Dealing with missing phase and missing data in phylogeny-based analysis.
We recently described a new method to identify disease susceptibility loci, based on the analysis of the evolutionary relationships between haplotypes of cases and controls. However, haplotypes are often unknown and the problem of phase inference is even more crucial when there are missing data. In this work, we suggest using a multiple imputation algorithm to deal with missing phase and missing data, prior to a phylogeny-based analysis. We used the simulated data of Genetic Analysis Workshop 15 (Problem 3, answer known) to assess the power of the phylogeny-based analysis to detect disease susceptibility loci after reconstruction of haplotypes by a multiple-imputation method. We compare, for various rates of missing data, the performance of the multiple imputation method with the performance achieved when considering only the most probable haplotypic configurations or the true phase. When only the phase is unknown, all methods perform approximately the same to identify disease susceptibility sites. In the presence of missing data however, the detection of disease susceptibility sites is significantly better when reconstructing haplotypes by multiple imputation than when considering only the best haplotype configurations.


Medicaid coverage accuracy in electronic health records.
Health insurance coverage facilitates access to preventive screenings and other essential health care services, and is linked to improved health outcomes; therefore, it is critical to understand how well coverage information is documented in the electronic health record (EHR) and which characteristics are associated with accurate documentation. Our objective was to evaluate the validity of EHR data for monitoring longitudinal Medicaid coverage and assess variation by patient demographics, visit types, and clinic characteristics. We conducted a retrospective, observational study comparing Medicaid status agreement between Oregon community health center EHR data linked at the patient-level to Medicaid enrollment data (gold standard). We included adult patients with a Medicaid identification number and ≥1 clinic visit between 1/1/2013-12/31/2014 [>1 million visits (n = 135,514 patients)]. We estimated statistical correspondence between EHR and Medicaid data at each visit (visit-level) and for different insurance cohorts over time (patient-level). Data were collected in 2016 and analyzed 2017-2018. We observed excellent agreement between EHR and Medicaid data for health insurance information: kappa (>0.80), sensitivity (>0.80), and specificity (>0.85). Several characteristics were associated with agreement; at the visit-level, agreement was lower for patients who preferred a non-English language and for visits missing income information. At the patient-level, agreement was lower for black patients and higher for older patients seen in primary care community health centers. Community health center EHR data are a valid source of Medicaid coverage information. Agreement varied with several characteristics, something researchers and clinic staff should consider when using health insurance information from EHR data.


Buprenorphine Induction in a Rural Maryland Detention Center During COVID-19: Implementation and Preliminary Outcomes of a Novel Telemedicine Treatment Program for Incarcerated Individuals With Opioid Use Disorder.
Over 10 million individuals pass through U.S. detention centers on an annual basis, with nearly two-thirds meeting criteria for drug dependence/abuse. Despite proven efficacy, treatment with medications for opioid use disorder (MOUD) is underutilized in jail settings-a gap that could be addressed using telemedicine. Here we describe a new program of telemedicine-based clinical provision of new/continuing buprenorphine treatment for individuals detained in a rural jail. Implementation objectives were completed between January and August 2020, and patient encounters were conducted between August 2020 and February 2021. We established (i) telemedicine hardware/software capability; (ii) a screening process; (iii) buprenorphine administration methods; (iv) necessary medical release procedures; (v) telemedicine encounter coordination and medication prescription procedures; and (vi) a research platform. Seven incarcerated patients have been treated, two of whom were referred from community treatment. Patients were mostly male (71%), non-Hispanic White (86%), and averaged 33 years old. All patients tested positive for an opioid upon intake and began/continued buprenorphine treatment in the jail. Average time to first MOUD appointment was 9 days and patients were maintained in treatment an average 21 days. Referrals for continuing community treatment were offered to all patients prior to discharge. We report successful implementation of telemedicine MOUD in a rural detention center, with treatment engagement and initiation occurring prior to the high-risk period of discharge. The fact that this program was launched during the height of the pandemic highlights the flexibility of telemedicine-based buprenorphine treatment. Challenges and obstacles to implementation of buprenorphine treatment in a correctional system are discussed.


Training-Induced Acute Neuromuscular Responses to Military Specific Test during a Six-Month Military Operation.
Limited data are available regarding strength and endurance training adaptations to occupational physical performance during deployment. This study assessed acute training-induced changes in neuromuscular (electromyography; EMG) and metabolic (blood lactate, BLa) responses during a high-intensity military simulation test (MST), performed in the beginning (PRE) and at the end (POST) of a six-month crisis-management operation. MST time shortened (145 ± 21 vs. 129 ± 16 s, -10 ± 7%, p < 0.001) during the operation. Normalized muscle activity increased from PRE to POST in the hamstring muscles by 87 ± 146% (116 ± 52 vs. 195 ± 139%EMGMVC, p < 0.001) and in the quadriceps by 54 ± 81% (26 ± 8 vs. 40 ± 20%EMGMVC, p < 0.001). In addition, higher acute BLa values were measured after MST during POST. Changes in BLa and EMG suggested an increased neural input and metabolic rate during POST MST, likely leading to faster performance times at the end of the operation. High EMG values throughout the different phases of MST suggested that despite the anaerobic nature of the test, the soldiers were able to maintain their voluntary muscle activation level until the end of the test. This indicates only limited neural fatigue during the two-minute high-intensity military specific performance. While learning effect may explain some part of the improvement in the MST performance times, combined strength and endurance training three times per week may improve neuromuscular performance in occupationally relevant tasks.


Biphasic mechanisms of neurovascular unit injury and protection in CNS diseases.
In the past decade, evidence has emerged that there is a variety of bidirectional cell-cell and/or cell-extracellular matrix interactions within the neurovascular unit (NVU), which is composed of neuronal, glial, and vascular cells along with extracellular matrix. Many central nervous system diseases, which lead to NVU dysfunction, have common features such as glial activation/transformation and vascular/blood-brain-barrier alteration. These phenomena show dual opposite roles, harmful at acute phase and beneficial at chronic phase. This diverse heterogeneity may induce biphasic clinical courses, i.e. degenerative and regenerative processes in the context of dynamically coordinated cellcell/ cell-matrix interactions in the NVU. A deeper understanding of the seemingly contradictory actions in cellular levels is essential for NVU protection or regeneration to suppress the deleterious inflammatory reactions and promote adaptive remodeling after central nervous system injury. This mini-review will present an overview of recent progress in the biphasic roles of the NVU and discuss the clinical relevance of NVU responses associated with central nervous system diseases, such as stroke and other chronic neurodegenerative diseases.


Binder-free LiCoO2/carbon nanotube cathodes for high-performance lithium ion batteries.
Binder-free LiCoO(2) -SACNT cathodes with excellent flexibility and conductivity are obtained by constructing a continuous three-dimensional super-aligned carbon nanotube (SACNT) framework with embedded LiCoO(2) particles. These binder-free cathodes display much better cycling stability, greater rate performance, and higher energy density than classical cathodes with binder. Various functional binder-free SACNT composites can be mass produced by the ultrasonication and co-deposition method described in this paper.


OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FEATURES OF ANGIOID STREAKS.
To analyze the optical coherence tomography angiography features of eyes affected with angioid streaks (AS) and to evaluate their ability to predict choroidal neovascularization (CNV) activity. Angioid streaks were individuated from a pool of consecutive patients. Eyes with and without CNV were evaluated by multimodal imaging. Thirty-eight eyes of 19 consecutive patients diagnosed with AS were included. Thirty of 38 eyes with CNV and 8 of 38 eyes without CNV were included. In the majority of cases, CNV showed on optical coherence tomography angiography tangled appearance always associated with signs of neovascular inactivity on multimodal imaging (100%-0%, inactive-active, respectively). Choroidal neovascularization cases showing interlacing appearance were often associated with signs of neovascular activity on multimodal imaging (71.4%-28.6%, active-inactive, respectively). Optical coherence tomography angiography revealed a total of 27 AS, of which 20 appeared as a choriocapillary rarefaction, and in 7 AS, optical coherence tomography angiography choriocapillary segmentation revealed an irregular vascular network, possibly representing fibrovascular tissue over the crack-like breaks in Bruch membrane. Optical coherence tomography angiography is a noninvasive tool to detect the presence of CNV secondary to AS and to evaluate CNV activity. Optical coherence tomography angiography is able to add a novel element to the multimodal imaging characterization of AS.


Childhood socioeconomic position, gender, adult body mass index, and incidence of type 2 diabetes mellitus over 34 years in the Alameda County Study.
We examined the association between childhood socioeconomic position and incidence of type 2 diabetes and the effects of gender and adult body mass index (BMI). We studied 5913 participants in the Alameda County Study from 1965 to 1999 who were diabetes free at baseline (1965). Cox proportional hazards models estimated diabetes risk associated with childhood socioeconomic position and combined childhood socioeconomic position-adult BMI categories in pooled and gender-stratified samples. Demographic confounders and potential pathway components (physical inactivity, smoking, alcohol consumption, hypertension, depression, health care access) were included as covariates. Low childhood socioeconomic position was associated with excess diabetes risk, especially among women. Race and body composition accounted for some of this excess risk. The association between childhood socioeconomic position and diabetes incidence differed by adult BMI category in the pooled and women-only groups. Adjustment for race and behaviors attenuated the risk attributable to low childhood socioeconomic position among the obese group only. Childhood socioeconomic position was a robust predictor of incident diabetes, especially among women. A cumulative risk effect was observed for both childhood socioeconomic position and adult BMI, especially among women.


Collateral ligament injuries of the thumb metacarpophalangeal joint.
The ulnar and radial collateral ligaments are primary stabilizers of the thumb metacarpophalangeal (MP) joint. Injury to these ligaments can lead to instability and disability. Stress testing is essential to establish the diagnosis. Complete tear is diagnosed on physical examination when the proximal phalanx of the thumb can be angulated ulnarly or radially on the metacarpal head by 30° to 35° with the MP joint in either zero degrees of extension or 30° of flexion. Lack of a firm end point or angulation measuring >15° on stress testing compared with the contralateral thumb MP joint are also indicative of complete tear. Partial ligament injuries may be managed nonsurgically, but complete tears are usually managed surgically. Various techniques are used to reattach the ligament to bone, including suture anchors and, less commonly, repair of midsubstance tears. Options for managing chronic injuries include ligament repair, ligament reconstruction with a free tendon graft, and arthrodesis of the MP joint.


