacity of repair of sublethal damage in mouse lip mucosa have been investigated. To assess the rate of repair 2 and 5 irradiations have been given with intervals ranging from 1 to 24 hours. It was found that the sublethal damage induced by a dose of approximately 10 Gy was fully recovered in approximately 4 hr. After a dose of 5-6 Gy, cellular repair was completed within 3 hr. The half time of repair (T1/2) was estimated to be approximately 72 min for 10 Gy and approximately 54 min for 5-6 Gy. Although these results suggest that the rate of repair is dependent on the fraction size, the possible influence of the amount of repair of sublethal radiation damage with the various fraction sizes used can not be ruled out. To evaluate the capacity of repair, a single dose, 2, 4 and 10 fractions have been given in a maximal overall time of 3 days in order to minimize the influence of repopulation. The slope of the isoeffective curve was 0.32 and the alpha/beta ratio was 8.5 Gy. This indicates that the capacity of cellular repair of lip mucosa is similar to those of other rapidly proliferating tissues but smaller than those of late responding tissues. The results of the present and other studies demonstrate that there are considerable differences in the repair characteristics between acutely and late responding tissues. These features have to be dealt with when fractionation schedules are markedly altered.


Assembly of the antifreeze glycoprotein/trypsinogen-like protease genomic locus in the Antarctic toothfish Dissostichus mawsoni (Norman).
To investigate the genomic architecture underlying the quintessential adaptive phenotype, antifreeze glycoprotein (AFGP) that enables Antarctic notothenioid survival in the frigid Southern Ocean, we isolated the AFGP genomic locus from a bacterial artificial chromosome library for Dissostichus mawsoni. Through extensive shotgun sequencing of pertinent clones and sequence assembly verifications, we reconstructed the highly repetitive AFGP genomic locus. The locus comprises two haplotypes of different lengths (363.6 kbp and 467.4 kbp) containing tandem AFGP, two TLP (trypsinogen-like protease), and surprisingly three chimeric AFGP/TLP, one of which was previously hypothesized to be a TLP-to-AFGP evolutionary intermediate. The ~100 kbp haplotype length variation results from different AFGP copy number, suggesting substantial dynamism existed in the evolutionary history of the AFGP gene family. This study provided the data for fine resolution sequence analyses that would yield insight into the molecular mechanisms of notothenioid AFGP gene family evolution driven by Southern Ocean glaciation.


Folding kinetics of an entangled protein.
The possibility of the protein backbone adopting lasso-like entangled motifs has attracted increasing attention. After discovering the surprising abundance of natively entangled protein domain structures, it was shown that misfolded entangled subpopulations might become thermosensitive or escape the homeostasis network just after translation. To investigate the role of entanglement in shaping folding kinetics, we introduce a novel indicator and analyze simulations of a coarse-grained, structure-based model for two small single-domain proteins. The model recapitulates the well-known two-state folding mechanism of a non-entangled SH3 domain. However, despite its small size, a natively entangled antifreeze RD1 protein displays a rich refolding behavior, populating two distinct kinetic intermediates: a short-lived, entangled, near-unfolded state and a longer-lived, non-entangled, near-native state. The former directs refolding along a fast pathway, whereas the latter is a kinetic trap, consistently with known experimental evidence of two different characteristic times. Upon trapping, the natively entangled loop folds without being threaded by the N-terminal residues. After trapping, the native entangled structure emerges by either backtracking to the unfolded state or threading through the already formed but not yet entangled loop. Along the fast pathway, trapping does not occur because the native contacts at the closure of the lasso-like loop fold after those involved in the N-terminal thread, confirming previous predictions. Despite this, entanglement may appear already in unfolded configurations. Remarkably, a longer-lived, near-native intermediate, with non-native entanglement properties, recalls what was observed in cotranslational folding.


Adsorption of Co2+ and Sr2+ in aqueous solution by a novel fibrous chitosan biosorbent.
In this study, a novel fibrous chitosan biosorbent was prepared using LiOH/KOH/urea/H2O (4.5:7:8:80.5 by weight) as spinning solvent. The fibrous chitosan exhibited a higher adsorption capacity and a faster adsorption rate for Co2+ and Sr2+, compared with spherical chitosan due to its high specific surface area (16.9 m2 g-1), uniform fineness (24.1 μm), and good mechanical strength. The adsorption capacity of fibrous chitosan for Co2+ and Sr2+ was 31.3 mg g-1 and 20.0 mg g-1, respectively, which was higher than that of spherical chitosan (22.5 mg g-1for Co2+ and 8.9 mg g-1 for Sr2+). The coordination between -NH2/-OH of chitosan and the nuclide ions was the rate-limiting step. The improvement of adsorption performance was due to the higher specific surface area which increased the exposure degree of functional groups (adsorptive sites). This new wet-spun fibrous chitosan biosorbent showed great potential in the adsorptive removal of nuclides ions from aqueous solution.


