Specific IgE levels as an outcome predictor in egg-allergic children.
Diagnosis of immunoglobulin E (IgE)-mediated egg allergy is often based on both a compatible clinical history and either elevated IgE levels or a positive skin prick test. However, the gold standard is the oral food challenge (OFC). Previous studies have pointed to a correlation between IgE levels and OFC outcomes. This study aimed to determine the relationship between IgE levels and the outcome of OFC, seeking to establish cut-off OFC values that indicate a high likelihood of positive OFC results. A total of 198 patients who underwent OFC (and a serological IgE antibody assay within the three preceding months) were reviewed and divided by OFC type (i.e., baked, cooked, or raw egg). IgE-specific levels were assessed against the challenge outcome as well as cut-offs proposed by other authors. Receiver-operating characteristic (ROC) curve analysis yielded a potentially useful ovomucoid IgE-specific cutoff used in OFC with cooked egg and several egg white and ovalbumin IgE-specific cut-offs for OFC with raw egg. We found no significant relationship between other specific IgE concentrations and the challenge threshold level with baked eggs. IgE-specific concentrations are useful as predictors of OFC outcome and should be considered when selecting patients challenge testing with boiled or raw egg. However, patients should undergo OFC with baked egg regardless of IgE levels.


In vitro radiation-induced effects on rat tracheal epithelial cells. II) Different preneoplastic cell transformation after alpha and gamma irradiations.
In order to compare the cell transformation induced by alpha- and gamma-irradiation, primary cultures of tracheal epithelial cells from two rat strains, Sprague Dawley (SD) and Wistar Furth/Fisher F344 (WF/Fi) rats, were irradiated with 241Am alpha-particles or 60 Co gamma-rays. The relative transformation frequency (RTF) for WF/Fi primary cells was very close to the level of the spontaneous incidence and independent on the two irradiation types used. On the contrary, the RTF for the SD primary cells increased with a decrease of the LET radiation when the relative survival was higher than about 40%. Therefore, the RTF values reached 4-5 for alpha-particles and 10-12 for gamma-rays. The RTF can be related to the intrinsic radiosensitivity of the rat epithelial cells. However, the difference in the radiation-induced RTF for SD or WF/Fi primary cells seems to be due to the development, under genetic control, of the initial lesion to the neoplastic state.


Nutritional regulation of IGF-I and IGF binding proteins.
The secretion of both IGF-I and IGF-II, peptides that are structurally related to insulin, is linked to nutrient intake. These growth factors and their binding proteins appear to be major links between nutrient intake and cellular anabolic responses. Understanding the mechanisms by which nutrients control IGF synthesis and regulate transport to target tissues should permit the formulation of strategies for treatment of catabolic disorders. Understanding the alterations of such processes in catabolic states should enable development of better methods for nutritional repletion and wiser uses of anabolic agents in the treatment of these conditions.


The Novel Methylation Biomarker NPY5R Sensitizes Breast Cancer Cells to Chemotherapy.
Breast cancer (BC) is the most common tumor in women, and the molecular mechanism underlying its pathogenesis remains unclear. In this study, we aimed to investigate gene modules related to the phenotypes of BC, and identify representative candidate biomarkers for clinical prognosis of BC patients. Using weighted gene co-expression network analysis, we here identified NPY5R as a hub gene in BC. We further found that NPY5R was frequently downregulated in BC tissues compared with adjacent tumor-matched control tissues, due to its aberrant promoter CpG methylation which was confirmed by methylation analysis and treatment with demethylation agent. Higher expression of NPY5R was closely associated with better prognosis for BC patients. Gene set enrichment analysis showed that transcriptome signatures concerning apoptosis and cell cycle were critically enriched in specimens with elevated NPY5R. Ectopic expression of NPY5R significantly curbed breast tumor cell growth, induced cell apoptosis and G2/M arrest. Moreover, NPY5R also promoted the sensitivity of BC cells to doxorubicin. Mechanistically, we found that NPY5R restricted STAT3 signaling pathway activation through interacting with IL6, which may be responsible for the antitumor activity of NPY5R. Collectively, our findings indicate that NPY5R functions as a tumor suppressor but was frequently downregulated in BC.


Pediatric hypertension based on Japanese Society of Hypertension Guidelines (JSH 2019) with actual school blood pressure screening data in Japan.
Blood pressure (BP) in children and adolescents is associated with their growth. BP is most strongly associated with height during height gain and with degree of obesity after reaching final height. BP in childhood and adolescence is correlated with BP in adulthood. The pathophysiology of pediatric essential hypertension is associated with obesity, excess salt intake, and a low birth weight. The common causes of pediatric secondary hypertension are renal parenchymal and renovascular diseases. The significance of diagnosing pediatric hypertension involves detecting secondary hypertension and preventing organ damage due to hypertension as well as tracking essential hypertension in adulthood. Appropriate BP measurement procedures are required for diagnosing pediatric hypertension. The inflatable bladder of an appropriately sized cuff should exceed 40% of the arm circumference. BP measurements should be performed consecutively at least 3 times using an appropriately sized cuff. The diagnosis of hypertension requires that all BP values measured on 3 or more occasions be above the reference value. The criteria for pediatric hypertension are determined based on the distribution of BP in healthy children and adolescents, with values above the 95th percentile of normal representing hypertension. Japanese criteria define pediatric hypertension as ≥120/70 mmHg for preschool children, ≥130/80 mmHg for 1st-3rd graders, ≥135/80 mmHg for 4th-6th graders, ≥140/85 mmHg for 7th-9th grade boys, ≥135/80 mmHg for 7th-9th grade girls, and ≥140/85 mmHg for senior high school boys and girls. The prevalence of Japanese pediatric hypertension was 0.9% based on proper measurement protocols. The basis of managing pediatric essential hypertension is healthy lifestyle modifications. Pharmacotherapy is indicated for persistent hypertension, symptomatic hypertension, secondary hypertension, the development of target organ damage, the presence of chronic kidney disease, and diabetes mellitus. Screening for pediatric hypertension is important; therefore, BP should be routinely measured in children and adolescents.


Lessons Learnt from Recent Trials in Ischemic Heart Disease.
Four recently published randomized controlled trials have informed the care of patients with stable ischemic heart disease. The purpose of this clinical focus article is to offer a summary and critical appraisal of the recent evidence. We aim to aid clinicians in the translation of the trial evidence to patient care.


A Competitive Edge: Competitor Inspired Scaffold Hopping in Herbicide Lead Optimization.
Over the years, scaffold hopping has proven to be a powerful tool in the agrochemical optimization process. It offers the opportunity to modify known molecular lead structures to improve a range of parameters, including biological efficacy and spectrum, physicochemical properties, toxicity, stability, and to secure new intellectual property. Very often the disclosure of a new chemical structure can spark a multitude of competitor activities, where scaffold hopping plays a crucial role in the optimization process as well as for the generation of new intellectual property. Herein, recent examples of scaffold hopping in early phase herbicide research based on competitor inspired activities will be discussed using examples of how these research campaigns can often result in the registration of new crop protection products.


Rearrangement of the MLL gene confers a poor prognosis in childhood acute lymphoblastic leukemia, regardless of presenting age.
MLL gene rearrangements are associated with an extremely poor prognosis in infants with acute lymphoblastic leukemia (ALL), but little is known about their clinical significance in older children. Therefore, we studied 45 cases of childhood ALL with abnormalities of chromosome 11q23 for rearrangement of the MLL gene to determine if this feature confers a uniformly poor prognosis. MLL gene rearrangements were detected in all 18 cases with the common t(4;11), t(9;11) or t(11;19) translocations, whereas only 5 of 12 patients with either unbalanced or uncommon balanced translocations demonstrated a rearrangement. Abnormalities of the MLL gene were not detected in any of the 15 cases with a deletion or inversion of the chromosomes 11q23 region. The presence of an MLL rearrangement was significantly associated with age less than 1 year (P < .001), leukocyte count >50 x 10(9)/L (P = .003), and the absence of leukemic cell CD10 expression (P < .001). In a stratified statistical analysis adjusted for age and treatment protocol, MLL gene rearrangement was correlated with an inferior treatment outcome (P = .028). The 4-year event-free survival estimate (+/- SE) was 10% +/- 6.5% for cases with a rearranged MLL gene and 64% +/- 19.2% for other cases. When infants were excluded from the analysis, MLL rearrangement was still significantly associated with a poor outcome (P = .02), and remained so with the exclusion of t(4;11)-positive cases (P = .05). Thus, regardless of presenting age, MLL gene rearrangement identifies a high-risk subgroup of patients who are not likely to be cured with conventional treatment.


Leprosy in Eastern Nigeria and the social history of colonial skin.
To the historian, the 'historical' experience of leprosy control is not simply a backdrop to contemporary patterns or problems in disease control. The control of leprosy has been enacted in different ways in localities, territories and states across the world. The specific clinical, political, and institutional choices made in leprosy control have been highly significant in shaping attitudes and approaches to leprosy. The term stigma has a history of usage, contention and re-definition. Stigma, then, is a product of its intersecting social, economic, and medical contexts. In order to capture the degree to which stigma associated with leprosy has mutated and changed over time, this article concerns itself specifically with the colonial experience of leprosy, with a focus on the formerly leprosy-endemic area of southeastern Nigeria (known as the Eastern Region, or Eastern Nigeria) in the last quarter century of colonial rule ending in 1960. The article examines how leprosy was presented, identifying some of the forms in which ideas of stigma and taint with respect to leprosy were communicated. It goes on to examine how leprosy was encountered as a medical problem in Eastern Nigeria, placing leprosy in the context of skin diseases most commonly encountered by colonial medical services. It concludes by demonstrating how leprosy was understood, looking briefly at local and biomedical means of identifying and combating these diseases, and the meanings of these diseases in the rapidly changing contexts of mid- and late-colonial rule and the onset of Nigerian Independence in 1960.


Course of psychiatric disorders across the menstrual cycle.
Women of reproductive age with psychiatric disorders may experience a fluctuating course of illness over the menstrual cycle. Some data suggest an exacerbation of symptoms during the premenstrual and menstrual phases. The usefulness of such reports is limited, however, by the lack of prospective assessments and the small number of patients involved. Additionally, many reports do not specify whether the exacerbations reflect an intensification of the underlying psychiatric disorder or a new onset of symptoms that occur only during certain phases of the menstrual cycle. Because symptomatic intensification has been reported for illnesses including schizophrenia, bipolar disorder, depression, anxiety disorders, bulimia nervosa, and substance abuse, the data bring attention to the importance of assessing the relationship between a female patient's symptomatic exacerbation and the menstrual-cycle phase in which it occurs. We present a review of the literature on the course of psychiatric symptoms across the menstrual cycle and discuss the potential effects of estrogen and progesterone on these symptoms.