Genome-wide association analysis reveals genetic variations and candidate genes associated with salt tolerance related traits in Gossypium hirsutum.
Cotton is more resistant to salt and drought stresses as compared to other field crops, which makes itself as a pioneer industrial crop in saline-alkali lands. However, abiotic stresses still negatively affect its growth and development significantly. It is therefore important to breed salt tolerance varieties which can help accelerate the improvement of cotton production. The development of molecular markers linked to causal genes has provided an effective and efficient approach for improving salt tolerance. In this study, a genome-wide association study (GWAS) of salt tolerance related traits at seedling stage was performed based on 2 years of phenotype identification for 217 representative upland cotton cultivars by genotyping-by-sequencing (GBS) platform. A total of 51,060 single nucleotide polymorphisms (SNPs) unevenly distributed among 26 chromosomes were screened across the cotton cultivars, and 25 associations with 27 SNPs scattered over 12 chromosomes were detected significantly (-log10p > 4) associated with three salt tolerance related traits in 2016 and 2017. Among these, the associations on chromosome A13 and D08 for relative plant height (RPH), A07 for relative shoot fresh matter weight (RSFW), A08 and A13 for relative shoot dry matter weight (RSDW) were expressed in both environments, indicating that they were likely to be stable quantitative trait loci (QTLs). A total of 12 salt-induced candidate genes were identified differentially expressed by the combination of GWAS and transcriptome analysis. Three promising genes were selected for preliminary function verification of salt tolerance. The increase of GH_A13G0171-silenced plants in salt related traits under salt stress indicated its negative function in regulating the salt stress response. These results provided important genetic variations and candidate genes for accelerating the improvement of salt tolerance in cotton.


A genomic atlas of human adrenal and gonad development.
In humans, the adrenal glands and gonads undergo distinct biological events between 6-10 weeks post conception (wpc), such as testis determination, the onset of steroidogenesis and primordial germ cell development. However, relatively little is currently known about the genetic mechanisms underlying these processes. We therefore aimed to generate a detailed genomic atlas of adrenal and gonad development across these critical stages of human embryonic and fetal development. RNA was extracted from 53 tissue samples between 6-10 wpc (adrenal, testis, ovary and control). Affymetrix array analysis was performed and differential gene expression was analysed using Bioconductor. A mathematical model was constructed to investigate time-series changes across the dataset. Pathway analysis was performed using ClueGo and cellular localisation of novel factors confirmed using immunohistochemistry. Using this approach, we have identified novel components of adrenal development (e.g. ASB4, NPR3) and confirmed the role of SRY as the main human testis-determining gene. By mathematical modelling time-series data we have found new genes up-regulated with SOX9 in the testis (e.g. CITED1), which may represent components of the testis development pathway. We have shown that testicular steroidogenesis has a distinct onset at around 8 wpc and identified potential novel components in adrenal and testicular steroidogenesis (e.g. MGARP, FOXO4, MAP3K15, GRAMD1B, RMND2), as well as testis biomarkers (e.g. SCUBE1). We have also shown that the developing human ovary expresses distinct subsets of genes (e.g. OR10G9, OR4D5), but enrichment for established biological pathways is limited. This genomic atlas is revealing important novel aspects of human development and new candidate genes for adrenal and reproductive disorders.


Local awakening: regional reorganizations of brain oscillations after sleep.
Brain functions express rhythmic fluctuations accompanied by sleep and wakefulness each day, but how sleep regulates brain rhythms remains unclear. Following the dose-dependent local sleep concept, two succeeding questions emerge: (1) is the sleep regulation a network-specific process; and (2) is the awakening state dependent on the previous sleep stages? To answer the questions, we conducted simultaneous EEG and fMRI recordings over 22 healthy male participants, along pre-sleep, nocturnal sleep and awakening. Using paired comparisons between awakening and pre-sleep conditions, three scenarios of the regional specificity were demonstrated on awakening: (1) the default-mode and hippocampal networks maintained similar connectivity and spectral power; (2) the sensorimotor network presented reduced connectivity and spectral power; and (3) the thalamus demonstrated substantially enhanced connectivity to the neo-cortex with decreased spectral power. With regard to the stage effect, the deep sleep group had significant changes in both functional connectivity and spectral power on awakening, whereas the indices of light sleep group remained relatively quiescent after sleep. The phenomena implied that slow-wave sleep could be key to rebooting the BOLD fluctuations after sleep. In conclusion, the regional specificity and the stage effect were verified in support of the local awakening concept, indicating that sleep regulation leads to the reorganization of brain networks upon awakening.


Activity and stability of hyperthermophilic enzymes: a comparative study on two archaeal beta-glycosidases.
S beta gly and CelB are well-studied hyperthermophilic glycosyl hydrolases, isolated from the Archaea Sulfolobus solfataricus and Pyrococcus furiosus, respectively. Previous studies revealed that the two enzymes are phylogenetically related; they are very active and stable at high temperatures, and their overall three-dimensional structure is very well conserved. To acquire insight in the molecular determinants of thermostability and thermoactivity of these enzymes, we have performed a detailed comparison, under identical conditions, of enzymological and biochemical parameters of S beta gly and CelB, and we have probed the basis of their stability by perturbations induced by temperature, pH, ionic strength, and detergents. The major result of the present study is that, although the two enzymes are remarkably similar with respect to kinetic parameters, substrate specificity, and reaction mechanism, they are strikingly different in stability to the different physical or chemical perturbations induced. These results provide useful information for the design of further experiments aimed at understanding the structure-function relationships in these enzymes.


The outcome comparison of headless screws and Mini-plate for treating type B3 distal humerus fractures.
The purpose of this retrospective study was to evaluate the outcome of headless screws and Mini-plate for treating Type B3 fractures of distal humerus. Seventeen patients with type B3 fracture were included and divided into headless screws group and Mini-plate group. Outcome was evaluated using Mayo Elbow Performance Score (MEPS), Short form 36 questionnaire (SF-36), visual analog score (VAS), and range of motion (ROM) at 12 months' follow-up. All patients received a minimum follow-up of 12 months. Postoperative complications mainly included elbow stiffness, heterotrophic ossification and elbow instability. At 12months' follow-up, the MEPS and physical components score of SF-36 in Mini-plate group were significantly higher than that in screw group. Moreover, cases undergoing Mini-plate treatment showed a tendency towards improved ROM of elbow and VAS. The Mini-plate was superior to headless screws on elbow function restoration in the management of type B3 distal humerus fractures.


Serum pro-hepcidin could reflect disease activity in patients with rheumatoid arthritis.
The aim of this study was to analyze the relationship between serum pro-hepcidin concentration and the anemia profiles of rheumatoid arthritis (RA) and to estimate the pro-hepcidin could reflect the disease activity of RA. RA disease activities were measured using Disease Activity Score 28 (DAS28), tender/swollen joint counts, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Anemia profiles such as hemoglobin, iron, total iron binding capacity (TIBC), ferritin, and transferrin levels were measured. Serum concentration of pro-hepcidin, the prohormone of hepcidin, was measured using enzyme-linked immunosorbent assay (ELISA). Mean concentration of serum pro-hepcidin was 237.6+/-67.9 ng/mL in 40 RA patients. The pro-hepcidin concentration was correlated with rheumatoid factor, CRP, ESR, and DAS28. There was a significant correlation between pro-hepcidin with tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6. The pro-hepcidin concentration was significantly higher in the patients with active RA (DAS28>5.1) than those with inactive to moderate RA (DAS28< or =5.1). However, the pro-hepcidin concentration did not correlate with the anemia profiles except hemoglobin level. There was no difference of pro-hepcidin concentration between the patients with anemia of chronic disease and those without. In conclusion, serum concentration of pro-hepcidin reflects the disease activity, regardless of the anemia states in RA patients, thus it may be another potential marker for disease activity of RA.


Prenatal exposure to a phthalate mixture leads to multigenerational and transgenerational effects on uterine morphology and function in mice.
Phthalates are commonly used plasticizers and additives that are found in plastic containers, children's toys and medical equipment. Phthalates are classified as endocrine-disrupting chemicals and exposure to phthalates has been associated with several human health risks including reproductive defects. Most studies focus on a single phthalate; however, humans are exposed to a mixture of phthalates daily. We hypothesized that prenatal exposure to an environmentally relevant phthalate mixture would lead to changes in uterine morphology and function in mice in a multi-generational manner. To test this hypothesis, pregnant CD-1 dams were orally dosed with vehicle or a phthalate mixture (20 μg/kg/day, 200 μg/kg/day, 200 mg/kg/day, and 500 mg/kg/day) from gestational day 10.5 to parturition. The mixture contained 35 % diethyl phthalate, 21 % di-(2-ethylhexyl) phthalate, 15 % dibutyl phthalate, 15 % diisononyl phthalate, 8% diisobutyl phthalate, and 5% benzylbutyl phthalate. The F1 pups were maintained and mated to produce two more generations (F2 and F3). At the age of 13 months, all females were euthanized and tissue samples were collected in diestrus. Our results showed that exposure to a phthalate mixture caused a decrease in progesterone levels in the treated groups in the F2 generation. The 200 mg/kg/day treatment group showed a decreased and increased luminal epithelial cell proliferation in the F1 and F2 generations respectively. In addition, these mice in the F2 generation had reduced Hand2 expression in the sub-epithelial stroma compared to the controls. A higher incidence of multilayered luminal epithelium and large dilated endometrial glands were observed in the phthalate mixture exposed groups in all generations. The mixture also caused a higher incidence of smooth muscle actin expression and collagen deposition in the endometrium compared to controls. Collectively, our results demonstrate that prenatal exposure to an environmentally relevant phthalate mixture can have adverse effects on female reproductive functions.


Oral communication skills of international medical graduates: assessing empathy in discourse.
We examine a dataset consisting of 11 International Medical Graduates (IMGs) performing an Objective Structured Clinical Examination (OSCE). Our aim is to address questions about the linguistic realization of empathy in the clinical discourse of IMGs and the extent to which OSCE examiners are sensitive to relevant features of the discourse. We analyse three aspects of the dataset as manifestations of empathy: sequential organization to provide reassurance; responsiveness to the simulated patient's lexical choices for emotionally charged words; and the organization of turn-taking in the interaction. Our analysis suggests that in each of these areas it is possible to identify discourse strategies which realize empathy. These strategies are used by IMGs who are good communicators and not used by poor communicators. Our evidence suggests that of the features we examine, the most salient for the examiner is a greater than normal occurrence of transition pauses. We argue that it is only in the area of the organization of conversation that the problems displayed by some IMGs are due to differences in cultural background, and it is therefore significant that the feature we identify as salient comes from this area.


