Spectroscopic evidence for acid-base interaction driven interfacial segregation.
Quantification of interfacial composition and interfacial energy is essential for understanding prevalent phenomena such as purification and adhesion. However, for high-energy planar solid surfaces, traditional approaches for determining both parameters are inadequate. We take advantage of interface-sensitive spectroscopy to calculate the interfacial composition for acetone-chloroform, tetrahydrofuran-benzene, and N,N-dimethylformamide (DMF)-benzene mixtures. We calculate the differences in interfacial energy for the two components of each mixture from the adsorption isotherms and compare with that obtained from acid-base and dispersive interactions. The interfacial energy calculated using interfacial segregation agrees with the interfacial energy calculated by acid-base and dispersive interactions. The comparison illustrates how molecular interactions control macroscopic interfacial segregation. In all three mixtures, acid-base interactions dominate interfacial segregation. Comparing the two approaches for DMF-benzene mixtures leads to evidence of DMF dimerization in benzene. Using the present approach, the interfacial composition and interfacial energy can now be understood for interfacial behaviors including wetting and self-assembly.


Exploring the Correlation Between Nontraditional Variables and Student Success: A Longitudinal Study.
The purpose of this project was to determine whether a correlation exists between the traditional admission criteria of grade point averages with the potential admission criteria of emotional intelligence (EI) scores or critical thinking (CT) scores to predict upper division student outcomes. A quantitative, longitudinal design was selected to examine the identified variables to predict undergraduate student success. The recruiting sample included a convenience sample drawn from 112 junior-level undergraduate nursing students beginning their first of a five-semester nursing program. EI and HESI® CT scores did not significantly correlate with main analysis variables. Although EI and CT scores were not significant in this study, it remains vital to incorporate EI and CT activities throughout the curriculum to develop students' ability to think like a nurse and, therefore, be successful in nursing practice. [J Nurs Educ. 2017;56(6):351-355.].


A cluster randomized controlled trial to evaluate the efficacy of esophageal and gastric cancer screening in mortality reduction in a non-high-incidence area: methodology and initial results.
A cluster randomized controlled trial of endoscopy-based screening for esophageal cancer (EC) and gastric cancer (GC) was conducted to evaluate the efficacy and feasibility of this strategy in a non-high-incidence rural area of China. The trial design and baseline findings are presented here. A total of 33 eligible villages in Luoshan County in Henan Province were assigned randomly to the intervention or control group in a 1:1 ratio by a computer-generated randomization list. Local residents aged 40 to 69 years were enrolled from the villages. Participants in the intervention group were risk-stratified with a questionnaire, and high-risk individuals were subsequently screened by endoscopy. The primary outcomes were EC and GC mortality. The secondary outcomes comprised the detection rate, stage distribution, and the treatment rate. In this study, baseline characteristics were assessed by a questionnaire. Multivariate logistic regression analysis was performed to explore factors associated with endoscopy compliance. Trial recruitment was completed in 2017, and ultimately, there were 12,475 and 11,442 participants allocated to the intervention (17 clusters) and the control group (16 clusters), respectively. We included 23,653 participants in the analysis, with 12,402 in the intervention group and 11,251 in the control group. A total of 6,286 (50.7%) participants in the intervention group were estimated as high-risk individuals, and 2,719 (43.3%) underwent endoscopy. Multivariate logistic regression analysis demonstrated that some factors including age, gender, education, personality and mental health, and upper gastrointestinal diseases or symptoms might affect endoscopy compliance. The detection rates for positive cases of EC and GC were 0.22% and 0.55%, respectively. The rates for esophageal and gastric precancerous lesions were 0.70% and 2.35%, respectively. The early detection rates for EC and GC were 50.0% and 33.3%, respectively. Additionally, the overall treatment rate for positive cases was 90.0%. The diagnostic yield of endoscopy-based screening for EC and GC was relatively low in a non-high-incidence rural area. The study may offer clues for the improvement of endoscopy compliance and the optimization of screening strategies for upper gastrointestinal cancer in non-high-incidence areas. Chinese Clinical Trial Registry ChiCTR-EOR-16008577.