Glycolytic enzyme interactions with yeast and skeletal muscle F-actin.
Interaction of glycolytic enzymes with F-actin is suggested to be a mechanism for compartmentation of the glycolytic pathway. Earlier work demonstrates that muscle F-actin strongly binds glycolytic enzymes, allowing for the general conclusion that "actin binds enzymes", which may be a generalized phenomenon. By taking actin from a lower form, such as yeast, which is more deviant from muscle actin than other higher animal forms, the generality of glycolytic enzyme interactions with actin and the cytoskeleton can be tested and compared with higher eukaryotes, e.g., rabbit muscle. Cosedimentation of rabbit skeletal muscle and yeast F-actin with muscle fructose-1,6-bisphosphate aldolase (aldolase) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) followed by Scatchard analysis revealed a biphasic binding, indicating high- and low-affinity domains. Muscle aldolase and GAPDH showed low-affinity for binding yeast F-actin, presumably because of fewer acidic residues at the N-terminus of yeast actin; this difference in affinity is also seen in Brownian dynamics computer simulations. Yeast GAPDH and aldolase showed low-affinity binding to yeast actin, which suggests that actin-glycolytic enzyme interactions may also occur in yeast although with lower affinity than in higher eukaryotes. The cosedimentation results were supported by viscometry results that revealed significant cross-linking at lower concentrations of rabbit muscle enzymes than yeast enzymes. Brownian dynamics simulations of yeast and muscle aldolase and GAPDH with yeast and muscle actin compared the relative association free energy. Yeast aldolase did not specifically bind to either yeast or muscle actin. Yeast GAPDH did bind to yeast actin although with a much lower affinity than when binding muscle actin. The binding of yeast enzymes to yeast actin was much less site specific and showed much lower affinities than in the case with muscle enzymes and muscle actin.


Adults Hospitalized With Pneumonia in the United States: Incidence, Epidemiology, and Mortality.
Understanding the burden of community-acquired pneumonia (CAP) is critical to allocate resources for prevention, management, and research. The objectives of this study were to define incidence, epidemiology, and mortality of adult patients hospitalized with CAP in the city of Louisville, and to estimate burden of CAP in the US adult population. This was a prospective population-based cohort study of adult residents in Louisville, Kentucky, from 1 June 2014 to 31 May 2016. Consecutive hospitalized patients with CAP were enrolled at all adult hospitals in Louisville. The annual population-based CAP incidence was calculated. Geospatial epidemiology was used to define ecological associations among CAP and income level, race, and age. Mortality was evaluated during hospitalization and at 30 days, 6 months, and 1 year after hospitalization. During the 2-year study, from a Louisville population of 587499 adults, 186384 hospitalizations occurred. A total of 7449 unique patients hospitalized with CAP were documented. The annual age-adjusted incidence was 649 patients hospitalized with CAP per 100000 adults (95% confidence interval, 628.2-669.8), corresponding to 1591825 annual adult CAP hospitalizations in the United States. Clusters of CAP cases were found in areas with low-income and black/African American populations. Mortality during hospitalization was 6.5%, corresponding to 102821 annual deaths in the United States. Mortality at 30 days, 6 months, and 1 year was 13.0%, 23.4%, and 30.6%, respectively. The estimated US burden of CAP is substantial, with >1.5 million unique adults being hospitalized annually, 100000 deaths occurring during hospitalization, and approximately 1 of 3 patients hospitalized with CAP dying within 1 year.


Low Voltage CO(2) Laser Excitation.
A report of experiments on low voltage excitation of cw CO(2) lasers is presented. Pertinent plasma considerations are given along with the design of various electrode configurations tested. Preliminary results suggest that low voltage excitation of cw CO(2) lasers is practical using a grid structure and an inverted brush cathode assembly in a reduced height transverse geometry. The positive resistance V-I characteristics so obtained permit an order of magnitude reduction in external ballast.


Taxometric evidence for the dimensional structure of cluster-C, paranoid, and borderline personality disorders.
Despite a lively debate about the dimensional vs. categorical nature of Personality Disorders (PDs), direct empirical tests of the underlying structure are missing for most PDs. Taxometrics can be used to investigate whether latent structures are categorical or dimensional. We investigated the latent structure underlying Avoidant, Dependent, Obsessive-Compulsive, Depressive, Paranoid, and Borderline PD by means of three types of taxometric analyses. SCID-II based DSM-IV PD criterion scores from 1,816 patients from Mental Health and Forensic Institutes, and 63 nonpatients, were analyzed with three types of taxometric analyses. MAMBAC, MAXEIG, and L-MODE taxometric analyses were applied on multiple criteria sets, constituted both on theoretical grounds and randomly. Assumptions for taxometric analyses were generally met. All but two of the 78 taxometric analyses indicated greater evidence for a latent dimensional structure, with better fit of empirical data to dimensional than to taxonic simulations; mean Comparative Curve Fit Index (CCFI) = .23, SD = .09. Only two analyses yielded ambiguous evidence (CCFI in the .40-.60 range) and none indicated taxonic structure.


An integrated computational and laboratory approach for selective amplification of mRNAs containing the adenylate uridylate-rich element consensus sequence.
Messenger RNAs that have the stability determinants, adenylate uridylate-rich elements (AREs), in their 3' untranslated region (UTR) code for key products that regulate early and transient biological responses. We used a computational laboratory approach for amplification of large, including full-length, protein-coding regions for ARE genes. Statistical analysis of the initiation regions in the 5' UTR of ARE-mRNAs was performed. Accordingly, several 5' primers and a single universal 3' primer that targeted the initiation consensuses and ARE regions, respectively, were designed. Using optimized conditions, the primers were able to enrich and amplify large protein-coding regions for the ARE gene family. The selective amplification of ARE cDNAs was verified using specific polymerase chain reactions (PCRs) to known ARE mRNA molecules and monitoring the abundance of the non-ARE beta-actin signal. A mini-library from the amplified ARE products was constructed for further confirmation of ARE selection. Distinct ARE amplified cDNA pools were selectively generated by distinct 5' primers. The biological utility of the method was shown with differential display. The up-regulation of several ARE-mRNAs, including the full-length coding region of the small inducible cytokine A4 (SCYA4) gene, was shown in endotoxin-stimulated monocytic cells. The integrated computational and laboratory approach should lead to enhanced capability for discovery and expression analysis of early and transient response genes.


Recent Progress and Challenges in Hollow Fiber Membranes for Wastewater Treatment and Resource Recovery.
Membrane processes have been extensively employed in diverse applications, specifically in industrial wastewater treatment. The technological development in membrane processes has rapidly advanced and accelerated beyond its common principle and operation. Tremendous efforts have been made in the advancement of membrane materials, fabrication method, membrane modification and integration with other technologies that can augment the existing membrane processes to another level. This review presents the recent development of hollow fiber membranes applied in wastewater treatment and resource recovery. The membrane working principles and treatment mechanism were discussed thoroughly, with the recent development of these hollow fiber membranes highlighted based on several types of membrane application. The current challenges and limitations which may hinder this technology from expanding were critically described to offer a better perspective for this technology to be adopted in various potential applications.


Permanent or temporary IVC filtration with a novel double-ring anchoring technology optional nitinol filter.
Permanent or temporary implantation of inferior vena cava filters for protection against pulmonary embolism is well established. There have been numerous devices developed for this purpose, each of which has proprietary design considerations that affect performance and potentially impose limitations with regard to positioning, efficacy and risk profile. This article describes a recently developed, unique inferior vena cava filter design that employs a separated filtration component and a novel double-ring anchoring system that allows intraprocedural capture and repositioning for optimized placement. In addition, early experience suggests easy removal when desired, a high rate of filtration success and excellent caval patency.


[Brown tumors in the technetium-99m methyldiphosphonate bone scan mimicking metastases of parathyroid carcinoma].
This is a case of a 78 year old male with parathyroid carcinoma and multiple bone lesions in the technetium-99m methyldiphosphonate ((99m)Tc-MDP) bone scan, initially interpreted as metastatic bone disease, but finally proved to be brown tumors. The interest of this case lies on the rarity of the disease, as well as the co-existence of osteitis fibrosa cystica, which often resembles metastatic bone disease and leads to diagnostic pitfalls.


Prevalence of hepatitis C virus antibodies among patients infected with human immunodeficiency virus.
A study was undertaken to determine the prevalence and risk factors for serological evidence of hepatitis C virus (HCV) infection in patients infected with the human immunodeficiency virus (HIV). Tests for anti-HCV antibody were carried out by enzyme-linked immunoassay (EIA) on 101 HIV-infected patients from two university-based outpatient clinics. Anti-HCV antibody reactive samples were tested by using a recombinant immunoblot assay (RIBA) for HCV antibodies. Fourteen of 101 (13.9%) HIV-infected patients were anti-HCV reactive by EIA. Of these 14, only seven were reactive by RIBA: four were intravenous drug users as a sole risk factor for HIV infection; and the remaining three acquired HIV by blood transfusion, contaminated instrument exposure or IV drug use and sexual contact. Acquisition of HIV by sexual activity alone was not associated with HCV infection. It is concluded that HCV infection is found in approximately 7% of a university HIV clinic population. False-positive anti-HCV antibody serology may lead to overestimation of the prevalence of HCV infection. Female sex and intravenous drug use are significantly associated with HCV infection among HIV-infected individuals.


Taxol induces bcl-2 phosphorylation and death of prostate cancer cells.
Treatment of prostate cancer cell lines expressing bcl-2 with taxol induces bcl-2 phosphorylation and programmed cell death, whereas treatment of bcl-2-negative prostate cancer cells with taxol does not induce apoptosis. bcl-2 phosphorylation seems to inhibit its binding to bax since less bax was observed in immunocomplex with bcl-2 in taxol-treated cancer cells. These findings support the use of the anticancer drug taxol for the treatment of bcl-2-positive prostate cancers and other bcl-2-positive malignancies, such as follicular lymphoma.


