Jasmonates and Na-orthovanadate promote resveratrol production in Vitis vinifera cv. Barbera cell cultures.
Here the effect of jasmonic acid, methyljasmonate and Na-orthovanadate on the production of resveratrol was studied in Vitis vinifera cv. Barbera cell suspension cultures. Na-orthovanadate at 0.1 mm and 1 mm concentration was efficient in promoting the production and/or accumulation and release in the culture medium of cis-resveratrol while trans-resveratrol levels were not affected by this treatment. Methyljasmonate was highly effective in stimulating both trans- and cis-resveratrol endogenous accumulation, as well as their release into the culture medium. Cis-resveratrol was absent or detected in very low amounts in the controls. Jasmonic acid was less efficient than methyljasmonate in promoting endogenous resveratrol accumulation, but it stimulated the release in the culture medium especially of cis-resveratrol. Gel analysis was performed on control and 10 microm MeJA treated cell suspensions. Results showed an up-regulation of the stilbene synthase demonstrating that MeJA stimulated the synthesis ex-novo of this protein.


Improved removal of arsenic from groundwater using pre-corroded steel and iron tailored granular activated carbon.
The authors have combined corrosion of steel fittings or perforated sheets with granular activated carbon (GAC) that had been pre-treated with Fe(III)-citrate, to produce an innovative and low-maintenance technique for removing arsenic from groundwater. Removal of arsenic was measured using two GAC column configurations: rapid small scale column tests (RSSCT's) and mini-column tests. Independent variables included pH, pre-corrosion procedure, and idling of the column (i.e. intentionally stopping flow for defined times in order to create reducing conditions). Use of corroded steel plus pre-treated GAC removed arsenic to below 10 microg/L for up to 248,000 bed volumes (BV) at pH 6, compared to 7,000 BVs for pre-treated GAC without pre-corroded steel. Performance was not as good at pH 6.5 or 7.5. Idling the system recovered the iron corrosion ability by reducing the passive Fe(III) layer on pre-corroded steel surface, as a result the BVs to arsenic breakthrough was doubled. But idling also caused brief periods of arsenic and iron release after restart, due to reductive dissolution of arsenic-containing ferric oxides. GAC was also effective as filtration media for removal of iron (hydr)oxide particles (and associated arsenic) that was released from the pre-corroded iron.


Heparan sulfate interacting protein (HIP/L29) negatively regulates growth responses to basic fibroblast growth factor in gingival fibroblasts.
Basic fibroblast growth factor (bFGF) modulates gingival growth, and its release from heparan sulfate (HS) in the extracellular matrix (ECM) governs local tissue bioavailability. We identified a heparin/HS interacting protein (HIP/L29) that recognizes specific HS sequences. We hypothesize that HIP/L29, by modulating the interactions of bFGF with HS chains on proteoglycans, could regulate bFGF bioavailability. To investigate interactions between bFGF and HIP/L29, we isolated and cultured fibroblasts from normal gingiva and overgrown gingiva from patients on cyclosporine (CSA). bFGF significantly stimulated gingival fibroblast proliferation with or without heparin. Recombinant human HIP/L29 dramatically decreased bFGF-induced proliferation, but did not alter responses to insulin-like growth factor-1 (IGF-1). Analysis of mitogen-activated protein kinase (MAPK) phosphorylation patterns showed that bFGF stimulation of p44 (Erk-1), but not p42 (Erk-2), also was inhibited by HIP/L29 in a dose-dependent manner. Together, these results support our hypothesis that HIP/L29 modulates the bioavailability and action of bFGF.


Serotyping of avian mycoplasma species in India.
Two-hundred and two strains of avian mycoplasma species belonging to 10 biotypes were typed serologically by employing disk growth inhibition (DGI) and indirect hemagglutination (IHA) tests. These could be placed into seven serotypes, namely A (80), B (50), C (3), E (34), L (13), P (4), and 1 and R (18). The figures in parentheses show the number of strains within each type. A close relationship was observed between DGI and IHA tests. The IHA test, however, was more sensitive and specific. It was also noticed that biochemically identical biotypes, namely E and G, and B and M were also found identical in serotyping, thus confirming the biochemical identity. In view of these facts, the strains of biotypes M and G were grouped under serotypes B and E, respectively. The antigenic relationships between the serotypes are also discussed.


[Comparative study of central hemodynamics, myocardial contractility and left-ventricular wall tension in athletes and patients].
The purpose of the study was to extend our knowledge about the "athletic" heart and improve diagnosis of latent manifestations of cardiac insufficiency. Echocardiography was used to examine central hemodynamics, myocardial contractility and left-ventricle wall tension in athletes and patients with ischemic heart disease (IHD) and arterial hypertension at rest and after exercise tests. The study of time-course variations of these parameters revealed different patterns of initial dilation and development of further dilation and hypertrophy in athletes and patients. The most sensitive index of contractility was meridional and circular tension of the left-ventricle wall which was the lowest in athletes and the highest in IHD patients.


Rate of change of blood pressure in premature and full term infants from birth to 4 months.
Systolic and diastolic blood pressures were evaluated in a cohort of 61 non-hypertensive premature [very low birth weight (VLBW), n = 16; low birth weight (LBW), n = 22] and full-term [normal birth weight (NBW), n = 23] newborn infants admitted to a neonatal intensive care unit (NICU) and followed to their 4-month age-adjusted outpatient examination. All were receiving routine postnatal care by 7 days of age. Blood pressure was measured at 7 days of age, at discharge from the NICU, and at the outpatient examination. Simple linear regression of blood pressure on weight was used to fit a straight line to the three measurements for each infant and the average regression line for each birth weight group was then obtained. There was a significant correlation between systolic blood pressure and both weight and length at each of the measurement points and also between the change in systolic blood pressure and change in weight from the discharge to the 4-month examination. Diastolic blood pressure tended to follow this same pattern. Gestational age was correlated significantly with the 7-day blood pressure, but postnatal age at the outpatient examination was not correlated with either systolic or diastolic blood pressure. The average slopes of systolic and diastolic blood pressure on weight (mmHg/kg body weight) were virtually identical for the LBW and NBW groups; in contrast, the average slope of the VLBW group was greater than the other two groups, and the difference was statistically significant for diastolic blood pressure. These results show significant group differences in mean blood pressure prior to 4 months of age between VLBW, LBW, and NBW groups and, for the VLBW infants, a steeper slope of the estimated regression line of blood pressure on weight between birth and 4 months.


Single-photon emission computed tomography myocardial perfusion imaging and the risk of sudden cardiac death in patients with coronary disease and left ventricular ejection fraction>35%.
The aim of this study was to determine whether single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is an effective method of risk stratification for sudden cardiac death (SCD) in patients with coronary artery disease (CAD) and left ventricular ejection fraction (LVEF)>35%. Most victims of SCD have an LVEF>35%. The study population included 4,865 patients with CAD and LVEF>35% who underwent gated SPECT MPI. We used Cox proportional hazard modeling to examine the relationship between patient characteristics and SCD. The median age of the population was 63 years (25th, 75th percentile: 54, 71 years), and the median LVEF was 56% (25th, 75th percentile: 50%, 64%). The median follow-up for all patients was 6.5 years (25th, 75th percentile: 3.6, 9.3 years). During follow-up, there were 161 SCDs (3.3%). After multivariable adjustment, LVEF, the Charlson index, hypertension, smoking, antiarrhythmic drug therapy, and the summed stress score (SSS) were associated with SCD (all p<0.05). For each 3-U increase in the SSS, the hazard ratio for SCD was 1.13 (95% confidence interval: 1.04 to 1.23). The addition of perfusion data to the clinical history and LVEF was associated with increased discrimination for SCD events (c-index 0.728). Risk stratification with a derived SPECT nomogram did not result in statistically significant net reclassification improvement (p=0.26) or integrated discrimination improvement (p=0.38). Among patients with CAD and LVEF>35%, the extent of stress MPI perfusion defects is associated with an increased risk of SCD. Future large prospective studies should address the role of perfusion imaging in the identification of high-risk patients with LVEF>35% who might benefit from ICD implantation.


Harmine shows therapeutic activity on nicotine-induced liver failure in mice.
This experiment evaluated the effects of harmine against nicotine-induced damage to the liver of mice. Nicotine is a major toxic component of cigarette smoke and a major risk factor for functional disorders in the liver, because it induces oxidative stress. Harmine is a harmal-derived alkaloid with therapeutic and antioxidant properties. In this study, 80 male mice were randomly assigned to 10 groups: the normal control and nicotine control groups (2.5 mg/kg); the harmine groups (5, 10, 15, and 20 mg/kg), and the nicotine + harmine groups (5, 10, 15 and 20 mg/kg mg/kg). Treatments were administered intraperitoneally daily for 28 days. Nitric oxide (NO) level, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) concentrations were determined. In addition, thiobarbituric acid reactive species, antioxidant capacity, and the diameters of the hepatocytes and central hepatic vein (CHV) were investigated. Nicotine administration significantly improved liver MDA and NO levels, CHV and hepatocyte diameters, and liver enzymes, and it decreased tissue FRAP levels compared to the normal control group (p<0.05). In the harmine and harmine + nicotine groups, in all dosages, all measured factors decreased significantly, while the FRAP tissue level increased compared with the nicotine control group (p<0.05). It seems that liver injury was improved by harmine administration in mice because of nicotine.


Frontoethmoidal meningoencephalocele: challenges and the Tawanchai center's long-term integrated management.
The challenges for the management of patients with fronto-ethmoidal meningoencephalocele (FEEM) include: classification, assessment and analysis of the deformities, craniofacial reconstruction and long-term management. To present experience of the Tawanchai Craniofacial Center of long-term integrated management and outcome of patients with FEEM. Medical records were reviewed of 32 patients with FEEM treated by the authors between 1993 and 2011 at the Tawanchai Center, Srinagarind Hospital; the referral center for Northeast Thailand. Geographic Information System (GIS) analysis was used to examine the incidence and pattern of referrals to our Center. Most of the patients had the nasoethmoidal type (12 patients) followed by the combined naso-ethmoidal/-orbital type (8 patients). The surgical procedures included craniofacial reconstruction with medial canthopexy, orbital translocation, external repair and nasal reconstruction. Ultimately, most patients were satisfied with their remedied facial appearance. The Center's interdisciplinary protocol for the care of patients with FEEM was established. Experience demonstrated that a craniofacial center with interdisciplinary management was necessary to provide proper, early and longitudinal care and to achieve optimum outcomes for the patients with FEEM. In each case, the surgical outcome depended on the severity and classification of the deformities and the extent of associated brain anomalies. Nevertheless, in every case the final measurement should be done at the age of complete skeletal maturity. Funding from a number of sources, including the Foundation, is needed to ensure patients' access to treatment and follow-up and for the Craniofacial Cleft Center to improve the quality of treatment and programing.