Current evidence for the risk of PR prolongation, QRS widening, QT prolongation, from lopinavir, ritonavir, atazanavir, and saquinavir: A systematic review.
Lopinavir, ritonavir, atazanavir, and saquinavir had been reportedly used or suggested for coronavirus disease 2019 (COVID-19) treatment. They may cause electrocardiography changes. We aim to evaluate risk of PR prolongation, QRS widening, and QT prolongation from lopinavir, ritonavir, atazanavir, and saquinavir. In accordance with preferred reporting items for systematic reviews and meta-analyses guidelines, our search was conducted in PubMed Central, PubMed, EBSCOhost, and ProQuest from inception to June 25, 2020. Titles and abstracts were reviewed for relevance. Cochrane Risk of Bias Tool 2.0 and Downs and Black criteria was used to evaluate quality of studies. We retrieved 9 articles. Most randomized controlled trials have low risk of biases while all quasi-experimental studies have a positive rating. Four studies reporting PR prolongation however only 2 studies with PR interval >200 ms. One of which, reported its association after treatment with ritonavir-boosted saquinavir treatment while another, during treatment with ritonavir-boosted atazanavir. No study reported QRS widening >120 ms with treatment. Four studies reporting QT prolongation, with only one study reaching QT interval >450 ms after ritonavir-boosted saquinavir treatment on healthy patients. There is only one study on COVID-19 patients reporting QT prolongation in 1 out of 95 patients after ritonavir-boosted lopinavir treatment. Limited evidence suggests that lopinavir, ritonavir, atazanavir, and saquinavir could cause PR prolongation, QRS widening, and QT prolongation. Further trials with closer monitoring and assessment of electrocardiography are needed to ascertain usage safety of antivirals in COVID-19 era.


Recent advances in gossypol derivatives and analogs: a chemistry and biology view.
Gossypol as a natural occurring polyphenol has been studied in a wide range of therapeutic contexts for a long time. The chemical modifications on gossypol were limited due to the unique chemical properties of polyphenols. The design and synthesis of gossypol derivatives and the exploration of their biological activities are the interest of the synthetic chemists, medicinal chemists and pharmacologists. Thus, the progress of diverse gossypol derivatives and analogs' synthesis, biological activities, mechanism elucidation and drug discovery based on gossypol scaffold is summarized.


A latent profile analysis of psychological sense of community and ethnic identity among racial-ethnic minority young adults from the southwestern United States.
Among young adults fof color, both sense of community and ethnic identity, as developmental processes, have been associated with wellness, empowerment, and civic action. Additional research is needed that provides empirical support for the connection between psychological sense of community and ethnic identity on outcomes that relate to human development such as intrapersonal psychological empowerment, civic engagement, and depression symptoms. The current study of young adults of color (N = 243; 70% Hispanic/Chicano(a)/Spanish and 10% American Indian/Native American; 70% female) investigates heterogeneity according to dimensions of psychological sense of community and the ethnic identity construct. Latent profile analyses (LPA) were conducted. Using LPA, five profile groups emerged. Profile group differences were present on reported levels of intrapersonal psychological empowerment, civic engagement, and depression symptoms. Majority of sample participants were classified with moderate to high psychological sense of community and ethnic identity. Findings provide insights for efforts on developing community belongingness based on ethnic group identity and engaging young adults in civic life.


A clinically relevant HIV-1 subunit vaccine protects rhesus macaques from in vivo passaged simian-human immunodeficiency virus infection.
To investigate whether immunization with recombinant HIV-1 envelope protein derived from a clinical isolate could protect macaques from infection with an in vivo passaged chimeric simian-human immunodeficiency virus (SHIV). A total of 16 animals were studied from which three groups of four animals were immunized with vaccine formulations of the CC-chemokine receptor-5-binding recombinant gp120 of HIV-1W6.1D. Four weeks after the last immunization, all 16 animals were intravenously challenged with in vivo passaged SHIV derived from the same HIV-1 group B clinical isolate (W6.1D) as the vaccines. Vaccine protection from infection was demonstrated in 10 out of 12 macaques immunized with recombinant gp120. Complete protection from infection was achieved with all of the animals that received the SBAS2-W6.1D formulation, a potent inducer of both T-cell and humoral immune responses. Partial protection was achieved with SBAS1-W6.1D, a formulation based on immunomodulators known to induce T-cell responses in humans. In vaccinated animals that were infected, virus load was reduced and infection was delayed. In a relatively large number of primates, vaccine efficacy was demonstrated with a clinically relevant HIV-1 vaccine. These results reveal that it is possible to induce sterilizing immunity sufficient to protect from infection with SHIV which was passaged multiple times in vivo. Our findings have implications for current HIV-1 clinical vaccine trials and ongoing efforts to develop safe prophylactic AIDS vaccines.