A novel insight into the mode of action of glufosinate: how reactive oxygen species are formed.
Glufosinate targets glutamine synthetase (GS), but its fast herbicidal action is triggered by reactive oxygen species (ROS). The relationship between GS inhibition and ROS accumulation was investigated in Amaranthus palmeri. Glufosinate's fast action is light-dependent with no visual symptoms or ROS formation in the dark. Inhibition of GS leads to accumulation of ammonia and metabolites of the photorespiration pathway, such as glycolate and glyoxylate, as well as depletion of other intermediates such as glycine, serine, hydroxypyruvate, and glycerate. Exogenous supply of glycolate to glufosinate-treated plants enhanced herbicidal activity and dramatically increased hydrogen peroxide accumulation (possibly from peroxisomal glycolate oxidase activity). Glufosinate affected the balance between ROS generation and scavenging. The activity of superoxide dismutase, catalase, ascorbate peroxidase, and glutathione reductase increased after glufosinate treatment in an attempt to quench the nascent ROS burst. Low doses of atrazine and dinoseb were used to investigate the sources of ROS by manipulating photosynthetic electron transport and oxygen (O2) evolution. ROS formation depended on electron flow and O2 evolution in photosystem II (PSII). Inhibition of GS disrupted photorespiration, carbon assimilation, and linear electron flow in the light reactions. Consequently, the antioxidant machinery and the water-water cycle are overwhelmed in the presence of light and glufosinate. The O2 generated by the splitting of water in PSII becomes the acceptor of electrons, generating ROS. The cascade of events leads to lipid peroxidation and forms the basis for the fast action of glufosinate.


A longitudinal examination of school-related and mental health mediators linking emotion regulation to academic achievement.
Emotion regulation is assumed to underlie academic achievement through different mechanisms (e.g., a positive orientation toward school and schoolwork, better mental health). However, few studies have contrasted these mediating mechanisms within a longitudinal analytic framework, which is necessary to determine which mechanism(s) are most likely to translate emotion regulation into academic success over time. The present study addressed this gap by examining whether children's emotion regulation capacities were associated with later academic achievement through school-related (i.e., school bonding and academic motivation) and mental health mediators (i.e., internalizing and externalizing symptoms). Participants included 300 4- and 8-year-old children (n = 150 in each age cohort; 50% female) and their caregivers from Canada. Measures were collected over 4 years. Path analyses indicated that higher emotion regulation (T1; age 4/8 years) was associated with better academic achievement 3 years later (T4; age 7/11 years) through stronger school bonding and lower internalizing symptoms in the interim (T2; age 5/9 years; the indirect effect through internalizing symptoms held after controlling for initial levels of internalizing symptoms). Significant effects were derived from both caregiver and child informants when applicable and indirect effects held across age cohorts and genders. Findings highlight the interplay of social-emotional, academic, and mental health development across childhood, as well as the potential benefits of extending academic interventions to the social-emotional and mental health domains.


Early ion-channel remodeling and arrhythmias precede hypertrophy in a mouse model of complete atrioventricular block.
Complete atrioventricular block (CAVB) and related ventricular bradycardia are known to induce ventricular hypertrophy and arrhythmias. Different animal models of CAVB have been established with the most common being the dog model. Related studies were mainly focused on the consequences on the main repolarizing currents in these species, i.e. IKr and IKs, with a limited time point kinetics post-AVB. In order to explore at a genomic scale the electrical remodeling induced by AVB and its chronology, we have developed a novel model of CAVB in the mouse using a radiofrequency-mediated ablation procedure. We investigated transcriptional changes in ion channels and contractile proteins in the left ventricles as a function of time (12h, 1, 2 and 5 days after CAVB), using high-throughput real-time RT-PCR. ECG in conscious and anesthetized mice, left ventricular pressure recordings and patch-clamp were used for characterization of this new mouse model. As expected, CAVB was associated with a lengthening of the QT interval. Moreover, polymorphic ventricular tachycardia was recorded in 6/9 freely-moving mice during the first 24h post-ablation. Remarkably, myocardial hypertrophy was only evident 48 h post-ablation and was associated with increased heart weight and altered expression of contractile proteins. During the first 24 hours post-CAVB, genes encoding ion channel subunits were either up-regulated (such as Nav1.5, +74%) or down-regulated (Kv4.2, -43%; KChIP2, -47%; Navβ1, -31%; Cx43, -29%). Consistent with the transient alteration of Kv4.2 expression, I(to) was reduced at day 1, but restored at day 5. In conclusion, CAVB induces two waves of molecular remodeling: an early one (≤24 h) leading to arrhythmias, a later one related to hypertrophy. These results provide new molecular basis for ventricular tachycardia induced by AV block.


In Situ Implanting of Single Tungsten Sites into Defective UiO-66(Zr) by Solvent-Free Route for Efficient Oxidative Desulfurization at Room Temperature.
Design of single-site catalysts with catalytic sites at atomic-scale and high atom utilization, provides new opportunities to gain superior catalytic performance for targeted reactions. In this contribution, we report a one-pot green approach for in situ implanting of single tungsten sites (up to 12.7 wt.%) onto the nodes of defective UiO-66(Zr) structure via forming Zr-O-W bonds under solvent-free condition. The catalysts displayed extraordinary activity for the oxidative removal of sulfur compounds (1000 ppm S) at room temperature within 30 min. The turnover frequency (TOF) value can reach 44.0 h-1 at 30 °C, which is 109.0, 12.3 and 1.2 times higher than that of pristine UiO-66(Zr), WO3 , and WCl6 (homogeneous catalyst). Theoretical and experimental studies show that the anchored W sites can react with oxidant readily and generate WVI -peroxo intermediates that determine the reaction activity. Our work not only manifests the application of SSCs in the field of desulfurization of fuel oil but also opens a new solvent-free avenue for fabricating MOFs based SSCs.


Synthesis and anticancer evaluation of bis(benzimidazoles), bis(benzoxazoles), and benzothiazoles.
Four classes of UK-1 analogues were synthesized and their cytotoxicity testing against human A-549, BFTC-905, RD, MES-SA, and HeLa carcinoma cell lines was determined. The results revealed that UK-1 and four of these analogues (15-18) are potent against the cancer cell lines. In particular, compound 16 is more potent than UK-1 against A-549 and HeLa cell lines, and compounds 15, 17, and 18 selectively exhibit potent cytotoxic activity against the BFTV-905 cells (IC50 9.6 microM), A-549 cells (IC50 6.6 microM), and MES-SA cells (IC50 9.2 microM), respectively.


