Immunologically Induced and Elicited Local Resistance to Staphylococcus aureus.
Allergy characterized by delayed hypersensitivity was induced in populations of mice by injection, respectively, of Staphylococcus aureus and of tubercle bacilli. Eliciting doses of staphylococcal antigen or of old tuberculin antigen were injected subcutaneously into the nape of the neck of samples of these mice. A challenge dose of S. aureus was injected into the site of the eliciting injection, and the subsequent survival curves of the infecting staphylococci were determined by plate counts. Survival of the challenge staphylococci was significantly reduced only when the eliciting antigen was homologous with the inducing antigen. Thus induction and elicitation were specific, but the local resistance was nonspecifically effective against staphylococci.


Unmasking the anti-La/SSB response in sera from patients with Sjogren's syndrome by specific blocking of anti-idiotypic antibodies to La/SSB antigenic determinants.
Autoantigen La/SSB is molecular target of humoral autoimmunity in patients with primary Sjogren's Syndrome (pSS) and systemic lupus erythematosus (SLE). In this study, we investigated the existence and possible influence of anti-idiotypic response to anti-La/SSB antibodies. Synthetic peptide analogs (pep) of the major antigenic determinants of La/SSB (289-308 aa and 349-364 aa) were prepared. Based on "molecular recognition" theory, complementary peptides (cpep), derived by anti-parallel readings of the noncoding strand of La/SSB DNA encoding for its antigenic determinants, were constructed. Sera from 150 patients with anti-La/SSB antibodies, 30 patients without anti-La/SSB antibodies, and 42 normal individuals were tested against all four peptides. F(ab')(2) fragments from anti-peptide IgG were prepared and F(ab')(2) - IgG interactions were evaluated using a specific anti-idiotypic ELISA. All four peptides were recognized by anti-La positive sera (83% and 51% for pep and cpep 349-364 and 51% and 28% for pep and cpep289-308, respectively). Anti-cpep F(ab')(2 )bound to a common idiotype (Id) located within or spatially close to the antigen combining site of anti La/SSB (anti-pep) antibodies. Homologous and cross-inhibition experiments further confirmed this relation. The anti-idiotypic antibodies inhibited the anti-La/SSB antibody binding to recombinant La/SSB by 91%. To overcome the anti-idiotypic interference in anti-La/SSB detection, a specific assay was developed. Sera were heated for dissociation of Id-anti-Id complexes, anti-Id antibodies blocked with cpep, and anti-La/SSB reactivity was recovered. Application of this method to anti-Ro positive-anti-La/SSB "negative" sera showed that all anti-Ro/SSA positive autoimmune sera also possess anti-La/SSB antibodies. This reaction was not observed in 14 anti-Ro negative- anti-Sm/RNP positive sera from patients with SLE. Autoimmune sera from patients with pSS and SLE contain anti-idiotypic antibodies targeting a common anti-La/SSB idiotype. These antibodies can be detected using complementary peptides of La/SSB epitopes. The antiidiotypic antibodies mask the anti-La/SSB response. Hidden anti-La/SSB antibodies can be released and detected using complementary epitope analogs.


Synthesis of carbon nanotubes using SBA-15 as a template by the reaction of methane and carbon dioxide.
Multiwalled carbon nanotubes (CNTs) were synthesized using Ni loaded mesoporous SBA-15 as a template by reaction of methane and carbon dioxide. The influences of nickel content on the selectivity and crystallinity of CNTs were investigated. It can be seen that the crooked CNTs with a diameter varied from 9.9, 12.5 to 36.5 nm with creasing content of Ni from 5, 15, and 30 wt%/SBA-15. A uniform diameter and good quality CNTs were obtained in our system.


Synthesis and Properties of Ethene-Bridged Terthiophenes.
A method for the facile synthesis of ethene-bridged terthiophenes (EBTTs) in two steps has been developed. The first step is a double Sonogashira coupling between 3',4'-dibromo-2,2':5',2″-terthiophene and terminal alkynes to give dialkynylated terthiophenes, and the second step is a cyclization reaction to afford EBTTs. The fundamental physical properties of EBTTs were also studied.


Clostridium Bacteria and Autism Spectrum Conditions: A Systematic Review and Hypothetical Contribution of Environmental Glyphosate Levels.
Nowadays, there seems to be a consensus about the multifactorial nature of autism spectrum disorders (ASD). The literature provides hypotheses dealing with numerous environmental factors and genes accounting for the apparently higher prevalence of this condition. Researchers have shown evidence regarding the impact of gut bacteria on neurological outcomes, altering behavior and potentially affecting the onset and/or severity of psychiatric disorders. Pesticides and agrotoxics are also included among this long list of ASD-related environmental stressors. Of note, ingestion of glyphosate (GLY), a broad-spectrum systemic herbicide, can reduce beneficial bacteria in the gastrointestinal tract microbiota without exerting any effects on the Clostridium population, which is highly resistant to this herbicide. In the present study, (i) we performed a systematic review to evaluate the relationship between Clostridium bacteria and the probability of developing and/or aggravating autism among children. For that purpose, electronic searches were performed on Medline/PubMed and Scielo databases for identification of relevant studies published in English up to December 2017. Two independent researches selected the studies and analyzed the data. The results of the present systematic review demonstrate an interrelation between Clostridium bacteria colonization of the intestinal tract and autism. Finally, (ii) we also hypothesize about how environmental GLY levels may deleteriously influence the gut-brain axis by boosting the growth of Clostridium bacteria in autistic toddlers.


Parallel gold enhancement of quantum dots 565/655 for double-labelling correlative light and electron microscopy on human autopsied samples.
Cadmium selenide quantum dots (QDs) are fluorescent and electron-dense nanoparticles. When used as reporter of immunolabeling, this dual visibility is essential for direct comparison of its fluorescent signals on light microscopy (LM) and their ultrastructrual counterparts on electron microscopy (EM) as correlative light and electron microscopy (CLEM). To facilitate EM recognition, QDs on EM grid were gold enhanced, which increased their size and electron density. On histological sections as well, gold-enhanced QDs, used as a reporter of immunolabeling, were easily recognized on EM. Because target structures are visible on bright field microscopy, gold enhancement facilitated trimming the target structures into final EM sections. Furthermore, gold enhancement of rod-shaped QD655 on EM grid was accentuated on their tips while spherical QD565 was gold-enhanced as sphere in contrast. This EM distinction was evident on histological sections where QD565 (green fluorescence) and QD655 (red fluorescence) were used as a reporter pair for double immunolabeling. Double-labeled immuno-fluorescent images, initially captured before EM processing, are now compared with their respective immuno EM counterparts. Specific labeling of each epitope was corroborated by mutual comparison between LM and EM. Although fluoronanogold may be a candidate reporter partner with QDs for gold-enhanced, double-labeling CLEM, its limited penetration into fixed tissue hampers universal use for thick histological sections. Gold-enhancement of QD immunolabeling, now expanded to double-labeling CLEM for human brain samples, will pave the way to translate molecular events into ultrastructural morphopathogenesis in situ.


Case Report: 18F-PSMA PET/CT Scan in Castration Resistant Prostate Cancer With Aggressive Neuroendocrine Differentiation.
The development of a neuroendocrine phenotype as a mechanism of resistance to hormonal treatment is observed in up to 20% of advanced prostate cancer patients. High grade neuroendocrine prostate cancer (NEPC) is associated to poor prognosis and the therapeutic armamentarium is restricted to platinum-based chemotherapy. Prostate-specific membrane antigen (PSMA)-based positron emission tomography (PET)/computed tomography (CT) imaging has recently emerged as a potential new standard for the staging of prostate cancer and PSMA-based radioligand therapy (RLT) as a therapeutic option in advanced metastatic castration resistant prostate cancer (mCRPC). PSMA-based theranostic is not currently applied in the staging and treatment of NEPC since PSMA expression on neuroendocrine differentiated cells was shown to be lost. In this case series, we present 3 consecutive mCRPC patients with histologically proven high grade neuroendocrine differentiation who underwent PSMA-PET/CT and surprisingly showed high tracer uptake. This observation stimulates further research on the use of PSMA-based theranostic in the management of NEPC.


Blocking matrix metalloproteinase-mediated syndecan-4 shedding restores the endothelial glycocalyx and glomerular filtration barrier function in early diabetic kidney disease.
The endothelial glycocalyx is a key component of the glomerular filtration barrier. We have shown that matrix metalloproteinase (MMP)-mediated syndecan 4 shedding is a mechanism of glomerular endothelial glycocalyx damage in vitro, resulting in increased albumin permeability. Here we sought to determine whether this mechanism is important in early diabetic kidney disease, by studying streptozotocin-induced type 1 diabetes in DBA2/J mice. Diabetic mice were albuminuric, had increased glomerular albumin permeability and endothelial glycocalyx damage. Syndecan 4 mRNA expression was found to be upregulated in isolated glomeruli and in flow cytometry-sorted glomerular endothelial cells. In contrast, glomerular endothelial luminal surface syndecan 4 and Marasmium oreades agglutinin lectin labelling measurements were reduced in the diabetic mice. Similarly, syndecan 4 protein expression was significantly decreased in isolated glomeruli but increased in plasma and urine, suggesting syndecan 4 shedding. Mmp-2, 9 and 14 mRNA expression were upregulated in isolated glomeruli, suggesting a possible mechanism of glycocalyx damage and albuminuria. We therefore characterised in detail the activity of MMP-2 and 9 and found significant increases in kidney cortex, plasma and urine. Treatment with MMP-2/9 inhibitor I for 21 days, started six weeks after diabetes induction, restored endothelial glycocalyx depth and coverage and attenuated diabetes-induced albuminuria and reduced glomerular albumin permeability. MMP inhibitor treatment significantly attenuated glomerular endothelial and plasma syndecan 4 shedding and inhibited plasma MMP activity. Thus, our studies confirm the importance of MMPs in endothelial glycocalyx damage and albuminuria in early diabetes and demonstrate that this pathway is amenable to therapeutic intervention. Hence, treatments targeted at glycocalyx protection by MMP inhibition may be of benefit in diabetic kidney disease.