Processing of Rhythm in Speech and Music in Adult Dyslexia.
Recent studies have suggested that musical rhythm perception ability can affect the phonological system. The most prevalent causal account for developmental dyslexia is the phonological deficit hypothesis. As rhythm is a subpart of phonology, we hypothesized that reading deficits in dyslexia are associated with rhythm processing in speech and in music. In a rhythmic grouping task, adults with diagnosed dyslexia and age-matched controls listened to speech streams with syllables alternating in intensity, duration, or neither, and indicated whether they perceived a strong-weak or weak-strong rhythm pattern. Additionally, their reading and musical rhythm abilities were measured. Results showed that adults with dyslexia had lower musical rhythm abilities than adults without dyslexia. Moreover, lower musical rhythm ability was associated with lower reading ability in dyslexia. However, speech grouping by adults with dyslexia was not impaired when musical rhythm perception ability was controlled: like adults without dyslexia, they showed consistent preferences. However, rhythmic grouping was predicted by musical rhythm perception ability, irrespective of dyslexia. The results suggest associations among musical rhythm perception ability, speech rhythm perception, and reading ability. This highlights the importance of considering individual variability to better understand dyslexia and raises the possibility that musical rhythm perception ability is a key to phonological and reading acquisition.


Place of sodium-glucose co-transporter type 2 inhibitors for treatment of type 2 diabetes.
Inhibitors of sodium-glucose co-transporter type 2 (SGLT2), such as canagliflozin and dapagliflozin, are recently approved for treatment of type 2 diabetes. These agents lower blood glucose mainly by increasing urinary glucose excretion. Compared with placebo, SGLT2 inhibitors reduce hemoglobin A1c (HbA1c) levels by an average of 0.5%-0.8% when used as monotherapy or add-on therapy. Advantages of this drug class include modest weight loss of approximately 2 kg, low risk of hypoglycemia, and decrease blood pressure of approximately 4 mmHg systolic and 2 mmHg diastolic. These characteristics make these agents potential add-on therapy in patients with HbA1c levels close to 7%-8.0%, particularly if these patients are obese, hypertensive, and/or prone for hypoglycemia. Meanwhile, these drugs are limited by high frequency of genital mycotic infections. Less common adverse effects include urinary tract infections, hypotension, dizziness, and worsening renal function. SGLT2 inhibitors should be used with caution in the elderly because of increased adverse effects, and should not be used in chronic kidney disease due to decreased or lack of efficacy and nephrotoxicity. Overall, SGLT2 inhibitors are useful addition for treatment of select groups of patients with type 2 diabetes, but their efficacy and safety need to be established in long-term clinical trials.


A real time finite element based tissue simulation method incorporating nonlinear elastic behavior.
This paper presents a new finite element simulation approach for surgical simulators. Based on the solution of the algebraic equations derived from a nonlinear elastic model, we propose a real time simulation rule based on the implicit relation between the displacements of contacted and free nodes. This rule is an analytic expression in the linear case, and an approximation of the implicit relation in the non-linear case. We also remove some of the restrictions on flexibility exhibited by previous linear and nonlinear approaches. In the linear case, real time reconfiguration of the contacted nodes and the boundary constraints is realized using the simulation rule, while in the nonlinear case, a similar result is obtained by employing affine mapping. These methods allow nonlinear material properties to be applied to real time tissue simulation, with an efficiency comparable to that of the tensor matrix method for linear elastic models.


Developing PCR primers using a new computer program for detection of multiple animal-derived materials in feed.
To reduce the risk of the bovine spongiform encephalopathy agent being recycled to cattle through animal feed, in October 2001 Japan introduced a feed ban prohibiting the use of animal proteins in feed. PCR identification of feed ingredients is part of the audit program to ensure the proper implementation of the feed ban. For efficient analysis, screening of feed products for materials from multiple species is essential. In our study, we developed a computer program GSPRIMER (http://www. famic.go.jp/ffis/feed/gsprimer/) that facilitates development of PCR primers specific to multiple species. The most important feature of GSPRIMER is its ability to estimate the specificity and homology of a potential primer in incremental steps from the 3' terminal. We analyzed all regions of mitochondrial DNA from the target and nontarget species using GSPRIMER. We designed species-specific primer sets for three animal species (sheep, goats, and swine) and group-specific primer sets for ruminants and animals susceptible to transmissible spongiform encephalopathy. The primers were efficiently screened by the PCR protocol using a mixture of mitochondrial DNA from nontarget species as a template. As a result, one primer set each for sheep and goats, two for swine, and three for a group of ruminant species were developed. The detection limit of one of the ruminant primer sets ranged from 0.05 to 0.01% bovine meat and bone meal and 0.1 pg of bovine DNA. We also successfully applied the primer set to 17 commercial feed samples that were known to be free from ruminant-derived materials. No false-positive results were found.