Effect of ultrasound-guided aspiration of hydrosalpingeal fluid during oocyte retrieval on the outcomes of in vitro fertilisation-embryo transfer: a randomised controlled trial (NCT01040351).
To determine whether the ultrasound-guided aspiration of hydrosalpingeal fluid at the time of oocyte retrieval can improve the outcomes of in vitro fertilisation-embryo transfer (IVF-ET). One hundred and ten women with ultrasound-visible hydrosalpinges were randomised to two groups based on computer generated randomisation list. Fifty-four women underwent ultrasound-guided aspiration of hydrosalpingeal fluid prior to IVF-ET and 53 women underwent IVF-ET without any prior intervention. Patients who underwent aspiration of hydrosalpinges demonstrated a significantly increased implantation, clinical pregnancy rates. Among the patients in the aspiration group, the implantation rate and pregnancy rates were higher in the subgroup of patients with no reaccumulation of hydrosalpingeal fluid within the first 2 weeks after aspiration compared to patients with reaccumulation of hydrosalpingeal fluid within the first 2 weeks after aspiration, but this difference failed to reach statistical significance. Furthermore, no pregnancies occurred in the four patients with uterine fluid collection detected during IVF-ET cycles. The aspiration of hydrosalpingeal fluid at the time of oocyte retrieval is simple, safe and effective procedure for treatment of patients with ultrasound-visible hydrosalpinges particularly those without rapid reaccumulation of hydrosalpingeal fluid after aspiration or uterine fluid collection during the IVF-ET cycles.


A bacterial enrichment study and overview of the extractable lipids from paleosols in the Dry Valleys, Antarctica: implications for future Mars reconnaissance.
The Dry Valleys of Antarctica are one of the coldest and driest environments on Earth with paleosols in selected areas that date to the emplacement of tills by warm-based ice during the Early Miocene. Cited as an analogue to the martian surface, the ability of the Antarctic environment to support microbial life-forms is a matter of special interest, particularly with the upcoming NASA/ESA 2018 ExoMars mission. Lipid biomarkers were extracted and analyzed by gas chromatography--mass spectrometry to assess sources of organic carbon and evaluate the contribution of microbial species to the organic matter of the paleosols. Paleosol samples from the ice-free Dry Valleys were also subsampled and cultivated in a growth medium from which DNA was extracted with the explicit purpose of the positive identification of bacteria. Several species of bacteria were grown in solution and the genus identified. A similar match of the data to sequenced DNA showed that Alphaproteobacteria, Gammaproteobacteria, Bacteriodetes, and Actinobacteridae species were cultivated. The results confirm the presence of bacteria within some paleosols, but no assumptions have been made with regard to in situ activity at present. These results underscore the need not only to further investigate Dry Valley cryosols but also to develop reconnaissance strategies to determine whether such likely Earth-like environments on the Red Planet also contain life.


Cholesteric Polymer Scaffolds Filled with Azobenzene-Containing Nematic Mixture with Phototunable Optical Properties.
The past two decades witnessed tremendous progress in the field of creation of different types of responsive materials. Cholesteric polymer networks present a very promising class of smart materials due to the combination of the unique optical properties of cholesteric mesophase and high mechanical properties of polymer networks. In the present work we demonstrate the possibility of fast and reversible photocontrol of the optical properties of cholesteric polymer networks. Several cholesteric photopolymerizable mixtures are prepared, and porous cholesteric network films with different helix pitches are produced by polymerization of these mixtures. An effective and simple method of the introduction of photochromic azobenzene-containing nematic mixture capable of isothermal photoinducing the nematic-isotropic phase transition into the porous polymer matrix is developed. It is found that cross-linking density and degree of polymer network filling with a photochromic nematic mixture strongly influence the photo-optical behavior of the obtained composite films. In particular, the densely cross-linked films are characterized by a decrease in selective light reflection bandwidth, whereas weakly cross-linked systems display two processes: the shift of selective light reflection peak and decrease of its width. It is noteworthy that the obtained cholesteric materials are shown to be very promising for the variety applications in optoelectronics and photonics.


Autotransplantation for Chronic Myelogenous Leukemia.
Alternate treatment strategies in the management of chronic myelogenous leukemia (CML) are essential if we are to impact on the ultimately fatal outcome for the majority of patients with this disease who are presently ineligible for allogeneic or syngeneic bone marrow transplantation. One such strategy is that of autologous stem cell rescue after high-dose therapy. Two essential aspects for success of this approach are the eradication of residual disease in the patient by myeloablative therapy and the eradication of disease in the collected stem cell product which is reinfused for restoration of hematopoiesis.


[Conditions and factors determining the etiological structure of dysentery and its changes. Report 1. Epidemiological theory of etiological selectivity of the main (primary) pathways of infection and their differences in various nosological forms of dysentery].
The authors present the elaborated and formed epidemiological theory ("conformity theory") according to which the etiological structure of dysentery is determined by the etiological selectivity of the main (primary) waves of transmission of the infection differing in various nosological forms of dysentery. In Grigoriev-Shiga dysentery the domestic way of the spread of infection plays the main role, in Flexner and Newcastle dysentery--the water way, and in Sonne dysentery--the food way (particularly through the milk). Evolution of the etiological structure of dysentery serves as the reflection of evolution of the principal ways of transmission. The complex of prophylactic and antiepidemic measures in individual noslogical forms of dysentery should be differentiated and be directed in epidemiological sense to the neutralization of the corresponding main (primary) way of transmission of the infection.


Examination of newborn DNA methylation among women with polycystic ovary syndrome/hirsutism.
Research suggests that polycystic ovary syndrome (PCOS) traits (e.g., hyperandrogenism) may create a suboptimal intrauterine environment and induce epigenetic modifications. Therefore, we assessed the associations of PCOS traits with neonatal DNA methylation (DNAm) using two independent cohorts. DNAm was measured in both cohorts using the Infinium MethylationEPIC array. Multivariable robust linear regression was used to determine associations of maternal PCOS exposure or preconception testosterone with methylation β-values at each CpG probe and corrected for multiple testing by false-discovery rate (FDR). In the birth cohort, 12% (102/849) had a PCOS diagnosis (8.1% PCOS without hirsutism; 3.9% PCOS with hirsutism). Infants exposed to maternal PCOS with hirsutism compared to no PCOS had differential DNAm at cg02372539 [β(SE): -0.080 (0.010); FDR p = 0.009], cg08471713 [β(SE):0.077 (0.014); FDR p = 0.016] and cg17897916 [β(SE):0.050 (0.009); FDR p = 0.009] with adjustment for maternal characteristics including pre-pregnancy BMI. PCOS with hirsutism was also associated with 8 differentially methylated regions (DMRs). PCOS without hirsutism was not associated with individual CpGs. In an independent preconception cohort, total testosterone concentrations were associated with 3 DMRs but not with individual CpGs, though the top quartile of testosterone compared to the lowest was marginally associated with increased DNAm at cg21472377 near an uncharacterized locus (FDR p = 0.09). Examination of these probes and DMRs indicate they may be under foetal genetic control. Overall, we found several associations among newborns exposed to PCOS, specifically when hirsutism was reported, and among newborns of women with relatively higher testosterone around conception.


Estrogen-induced increase in uptake of cholesterol-rich very low density lipoproteins in perfused rabbit liver.
A nonrecirculating rabbit liver perfusion system was developed to test whether estrogen increases hepatic uptake of radio-iodinated normal and/or cholesterol-rich very low density lipoproteins (VLDL, d less than 1.006 g/ml) from cholesterol-fed rabbits. When equal concentrations of VLDL protein from normal rabbits and from cholesterol-fed rabbits were perfused together through the same liver, there was a selectively higher (1.4-fold) uptake of cholesterol-rich VLDL. These particles were rich in apolipoprotein E, and the radioactivity bound to this apolipoprotein was selectively removed by the perfused normal rabbit liver relative to its uptake of apolipoproteins B and C. When livers from estrogen-treated rabbits were perfused under identical conditions as normal livers and with the same lipoproteins, the uptake of cholesterol-rich VLDL was increased by 76%, compared with 21% for normal VLDL.


Scientific Approaches on Extraction, Purification and Stability for the Commercialization of Fucoxanthin Recovered from Brown Algae.
The scientific community has corroborated the numerous beneficial activities of fucoxanthin, such as its antioxidant, anti-inflammatory, anticancer or neuroprotective effects, among others. These properties have attracted the attention of nutraceutical, cosmetic and pharmacological industries, giving rise to various possible applications. Fucoxanthin may be chemically produced, but the extraction from natural sources is considered more cost-effective, efficient and eco-friendly. Thus, identifying suitable sources of this compound and giving a general overview of efficient extraction, quantification, purification and stabilization studies is of great importance for the future production and commercialization of fucoxanthin. The scientific research showed that most of the studies are performed using conventional techniques, but non-conventional techniques begin to gain popularity in the recovery of this compound. High Performance Liquid Chromatography (HPLC), Nuclear Magnetic Resonance (NMR) and spectroscopy techniques have been employed in the quantification and identification of fucoxanthin. The further purification of extracts has been mainly accomplished using purification columns. Finally, the stability of fucoxanthin has been assessed as a free molecule, in an emulsion, or encapsulated to identify the variables that might affect its further industrial application.