The Cellular Composition of Bovine Coccygeal Intervertebral Discs: A Comprehensive Single-Cell RNAseq Analysis.
Intervertebral disc (IVD) degeneration and its medical consequences is still one of the leading causes of morbidity worldwide. To support potential regenerative treatments for degenerated IVDs, we sought to deconvolute the cell composition of the nucleus pulposus (NP) and the annulus fibrosus (AF) of bovine intervertebral discs. Bovine calf tails have been extensively used in intervertebral disc research as a readily available source of NP and AF material from healthy and young IVDs. We used single-cell RNA sequencing (scRNAseq) coupled to bulk RNA sequencing (RNAseq) to unravel the cell populations in these two structures and analyze developmental changes across the rostrocaudal axis. By integrating the scRNAseq data with the bulk RNAseq data to stabilize the clustering results of our study, we identified 27 NP structure/tissue specific genes and 24 AF structure/tissue specific genes. From our scRNAseq results, we could deconvolute the heterogeneous cell populations in both the NP and the AF. In the NP, we detected a notochordal-like cell cluster and a progenitor stem cell cluster. In the AF, we detected a stem cell-like cluster, a cluster with a predominantly fibroblast-like phenotype and a potential endothelial progenitor cluster. Taken together, our results illustrate the cell phenotypic complexity of the AF and NP in the young bovine IVDs.


Resource use, efficiency, and outcome prediction in pediatric intensive care of trauma patients.
To study the impact of trauma patients on Pediatric Intensive Care Units (PICUs), 164 trauma patients' data from 1,075 consecutive admissions to five PICUs were reviewed. Resource use (Therapeutic Intervention Scoring System [TISS] points) and mortality risks (Physiologic Stability Index [PSI] and Pediatric Risk of Mortality [PRISM] scores) were obtained daily for all patients. Trauma patients constituted 15.2% of all PICU patients, and used 14.9% of patient care days and 14.5% of TISS points. Efficiency of trauma patient care was 75% overall compared to 79% overall for nontrauma patients (p less than 0.001). Trauma patient mortality was 9.8%. Tests for goodness of fit showed the PSI and PRISM scores to be accurate outcome predictors for trauma patients (PSI: chi 2 (4) = 2.852, p greater than 0.50; PRISM: chi 2 (4) = 1.216, p greater than 0.50). Trauma patients are a minority of PICU patients and deaths. Their resource use is proportional to their numbers, although less efficient than for nontrauma patients. PSI and PRISM are accurate mortality risk predictors for trauma patients.


Virtual Reality in Neurointervention.
Virtual reality (VR) allows users to experience realistic, immersive 3D virtual environments with the depth perception and binocular field of view of real 3D settings. Newer VR technology has now allowed for interaction with 3D objects within these virtual environments through the use of VR controllers. This technical note describes our preliminary experience with VR as an adjunct tool to traditional angiographic imaging in the preprocedural workup of a patient with a complex pseudoaneurysm. Angiographic MRI data was imported and segmented to create 3D meshes of bilateral carotid vasculature. The 3D meshes were then projected into VR space, allowing the operator to inspect the carotid vasculature using a 3D VR headset as well as interact with the pseudoaneurysm (handling, rotation, magnification, and sectioning) using two VR controllers. 3D segmentation of a complex pseudoaneurysm in the distal cervical segment of the right internal carotid artery was successfully performed and projected into VR. Conventional and VR visualization modes were equally effective in identifying and classifying the pathology. VR visualization allowed the operators to manipulate the dataset to achieve a greater understanding of the anatomy of the parent vessel, the angioarchitecture of the pseudoaneurysm, and the surface contours of all visualized structures. This preliminary study demonstrates the feasibility of utilizing VR for preprocedural evaluation in patients with anatomically complex neurovascular disorders. This novel visualization approach may serve as a valuable adjunct tool in deciding patient-specific treatment plans and selection of devices prior to intervention.


"Gnothi Seauton": Leveraging the Host Response to Improve Influenza Virus Vaccine Efficacy.
Vaccination against the seasonal influenza virus is the best way to prevent infection. Nevertheless, vaccine efficacy remains far from optimal especially in high-risk populations such as the elderly. Recent technological advancements have facilitated rapid and precise identification of the B and T cell epitopes that are targets for protective responses. While these discoveries have undoubtedly brought the field closer to "universal" influenza virus vaccines, choosing the correct antigen is only one piece of the equation. Achieving efficacy and durability requires a detailed understanding of the diverse host factors and pathways that are required for attaining optimal responses. Sequencing technologies, systems biology, and immunological studies have recently advanced our understanding of the diverse aspects of the host response required for vaccine efficacy. In this paper, we review the critical role of the host response in determining efficacious responses and discuss the gaps in knowledge that will need to be addressed if the field is to be successful in developing new and more effective influenza virus vaccines.


Small-Molecule Inhibitors of Haemophilus influenzae IgA1 Protease.
Newly identified, nontypable Haemophilus influenzae (H. influenza) strains represent a serious threat to global health. Due to the increasing prevalence of antibiotic resistance, virulence factors have emerged as potential therapeutic targets that would be less likely to promote resistance. IgA1 proteases are secreted virulence factors of many Gram-negative human pathogens. These enzymes play important roles in tissue invasion as well as evasion of the immune response, yet there has been limited work on pharmacological inhibitors. Here, we report the discovery of the first small molecule, nonpeptidic inhibitors of H. influenzae IgA1 proteases. We screened over 47 000 compounds in a biochemical assay using recombinant protease and identified a hit compound with micromolar potency. Preliminary structure-activity relationships produced additional inhibitors, two of which showed improved inhibition and selectivity for IgA protease over other serine proteases. We further showed dose-dependent inhibition against four different IgA1 protease variants collected from clinical isolates. These data support further development of IgA protease inhibitors as potential therapeutics for antibiotic-resistant H. influenza strains. The newly discovered inhibitors also represent valuable probes for exploring the roles of these proteases in bacterial colonization, invasion, and infection of mucosal tissues.


[Decrease in the sensitivity to the anti-ischemic effect of propranolol and prospects for correcting it in patients with stable angina pectoris].
To study incidence of low sensitivity to an antiischemic effect of propranolol and feasibility of its correction with a metabolic drug--trimetazidine. Paired treadmill and bicycle exercise tests were made until depression of segment ST > 1 mm and a typical angina episode. The trial included 147 men with ischemic heart disease, stable angina pectoris (functional class II-III). The antiischemic effect of propranolol single doses 40 or 80 mg were assessed in 117 patients. Single doses of propranolol 40 mg, trimetazidine 20 mg and their combination were examined for an antiischemic effect in 30 patients. The absence of the above effect of propranolol was stated in 20 patients who participated in a double blind, randomised, placebo-controlled study with conduction of 2-week courses of regular administration of propranolol in a dose 120 mg/day, trimetazidine 60 mg/day and their combination. Echo-CG was made initially and in the end of each course. Propranolol's antiischemic effect of a single dose 40 mg was not found in 45.3% patients, 40-80 mg--in 21%. Among 20 patients without effect of the single propranolol dose, an increment of the threshold load made up 20.7 +/- 15.7 s, after intake of trimetazidine 16.3 +/- 18.6 s. The combination of these drugs significantly increases the increment of the threshold load duration to 90.8 +/- 80.4 s. The same picture was observed in the course treatment. The above increment in the course administration of propranolol was 46.3 +/- 15.3 s, of trimetazidine 22.8 +/- 20.2 s, of their combination 122.7 +/- 21.8 s (p = 0.02). In the absence of propranolol effect, echo-CG registered deterioration of disorder of left ventricular diastolic function. 10 patients with effect of the single propranolol dose this deterioration was not observed in combined use of propranolol and trimetazidine. The antiischemic effect of propranolol in a single dose 40 mg was not recorded in about half of the examined anginal patients. Combined use of propranolol and trimetazidine in cases with no propranolol effect provides a synergetic effect both in single and course administration.


The change of susceptibility of Streptococcus pneumoniae strains isolated from pediatric patients at Asahikawa Kosei Hospital between 2011 and 2015.
The susceptibility of 1578 Streptococcus pneumoniae strains isolated from pediatric patients at Asahikawa Kosei Hospital between 2011 and 2015 was tested to penicillin G (PCG), cefotaxime (CTX), ceftriaxone (CTRX), cefditoren (CDTR), meropenem (MEPM), erythromycin (EM) and levofloxacin (LVFX). Although no significant differences were observed, the percentage of strains with a minimal inhibitory concentration (MIC) of PCG of <0.1pg/mL increased from 55.5% (2011) to 64.0% (2015), whereas that of strains with MIC of ≥2μg/mL decreased from 14.8% to 9.5%. From 2011 to 2015, the percentage of strains with MIC ≤0.12ug/mL increased from 18.9% to 28.9% for CTX, from 20.5% to 30.2% for CTRX, from 29.2% to 40.9% for CDTR, and from 69.6% to 80.6% for MEPM. EM-resistant strains with MIC ≥22μg/mL accounted for as much as approximately 90% each year. One LVFX-resistant strain with MIC 8pg/mL has been detected each year since 2013.


Connections of Barrington's nucleus to the sympathetic nervous system in rats.
Barrington's nucleus (BN) has been considered a pontine center related exclusively to the control of pelvic parasympathetic activity. The present study demonstrates an anatomical linkage between BN and autonomic outflow to visceral targets innervated exclusively by the sympathetic division of the autonomic nervous system. Temporal analysis of infection after injection of pseudorabies virus (PRV), a retrograde transynaptic tracer, into two sympathetically innervated organs, the spleen and the kidney, revealed the presence of infected neurons in BN at early post-inoculation survival intervals. Immunohistochemical localization of PRV after spleen injections showed that a small subpopulation of BN neurons became labeled in a time frame coincident with the appearance of infected neurons in other brain regions known to project to sympathetic preganglionic neurons (SPNs) in the thoracic spinal cord; a larger number of infected neurons appeared in BN at intermediate intervals after PRV injections into the spleen or kidney. Coinjection of the retrograde tracer Fluoro-Gold i.p. and PRV into the spleen demonstrated that parasympathetic preganglionic neurons in the caudal medulla or lumbo-sacral spinal cord were not infected, indicating that infected BN neurons were not infected via a parasympathetic route. Thus, BN neurons become infected after PRV injections into the spleen or kidney either directly through BN projections to SPNs, or secondarily via BN projections to infected pre-preganglionic neurons. These results demonstrate an anatomical linkage, either direct or indirect, between BN and sympathetic activity. Because BN receives numerous inputs from diverse brain regions, the relation of BN with both branches of the autonomic nervous system suggests that this nucleus might play a role in the integration of supraspinal inputs relevant to the central coordination of sympathetic and parasympathetic activity.