Axonal varicosity distributions along parallel fibers: a new angle on a cerebellar circuit.
Presynaptic terminals occur along unmyelinated axons in specialized compartments called axonal varicosities or synaptic boutons. Since the first descriptions of varicose axons by Cajal and others, the spatial organization of varicosities along axons has attracted the attention of neuroscientists. Quantitative light- and electron-microscopic analyses of varicosity spacing in the cerebellum and elsewhere have recently provided a clearer picture of this organization, and theoretical analyses now incorporate varicosity spacing as an essential parameter in structural models of neural connectivity. Here we review the salient features of varicosity spacing, with emphasis on cerebellar parallel fibers as a model system. Measured globally across the entire approximately 5 mm lengths of parallel fibers, the overall mean spacing of varicosities is 5.2 microm. Measured locally, however, mean spacing follows a proximodistal gradient, increasing with distance from the point of bifurcation from the ascending axon. Measured at the level of individual varicosities, parallel fiber varicosity distributions follow a distinct pattern characterized by a fixed relationship between the spacing variability and mean. This pattern equally describes varicosity distributions in a number of other brain regions, and therefore appears to constitute a general scaling relationship for excitatory varicose axons. We further discuss evidence for common principles underlying the placement of both varicosities and synapses along axons.


Hyperosmotic NaCl and urea synergistically regulate the expression of the UT-A2 urea transporter in vitro and in vivo.
The UT-A2 urea transporter is involved in the recycling of urea through the kidney, a process required to maintain high osmotic gradients. Dehydration increases UT-A2 expression in vivo. The tissue distribution of UT-A2 suggested that hyperosmolarity, and not vasopressin, might mediate this effect. We have analyzed the regulation of UT-A2 expression by ambiant osmolarity both in vitro (mIMCD3 cell line) and in vivo (rat kidney medulla). The UT-A2 mRNA was found to be synergistically up-regulated by a combination of NaCl and urea. Curiously, the UT-A2 protein was undetectable in this hypertonic culture condition, or after transfection of the UT-A2 cDNA, whereas it could be detected in HEK-293 transfected cells. Treating rats with furosemide, a diuretic which decreases the kidney interstitium osmolarity without affecting vasopressin levels, led to decreased levels of the UT-A2 protein. Our results show that the UT-A2 urea transporter is regulated by hyperosmolarity both in vitro and in vivo.


Epidemiology of Pediatric Critical Illness in a Population-Based Birth Cohort in Olmsted County, MN.
Investigations of pediatric critical illness typically focus on inpatient cohorts drawn from wide referral areas and diverse healthcare systems. Cohorts amenable to investigating the full spectrum of critical illness as it develops within a community have yet to be studied in the United States. Our objective was to provide the first epidemiologic report of the incidence and presentation of pediatric critical illness within a U.S. population-based birth cohort. Retrospective cohort study. A geographically defined community (Olmsted, MN) with medical record linkage across all health systems. All ICU services are provided within a single children's hospital. A birth cohort of children (n =9,441) born 2003-2007 in Olmsted County, MN. During the study period, there were a total of 15,277 ICU admissions to Mayo Clinic Children's Hospital. A total of 577 birth cohort children accounted for 824 of these admissions during the 61,770 person-years of follow-up accumulated. Incidence of first-time ICU admission was 9.3 admits per 1,000 person-years. Admission rates were highest in the first year of life and then declined steadily. Respiratory problems were among the most common reasons for admission at any age and diagnoses reflect changes in health risk factors as children grow and develop over time. After 1 year old, a majority of children admitted have preexisting chronic comorbidities and/or prior ICU stays. In-hospital mortality occurred exclusively in children admitted prior to 5 days of age (n = 4). Seven children died after hospital discharge. This is the first report characterizing critical illness within a population-based birth cohort of U.S. children. The results demonstrate the changing incidence, presentation, and healthcare requirements associated with critical illness across the developmental spectrum as a population of children ages.


Targeted photothermal therapy of mice and rabbits realized by macrophage-loaded tungsten carbide.
Although great advances have been made in photothermal therapy, the efforts hitherto have mainly achieved antitumor effects in mice with a subcutaneous tumor model, which is less clinically relevant. Therefore, it is very urgent to make further progress in investigating the possibility of larger animal models with orthotopically xenografted tumors for further clinical trials. Herein, macrophage-loaded tungsten carbide has been employed for the photothermal ablation of orthotopic breast tumors in rabbits in a targetable way. Tungsten carbide as an excellent photoactive material can induce on-site hyperthermia and even reactive oxygen species for tumor destruction; meanwhile, the macrophage is a biocarrier that behaves as a "Trojan horse" for tumor targeting. Both experimental results and theoretical simulations verified the broadband photoabsorption of WC. The WC loaded in the macrophages readily maintains the photothermal and photodynamic effects of the bare WC, while its accumulation at the tumor site is nearly 10 times that of bare WC. As such, the complete removal of solid tumors in rabbits was confirmed with the aid of B-mode ultrasound and contrast-enhanced ultrasound surveillance. Apparently, this work advances photothermal therapy one step further to large animal models with orthotopic tumors.


Wafer-scale integration of sacrificial nanofluidic chips for detecting and manipulating single DNA molecules.
Wafer-scale fabrication of complex nanofluidic systems with integrated electronics is essential to realizing ubiquitous, compact, reliable, high-sensitivity and low-cost biomolecular sensors. Here we report a scalable fabrication strategy capable of producing nanofluidic chips with complex designs and down to single-digit nanometre dimensions over 200 mm wafer scale. Compatible with semiconductor industry standard complementary metal-oxide semiconductor logic circuit fabrication processes, this strategy extracts a patterned sacrificial silicon layer through hundreds of millions of nanoscale vent holes on each chip by gas-phase Xenon difluoride etching. Using single-molecule fluorescence imaging, we demonstrate these sacrificial nanofluidic chips can function to controllably and completely stretch lambda DNA in a two-dimensional nanofluidic network comprising channels and pillars. The flexible nanofluidic structure design, wafer-scale fabrication, single-digit nanometre channels, reliable fluidic sealing and low thermal budget make our strategy a potentially universal approach to integrating functional planar nanofluidic systems with logic circuits for lab-on-a-chip applications.


Pain assessment tools in palliative care: an urgent need for consensus.
At present, there is no universally accepted cancer pain assessment tool for use in palliative care (PC). The European Palliative Care Research Collaborative (EPCRC), therefore, aims to develop an international consensus-based computerised pain assessment tool. As part of this process, we have performed (1) a literature review on pain assessment tools for use in the PC and (2) an international expert survey to gain information on the relevant dimensions for pain assessment in PC. 230 publications were identified, only six met the inclusion criteria. Three further articles were identified through manual searching, totalling 11 different pain assessment tools. Nine tools were multidimensional. Pain intensity was assessed in seven, using various numerical/verbal rating scales (NRS/VRS); five tools focused on pain management. Three publications did not identify the rationale for the need to develop a new tool, and the selection procedure for items/dimensions was not described in six tools. Patient and/or professional expert groups were involved in the development of five tools and only two tools were extensively validated or cross-culturally tested. Thirty-two experts (71%) completed the expert survey and identified 'intensity', 'temporal pattern', 'relief/exacerbation', 'pain quality' and 'location' as the five most relevant dimensions. Most preferred assessment of 'pain intensity' was by NRS rather than VRS. Time windows extending 24 h were regarded as less relevant. Development of PC pain assessment tools seems to be a continuous process, which does not adhere to systematic guidelines, thus does not contribute to a universally accepted tool. No tool contained all relevant dimensions as defined by the experts. Many tools focused on particular dimensions, suggesting that specific research interests may drive the tool development process. Extensive literature reviews, expert and patient input and clinical studies are a needed approach in the development of a new consensus-based pain assessment tool.


The Use of Lean Six Sigma for Improving Availability of and Access to Emergency Department Data to Facilitate Patient Flow.
The aim of this study was to redesign an emergency department [ED] data management system to improve the availability of, and access to, data to facilitate patient flow. A pre-/post-intervention design was employed using Lean Six Sigma methodology with a focus on the voice of the customer, Gemba, and 5S to identify areas for improvement in ED data management processes and to inform solutions for improved ED patient flow processes. A multidisciplinary ED team includes medical consultants and registrars, nurses, patient service staff, radiology staff, as well as information technology and hospital management staff. Lean Six Sigma [LSS] diagnostic tools identified areas for improvement in the current process for data availability and access. A set of improvements were implemented to redesign the pathway for data collection in the ED to improve data availability and access. We achieved a reduction in the time taken to access ED patient flow data from a mean of 9 min per patient pre-intervention to immediate post-intervention. This enabled faster decision-making by the ED team related to patient assessment and treatment and informed improvements in patient flow. Optimizing patient flow through a hospital's ED is a complex task involving collaboration and participation from multiple disciplines. Through the use of LSS methodology, we improved the availability of, and fast access to, accurate, current information regarding ED patient flow. This allows ED and hospital management teams to identify and rapidly respond to actions impacting patient flow.