Extraneural metastases in gliosarcoma: a case report and review of the literature.
This report details the case of an 11-year-old girl with gliosarcoma and her rapid demise after a brief asymptomatic postcraniotomy period. The discussion that follows is a collective review of the several aspects illustrated by the case history. Special attention is directed toward the pathological features of this histological variant of glioblastoma multiforme. The topic of extraneural metastasis is reviewed with regard to frequency, mechanisms, sites, and prognosis.


Ethically justified clinically comprehensive guidelines for the management of the depressed pregnant patient.
This article proposes ethically justified clinical guidelines for managing depressed patients during pregnancy. We reviewed literature on depression and its consequences for pregnancy and related that literature to ethical principles. The health effects of depression on the pregnant woman and her fetus cannot be managed without consideration of the chronic and variable impairment of autonomy that may result from the effects of depression on the pregnant woman's decision-making capacity. When the fetus is previable, recommendations concerning the disposition and prenatal diagnosis of the pregnancy should be nondirective, whereas strong treatment recommendations are justifiable if the pregnant woman has decided to continue her pregnancy and is severely depressed. After viability, directive counseling for fetal benefit is ethically justified. The guidelines focus on preventive ethics strategies to enhance the decision-making capacity of the depressed pregnant patient.


A 26-week, placebo- and pioglitazone-controlled, dose-ranging study of rivoglitazone, a novel thiazolidinedione for the treatment of type 2 diabetes.
To examine the efficacy and general safety of rivoglitazone, a novel thiazolidinedione, as a treatment for type 2 diabetes in a dose-ranging study over a period of up to 6 months. A 26-week, randomized, double-blind, double-dummy, placebo- and active comparator (pioglitazone 45 mg)-controlled study designed to evaluate the efficacy and safety of once-daily rivoglitazone 1, 2, or 3 mg in subjects with type 2 diabetes. The study was conducted in adults with type 2 diabetes (glycated hemoglobin [HbA(1c)] >or=7.0% and <10.5%) who were either naïve to prior antidiabetes drug treatment or discontinued pre-study antidiabetes medications and were switched to study medication. A total of 441 subjects were randomized, using an equal allocation schedule to one of five treatment arms, including placebo. The primary efficacy measurement was the change in HbA(1c) from baseline to week 26 in the intent-to-treat population (last observation carried forward), for drug treatments minus placebo (placebo-subtracted). ClinicalTrials.gov Identifier NCT00143520. The incidence of early discontinuations was >50%, with most cases being related to a lack of efficacy (highest on placebo) or adverse experiences (highest on rivoglitazone 3 mg). Rivoglitazone 1, 2, and 3 mg and pioglitazone 45 mg were more effective than placebo in reducing HbA(1c) from baseline to week 26 (placebo-subtracted change from baseline: -0.55% [p = 0.0034], -0.99% [p < 0.0001], -1.10% [p < 0.0001], and -0.59% [p = 0.0016], respectively). In general, all treatments were safe. The most common drug-related adverse events reported with rivoglitazone were peripheral edema and weight gain; incidences increased with dose and were higher with rivoglitazone 2 and 3 mg than with pioglitazone or rivoglitazone 1 mg. Rivoglitazone is a potent thiazolidinedione agent with demonstrated glycemic benefits over a 6-month period in subjects with type 2 diabetes. Once-daily doses of 1, 2, and 3 mg rivoglitazone demonstrated HbA(1c) reduction similar or superior to those observed for pioglitazone 45 mg. Limitations in generalizing from this study include a modest sample size and a high rate of discontinuation prior to the last scheduled visit.


Heat extraction of animal plasma in preparation for endotoxin testing with the limulus amebocyte lysate test.
A heat-extraction procedure for endotoxin extraction from animal plasma has been developed for use with the limulus amebocyte lysate test. The procedure is simple to use, is accurate, and has shown good sensitivity with blood from several animal species.


Post-learning micro- and macro-structural neuroplasticity changes with time and sleep.
Neuroplasticity refers to the fact that our brain can partially modify both structure and function to adequately respond to novel environmental stimulations. Neuroplasticity mechanisms are not only operating during the acquisition of novel information (i.e., online) but also during the offline periods that take place after the end of the actual learning episode. Structural brain changes as a consequence of learning have been consistently demonstrated on the long term using non-invasive neuroimaging methods, but short-term changes remained more elusive. Fortunately, the swift development of advanced MR methods over the last decade now allows tracking fine-grained cerebral changes on short timescales beyond gross volumetric modifications stretching over several days or weeks. Besides a mere effect of time, post-learning sleep mechanisms have been shown to play an important role in memory consolidation and promote long-lasting changes in neural networks. Sleep was shown to contribute to structural modifications over weeks of prolonged training, but studies evidencing more rapid post-training sleep structural effects linked to memory consolidation are still scarce in human. On the other hand, animal studies convincingly show how sleep might modulate synaptic microstructure. We aim here at reviewing the literature establishing a link between different types of training/learning and the resulting structural changes, with an emphasis on the role of post-training sleep and time in tuning these modifications. Open questions are raised such as the role of post-learning sleep in macrostructural changes, the links between different MR structural measurement-related modifications and the underlying microstructural brain processes, and bidirectional influences between structural and functional brain changes.