A calcium antagonist vs a non-calcium antagonist hypertension treatment strategy for patients with coronary artery disease. The International Verapamil-Trandolapril Study (INVEST): a randomized controlled trial.
Despite evidence of efficacy of antihypertensive agents in treating hypertensive patients, safety and efficacy of antihypertensive agents for coronary artery disease (CAD) have been discerned only from subgroup analyses in large trials. To compare mortality and morbidity outcomes in patients with hypertension and CAD treated with a calcium antagonist strategy (CAS) or a non-calcium antagonist strategy (NCAS). Randomized, open label, blinded end point study of 22 576 hypertensive CAD patients aged 50 years or older, which was conducted September 1997 to February 2003 at 862 sites in 14 countries. Patients were randomly assigned to either CAS (verapamil sustained release) or NCAS (atenolol). Strategies specified dose and additional drug regimens. Trandolapril and/or hydrochlorothiazide was administered to achieve blood pressure goals according to guidelines from the sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) of less than 140 mm Hg (systolic) and less than 90 mm Hg (diastolic); and less than 130 mm Hg (systolic) and less than 85 mm Hg (diastolic) if diabetes or renal impairment was present. Trandolapril was also recommended for patients with heart failure, diabetes, or renal impairment. Primary: first occurrence of death (all cause), nonfatal myocardial infarction, or nonfatal stroke; other: cardiovascular death, angina, adverse experiences, hospitalizations, and blood pressure control at 24 months. At 24 months, in the CAS group, 6391 patients (81.5%) were taking verapamil sustained release; 4934 (62.9%) were taking trandolapril; and 3430 (43.7%) were taking hydrochlorothiazide. In the NCAS group, 6083 patients (77.5%) were taking atenolol; 4733 (60.3%) were taking hydrochlorothiazide; and 4113 (52.4%) were taking trandolapril. After a follow-up of 61 835 patient-years (mean, 2.7 years per patient), 2269 patients had a primary outcome event with no statistically significant difference between treatment strategies (9.93% in CAS and 10.17% in NCAS; relative risk [RR], 0.98; 95% confidence interval [CI], 0.90-1.06). Two-year blood pressure control was similar between groups. The JNC VI blood pressure goals were achieved by 65.0% (systolic) and 88.5% (diastolic) of CAS and 64.0% (systolic) and 88.1% (diastolic) of NCAS patients. A total of 71.7% of CAS and 70.7% of NCAS patients achieved a systolic blood pressure of less than 140 mm Hg and diastolic blood pressure of less than 90 mm Hg. The verapamil-trandolapril-based strategy was as clinically effective as the atenolol-hydrochlorothiazide-based strategy in hypertensive CAD patients.


A lysinated thiophene-based semiconductor as a multifunctional neural bioorganic interface.
Lysinated molecular organic semiconductors are introduced as valuable multifunctional platforms for neural cells growth and interfacing. Cast films of quaterthiophene (T4) semiconductor covalently modified with lysine-end moieties (T4Lys) are fabricated and their stability, morphology, optical/electrical, and biocompatibility properties are characterized. T4Lys films exhibit fluorescence and electronic transport as generally observed for unsubstituted oligothiophenes combined to humidity-activated ionic conduction promoted by the charged lysine-end moieties. The Lys insertion in T4 enables adhesion of primary culture of rat dorsal root ganglion (DRG), which is not achievable by plating cells on T4. Notably, on T4Lys, the number on adhering neurons/area is higher and displays a twofold longer neurite length than neurons plated on glass coated with poly-l-lysine. Finally, by whole-cell patch-clamp, it is shown that the biofunctionality of neurons cultured on T4Lys is preserved. The present study introduces an innovative concept for organic material neural interface that combines optical and iono-electronic functionalities with improved biocompatibility and neuron affinity promoted by Lys linkage and the softness of organic semiconductors. Lysinated organic semiconductors could set the scene for the fabrication of simplified bioorganic devices geometry for cells bidirectional communication or optoelectronic control of neural cells biofunctionality.


Isolation and characterization of satellite antibiotics, mimosamycin and chlorocarcins from Streptomyces lavendulae, streptothricin source.
Under novel conditions of culture, Streptomyces lavendulae No. 314 was found to produce new antibiotics, chlorocarcins and mimosamycin in addition to streptothricin. The antibiotics are extracted from culture filtrate with organic solvents and further purified by silica gel chromatography. Chlorocarcins A, B and C are closely related basic antibiotics which are active against gram-positive bacteria, EHRLICH carcinoma and L 1210 leukemia of mice. Mimosamycin is a neutral antibiotic which is mainly active against mycobacteria. Production, isolation and physicochemical properties of the antibiotics are described.


Soil bacterial community response to differences in agricultural management along with seasonal changes in a Mediterranean region.
Land-use change is considered likely to be one of main drivers of biodiversity changes in grassland ecosystems. To gain insight into the impact of land use on the underlying soil bacterial communities, we aimed at determining the effects of agricultural management, along with seasonal variations, on soil bacterial community in a Mediterranean ecosystem where different land-use and plant cover types led to the creation of a soil and vegetation gradient. A set of soils subjected to different anthropogenic impact in a typical Mediterranean landscape, dominated by Quercus suber L., was examined in spring and autumn: a natural cork-oak forest, a pasture, a managed meadow, and two vineyards (ploughed and grass covered). Land uses affected the chemical and structural composition of the most stabilised fractions of soil organic matter and reduced soil C stocks and labile organic matter at both sampling season. A significant effect of land uses on bacterial community structure as well as an interaction effect between land uses and season was revealed by the EP index. Cluster analysis of culture-dependent DGGE patterns showed a different seasonal distribution of soil bacterial populations with subgroups associated to different land uses, in agreement with culture-independent T-RFLP results. Soils subjected to low human inputs (cork-oak forest and pasture) showed a more stable bacterial community than those with high human input (vineyards and managed meadow). Phylogenetic analysis revealed the predominance of Proteobacteria, Actinobacteria, Bacteroidetes, and Firmicutes phyla with differences in class composition across the site, suggesting that the microbial composition changes in response to land uses. Taken altogether, our data suggest that soil bacterial communities were seasonally distinct and exhibited compositional shifts that tracked with changes in land use and soil management. These findings may contribute to future searches for bacterial bio-indicators of soil health and sustainable productivity.


Randomized controlled trial of a telephone-based intervention for child fruit and vegetable intake: long-term follow-up.
Telephone-based interventions can be effective in increasing child fruit and vegetable intake in the short term (<6 mo). The long-term efficacy of such interventions, however, is unknown. The primary aim of this study was to determine whether the short-term (<6 mo) impact of a telephone-based intervention on children's fruit and vegetable intake was sustained over a longer term. A secondary aim of the study was to assess the long-term impact of the intervention on the intake of foods high in fat, salt, or sugar (noncore foods). The study used a cluster randomized controlled trial design. Parents were recruited from Australian preschools between February and August 2010 and allocated to receive an intervention consisting of print materials and 4 telephone-counseling calls delivered over 1 mo or to a print information-only control group. The primary endpoint for the trial was the 18-mo postbaseline follow-up. Linear regression models were used to assess between-group differences in child consumption of fruit and vegetables and noncore foods by subscales of the Children's Dietary Questionnaire. Fruit and vegetable subscale scores were significantly higher, indicating greater child fruit and vegetable intake, among children in the intervention group at the 12-mo (16.77 compared with 14.89; P < 0.01) but not the 18-mo (15.98 compared with 16.82; P = 0.14) follow-up. There were no significant differences between groups at either of the follow-up periods in the noncore food subscale score. Further research to identify effective maintenance strategies is required to maximize the benefits of telephone-based interventions on child diet.


[Lengthening Osteotomy of the Calcaneus in the Treatment of the Flat Foot in Children - Short-term Results.].
The aim of this communication is to provide both clinical and radiological evaluation of short-term results of the lengthening osteotomy of the anterior part of the calcaneus after Evans in the treatment of the flat foot in children and determine indication criteria of this operation. In the 1996-1999 period 35 feet were operated on in 23 children (13 boys, 10 girls), 12 children underwent bilateral surgery in the interval of 6-12 months. The average age at the time of surgery was 10,5 years and the age range 4,3-18,5. Most operations were performed in the age range of 11-15 years (16 operations). Indication to the operation was a symptomatic flexible pes planus (29 times), the flat foot with a neurogenic defect twice, with talus obliquus twice, deformity after the treatment of pes equinovarus congenitus once and the flat foot after a burn injury once. The period of postoperative follow-up ranged between 3 months and 2,5 years. The evaluation focussed on subjective complaints, clinical finding, plantogram and radiological indicators of flat foot. For the purpose of the objectivization of the shortening of the lateral pillar of the foot the so called talocalcanear differential index was monitored under weightbearing from the lateral radiograph. This index was calculated on the basis of the difference of the distance between the distal edge of talus and the calcaneus against the length of the medial pillar of the foot. The postoperative monitoring did not record any infection complications or failure of the surgical technique. Based on the subjective evaluation the condition in 21 patients with the operation of 32 feet (91 %) improved after the surgery and in 2 patients with the operation of 3 feet (9 %) the condition did not improve. In no patient the complaints were worse. Valgus position of the heel of all patients was corrected after the surgery to the normal. There was no functional limitation of the ankle and subtalar joints in any of the patients. Plantograms changed after the surgery by 2 degrees in 16 feet (52 %), by 1 degree in 13 feet (42 %), the plantogram did not change in 2 feet (6 %). Plantogram got to its normal in 12 feet operated on (38 %). Radiological evaluation showed in all feet operated on a change in the course of the joint line of the Chopart joint in both projections and the monitored angles either improved or became normal. Tolacalcanear differential index descreased except for one foot in all feet operated on. This index was directly proportionate to the preoperative and postoperative clinical finding or to the severity of the flat foot or the correction according to the plantogram and on average it was preoperatively four times higher than in normal healthy feet. In most operated feet a shift was found in the calcaneocuboid joind which did not have any relation to the subjective evaluation. Radiological indicators did not correspond unequivocally to the resulting subjective evaluation of the operation but in the case of a satisfactory clinical correction of the deformity of the foot both the subjective evaluation and radiological correction were mostly very good. The lengthening osteotomy of the calcaneus is a safe surgical method which leads to a significant clinical and radiological correction of the valgus deformity of the hindfoot and elevation of the foot arch. Indicated to the surgery are symptomatic flat feet with the symptoms of eversion in the subtalar joint and shortening of the lateral pillar in the radiograph which are not fixed by articular contractures. It is recommended to evaluate the shortening and lengthening of the lateral pillar of the foot according to the proposed talocalcanear differential index which can be used for the indication consideration as well as for the evaluation of the correction achieved. Key words: flat foot in children, surgical treatment, lengthening osteotomy of the calcaneus, radiological evaluation.