Prediction of Near-Term Breast Cancer Occurrence using Subtraction of Temporally Sequential Digital Mammograms.
Breast cancer remains one of the leading cancers for women worldwide. Fortunately, with the introduction of mammography, the mortality rate has significantly decreased. However, earlier breast cancer prediction could effectively increase the survival rates, improve patient outcomes, and avoid unnecessary biopsies. For that purpose, prediction of breast cancer, using subtraction of temporally sequential digital mammograms and machine learning, is proposed. A new dataset was collected with 192 images from 32 patients (three screening rounds, with two views of each breast). This dataset included precise annotation of each individual malignant mass, present in the most recent mammogram, with the two priors being radiologically evaluated as normal. The most recent mammogram was considered as the "future" screening round and provided the location of the mass as the ground truth for the training. The two previous mammograms, the "current" and the "prior", were processed and a new, difference image was formed for the prediction. Ninety-six features were extracted and five feature selection algorithms were combined to identify the most important features. Ten classifiers were tested in leave-one-patient-out and k-fold-patient cross-validation (k = 4 and 8). Ensemble Voting achieved the highest performance in the prediction of the development of breast mass in the next screening round, with 85.7% sensitivity, 83.7% specificity, 83.7% accuracy and 0.85 AUC. The proposed methodology could lead to a new mammography-based model that could predict the short-term risk for developing a malignancy, thus providing an earlier diagnosis.


A cost analysis of a community health worker program in rural Vermont.
Studies have shown that community health workers (CHWs) can improve the effectiveness of health care systems; however, little has been reported about CHW program costs. We examined the costs of a program staffed by three CHWs associated with a small, rural hospital in Vermont. We used a standardized data collection tool to compile cost information from administrative data and personal interviews. We analyzed personnel and operational costs from October 2010 to September 2011. The estimated total program cost was $420,348, a figure comprised of $281,063 (67%) for personnel and $139,285 (33%) for operations. CHW salaries and office space were the major cost components. Our cost analysis approach may be adapted by others to conduct cost analyses of their CHW program. Our cost estimates can help inform future economic studies of CHW programs and resource allocation decisions.


Associations between responses to interferon therapy and genetic variation in interleukin-28B and the core region of hepatitis C virus genotype 3a.
The single-nucleotide polymorphism (SNP) of interleukin-28B (IL-28B) and mutations in the core region of hepatitis C virus (HCV) genotype 1b have been associated with response to interferon (IFN) therapy. However, whether this IL-28B SNP affects responses to INF therapy for HCV genotype 3a is not known. The aim of this study is to investigate whether this IL-28B SNP (rs8099917) and specific missense mutations in the HCV core region affect the response to IFN therapy for HCV genotype 3a. Patients (n = 19; median age 44.5) infected with HCV genotype 3a who received IFN therapy were studied. Of the 19 patients, 12 (63.1%) achieved sustained virological response. Of those 12 patients, 11 had the TT genotype (11/16; 68.7%), and one had the TG genotype (1/3; 33.3%). The difference in the sustained virological response rate between IL-28B genotype groups was not significant (P = 0.5232). HCV core region was well conserved; however, polymorphisms at position 72 were identified. Of the 19 HCV samples; 15 carried a glutamic acid at position 72, and these were defined as E type; the others (4/19) were defined as non-E type. Notably, there was a significant difference in the sustained virological response rate between E type and non-E-type; 12 of the 15 patients with E-type achieved sustained virological response, but none of the four patients with non-E-type achieved sustained virological response (P = 0.009). A glutamic acid at position 72 in the core region of HCV genotype 3a was associated with a good response to IFN therapy. J. Med. Virol. 87:1361-1367, 2015. © 2015 Wiley Periodicals, Inc.


Pharmacodynamic evaluation of the target efficacy of SB939, an oral HDAC inhibitor with selectivity for tumor tissue.
SB939 is an oral histone deacetylase (HDAC) inhibitor currently in phase II clinical trials potently inhibiting class I, II, and IV HDACs with favorable pharmacokinetic properties, resulting in tumor tissue accumulation. To show target efficacy, a Western blot assay measuring histone H3 acetylation (acH3) relative to a loading control was developed, validated on cancer cell lines, peripheral blood mononuclear cells (PBMC), and in animal tumor models. Exposure of cells to 60 nmol/L (22 ng/mL) SB939 for 24 hours was sufficient to detect an acH3 signal in 25 μg of protein lysate. AcH3 levels of liver, spleen, PBMCs, bone marrow and tumor were measured in BALB/c mice, HCT-116 xenografted BALB/c nude mice, or in SCID mice orthotopically engrafted with AML (HL-60) after oral treatment with SB939. AcH3 could only be detected after treatment. In all tissues, the highest signal detected was at the 3-hour time point on day 1. On day 15, the signal decreased in normal tissues but increased in cancerous tissues and became detectable in the bone marrow of leukemic mice. In all tissues, acH3 correlated with SB939 dose levels (r(2)=0.76-0.94). When applied to PBMCs from 30 patients with advanced solid malignancies in a phase I clinical trial, a dose-dependent (10-80 mg) increase in relative acH3 was observed 3-hour postdose on day 1, correlating with C(max) and AUC of SB939 concentrations in plasma (r=0.97, P=0.014). Our data show that the favorable pharmacokinetic and pharmacodynamic properties of SB939 are translated from preclinical models to patients.


Genotype-specific acquisition, evolution and adaptation of characteristic mutations in hepatitis E virus.
Hepatitis E virus (HEV) infection is a major cause of acute hepatitis but also provokes chronic infection in immunocompromised patients. Although the pathogenesis and treatment outcome involve complex interplay between the virus and host, the nature of adaptive responses of HEV to the host immune system remain obscure at best. In this study, we used large-scale proteomic bioinformatics to profile characteristic mutations in human HEV isolates associated to ribavirin treatment failure, chronic hepatitis, hepatic failure or altered immunoreactivity. The prevalence of specific mutations was examined in a large number of protein sequences of ORF1 and ORF2 regions of the 3 major human-derived HEV genotypes (1, 3 and 4). By analyzing potential B, CD4+ and CD8+ T cell epitopes, we found that many of these mutations overlap with the predicted epitopes and are frequently present among the 3 HEV genotypes. These overlapping mutations mediate reduced antigenicity. Finally, by delineation of diversification and evolution of the underlying epitopes, we observe that most of these variants apparently evolved earlier in genotype 1 when compared with genotypes 3 and 4. These results indicate that HEV is under substantial evolutionary pressure to develop mutations enabling evasion of the host immune response and resistance to antiviral treatment. This indicates the existence of an ongoing evolutionary arms race between human immunity, antiviral medication and HEV.


Human parasitic meningitis caused by Angiostrongylus cantonensis infection in Taiwan.
The major cause of eosinophilic meningitis in Taiwan is Angiostrongylus cantonensis. Humans are infected by ingesting terrestrial and freshwater snails and slugs. In 1998 and 1999, two outbreaks of eosinophilic meningitis caused by A. cantonensis infection were reported among 17 adult male immigrant Thai laborers who had eaten raw golden apple snails (Pomacea canaliculata). Another outbreak associated with consuming a health drink consisting of raw vegetable juice was reported in 2001. These adult cases differed from reports in the 1970s and 1980s, in which most of the cases were in children. With improvements in public health and education of foreign laborers, there have since been only sporadic cases in Taiwan. Review of clinical research indicates inconsistent association of Magnetic Resonance Imaging (MRI) results with clinical features of eosinophilic meningitis. MRI features were nonspecific but there was an association between the presence of high brain MRI signal intensities and severity of peripheral and cerebrospinal fluid (CSF) eosinophilia. Inflammatory markers have been identified in the CSF of patients with eosinophilic meningitis caused by A. cantonensis infection, and vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and the matrix metalloproteinase system may be associated with blood-brain barrier disruption. Eosinophilic meningitis caused by A. cantonensis infection is not a reportable disease in Taiwan. It is important that a public advisory and education program be developed to reduce future accidental infection.


Intraflagellar transport and the flagellar tip complex.
Intraflagellar transport (IFT) is the term that refers to the microtubule dependent particle motility that is common to almost all flagella and cilia and is distinct from the mechanism of flagellar beating. IFT involves the rapid, bi-directional transport of molecular motors and their cargo proteins from the base to the tip of the flagellum and back again. While the basic mechanism of IFT is well established, the varied functions of this process are continually being elucidated. For example, although IFT plays a clear role in flagellar assembly, disassembly and stability, the exact sequence of events that take place when tubulin subunit addition and loss occur during flagellar assembly and disassembly, respectively, are unknown. Key to furthering our understanding of IFT is greater knowledge of the flagellar tip complex (FTC) because it is at the FTC that flagellar assembly and disassembly, cargo loading and unloading, and motor protein regulation occur. Yet these related processes may only represent one aspect of the importance of IFT in flagellar dynamics. IFT may also provide the basic elements of a signal transduction mechanism that functions to provide the nucleus with information about the outside environment and even about the state of the flagellum itself. Thus, IFT may function as the central component of a signal transduction system that controls flagellar gene transcription.


A Bayesian Supertree Model for Genome-Wide Species Tree Reconstruction.
Current phylogenomic data sets highlight the need for species tree methods able to deal with several sources of gene tree/species tree incongruence. At the same time, we need to make most use of all available data. Most species tree methods deal with single processes of phylogenetic discordance, namely, gene duplication and loss, incomplete lineage sorting (ILS) or horizontal gene transfer. In this manuscript, we address the problem of species tree inference from multilocus, genome-wide data sets regardless of the presence of gene duplication and loss and ILS therefore without the need to identify orthologs or to use a single individual per species. We do this by extending the idea of Maximum Likelihood (ML) supertrees to a hierarchical Bayesian model where several sources of gene tree/species tree disagreement can be accounted for in a modular manner. We implemented this model in a computer program called guenomu whose inputs are posterior distributions of unrooted gene tree topologies for multiple gene families, and whose output is the posterior distribution of rooted species tree topologies. We conducted extensive simulations to evaluate the performance of our approach in comparison with other species tree approaches able to deal with more than one leaf from the same species. Our method ranked best under simulated data sets, in spite of ignoring branch lengths, and performed well on empirical data, as well as being fast enough to analyze relatively large data sets. Our Bayesian supertree method was also very successful in obtaining better estimates of gene trees, by reducing the uncertainty in their distributions. In addition, our results show that under complex simulation scenarios, gene tree parsimony is also a competitive approach once we consider its speed, in contrast to more sophisticated models.