Positive surgical margins at radical prostatectomy in the United States: Institutional variations and predictive factors.
Positive surgical margins (PSMs) are associated with treatment failure after radical prostatectomy (RP) for patients with prostate cancer (CaP). We investigated institutional variations in PSM after RP, as well as clinical and demographic factors predicting PSM. Patients undergoing RP for clinically localized CaP were identified in the National Cancer Database in 2010 to 2013 and clinicodemographics were recorded. Treating institution was defined as academic (AMC) or nonacademic medical centers (nAMC). The primary outcome was the PSM rate. Multivariable logistic regression and propensity matching with inverse probability treatment weighing were used to both compare outcomes between AMC and nAMC and to identify predictors of PSM following RP. A total of 167,260 patients met our inclusion criteria. PSM rate was significantly lower in patients treated at AMC (13,435, 18.9%) compared with 22,145 (23.0%) in those treated at nAMC (P < 0.01). The difference between PSM rate in AMC and nAMC was more pronounced in lower volume centers while it was not significant in higher volume centers. On multivariable analysis, age, race, prostate-specific antigen (PSA), biopsy Gleason score, comorbidity profile, insurance type, income, and treatment facility were significantly associated with PSM rate. PSM rates appear to be lower at AMC and higher volume facilities, which can potentially reflect institutional differences in surgical quality. In addition, we identified several socioeconomic and demographic factors that contribute to the likelihood of PSM following RP for localized CaP, suggesting potential systematic variation in the quality of surgical care. The cause of this variation warrants further investigation and evaluation.


GM1 antibodies in post-polio syndrome and previous paralytic polio.
We studied the relationship between post-polio syndrome (PPS) and GM1 antibodies, since such antibodies have been associated with PPS and motor neuron disorders. Sera from 144 patients with previous poliomyelitis (105 paralytic, 22 nonparalytic and 17 PPS), 60 with previous Guillain-Barré syndrome, 44 with amyotrophic lateral sclerosis (ALS) and 22 healthy blood donors were analyzed with ELISA for GM1 IgM, IgG and IgA antibodies. GM1 antibodies were present in 14% of the PPS patients, but the prevalence did not differ significantly from that of the other groups. Our study does not support the hypothesis that GM1 antibodies are involved in the pathogenesis of PPS.


Five-year experience with the 'Sheba' model of comprehensive orthogeriatric care for elderly hip fracture patients.
The Sheba model of orthogerioatric medicine is a unique model of in-hospital care for elderly hip fractured patients, based upon the concept that a hip fracture represents a geriatric, rather than an orthopedic disease. The nature and feasibility of such a comprehensive orthogeriatric unit, taking care of all surgical, medical and rehabilitation needs, in a single geriatric-based setting (rather than orthopedic-based), were questioned. The aim of the study is to describe the results of its operation during a five-year period. A retrospective charts analysis of consecutive older patients with hip fractures, admitted from the emergency unit directly to the orthogeriatric unit of a department of geriatric medicine. A total number of 592 patients were admitted. Mean age of patients was 83.2 years, mostly women. A total of 538 (91%) were treated surgically. Delay to surgery was 3.6 +/- 2.9 days. A total of 65.6% were suitable for rehabilitation, and had a mean Functional Independence Measure (FIM) gain of 22.3 +/- 7.9. Mean total hospital length of stay was 29.9 days and 68.7% of patients returned to their previous living residence. Rates of major complications (4.1%) and in-hospital mortality (3.2%, equivalent to 30 days mortality) were low. Treatment within this unit was associated with low rates of major morbidity and mortality, short stay and acceptable functional outcomes. The data provide clinical evidence supporting the implementation of this model of comprehensive orthogeriatric care, being a practical, applicable and feasible service for elderly hip fractured patients, and covering the various needs of these patients. The present model of organization could also help in skillful use of economic resources, facilitating effective treatment strategies.


Immunohistochemical detection of blood-retinal barrier breakdown in streptozotocin-diabetic rats.
Immunohistochemical staining for albumin (69 kDa) and fibrinogen (340 kDa), as markers of blood-retinal barrier (BRB) breakdown of the retinas of streptozotocin-treated diabetic rats, was performed. The number of rats with BRB breakdown was three of nine at 6 months, four of seven at 12 months, and three of three at 18 months. Extravasation of albumin from the retinal vessels was detected in the retinas of rats maintained for 6, 12, and 18 months, while extravasation of fibrinogen was detected only in the retinas of rats maintained for 18 months. These findings suggested that the duration of diabetes has an influence on BRB breakdown and that each substance in the blood starts to permeate the vascular wall individually.


Revisit ligand-receptor interaction at the human vasopressin V2 receptor: A kinetic perspective.
The vasopressin V2 receptor belongs to the superfamily of G protein-coupled receptors (GPCRs) and is a potential drug target for water balance disorders such as polycystic kidney disease. Traditionally, the discovery of novel agents for the vasopressin V2 receptor has been guided by evaluating their receptor affinity, largely ignoring the binding kinetics. However, the latter is receiving increasing attention in the drug research community and has been proved to be a more complete descriptor of the dynamic process of ligand-receptor interaction. Herein we aim to revisit the molecular basis of ligand-vasopressin V2 receptor interaction from the less-investigated kinetic perspective. A homogenous time-resolved fluorescence resonance energy transfer (TR-FRET) assay was set up and optimized, which enabled accurate kinetic profiling of unlabeled vasopressin V2 receptor ligands. Receptor occupancy profiles of two representative antagonists with distinct target residence time were simulated. Their functional effects were further explored in cAMP assays. Our results showed that the antagonist with longer receptor residence time (lixivaptan) displayed sustained target occupancy than the antagonist with shorter receptor residence time (mozavaptan). In accordance, lixivaptan displayed insurmountable antagonism and wash-resistant inhibitory effect on the cellular cAMP level, while not so for mozavaptan. Together, our data provide evidence that binding kinetics, next to their affinity, offers additional information for the dynamic process of ligand-receptor interaction. Hopefully, this study may lead to more kinetics-directed medicinal chemistry efforts and aid the design and discovery of different-in-class of vasopressin V2 receptor ligands for clinical applications.