Uniform Fabrication of Hollow Titania Using Anionic Modified Acrylated Polymer Template for Phase Composition Effect as Photocatalyst and Infrared Reflective Coating.
Polymer coatings containing thermal blocking and near-infrared (NIR)-reflective pigments have received much attention for their potential applications in energy-saving fields. A drawback of these coatings is sustainability providing similar long-term performance. Surface cleaning is mandatory to remove contaminants that decrease reflectance. In this study, synthesized hollow titania as photocatalyst was used to impart anti-contamination to infrared (IR)-reflective coatings. A TiO2 shell was selectively formed on an anionic polystyrene core, modified by methacrylic acid. According to sintering temperature, the enhancement of light absorption ability and photocatalytic activity as methyl orange decomposition was observed with phase composition change. The methylene blue decomposition reaction, reflectance measurement, and measuring thermal profiling of coated steel confirmed the manifestation of hollow particles to dust degradation characteristics and the enhancement of reflection and thermal shielding.


Theoretical investigation on the concentration dependence of the Landolt time.
Based on the modified kinetic model of the Landolt and the Dushman reactions published recently, an exact expression has been derived for the concentration dependence of the Landolt time. It is also shown that all the apparently contradictory formulas, regarding the concentration dependence of the Landolt time, reported previously at quite different experimental circumstances can easily be reconciled from the simplification of the newly proposed equation. It also means that the formula derived may satisfactorily be applied to calculate the Landolt time basically with no restrictions for the concentration of the reactants.


A putative nuclear receptor coactivator (TMF/ARA160) associates with hbrm/hSNF2 alpha and BRG-1/hSNF2 beta and localizes in the Golgi apparatus.
An ATP-dependent chromatin remodeling factor, SNF/SWI complex, acts as a coactivator for numerous transcriptional factors. One of the best-documented examples is nuclear receptors, although the molecular mechanism for this coactivation has not been sufficiently elucidated. Here we show that hbrm/hSNF2 alpha and BRG-1/hSNF2 beta, the ATPase subunits of the human SNF/SWI complexes, specifically associate in vitro and in vivo with TATA element modulatory factor (TMF)/ARA160, which has been described as a binding protein to and coactivator for the androgen receptor. This interaction requires highly conserved N-terminal regions of hbrm/hSNF2 alpha and BRG-1/hSNF2 beta and a C-terminal region of TMF/ARA160. Immunofluorescence and Western blot studies revealed that the TMF isoforms differentially localize in the Golgi apparatus and the nucleus.


Loneliness and cardiovascular reactivity to acute stress in older adults.
Loneliness has been linked to cardiovascular health outcomes in older adulthood. One proposed mechanism by which loneliness influences cardiovascular health is through atypical cardiovascular reactivity (CVR) to stress. This study is an examination of loneliness and CVR in older adults, comparing associations across two stressors and two commonly used measures of loneliness, with a particular focus on underlying hemodynamic variables including cardiac output, total peripheral resistance, and ejection time (EJT). Eighty older adults, ranging in age from 55 to 88 years (M = 68.93, SD = 8.28), completed two versions of the UCLA loneliness scale (a 20-item and a briefer, three-item) and took part in a laboratory stress-testing procedure which included a mental arithmetic challenge and a public speaking task. Cardiovascular activity was monitored continuously throughout. For the 20-item version of the UCLA loneliness scale, loneliness was not significantly related to CVR, and was only significantly associated with lower levels of overall EJT. For the three-item version of the UCLA, no associations withstood adjustment for multiple testing. Loneliness was not reliably associated with CVR. Further, although greater loneliness was related to lower levels of overall EJT, this was only observed for the 20-item scale. The findings do not strongly provide support for reactivity to acute stress as a pathway linking loneliness to disease outcomes, and highlight key methodological issues related to the assessment of loneliness-reactivity associations for future.


Evidence-based health care in home care.
How do you make decisions about which treatment to use when you have a patient with an eschar-covered pressure ulcer on the sacrum or a patient with diabetes who develops an ulceration on the metatarsal head? For years, health care professionals relied on past experience, the experience of colleagues, or new product sales literature. In today's cost-conscious, outcomes-driven health care environment, however, approaches such as clinical reasoning are often not enough and, in fact, are often unacceptable. But why is that?


Circuitry for the contactless detection of superconducting transitions.
Complete circuitry is presented for the detection of the superconducting transition in powders, or specimens for which the standard four-point resistance measurement cannot be performed. Specimens are placed within an inductance coil, and the change in the coil reactance is monitored as a function of temperature. The sensitivity is sufficient to detect the superconducting transition in 10(-3) cm(3) of lead, and only four integrated circuit packages are required.


Takotsubo cardiomyopathy triggered by wasabi consumption: can sushi break your heart?
Takotsubo cardiomyopathy is a left ventricular dysfunction that typically occurs after sudden intense emotional or physical stress and mimics myocardial infarction. We describe a case of a 60-year-old woman that presented to the emergency department with chest pain after she attended a wedding and ate a large amount of wasabi, assuming it to be an avocado. To the best of our knowledge, this is the first report of takotsubo cardiomyopathy triggered by wasabi consumption.


Pulsed field gradients in simulations of one- and two-dimensional NMR spectra.
A method for the inclusion of the effects of z-axis pulsed field gradients in computer simulations of an arbitrary pulsed NMR experiment with spin (1/2) nuclei is described. Recognizing that the phase acquired by a coherence following the application of a z-axis pulsed field gradient bears a fixed relation to its order and the spatial position of the spins in the sample tube, the sample is regarded as a collection of volume elements, each phase-encoded by a characteristic, spatially dependent precession frequency. The evolution of the sample's density matrix is thus obtained by computing the evolution of the density matrix for each volume element. Following the last gradient pulse, these density matrices are combined to form a composite density matrix which evolves through the rest of the experiment to yield the observable signal. This approach is implemented in a program which includes capabilities for rigorous inclusion of spin relaxation by dipole-dipole, chemical shift anisotropy, and random field mechanisms, plus the effects of arbitrary RF fields. Mathematical procedures for accelerating these calculations are described. The approach is illustrated by simulations of representative one- and two-dimensional NMR experiments.


Planar microlens relay optics utilizing lateral focusing.
We have proposed a novel concept of planar microlens relay optics with the goal of realizing alignment-free and multifunctional integrated optical subsystems. Since the planar microlens is one of its key elements, its lateral focusing characteristics were examined. The measured focusing spot size was 3 microm x 7 microm, which is comparable with the core of single-mode optical fibers. By measuring the refractive-index distribution, we found that the planar microlens produced by the electromigration method has a desirable index distribution that resembles that of a Luneburg lens. Thus we conclude that planar microlens relay optics may be facilitated when the lateral focusing property of planar microlenses is used.


Co-occurrence of dual carbapenemases KPC-2 and OXA-48 with the mobile colistin resistance gene mcr-9.1 in Enterobacter xiangfangensis.
Bacterial infections with the genus Enterobacter are notoriously difficult to treat and often associated with resistance to penicillin, aminoglycosides, fluoroquinolones, and third-generation cephalosporins. Also, Enterobacter species have emerged as the third most common hosts for carbapenemases worldwide, forcing the use of colistin as a "last-resort" antibiotic for the treatment. Studies on the population structure of the genus Enterobacter repeatedly detect E. xiangfangensis as a common clinical species present worldwide. Here, we report on the characteristics of an extreme drug-resistant E. xiangfangensis isolate va18651 (ST88), obtained from a cervical swab of an expectant mother. The isolate was resistant to almost all the classes of antibiotics tested, including β-lactams (viz., penicillins, carbapenems, cephalosporin, monobactams, and their combinations), quinolone, aminoglycosides, and sulfonamide/dihydrofolate reductase inhibitor, and exhibited heteroresistance towards colistin. Analysis of its complete genome sequence revealed 37 antibiotic resistance genes (ARGs), including mcr-9.1, blaKPC-2 , and blaOXA-48 , encoded on three of the four different plasmids (cumulative plasmidome size 604,632 bp). An unusually high number of plasmid-based heavy metal resistance gene (HRG) clusters towards silver, arsenate, cadmium, copper, mercury, and tellurite were also detected. Virulence genes (VGs) for the lipopolysaccharide and capsular polysaccharide structures, iron acquisition (iroBCDEN, ent/fep/fes, sitABCD, iut, and fur), and a type VI secretion system, together with motility genes and Type IV pili, were encoded chromosomally. Thus, a unique combination of chromosomally encoded VGs, together with plasmid-encoded ARGs and HRGs, converged to result in an extreme drug-resistant, pathogenic isolate with survival potential in environmental settings. The use of a disinfectant, octenidine, led to its eradication; however, the existence of a highly antibiotic-resistant isolate with significant virulence potential is a matter of concern in public health settings and warrants further surveillance for extreme drug-resistant Enterobacter isolates.


Defective glomerulogenesis in the absence of laminin alpha5 demonstrates a developmental role for the kidney glomerular basement membrane.
Laminins are major components of all basement membranes. They are a diverse group of alpha/beta/gamma heterotrimers formed from five alpha, three beta, and three gamma chains. Laminin alpha5 is a widely expressed chain found in many embryonic and adult basement membranes. During embryogenesis, alpha5 has a role in disparate developmental processes, including neural tube closure, digit septation, and placentation. Here, we analyzed kidney development in Lama5 mutant embryos and found a striking defect in glomerulogenesis associated with an abnormal glomerular basement membrane (GBM). This correlates with failure of the developmental switch in laminin alpha chain deposition in which alpha5 replaces alpha1 in the GBM at the capillary loop stage of glomerulogenesis. In the absence of a normal GBM, glomerular epithelial cells were in disarray, and endothelial and mesangial cells were extruded from within the constricting glomerulus, leading to a complete absence of vascularized glomeruli. In addition, a minority of Lama5 mutant mice lacked one or both kidneys, indicating that laminin alpha5 is also important in earlier kidney development. Our results demonstrate a dual role for laminin alpha5 in kidney development, illustrate a novel defect in glomerulogenesis, and indicate a heretofore unappreciated developmental role for the GBM in influencing the behavior of epithelial and endothelial cells.


Dermoscopic features of eccrine porocarcinoma arising from hidroacanthoma simplex.
Eccrine porocarcinoma is a rare cutaneous neoplasm that mainly affects elderly people and grows slowly over a long period of time but often experiences an accelerated growth phase. Eccrine porocarcinoma may arise de novo or evolve from a pre-existing benign eccrine poroma. We reported a 86-year-old Japanese woman presenting with two reddish-colored pendulated lesions on a keratotic light brown plaque on the right thigh. Dermoscopic examination of the light-brown plaque demonstrated many whitish globular structures in a light-brown background. At the two reddish-colored pendulated lesions, polymorphous and prominent vessel proliferation was observed together with irregularly shaped whitish negative network. Immunohistochemical study demonstrated a positive CEA staining at ductal structures and atypical clear cells of reddish nodules. A diagnosis of eccrine porocarcinoma arising in a pigmented hidroacanthoma simplex was eventually established, and the dermoscopic features of eccrine porocarcinoma from hidroacanthoma simplex was described for the first time.