Anatomic correlates of deep brain stimulation electrode impedance.
The location of the optimal target for deep brain stimulation (DBS) of the subthalamic nucleus (STN) remains controversial. Electrode impedance affects tissue activation by DBS and has been found to vary by contact number, but no studies have examined association between impedance and anatomic location. To evaluate the relationship between electrode impedance and anatomic contact location, and to assess the clinical significance of impedance. We gathered retrospective impedance data from 101 electrodes in 73 patients with Parkinson's disease. We determined contact location using microelectrode recording (MER) and high-field 7T MRI, and assessed the relationship between impedance and contact location. For contact location as assessed via MER, impedance was significantly higher for contacts in STN, at baseline (111 Ω vs STN border, p=0.03; 169 Ω vs white matter, p<0.001) and over time (90 Ω vs STN border, p<0.001; 54 Ω vs white matter, p<0.001). Over time, impedance was lowest in contacts situated at STN border (p=0.03). Impedance did not vary by contact location as assessed via imaging. Location determination was 75% consistent between MER and imaging. Impedance was inversely related to absolute symptom reduction during stimulation (-2.5 motor portion of the Unified Parkinson's Disease Rating Scale (mUPDRS) points per 1000 Ω, p=0.01). In the vicinity of DBS electrodes chronically implanted in STN, impedance is lower at the rostral STN border and in white matter, than in STN. This finding suggests that current reaches white matter fibres more readily than neuronal cell bodies in STN, which may help explain anatomic variation in stimulation efficacy.


Cooperative effects between two acyclovir resistance loci in herpes simplex virus.
The acyclovir-resistant mutant SC16 R9C2 (H.J. Field, G. Darby, and P. Wildy , J. Gen. Virol. 49:115-124, 1980) has been shown to contain two resistance loci which segregate independently on recombination with wild-type virus. One locus is in thymidine kinase, and the other is in DNA polymerase. Both induced enzymes have altered properties, thymidine kinase showing a low affinity for acyclovir and low activity, and DNA polymerase showing a low affinity for acyclovir triphosphate. Other properties of both enzymes are described which distinguish them from their wild-type counterparts. Recombinants containing either mutant thymidine kinase ( RSC -11) or mutant DNA polymerase ( RSC -26), but not both, have been used to investigate the relative contribution of each lesion to resistance and pathogenicity. Although SC16 R9C2 and both recombinants grow as well as does wild-type virus in tissue culture, they are considerably attenuated in vivo, the greatest attenuation of virulence being seen with SC16 R9C2 and RSC -26. With respect to both acyclovir resistance and in vivo growth, the lesions appear to behave synergistically. Cross resistance studies have shown the recombinant RSC -26, which contains mutant DNA polymerase but which evidently expresses wild-type thymidine kinase, to be cross resistant to both 5-iodo-2'-deoxyuridine and 5-trifluoromethyl-2'-deoxyuridine but not to (E)-5-(2-bromovinyl)-2'-deoxyuridine or 9-beta-D-arabinofuranosyladenine.


[Globus pharyngis and gastroesophageal equivalents].
Globus sensation is a phenomenon of largely unknown etiology. Dyskinesia of the upper esophageal sphincter is quite often evident without pathological ENT findings elsewhere. One hundred ten patients were examined in a interdisciplinary approach. The investigation included videofluoroscopy, esophagogastroduodenoscopy with biopsy, pharyngoesophageal computer manometry, and esophageal pH monitoring. One hundred five cases were evaluated. In 13 cases (12.4%) there was no evidence for any organic or functional disorder. In 92 cases (87.6%) abnormal findings were seen with two constellations being predominant. These are primarily inflammatory lesions in the stomach or the duodenum in 69.5% of all patients (73/105) associated with helicobacter pylori colonization in 58% (42/73) as well as ulcera and/or erosions in 8.2% (6/73). Concurrent disorders of the lower esophageal sphincter play the second role. Sixty-one point nine percent of all patients (65/105) had an hiatal hernia, with gastroesophageal reflux in 36.9% (24/65). In 21.5% (14/65) a reflux esophagitis was evident. A cardiac sphincter insufficiency was found in 6.7% (7/105). Based on these findings a gastroenterologic diagnosis is recommended in all patients with globus sensation as the symptom may be associated with corresponding disorders.


Trend breaks in incidence of non-cardia gastric cancer in the Netherlands.
The incidence of gastric cancer declined over the past decades. Recently, unfavorable trend breaks (i.e. rise in incidence) were seen for non-cardia cancer in younger age groups in the US. It is unclear whether these also occur in other Western countries. We aimed to analyze the gastric cancer incidence trends by age, sex, subsite and stage in the Netherlands. Data on all patients with gastric adenocarcinoma diagnosed from 1973 to 2011 (n=9093) were obtained from the population-based Eindhoven cancer registry. Incidence time trends (European standardized rates per 100,000) were separately analyzed by sex, age group (<60, 60-74, and >75 years), subsite, and pathological stage. Joinpoint analyses were performed to discern trend breaks, age-period-cohort analyses to examine the influence of longitudinal and cross-sectional changes. The incidence of non-cardia cancer declined annually by 3.5% (95% CI -3.8; -3.3). However, in males <60 years, the incidence flattened since 2006, and tended to rise in those >74 years. This pertained to corpus cancers. The incidence of cardia cancer peaked in 1985 and decreased subsequently by 2.4% (95% CI -3.2; -1.5) yearly. The absolute incidence of stage IV disease at first diagnosis initially decreased, but then remained stable over the past 15-20 years. The incidence of non-cardia cancer declined over the past four decades in the Netherlands, but now seems to be stabilizing particularly in males. Unfavorable trend breaks are seen for corpus cancer in younger and older males. The trend breaks in the Netherlands are however not similar to those observed in the US.


The pathology of 111 cases of primary hepatic malignancy collected in the Liverpool region.
The clinical records and preserved specimens of 111 cases of primary malignant disease of the liver have been analysed. All were diagnosed in the Merseyside area, chiefly in Liverpool and Birkenhead, and all but nine were Europeans. Necropsy was done in 89. The tumours consisted of 108 carcinomas, two sarcomas, and one mixed tumour. Liver cell carcinoma was nearly four times more frequent than carcinoma of the intrahepatic bile ducts. Both types were commoner in males, the difference between the sexes being greater in the case of liver cell carcinoma. Predisposing conditions included portal cirrhosis, haemochromatosis, and cystic malformations of bile ducts. The gross and microscopic appearances are described and the pathological effects discussed. Liver cell carcinoma tends to invade and permeate veins within the liver but seems, nevertheless, to remain limited to the liver for longer than carcinoma of the intrahepatic bile ducts. Liver cell carcinoma is more characteristic microscopically. The commonest occupation among the male cases was seafarer.


Single laparoscopic incision transabdominal (SLIT) surgery-adjustable gastric banding: a novel minimally invasive surgical approach.
Natural orifice transluminal endoscopic surgery (NOTES) has become an exciting area of surgical development. However, there are significant limitations to this surgical concept due to the lack of surgical expertise and appropriate flexible instrumentation. An alternative and competing technology to NOTES is single-access surgery. We present a novel surgical technique for placement of an adjustable gastric band utilizing a single laparoscopic incision which was ultimately used for implanting the subcutaneous access port. This new technique is called single laparoscopic incision transabdominal (SLIT) surgery which describes an advanced laparoscopic bariatric operation that can be performed through a tiny slit. The operative time was 55 min. There were no intraoperative complications. The patient did well postoperatively and was discharged on postoperative day 1. There were no postoperative complications at 1-month follow-up. Adjustable gastric banding performed through a single laparoscopic incision is technically feasible. The procedure was performed with mostly existing ports, laparoscopic instrumentations, and visualization platform. Advantages of SLIT surgery compared to conventional laparoscopic surgery will ultimately require further randomized clinical trials.


Making sense of the global economy: 10 resources for health promoters.
Population health is shaped by more than local or national influences-the global matters. Health promotion practitioners and researchers increasingly are challenged to engage with upstream factors related to the global economy, such as global prescriptions for national macroeconomic policies, debt relief and international trade. This paper identifies 10 books (A Brief History of Neoliberalism, Bad Samaritans: The Myth of Free Trade and the Secret History of Capitalism, The World is Not Flat: Inequality and Injustice in Our Global Economy, Globalization and its Discontents, The Debt Threat: How Debt is Destroying the Developing World, Global Woman: Nannies, Maids, and Sex Workers in the New Economy, A Race Against Time, Globalization and Health: An Introduction, Global Public Goods for Health: Health Economics and Public Health Perspectives, Trade and Health: Seeking Common Ground) and several key reports that we found to be particularly useful for understanding the global economy's effects on people's health. We draw attention to issues helpful in understanding the present global financial crisis.


The value of asthma camps for young people in Victoria, Australia.
This paper investigates the impact of the Asthma Foundation of Victoria's educational camp program on children's knowledge of asthma and its management, their feelings about asthma, and their attitudes toward physical and social activities. Parents' observations of changes in their child's behaviour and attitudes are also reported. This research was descriptive and applied. It used questionnaires atfour stages (directly pre- and post-camp, three-four months and ten-15 months post-camp) of an asthma education camp program to assess child asthma knowledge levels. At three months post-camp, parental observations of children's attitudes and behaviours were assessed using a questionnaire. Children's feelings toward asthma were also assessed using a questionnaire pre- and post-camp. The children surveyed displayed a better knowledge of asthma and how to manage their condition immediately after the camp. This knowledge tended to return to pre-camp levels after ten months. The children also reported less anxiety and fear about their illness, a greater sense of wellbeing, and more confidence in participating in a whole range of physical and social activities. Many parents also noted positive changes in their children in terms of activities and asthma management at three months post-camp. Although there were limitations to sustaining knowledge gained in the asthma camping program, the camping experience provided a benefit for children in terms of promoting their mental and social wellbeing. When readers consider modernising asthma education (e.g. shorter camps, education in everyday social settings such as schools), they need to consider retaining the key ingredients of the more traditional camping program that supports good asthma management, wellbeing and social participation.