Sex and Race Differences in the Relationship between Obesity and C-Reactive Protein.
C-reactive protein (CRP) is a risk factor for cardiovascular disease and mortality; it is known to be positively associated with obesity but there is some evidence that this association differs by race or sex. We used nationally representative data of adults aged >50 years to investigate sex and race modifiers of the associations between obesity and CRP in non-Hispanic White males (n=3,517) and females (n=4,658), and non-Hispanic Black males (n=464) and females (n=826). Using multiple linear regression models with the natural logarithm of CRP as the dependent variable, we sequentially included body mass index (BMI), a body shape index (ABSI), and socioeconomic, health and health behavior covariates in the model. The association between BMI and CRP was significantly stronger in females than males. Obese White females had mean CRP values slightly above 3 mg/liter (vs 2 for White males) and Black females had mean CRP values >4 mg/liter (vs 3 for Black males). More than 50% of Black females in the United States have obesity. Continued research into racial and sex differences in the relationship between obesity, inflammation, and health risks may ultimately lead to more personalized weight loss recommendations.


Human frequency-following response: representation of tonal sweeps.
Auditory nerve single-unit population studies have demonstrated that phase locking plays a dominant role in the neural encoding of steady-state speech sounds. Recently, we have reported that the phase-locked activity underlying the human frequency-following response (FFR) could also encode the first two formants of several tonal approximations of steady-state vowels. Since auditory nerve single-unit population studies have also demonstrated that phase locking is used to represent time-varying speech-like sounds, it was reasoned that the phase-locked neural activity underlying the human FFR, likewise, is dynamic enough to represent time-varying sounds. FFRs to a rising and a falling tone were obtained from 8 normal-hearing adults at 95, 85, 75 and 65 dB nHL. Results clearly demonstrated that the human FFR does indeed follow the trajectory of the rising and falling tones. Also, amplitude changes in the FFR supported the view that neural phase locking decreases with increasing frequency. Finally, the relatively smaller FFR amplitude for the falling tone compared to its rising counterpart lends further support to the notion that rising tones produce greater neural synchrony than falling tones. These results indicate that the human FFR may be used to evaluate encoding of time-varying speech sounds like diphthongs and certain consonant-vowel syllables.


The starving patient: supportive care for people with cancer.
Unintentional weight loss in people with cancer is associated with decreased quality of life and increased mortality. Addressing risk factors that lead to weight loss may improve quality of life and prevent cachexia. Specific, individualized counseling is the most beneficial and economic intervention for nutritional health. Appetite stimulants promote oral intake, and oral supplements help to meet the increased need for calories and protein during the course of the disease and its treatment. Utilizing the gut for digestion and absorption of food maintains the critical functions of the bowel lumen. Tube feeding and parenteral nutrition may be indicated for prevention of malnutrition in some disease conditions and during certain types of cancer treatment.


Phoneme-Order Encoding During Spoken Word Recognition: A Priming Investigation.
In three experiments, we examined priming effects where primes were formed by transposing the first and last phoneme of tri-phonemic target words (e.g., /byt/ as a prime for /tyb/). Auditory lexical decisions were found not to be sensitive to this transposed-phoneme priming manipulation in long-term priming (Experiment 1), with primes and targets presented in two separated blocks of stimuli and with unrelated primes used as control condition (/mul/-/tyb/), while a long-term repetition priming effect was observed (/tyb/-/tyb/). However, a clear transposed-phoneme priming effect was found in two short-term priming experiments (Experiments 2 and 3), with primes and targets presented in close temporal succession. The transposed-phoneme priming effect was found when unrelated prime-target pairs (/mul/-/tyb/) were used as control and more important when prime-target pairs sharing the medial vowel (/pys/-/tyb/) served as control condition, thus indicating that the effect is not due to vocalic overlap. Finally, in Experiment 3, a transposed-phoneme priming effect was found when primes sharing the medial vowel plus one consonant in an incorrect position with the targets (/byl/-/tyb/) served as control condition, and this condition did not differ significantly from the vowel-only condition. Altogether, these results provide further evidence for a role for position-independent phonemes in spoken word recognition, such that a phoneme at a given position in a word also provides evidence for the presence of words that contain that phoneme at a different position.


Cutting edge: stimulation with the cognate self-antigen induces expression of the Ly49A receptor on self-reactive T cells which modulates their responsiveness.
NK cell self-tolerance is maintained by inhibitory receptors specific for MHC class I molecules. Inhibitory NK receptors are also expressed on memory CD8 T cells but their biological relevance on T cells is unclear. In this study, we describe the expression of the Ly49A receptor on a subset of autoreactive T cells which persist in mice double-transgenic for the lymphocytic choriomeningitis virus-derived peptide gp33 and a TCRalphabeta specific for the gp33. No Ly49A-expressing cells are found in TCRalphabeta single-transgenic mice, indicating that the presence of the autoantigen is required for Ly49A induction. Direct evidence for an Ag-specific initiation of Ly49A expression has been obtained in vitro after stimulation of autoreactive TCRalphabeta T cells with the cognate self-Ag. This expression of Ly49A substantially reduces Ag-specific activation of autoreactive T cells. These findings thus suggest that autoantigen-specific induction of inhibitory NK cell receptors on T cells may contribute to peripheral self-tolerance.


Phytoplankton cell size: intra- and interspecific effects of warming and grazing.
Decreasing body size has been suggested as the third universal biological response to global warming after latitudinal/altitudinal range shifts and shifts in phenology. Size shifts in a community can be the composite result of intraspecific size shifts and of shifts between differently sized species. Metabolic explanations for the size shifts dominate in the literature but top down effects, i.e. intensified size-selective consumption at higher temperatures, have been proposed as alternative explanation. Therefore, we performed phytoplankton experiments with a factorial combination of warming and consumer type (protist feeding mainly on small algae vs. copepods mainly feeding on large algae). Natural phytoplankton was exposed to 3 (1(st) experiment) or 4 (2(nd) experiment) temperature levels and 3 (1(st) experiment: nano-, microzooplankton, copepods) or 2 (2(nd) experiment: microzooplankton, copepods) types of consumers. Size shifts of individual phytoplankton species and community mean size were analyzed. Both, mean cell size of most of the individual species and mean community cell size decreased with temperature under all grazing regimes. Grazing by copepods caused an additional reduction in cell size. Our results reject the hypothesis, that intensified size selective consumption at higher temperature would be the dominant explanation of decreasing body size. In this case, the size reduction would have taken place only in the copepod treatments but not in the treatments with protist grazing (nano- and microzooplankton).


General anesthetic and the risk of dementia in elderly patients: current insights.
In this review, we aim to provide clinical insights into the relationship between surgery, general anesthesia (GA), and dementia, particularly Alzheimer's disease (AD). The pathogenesis of AD is complex, involving specific disease-linked proteins (amyloid-beta [Aβ] and tau), inflammation, and neurotransmitter dysregulation. Many points in this complex pathogenesis can potentially be influenced by both surgery and anesthetics. It has been demonstrated in some in vitro, animal, and human studies that some anesthetics are associated with increased aggregation and oligomerization of Aβ peptide and enhanced accumulation and hyperphosphorylation of tau protein. Two neurocognitive syndromes that have been studied in relation to surgery and anesthesia are postoperative delirium and postoperative cognitive dysfunction, both of which occur more commonly in older adults after surgery and anesthesia. Neither the route of anesthesia nor the type of anesthetic appears to be significantly associated with the development of postoperative delirium or postoperative cognitive dysfunction. A meta-analysis of case-control studies found no association between prior exposure to surgery utilizing GA and incident AD (pooled odds ratio =1.05, P=0.43). The few cohort studies on this topic have shown varying associations between surgery, GA, and AD, with one showing an increased risk, and another demonstrating a decreased risk. A recent randomized trial has shown that patients who received sevoflurane during spinal surgery were more likely to have progression of preexisting mild cognitive impairment compared to controls and to patients who received propofol or epidural anesthesia. Given the inconsistent evidence on the association between surgery, anesthetic type, and AD, well-designed and adequately powered studies with longer follow-up periods are required to establish a clear causal association between surgery, GA, and AD.


Determination of the systematic position of the genus Asticcacaulis Poindexter by a polyphasic analysis.
The genus Asticcacaulis, to date, comprises two species of unicellular, stalked bacteria, developing a stalk at a site which is not coincidental with the centre of the pole of the cell. Multiplication is similar to that demonstrated by the prosthecate species of the genera Caulobacter, Brevundimonas and Maricaulis. A polyphasic approach, comprising 16S rRNA gene sequencing, lipid analysis and NaCl tolerance characterizations, was used to clarify the taxonomy of the two Asticcacaulis species. From the analysis of the 16S rRNA gene sequences, a close phylogenetic relationship between the species that comprise the genera Asticcacaulis, Caulobacter and Brevundimonas could be deduced wherein the three genera form three distinct branches. The individual genera could also be discerned by different characteristic polar lipids. The species of Asticcacaulis differed from species of Caulobacter and Brevundimonas by the lack of 1,2-diacyl-3-O-[6'-phosphatidyl-alpha-D-glucopyranosyl]glycerol. They also did not contain 1,2-di-O-acyl-3-O-[D-glucopyranosyl-(1-->4)-alpha-D-glucuronopyranosyl]glycerol, which is found in most Brevundimonas species but not in strains of the genus Caulobacter. The morphological differences seen between the two species Asticcacaulis excentricus and Asticcacaulis biprosthecium are mirrored by the observed 16S rDNA sequence similarity value of 95.3%, which is relatively low compared to the interspecies similarity values observed within the genera Brevundimonas or Caulobacter.


Analysis of abnormalities in purine metabolism leading to gout and to neurological dysfunctions in man.
A modelling approach is used to analyse diseases associated with purine metabolism in man. The specific focus is on deficiencies in two enzymes, hypoxanthine:guanine phosphoribosyltransferase and adenylosuccinate lyase. These deficiencies can lead to a number of symptoms, including neurological dysfunctions and mental retardation. Although the biochemical mechanisms of dysfunctions associated with adenylosuccinate lyase deficiency are not completely understood, there is at least general agreement in the literature about possible causes. Simulations with our model confirm that accumulation of the two substrates of the enzyme can lead to significant biochemical imbalance. In hypoxanthine:guanine phosphoribosyltransferase deficiency the biochemical mechanisms associated with neurological dysfunctions are less clear. Model analyses support some old hypotheses but also suggest new indicators for possible causes of neurological dysfunctions associated with this deficiency. Hypoxanthine:guanine phosphoribosyltransferase deficiency is known to cause hyperuricaemia and gout. We compare the relative importance of this deficiency with other known causes of gout in humans. The analysis suggests that defects in the excretion of uric acid are more consequential than defects in uric acid synthesis such as hypoxanthine:guanine phosphoribosyltransferase deficiency.