Effects of additives on the rheological properties and injectability of a calcium phosphate bone substitute material.
An injectable calcium phosphate bone substitute material has been prepared by mixing amorphous calcium phosphate (ACP) and dicalcium phosphate dihydrate (DCPD) for use in noninvasive surgery, and the influence of additives, such as disodium hydrogen phosphate, polyethylene glycol (PEG), glycerin, and citric acid, on the rheological properties and injectability of the ACP + DCPD cement system have been studied in this work. Novel approach of thixotropy measurement has been used to characterize the stability of the pastes. The results show that the injectability and the setting time can be augmented by the addition of disodium phosphate solution to the paste but reduced by the addition of PEG 200, glycerin, or citric acid to the paste. This study suggests that the injectability and the setting time of the ACP + DCPD bone substitute material can be balanced, and the injectable calcium phosphate bone substitute material with satisfied fluidity and injectability for clinical operation can be prepared by optimizing the additives and their concentrations, according to different clinical requirements.


Understanding Na₂Ti₃O₇ as an ultra-low voltage anode material for a Na-ion battery.
An in-depth understanding of Na2Ti3O7 as a Na-ion battery anode is reported. The battery performance is enhanced by carbon coating, due to increased electronic conductivity and reduced solid electrolyte interphase formation. Ti(4+) reduction upon discharge is demonstrated using in situ XAS. The self-relaxation behaviour of the fully intercalated phase is revealed.


DAZ gene copies: evidence of Y chromosome evolution.
The DAZ gene, a contributing factor in infertility, lies on the human Y chromosome's AZFc region, whose deletion is a common cause of spermatogenic failure. Y chromosome binary polymorphisms on the non-recombining Y (NRY) region, believed to be a single occurrence on an evolutionary scale, were typed in a sample of fertile and infertile men with known DAZ backgrounds. The Y single-nucleotide polymorphisms (Y-SNPs) with low mutation rates are currently well characterized and permit the construction of a unique phylogeny of haplogroups. DAZ haplotypes were defined using single-nucleotide variant (SNV)/sequence tagged-site (STS) markers to distinguish between the four copies of the gene. The variation of 10 Y chromosome short tandem repeat (STRs) was used to determine the coalescence age of DAZ haplotypes in a comparable time frame similar to that of SNP haplogroups. An association between DAZ haplotypes and Y chromosome haplogroups was found, and our data show that the DAZ gene is not under selective constraints and its evolution depends only on the mutation rate. The same variants were common to fertile and infertile men, although partial DAZ deletions occurred only in infertile men, suggesting that those should only be used as a tool for infertility diagnosis when analysed in combination with haplogroup determinations.


Shrinkage of spray-freeze-dried microparticles of pure protein for ballistic injection by manipulation of freeze-drying cycle.
Spray-freeze-drying was used to produce shrivelled, partially-collapsed microparticles of pure proteins that may be suitable for use in a ballistic injector. Various modifications of the freeze drying cycle were examined for their effects on collapse of the pure protein microparticles. The use of annealing at a shelf temperature of up to +10°C resulted in no visible particle shrinkage. This was because of the high Tg' of the pure protein. Inclusion of trehalose or sucrose led to particle shrinkage because of the plasticizing effects of the disaccharides on the protein. Only by extending the duration of primary drying from 240 to 2745min at shelf temperatures in the range -12 to -8°C were shrivelled, wrinkled particles of bSA and bCA of reduced porosity obtained. Manipulation of the freeze-drying cycle used for SFD can therefore be used to modify particle morphology and increase particle density.


Prevalence and risk factors for intimate partner violence and indigenous women: A scoping review.
This study aims to map intimate partner violence evidence among indigenous women and explore the prevalence, social and systemic factors contributing to this occurrence. This is a scoping review following the steps recommended by the JBI. We searched the MEDLINE/PubMed®, Web of Science™, Embase, CINAHL and LILACS databases on March 2023. Studies that addressed the intimate partner violence topic among indigenous women and risk factors, without time and language limitations, were included. Detailed information was extracted, standardized by JBI. Twenty studies of different designs were included, all published in English, between 2004 and 2022. A high intimate partner violence prevalence among indigenous women was identified, associated with a great diversity of risk factors. The great diversity of identified factors associated with its occurrence shows the complexity of this problem and the vulnerability of indigenous women.


Hemorrhagic shock 3 days after catheterization from the axillary vein.
A 72-year-old woman presented pulmonary embolism. Continuous intravenous administration of heparin was controlled with values of activated clotting time targeted from 150 to 180 s. On the sixth intensive care unit (ICU) day, a central vein (CV) catheter was inserted through the right axillary vein. On the ninth ICU day, her blood pressure dropped and her right breast was obviously larger than the left. Chest computed tomography showed a large hematoma under the greater pectoral muscle. CV catheterization under anticoagulant therapy is risky for bleeding, but catheterization of the internal jugular vein rarely leads to hemorrhagic shock, even if it causes airway obstruction. The axillary vein is in a compartment filled with loose tissue. As there is no structure to cover the bleeding site, the hematoma would expand from the lateral region of the thorax to near the fifth or sixth rib, to which greater and smaller pectoral muscles are attached. Ultrasound-guided catheterization from the axillary vein is introduced as a new and promising alternative to that from the subclavian vein because of its safety, but we should be conservative about applying the axillary approach to patients with anticoagulant therapy, especially in case of an unskilled operator, and be aware of the possibility of late-onset bleeding.


Facility characteristics as independent prognostic factors of nursing home-acquired pneumonia.
Recently, the incidence of nursing home-acquired pneumonia (NHAP) has been increasing and is now the leading cause of death among nursing home residents. This study was performed to identify risk factors associated with NHAP mortality, focusing on facility characteristics. Data on all patients ≥ 70 years of age admitted with newly diagnosed pneumonia were reviewed. To compare the quality of care in nursing facilities, the following three groups were defined: patients who acquired pneumonia in the community, care homes, and care hospitals. In these patients, 90-day mortality was compared. Survival analyses were performed in 282 patients with pneumonia. In the analyses, 90-day mortality was higher in patients in care homes (12.2%, 40.3%, and 19.6% in community, care homes, and care hospitals, respectively). Among the 118 NHAP patients, residence in a care home, structural lung diseases, treatment with inappropriate antimicrobial agents for accompanying infections, and a high pneumonia severity index score were risk factors associated with higher 90-day mortality. However, infection by potentially drug-resistant pathogens was not important. Unfavorable institutional factors in care homes are important prognostic factors for NHAP.


Direct and indirect effects of the fungicide azoxystrobin in outdoor brackish water microcosms.
The effects of the strobilurin fungicide azoxystrobin were studied in brackish water microcosms, with natural plankton communities and sediment. Two experiments were conducted: Experiment 1 (nominal conc. 0, 15 and 60 microg/L, 24-L outdoor microcosms for 21 days) and a second, follow-up, Experiment 2 (nominal conc. 0, 3, 7.5, 15 microg/L, 4-L indoor microcosms for 12 days). The microcosms represent a simplified brackish water community found in shallow semi-enclosed coastal areas in agricultural districts in the Baltic Sea region. Measured water concentrations of the fungicide (Experiment 1) were, on average, 83 and 62% of nominal concentrations directly after application, and 25 and 30% after 21 days, for the low and high dose treatments, respectively, corresponding to mean DT50-values of 15.1 and 25.8 days, for low and high dose treatments, respectively. In Experiment 1, direct toxic effects on calanoid copepods at both test concentrations were observed. Similarly, in Experiment 2, the copepod abundance was significantly reduced at all tested concentrations. There were also significant secondary effects on zooplankton and phytoplankton community structure, standing stocks and primary production. Very few ecotoxicological studies have investigated effects of plant protection products on Baltic organisms in general and effects on community structure and function specifically. Our results show that azoxystrobin is toxic to brackish water copepods at considerably lower concentrations than previously reported from single species tests on freshwater crustaceans, and that direct toxic effects on this ecologically important group may lead to cascade effects altering lower food webs and ecosystem functioning.


[Monitoring of pregnancy in HIV seropositive women].
The management of pregnancy in a seropositive woman implies awareness of the effects of the disease on pregnancy and, inversely, of the pregnancy on HIV infection. It is important to be aware of the risk of materno-fetal transmission, as well as of the recent positive results of therapeutic trials of AZT during pregnancy regarding the prevention of such transmission. This quite stereotyped management approach is relatively simple, both clinically and regarding laboratory investigations, and in particular when the patient is at an asymptomatic stage of the disease. Obstetric management is, for the present, the same as in normal women. It is important to stress the need for specialised management of the newborn infant and of taking advantage of the postpartum period to ensure future effective contraception.


Microsurgical Breast Reconstruction in Patients with Disorders of Hemostasis: Perioperative Risks and Management.
Surgical and technological advances have resulted in the widespread adoption of microsurgical breast reconstruction. Many comorbidities that potentially might impair vasculature and wound healing are no longer considered contraindications for these procedures. However, some uncertainty still prevails regarding the perioperative management of patients with disorders of hemostasis. The authors combined a literature review with a retrospective chart review of patients with disorders of hemostasis who had undergone microsurgical breast reconstruction at the senior author's (J.F.) center between 2015 to 2020. Several disorders associated with thrombotic and/or hemorrhagic complications were identified, and a standardized risk assessment and management strategy was developed in cooperation with a hematologist. Overall, 10 studies were identified comprising 29 patients who had a defined disorder of hemostasis and underwent microsurgical breast reconstruction. Seventeen microsurgical breast reconstructions were performed on 11 patients at the senior author's (J.F.) center. High factor VIII levels, heterozygous factor V Leiden, and heterozygous prothrombin mutation G20210A were the most common genetic or mixed genetic/acquired thrombophilic conditions. As expected, hereditary antithrombin, protein C, or protein S deficiencies were rare. Among hemorrhagic disorders, thrombocytopenia, platelet dysfunction, and von Willebrand disease or low von Willebrand factor levels were those factors most frequently associated with increased perioperative bleeding. Patients should be screened for elevated risk of thrombosis or bleeding before undergoing microsurgical breast reconstruction, and positive screening should prompt a complete hematologic evaluation. Interdisciplinary management of these disorders with a hematologist is essential to minimize risks and to obtain optimal reconstructive results. Risk, IV.