Multi-method assessment of distress tolerance and smoking-related factors among adult daily smokers.
Although distress tolerance (DT) is associated with smoking lapse and relapse outcomes, few studies have conducted a rigorous assessment of DT across domain and method in the context of acute abstinence. In a human laboratory-based study of 106 adult daily smokers, we examined between multiple indices of DT and smoking lapse, withdrawal processes, and motivation to quit. We expected that low DT would be associated with shorter latency to smoke, greater withdrawal severity, and lower motivation to quit. Following a smoking abstinence period (≥ 6 hr deprived), participants completed an assessment battery including both behavioral (mirror-tracing, serial addition, cold pressor, and breath-holding tasks) and self-report measures of DT (general and smoking-specific), withdrawal processes (craving, negative affect, and positive affect), and motivation to quit. Latency to smoke (range = 0-50 min) was assessed in a laboratory analogue task in which delaying smoking was monetarily rewarded. Behavioral and self-report DT indices displayed only modest intercorrelations, indicating different facets of this construct by domain and method of assessment. Tolerance of physical pain was uniquely associated with smoking choice. Both self-report DT measures were associated with abstinence-induced increases in negative affect, while only smoking-specific DT was positively associated with craving. Results are discussed within the context of guiding targeted behavioral interventions. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Interferon-beta prevents the upregulation of interleukin-8 expression in human melanoma cells.
The constitutive expression of interleukin-8 (IL-8) by human melanoma cells correlates with their metastatic potential. The exposure of human melanoma cells to the inflammatory cytokines IL-1 beta or tumor necrosis factor-alpha (TNF-alpha) upregulated IL-8 expression in a time-dependent and concentration-dependent manner. This enhanced expression of IL-8 was inhibited by cycloheximide or actinomycin-D. Treatment of melanoma cells with interferon (IFN) alpha, beta, or gamma did not affect the constitutive expression of IL-8, but IFN-alpha and IFN-beta blocked the upregulation of IL-8 expression in cells treated with IL-1 beta or TNF-alpha subsequent to or simultaneously with the IFN. These data suggest that the expression of IL-8 in human melanoma cells can be upregulated by inflammatory cytokines and that IFN-alpha and IFN-beta can counterregulate this stimulation.


Electrostimulation for Refractory Epilepsy: A Review.
Epilepsy is a neurological disorder that has been diagnosed in approximately 1% of the world's population. In North America alone, more than 3 million individuals suffer from epilepsy. Antiepileptic drugs are not fully effective in some patients, and most drugs have adverse side effects. Recently, several stimulation techniques (responsive neural, vagal nerve, transcranial magnetic, and deep brain) have been used as adjunct therapies to treat medically refractive seizures. Since its Food and Drug Administration approval in 2013, responsive neural stimulation (RNS), a closed-loop electrical stimulation system, has emerged as a potential therapeutic alternative to treat patients with epilepsy (PWE). RNS consists of a cranially implantable neurostimulator that sends electrical pulses using depth electrodes to epileptic foci/focus after the device senses irregular electrical activity, thus avoiding the onset of a seizure. In a long-term study that lasted 7 yr and involved more than 245 patients using RNS, results showed that16% of patients were seizure free, 60% had 50% or greater seizure reduction, and 84% had some improvement. Quality of life improved in 44% of the patients by the end of the second year. There is a need for more, larger, well-designed, randomized, controlled trials to validate and optimize efficacy and safety of invasive intracranial neurostimulation treatments in PWE. This article highlights the effects of treating patients with medically refractive seizures using RNS.


Does load carrying influence sagittal plane locomotive stability?
We used methods from dynamical system analysis to investigate the effect of carrying external loads on the stability of the locomotive system and sagittal plane kinematics. We hypothesized that carrying an additional load at the waist would 1) decrease the dynamic stability of the locomotive system and 2) cause changes in the location of the Poincaré map's equilibrium point for the hip, the knee, and the ankle joint kinematics. Lower extremity kinematics were recorded for 23 subjects as they walked on a treadmill at their preferred speed while carrying external loads of 10%, 20%, and 30% of their body weight around their waist. Gait stability was evaluated by computing the eigenvalues of the locomotive system at the instance of heel contact and midswing. Changes in the hip, the knee, and the ankle's equilibrium point of the Poincaré sections were used to determine whether there were changes in the joint kinematics while carrying external loads. No significant differences in sagittal plane stability were found between the respective load carrying conditions (P > 0.05). Significant changes (P < 0.05) in the equilibrium points of the hip and the knee were found at heel contact and midswing. The data suggest that humans are capable of maintaining sagittal plane stability while carrying loads up to 30% of their body weight.


Changes in peri-calcarine cortical thickness in blindsight.
Blindsight is the ability of patients with primary visual cortex (V1) damage to process information in their clinically blind visual field in the absence of conscious awareness. In addition to those with localized V1 lesions, some patients exhibiting this phenomenon have had a cerebral hemisphere removed or disconnected from the rest of the brain for the treatment of drug-resistant epilepsy (hemispherectomy). Research into the underlying neural substrates of blindsight has long implicated the intact visual cortex in maintaining residual vision and supporting visuo-guided responses to stimuli presented ipsilaterally within the blind visual field while operating outside the geniculo-striate pathway. A recent study demonstrated functional reorganization in the dorsal visual areas of the intact hemisphere, thereby supporting its compensatory role in non-conscious vision. In this study, we used cortical thickness analysis to examine anatomical differences in the visual cortex of the intact hemisphere of three subjects with varying degrees of cortical damage and well documented blindsight: two with a right hemispherectomy (complete and partial), and one with a left V1 lesion. T1-weighted MRI data were obtained for the subjects while control data were chosen from publicly available NKI-dataset to match closely the acquisition parameters of our blindsight cases. Our results show significant increases in cortical thickness in the visual cortex of all blindsight subjects compared to healthy controls, irrespective of age-onset, etiology, and extent of the damage. Our findings add to accumulating evidence from behavioral, functional imaging, and tractography studies of cerebral compensation and reorganization.


Recognition of galactose-deficient O-glycans in the hinge region of IgA1 by N-acetylgalactosamine-specific snail lectins: a comparative binding study.
Aberrancies in IgA1 glycosylation have been linked to the pathogenesis of IgA nephropathy (IgAN), a kidney disease characterized by deposits of IgA1-containing immune complexes in the glomerular mesangium. IgA1 from IgAN patients is characterized by the presence of galactose (Gal)-deficient O-glycans in the hinge region that can act as epitopes for anti-glycan IgG or IgA1 antibodies. The resulting circulating immune complexes are trapped in the glomerular mesangium of the kidney where they trigger localized inflammatory responses by activating mesangial cells. Certain lectins recognize the terminal N-acetylgalactosamine (GalNAc)-containing O-glycans on Gal-deficient IgA1 and can be potentially used as diagnostic tools. To improve our understanding of GalNAc recognition by these lectins, we have conducted binding studies to assess the interaction of Helix aspersa agglutinin (HAA) and Helix pomatia agglutinin (HPA) with Gal-deficient IgA1. Surface plasmon resonance spectroscopy revealed that both HAA and HPA bind to a Gal-deficient synthetic hinge region glycopeptide (HR-GalNAc) as well as various aberrantly glycosylated IgA1 myeloma proteins. Despite having six binding sites, both HAA and HPA bind IgA1 in a functionally bivalent manner, with the apparent affinity for IgA1 related to the number of exposed GalNAc groups in the IgA1 hinge. Finally, HAA and HPA were shown to discriminate very effectively between the IgA1 secreted by cell lines derived from peripheral blood cells of patients with IgAN and that from cells of healthy controls. These studies provide insight into lectin recognition of the Gal-deficient IgA1 hinge region and lay the groundwork for the development of reliable diagnostic tools for IgAN.


Variability of the area under the receiver operating characteristic curves in the diagnostic evaluation of liver fibrosis markers: impact of biopsy length and fragmentation.
The area under the receiver operating characteristic (ROC) curve is widely used as an estimate of the diagnostic value for fibrosis markers. Biopsy length and fragmentation are known as risk factors of false positive or false negative of biopsy but their quantitative impact on area under the receiver operating characteristic curve variability has not been assessed. To assess these relationships to better compare the fibrosis markers. The area under the ROC curves of FibroTest for the diagnosis of fibrosis was estimated in patients with chronic hepatitis C using an integrated database including 1312 patients with FibroTest and biopsy. To take into account the biopsy length, we used two adjustment factors: one in which an observed area under the ROC curve could be adjusted according to the relative area under the receiver operating characteristic curve of a biopsy of a given length vs. the entire liver and one taking into account the prevalence of each fibrosis stage defining advanced and non-advanced fibrosis. The mean biopsy length was smaller for cirrhosis (F4, 16 mm) vs. F3, (18 mm, P=0.01) and F0 (19 mm, P=0.01). The mean number of fragments was higher for cirrhosis (F4=4.1 fragments) vs. all the other stages (F0=1.9, F1=1.9, F2=1.9, F3=2.3; P<0.001 vs. F4). The FibroTest area under the ROC curves for the diagnosis of advanced fibrosis, adjusted for stages' prevalence, ranged from 0.80 to 0.98 depending on biopsy length and fragmentation, respectively. The comparison of the area under the ROC curves of fibrosis markers should take into account the biopsy length and fragmentation.


GABA-glutamate supramammillary neurons control theta and gamma oscillations in the dentate gyrus during paradoxical (REM) sleep.
Several studies suggest that neurons from the lateral region of the SuM (SuML) innervating the dorsal dentate gyrus (DG) display a dual GABAergic and glutamatergic transmission and are specifically activated during paradoxical (REM) sleep (PS). The objective of the present study is to characterize the anatomical, neurochemical and electrophysiological properties of the SuML-DG projection neurons and to determine how they control DG oscillations and neuronal activation during PS and other vigilance states. For this purpose, we combine structural connectivity techniques using neurotropic viral vectors (rabies virus, AAV), neurochemical anatomy (immunohistochemistry, in situ hybridization) and imaging (light, electron and confocal microscopy) with in vitro (patch clamp) and in vivo (LFP, EEG) optogenetic and electrophysiological recordings performed in transgenic VGLUT2-cre male mice. At the cellular level, we show that the SuML-DG neurons co-release GABA and glutamate on dentate granule cells and increase the activity of a subset of DG granule cells. At the network level, we show that activation of the SuML-DG pathway increases theta power and frequency during PS as well as gamma power during PS and waking in the DG. At the behavioral level, we show that the activation of this pathway does not change animal behavior during PS, induces awakening during slow wave sleep and increases motor activity during waking. These results suggest that the SuML-DG pathway is capable of supporting the increase of theta and gamma power in the DG observed during PS and plays an important modulatory role of DG network activity during this state.