Lubricant-Infused Surfaces for Low-Surface-Tension Fluids: Promise versus Reality.
The past few decades have seen substantial effort for the design and manufacturing of hydrophobic structured surfaces for enhanced steam condensation in water-based applications. Such surfaces promote dropwise condensation and easy droplet removal. However, less priority has been given to applications utilizing low-surface-tension fluids as the condensate. Lubricant-infused surfaces (LISs) or slippery liquid-infused porous surfaces (SLIPSs) have recently been developed, where the atomically smooth, defect-free slippery surface leads to reduced pinning of water droplets and omniphobic characteristics. The remarkable results of LISs and SLIPSs with a range of working fluid droplets give hope of their viability with low-surface-tension condensates. However, the presence of the additional liquid in the form of lubricant brings other issues to consider. Here, in an effort to study the dropwise condensation potential of LISs and SLIPSs, we investigate the miscibility of a range of low-surface-tension fluids with widely used lubricants in LIS and SLIPS design. We consider a wide range of condensate surface tensions (12-73 mN/m) and different categories of lubricants with varied viscosities (5-2700 cSt), namely, fluorinated Krytox oils, hydrocarbon silicone oils, mineral oil, and ionic liquids. In addition, we use both theory and pendant drop experiments to predict the cloaking behavior of the lubricants and immiscible condensate working fluid pairs. Our work not only shows that careful attention must be paid to lubricant-condensate selection to create long-lasting LISs or SLIPSs but also develops lubricant selection design guidelines for stable LISs and SLIPSs for enhanced condensation in applications utilizing low-surface-tension working fluids.


Course of subthreshold depression into a depressive disorder and its risk factors.
Information on the natural course of subthreshold depression and risk factors for the development of a full-blown depressive disorder in the general population is scarce. This information is crucial to understand the development of depression and to advance indicated depression prevention. Using longitudinal data from a representative population-based study (the Netherlands Mental Health Survey and Incidence Study-2) we assessed 3-year course of subthreshold depression (depressive symptoms causing clinically significant distress for at least 2 weeks, or for 3 days per month for a year; n = 120), compared to an asymptomatic group (n = 4111) and a depressive disorder group (major depression or dysthymia; n = 294). Next, risk factors for the development of a depressive disorder among adults with subthreshold depression were determined. Twelve percent of the subthreshold cases developed a full-blown depressive disorder during 3-year follow-up. Risk factors were lower social support, having recurrent short episodes of depressive symptomatology, remitted and current anxiety disorder, remitted substance use disorder, lifetime suicide thoughts, a chronic physical disorder and diminished mental and physical functioning. The number of subjects with subthreshold depression that developed a depressive disorder was small. This limits the possibility to detect significant risk factors. Only a minority of the subthreshold cases developed a full-blown depressive disorder over three years. This shows that subthreshold depression does not, by itself, carry an a priori risk to warrant focusing indicated prevention. The identified risk factors could help to detect those subthreshold cases in whom depression prevention is economically and practically viable.


The pathogenesis of multiple sclerosis: is it really a primary inflammatory process?
The pathogenesis of multiple sclerosis (MS) remains unknown. Although inflammation, demyelination and axonal injury are all involved, the primary pathogenic process is not clear. In this paper we challenge the hypothesis that MS is a primary inflammatory condition, and suggest that axonal damage may occur independently.


How do consumers perceive differences in risk across nicotine products? A review of relative risk perceptions across smokeless tobacco, e-cigarettes, nicotine replacement therapy and combustible cigarettes.
To systematically review the literature regarding relative risk perceptions (RRPs) across non-combustible nicotine products. MEDLINE and PsycINFO databases were searched for articles published up to October 2014. Of the 5266 records identified, articles not published in English that did not quantitatively assess RRPs across categories of non-combustible nicotine products were excluded, yielding 55 records. One reviewer extracted measures and findings of RRPs for product comparisons of smokeless tobacco (SLT), e-cigarettes (ECs) and nicotine replacement therapy (NRT) to one another, and to combustible cigarettes (CCs). A total of 157 samples from 54 studies were included in the analyses. The accuracy of RRPs differed based on the products being compared: although the accuracy of RRPs was variable across studies, substantial proportions of respondents reported inaccurate beliefs about the relative harmfulness of SLT versus CCs, as well as of ECs versus NRT. In addition, in most studies, respondents did not know the relative harmfulness of SLT versus NRT. In contrast, respondents in many studies correctly perceived NRT and ECs as less harmful than CCs. Cigarette smokers and users of non-combustible nicotine products tended to correctly perceive the relative harmfulness of products more often than non-users. Measures used to assess RRPs varied across studies, with different approaches characterised by certain strengths and limitations. The highly variable and context-specific nature of non-combustible nicotine product RRPs have direct implications for researchers and present several challenges for policymakers working with modified risk products, including issues of measurement, health risk communication and behaviour change.


Temperature and Nitrogen Effects on Phosphorus Uptake by Agricultural Stream-Bed Sediments.
Climate change will likely increase the growing season, temperatures, and ratio of nitrogen (N) to phosphorus (P) loss from land to water. However, it is unknown how these factors influence P concentrations in streams. We sought to evaluate differences in biotic and abiotic processes affecting stream sediment P dynamics under different temperature and N-enrichment regimes. Three sediments of varying P composition and sorption characteristics were placed into a fluvarium. Synthetic runoff water, with or without added N, was added to the flume's reservoir, and the solution was maintained at 19 or 26°C. Water and sediment samples were taken with time since runoff was introduced. The rate and magnitude of P uptake by sediment was greater at 19°C compared with 26°C, and also when N was added compared with no N added. Analysis of sediment samples indicated that P uptake via abiotic processes was greater at 19 than at 26°C. The addition of N stimulated P uptake by the microbial biomass at 19°C, but microbial uptake was potentially inhibited at 26°C. Because microbial biomass is a temporary store of P, these data suggest that more P may be available with increasing temperatures during the growing season, especially under baseflow, implying that strategies to mitigate P losses from land to water should be strengthened to prevent potential water quality impairment.


Development of Multimodal Machine Learning Potentials: Toward a Physics-Aware Artificial Intelligence.
Machine learning interatomic potentials (MLIPs) are widely used for describing molecular energy and continue bridging the speed and accuracy gap between quantum mechanical (QM) and classical approaches like force fields. In this Account, we focus on the out-of-the-box approaches to developing transferable MLIPs for diverse chemical tasks. First, we introduce the "Accurate Neural Network engine for Molecular Energies," ANAKIN-ME, method (or ANI for short). The ANI model utilizes Justin Smith Symmetry Functions (JSSFs) and realizes training for vast data sets. The training data set of several orders of magnitude larger than before has become the key factor of the knowledge transferability and flexibility of MLIPs. As the quantity, quality, and types of interactions included in the training data set will dictate the accuracy of MLIPs, the task of proper data selection and model training could be assisted with advanced methods like active learning (AL), transfer learning (TL), and multitask learning (MTL).Next, we describe the AIMNet "Atoms-in-Molecules Network" that was inspired by the quantum theory of atoms in molecules. The AIMNet architecture lifts multiple limitations in MLIPs. It encodes long-range interactions and learnable representations of chemical elements. We also discuss the AIMNet-ME model that expands the applicability domain of AIMNet from neutral molecules toward open-shell systems. The AIMNet-ME encompasses a dependence of the potential on molecular charge and spin. It brings ML and physical models one step closer, ensuring the correct molecular energy behavior over the total molecular charge.We finally describe perhaps the simplest possible physics-aware model, which combines ML and the extended Hückel method. In ML-EHM, "Hierarchically Interacting Particle Neural Network," HIP-NN generates the set of a molecule- and environment-dependent Hamiltonian elements αμμ and K‡. As a test example, we show how in contrast to traditional Hückel theory, ML-EHM correctly describes orbital crossing with bond rotations. Hence it learns the underlying physics, highlighting that the inclusion of proper physical constraints and symmetries could significantly improve ML model generalization.


Novel Insights into Pathophysiology of Delayed Cerebral Ischemia: Effects of Current Rescue Therapy on Microvascular Perfusion Heterogeneity.
General microvascular perfusion and its heterogeneity are pathophysiological features of delayed cerebral ischemia (DCI) that are gaining increasing attention. Recently, CT perfusion (CTP) imaging has made it possible to evaluate them radiologically using mean transit time (MTT) and its heterogeneity (measured by cvMTT). This study evaluates the effect of multimodal rescue therapy (intra-arterial nimodipine administration and elevation of blood pressure) on MTT and cvMTT during DCI in aneurysmal subarachnoid haemorrhage (aSAH) patients. A total of seventy-nine aSAH patients who underwent multimodal rescue therapy between May 2012 and December 2019 were retrospectively included in this study. CTP-based perfusion impairment (MTT and cvMTT) on the day of DCI diagnosis was compared with follow-up CTP after initiation of combined multimodal therapy. The mean MTT was significantly reduced in the follow-up CTP compared to the first CTP (3.7 ± 0.7 s vs. 3.3 ± 0.6 s; p < 0.0001). However, no significant reduction of cvMTT was observed (0.16 ± 0.06 vs. 0.15 ± 0.06; p = 0.44). Mean arterial pressure was significantly increased between follow-up and first CTP (98 ± 17 mmHg vs. 104 ± 15 mmHg; p < 0.0001). The combined multimodal rescue therapy was effective in addressing the general microvascular perfusion impairment but did not affect the mechanisms underlying microvascular perfusion heterogeneity. This highlights the need for research into new therapeutic approaches that also target these pathophysiological mechanisms of DCI.