Role of chronic infection and inflammation in the gastrointestinal tract in the etiology and pathogenesis of idiopathic parkinsonism. Part 2: response of facets of clinical idiopathic parkinsonism to Helicobacter pylori eradication. A randomized, double-blind, placebo-controlled efficacy study.
Links between etiology/pathogenesis of neuropsychiatric disease and infection are increasingly recognized. Proof-of-principle that infection contributes to idiopathic parkinsonism. Randomized, double-blind, placebo-controlled efficacy study of proven Helicobacter pylori eradication on the time course of facets of parkinsonism. Intervention was 1 week's triple eradication therapy/placebos. Routine deblinding at 1 year (those still infected received open-active), with follow-up to 5 years post-eradication. Primary outcome was mean stride length at free-walking speed, sample size 56 for a difference, active vs. placebo, of 3/4 (between-subject standard deviation). Recruitment of subjects with idiopathic parkinsonism and H. pylori infection was stopped at 31, because of marked deterioration with eradication failure. Interim analysis was made in the 20 who had reached deblinding, seven of whom were receiving antiparkinsonian medication (long-t(1/2), evenly spaced) which remained unchanged. Improvement in stride-length, on active (n = 9) vs. placebo (11), exceeded size of effect on which the sample size was calculated when analyzed on intention-to-treat basis (p = .02), and on protocol analysis of six weekly assessments, including (p = .02) and excluding (p = .05) those on antiparkinsonian medication. Active eradication (blind or open) failed in 4/20, in whom B-lymphocyte count was lower. Their mean time course was: for stride-length, -243 (95% CI -427, -60) vs. 45 (-10, 100) mm/year in the remainder (p = .001); for the ratio, torque to extend to flex relaxed arm, 349 (146, 718) vs. 58 (27, 96)%/ year (p < .001); and for independently rated, visual-analog scale of stance-walk videos (worst-best per individual identical with 0-100 mm), -64 vs. -3 mm from anterior and -50 vs. 11 lateral (p = .004 and .02). Interim analysis points to a direct or surrogate (not necessarily unique) role of a particular infection in the pathogenesis of parkinsonism. With eradication failure, bolus release of antigen from killed bacteria could aggravate an effect of ongoing infection.


[Comparison of enzyme activity in two insect cell lines: Anthera eucalypti and Malacosoma disstria (Lepidoptera)].
A new micromethod has been used to compare the enzymic profiles of two cell lines of Lepidoptera (Antheraea eucalypti and Malacosoma disstria). Differences are observed on alkaline phosphatase, on two aminopeptidases, on alpha and beta galactosidases and on alpha mannosidase. The whole intracellular activity of the enzymes revealed is detected without any previous treatment of the cells.


Heavy and light chains all at once: A new immunofluorescence technique to evaluate monoclonal immunoglobulin deposits.
Tools to identify monoclonal Ig deposits within tissue specimens include immunofluorescence (IF) staining on frozen tissue for Ig heavy chains and light chains, pronase IF to unmask monoclonal Ig deposits not seen by IF staining on frozen tissue, and IF staining for IgG subclasses (IgG1-IgG4). In this issue of Kidney International, a novel diagnostic tool is introduced: IF staining for conformational epitopes at the junction of the Ig heavy chains and light chains. This technique has the potential to significantly enhance our ability to evaluate apparent monoclonal forms of renal disease.


A signal transducer and activator of transcription 6 haplotype influences the regulation of serum IgE levels.
Because of its central role in the IL-4/IL-13 pathway, the intracellular signaling molecule signal transducer and activator of transcription 6 ( STAT6 ) may be crucial for IgE production in asthma and allergy. We analyzed the association between polymorphisms in the STAT6 gene and the regulation of serum IgE levels. Methods In a population of 1120 German schoolchildren (age 9-11 years), we genotyped 6 previously identified polymorphisms spanning the STAT6 gene by using the matrix-assisted laser desorption ionization-time of flight mass spectrometry method. Haplotypes were estimated and population-derived IgE percentiles (50% IgE > 60 IU/mL, 66% IgE > 115 IU/mL, and 90% IgE > 457 IU/mL) were modeled as outcome variables in haplotype-trend regression analysis. Polymorphisms located in intron 2 (C2892T) and the 3' untranslated region (T12888C) significantly and consistently contributed to elevated total serum IgE levels. One STAT6 haplotype showed increased odds ratios of 1.58 (95% CI, 1.08-2.32; P = .020), 1.82 (95% CI, 1.19-2.77; P = .006), and 3.92 (95% CI, 1.93-7.96; P = .0002) for elevated IgE levels at percentiles 50%, 66%, and 90%, respectively. Because C2892T is located within a nuclear factor kappaB transcription factor binding site, a functional role of this polymorphism is very likely. The data indicate that within the IL-4/IL-13 pathway, genetic variants in the STAT6 gene significantly contribute to the regulation of serum IgE levels.