A new species of Leptobrachella (Anura: Megophryidae) Smith, 1925 from Wuling Mountains in Hunan Province, China.
A new species of Leptobrachella, Leptobrachella wulingensis sp. nov. is described based on specimens collected from the Wuling mountains in Hunan Province, China. The new species can be distinguished from its congeners by a combination of having a SVL body size range of 24.5-32.8 mm in four adult males and 29.9-38.5 mm in three adult females; dorsal surface brown to reddish brown with indistinct markings; ventral surface creamy white, often with pale brown speckling on chest and margins; flanks with small to moderate black spots; skin on dorsum shagreened with sparse large warts, sometimes with short longitudinal ridges; toes with rudimentary webbing and narrow lateral fringes; dermal ridges under toes interrupted at the articulations; and iris bicolored with a bright orange or golden upper half, fading to silver in the lower half. Uncorrected sequence divergence between L. wulingensis sp. nov. and homologous 16S rRNA sequences available for all known species in the genus are ≥ 2.3%-2.9%.


Using surface-bound rubidium ions for protein phasing.
Rubidium is a monovalent metal that can be used as a counterion in protein solutions. X-ray anomalous scattering from rubidium ions bound to the protein surface was used for phasing of the crystal structure of the hsp60 apical domain from Thermus thermophilus. Multiple-wavelength anomalous dispersion (MAD) data were collected from a crystal obtained from a solution containing 0.2 M rubidium salt. One molecule of protein (147 amino acids) binds one well ordered and one poorly ordered Rb atom. Phases calculated with the program SHARP were sufficient for automatic tracing and side-chain assignment using the program ARP/wARP. The data show that bound rubidium ions can be used to determine protein structures and to study the interaction of monovalent metal ions with proteins and other macromolecules.


Current therapies in the management of systolic and diastolic dysfunction.
Heart failure, especially caused by systolic dysfunction, is the most common cause of hospitalization in the elderly population and the annual expenditure required for its management is at least $10 billion. The critical care nurse can play an active role in recognizing the differences between systolic and diastolic dysfunction, and teaching the patient and family that improper management or underuse of therapies can lead to disease progression.


"Kango-net": A community website connecting citizens and nursing personnel.
The "Kango-net" website (http://www.kango-net.jp/), aims at promoting communication and collaboration between citizens and nursing personnel. Through this website, we provide useful healthcare information for the citizens.


Functional outcomes of nonunion scaphoid fracture treated by pronator quadratus pedicled bone graft.
Between 1998 and 2007, a pronator quadratus pedicled bone graft was performed for 45 patients of ununited scaphoid fracture. One of them had bilateral ununited scaphoid fracture. There were 29 men and 16 women with a median age at operation of 24 (16-32) years. The affected side was the right side (dominant hand) in 32 patients whereas 13 patients had fracture of the nondominant left side. There had been 32 proximal pseudoarthrosis (through or proximal to the junction of the proximal and middle thirds of the bone) and 14 of the middle third of the scaphoid. The original fractures were caused by motor cycle accidents in 23 patients, falling on outstretched hand in 15 patients, and sport injuries in the remaining 7 patients. Surgery was indicated from 5 months to 6 years after injury (average 43 months) because of complaints of pain on heavy work. The fracture has been missed at the initial examination in 23 patients whereas cast immobilization was done for 6 weeks and 3 months in 15 and 7 cases, respectively, that had failed to result in union. There were no preoperative osteoarthritic changes, but in 25 cases, there were avascular necrosis of the proximal fragment of the scaphoid. Forty-three patients showed radiographic union after an average of 14 weeks (12-16 weeks). One patient had dislodgement of the graft and refused to do it again. The average range of movement of wrist improved after operation. Taken as a percentage of the normal range, dorsiflexion increased from 69% to 80%, palmar flexion from 66% to 76%, radial deviation from 45% to 70%, and ulnar deviation from 67% to 84%. Grip strength improved from 82% to 92% of normal. All the patients have been able to return to their former activities with no pain.


[Diagnostic value of F wave changes in patients with Charcot-Marie-Tooth1A and chronic inflammatory demyelinating polyneuropathy].
To analyze and compare the characteristics and causes of F wave changes in patients with Charcot-Marie-Tooth1A (CMT1A) and chronic inflammatory demyelinating polyneuropathy (CIDP). Thirty patients with CMT1A and 30 patients with CIDP were enrolled in Peking University Third Hospital from January 2012 to December 2018. Their clinical data, electrophysiological data(nerve conduction velocity, F wave and H reflex) and neurological function scores were recorded. Some patients underwent magnetic resonance imaging of brachial plexus and lumbar plexus, and the results were analyzed and compared. The average motor conduction velocity (MCV) of median nerve was (21.10±10.60) m/s in CMT1A and (31.52±12.46) m/s in CIDP. There was a significant difference between the two groups (t=-6.75, P < 0.001). About 43.3% (13/30) of the patients with CMT1A did not elicit F wave in ulnar nerve, which was significantly higher than that of the patients with CIDP (4/30, 13.3%), χ2=6.65, P=0.010. Among the patients who could elicit F wave, the latency of F wave in CMT1A group was (52.40±17.56) ms and that in CIDP group was (42.20±12.73) ms. There was a significant difference between the two groups (t=2.96, P=0.006). The occurrence rate of F wave in CMT1A group was 34.6%±39%, and that in CIDP group was 70.7%±15.2%. There was a significant difference between the two groups (t=-5.13, P < 0.001). The MCV of median nerve in a patient with anti neurofascin 155 (NF155) was 23.22 m/s, the latency of F wave was 62.9-70.7 ms, and the occurrence rate was 85%-95%. The proportion of brachial plexus and lumbar plexus thickening in CMT1A was 83.3% (5/6) and 85.7% (6/7), respectively. The proportion of brachial plexus and lumbar plexus thickening in the CIDP patients was only 25.0% (1/4, 2/8). The nerve roots of brachial plexus and lumbar plexus were significantly thickened in a patient with anti NF155 antibody. The prolonged latency of F wave in patients with CMT1A reflects the homogenous changes in both proximal and distal peripheral nerves, which can be used as a method to differentiate the CIDP patients characterized by focal demyelinating pathology. Moreover, attention should be paid to differentiate it from the peripheral neuropathy caused by anti NF155 CIDP. Although F wave is often used as an indicator of proximal nerve injury, motor neuron excitability, anterior horn cells, and motor nerve myelin sheath lesions can affect its latency and occurrence rate. F wave abnormalities need to be comprehensively analyzed in combination with the etiology, other electrophysiological results, and MRI imaging.


Clinical pharmacokinetics of tegaserod, a serotonin 5-HT(4) receptor partial agonist with promotile activity.
Tegaserod, a selective serotonin (5-hydroxytryptamine; 5-HT) 5-HT(4) receptor partial agonist, is indicated in patients with irritable bowel syndrome (IBS) who identify abdominal pain or discomfort and constipation as their predominant symptoms. Tegaserod at dosages of 1 to 12 mg/day exerts pharmacodynamic actions in the upper and the lower gastrointestinal tract, accelerating small bowel and colonic transit in patients with IBS. Tegaserod is rapidly absorbed following oral administration; peak plasma concentrations (C(max)) are reached after approximately 1 hour. Absolute bioavailability is about 10% under fasted conditions. Food reduces the bioavailability of tegaserod by 40 to 65% and the C(max) by 20 to 40%. Systemic exposure to tegaserod is not significantly altered at neutral gastric pH compared with the fasted state (pH 2). Tegaserod is approximately 98% bound to plasma proteins, primarily to alpha(1)-acid glycoprotein, and has a volume of distribution at steady-state of 368 +/- 223L. Tegaserod is metabolised mainly via two pathways. The first is a presystemic acid-catalysed hydrolysis in the stomach followed by oxidation and conjugation which produces the main metabolite of tegaserod, 5-methoxyindole-3-carboxylic acid glucuronide (M 29.0). This metabolite has negligible affinity for 5-HT(4) receptors and is devoid of promotile activity. The second is direct glucuronidation which leads to generation of three isomeric N-glucuronides. The plasma clearance of tegaserod is 77 +/- 15 L/h, with an estimated terminal half-life of 11 +/- 5 hours following intravenous administration. Approximately two-thirds of the orally administered dose of tegaserod is excreted unchanged in faeces, with the remainder excreted in urine, primarily as M 29.0. The pharmacokinetics of tegaserod are dose-proportional over the range 2 to 12mg given twice daily for 5 days, with no relevant accumulation. The pharmacokinetics of tegaserod in patients with IBS are comparable to those in healthy individuals, and similar between men and women. No dosage adjustment is required in elderly patients or those with mild to moderate hepatic or renal impairment. Tegaserod should not be used in patients with severe hepatic or renal impairment. No clinically relevant drug-drug interactions with tegaserod have been identified. In vivo drug-drug interaction studies with theophylline [a cytochrome P450 (CYP) 1A2 prototype substrate], dextromethorphan (a CYP2D6 prototype substrate), digoxin, warfarin and oral contraceptives have indicated no clinically relevant interactions and no requirement for dosage adjustment.


Development and evaluation of an in vivo mouse model for studying myocutaneous flap microcirculation and viability before and after suturing or stapling.
A model was developed in albino hairless mice to study microcirculation and viability of dorsal distally based myocutaneous flaps. The efficacy of this model was tested in 120 mice by evaluating the effects of excessive crimping and tension attributed to Proximate or Signet staples or to simple or mattress nylon sutures. Microhemodynamics were assessed using computer-assisted intravital videomicroscopic and electro-optical methods. Volumetric rates of blood flow were calculated within terminal arterioles from measurements of internal diameter and mean centerline cellular velocity. The viability was determined on day 5 by measuring the areas of necrosis (mm2) along the cut edges of these flaps. In 80 mice, flaps were elevated and examined at 0 h and then again at 24 or 48 h. There were 40 mice in each of these disturbed groups. In a third group of 40 mice, flaps were raised at 0 h without videomicroscopic examination at 0, 24, or 48 h (undisturbed group). All flaps were stapled or sutured to the original donor site with one of the four methods of closure. The results of this study indicate that sutures produce the highest incidence of necrosis at 5 days when compared to staples in the undisturbed groups of mice. However, no significant differences in necrosis were observed when flaps were disturbed at 48 h despite videomicroscopic evidence of depressed blood flow along their cut edges. In contrast, results at 24 h were equivocal and statistically not significant. These data suggest that the phenomenon of delay and/or flap recirculation following removal and reapproximation of sutures or staples drastically improves perfusion and viability of disturbed flaps.(ABSTRACT TRUNCATED AT 250 WORDS)


[Early and mid-term results of all arterial graft coronary artery bypass grafting using bilateral internal thoracic and radial arterial conduits].
From March 1996 to May 2000, 41 patients [age 39-78 (mean 63.5 +/- 8.8) years, 90.2% male] underwent all arterial multiple coronary artery bypass grafting (CABG) using bilateral internal thoracic (BiITA) and radial (RA) arterial conduits. The reason for using RA was that the right gastroepiploic artery (RGEA) was small or occluded on preoperative angiography, a history of upper abdominal surgery or disease, or the right coronary arterial lesion was proximal and mild. The BiITA were used as in situ grafts and the proximal anastomosis of RA was to the ascending aorta in all cases. All patients underwent conventional elective CABG with median sternotomy using cardiopulmonary bypass. The mean number of anastomoses was 3.3 +/- 0.5 branches and complete revascularization rate was 80.5%. Postoperative follow-up averaged 20 months and the longest was 50 months. There was no early death, and overall graft patency 2-3 weeks after surgery was 96.2% (LITA 94.0%, RITA 97.6%, RA 97.6%). Four-year actuarial survival rate was 96.4 +/- 3.5% (1 patient: 9 months, no cardiac death), and cardiac event-free rate after surgery was 89.7 +/- 4.9% [4 patients: percutaneous transluminal coronary angioplasty (PTCA)]. However, once patients were discharged from hospital, cardiac event-free rate was 100%. These excellent results suggest that all arterial graft CABG was satisfactory, and RA can be used as a third suitable arterial bypass conduit, if RGEA cannot be used or is unsuitable for use.