Immediate hypersensitivity to Cryptococcus neoformans.
The role of the capsular polysaccharide in anaphylactic reactions to Cryptococcus neoformans was investigated. Groups of mice were sensitized with viable cells of either a moderately encapsulated strain of C. neoformans or a non-encapsulated variant. Anaphylactic reactions were observed in both groups of mice to a similar extent when challenged with whole cells. Mice sensitized with the encapsulated strain and challenged with homologous polysaccharide showed only mild hypersensitivity symptoms. Mice sensitized with either the encapsulated or the nonencapsulated strain showed cross-reactivity when challenged with killed cells of the heterologous strain. These data indicate that the capsular polysaccharide plays a minor role in anaphylactic reactions to C. neoformans and that the sensitizing antigen is probably located in the cell wall of the yeast.


Polyplexes and lipoplexes for mammalian gene delivery: from traditional to microarray screening.
Gene therapy requires the development of non-toxic and highly efficient delivery systems for DNA and RNAi. Polycations, especially dendrimers, have shown enormous potential as gene transfer vehicles, displaying minimal toxicity with a broad range of cell lines. In this paper, a total of 13 dendrimers, up to G3.0, were constructed from AB(3) type isocyanate monomers using solid phase methodology and evaluated for transfection activity. Among the library of compounds prepared, a G3.0 dendrimer displayed comparable activity to Superfect. Gel retardation assays demonstrated that all of the compounds completely bound plasmid DNA, indicating the efficient formation of complexes between DNA and the dendrimers. A "transfection microarray" approach was developed for screening these compounds as well as a panel of lipoplexes (complexes of DNA with cationic lipids) and polyplexes (complexes of DNA with synthetic polycationic polymers), in 3D solution like micro-assay). Five cationic lipids with a cholesterol tail showed stronger or comparable transfection activity relative to Effectene. The new, micro-array screening method was rapid and miniaturized, offering the potential of high throughput screening of large libraries of transfection candidates, with thousands of library members per array, and the ability to rapidly screen a broad range of cell types.


Can typical US home visits affect infant attachment? Preliminary findings from a randomized trial of Healthy Families Durham.
US government-funded early home visiting services are expanding significantly. The most widely implemented home visiting models target at-risk new mothers and their infants. Such home visiting programs typically aim to support infant-parent relationships; yet, such programs' effects on infant attachment quality per se are as yet untested. Given these programs' aims, and the crucial role of early attachments in human development, it is important to understand attachment processes in home visited families. The current, preliminary study examined 94 high-risk mother-infant dyads participating in a randomized evaluation of the Healthy Families Durham (HFD) home visiting program. We tested (a) infant attachment security and disorganization as predictors of toddler behavior problems and (b) program effects on attachment security and disorganization. We found that (a) infant attachment disorganization (but not security) predicted toddler behavior problems and (b) participation in HFD did not significantly affect infant attachment security or disorganization. Findings are discussed in terms of the potential for attachment-specific interventions to enhance the typical array of home visiting services.


[Immunohistochemical receptor findings in the endometrium and therapeutic consequences in endogenous and exogenous functional disorders and cancer].
We studied immunohistochemically cryostat sections made from fresh endometrial tissue, immediately frozen after removal (86 hysterectomy specimens, 6 curettages) for their content of oestrogen receptors (ER) using the ER-ICA assay. Routine histological sections were prepared from parallel specimens of the endometria for determining endometrial functions. The evaluation of the immunohistiological preparations showed that the ER content in the endometrium was closely related to the endogenous hormone stimulation. A further refinement and differentiation of that relationship became possible and correlated well with the various forms of follicle and corpus-luteum insufficiencies. The results indicated that it is now possible to recommend therapy of functional disorders of the endometrium, esp. in sterility cases, without need or knowledge of serum hormone levels. As the endometrial glandular proliferation increases, the density of the ER becomes more intense. In contrast, under therapy with predominantly gestagenic preparations or after these are discontinued, the ER are decreased more than found in normal glands at that degree of proliferation. Whereas the atrophic endometria of old age contained greatly diminished but still detectable ER, no ER could be found in endometrial atrophy induced by oral contraceptives. Carcinomatous endometria revealed a heterogeneous distribution of ER. The better the tumour cells were differentiated, the greater was the density of the ER. By contrast, the carcinomas derived from metaplastic Müllerian epithelium contained few or no ER. This difference is of practical importance, since an adjuvant anti-oestrogen therapy seems of value only with ER-positive carcinomas. The immunohistochemical determination of ER is more exact than the biochemical determination, for each single cell can be evaluated.(ABSTRACT TRUNCATED AT 250 WORDS)


The basolateral sorting signal of the polymeric immunoglobulin receptor contains two functional domains.
Basolateral sorting of the polymeric immunoglobulin receptor (pIgR) expressed in Madin-Darby canine kidney (MDCK) cells is mediated by a 17-residue sorting signal that resides in the cytoplasmic domain. We have recently analyzed the sequence requirements of the signal by alanine scanning mutagenesis. We found that basolateral sorting is mediated primarily by three amino acids: H656, R657 and V660. Individual mutations of each of these residues to Ala caused a substantial decrease in basolateral sorting and a corresponding increase in targeting to the apical surface. Structural analysis of 17-residue peptides corresponding to the signal revealed that V660 is in a beta-turn (probably type I) secondary structure, and its mutation to Ala destabilized the turn. H656 and R657 were not part of the turn and substitution of Arg657 to Ala had no effect on the turn stability. These results suggested that the signal is comprised of two structurally distinct domains: a critical V660 in the context of the beta-turn and an additional two residues (H656 and R657) that are not in the turn and probably are unimportant for its stability. Here we provide evidence suggesting that the two domains are distinguishable not only by their structure but also by their function. Basolateral targeting of pIgR mutants bearing Ala mutations at either 656 or 657 was not affected by treatment with brefeldin A (BFA), while basolateral targeting of pIgR containing an Ala substitution at position 660 was markedly and uniquely stimulated by BFA. Compared to single Ala substitutions, simultaneous mutations of H656 and R657 to Ala caused an additional minor effect on basolateral and apical sorting, whereas double mutations of V660 and either H656 or R657 resulted in a maximal decrease in basolateral targeting and corresponding increase in apical targeting. These results suggest the existence of two domains in the signal. When both domains are destroyed, basolateral targeting is maximally inhibited. The results also imply that V660 mediates basolateral sorting by a different mechanism from H656 and R657. We suggest that V660 and perhaps more generally the beta-turn may interact with BFA-sensitive adaptor complexes.


Evaluation and characterization of congenital hypothyroidism in rdw dwarf rats.
The rdw rat is a new strain of dwarf mutant that has decreased blood thyroxine (T4) and growth hormone (GH) concentrations and testicular enlargement during development and aging. To confirm whether this strain can be used as a new hypothyroid model, the experiments reported here were carried out, using adult rdw rats, rdw rats treated with thyroxine, and clinically normal (N) Wistar-Imamichi rats. Clinical parameters of deficient thyroid function in rdw rats were chosen for evaluation and characterization. Body weight, hemoglobin (Hb) concentration, hematocrit (Hct), glucose (GLU), and systolic blood pressure were significantly lower, and serum values for aspartate transaminase (AST), total cholesterol (TC), total protein (TP), and blood urea nitrogen (BUN) were higher in rdw than in N rats. Serum concentrations of total T4 and free triiodothyronine (FT3) were significantly lower, and serum thyroid-stimulation hormone (TSH) concentration was markedly higher in rdw than in N rats. Serum GH concentration was significantly lower in rdw than in N rats. Results of histologic examination indicated that the thyroid gland of rdw rats was markedly atrophied, compared with that of N rats. Results of clinical examination of organs and hematologic and biochemical values in rdw rats corresponded to those of the hypothyroid state in humans. Most organ weights (heart, kidney, spleen, and adrenal gland), hematologic and biochemical values (Hb, Hct TC, TP, BUN), blood pressure, and serum hormone (TSH and GH) values underwent substantial restoration (partial or complete) toward normal in response to replacement therapy. In conclusion, the rdw rat is a useful model of congenital hypothyroidism.


Application of multimodal perception scenario construction based on IoT technology in university music teaching.
In the contemporary landscape of diversified talent cultivation, enhancing education through intelligent means and expediting the process of talent development stand as paramount pursuits. Within the domain of instrumental music education, beyond merely listening to student performances, it becomes imperative to assess their movements, thus furnishing additional insights to fuel their subsequent growth. This article introduces a novel multimodal information fusion evaluation approach, combining sound information and movement data to address the challenge of evaluating students' learning status in college music instruction. The proposed framework leverages Internet of Things (IoT) technology, utilizing strategically positioned microphones and cameras within the local area network to accomplish data acquisition. Sound feature extraction is accomplished through the employment of Mel-scale frequency cepstral coefficients (MFCC), while the OpenPose framework in deep learning and convolutional neural networks (CNN) is harnessed to extract action features during students' performances. Subsequently, the fusion of feature layers is achieved through CNN, culminating in the evaluation of students' academic efficacy, facilitated by a fully connected network (FCN) and an activation function. In comparison to evaluations conducted by the teacher in the class, this approach achieves an impressive accuracy of 95.7% across the three categories of Excellent, Good, and Failed students' evaluation processes. This breakthrough offers novel insights for the future of music teaching and interactive class evaluations while expanding the horizons of multimodal information fusion methods' applications.


New frontiers in patient-reported outcomes: adverse event reporting, comparative effectiveness, and quality assessment.
Patient-reported outcomes (PROs) are data elements directly reported by patients or their surrogates about experiences with care, including symptoms, functional status, or quality of life. PROs have commonly been evaluated in clinical trials for drug and medical device development. Interest is growing in the ability to integrate PROs into additional contexts, particularly product safety evaluation, comparative effectiveness research, and measurement of care quality. This interest reflects a growing focus on patient-centeredness in health care broadly and on provisions of the US Patient Protection and Affordable Care Act of 2010. Multiple initiatives demonstrate the feasibility and value of patient reporting in these areas. Inclusion of PROs in electronic health records and hospital patient portals, as well as longitudinal registries, can facilitate use of these data for multiple analytic purposes as well as enhance delivery of care and patient-provider communication. Challenges include the logistics and cost of implementing PRO programs; missing data, particularly from hard-to-reach and ill patients; and the need for standardization of outcome measures and electronic data representation. These challenges have been surmounted in limited initiatives and now must be translated to larger implementations.