Enhancement of Virus Replication in An Influenza A Virus NS1-Expresssing 293 Cell Line.
The nonstructural protein 1 (NS1) of influenza A virus, which is absent from the viral particle, but highly expressed in infected cells, strongly antagonizes the interferon (IFN)-mediated antiviral response. We engineered an NS1-expressing 293 (293-NS1) cell line with no response to IFN stimulation. Compared with the parental 293 cells, the IFN-nonresponsive 293-NS1 cells improved the growth capacity of various viruses, but the introduction of NS1 barely enhanced the propagation of Tahyna virus, a negative-strand RNA virus. In particular, fastidious enteric adenovirus that replicates poorly in 293 cells may grow more efficiently in 293-NS1 cells; thus, IFN-nonresponsive 293-NS1 cells might be of great value in diagnostic laboratories for the cultivation and isolation of human enteric adenoviruses.


[Malignant pertussis: an underdiagnosed illness].
Malignant pertussis is a rare life-threatening illness characterized by severe respiratory failure, severe leukocytosis, and pulmonary hypertension. The purpose of this study was to determine the prevalence of malignant pertussis in infants admitted to a pediatric intensive care unit (PICU) for severe acute respiratory failure associated with severe leukocytosis. This retrospective study was based on review of the medical charts of infants aged less than 3 months admitted to the PICU between 2006 and 2008 for severe acute respiratory failure requiring mechanical ventilation with leukocytosis greater than 50,000/mm3. Clinical and laboratory data were collected. Polymerase chain reaction (PCR) for detection of Bordetella pertussis was performed on nasopharyngeal washes (NPW) stored at -70 degrees C. Ten patients meeting inclusion criteria were identified. Median age was 2.1 months (range, 0.6 - 3). None of the infants had been vaccinated against pertussis. Although PCR for pertussis was positive in all ten cases, presumptive diagnosis was made in only 3 patients during hospitalization. Nine patients died within a mean of 4.7 +/- 3.3 days after admission. The cause of death was refractory shock and hypoxemia in all cases. Only one patient survived. Malignant pertussis is a severe disease that is almost always fatal. It was underdiagnosed in our PICU. Use of PCR for detection of B. pertussis, i.e., the reference method, should be promoted in developing countries.


Data-Driven Classification of Dysarthria Profiles in Children With Cerebral Palsy.
The objectives of this study were to examine different speech profiles among children with dysarthria secondary to cerebral palsy (CP) and to characterize the effect of different speech profiles on intelligibility. Twenty 5-year-old children with dysarthria secondary to CP and 20 typically developing children were included in this study. Six acoustic and perceptual speech measures were selected to quantify a range of segmental and suprasegmental speech characteristics and were measured from children's sentence productions. Hierarchical cluster analysis was used to identify naturally occurring subgroups of children who had similar profiles of speech features. Results revealed 4 naturally occurring speech clusters among children: 1 cluster of children with typical development and 3 clusters of children with dysarthria secondary to CP. Two of the 3 dysarthria clusters had statistically equivalent intelligibility levels but significantly differed in articulation rate and degree of hypernasality. This study provides initial evidence that different speech profiles exist among 5-year-old children with dysarthria secondary to CP, even among children with similar intelligibility levels, suggesting the potential for developing a pediatric dysarthria classification system that could be used to stratify children with dysarthria into meaningful subgroups for studying speech motor development and efficacy of interventions.


IPF: new insight on pathogenesis and treatment.
Recent years have seen a robust influx of exciting new observations regarding the mechanisms that regulate the initiation and progression of pulmonary fibrosis but the pathogenesis remains poorly understood. The search for an alternative hypothesis to unremitting, chronic inflammation as the primary explanation for the pathophysiology of idiopathic pulmonary fibrosis (IPF) derives, in part, from the lack of therapeutic efficacy of high-dose immunosuppressive therapy in patients with IPF. The inflammatory hypothesis of IPF has since been challenged by the epithelial injury hypothesis, in which fibrosis is believed to result from epithelial injury, activation, and/or apoptosis with abnormal wound healing. This hypothesis suggests that recurrent unknown injury to distal pulmonary parenchyma causes repeated epithelial injury and apoptosis. The resultant loss of alveolar epithelium exposes the underlying basement membrane to oxidative damage and degradation. Emerging concepts suggest that IPF is the result of epithelial-mesenchymal interaction. The initiation of this fibrotic response may depend upon genetic factors and environmental triggers; the role of Th1 or Th2 cell-derived cytokines may also be important. This process appears to be unique to usual interstitial pneumonia/IPF. It is clear that IPF is a heterogeneous disease with variations in pathology, high-resolution computed tomography findings, and patterns of progression. Idiopathic pulmonary fibrosis is a complex disorder, and no unifying hypothesis has been identified at present that explains all the abnormalities.


Stabilizing Cellular Barriers: Raising the Shields Against COVID-19.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its clinical manifestation (COVID-19; coronavirus disease 2019) have caused a worldwide health crisis. Disruption of epithelial and endothelial barriers is a key clinical turning point that differentiates patients who are likely to develop severe COVID-19 outcomes: it marks a significant escalation in respiratory symptoms, loss of viral containment and a progression toward multi-organ dysfunction. These barrier mechanisms are independently compromised by known COVID-19 risk factors, including diabetes, obesity and aging: thus, a synergism between these underlying conditions and SARS-CoV-2 mechanisms may explain why these risk factors correlate with more severe outcomes. This review examines the key cellular mechanisms that SARS-CoV-2 and its underlying risk factors utilize to disrupt barrier function. As an outlook, we propose that glucagon-like peptide 1 (GLP-1) may be a therapeutic intervention that can slow COVID-19 progression and improve clinical outcome following SARS-CoV-2 infection. GLP-1 signaling activates barrier-promoting processes that directly oppose the pro-inflammatory mechanisms commandeered by SARS-CoV-2 and its underlying risk factors.


The stealth expatriate.
Global business practices have created a new category of worker, the stealth expatriate. Tax, immigration, and political risks exist for corporations that do not track this type of worker. Critical implications exist for occupational health nurses in the areas of travel health, fitness for duty, and emergency response.


Multiple cutaneous plexiform schwannomas. Report of a case and review of the literature with particular reference to the association with types 1 and 2 neurofibromatosis and schwannomatosis.
Plexiform schwannomas are relatively rare, benign peripheral nerve sheath tumors, which usually arise in either the dermis or subcutaneous tissue, although rare cases originate in skeletal muscle or other deep somatic soft tissue sites. These tumors may occur singly or as multiple lesions and may be localized to one anatomic site or diffusely distributed. Rare cases have been associated with "schwannomatosis" as well as type 1 neurofibromatosis (von Recklinghausen's disease). We report an unusual case of multiple cutaneous plexiform schwannomas associated with bilateral acoustic neuromas as well as other intracranial and intraspinal neoplasms. In addition, we examine the relationship between the various forms of cutaneous schwannoma, particularly the plexiform variant, and both types 1 and 2 neurofibromatosis; we also examine several purported cases of schwannomatosis.


Protein Corona Liposomes Achieve Efficient Oral Insulin Delivery by Overcoming Mucus and Epithelial Barriers.
Oral delivery of peptide/protein drugs has attracted worldwide attention due to its good patient compliance and convenience of administration. Orally administered nanocarriers always encounter the rigorous defenses of the gastrointestinal tract, which mainly consist of mucus and epithelium barriers. However, diametrically opposite surface properties of nanocarriers are required for good mucus penetration and high epithelial uptake. Here, bovine serum albumin (BSA) is adsorbed to cationic liposomes (CLs) to form protein corona liposomes (PcCLs). The aim of using PcCLs is to conquer the mucus and epithelium barriers, eventually improving the oral bioavailability of insulin. Investigations using in vitro and in vivo experiments show that the uptake amounts and transepithelial permeability of PcCLs are 3.24- and 7.91-fold higher than that of free insulin, respectively. Further study of the behavior of PcCLs implies that BSA corona can be shed from PcCLs as they cross the mucus layer, which results in the exposure of CLs to improve the transepithelial transport. Intrajejunal administration of PcCLs in type I diabetic rats produces a remarkable hypoglycemic effect and increases the oral bioavailability up to 11.9%. All of these results imply that PcCLs may provide a new insight into the method for oral insulin delivery by overcoming the multiple barriers.


Evidence of endoplasmic reticulum stress and protein synthesis inhibition in the placenta of non-native women at high altitude.
Pregnancy at high altitude is associated with a reduction in birth weight of ∼100 g/1000 m of ascent. The underlying mechanisms are unclear but may involve alteration in energy-demanding activities, such as protein synthesis. To test this hypothesis, both in vivo and in vitro approaches were used. Placental tissues from pregnant women residing at 3100 m were studied, and placental cells were incubated under hypoxia. In the 3100-m placentas, we observed dilation of endoplasmic reticulum (ER) cisternae, increased phosphorylation of eukaryotic initiation factor 2 subunit α (P-eIF2α), reduced AKT phosphorylation, and reduced P-4E-BP1 but increased 4E-BP1 protein compared to sea level controls. These findings suggest the presence of ER stress and protein synthesis inhibition. Hypoxia (1% O(2)) reduced proliferation of trophoblast-like JEG-3 cells, BeWo cells, and placental fibroblasts by ∼40, ∼60, and ∼18%, respectively. Sublethal dosage of salubrinal, an eIF2α phosphatase inhibitor, increased P-eIF2α and reduced BeWo cell and placental fibroblast proliferation by ∼50%. Administration of the PI-3K inhibitor LY294002 also reduced JEG-3 proliferation. Our results demonstrate that exposure to chronic hypobaric hypoxia causes mild placental ER stress, which, in turn, modulates protein synthesis and slows proliferation. These effects may account for the reduced placental villous volume, and contribute to the low birth weight that typifies high-altitude populations.