Ocular findings in the facioauriculovertebral sequence (Goldenhar-Gorlin syndrome).
We reviewed the ocular findings in 57 consecutive patients with the facioauriculovertebral sequence (Goldenhar-Gorlin syndrome). Epibulbar choristomas were detected in 18 cases (32%), a much lower occurrence than reported previously. Various motility disorders (11 cases, 19%), blepharoptosis or narrow palpebral fissures (seven cases, 12%), eyelid colobomas (six cases, 11%), and lacrimal drainage system anomalies (six cases, 11%) were more frequent than previously noted. These ocular findings were more common in the patients with epibulbar choristomas. Of the various features of the Goldenhar-Gorlin syndrome (skin tags, microtia, hemifacial microsomia, and vertebral anomalies), only skin tags correlated positively with the laterality of epibulbar choristomas. Preauricular and facial tags represent choristomas, explaining their association with epibulbar choristomas and the laterality they share.


Extra meetings: a tool for decisions and therapy.
An Adolescent Unit uses the tool of any member of staff or patient group having the right to call a meeting. The development of this idea, anxieties about it, its usefulness and examples are presented. The meetings are used for communication, support or decisions and are often in themselves the vehicles for change.


Soft tissue angiomatosis: another PIK3CA-related disorder.
Angiomatosis of soft tissue (AST) is a rare, high-flow, intramuscular vascular anomaly. In the context of PTEN hamartoma tumour syndrome (PHTS), this AST is referred to as PTEN hamartoma of soft tissue. Given that AST is observed in patients with no history of PHTS, we hypothesised that non-syndromic AST arises as a consequence of a somatic mutation. Thirteen patients with histologically confirmed AST were retrospectively studied. Details of the patients' personal and family medical histories and symptoms were retrieved from their medical records. The histological analyses were reviewed and a tissue sample was used for genetic testing. Somatic mutations in the PIK3CA gene (p.Glu542Lys; p.Glu545Lys; p.His1047Arg) were identified in the tissue samples from seven patients, all of whom had unremarkable medical histories and had presented with a single lesion located in the lower limb. Five pathogenic variations in the PTEN gene (mutations: p.Lys263Arg; c.1026+2T>A; p.Ala126Thr; p.Leu108Arg; deletion, log ratio -0.55) were identified in the lesions of four patients; two of the latter had multifocal lesions. All four patients displayed macrocephaly, three boys presented with penile freckles, but none had a family history of PHTS. There were no histological differences between the PIK3CA and PTEN groups. AST can be related to either PTEN or PIK3CA mutations and may be multifocal in PHTS. AST appears to be a manifestation of PHTS that occurs in early childhood. The patient's medical history and clinical presentation should prompt the physician to perform specific genetic testing.


Comorbidities complicating heart failure: changes over the last 15 years.
Management of comorbidities represents a critical step in optimal treatment of heart failure (HF) patients. However, minimal attention has been paid whether comorbidity burden and their prognostic value changes over time. Therefore, we examined the association between comorbidities and clinical outcomes in HF patients between 2002 and 2017. The 2002-HF cohort consisted of patients from The Coordinating Study Evaluating Outcomes of Advising and Counseling in Heart Failure (COACH) trial (n = 1,032). The 2017-HF cohort were outpatient HF patients enrolled after hospitalization for HF in a tertiary referral academic hospital (n = 382). Kaplan meier and cox regression analyses were used to assess the association of comorbidities with HF hospitalization and all-cause mortality. Patients from the 2017-cohort were more likely to be classified as HF with preserved ejection fraction (24 vs 15%, p < 0.001), compared to patients from the 2002-cohort. Comorbidity burden was comparable between both cohorts (mean of 3.9 comorbidities per patient) and substantially increased with age. Higher comorbidity burden was significantly associated with a comparable increased risk for HF hospitalization and all-cause mortality (HR 1.12 [1.02-1.22] and HR 1.18 [1.05-1.32]), in the 2002- and 2017-cohort respectively. When assessing individual comorbidities, obesity yielded a statistically higher prognostic effect on outcome in the 2017-cohort compared to the 2002-HF cohort (p for interaction 0.026). Despite major advances in HF treatment over the past decades, comorbidity burden remains high in HF and influences outcome to a large extent. Obesity emerges as a prominent comorbidity, and efforts should be made for prevention and treatment. Created with BioRender.com.


Red Blood Cell Transfusion.
Red blood cell (RBC) transfusions are necessary to increase a patient's oxygen carrying capacity. The optimal transfusion trigger remains elusive, but a restrictive transfusion trigger of 7 g/dL has been shown in studies to reduce RBC transfusions without adversely affecting patient outcomes. Patient blood management programs have been shown effective at reducing RBC transfusions. Hemoglobin-based oxygen carriers and induced pluripotent stem cell derived RBCs are being developed to help mitigate RBC shortages and RBC transfusion limitations. Numerous challenges still exist that need to be overcome before they can have widespread clinical use.


Rapid diagnosis of type III group B streptococcal meningitis by latex particle agglutination.
A latex particle agglutination assay was developed to detect type III group B streptococcal antigen in cerebrospinal fluid. Agglutination was observed in each of 12 initial and 54% of 26 subsequent CSF specimens obtained a mean of 53 hours after the institution of antimicrobial therapy. Latex agglutination was more sensitive than countercurrent immunoelectrophoresis for the detection of type III group B streptococcal antigen in CSF from neonates and young infants with meningitis.


Cyclic AMP, the reluctant messenger in plants.
The possible role of cyclic AMP (cAMP) in plants has been an area of controversy for nearly 20 years: although cAMP and putative components of its synthesis, degradation and site of action can be demonstrated, there has been no clear identification of a signal transduction pathway dependent upon cAMP in plants. However, stronger evidence is accumulating for its possible role in stress signalling.