Hamstring and psoas length of crouch gait in cerebral palsy: a comparison with induced crouch gait in age- and sex-matched controls.
Previous studies have shown that hamstring lengths are often not short in patients with cerebral palsy, which raises concerns over the benefits of distal hamstring lengthening in patients with crouch gait. In this study, the authors measured lengths of hamstrings and psoas muscles in normal subjects mimicking crouch gait and compared these with lengths in cerebral palsy patients with crouch gait. Thirty-six patients with cerebral palsy and crouch gait were included in this study, and in addition, 36 age- and sex-matched normal controls were recruited. Hamstring and psoas muscle lengths in patients were evaluated using gait analysis and interactive musculoskeletal modeling software. Muscle lengths were also measured in the normal control group during normal gait and while mimicking crouch gait, and these were compared with those of cerebral palsy patient with crouch gait. No significant differences were observed between maximum hamstring (p=0.810) and maximum psoas (p=0.456) lengths of patients and controls mimicking crouch gait. However, patients showed significantly shorter excursions of hamstring (p=0.022) and psoas (p=0.036) muscles than controls, whereas no significant excursion differences were observed between controls during normal gait and mimicking crouch gait. Normal controls mimicking crouch gait and cerebral palsy patients with crouch gait demonstrate similar muscle length patterns. However, mimicked crouch gait did not reproduce the excursion pattern shown by patients with crouch gait, which suggests that reduced hamstring and psoas excursion is an innate characteristic of pathologic crouch gait.


The role of the transcription factor SIM2 in prostate cancer.
Recent reports have suggested a possible involvement of Single-minded homolog 2 (SIM2) in human solid cancers, including prostate cancer. However, the exact role of SIM2 in cancer in general, and in prostate cancer in particular, remains largely unknown. This study was designed to elucidate the role of SIM2 in prostate cancer using a shRNA-based approach in the PC3 prostate cancer cell line. Lentiviral shRNAs were used to inhibit SIM2 gene and protein levels in PC3 cells. Quantitative RT-PCR and branched DNA were performed to evaluate transcript expression. SIM2 protein expression level was measured by western blot. Profiling of gene expression spanning the whole genome, as well as polar metabolomics of several major metabolic pathways was performed to identify major pathway dysregulations. SIM2 gene and protein products were significantly downregulated by lenti-shRNA in PC3 cell line. This low expression of SIM2 affected gene expression profile, revealing significant changes in major signaling pathways, networks and functions. In addition, major metabolic pathways were affected. Taken together, our results suggest an involvement of SIM2 in key traits of prostate tumor cell biology and might underlie a contribution of this transcription factor to prostate cancer onset and progression.


Constructing Mutants in Serotype 1 Streptococcus pneumoniae strain 519/43.
Streptococcus pneumoniae serotype 1 remains a huge problem in low-and-middle income countries, particularly in sub-Saharan Africa. Despite its importance, studies in this serotype have been hindered by the lack of genetic tools to modify it. In this study, we describe a method to genetically modify a serotype 1 clinical isolate (strain 519/43). Interestingly, this was achieved by exploiting the Pneumococcus' ability to naturally acquire DNA. However, unlike most pneumococci, the use of linear DNA was not successful; to mutate this important strain, a suicide plasmid had to be used. This methodology has provided the means for a deeper understanding of this elusive serotype, both in terms of its biology and pathogenicity. To validate the method, the major known pneumococcal toxin, pneumolysin, was mutated because it has a well-known and easy to follow phenotype. We showed that the mutant, as expected, lost its ability to lyse red blood cells. By being able to mutate an important gene in the serotype of interest, we were able to observe different phenotypes for loss of function mutants upon intraperitoneal and intranasal infections from the ones observed for other serotypes. In summary, this study proves that strain 519/43 (serotype 1) can be genetically modified.


Presence of enteric viruses in water samples for consumption in Colombia: Challenges for supply systems.
Since drinking water can be a vehicle for the transmission of pathogens, the detection of enteric viruses in these water samples is essential to establish the appropriate measures to control and prevent associated diseases. To analyze the results obtained for enteric viruses in water samples for human consumption received at the Colombian Instituto Nacional de Salud and establish their association with the data on water quality in Colombian municipalities. We conducted a descriptive-retrospective analysis of the results obtained in the detection of rotavirus, enterovirus, hepatitis A virus and adenovirus in water samples received for complementary studies of enteric hepatitis, acute diarrheal disease and foodborne diseases. Data were correlated with the results of water quality surveillance determined by the national human consumption water quality index (IRCA). Of the 288 samples processed from 102 Colombian municipalities, 50.7% were positive for viruses: 26.73% for hepatitis A virus, 20.48% for enterovirus and rotavirus and 18.05% for adenovirus. Viruses were detected in 48.26% of non-treated water samples and in 45.83% of treated water samples. The IRCA index showed no correlation with the presence of viruses. The presence of viruses in water represents a public health risk and, therefore, the prevention of virus transmission through water requires appropriate policies to reinforce water supply systems and improve epidemiological surveillance.


Amyloidogenesis of type III-dependent harpins from plant pathogenic bacteria.
Harpins are heat-stable, glycine-rich type III-secreted proteins produced by plant pathogenic bacteria, which cause a hypersensitive response (HR) when infiltrated into the intercellular space of tobacco leaves; however, the biochemical mechanisms by which harpins cause plant cell death remain unclear. In this study, we determined the biochemical characteristics of HpaG, the first harpin identified from a Xanthomonas species, under plant apoplast-like conditions using electron microscopy and circular dichroism spectroscopy. We found that His(6)-HpaG formed biologically active spherical oligomers, protofibrils, and beta-sheet-rich fibrils, whereas the null HR mutant His(6)-HpaG(L50P) did not. Biochemical analysis and HR assay of various forms of HpaG demonstrated that the transition from an alpha-helix to beta-sheet-rich fibrils is important for the biological activity of protein. The fibrillar form of His(6)-HpaG is an amyloid protein based on positive staining with Congo red to produce green birefringence under polarized light, increased protease resistance, and beta-sheet fibril structure. Other harpins, such as HrpN from Erwinia amylovora and HrpZ from Pseudomonas syringae pv. syringae, also formed curvilinear protofibrils or fibrils under plant apoplast-like conditions, suggesting that amyloidogenesis is a common feature of harpins. Missense and deletion mutagenesis of HpaG indicated that the rate of HpaG fibril formation is modulated by a motif present in the C terminus. The plant cytotoxicity of HpaG is unique among the amyloid-forming proteins that occur in several microorganisms. Structural and morphological analogies between HpaG and disease-related amyloidogenic proteins, such as Abeta protein, suggest possible common biochemical characteristics in the induction of plant and animal cell death.


The frequency of inappropriate nonformulary medication alert overrides in the inpatient setting.
Experts suggest that formulary alerts at the time of medication order entry are the most effective form of clinical decision support to automate formulary management. Our objectives were to quantify the frequency of inappropriate nonformulary medication (NFM) alert overrides in the inpatient setting and provide insight on how the design of formulary alerts could be improved. Alert overrides of the top 11 (n = 206) most-utilized and highest-costing NFMs, from January 1 to December 31, 2012, were randomly selected for appropriateness evaluation. Using an empirically developed appropriateness algorithm, appropriateness of NFM alert overrides was assessed by 2 pharmacists via chart review. Appropriateness agreement of overrides was assessed with a Cohen's kappa. We also assessed which types of NFMs were most likely to be inappropriately overridden, the override reasons that were disproportionately provided in the inappropriate overrides, and the specific reasons the overrides were considered inappropriate. Approximately 17.2% (n = 35.4/206) of NFM alerts were inappropriately overridden. Non-oral NFM alerts were more likely to be inappropriately overridden compared to orals. Alerts overridden with "blank" reasons were more likely to be inappropriate. The failure to first try a formulary alternative was the most common reason for alerts being overridden inappropriately. Approximately 1 in 5 NFM alert overrides are overridden inappropriately. Future research should evaluate the impact of mandating a valid override reason and adding a list of formulary alternatives to each NFM alert; we speculate these NFM alert features may decrease the frequency of inappropriate overrides.


Neural network and regression predictions of 5-year survival after colon carcinoma treatment.
The Commission on Cancer data from the National Cancer Data Base (NCDB) for patients with colon carcinoma was used to develop several artificial neural network and regression-based models. These models were designed to predict the likelihood of 5-year survival after primary treatment for colon carcinoma. Two modeling methods were used in the study. Artificial neural networks were used to select the more important variables from the NCDB database and model 5-year survival. A standard parametric logistic regression also was used to model survival and the two methods compared on a prospective set of patients not used in model development. The neural network yielded a receiver operating characteristic (ROC) area of 87.6%. At a sensitivity to mortality of 95% the specificity was 41%. The logistic regression yielded a ROC area of 82% and at a sensitivity to mortality of 95% gave a specificity of 27%. The neural network found a strong pattern in the database predictive of 5-year survival status. The logistic regression produced somewhat less accurate, but good, results.


Recent Canadian efforts to develop population-level pregnancy intervention studies to mitigate effects of natural disasters and other tragedies.
The preconception, pregnancy and immediate postpartum and newborn periods are times for mothers and their offspring when they are especially vulnerable to major stressors - those that are sudden and unexpected and those that are chronic. Their adverse effects can transcend generations. Stressors can include natural disasters or political stressors such as conflict and/or migration. Considerable evidence has accumulated demonstrating the adverse effects of natural disasters on pregnancy outcomes and developmental trajectories. However, beyond tracking outcomes, the time has arrived for gathering more information related to identifying mechanisms, predicting risk and developing stress-reducing and resilience-building interventions to improve outcomes. Further, we need to learn how to encapsulate both the quantitative and qualitative information available and share it with communities and authorities to mitigate the adverse developmental effects of future disasters, conflicts and migrations. This article briefly reviews prenatal maternal stress and identifies three contemporary situations (wildfire in Fort McMurray, Alberta, Canada; hurricane Harvey in Houston, USA and transgenerational and migrant stress in Pforzheim, Germany) where current studies are being established by Canadian investigators to test an intervention. The experiences from these efforts are related along with attempts to involve communities in the studies and share the new knowledge to plan for future disasters or tragedies.