Human telomerase inhibition and cytotoxicity of regioisomeric disubstituted amidoanthraquinones and aminoanthraquinones.
Telomerase is an attractive target for the rational design of new anticancer drugs due to its central role in the control of cellular proliferation. A number of 1,4-disubstituted amidoanthraquinones and 1,5-disubstituted aminoanthraquinones that are related to mitoxantrone and ametantrone have previously been prepared. The present study details the effects on human telomerase of these new classes of 1,4- and 1,5-difunctionalized tricyclic anthraquinone compounds. We have used cytotoxicity assay, reporter SEAP assay to monitor the hTERT expression, and TRAP-G4 assay to measure the relative activity of these compounds, and have examined how the attached substituents affect their ability to influence telomerase. Cytotoxicity levels in human tumor cell lines were at comparable levels for several compounds. Structural and activity relationships indicated that the position of disubstituent side chains is important for its inhibitory effect. Moreover, a primary amine or tertiary amine on the substitution group appears to be required for the telomerase inhibitory effect. There is no significant correlation between telomerase activity and cytotoxicity. These symmetrical disubstituted anthraquinones may represent useful leads for the development of human telomerase inhibitors as potential anticancer agents, and the exact mode of intercalative binding is dictated by the positional placement of substituent side chains for effective telomerase inhibition.


Surgical outcomes with anatomic reduction of high-grade spondylolisthesis revisited: an analysis of 101 patients.
The ideal strategy for high-grade L5-S1 isthmic spondylolisthesis (HGS) remains controversial. Critical questions include the impact of reduction on clinical outcomes, rate of pseudarthrosis, and postoperative foot drop. The scope of this study was to delineate predictors of radiographic and clinical outcome factors after surgery for HGS and to identify risk factors of foot drop. This was a single-center analysis of patients who were admitted for HGS, defined as grade III or greater L5 translation according to the Meyerding (MD) classification. Complete postoperative reduction was defined as MD grade I or less and L5 slip < 20%. Forty-six patients completed health-related quality-of-life questionnaires (Oswestry Disability Index, Physical Component Summary of SF-36, and visual analog scale) and ≥ 2 years' follow-up (average 105 months). A 540° approach was used in 61 patients, a 360° approach was used in 40, and L5 corpectomy was used in 17. Radiographic analysis included measures of global spinopelvic balance (e.g., pelvic incidence [PI], lumbar lordosis) and measurement of lumbosacral kyphosis angle (LSA), L4 slope (L4S), L5 slip (%), and postoperative increase of L5-S1 height. The authors included 101 patients with > 1 year of clinical and radiographic follow-up. The mean age was 26 years. Average preoperative MD grade was 3.8 and average L5 slip was 81%; complete reduction was achieved in 55 and 42 patients, respectively, according to these criteria. At follow-up, LSA correlated with all clinical outcomes (r ≥ 0.4, p < 0.05). Forty patients experienced a major complication. Risk was increased in patients with greater preoperative deformity (i.e., LSA) (p = 0.04) and those who underwent L5 corpectomy (p < 0.01) and correlated with greater deformity correction. Thirty-one patients needed revision surgery, including 17 for pseudarthrosis. Patients who needed revision surgery had greater preoperative deformity (i.e., MD grade and L5 slip) (p < 0.01), greater PI (p = 0.02), and greater postoperative L4S (p < 0.01) and were older (p = 0.02), and these patients more often underwent L5 corpectomy (p < 0.01). Complete reduction was associated with lower likelihood of pseudarthrosis (p = 0.08) and resulted in better lumbar lordosis correction (p = 0.03). Thirty patients had foot drop, and these patients had greater MD grade and L5 slip (p < 0.01) and greater preoperative LSA (p < 0.01). These patients with foot drop more often required L5 corpectomy (p < 0.01). Change in preoperative L4S (p = 0.02), LSA (p < 0.01), and L5-S1 height (p = 0.02) were significantly different between patients with foot drop and those without foot drop. A significant risk model was established that included L4S change and PI as independent variables and foot drop as a dependent variable (82% negative predictive value and 71% positive predictive value, p < 0.01). Multivariable analysis identified factors associated with foot drop, major complications, and need for revision surgery, including degree of deformity (MD grade and L5 slip) and correction of LSA. Functional outcome correlated with LSA correction.


[Extramural Gastral GIST Manifested by Spontaneous Perforation with Acute Intraabdominal Bleeding and Haemoperitoneum].
We report on the case of a 38-year-old male patient with a huge extramural gastrointestinal stromal tumour (GIST) of the stomach, located in the left upper and middle abdominal cavity that was diagnosed on the basis of a spontaneous -rupture and consecutive haemoperitoneum. The lesion was resected completely in an emergency operation. The tumour was classified as a high-risk lesion for aggressive biological behaviour and with regard to tumour rupture with perforation of the serosa, an adjuvant systemic therapy was indicated.


Epidemiology of primary hyperoxaluria type 1. Société de Néphrologie and the Société de Néphrologie Pédiatrique.
Primary hyperoxaluria type 1 (PH1) always leads to oxalate accumulation throughout the body (oxalosis). Currently available epidemiological data only concern patients with end-stage kidney disease requiring renal replacement therapy (RRT). French nephrologists have been questioned about PH1 patients who were under their care between 1988 and 1992. Exhaustive answers were obtained and 90 cases of PH1 were collected. The average prevalence rate of PH1 was 1.05/10(6) and its average incidence rate was 0.12/10(6)/year. The median age at onset was 5 years (0-63) and initial symptoms involved the urinary tract in 82% of the cases. Half the patients were younger than 10 years at the time of diagnosis on the basis of urine oxalate (89%) +/- urine glycolate (43%) +/- plasma oxalate (71%) +/- hepatic alanine:glyoxylate amino-transferase activity (48%). At the time of the survey, 36% of patients were on a conservative treatment, 37% were transplanted and 27% were on maintenance haemodialysis; the crude mortality rate was 19% (median age 36 years). Patients on dialysis started RRT at a median age of 25 years. Transplanted patients received their first transplant at a median age of 29.5 years; among those patients with more than 1 year follow-up, 15 received an isolated kidney transplant (one success), one had a isolated liver transplant (one success) and 10 combined liver-kidney transplant (eight successes). These data confirm the rarity of PH1 together with its poor prognosis; as shown in the European experience, early combined liver-kidney transplantation seems to be the best therapeutic proposal.


Axonal variants of Guillain-Barré syndrome: an update.
Axonal variants of Guillain-Barré syndrome (GBS) mainly include acute motor axonal neuropathy, acute motor and sensory axonal neuropathy, and pharyngeal-cervical-brachial weakness. Molecular mimicry of human gangliosides by a pathogen's lipooligosaccharides is a well-established mechanism for Campylobacter jejuni-associated GBS. New triggers of the axonal variants of GBS (axonal GBS), such as Zika virus, hepatitis viruses, intravenous administration of ganglioside, vaccination, and surgery, are being identified. However, the pathogenetic mechanisms of axonal GBS related to antecedent bacterial or viral infections other than Campylobacter jejuni remain unknown. Currently, autoantibody classification and serial electrophysiology are cardinal approaches to differentiate axonal GBS from the prototype of GBS, acute inflammatory demyelinating polyneuropathy. Newly developed technologies, including metabolite analysis, peripheral nerve ultrasound, and feature selection via artificial intelligence are facilitating more accurate diagnosis of axonal GBS. Nevertheless, some key issues, such as genetic susceptibilities, remain unanswered and moreover, current therapies bear limitations. Although several therapies have shown considerable benefits to experimental animals, randomized controlled trials are still needed to validate their efficacy.


Live fast, die young: Behavioural and physiological impacts of light pollution on a marine fish during larval recruitment.
Artificial light at night (ALAN) is a recently acknowledged form of anthropogenic pollution of growing concern to the biology and ecology of exposed organisms. Though ALAN can have detrimental effects on physiology and behaviour, we have little understanding of how marine organisms in coastal areas may be impacted. Here, we investigated the effects of ALAN exposure on coral reef fish larvae during the critical recruitment stage, encompassing settlement, metamorphosis, and post-settlement survival. We found that larvae avoided illuminated settlement habitats, however those living under ALAN conditions for 10 days post-settlement experienced changes in swimming behaviour and higher susceptibility to nocturnal predation. Although ALAN-exposed fish grew faster and heavier than control fish, they also experienced significantly higher mortality rates by the end of the experimental period. This is the first study on the ecological impacts of ALAN during the early life history of marine fish.


[A defense mechanism of human cells in the radioadaptive response and antimutagenic activity of interferon has common paths].
The radioadaptive response was assessed by the chromosome aberration test in lymphocytes of humans with hereditary diseases of connective tissue, which were earlier characterized as repair-deficient: Marfan syndrome (SM), Elers-Danlos syndrome (E-D), and homocystinurea (HCU). The radioadaptive response was observed in cells of patients with Marfan syndrome and Elers-Danlos syndrome but not in cells of patients with homocystinurea. Parameters of cell protection against gamma-irradiation at radioadaptive response were similar to those obtained in cells pretreated with interferon. These data indicate, first, the possibility that repair pathways and the radioadaptive response are independent and second, that there are common pathways of protection upon radioadaptive response and the antimutagenic action of interferon.


The Potential of South African Herbal Tisanes, Rooibos and Honeybush in the Management of Type 2 Diabetes Mellitus.
Diabetes mellitus is a metabolic disease that can lead to high morbidity, mortality and long-term complications. Available treatment strategies, which are mainly based on treating hyperglycemia, with insulin and other pharmacological agents are not completely efficient and can even lead to development of unwanted side effects. Scientific evidence suggests that bioactive compounds from teas and other plant-based foods, which are known source of natural antioxidants, could be an attractive strategy to preferentially treat and manage type 2 diabetes mellitus (T2DM) and thus, have significant therapeutic implications. In this review, we attempt an in-depth analysis and discussion of the current progress in our understanding of the antidiabetic potential of two commercialized South Africa herbal tisanes-Rooibos and Honeybush and their polyphenols.