ULTRASONOGRAPHY IN DETERMINING THE RECTAL DIAMETER AND RECTAL WALL THICKNESS IN CHILDREN WITH AND WITHOUT CONSTIPATION: A CASE-CONTROL STUDY.
Ultrasonography has shown to be useful in the diagnosis of constipation. The aim of this study was to compare the rectal diameter and rectal wall thickness in children with and without constipation. Children with the diagnosis of constipation according to Rome III criteria were included in the study. The children underwent transabdominal sonography for the evaluation of rectal diameter and rectal wall thickness. Ultrasonography was performed with a full bladder. Children without constipation who underwent abdominal sonography were assigned to the control group. The rectal diameter was larger in children with constipation than in children without constipation (31.72±9.63 mm vs 19.85±4.37 mm; P=0.001). The rectal wall was thinner in children with constipation than in children without constipation (1.75±0.33 mm vs 1.90±0.22 mm; P=0.032). There was no significant difference between boys and girls with constipation in terms of rectal diameter (31.02±8.57 mm 32.77±11.35 mm; P=0.63). Transabdominal rectal diameter measurement may be useful in the diagnosis of constipation.


Cutting voices. Self-injury in three adolescent girls.
1. Adolescent girls with a trauma history discover that violence, in the form of cutting themselves, heeds a response from others when others do not listen to their speaking voices. 2. Cutting may begin as an effort to communicate psychological distress and a plea for relationship but becomes a developmental pathway to cutting as a form of regulating unbearable affect, indicating the need for early intervention. 3. Adults actively and genuinely listening to girls is a critical component for both prevention and intervention of cutting.


[Hypertrophic cardiomyopathy: a rare cause of vascular dementia. A case report].
Herein, we report a case of a 51 year old man who experienced three ischemic cerebral infarcts in a time of few months. The patient consulted after the third accident. Neurological presentation included pseudobulbar syndrome with a mild cognitive deficit, aphasia, left hemiparesia, hemiasomatognosia and homonymous lateral hemianopsia. Cerebral tomodensitometry and magnetic resonance imaging evidenced large infarcts images involving right middle cerebral artery territory and bilateral borderline zones in the junction of the territories of the middle and posterior cerebral arteries. Ambulatory 24 hours ECG recording (Holter) revealed two hits of non-sustained ventricular tachycardia. Transoesophageal echocardiography conveyed to the diagnosis of hypertrophic cardiomyopathy and displayed the presence of a left auricular thrombus. Anticoagulant therapy and rehabilitation allowed a substantial recovering of the patient's cognitive functions and wasting of the intracardiac thrombus. The clinical features observed in our patient meet the recommended DSM IV diagnosis criteria of vascular dementia, an exceptional complication of HCM. The clinical findings, neuroimagery investigation results, and the chronological link between cerebral attacks and cognitive function deterioration argue for a demential syndrome of vascular origin resulting from multiple embolic infarcts involving medium sized arteries (multi-infarct dementia). The authors emphasize the rarity of such observation. HCM must be considered as a potential cause of embolic stroke and likewise a multi-infarct dementia.


A Systematic Review of the Impact of Dedicated Emergency Surgical Services on Patient Outcomes.
This review aims to assess the impact of implementing dedicated emergency surgical services, in particular acute care surgery, on clinical outcomes. The optimal model for delivering high-quality emergency surgical care remains unknown. Acute Care Surgery (ACS) is a health care model combining emergency general surgery, trauma, and critical care. It has been adopted across the United States in the management of surgical emergencies. A systematic review was performed after PRISMA recommendations using the MEDLINE, Embase, and Psych-Info databases. Studies assessing different care models and institutional factors affecting the delivery of emergency general surgery were included. Twenty-seven studies comprising 744,238 patients were included in this review. In studies comparing ACS with traditional practice, mortality and morbidity were improved. Moreover, time to senior review, delays to operating theater, and financial expenditure were often reduced. The elements of ACS models varied but included senior clinicians present onsite during office hours and dedicated to emergency care while on-call. Referrals were made to specialist centers with primary surgical assessments taking place on surgical admissions units rather than in the emergency department. Twenty-four-hour access to dedicated emergency operating rooms was also described. ACS models as well as centralized units and hospitals with dedicated emergency operating rooms, access to radiology and intensive care facilities (ITU) are all factors associated with improved clinical and financial outcomes in the delivery of emergency general surgery. There is, however, no consensus on the elements that constitute an ideal ACS model and how it can be implemented into current surgical practice.


Usefulness of real-time PCR for lytA, ply, and Spn9802 on plasma samples for the diagnosis of pneumococcal pneumonia.
In the present study, we evaluated rapid real-time PCR assays for ply, Spn9802, and lytA applied to plasma samples for the detection of Streptococcus pneumoniae in patients with community-acquired pneumonia (CAP). In a prospective study of CAP aetiology, an EDTA plasma sample was collected together with blood culture in 92 adult CAP patients and 91 adult controls. Among the 92 CAP patients, lytA PCR was positive in eight (9%), Spn9802 PCR was positive in 11 (12%) and ply PCR was positive in 19 (21%) cases. Of 91 controls, the ply PCR was positive in eight cases (9%), but no positive cases were noted by Spn9802 or lytA PCRs. Ten CAP patients had pneumococcal bacteraemia. Compared to blood culture, PCR for lytA, Spn9802 and ply had sensitivities of 70% (7/10), 60% (6/10) and 70% (7/10), and specificities of 96% (79/82), 94% (77/82) and 85% (70/82) respectively. With blood culture and/or culture of representative sputum, and/or urinary antigen detection, S. pneumoniae was identified in 31 CAP patients. Compared to these tests in combination, PCR for lytA, Spn9802 and ply showed sensitivities of 26% (8/31), 32% (10/31) and 42% (13/31), and specificities of 100% (61/61), 98% (60/61) and 90% (55/61) respectively. We conclude that Spn9802 and lytA PCRs may be useful for the rapid detection of bacteraemic pneumococcal pneumonia, whereas ply PCR is not specific enough for routine use and blood PCR with small plasma volumes is not useful for the detection of nonbacteraemic pneumococcal pneumonia.


The antagonist function of Arabidopsis WRKY53 and ESR/ESP in leaf senescence is modulated by the jasmonic and salicylic acid equilibrium.
Crosstalk between salicylic acid (SA) and jasmonic acid (JA) signaling is well-studied but not during leaf senescence. We found that the senescence-specific WRKY53 transcription factor interacts with the JA-inducible protein EPITHIOSPECIFYING SENESCENCE REGULATOR (ESR/ESP). The expression of these genes is antagonistically regulated in response to JA and SA, respectively, and each negatively influences the other. Leaf senescence is accelerated in ESR knockout plants (ESR-KO) but retarded in ESR overexpressors (ESR-OE), with the reverse true for WRKY53. ESR-OE showed higher resistance than ESR-KO to bacterial and fungal pathogens. However, pathogen resistance was not altered in WRKY53 overexpressors or knockouts (W53-KO), suggesting that ESR has a greater impact on WRKY53 function in senescence than WRKY53 on ESR function in pathogen resistance. ESR inhibits WRKY53 DNA binding in vitro, and their interaction is localized to the nucleus in vivo; however, ESR is exclusively in the cytoplasm in W53-KO cells, indicating that ESR is brought to the nucleus by the interaction. Therefore, ESR has dual functions: as cytoplasmic epithiospecifier and as negative regulator of WRKY53 in the nucleus. These results suggest that WRKY53 and ESR mediate negative crosstalk between pathogen resistance and senescence, which is most likely governed by the JA and SA equilibrium.


Coronin 1A inhibits neurite outgrowth in PC12 cells.
Regenerative response to central nervous system damage in mammals is limited because of inhibitor signals which consist of myelin associated inhibitor proteins and chondroitin sulfate proteoglycans. Inhibitor signals mainly affect cytoskeleton elements which are important for axonal sprouting and neurite outgrowth. Coronin 1A is an actin cytoskeleton associated protein. Coronin 1A shows its effect on actin cytoskeleton through binding to the Arp2/3 complex which is a key nucleator of actin polymerization and regulates its activation on actin cytoskeleton. Coronin 1A-Arp2/3 interaction is regulated by phosphorylation of Coronin 1A from the C and N terminal region. Thus, Coronin 1A-Arp2/3 complex is one of the targets of inhibitory signaling cascades. The aim of this study was to investigate the effect of Coronin 1A on neurite outgrowth in PC12 cells in vitro. The results showed that Coronin 1A is expressed in differentiated PC12 cells and localized along axonal sprouting region of the neurites. Other results showed that overexpression of Coronin 1A in PC12 cells effects neurite outgrowth. Neurite lengths of the Coronin 1A overexpressing PC12 cells were lower than the untransfected (p<0.001) and control transfected (p=0.002) PC12 cells. These results indicate that Coronin 1A has an inhibitory effect on neurite outgrowth in vitro.