Identification of a jasmonate-regulated allene oxide synthase that metabolizes 9-hydroperoxides of linoleic and linolenic acids.
Allene oxide synthase (AOS) is a cytochrome P-450 (CYP74A) that catalyzes the first step in the conversion of 13-hydroperoxy linolenic acid to jasmonic acid and related signaling molecules in plants. Here, we report the molecular cloning and characterization of a novel AOS-encoding cDNA (LeAOS3) from Lycopersicon esculentum whose predicted amino acid sequence classifies it as a member of the CYP74C subfamily of enzymes that was hitherto not known to include AOSs. Recombinant LeAOS3 expressed in Escherichia coli showed spectral characteristics of a P-450. The enzyme transformed 9- and 13-hydroperoxides of linoleic and linolenic acid to alpha-ketol, gamma-ketol, and cyclopentenone compounds that arise from spontaneous hydrolysis of unstable allene oxides, indicating that the enzyme is an AOS. Kinetic assays demonstrated that LeAOS3 was approximately 10-fold more active against 9-hydroperoxides than the corresponding 13-isomers. LeAOS3 transcripts accumulated in roots, but were undetectable in aerial parts of mature plants. In contrast to wild-type plants, LeAOS3 expression was undetectable in roots of a tomato mutant that is defective in jasmonic acid signaling. These findings suggest that LeAOS3 plays a role in the metabolism of 9-lipoxygenase-derived hydroperoxides in roots, and that this branch of oxylipin biosynthesis is regulated by the jasmonate signaling cascade.


A dedicated feeding tube clinic reduces emergency department utilization for gastrostomy tube complications.
Enteral access is required for a variety of reasons from neuromuscular disorders to dysphagia. Gastrostomy tubes (GTs) can be placed endoscopically, surgically, or radiographically and complications include infection, bleeding, leakage and unintentional removal. Routine post-procedural follow-up is limited by inconsistent guidelines and management by different specialty teams. We established a dedicated GT clinic to provide continuity of care and prophylactic GT exchange. We hypothesized that patients followed in the GT clinic would have reduced Emergency Department (ED) utilization. A retrospective review of patients who underwent GT placement from January 2010 to January 2020 was conducted. Baseline demographics, indications for GT placement, number and reason for ED visits and utilization of a multidisciplinary GT clinic were studied. A total of 97 patients were included. The most common indication for placement was dysphagia (88, 91%) and the most common primary diagnosis was head and neck malignancy (51, 51%). The GT clinic is a multidisciplinary clinic staffed by surgeons and residents, dieticians, and wound care specialists and cared for 16 patients in this study. Three patients (19%) in the GT clinic group required ED visits compared to 44 (54%) in the standard of care (SOC) group (p < 0.05). There was an average of 0.9 ED visits per patient (range 0-7) in the GT clinic group vs 1.6 ED visits per patient (range 0-20) in the SOC group (p = 0.34). Feeding tubes were prophylactically exchanged an average of 7 times per patient in the GT clinic group vs 3 times per patient in the SOC group (p < 0.05). A multidisciplinary clinic dedicated to GT care limits ED visits for associated complications by more than 50%. Follow-up in a dedicated clinic with prophylactic tube exchange decreases ED visits and should be considered at facilities that care for patients with GTs.


High-Dose Convalescent Plasma for Treatment of Severe COVID-19.
To assess whether high-dose coronavirus disease (COVID-19) convalescent plasma (CCP) transfusion may benefit patients with severe COVID-19, we conducted a multicenter randomized trial in Brazil. Patients with severe COVID-19 who were within 10 days of initial symptom onset were eligible. Patients in the CCP group received 3 daily doses of CCP (600 mL/d) in addition to standard treatment; control patients received standard treatment only. Primary outcomes were death rates at days 30 and 60 of study randomization. Secondary outcomes were ventilator-free days and hospital-free days. We enrolled 107 patients: 36 CCP and 71 control. At day 30, death rates were 22% for CCP and 25% for the control group; at day 60, rates were 31% for CCP and 35% for control. Needs for invasive mechanical ventilation and durations of hospital stay were similar between groups. We conclude that high-dose CCP transfused within 10 days of symptom onset provided no benefit for patients with severe COVID-19.


Natural Language Processing in Spine Surgery: A Systematic Review of Applications, Bias, and Reporting Transparency.
Natural language processing (NLP) is a discipline of machine learning concerned with the analysis of language and text. Although NLP has been applied to various forms of clinical text, the applications and utility of NLP in spine surgery remain poorly characterized. Here, we systematically reviewed studies that use NLP for spine surgery applications, and analyzed applications, bias, and reporting transparency of the studies. We performed a literature search using the PubMed, Scopus, and Embase databases. Data extraction was performed after appropriate screening. The risk of bias and reporting quality were assessed using the PROBAST and TRIPOD tools. A total of 12 full-text articles were included. The most common diseases represented include spondylolisthesis (25%), scoliosis (17%), and lumbar disk herniation (17%). The most common procedures included spinal fusion (42%), imaging (e.g. magnetic resonance, X-ray) (25%), and scoliosis correction (17%). Reported outcomes were diverse and included incidental durotomy, venous thromboembolism, and the tone of social media posts regarding scoliosis surgery. Common sources of bias identified included the use of older methods that do not capture the nuance of a text, and not using a prespecified or standard outcome measure when evaluating NLP methods. Although the application of NLP to spine surgery is expanding, current studies face limitations and none are indicated as ready for clinical use. Thus, for future studies we recommend an emphasis on transparent reporting and collaboration with NLP experts to incorporate the latest developments to improve models and contribute to further innovation.


Low brain intracellular free magnesium in mitochondrial cytopathies.
The authors studied, by in vivo phosphorus magnetic resonance spectroscopy (31P-MRS), the occipital lobes of 19 patients with mitochondrial cytopathies to clarify the functional relation between energy metabolism and concentration of cytosolic free magnesium. All patients displayed defective mitochondrial respiration with low phosphocreatine concentration [PCr] and high inorganic phosphate concentration [Pi] and [ADP]. Cytosolic free [Mg2+] and the readily available free energy (defined as the actual free energy released by the exoergonic reaction of ATP hydrolysis, i.e., deltaG(ATPhyd)) were abnormally low in all patients. Nine patients were treated with coenzyme Q10 (CoQ), which improved the efficiency of the respiratory chain, as shown by an increased [PCr], decreased [Pi] and [ADP], and increased availability of free energy (more negative value of deltaG(ATPhyd)). Treatment with CoQ also increased cytosolic free [Mg2+] in all treated patients. The authors findings demonstrate low brain free [Mg2+] in our patients and indicate that it resulted from failure of the respiratory chain. Free Mg2+ contributes to the absolute value of deltaG(ATPhyd). The results also are consistent with the view that cytosolic [Mg2+] is regulated in the intact brain cell to equilibrate, at least in part, any changes in rapidly available free energy.


An unusual clinical presentation of gingival melanoacanthoma.
Gingival melanoacanthoma is a rare, benign pigmented lesion characterized clinically by sudden onset and rapid growth of a macular brown black lesion and histologically by acanthosis of superficial epithelium and proliferation of dendritic melanocytes. This article reports a previously undescribed case of pigmented unilateral diffuse gingival enlargement, which on histopathological examination proved to be melanoacanthoma. Intraoral examination revealed pigmented unilateral diffuse gingival enlargement in relation to second and third quadrants buccally, palatally/lingually. Based on these clinical findings, gingivectomy was performed and the excised tissue was sent for biopsy. Microscopic examination revealed acanthotic and parakeratotic surface epithelium with dendritic melanocytes distributed in basal and suprabasal layers of the epithelium. 1 year follow-up recall revealed no recurrence of lesion at the surgical sites. Our patient exhibits an unusual clinical presentation of melanoacanthoma of gingiva. Pigmented gingival overgrowth of recent origin and without any etiologic factors warrants histopathologic examination.


Positive Sentiment and the Donation Amount: Social Norms in Crowdfunding Donations During the COVID-19 Pandemic.
Public welfare fundraising has been used to collect donations for medical supplies and has played an important role in the fight against the COVID-19 pandemic. This paper studies online crowdfunding donations from the Alumni Association of Wuhan University to North American alumni; donation data are used to investigate how individuals' donation behavior is affected by the previous donation amount and information provided by the fundraising platform. First, our results show that one's donation amount is positively affected by the previous donation amount. Second, the donor's positive sentiment in the message that he or she leaves, as measured by either natural language processing or a manual rating, can affect the subsequent anonymity and messages but not the subsequent donation amount. Third, anonymous donations are much smaller than non-anonymous donations.


Effects of emotion on oxytocin, prolactin, and ACTH in women.
Research on both non-human mammals and humans has raised interest in the role that oxytocin may play in human attachment and attachment-related emotions. This study examined changes in plasma oxytocin, prolactin, and ACTH concentrations in response to laboratory-induced positive and negative emotions related to close, interpersonal relationships. Participants were 32 female volunteers recruited from university communities. During positive emotion induction, oxytocin decreased over time (F(1,3) = 4.41, p < 0.007), prolactin increased (F(1,3) = 4.80, p < 0.004) and ACTH remained constant. During negative emotion induction, prolactin levels increased (F(1,3) = 2.81, p < 0.05), ACTH decreased only after the induction terminated (F(1,3) = 4.02, p < 0.01) and oxytocin remained constant. While oxytocin decreased during positive emotion, this finding contrasted previous research that showed decreases in response to negative emotion. In conclusion, plasma oxytocin levels were not reliably altered by positive or negative emotion induction. While prolactin and ACTH were expected to decrease over time due to diurnal variation, they instead either increased or remained level during emotion induction, or decreased only after the induction. Overall, the degree of change in circulating hormones in response to happy and sad emotions was very small and possibly not functionally significant.


c-met is overexpressed in type I ovarian cancer: Results of an investigative analysis in a cohort of consecutive ovarian cancer patients.
The tyrosine kinase c-met alters signaling cascades such as the BRAF-MAPK and PI3K-PKB pathways. These alterations are involved in the carcinogenesis of type I but not type II ovarian cancer (OC). Therefore, the present study investigated the patterns of c-met expression in a cohort of consecutive patients with OC. c-met expression was determined by immunohistochemical analysis. Differences in c-met overexpression among subgroups of established clinicopathological features, including age, histological subtype, tumor stage, histological grading, post-operative tumor burden and completeness of chemotherapy, were determined by χ2 test. Cox regression analyses were performed to determine the prognostic effect of c-met. Survival rates were estimated using the Kaplan-Meier method. A total of 106 patients were enrolled into the study. c-met was overexpressed in 20.8% of the entire cohort; 35.7% of patients with type I OC and 8.6% of patients with type II OC showed overexpression (P=0.001). However, c-met overexpression was not associated with any other established clinicopathological features (all P-values >0.05). Univariate Cox regression analysis showed that overexpression of c-met was associated neither with progression-free survival (PFS) nor with disease-specific survival (DSS) (P=0.835 and P=0.414, respectively). Kaplan-Meier plots also failed to demonstrate an effect of c-met on the 5-year PFS and DSS rates (P=0.938 and P=0.412, respectively). These findings support the hypotheses that the overexpression of c-met is associated with type I but not type II OC, and that overexpression of c-met does not affect the prognosis of OC.