F-wave velocity in motor neurone disease.
The F-wave velocity in the central segment (axilla to spinal cord) was studied employing the "collison technique" described by Kimura (1974), and compared with the conduction velocity obtained with the usual methods. In 25 normal subjects the F-wave velocity increased proceeding proximally, reaching the maximum values in the central tract (64.86 +/- 2.23 m/sec in ulnar nerve). In 11 patients affected by motor neurone disease and 11 patients affected by amyotrophic lateral sclerosis the F-wave velocity decreased significantly proceeding proximally and the minimum values were found in the central tract (52.51 +/- 2.15 m/sec in MND and 48.64 +/- 5.60 m/sec in ALS). We therefore suggest the use of F-wave velocity as a more complete element for precise localization of the lesion in the central segment when the motoneurone is primarily involved.


Can Rouvière's lymph nodes in non-malignant subjects be identified with MRI?
The lateral retropharyngeal lymph nodes lie between the carotid artery and prevertebral muscles. These are most obvious anterior to the arch of C1, but can be seen to the level of the soft palate. The uppermost-positioning nodes anterior to the atlas are called as the nodes of Rouvière. Introduction of CT and MR has provided us the chance to detect them. In order to find out the frequency of identifying them in normal subjects, I examined axial MR images which had been taken for the last 3 years. A total of 90 patients (86 adults and 4 children) with a variety of diseases except for malignancies were selected. All 4 children showed Rouvière's nodes bilaterally, while only 5 of 86 adults (5.8%) depicted them. The lymph nodes were identified as isointense masses as nasopharyngeal lymphoid tissues (adenoids), when presented, with the size ranged from 4 to 13 mm. The nodes with a diameter of 5 mm or more were easily identified particularly with T2-weighted images. The benign reactive adenopathy appeared indistinguishable from that demonstrated in patients with malignant tumors in the head and neck.


Recombinant herpes vector-mediated analgesia in a primate model of hyperalgesia.
Some chronic pain syndromes are characterized by episodes of intense burning and hyperalgesia in localized areas of skin. These sensations are thought to be mediated, at least in part, by the activity of damaged, unmyelinated C nociceptors. These phenomena were modeled by assaying responses of macaques to thermal and chemical stimuli that produced periodic activation and sensitization of C nociceptors. Upon validation of this method, a recombinant herpes simplex vector encoding human preproenkephalin was topically applied to the dorsal surface of the feet of the monkeys. Immunohistochemistry and radioimmunoassay revealed that enkephalin peptides were being produced in releasable pools in sensory neurons innervating the treated skin area. Behavioral responses evoked by periodic sensitization and activation of C nociceptors innervating the vector-treated skin area revealed a substantial and long-lasting (at least 20 weeks) antihyperalgesic and analgesic effect limited to the areas to which the virus was applied. This approach may be a viable means of treating localized cutaneous burning pain and hyperalgesia.


Magnetic resonance imaging of the kinked fetal brain stem: a sign of severe dysgenesis.
Magnetic resonance imaging (MRI) allows visualization of the fetal brain stem in a manner not previously possible. A "kinked" brain stem is a sign of severe neurodysgenesis. The purpose of this series was to describe cases of a kinked brain stem detected on prenatal MRI and to discuss the possible genetic and syndromic etiologies. Seven cases of a kinked brain stem on fetal MRI (gestational age range, 18-34 weeks) were reviewed and correlated with other clinical, genetic, imaging, and autopsy findings. In all cases, there was associated cerebellar hypogenesis. Additional findings were ventriculomegaly (4 cases), cerebral hypogenesis (3 cases), microcephaly (4 cases), schizencephaly (1 case), cephalocele (1 case), hypogenesis of the corpus callosum (1 case), and hydrocephalus (1 case). In 2 cases, prenatal sonography misidentified the kinked brain stem as the cerebellum. A kinked brain stem is an indicator of severe neurodysgenesis arising early in gestation. Magnetic resonance imaging provides the necessary resolution to detect this sign and delineate any associated anomalies in utero to assist with further genetic evaluation, management, and counseling.


Impacts of COVID-19 outbreak on the spillovers between US and Chinese stock sectors.
This paper examines the impacts of COVID-19 outbreak on the spillover between ten US and Chinese equity sectors. We use Copula and Conditional Value at Risk approaches. The results show evidence of asymmetric tail dependence during the COVID-19 outbreak with the exception of the Utilities sector, where a symmetric tail dependence is found. Moreover, we find time-varying bidirectional asymmetric risk spillovers from the US to China and vice versa. The risk spillover is higher from the US to China before COVID-19 and from China to the US during COVD-19 spread, which is significantly intensified between March 2020 and April 2020.


Nationwide Measles and Rubella Outbreaks in South Sudan, 2019.
South Sudan confirmed a measles outbreak in December 2018. An investigation was conducted to assess underlying causes of the outbreak. Vaccination coverage and measles surveillance data were analyzed. A suspected measles case had fever, maculopapular rash, and cough or conjunctivitis. A confirmed measles case had generalized maculopapular rash lasting >3 days, a temperature >38°C, and cough or conjunctivitis; or serologic confirmation (anti-measles immunoglobin M [IgM] antibody detection) in serum samples collected ≤30 days from rash onset. A confirmed rubella case tested measles IgM-negative and rubella IgM-positive. Nationwide, 3727 suspected measles cases were reported in 2019. Seventy-five percent of all suspected measles cases were in children aged <5 years. Thirty-six percent of patients with suspected measles were admitted to the hospital, and 36 measles-related deaths were reported. Among cases, 922 (25%) were tested for measles; of these, 317 (34%) were measles IgM-positive. Among cases that tested measles IgM-negative, 149 (33%) were rubella IgM-positive. Immunization coverage for 1 dose of measles-containing vaccine (MCV) varied by state, ranging from 6% to 67%. Measles and rubella remain public health problems in South Sudan. To reduce measles incidence, South Sudan needs to achieve >95% coverage with 2 doses of MCV.