High energy fast neutrons from the Harwell variable energy cyclotron. I. Physical characteristics.
A high energy fast neutron beam potentially suitable for radiotherapy was built at the Harwell variable energy cyclotron. The beam line is described and results are given of physical measurements on the fast neutron beams produced by 42 MeV deuterons on thick (4 mm) and thin (2 mm) beryllium targets. With 20 muA beam current the entrance dose rate in a phantom 150 cm from the target was about 130 rad min-1 with the thick target and about 60 rad min-1 with the thin target. Therefore, it is possible to use both the thin target and the relatively large target-skin distance of 150 cm to improve depth dose for radiotherapy or radiobiology. With this arrangement the dose rate decreased to 50% at depths in the phantom of 11.3-15.4 cm, depending on the field size. The use of primarily hydrogenous materials for shielding and collimation provided beam edge definition similar to that of 60Co teletherapy units, and off-axis radiation levels of approximately 1% which compare favorably with 14 MeV deuteron-tritium generators. The copper backing of the thin target became highly radioactive and an alterative material may be preferable. Biologic characteristics of the beam are described in a companion paper.


Association of genetic variants in ATR-CHEK1 and ATM-CHEK2 pathway genes with risk of colorectal cancer in a Chinese population.
The ATR-CHEK1 and ATM-CHEK2 pathway have been confirmed to be related with the DNA damage response (DDR). Many studies have reported that genetic variants in ATR/CHEK1 and ATM/CHEK2 are associated with cancer risk. However, the association between genetic variants in ATR-CHEK1, ATM-CHEK2 pathway genes and colorectal cancer susceptibility is still unknown. In this study, we aim to explore whether these variants are correlated with the risk of colorectal cancer in a Chinese population. A hospital-based case-control study, including 1,121 cases and 1,056 controls was conducted to evaluate the association between eight selected single nucleotide polymorphisms (SNPs) (rs35514263 in ATR; rs492510, rs558351 in CHKE1; rs189037 in ATM; rs2236141, rs5762748, rs2236142 and rs9620817 in CHEK2) in ATR-CHEK1 and ATM-CHEK2 pathways and the risk of colorectal cancer in a Chinese population by using TaqMan method. Individuals with rs189037 A allele were found to have a significantly increased risk of colorectal cancer, compared to those carrying G allele [odds ratio(OR) = 1.23, 95% confidence interval (CI) = 1.02-1.47 in dominant model and OR= 1.14, 95%CI= 1.01-1.29 in additive model]. And this risk is more pronounced in elder people (>69), rectum, early stage and poorly grade. In addition, bioinformatic analysis showed that rs189037 may change the secondary structure. Our results provide the evidence that rs189037 in ATM may increase the susceptibility of colorectal cancer in a Chinese population.


How hopeful is too hopeful? Responding to unreasonably optimistic parents.
Some parents are unreasonably hopeful, insisting on aggressive therapy for their children even when such treatment would cause additional suffering with little or no chance of success. The various sources of and influences upon such hopes are examined, and suggestions are offered about how to help these parents see the situation more realistically. This discussion covers such issues as religious beliefs, confusions about causation and responsibility, concern about how others see us, and the simple tragedy of children who die. The failure to address these hopes undermines parental decision making, leads to unnecessary tragedies, and can result in costly litigation. Communication is an essential part of dealing with unreasonable hopes, but there is also a place for medical futility judgments and limitation contracts. The goal is not to deprive parents of their hope, but to transform it into something that is both valuable and anchored in reality.


Widespread estrogen-dependent repression of micrornas involved in breast tumor cell growth.
Altered expression of microRNAs (miRNA), an abundant class of small nonprotein-coding RNAs that mostly function as negative regulators of protein-coding gene expression, is common in cancer. Here, we analyze the regulation of miRNA expression in response to estrogen, a steroid hormone that is involved in the development and progression of breast carcinomas and that is acting via the estrogen receptors (ER) transcription factors. We set out to thoroughly describe miRNA expression, by using miRNA microarrays and real-time reverse transcription-PCR (RT-PCR) experiments, in various breast tumor cell lines in which estrogen signaling has been induced by 17beta-estradiol (E(2)). We show that the expression of a broad set of miRNAs decreases following E(2) treatment in an ER-dependent manner. We further show that enforced expression of several of the repressed miRNAs reduces E(2)-dependent cell growth, thus linking expression of specific miRNAs with estrogen-dependent cellular response. In addition, a transcriptome analysis revealed that the E(2)-repressed miR-26a and miR-181a regulate many genes associated with cell growth and proliferation, including the progesterone receptor gene, a key actor in estrogen signaling. Strikingly, miRNA expression is also regulated in breast cancers of women who had received antiestrogen neoadjuvant therapy. Overall, our data indicate that the extensive alterations in miRNA regulation upon estrogen signaling pathway play a key role in estrogen-dependent functions and highlight the utility of considering miRNA expression in the understanding of antiestrogen resistance of breast cancer.


Self-efficacy and importance of participation reasons as predictors for prostate cancer screening intention in African American men.
Objective: African American men have higher lifetime risk of developing prostate cancer (PCa), and face more health burdens from this disease due in part to limited participation in cancer screening. Therefore, it is important to study psychosocial factors associated with screening intention in African American men. Guided by social cognitive theory, the current study aims to examine the role of self-efficacy and importance of participation reasons as predictors of PCa screening intention in African American men.Design: This is a primary analysis using data collected from African American men in northeast Ohio and the Southeastern United States. PCa screening intention and self-efficacy were measured by single-item questions. Importance of participation reasons was measured in four domains: psychological, convenience, awareness, and medical. Hierarchical binary logistic regression was used to predict PCa screening intention in African American men.Results: The sample size was 174. The average age was 46.52. Adding self-efficacy and reasons for participation significantly improved prediction for PCa screening intention in African American men (Δχ2 = 55.28, p < .001). The final model had χ2 = 69.63 (p < .001). Higher self-efficacy (OR = 2.56, p < .05), more perceived importance of psychological reasons (OR = 2.42, p < .001) and medical reasons (OR = 1.10, p < .05) were significant predictors. Also, the perceived chance of developing PCa predicted higher odds of PCa screening intention.Conclusions: Enhancing self-efficacy might be an important intervention focus for African American men to improve PCa screening intention. In addition, the findings suggest that African American men intend to have PCa screening because they experience worries or physical symptoms, and unlikely because it is convenient to get screening or recommended by family members and friends. Thus, intervention efforts could focus on enhancing PCa knowledge and informed decision-making about PCa screening among African American men.


A novel NMDA receptor glycine-site partial agonist, GLYX-13, has therapeutic potential for the treatment of autism.
Deficits in social approach behavior, rough-and-tumble play, and speech abnormalities are core features of autism that can be modeled in laboratory rats. Human twin studies show that autism has a strong genetic component, and a recent review has identified 99 genes that are dysregulated in human autism. Bioinformatic analysis of these 99 genes identified the NMDA receptor complex as a significant interaction hub based on protein-protein interactions. The NMDA receptor glycine site partial agonist d-cycloserine has been shown to treat the core symptom of social withdrawal in autistic children. Here, we show that rats selectively bred for low rates of play-induced pro-social ultrasonic vocalizations (USVs) can be used to model certain core symptoms of autism. Low-line animals engage in less social contact time with conspecifics, show lower rates of play induced pro-social USVs, and show an increased proportion of non-frequency modulated (i.e. monotonous) ultrasonic vocalizations, compared to non-selectively bred random-line animals. Gene expression patterns in the low-line animals show significant enrichment in autism-associated genes and the NMDA receptor family was identified as a significant hub. Treatment of low-line animals with the NMDAR glycine site partial agonist GLYX-13 rescued the deficits in play-induced pro-social 50-kHz and reduced monotonous USVs. Thus, the NMDA receptor has been shown to play a functional role in autism, and GLYX-13 shows promise for the treatment of autism. We dedicate this paper to Ole Ivar Lovaas (May 8, 1927-August 2, 2010), a pioneer in the field of autism.


[Neurophysiologic findings in chronic alcohol abuse].
Neurophysiological examinations of 100 long term alcohol dependent patients who were having neuropsychiatric treatment, showed symptoms of polytopic damage of the peripheral and central nervous system. The results show that for recognition of the damage an extensive diagnostic programme must be used.


Continuous multiple vertebral compression fractures in multiple myeloma patient.
Multiple myeloma is a B-cell origin tumor characterized by hypercalcemia, osteolytic bony lesions, and pathologic fractures. Back pain is one of the most common presenting symptoms of multiple myeloma and about 60% of patients have vertebral involvement at the time of diagnosis7). Minimally invasive surgeries such as vertebroplasty and kyphoplasty are effective to relieve pain and improve the quality of life when a compression fracture occurs in multiple myeloma patients. We report a case of continuous multiple compression fractures associated with multiple myeloma. We should check for the possibility of pathologic vertebral fractures resulting from multiple myeloma in non-osteoporotic compression fracture patients, and especially in cases of continuous fracture occurring in relatively non-elderly patients, even though a history of trauma may be present.


Inhibitory effects of neurotoxin β-N-methylamino-L-alanine on fertilization and early development of the sea urchin Lytechinus pictus.
Neurotoxin β-N-methylamino-L-alanine (BMAA) has been widely detected in diverse aquatic organisms and hypothesized as an environmental risk to neurodegenerative diseases in humans. However, the knowledge of its toxicity to marine organisms requires attention. In the present study, embryos and sperm of the sea urchin, Lytechinus pictus, were used to assess the toxicity of BMAA. Effects of BMAA on fertilization and development of sea urchin embryos were measured, and its impacts on efflux transport of sea urchin blastula were also assayed. Results demonstrated that the fertilization and development of embryos were significantly inhibited by high concentrations of BMAA above 300 μg L-1. The EC50 values indicated by active swimming larvae and total larvae numbers at 96 HPF (hours post fertilization) were 165 μg L-1 (1.4 μmol L-1) and 329 μg L-1 (2.8 μmol L-1), respectively. Additionally, sperm exposed to BMAA for 10 min significantly reduced the fertilization ratio of sea urchin eggs. However, the ABC transport activity on the cytomembrane of sea urchin blastula was not inhibited by the presence of BMAA at 50 μg L-1, even up to 500 μg L-1. Abnormal division and developmental malformations occurred at different developmental stages for sea urchin embryos exposed to BMAA at 500 μg L-1. The inhibitory effects of BMAA on sea urchin embryos were reported at the first time in this study, for which the toxicological mechanisms will be explored in future studies.