Characteristics of First Visit Pediatric Patients with Suicidal Ideation and Behavior: An 8-Year Retrospective Chart Review.
Our study aimed to analyze the demographic and clinical characteristics of children and adolescents during their first visit to psychiatric outpatient departments for the management of suicidal ideation and behavior, and to compare the changes before and in 2012 or later. This multicenter study was conducted at five university hospitals in a metropolitan area in South Korea. Medical records of patients aged 6-18 years were retrospectively reviewed from January 2009 to December 2016. Patients were analyzed by classifying them into suicidal and non-suicidal groups based on their visit to the hospital for management of suicidal ideation or suicide attempt and other mental problems, respectively. There were differences in the year of visit, diagnosis, education level, and referral sources between patients in the suicidal and non-suicidal groups. Multiple regression analysis was conducted based on the sex, education level, referral by school, and diagnosis of depression in patients in the suicidal group, which revealed significant association. Suicide-related problems were significantly associated with the sex, education level, referral by school, and a diagnosis of depression in the patients. A well-connected referral system would be necessary for professional mental health management of high-risk children and adolescents.


The Essential Role of Stathmin in Myoblast C2C12 for Vertical Vibration-Induced Myotube Formation.
Vertical vibration (VV) is a type of whole body vibration, which induces muscle contraction through vibration to improve muscle strength and bone density. However, the mechanism of VV on muscle cell myotube formation is still unclear. In the current study, we aim to clarify the mechanism involved in VV's stimulation of myotube formation. In order to identify the molecules regulated by VV, we performed proteomics analysis including 2D electrophoresis combined with MALDI-TOF/TOF Mass. Stathmin was identified as a high potential molecule responding to VV stimulation, and we found that under VV stimulation, the expression of stathmin gene and protein increased in a time-dependent manner. In addition, we also confirmed that the increase of stathmin stimulated by VV is mediated through the PI3K/Akt pathway. Furthermore, stathmin siRNA significantly down-regulated the expression of myogenic regulatory factor (MRF) MyoD, decorin, and type I collagen (Col-I), and down-regulated the cellular process regulators such as FGF7, TGFBr1 and PAK3. Taken together, our results confirm that under the stimulation of VV, PI3K/Akt and stathmin would be activated, as well as the up-regulation of MRFs, such as FGF7, TGFBr1 and PAK3 to initiate myogenesis. It also showed that the response of MRF to VV stimulation was significantly related to stathmin expression, which also confirmed the importance of stathmin in the entire myotube formation process. This study may provide evidence of stathmin as a biological indicator of VV to increase muscle strength.


Increasing Voluntary Myoelectric Training Time Through Game Design.
In virtual prosthetic training research, serious games have been investigated for over 30 years. However, few game design elements are used and assessed for their effect on the voluntary adherence and repetition of the performed task. We compared two game-based versions of an established myoelectric-controlled virtual prosthetic training task with an interface without game elements of the same task [for video, see (Garske, 2022)]. Twelve limb-intact participants were sorted into three groups of comparable ability and asked to perform the task as long as they were motivated. Following the task, they completed a questionnaire regarding their motivation and engagement in the task. The investigation established that participants in the game-based groups performed the task significantly longer when more game design elements were implemented in the task (medians of 6 vs. 9.5 vs. 14 blocks for groups with increasing number of different game design elements). The participants in the game-based versions were also more likely to end the task out of fatigue than for reasons of boredom or frustration, which was verified by a fatigue analysis of the myoelectric signal. We demonstrated that the utilization of game design methodically in virtual myoelectric training tasks can support adherence and duration of a virtual training, in the short-term. Whether such short-term enhanced engagement would lead to long-term adherence remains an open question.


Simultaneous live-imaging of peroxisomes and the ER in plant cells suggests contiguity but no luminal continuity between the two organelles.
Transmission electron micrographs of peroxisomes in diverse organisms, including plants, suggest their close association and even luminal connectivity with the endoplasmic reticulum (ER). After several decades of debate de novo peroxisome biogenesis from the ER is strongly favored in yeasts and mammals. Unfortunately many of the proteins whose transit through the ER constitutes a major evidence for peroxisome biogenesis from the ER do not exhibit a similar localization in plants. Consequently, at best the ER acts as a membrane source for peroxisome in plants. However, in addition to their de novo biogenesis from the ER an increase in peroxisome numbers also occurs through fission of existing peroxisomes. In recent years live-imaging has been used to visualize peroxisomes and the ER but the precise spatio-temporal relationship between the two organelles has not been well-explored. Here we present our assessment of the peroxisome-ER relationship through imaging of living Arabidopsis thaliana plants simultaneously expressing different color combinations of fluorescent proteins targeted to both organelles. Our observations on double transgenic wild type and a drp3a/apm1 mutant Arabidopsis plants suggest strong correlations between the dynamic behavior of peroxisomes and the neighboring ER. Although peroxisomes and ER are closely aligned there appears to be no luminal continuity between the two. Similarly, differentially colored elongated peroxisomes of a drp3a mutant expressing a photoconvertible peroxisomal matrix protein are unable to fuse and share luminal protein despite considerable intermingling. Substantiation of our observations is suggested through 3D iso-surface rendering of image stacks, which shows closed ended peroxisomes enmeshed among ER tubules possibly through membrane contact sites (MCS). Our observations support the idea that increase in peroxisome numbers in a plant cell occurs mainly through the fission of existing peroxisomes in an ER aided manner.


Infectious coryza in a grey crowned crane (Balearica regulorum) recovered from captivity.
We report Avibacterium paragallinarum and Klebsiella pneumoniae coinfection in a grey crowned crane (Balearica regulorum). The crane was recovered from illegal captivity and released at a grey crowned crane (GCC) rehabilitation facility located at Akagera National Park in Rwanda. One year after being transferred, the bird presented with clinical signs suggesting a respiratory disease. Those signs included severe dyspnoea with mouth breathing, sneezing and nasal discharge. The crane was put on a 3-day treatment with antibiotics (ceftiofur 200 mg/ml at 50 mg/kg intramuscularly) and anti-inflammatory drug (meloxicam, intramuscular injection at a dose of 2 mg/kg), after which the crane seemed to have recovered. A month later, the same crane presented similar clinical signs and was treated with enrofloxacin at 10 mg/kg intramuscularly. Despite the treatment, the crane died 19 h later. At necropsy, adhesive air sacculitis and hydroperitoneum were observed, and a reddish fluid in air sacs and in the abdominal cavity was found. Also, a marked hepatomegaly and splenomegaly were observed. Samples were collected for laboratory examination. Molecular tests done on the tracheal and cloacal swabs revealed A. paragallinarum and K. pneumoniae, respectively. This is the first case of A. paragallinarum and K. pneumoniae coinfection reported in a grey crowned crane. Our study contributes to knowledge on the ecological distribution of both these pathogens in wild birds. It provides an opportunity to investigate further the clinical significance of infectious coryza in Rwanda's wild and domestic birds.


Microglial tau undergoes phosphorylation-independent modification after ischemia.
Tau2 is a phosphorylation-independent antibody that immunolabels neurofibrillary tangles (NFTs) of Alzheimer type and microglia around ischemic foci on formalin-fixed, paraffin-embedded sections. We found that copresence of polyethyleneglycol-p-isooctylphenyl ether (Triton X-100; TX) with tau2 abolished its immunoreactivity (IR) in these microglia but not its IR on NFTs. Tau2-immunoreactive bands, exclusively retrieved in Tris-soluble fraction of brain homogenates from ischemic foci, normal human and bovine brains, were of similar electrophoretic mobility, indicating that tau2 IR in these microglia is unrelated to hyperphosphorylation of tau. These tau2-immunoreactive bands except those from bovine brain were abolished in the copresence of TX. This was not due to washing out of tau, because similar immunoreactive bands were detectable with another antitau antibody even under a higher concentration of TX and because washing after TX exposure restored similar tau2 IR both on immunohistochemistry and immunoblot. These findings are explained if tau, modified after ischemia, undergoes a reversible conformational change on TX exposure. Because conformation at Ser101 of bovine tau is crucial for its affinity to tau2, this Ser-like conformation mimicked by its human counterpart Pro may represent pathological modification of tau shared by microglia around ischemic foci and NFTs. Relative resistance of tau2 epitope in NFTs to TX exposure suggests that tau woven into NFTs confers additional stability to this pathological modification on tau2 epitope. Susceptibility of tau2 epitope to TX, seen in these microglia, is shared with glial cytoplasmic inclusions and will show its conformational state to be different from that in NFTs.


Morphology transitions in nonionic surfactant adsorbed layers near their cloud points.
The structure of adsorbed layers of several polyoxyethylene alkyl ether (C(n)E(m)) nonionic surfactants on silica and graphite surfaces has been imaged using atomic force microscopy as a function of temperature up to their cloud points. For all surfactants with a cloud point within the experimentally accessible range, the adsorbed layer morphology on silica evolved from globules at low temperatures first into rods and then a mesh with increasing temperature. This mesh structure was retained even when the solutions were heated above their cloud points into the two-phase coexistence region. Only C(12)E(3) was observed to form a laterally unstructured bilayer. On graphite, all surfactants formed straight, parallel hemicylinders at all temperatures examined.


Improving Wettability at Positive Electrodes to Enhance the Cycling Stability of Bi-Based Liquid Metal Batteries.
Liquid metal batteries (LMBs) are promising candidates for grid-scale energy storage due to their exceptional kinetics, scalability, and long lifespan derived from the distinctive three-liquid-layer structure. However, the positive electrode (such as Bi) suffers from insufficient wettability on the current collector, resulting in excess electrical resistance and uneven current distribution, thus deteriorating the cycling stability. Here the incorporation of 4 mol% Se into Bi-based metal is proposed producing an interface layer with highly surface-active property that decreases the electrode's contact angle with the 304 stainless-steel (SUS304) from 144.7° to 74.3°, so as to improve the wettability. The as-prepared 20 Ah Li || Bi-Se4 (the content of Se is 4 mol% of Bi) cell cycled 1200 times with capacity fade rate of merely 0.00174% per cycle. This facile and effective approach provides a pathway toward the production of stable cells with an extended lifespan and boosts the practical implementation of LMBs.