Immunohistologic labeling as an indicator of liver allograft rejection.
Monoclonal antibodies were used to identify T-helper cells (TH) and T-suppressor/cytotoxic cells (TS/C) in biopsy specimens obtained 7, 21, 90, 180, and 365 days postoperatively, and during episodes of graft dysfunction, from 34 consecutive liver transplant patients treated with cyclosporine and steroids. Rejection was diagnosed by the presence of appropriate laboratory and light microscopic findings and at least 8 weeks of follow-up to exclude other causes of graft dysfunction. Four immunohistologic patterns were seen--no labeled cells (No), only lobular TS/C, only portal TH, and a portal mixture of TH and TS/C (mix). Of 36 specimens with the No or only lobular TS/C pattern, 29 were not associated with rejection. Of the 39 specimens with the portal TH or portal Mix pattern, 33 were associated with a rejection episode. In addition, in nine specimens from patients with no biochemical or routine histologic evidence of rejection, the presence of portal TH or a portal mix indicated immunologic rejection 5 days to 5 weeks before biochemical and routine histologic evidence of it was manifested. Immunohistologic labeling appears to be an early indicator of liver allograft rejection.


Human Adipose-Derived Mesenchymal Stem Cells Modify Lung Immunity and Improve Antibacterial Defense in Pneumosepsis Caused by Klebsiella pneumoniae.
Adult mesenchymal stem cells exert immunomodulatory effects that might improve the host response during sepsis. Knowledge on the effect of adipose-derived mesenchymal stem cells (ASCs) in sepsis is limited. Klebsiella (K.) pneumoniae is a common cause of gram-negative pneumonia and sepsis. This study sought to determine the effect of human ASCs on the host response during pneumosepsis in mice. Mice were infected with K. pneumoniae via the airways to induce a gradually evolving infection in the lung culminating pneumosepsis. One or 6 hours after infection, mice were infused intravenously with ASCs or vehicle, and euthanized after 16 hours or 48 hours, respectively. The effects of freshly cultured and cryopreserved ASCs were compared, the latter formulation being more clinically relevant. Intravenously administered ASCs were visualized in lung tissue by immunostaining at 1 and 3 hours, but not at 15 hours after infusion. Although early after infection, ASCs did not or only modestly influence bacterial loads, they reduced bacterial burdens in lungs and distant organs at 48 hours. ASCs reduced the lung levels of pro-inflammatory cytokines and attenuated lung pathology, but did not influence distant organ injury. ASCs strongly modified the lung transcriptome in uninfected mice and especially mice with pneumosepsis. Cryopreserved and cultured ASCs induced largely similar effects on the lung transcriptome. These data indicate that human ASCs induce profound immune modulatory effects in the lungs, resulting in reduced bacterial burdens and lung inflammation during pneumosepsis caused by a common human pathogen, suggesting that ASCs may be an adjunctive therapeutic in this condition. Stem Cells Translational Medicine 2019;8:785&796.


Prospects for in vivo estimation of photon linear attenuation coefficients using postprocessing dual-energy CT imaging on a commercial scanner: comparison of analytic and polyenergetic statistical reconstruction algorithms.
Accurate patient-specific photon cross-section information is needed to support more accurate model-based dose calculation for low energy photon-emitting modalities in medicine such as brachytherapy and kilovoltage x-ray imaging procedures. A postprocessing dual-energy CT (pDECT) technique for noninvasive in vivo estimation of photon linear attenuation coefficients has been experimentally implemented on a commercial CT scanner and its accuracy assessed in idealized phantom geometries. Eight test materials of known composition and density were used to compare pDECT-estimated linear attenuation coefficients to NIST reference values over an energy range from 10 keV to 1 MeV. As statistical image reconstruction (SIR) has been shown to reconstruct images with less random and systematic error than conventional filtered backprojection (FBP), the pDECT technique was implemented with both an in-house polyenergetic SIR algorithm, alternating minimization (AM), as well as a conventional FBP reconstruction algorithm. Improvement from increased spectral separation was also investigated by filtering the high-energy beam with an additional 0.5 mm of tin. The law of propagated uncertainty was employed to assess the sensitivity of the pDECT process to errors in reconstructed images. Mean pDECT-estimated linear attenuation coefficients for the eight test materials agreed within 1% of NIST reference values for energies from 1 MeV down to 30 keV, with mean errors rising to between 3% and 6% at 10 keV, indicating that the method is unbiased when measurement and calibration phantom geometries are matched. Reconstruction with FBP and AM algorithms conferred similar mean pDECT accuracy. However, single-voxel pDECT estimates reconstructed on a 1 × 1 × 3 mm(3) grid are shown to be highly sensitive to reconstructed image uncertainty; in some cases pDECT attenuation coefficient estimates exhibited standard deviations on the order of 20% around the mean. Reconstruction with the statistical AM algorithm led to standard deviations roughly 40% to 60% less than FBP reconstruction. Additional tin filtration of the high energy beam exhibits similar pDECT estimation accuracy as the unfiltered beam, even when scanning with only 25% of the dose. Using the law of propagated uncertainty, low Z materials are found to be more sensitive to image reconstruction errors than high Z materials. Furthermore, it is estimated that reconstructed CT image uncertainty must be limited to less than 0.25% to achieve a target linear-attenuation coefficient estimation uncertainty of 3% at 28 keV. That pDECT supports mean linear attenuation coefficient measurement accuracies of 1% of reference values for energies greater than 30 keV is encouraging. However, the sensitivity of the pDECT measurements to noise and systematic errors in reconstructed CT images warrants further investigation in more complex phantom geometries. The investigated statistical reconstruction algorithm, AM, reduced random measurement uncertainty relative to FBP owing to improved noise performance. These early results also support efforts to increase DE spectral separation, which can further reduce the pDECT sensitivity to measurement uncertainty.


Selection of Autochthonous LAB Strains of Unripe Green Tomato towards the Production of Highly Nutritious Lacto-Fermented Ingredients.
Lactic fermentation of unripe green tomatoes as a tool to produce food ingredients is a viable alternative for adding value to industrial tomatoes unsuitable for processing and left in large quantities in the fields. Fermentation using starter cultures isolated from the fruit (plant-matrix adapted) can have advantages over allochthonous strains in obtaining fermented products with sensory acceptability and potentially probiotic characteristics. This paper details the characterisation of the unripe green tomato lactic microbiota to screen LAB strains for use as starter cultures in fermentation processes, along with LAB strains available from INIAV's collection. Morphological, biochemical (API system), and genomic (16S rDNA gene sequencing) identification showed that the dominant LAB genera in unripe green tomato are Lactiplantibacillus, Leuconostoc, and Weissella. Among nine tested strains, autochthonous Lactiplantibacillus plantarum and allochthonous Weissella paramesenteroides showed tolerance to added solanine (200 ppm) and the best in vitro probiotic potential. The results indicate that the two LAB strains are promising candidates for manufacturing probiotic fermented foods from unripe green tomatoes.


A prediction model of outcome of SARS-CoV-2 pneumonia based on laboratory findings.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in thousands of deaths in the world. Information about prediction model of prognosis of SARS-CoV-2 infection is scarce. We used machine learning for processing laboratory findings of 110 patients with SARS-CoV-2 pneumonia (including 51 non-survivors and 59 discharged patients). The maximum relevance minimum redundancy (mRMR) algorithm and the least absolute shrinkage and selection operator logistic regression model were used for selection of laboratory features. Seven laboratory features selected in the model were: prothrombin activity, urea, white blood cell, interleukin-2 receptor, indirect bilirubin, myoglobin, and fibrinogen degradation products. The signature constructed using the seven features had 98% [93%, 100%] sensitivity and 91% [84%, 99%] specificity in predicting outcome of SARS-CoV-2 pneumonia. Thus it is feasible to establish an accurate prediction model of outcome of SARS-CoV-2 pneumonia based on laboratory findings.


Repetitive Transcranial Magnetic Stimulation, a Novel Therapeutic Strategy for Refractory Paradoxical Vocal Fold Motion Disorder.
Paradoxical vocal fold motion disorder (PVFMD) is a condition involving the inappropriate narrowing of the larynx with symptoms of laryngeal tightness and dyspnea. A 23-year-old woman was diagnosed with PVFMD by imaging, revealing dynamically constricted, supraglottic tissue, an abnormal adduction of the vocal cords with a characteristic "posterior chink" observed. After diagnosis, laryngeal control retraining protocols and biofeedback therapy were initiated. To treat persistent symptoms, interventions such as vocal fold botulinum toxin (BoNT) injections were performed with slight improvements. Ultimately, psychiatry performed 10 repetitive transcranial magnetic stimulations (rTMS) with a right-sided, low-frequency approach to treat the patient's underlying major depressive disorder and comorbid anxious distress. Afterward, the patient's symptoms were successfully reduced with an improvement in Dyspnea Severity Index. Although most patients with PVFMD were relieved with laryngeal control therapy, some are refractory and lack the literature on the best treatment. In this case, we followed the multidisciplinary approach and individualized our novel therapeutic strategies including especially rTMS, which successfully reduced symptoms. This is the first reported case of refractory PVFMD to be treated with novel interventions, and rTMS might play a role in PVFMD mitigation.


Computational signal-to-noise ratio analysis for optical quadrature microscopy.
Optical quadrature microscopy (OQM) was invented in 1997 to reconstruct a full-field image of quantitative phase, and has been used to count the number of cells in live mouse embryos. Here we present a thorough SNR analysis that incorporates noise terms for fluctuations in the laser, aberrations within the individual paths of the Mach-Zehnder interferometer, and imperfections within the beamsplitters and CCD cameras to create a model for the resultant phase measurements. The current RMS error of the OQM phase images has been calculated to be 0.08 radians from substituting images from the instrumentation into the model.


Associations between the perceived environment and physical activity among adults aged 55-65 years: does urban-rural area of residence matter?
This study aimed to determine whether associations between the perceived environment and physical activity are moderated by urban-rural status among midolder aged adults. Environmental (safety, aesthetics, physical activity environment) and physical activity (total, leisure, transport) data from 3,888 adults (55 to 65 years) from urban and rural areas of Victoria, Australia, were analyzed. Multinomial logistic regression examined interactions between urban-rural status and environments in associations with physical activity. Significant (P < .05) interactions were evident and indicated positive associations only among older rural adults for both safety and aesthetics with total and transport physical activity (e.g., rural adults reporting higher safety were 91% to 118% more likely to have higher activity than rural adults reporting low safety). In contrast, the physical activity environment was positively associated with leisure activity among only urban adults. Findings suggest that some tailoring of physical activity promotion strategies targeting the environment may be required for urban and rural midolder aged adults.