Robotic bariatric surgery: bypass, band and sleeve. Where are we now? And what is the future?
Rates of Obesity and Bariatric surgery continue to increase worldwide. Obese patients represent a unique cohort with important anatomical and physiological challenges that can influence operative outcome. The aim of this review is to evaluate the current evidence regarding the role of robotics in bariatric surgery. Robotic surgery confers several technical advantages including better visual field with improved three-dimensional image, seven degrees of freedom and anti-tremor filters to enable more precise manipulations and increased dexterity by downscaling the surgeon's movements. These technical advantages are more likely to confer a benefit in terms of clinical outcome in more complicated minimally invasive procedures especially gastric bypass and in particular with important steps of the procedure such as anastomotic suturing. Despite these advantages robotic bariatric surgery is associated with increased cost and operative time, which may limit its use in less complicated procedures such as gastric band surgery. Future highly powered randomized controlled trials are required to accurately evaluate clinical outcome and cost-effectiveness of robotics both in gastric bypass and in sleeve gastrectomy.


Metabolic profiling, in-situ spatial distribution, and biosynthetic pathway of functional metabolites in Dendrobium nobile stem revealed by combining UPLC-QTOF-MS with MALDI-TOF-MSI.
The stem of Dendrobium nobile Lindl. (Orchidaceae), called "Shihu" in traditional Chinese medicine, is a well-known medicinal and edible plant material in China. It is used as an antipyretic, analgesic, and tonic to nourish the stomach and Yin (i.e., to improve the production of body fluids). These therapeutic properties are attributed to its alkaloids, sesquiterpenoids, bibenzyls, fluorenones, and phenanthrenes. However, a comprehensive understanding of these metabolites and their spatial distribution in stems is lacking. In this study, ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was performed to obtain detailed metabolites information about D. nobile stems. Then, the spatial distributions of diverse metabolites, including alkaloids and sesquiterpenoids, were characterized and visualized by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry imaging (MALDI-TOF-MSI). Based on the spatial and metabolic profiling data, sesquiterpene alkaloid dendrobine was chosen for the exhaustive study of a biosynthetic pathway in D. nobile. This is the first report on mass spectrometry imaging for Dendrobium species. As a result, critical bioactive metabolites such as 11 alkaloids, 10 sesquiterpenes, and 13 other metabolites were putatively identified and relatively quantified. The identified alkaloids were distributed in the parenchyma or vascular bundle, and sesquiterpenes were present in all regions of the stem with higher abundance in the vascular bundle and cuticle, or in the cuticle and epidermis. The biosynthetic pathway and accumulation pattern of dendrobine in D. nobile stem were also proposed. Our findings not only provided a critical methodology for the thorough understanding of physiological changes in metabolites and precise utilization of D. nobile stem, but also displayed an effective strategy for insight into the biosynthesis of bioactive metabolites in plants.


Preparation and 4D fluorescent imaging of quail embryos.
Traditionally, our understanding of developmental biology has been based on the fixation and study of embryonic samples. Detailed microscopic scrutiny of static specimens at varying ages allowed for anatomical assessment of tissue development. The advent of confocal and two-photon excitation (2PE) microscopy enables researchers to acquire volumetric images in three dimensions (x, y, and z) plus time (t). The development of transgenic Japanese quail has provided an embryonic model system that is more easily accessible than mammalian models and more efficient to breed than the classic avian model, the chicken. This protocol describes the methods necessary to prepare transgenic quail embryos for imaging in vitro, and for acquiring, processing, and analyzing three-dimensional (3D) time-lapse images.


Glial restricted precursor cells in central nervous system disorders: Current applications and future perspectives.
The crosstalk between glial cells and neurons represents an exceptional feature for maintaining the normal function of the central nervous system (CNS). Increasing evidence has revealed the importance of glial progenitor cells in adult neurogenesis, reestablishment of cellular pools, neuroregeneration, and axonal (re)myelination. Several types of glial progenitors have been described, as well as their potentialities for recovering the CNS from certain traumas or pathologies. Among these precursors, glial-restricted precursor cells (GRPs) are considered the earliest glial progenitors and exhibit tripotency for both Type I/II astrocytes and oligodendrocytes. GRPs have been derived from embryos and embryonic stem cells in animal models and have maintained their capacity for self-renewal. Despite the relatively limited knowledge regarding the isolation, characterization, and function of these progenitors, GRPs are promising candidates for transplantation therapy and reestablishment/repair of CNS functions in neurodegenerative and neuropsychiatric disorders, as well as in traumatic injuries. Herein, we review the definition, isolation, characterization and potentialities of GRPs as cell-based therapies in different neurological conditions. We briefly discuss the implications of using GRPs in CNS regenerative medicine and their possible application in a clinical setting. MAIN POINTS: GRPs are progenitors present in the CNS with differentiation potential restricted to the glial lineage. These cells have been employed in the treatment of a myriad of neurodegenerative and traumatic pathologies, accompanied by promising results, herein reviewed.


Axial-Plane Biomechanical Evaluation of 2 Suspensory Cortical Button Fixation Constructs for Acromioclavicular Joint Reconstruction.
Although numerous suture-button fixation techniques for acromioclavicular (AC) joint reconstruction have been validated with biomechanical testing in the superior direction, clinical reports continue to demonstrate high rates of construct slippage and breakage. To compare the stability of a novel closed-loop double Endobutton construct with a commercially available cortical button system in both the axial and superior directions. Controlled laboratory study. Six matched pairs of fresh-frozen cadaveric upper extremities were anatomically dissected and prepared to simulate a complete AC joint dislocation. One side of each pair was reconstructed with the double Endobutton (DE) construct and other side with the dog bone button (DB) construct. The specimens were then tested using a materials testing machine, determining initial superior and axial displacements with a preload, and then cyclically loaded in the axial direction with 70 N for 5000 cycles. Displacement was again measured with the same preloads at fixed cycle intervals. The specimens were then loaded superiorly to failure. At 5000 cycles, the mean axial displacement was 1.7 mm for the DB group and 1.2 mm for the DE group (P = .19), and the mean superior displacement was 1.1 mm for the DB group and 0.7 mm for the DE group (P = .32). Load at failure was similar (558 N for DE, 552 N for DB; P = .96). There was no statistically significant difference in the modes of failure. Biomechanical testing of both constructs showed similar fixation stability after cyclical axial loading and similar loads to failure. The strength of both constructs after cyclical loading in the axial plane and load-to-failure testing in the superior plane validate their continued clinical use for achieving stability in AC joint reconstruction procedures.


An Azimuth Antenna Pattern Estimation Method Based on Doppler Spectrum in SAR Ocean Images.
In synthetic aperture radar (SAR) ocean remote sensing, it is very difficult to estimate an accurate azimuth antenna pattern (AAP) from low-scattering SAR images without strong scattering targets. Therefore, an azimuth antenna pattern estimation method based on Doppler spectrum in SAR ocean images is proposed in this paper. In order to preserve the complete AAP information, an azimuth unweighted matched filter is used to re-image the SAR raw data in the proposed method. Then, the shape factor of AAP can be obtained by linear statistics of the relationship between Doppler center and edge frequency spectrum in Doppler spectrum of each distance gate. In addition, the impact of the uniformity and signal-to-noise ratio of SAR ocean images on the estimation results are also analyzed by simulation. Finally, the feasibility of proposed method is verified by data from ERS-2 (European remote sensing satellite (ERS) was the European Space Agency's first Earth-observing satellite). Experimental results show that the AAP estimated by proposed method has a good estimation result.


Aldehyde dehydrogenase 2 polymorphism as a protective factor for intracranial vascular stenosis in ischemic stroke in Han Chinese.
Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme that metabolizes acetaldehyde to acetic acid. ALDH2 gene polymorphism modifies its activity and the mutation of ALDH2 gene has been reported to be associated with the protection against ischemic stroke. However, the potential association of allelic variation of ALDH2 with intracranial vascular stenosis and the clinical characteristics of ischemic stroke without coronary artery disease remains unclear. In this study, ischemic stroke patients were recruited, National Institutes of Health Stroke Scale scores were analyzed, intracranial arterial stenosis were evaluated by magnetic resonance angiography and gene typing of ALDH2 was determined by polymerase chain reaction and sequencing. We found that the rate of heavy drinking was significantly lower in the ALDH2 mutation group ((*)1/(*)2 and (*)2/(*)2) than in wild-type group ((*)1/(*)1) (18.6% vs. 38.0%, p = 0.01). Plasma homocysteine (Hcy) levels were significantly different in the two groups (15.45 ± 6.39 vs. 13.14 ± 4.45, p = 0.015). The ALDH2 mutation genotype was negatively correlated with severe intracranial vascular stenosis (OR, 0.34; p = 0.002), even after adjustment for high-density lipoprotein cholesterol, Hcy, and heavy drinking (adjusted OR, 0.44; p = 0.03). ALDH2(*)2 could be a protective factor and negative predictor for severe intracranial vascular stenosis in ischemic stroke in Han Chinese.


Direct oral anticoagulant-related medication incidents and pharmacists' interventions in hospital in-patients: evaluation using reason's accident causation theory.
Background Direct oral anticoagulants (DOACs) have revolutionised anticoagulant pharmacotherapy. However, DOAC-related medication incidents are known to be common. Objective To assess medication incidents associated with DOACs using an error theory and to analyse pharmacists' contributions in minimising medication incidents in hospital in-patients. Setting A large University academic hospital in the West Midlands of England. Methods Medication incident data from the incident reporting system (48-months period) and pharmacists' interventions data from the prescribing system (26-month period) relating to hospital in-patients were extracted. Reason's Accident Causation Model was used to identify potential causality of the incidents. Pharmacists' intervention data were thematically analysed. Main outcome measure (a) Frequency, type and potential causality of DOAC-related incidents; (b) nature of pharmacists' interventions. Results A total of 812 reports were included in the study (124 medication incidents and 688 intervention reports). Missing drug/omission was the most common incident type (26.6%, n = 33) followed by wrong drug (16.1%, n = 20) and wrong dose/strength (11.3%, n = 14). A high majority (89.5%, n = 111) of medication incidents were caused by active failures. Patient discharge without anticoagulation supply and failure to restart DOACs post procedure/scan were commonly recurring themes. Pharmacists' interventions most frequently related to changes in pharmacological strategy, including drug or dose changes (38.1%, n = 262). Impaired renal function was the most common reason for dose adjustments. Conclusion Prescribers' active failure rather than system errors (i.e. latent failures) contributed to the majority of DOAC-related incidents. Reinforcement of guideline adherence, prescriber education, harnessing pharmacists' roles and mandating renal function information in prescriptions are likely to improve patient safety.