Identifying main effects and epistatic interactions from large-scale SNP data via adaptive group Lasso.
Single nucleotide polymorphism (SNP) based association studies aim at identifying SNPs associated with phenotypes, for example, complex diseases. The associated SNPs may influence the disease risk individually (main effects) or behave jointly (epistatic interactions). For the analysis of high throughput data, the main difficulty is that the number of SNPs far exceeds the number of samples. This difficulty is amplified when identifying interactions. In this paper, we propose an Adaptive Group Lasso (AGL) model for large-scale association studies. Our model enables us to analyze SNPs and their interactions simultaneously. We achieve this by introducing a sparsity constraint in our model based on the fact that only a small fraction of SNPs is disease-associated. In order to reduce the number of false positive findings, we develop an adaptive reweighting scheme to enhance sparsity. In addition, our method treats SNPs and their interactions as factors, and identifies them in a grouped manner. Thus, it is flexible to analyze various disease models, especially for interaction detection. However, due to the intensive computation when millions of interaction terms needs to be searched in the model fitting, our method needs to combined with some filtering methods when applied to genome-wide data for detecting interactions. By using a wide range of simulated datasets and a real dataset from WTCCC, we demonstrate the advantages of our method.


Glucose, insulin, and glucagon levels during exercise in pancreas transplant recipients.
To determine whether pancreas transplant recipients maintain normal blood glucose levels during physical exercise. We measured serum glucose, insulin, C-peptide, and plasma glucagon levels in six pancreas transplant recipients and six healthy control subjects matched for age, sex, body size, and level of conditioning during 1 h of bicycle exercise at a workload set to achieve 40% of each individual's previously determined peak oxygen consumption (VO2). Serum glucose values were not different between control subjects and transplant recipients before the start of exercise (5.0 +/- 0.1 and 4.9 +/-0.1 mmol/l, respectively). Serum glucose levels fell slightly but significantly in both recipients and control subjects during exercise. There were no significant differences in glucose levels between the two groups at any time point during exercise, although mean nadir glucose during exercise was slightly lower in transplant recipients compared with control subjects (4.4 +/- 0.1 vs. 4.8 +/- 0.1 mmol/l, P = 0.04). In control subjects, insulin and C-peptide levels fell significantly within 15-30 min of exercise and glucagon levels rose significantly after 60 min of exercise. In transplant recipients, there was a trend for insulin and C-peptide levels to fall and glucagon levels to rise during exercise, although these changes were delayed and were not statistically significant. No significant abnormalities in blood glucose were detected in pancreas transplant recipients during bicycle exercise at 40% of peak VO2 for 1 h. Compared with levels in control subjects, subtle alterations in insulin and glucagon levels may occur in transplant recipients during exercise. However, these alterations do not appear to result in either hyperglycemia or hypoglycemia during light exercise for up to 1 h.


Enhanced Metabolic Stress Augments Ischemic Preconditioning for Exercise Performance.
Purpose: To identify the combined effect of increasing tissue level oxygen consumption and metabolite accumulation on the ergogenic efficacy of ischemic preconditioning (IPC) during both maximal aerobic and maximal anaerobic exercise. Methods: Twelve healthy males (22 ± 2 years, 179 ± 2 cm, 80 ± 10 kg, 48 ± 4 ml.kg-1.min-1) underwent four experimental conditions: (i) no IPC control, (ii) traditional IPC, (iii) IPC with EMS, and (iv) IPC with treadmill walking. IPC involved bilateral leg occlusion at 220 mmHg for 5 min, repeated three times, separated by 5 min of reperfusion. Within 10 min following the IPC procedures, a 30 s Wingate test and subsequent (after 25 min rest) incremental maximal aerobic test were performed on a cycle ergometer. Results: There was no statistical difference in anaerobic peak power between the no IPC control (1211 ± 290 W), traditional IPC (1209 ± 300 W), IPC + EMS (1206 ± 311 W), and IPC + Walk (1220 ± 288 W; P = 0.7); nor did VO2max change between no IPC control (48 ± 2 ml.kg-1.min-1), traditional IPC (48 ± 6 ml.kg-1.min-1), IPC + EMS (49 ± 4 ml.kg-1.min-1) and IPC + Walk (48 ± 6 ml.kg-1.min-1; P = 0.3). However, the maximal watts during the VO2max increased when IPC was combined with both EMS (304 ± 38 W) and walking (308 ± 40 W) compared to traditional IPC (296 ± 39 W) and no IPC control (293 ± 48 W; P = 0.02). Conclusion: This study shows that in a group of participants for whom a traditional IPC stimulus was not effective, the magnification of the IPC stress through muscle contractions while under occlusion led to a subsequent exercise performance response. These findings support that amplification of the ischemic preconditioning stimulus augments the effect for exercise capacity.


Myeloperoxidase in the plasma and placenta of normal pregnant women and women with pregnancies complicated by preeclampsia and intrauterine growth restriction.
Myeloperoxidase (MPO) is a heme protein produced and released by activated neutrophils and monocytes, and increased MPO is considered important in the pathophysiology of cardiovascular diseases (CVD). Accumulating evidence suggests that preeclampsia (PE), idiopathic intrauterine growth restriction (IUGR), and CVD share many similar metabolic disturbances, including an enhanced systemic inflammatory response and endothelial dysfunction. We hypothesized that MPO plays an important role in the development of PE and IUGR. Plasma samples were collected mid-gestation and at delivery from women with normal pregnancies (n = 40) and those who subsequently developed PE (n = 20), IUGR (n = 11) or both (PE + IUGR, n = 8). Placental samples were obtained immediately after delivery from 22 women with normal pregnancies, 19 women with PE, 14 women with IUGR, and 14 women with PE + IUGR. The MPO concentrations were measured using ELISA. Women with PE + IUGR had significantly higher plasma MPO before delivery than normal pregnant women. There was no difference in plasma levels at mid-gestation or the placental concentrations between women with normal pregnancies and those who developed PE, IUGR, or PE + IUGR. Using explants prepared from the placentas of 8 women with normal pregnancies and 8 women with PE, we found no difference in the levels of MPO in the tissue homogenates and culture media between these two groups of women. Together, these results indicate that increased maternal circulating MPO in women with PE + IUGR is likely a result of enhanced systemic inflammation caused by the established disease rather than a primary pathophysiological factor.


Continuous EEG monitoring in the intensive care unit.
Continuous EEG (CEEG) monitoring allows uninterrupted assessment of cerebral cortical activity with good spatial resolution and excellent temporal resolution. Thus, this procedure provides a means of constantly assessing brain function in critically ill obtunded and comatose patients. Recent advances in digital EEG acquisition, storage, quantitative analysis, and transmission have made CEEG monitoring in the intensive care unit (ICU) technically feasible and useful. This article summarizes the indications and methodology of CEEG monitoring in the ICU, and discusses the role of some quantitative EEG analysis techniques in near real-time remote observation of CEEG recordings. Clinical examples of CEEG use, including monitoring of status epilepticus, assessment of ongoing therapy for treatment of seizures in critically ill patients, and monitoring for cerebral ischemia, are presented. Areas requiring further development of CEEG monitoring techniques and indications are discussed.


Basic fibroblast growth factor accelerates myelin debris clearance through activating autophagy to facilitate early peripheral nerve regeneration.
The successful removal of damaged myelin sheaths during Wallerian degeneration (WD) is essential for ensuring structural remodelling and functional recovery following traumatic peripheral nerve injury (PNI). Recent studies have established that autophagy involves myelin phagocytosis and cellular homoeostasis, and its disorder impairs myelin clearance. Based on the role of basic fibroblast growth factor (bFGF) on exerting neuroprotection and angiogenesis during nerve tissue regeneration, we now explicitly focus on the issue about whether the therapeutic effect of bFGF on supporting nerve regeneration is closely related to accelerate the autophagic clearance of myelin debris during WD. Using sciatic nerve crushed model, we found that bFGF remarkedly improved axonal outgrowth and nerve reconstruction at the early phase of PNI (14 days after PNI). More importantly, we further observed that bFGF could enhance phagocytic capacity of Schwann cells (SCs) to engulf myelin debris. Additionally, this enhancing effect is accomplished by autophagy activation and the increase of autophagy flux by immunoblotting and immune-histochemical analyses. Taken together, our data suggest that the action of bFGF on modulating early peripheral nerve regeneration is closely associated with myelin debris removal by SCs, which might result in SC-mediated autophagy activation, highlighting its insight molecular mechanism as a neuroprotective agent for repairing PNI.


Disease vector occurrence and ecological characteristics of chiggers on the chestnut white-bellied rat Niviventer fulvescens in Southwest China between 2001 and 2019.
Chigger mites are the vector of scrub typhus. This study estimates the infestation status and ecological characteristics of chiggers on the chestnut white-bellied rat Niviventer fulvescens in Southwest China between 2001 and 2019. Chiggers were identified under the microscope, and infestation indices were calculated. The Preston's log-normal model was used to fit the curve of species abundance distribution. A total of 6,557 chiggers were collected in 136 of 342 N. fulvescens rats, showing high overall infestation indices (prevalence=39.8%, mean abundance=19.2, mean intensity=48.2) and high species diversity (S=100, H'=3.0). Leptotrombidium cangjiangense, Neotrombicula japonica, and Ascoschoengastia sifanga were the three dominant chigger species (constituent ratio=42.9%; 2,736/6,384) and exhibited an aggregated distribution among different rat individuals. We identified 100 chigger species, with 3 of them (Leptotrombidium scutellare, Leptotrombidium wenense, and Leptotrombidium deliense) as the main vectors of scrub typhus in China and nine species as potential vectors of this disease. Disease vector occurrence on N. fulvescens may increase the risk of spreading scrub typhus from rats to humans. Chigger infestation on N. fulvescens varied significantly in different environments. The species abundance distribution showed a log-normal distribution pattern. The estimated number of chigger species on N. fulvescens was 126 species.