A possible link between the pubertal growth of girls and ovarian cancer in their daughters.
At puberty, the distance between the iliac crests of the female pelvis, measured by the intercristal and interspinous diameters, increases rapidly. This is mainly controlled by estrogens. We have followed up 6,370 women who were born in Helsinki during 1934-1944, and whose mothers' pelvic bones were measured during routine antenatal care. We have previously reported that women whose mothers had larger intercristal diameters had higher rates of breast cancer. We postulated that large intercristal diameters are markers of high circulating concentrations of estrogen, which are established at puberty, persist through reproductive life and cause genetic instability in differentiating breast cells in female embryos. We now report on ovarian cancer in the same cohort. Our hypothesis was that the risk of this cancer would also be higher in women whose mothers had broader hips. We found that, when compared with all other women, the hazard ratio for ovarian cancer was 3.3 (95% CI 1.6-7.0, P = 0.004) in the daughters of mothers whose interspinous diameter was greater than 27 cm. Among mothers who had an early menarche, each measure of broad hips was associated with increased risk of ovarian cancer in their daughters. We postulate that ovarian cancer is initiated by exposure of the fetal ovary to maternal sex hormones. Concentrations of these hormones may be higher in mothers who had an early menarche. The maternal sex hormone profile that initiates ovarian cancer may be the product of poor nutrition and growth in early childhood followed by catch-up pre-pubertal growth.


Perforin and IFN-gamma are involved in the antitumor effects of antibody-targeted superantigens.
The bacterial superantigen staphylococcal enterotoxin A (SEA) is a potent inducer of cytokine production and cytotoxic T cell responses. To target a T cell attack against tumor cells we have genetically engineered a fusion protein of SEA and the Fab part of the tumor-reactive mAb C215. Injection of this Fab-SEA fusion protein to mice carrying lung metastases of the poorly immunogenic B16 melanoma transfected with the C215 Ag resulted in infiltration of cytokine-producing T cells, perforin-containing CTL, and a marked tumor elimination. Fab-SEA therapy induced substantial levels of IFN-gamma and TNF-alpha in serum. In the present study we have characterized the molecular mechanisms of the antitumor effect induced by Fab-SEA treatment in vivo. Neutralization of cytokines by specific Abs demonstrated a major role for IFN-gamma in the suppression of tumor growth. In addition, a minor contribution of TNF-alpha was recorded. Injections of Fab-SEA into normal mice induced strong CTL activity but failed to promote cytotoxic function in perforin knockout mice. Also, a markedly reduced therapy was noted in perforin knockout mice, implicating a role for CTL in Fab-SEA-mediated tumor eradication. The data suggest that Fab-SEA-targeted T cells may suppress tumor growth by both perforin-dependent cytotoxicity and local release of cytokines such as IFN-gamma. The latter mechanism may have an important role in cytostatic effects against Ag-negative bystander tumor cells.


Standardised assessment in developing countries.
In developing countries, the standardised psychiatric assessment raises special problems: lack of trained manpower, lack of research facilities, transcultural aspects of concepts and wording originally elaborated by Western psychiatrists. The author gives a few examples, mainly from the PSE.


Rapid differentiation of pathogenesis in patients with pulmonary edema by protein measurement with refractometer.
No study has focused on using refractometer to rapidly determine total protein ratio of edema fluid to blood concentration (TPe/TPb) and, to differentiate hydrostatic pulmonary edema (HPE) from adult respiratory distress syndrome (ARDS). The reliability of refractometer was evaluated by correlating the protein concentration measured by refractometer with that by sequential multiple autoanalyzer (SMA) in 91 blood samples. In intensive care unit, thirteen patients with florid pulmonary edema were included. All had an unequivocal diagnosis of either HPE or ARDS. Edema fluid and blood were collected simultaneously for the measurement of protein concentration by refractometer. Protein concentration measured by refractometer correlated excellently with that by sequential multiple autoanalyzer (r = 0.991, p < 0.00001). In 7 patients with ARDS, the mean TPe/TPb was 0.75 +/- 0.13. In contrast, in 6 patients with HPE, the mean TPe/TPb was 0.36 +/- 0.14. The difference between groups was significant (p < 0.005). An inverse correlation between TPe/TPb and wedge pressure was also significant (r = -0.814, p < 0.001). Using refractometer to determine protein ratio of edema fluid to blood concentration can rapidly and effectively distinguish ARDS from HPE in patients with florid pulmonary edema. TPe/TPb correlates inversely with wedge pressure in these patients.


Assessment of strength, flexibility, and running mechanics in men with iliotibial band syndrome.
Cross-sectional laboratory study. To assess differences in hip strength, iliotibial band length, and hip and knee mechanics during running between male runners with iliotibial band syndrome (ITBS) and healthy controls. Flexibility, strength, and running mechanics are commonly assessed in patients with ITBS. However, these variables have not been evaluated concurrently in this population. Thirty-four men participated (17 healthy, 17 ITBS). Hip strength was measured with a handheld dynamometer, and iliotibial band length was assessed using an inclinometer while performing the Ober test. Kinetic and 3-D kinematic data were obtained during running. Kinematic variables of interest included frontal and transverse plane hip and knee joint angles during early stance. Independent-samples t tests, as well as effect sizes, were used to assess group differences. Compared to the control group, persons with ITBS had a significantly lower Ober measurement (1.2°), weaker hip external rotators (1.2 Nm/kg), greater hip internal rotation (3.7°), and greater knee adduction (3.6°). However, only hip internal rotation and knee adduction exceeded the minimal detectable difference value. Our results suggest that intervention strategies that target neuromuscular control of the hip and knee may be indicated for males with ITBS.


Reducing the risks to health care workers from blood and body fluid exposure in a small rural hospital in Thabo-Mofutsanyana, South Africa.
Health care workers in sub-Saharan Africa are at high risk of acquiring bloodborne diseases. A training program was launched to build the capacity of occupational health nurses to design and implement workplace-based projects. The study assessed the knowledge, attitudes, and practices of health care workers regarding blood and body fluid exposures in a small district hospital in a rural area of the Free State in South Africa. Under the guidance of two experienced mentors, an occupational health nurse designed a knowledge, attitudes, and practices questionnaire and distributed itto 101 health care workers at risk throughout the hospital; 88% of questionnaires were returned in sealed envelopes.Limited knowledge and ineffective practices were documented. For example, only 54.3% of the respondents reported that needles should never be recapped. A significant correlation (p < .001) was found between limited knowledge and recent blood and body fluid exposure. The study results provided the occupational health nurse with data to address the knowledge, attitudes, and practices deficits by implementing an injury prevention educational intervention. Such training initiatives can decrease the burden of occupational disease among health care workers in rural low-resourced areas.


[Significance of changes in individual indicators on intravascular homeostasis in development of circulatory hypoxia in aging].
The study comprised 45 healthy subjects aged 60-74. It was designed to examine the state of skin and bulbar microcirculation using the method of television capillaroscopy. The functional state of endothelial microvessels was studied with the help of laser doppler flowmeter by means of functional tests with postocclusion hyperaemia and intradermal injection of epinephrine solution in the dose of 0.1 ml (1.10-6 mol/l). The platelets aggregation activity was studied using the method of turbidimetry. The blood viscosity and functional state of erythrocytes were determined with the help of rotary viscosimeter at the shift velocity of 10 to 200s-1 with estimating the erythrocytes deformability and aggregation indexes. Oxygen saturation of the subcutaneous fat fibers was studied by polarography. It has been found that the increase of adrenalin-induction aggregation of platelets, the decrease of erythrocyte deformation and the endothelium synthesis disturbance caused relaxing factors play role in the circulatory hypoxia development.


Etiological and epidemiological features of acute respiratory infections in China.
Nationwide prospective surveillance of all-age patients with acute respiratory infections was conducted in China between 2009‒2019. Here we report the etiological and epidemiological features of the 231,107 eligible patients enrolled in this analysis. Children <5 years old and school-age children have the highest viral positivity rate (46.9%) and bacterial positivity rate (30.9%). Influenza virus, respiratory syncytial virus and human rhinovirus are the three leading viral pathogens with proportions of 28.5%, 16.8% and 16.7%, and Streptococcus pneumoniae, Mycoplasma pneumoniae and Klebsiella pneumoniae are the three leading bacterial pathogens (29.9%, 18.6% and 15.8%). Negative interactions between viruses and positive interactions between viral and bacterial pathogens are common. A Join-Point analysis reveals the age-specific positivity rate and how this varied for individual pathogens. These data indicate that differential priorities for diagnosis, prevention and control should be highlighted in terms of acute respiratory tract infection patients' demography, geographic locations and season of illness in China.


Functional brain network changes associated with maintenance of cognitive function in multiple sclerosis.
In multiple sclerosis (MS) functional changes in connectivity due to cortical reorganization could lead to cognitive impairment (CI), or reflect a re-adjustment to reduce the clinical effects of widespread tissue damage. Such alterations in connectivity could result in changes in neural activation as assayed by executive function tasks. We examined cognitive function in MS patients with mild to moderate CI and age-matched controls. We evaluated brain activity using functional magnetic resonance imaging (fMRI) during the successful performance of the Wisconsin card sorting (WCS) task by MS patients, showing compensatory maintenance of normal function, as measured by response latency and error rate. To assess changes in functional connectivity throughout the brain, we performed a global functional brain network analysis by computing voxel-by-voxel correlations on the fMRI time series data and carrying out a hierarchical cluster analysis. We found that during the WCS task there is a significant reduction in the number of smaller size brain functional networks, and a change in the brain areas representing the nodes of these networks in MS patients compared to age-matched controls. There is also a concomitant increase in the strength of functional connections between brain loci separated at intermediate-scale distances in these patients. These functional alterations might reflect compensatory neuroplastic reorganization underlying maintenance of relatively normal cognitive function in the face of white matter lesions and cortical atrophy produced by MS.