Optimal timing of a single dose of zoledronic acid to increase strength in rat fracture repair.
We hypothesized that ZA treatment would bolster fracture repair. In a rat model for closed fracture healing, a single dose of ZA at 0, 1, or 2 wk after fracture significantly increased BMC and strength of the healed fracture. Delaying the dose (1 or 2 wk after fracture) displayed superior results compared with dosing at the time of fracture. Bisphosphonates are known to increase bone strength and thus the resistance to fracture by decreasing osteoclastic bone resorption. These properties may enable bisphosphonates to also increase the strength of fracture repair. Zoledronic acid (ZA) is a potent bisphosphonate with a high affinity for bone mineral, allowing bolus intravenous dosing in a range of indications. In this study, we examined the application of bolus dose ZA in endochondral fracture repair. Carbon-14 labeled ZA was used in a closed rat fracture model. Rats were divided into five treatment groups (n = 25 per group): saline control, local ZA (0.01 mg/kg), and three systemic bolus ZA groups (0.1 mg/kg) with different administration times: at fracture, 1 wk after fracture, and 2 wk after fracture. Rats were killed 6 wk postoperatively. Postmortem analyses included radiography, QCT, microCT, biomechanical testing, scintillation counting, autoradiography, and histology. Single-dose systemic ZA administration significantly increased callus volume, callus BMC, and mechanical strength. Perioperative treatment increased mechanical strength by 30% compared with controls (p < 0.05). Administering the systemic dose at 1 or 2 wk after fracture further increased mechanical strength compared with controls by 44% and 50%, respectively (p < 0.05). No significant differences in mechanical parameters were seen with local injection at the dose studied. Autoradiographic analysis indicated that ZA binds significantly to bone that is present at the time of administration. ZA quantification indicated that delayed administration significantly increased the uptake efficiency in the callus. Histological and microCT analysis showed that ZA treated calluses had a distinctive internal structure consisting of an intricate network of retained trabecular bone. The timing of a single systemic dose of ZA plays an important role in the modulation of callus properties in this rat fracture model; delaying the single dose produces a larger and stronger callus.


The evolution of an experimental distal motor axonopathy. Physiological studies of changes in neuromuscular transmission caused by cycloleucine, an inhibitor of methionine adenosyltransferase.
Cycloleucine (CL), a synthetic amino acid is known to cause degeneration of motor nerve terminals. This paper describes the changes in neuromuscular transmission, the morphology of motor end-plates and the responses of muscle spindles after a single dose of CL was administered to weanling and adult mice. Animals were allowed to survive for between 12 h and 7 days. Twitch and tetanic responses of muscles stimulated through their nerves fell dramatically within 24 h in both young and adult mice and intracellular recordings revealed that a large proportion of end-plates in calf muscles became denervated, whilst at other end-plates intermittent failure of transmission and end-plate potentials (EPPs) with prolonged latency were demonstrated. End-plates with an abnormally high frequency of miniature end-plate potentials (mEPPs) were found in young mice at 12 h, and in the adult mice at 24 h. Morphological abnormalities in intramuscular nerves and nerve terminals included areas of electron lucent axoplasm, swollen degenerative mitochondria and loss of synaptic vesicles. Over the next 2-3 days further reductions occurred in the number of end-plates at which mEPPs or EPPs could be demonstrated. At 7 days a limited recovery of function occurred in distal muscles but proximal muscles, hitherto unaffected, now began to show abnormalities of transmission. Muscle spindles were found to be both functionally and structurally intact. It is suggested that this acute distal motor axonopathy is due to abnormalities in phospholipid composition of the axolemma of motor nerve terminals resulting from the failure of methyl-transfer pathways. These abnormalities in phospholipid composition might cause an increase in microviscosity of the axolemma and hence a decrease in efficiency of ion channels and pumps responsible for maintaining electrochemical gradients, essential for the structural and functional integrity of the neuromuscular junction.


AR collaborates with ERα in aromatase inhibitor-resistant breast cancer.
Androgen receptor (AR) is an attractive target in breast cancer because of its frequent expression in all the molecular subtypes, especially in estrogen receptor (ER)-positive luminal breast cancers. We have previously shown a role for AR overexpression in tamoxifen resistance. We engineered ER-positive MCF-7 cells to overexpress aromatase and AR (MCF-7 AR Arom cells) to explore the role of AR in aromatase inhibitor (AI) resistance. Androstendione (AD) was used as a substrate for aromatization to estrogen. The nonsteroidal AI anastrazole (Ana) inhibited AD-stimulated growth and ER transcriptional activity in MCF-7 Arom cells, but not in MCF-7 AR Arom cells. Enhanced activation of pIGF-1R and pAKT was found in AR-overexpressing cells, and their inhibitors restored sensitivity to Ana, suggesting that these pathways represent escape survival mechanisms. Sensitivity to Ana was restored with AR antagonists, or the antiestrogen fulvestrant. These results suggest that both AR and ERα must be blocked to restore sensitivity to hormonal therapies in AR-overexpressing ERα-positive breast cancers. AR contributed to ERα transcriptional activity in MCF-7 AR Arom cells, and AR and ERα co-localized in AD + Ana-treated cells, suggesting cooperation between the two receptors. AR-mediated resistance was associated with a failure to block ER transcriptional activity and enhanced up-regulation of AR and ER-responsive gene expression. Clinically, it may be necessary to block both AR and ERα in patients whose tumors express elevated levels of AR. In addition, inhibitors to the AKT/IGF-1R signaling pathways may provide alternative approaches to block escape pathways and restore hormone sensitivity in resistant breast tumors.


Fall Risk Prediction Models During the Initial COVID-19 Surge: Could Predictive Analytics Be Used in a Resource-Constrained Environment?
During the first COVID surge, multiple changes in nurse staffing and workflows were made to support care delivery in a resource-constrained environment. We hypothesized that there was a higher rate of inpatient falls during the COVID surge. Furthermore, we predicted that an automated predictive analytic algorithm would perform as well as the Johns Hopkins Fall Risk Assessment. A retrospective review of falls for 3 months before and the first 3 months of the first COVID surge was conducted. We determined the total number of falls and the overall fall rate and examined the distribution of scores and accuracy of fall predictive models for both groups. There was a statistically significant increase in fall rate during the first 3 months of the COVID surge compared with the 3 prior months (2.48/1000 patient-days vs 1.89/1000 patient-days respectively; P = .041). The Johns Hopkins instrument had a greater sensitivity of 78.9% compared with 57.0% for the predictive analytic model. Specificity and accuracy of the predictive analytic model were higher than the Johns Hopkins instrument (71.3% vs 54.1% and 71.2% vs 54.3%, respectively). These findings suggest that the automated predictive analytic model could be used in a resource-constrained environment to accurately classify patients' risk of fall.


Transfer of a fascicle from the posterior cord to the suprascapular nerve after injury of the upper roots of the brachial plexus: technical case report.
A new nerve transfer technique using a healthy fascicle of the posterior cord for suprascapular nerve reconstruction is presented. This technique was used in a patient with posttraumatic brachial plexopathy resulting in upper trunk injury with proximal root stumps that were unavailable for grafting associated with multiple nerve dysfunction. A 45-year-old man sustained a right brachial plexus injury after a bicycle accident. Clinical evaluation and electromyography indicated upper trunk involvement. Trapezius muscle function and triceps strength were normal on physical examination. The patient underwent a combined supra- and infraclavicular approach to the brachial plexus. A neuroma-in-continuity of the upper trunk and fibrotic C5 and C6 roots were identified. Electrical stimulation of the phrenic and spinal accessory nerves produced no response. The suprascapular nerve was dissected from the upper trunk, transected, and rerouted to the infraclavicular fossa. A healthy fascicle of the posterior cord to the triceps muscle was transferred to the suprascapular nerve. At the time of the 1-year follow-up evaluation, arm abduction against gravity and external rotation reached 40 and 34 degrees, respectively. The posterior cord can be used as a source of donor fascicle to the suprascapular nerve after its infraclavicular relocation. This new intraplexal nerve transfer could be applied in patients with isolated injury of the upper trunk and concomitant lesion of the extraplexal nerve donors usually used for reinnervation of the suprascapular nerve.


Computer-based tracking of living cells.
A computer-based tracing technique has been developed to follow the movement of living cells and keep them centered in the field of view of an optical microscope. With the use of an image-processing system, the video image of a cell can be sufficiently processed to allow computer-recognition of the cell boundaries. Determination of the location of the center of the cell enables comparison of successive cell positions and correction for any cell movement. In order to illustrate the versatility of this technique, patterns of movement were obtained of cancerous and non-cancerous cells in an effort to determine the difference in motility between the two cell types. After examination of the data gathered, it was found that there is no difference in the motility between the two cell types over 1-h periods.


Coffee berry borer Hypothenemus hampei (Coleoptera: Curculionidae): searching for sustainable control strategies.
The coffee berry borer Hypothenemus hampei (Ferrari) is the most serious pest of the world's most valuable tropical export crop. Since the last review on this insect was published six years ago, many new studies have contributed to an improved insight into the biology and ecology of the beetle, and have indicated new avenues for integrated and biological control. The latest developments in research, both laboratory and field, on the pest, its natural enemies and their implications for integrated control of H. hampei are summarized, with a particular focus on the situation in The Americas. Lately, the global coffee industry has changed radically; it has suffered a long cycle of lowest-ever world market prices caused by overproduction and technological change. At the same time, the advent of sustainable certification schemes has had a major impact on the industry. The role of integrated pest management and biological control of H. hampei in an era of changes in the coffee industry is discussed.


Industrial hygienic study on nursing activities comparison of energy expenditure between pedometer and Holter electrocardiograph.
Few objective and quantitative studies have been made on energy expenditure during hospital nursing activities. The pedometer is a light handy instrument, which gives highly accurate results, and is a minimal burden for subjects. To ascertain daily energy expenditures, we used a pedometer. Twelve day-shift nurses served as subjects, in whom the number of steps token in 16 hours, from getting up until going to bed, was measured. We used the data obtained to calculate energy expenditures for 24 hours. In addition, eight nurses were chosen from among these subjects to undergo simultaneous pedometry and Holter electrocardiography. These data were also used to calculate energy expenditures. The following results were obtained. 1) The maximum total number of steps was 13897, the minimum 9899 and the mean +/- standard deviation was 11478.4 +/- 1285.8. 2) As to the energy expenditure of the eight nurses who were both pedometer and Holter electrocardiograph, the highest energy expenditure calculated from pedometry results was 2648 kcal. the lowest 2455 kcal, and the mean +/- standard deviation was 2514.1 +/- 55.5. The highest energy calculated from Holter electrocardiographic data was 3040 kcal, the lowest 2683 kcal, and the mean +/- standard deviation was 2868.1 +/- 108.0. The correlation coefficient was r = 0.59, (P < 0.05).