Intravitreally transplanted dental pulp stem cells promote neuroprotection and axon regeneration of retinal ganglion cells after optic nerve injury.
To investigate the potential therapeutic benefit of intravitreally implanted dental pulp stem cells (DPSCs) on axotomized adult rat retinal ganglion cells (RGCs) using in vitro and in vivo neural injury models. Conditioned media collected from cultured rat DPSCs and bone marrow-derived mesenchymal stem cells (BMSCs) were assayed for nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) secretion using ELISA. DPSCs or BMSCs were cocultured with retinal cells, with or without Fc-TrK inhibitors, in a Transwell system, and the number of surviving βIII-tubulin⁺ retinal cells and length/number of βIII-tubulin⁺ neurites were quantified. For the in vivo study, DPSCs or BMSCs were transplanted into the vitreous body of the eye after a surgically induced optic nerve crush injury. At 7, 14, and 21 days postlesion (dpl), optical coherence tomography (OCT) was used to measure the retinal nerve fiber layer thickness as a measure of axonal atrophy. At 21 dpl, numbers of Brn-3a⁺ RGCs in parasagittal retinal sections and growth-associated protein-43⁺ axons in longitudinal optic nerve sections were quantified as measures of RGC survival and axon regeneration, respectively. Both DPSCs and BMSCs secreted NGF, BDNF, and NT-3, with DPSCs secreting significantly higher titers of NGF and BDNF than BMSCs. DPSCs, and to a lesser extent BMSCs, promoted statistically significant survival and neuritogenesis/axogenesis of βIII-tubulin⁺ retinal cells in vitro and in vivo where the effects were abolished after TrK receptor blockade. Intravitreal transplants of DPSCs promoted significant neurotrophin-mediated RGC survival and axon regeneration after optic nerve injury.


The role of terrestrial plants in limiting atmospheric CO(2) decline over the past 24 million years.
Environmental conditions during the past 24 million years are thought to have been favourable for enhanced rates of atmospheric carbon dioxide drawdown by silicate chemical weathering. Proxy records indicate, however, that the Earth's atmospheric carbon dioxide concentrations did not fall below about 200-250 parts per million during this period. The stabilization of atmospheric carbon dioxide concentrations near this minimum value suggests that strong negative feedback mechanisms inhibited further drawdown of atmospheric carbon dioxide by high rates of global silicate rock weathering. Here we investigate one possible negative feedback mechanism, occurring under relatively low carbon dioxide concentrations and in warm climates, that is related to terrestrial plant productivity and its role in the decomposition of silicate minerals. We use simulations of terrestrial and geochemical carbon cycles and available experimental evidence to show that vegetation activity in upland regions of active orogens was severely limited by near-starvation of carbon dioxide in combination with global warmth over this period. These conditions diminished biotic-driven silicate rock weathering and thereby attenuated an important long-term carbon dioxide sink. Although our modelling results are semi-quantitative and do not capture the full range of biogeochemical feedbacks that could influence the climate, our analysis indicates that the dynamic equilibrium between plants, climate and the geosphere probably buffered the minimum atmospheric carbon dioxide concentrations over the past 24 million years.


Comprehensive management of full-thickness luminal defects: The next frontier of gastrointestinal endoscopy.
Full thickness gastrointestinal defects such as perforations, leaks, and fistulae are a relatively common result of many of the endoscopic and surgical procedures performed in modern health care. As the number of these procedures increases, so too will the number of resultant defects. Historically, these were all treated by open surgical means with the associated morbidity and mortality. With the recent advent of advanced endoscopic techniques, these defects can be treated definitively while avoiding an open surgical procedure. Here we explore the various techniques and tools that are currently available for the treatment of gastrointestinal defects including through the scope clips, endoscopic suturing devices, over the scope clips, sealants, endoluminal stents, endoscopic suction devices, and fistula plugs. As fistulae represent the most recalcitrant of defects, we focus this editorial on a multimodal approach of treatment. This includes optimization of nutrition, treatment of infection, ablation of tracts, removal of foreign bodies, and treatment of distal obstructions. We believe that by addressing all of these factors at the time of attempted closure, the patient is optimized and has the best chance at long-term closure. However, even with all of these factors addressed, failure does occur and in those cases, endoscopic therapies may still play a role in that they allow the patient to avoid a definitive surgical therapy for a time while nutrition is optimized, and infections are addressed.


Good manufacturing practices and clinical supplies.
Quality characteristics must be assured through adherence to good manufacturing practices in the production, control, and testing of drug products intended for investigational as well as commercial use. A draft guideline on the preparation of investigational new drug products, soon to be available in final form, addresses questions that have been raised regarding acceptable practices and procedures to facilitate compliance with the CGMP regulations as applied to clinical supplies. Inspections of sterile clinical supplies production can be expected to include the areas most likely to influence product safety, quality, and uniformity in the same manner as would be expected regarding the manufacture of commercial batches. Some areas of particular significance in the manufacture of parenteral clinical supplies include validation of terminal sterilization, aseptic processing, and oxygen exclusion. The validation of the aseptic handling during lyophilization requires special attention. Other CGMP concerns include the provision of a quality control unit, avoiding packaging mixups, and being prepared for an amendment to the CGMP regulations regarding terminal sterilization.


Information needs related to antibiotic prescribing while using CPOE.
Antimicrobial resistance is an important patient safety issue related to inappropriate antibiotic use. As part of the Infobutton project, we examined antibiotic prescribing-related information needs of clinicians using CPOE. During 3 hours of observation, 20 information needs were observed, 74% were met. Understanding the information needs of clinicians related to antibiotic prescribing may help identify methods to meet information needs via the Infobutton manager and thereby improve the judicious use of antibiotics.


Anterior segment optical coherence tomography changes with introduction and discontinuation of tamsulosin.
The aim of this study was to quantify changes and reversibility in pupil dilation and iris dilator muscle region thickness associated with introduction and subsequent discontinuation of tamsulosin in patients naïve to this drug with the aid of an anterior OCT system. The study was carried out on 7 patients (14 eyes) naïve to tamsulosin and with benign prostatic hypertrophy (BHP). Measurements taken by Vistante OCT were done pre- and post-dilation of the following: pupil size, iris dilator muscle region (DMR) thickness, sphincter muscle region (SMR) thickness, and anterior chamber depth. These measurement were taken at Day 0 (tamsulosin naive), Day 30 (after one month of tamsulosin, the treatment period) and day 60 (after one month of no tamsulosin, the discontinuation period). Post-dilation pupil diameter significantly increased during the discontinuation period (P = 0.047). Iris DMR thickness measurements post-dilation significantly decreased during treatment (P = 0.00044), discontinuation (0.00011), and combined periods (P = 0.000050). Anterior chamber depth measurements in post-dilation were significantly decreased during treatment (P = 0.0016), discontinuation (P = 0.017), and combined periods (P = 0.00022). Tamsulosin discontinuation effectively increases dilated pupil size, a measure that has been inversely linked to IFIS incidence pre-operatively. Decreased DMR thickness in this short term likely illustrates changes aside from atrophy, such as vascular changes. Decreased anterior chamber depths suggest aqueous humor production is decreased as well.


Bandwidth-modulated adiabatic RF pulses for uniform selective saturation and inversion.
Radiofrequency (RF) inversion and saturation pulses with extremely high spatial selectivity and uniform profiles are a requirement for numerous MR techniques, such as pulsed arterial spin labeling and outer volume suppression. Adiabatic pulses used for inversion of longitudinal magnetization are ubiquitous, but the superior selectivity of adiabatic full passages has not been widely exploited for saturation because a simple way of calibrating the amplitude of these subadiabatic pulses is lacking. An analytically derived calibration equation is presented, applicable to a large class of pulses including the hyperbolic secant (HS) pulse and allowing the determination of the precise amplitude required to achieve any effective flip angle. The properties of this calibration are examined, and a highly selective and homogeneous HS saturation pulse is demonstrated. Based on this calibration a new class of RF pulses is developed. These bandwidth-modulated adiabatic selective saturation and inversion (BASSI) RF pulses afford optimal amplitude modulation, achieving uniform profiles at any effective flip angle. BASSI pulses are compared to existing gradient modulated adiabatic pulses in simulations and phantom experiments and shown to be superior in terms of selectivity and homogeneity, while requiring less RF energy. An application of BASSI pulses to pulsed arterial spin labeling is shown.


Developmental Dysplasia Of The Hip In Older Children; Prospects Of Functional And Radiological Outcome Following A Single Stage Triple Procedure.
Developmental dysplasia of the hip (DDH) is a diverse entity, which range from mild acetabular dysplasia to frank irreducible hip dislocation. Data regarding the safety and efficacy of one stage triple procedure is limited. Our aim was to analyse the mid-term functional and radiological outcome of single stage triple procedure for children with DDH after walking age. This is a prospective case series of 23 patients (26 hips) who were diagnosed as cases of DDH between July 2014 and June 2017. We included patients with age 20 months and above from both genders who underwent the single stage triple procedure of open reduction, femoral and pelvic osteotomy during the three years. Functional and radiological outcome were assessed according to McKay's and Severin's grading systems respectively.. Sixteen (69.6%) girls and 7 (30.4%) boys with a mean age of 4.4±1.9 years. The mean follow-up duration was 8.9±3.2 months. The mean preoperative acetabular index (AI) was 40.3º±2.7º which reduced to an average of 23.4º±3.8º at the end of follow-up. Eight (34.8%) of patients achieved grade I (excellent) of McKay's classification and 9 (39.1%) grade II (good). Postoperatively, 22 (95.7%) patients were below grade III and only one (4.3%) patient was in grade IVa. One case of avascular necrosis of femoral head was observed. The single stage triple procedure involving femoral and pelvic osteotomies have excellent functional and radiological outcomes, however, avascular necrosis of the femoral head, redislocation and osteoarthritis in long-term are the adverse events associated with the condition.


Making the Nēnē Matter: Valuing Life in Postwar Conservation.
In 1950, a group of scientists and public figures, based in Hawaii and England, launched a transnational "restoration project" to save the nēnē or Hawaiian goose from extinction. Scrutinizing this project highlights how endangered species were valued as part of a historically contingent process that reflected and linked the interests of different groups. People did not undertake the restoration project simply because they realized the nēnē were endangered, but, instead, they sought to rescue it at the "eleventh hour" in order to legitimize the new conservation organizations that they helped establish after the Second World War. They also engaged with broader political and socioeconomic concerns to justify the restoration project, publicly framing the nēnē as a valuable asset that benefited Hawaii's tourist economy and push for statehood. Disputes over the reintroduction of geese bred in England highlight how the nēnē were valued in complex and sometimes contradictory ways, with unforeseen consequences for both the restoration project and its animal subjects. This case study ultimately draws our attention to the inherently biopolitical nature of modern conservation, by showing that there is no simple trajectory from endangered life to valued life.