Induction of new ADAM related proteins from treated human Chang-liver cells.
Chang-liver cells is a cell line generated from human liver tissue, which is often used in scientific research. ADAMs are a family of proteins that consist of multi-domains, possess multi-functions and play a central role in normal or abnormal physiological conditions, such as regeneration and tumorigenesis. To investigate the expression and functional alteration of the ADAMs or ADAM related proteins in Chang-liver cells, this cell line was treated with heat stress, modified Hanks solution containing ATP or other buffers. Our results showed that the treatment with Hanks solution containing ATP induces Chang-liver cells to express new ADAM related proteins. To analyze these new ADAM related proteins, a cDNA expression library was constructed for the treated Chang-liver cells. A series of positive clones were obtained through immunoscreening with an ADAMs common antibody. A new ADAM related protein possessing alkaline protease activity was confirmed in these clones.


Insulin and insulin-like growth factor-I (IGF-I) binding in fish red muscle: regulation by high insulin levels.
Insulin and IGF-I binding to semi-purified red muscle receptors was characterized in brown trout, Salmo trutta and the common carp. Cyprinus carpio. The yield of glycoprotein obtained after semipurification of receptors with WGA-agarose affinity chromatography in microgram g-1 initial tissue was 210.6 +/- 21 micrograms g-1 in trout and 108.5 +/- 2.5 micrograms g-1 in carp. IGF-I specific binding (4.72 +/- 0.64%/10 micrograms glycoprotein) was 4-5-times higher than insulin binding (1.04 +/- 0.12%/10 micrograms glycoprotein) in trout red muscle. This difference in binding was due to a higher number and a greater affinity of the IGF-I (Kd, 0.21 +/- 0.03 nM) compared with the insulin (Kd, 0.67 +/- 0.06 nM) receptors in this tissue. Carp red muscle IGF-I binding (9.14 +/- 0.55%/10 micrograms glycoprotein) surpassed insulin binding (2.59 +/- 0.094%/10 micrograms glycoprotein) mainly because of a greater affinity of the IGF-I (Kd, 0.092 +/- 0.027 nM) compared with the insulin (Kd, 0.1515 +/- 0.0285 nM) receptor. IGF-I and insulin binding in carp red muscle were higher than in trout, as a consequence of a higher affinity of carp red muscle receptors. Arginine injection provoked acute hyperinsulinemia in both trout (23.3 +/- 1.01 ng ml-1) and carp (24.3 +/- 1.34 ng ml-1. Specific binding of insulin and IGF-I to the red muscle decreased 4 h after injection. In trout, a decrease of insulin and IGF-I binding of 47.0% and 63.3%, respectively was observed compared with controls, in carp, these values were 44.0% and 45.0%. The number of insulin and IGF-I receptors decreased (42-55%) but affinities did not change suggesting that receptor down-regulation is a consequence of high insulin levels.


Partial purification and characterization of cysteine proteinases from various developmental stages of Paragonimus westermani.
1. During development of Paragonimus westermani, larvae develop during migration within the host, and adult worms feed on pulmonary tissues, causing significant pathology in the mammalian host. In this report acidic extracts of various developmental stages (metacercariae and worms at one, two and three months of development) were examined for cysteine proteinase activity. 2. A soluble thiol-dependent proteinase activity with a native molecular weight of approximately 20,000 was isolated and partially purified. 3. The enzymes purified from the various developmental stages of the parasite had maximal activity at acidic pH and showed inhibitor susceptibilities similar to the vertebrate acidic cysteine proteinases. 4. Enzymatic activity was stable at pH 5.0 for at least two days when stored at 4 degrees C. 5. It is suggested that these enzymes may be involved in the nutrition of these parasites and/or during penetration and lysis of the tissues.


Magnetic Relaxation Dynamics of a Binuclear Diluted Er(III)/Y(III) Compound Influenced by Lattice Solvent.
It is crucial to investigate the slow relaxation mechanisms of binuclear ErIII -based single-molecule magnets (SMMs) and explore strategies for optimizing their magnetic properties. Herein, a doped compound, [Y1.75 Er0.25 (thd)4 Pc] ⋅ 2C6 H6 (YEr ⋅ 2C6 H6 , Hthd=2,2,6,6-tetramethylheptanedione, H2 Pc=phthalocyanine), was synthesized by doping the paramagnetic erbium(III) compound Er2 ⋅ 2C6 H6 in the diamagnetic yttrium(III) matrix Y2 ⋅ 2C6 H6 . The doping effect was studied using SQUID magnetization measurements. The results suggest that magnetic-site dilution improves the magnetic property from a fast relaxation of the pure ErIII compound to a typical SMM relaxation process of the doped sample. In this binuclear system, the dominant single-ion relaxation is entangled with the neighboring ErIII ion through the intramolecular ErIII ⋅⋅⋅ErIII interaction, which plays an important role in suppressing the quantum tunneling of the magnetization (QTM) process. Furthermore, the influence of lattice solvents on single-ion relaxation was studied. By releasing the benzene molecules, compound YEr ⋅ 2C6 H6 can be successfully transformed to a desolvated sample YEr accompanied by structural alteration and improved SMM performance.