First Report of Streptomyces stelliscabiei Causing Potato Common Scab in Guizhou Province, China.
Potato (Solanum tuberosum L.) common scab can be caused by multiple pathogenic Streptomyces spp. worldwide. Potato tubers (cv. Favorita) with severe pitted common scab symptoms were observed at a small farm (2 hectares) during harvest in Anshun, Guizhou province in early May 2020. The disease incidence was around 10%, and symptomatic samples were collected to isolate the pathogen. Two isolates, ZR-IMU141 and ZR-IMU146 (Accession number MW995958 and MW995959 respectively), showed more than 99% sequence identity to S. stelliscabiei sequences (Accession No. HM018085). Five house-keeping genes for multi-locus sequence analyze (MLSA) of Streptomycetaceae were amplified, sequenced and uploaded to NCBI: atpD (MZ343164 and MZ343165), gyrB (MZ343162 and MZ343163), recA (MZ343166 and MZ343167), rpoB (MZ343168and MZ343169) and trpB (MZ343170 and MZ343171). All the genes show over 98% identity with S. stelliscabiei. Phylogenetic trees of 16S rRNA gene sequence and multi-locus sequence analysis (MLSA) were constructed. The two isolates contain pathogenicity genes txtAB, nec1, and tomA, which was confirmed by PCR. To complete Koch's postulates, 9 potato seedlings (cv. Favorita, 15 centimeters high), were transferred to new pots and inoculated with spore suspensions of ZR-IMU141 and ZR-IMU146 (104 CFU/ml), or water as a negative control. Two months later, potato tubers inoculated with either ZR-IMU141 or ZR-IMU146 exhibited typical symptoms of potato common scab, such as superficial or deep, raised, pitted, or polygonal lesions like the field symptoms, but the negative controls remained asymptomatic. The pathogens were reisolated from the lesions and confirmed identical to the original isolate by 16s rRNA gene sequences. To our knowledge, this is the first report of S. stelliscabiei causing potato common scab in Guizhou province, China. We believe that this report will draw attention to the study and management of the increased pool of scab pathogens in China.


Novel methodologies for host-microbe interactions and microbiome-targeted therapeutics in 3D organotypic skin models.
Following descriptive studies on skin microbiota in health and disease, mechanistic studies on the interplay between skin and microbes are on the rise, for which experimental models are in great demand. Here, we present a novel methodology for microbial colonization of organotypic skin and analysis thereof. An inoculation device ensured a standardized application area on the stratum corneum and a homogenous distribution of bacteria, while preventing infection of the basolateral culture medium even during prolonged culture periods for up to 2 weeks at a specific culture temperature and humidity. Hereby, host-microbe interactions and antibiotic interventions could be studied, revealing diverse host responses to various skin-related bacteria and pathogens. Our methodology is easily transferable to a wide variety of organotypic skin or mucosal models and different microbes at every cell culture facility at low costs. We envision that this study will kick-start skin microbiome studies using human organotypic skin cultures, providing a powerful alternative to experimental animal models in pre-clinical research. Video Abstract.


Transcriptomic analysis reveals ethylene as stimulator and auxin as regulator of adventitious root formation in petunia cuttings.
Adventitious root (AR) formation in the stem base (SB) of cuttings is the basis for propagation of many plant species and petunia is used as model to study this developmental process. Following AR formation from 2 to 192 hours post-excision (hpe) of cuttings, transcriptome analysis by microarray revealed a change of the character of the rooting zone from SB to root identity. The greatest shift in the number of differentially expressed genes was observed between 24 and 72 hpe, when the categories storage, mineral nutrient acquisition, anti-oxidative and secondary metabolism, and biotic stimuli showed a notable high number of induced genes. Analyses of phytohormone-related genes disclosed multifaceted changes of the auxin transport system, auxin conjugation and the auxin signal perception machinery indicating a reduction in auxin sensitivity and phase-specific responses of particular auxin-regulated genes. Genes involved in ethylene biosynthesis and action showed a more uniform pattern as a high number of respective genes were generally induced during the whole process of AR formation. The important role of ethylene for stimulating AR formation was demonstrated by the application of inhibitors of ethylene biosynthesis and perception as well as of the precursor aminocyclopropane-1-carboxylic acid, all changing the number and length of AR. A model is proposed showing the putative role of polar auxin transport and resulting auxin accumulation in initiation of subsequent changes in auxin homeostasis and signal perception with a particular role of Aux/IAA expression. These changes might in turn guide the entrance into the different phases of AR formation. Ethylene biosynthesis, which is stimulated by wounding and does probably also respond to other stresses and auxin, acts as important stimulator of AR formation probably via the expression of ethylene responsive transcription factor genes, whereas the timing of different phases seems to be controlled by auxin.


Inhibition of Histone H3 Lysine-27 Demethylase Activity Relieves Rheumatoid Arthritis Symptoms via Repression of IL6 Transcription in Macrophages.
Rheumatoid arthritis (RA) occurs in about 5 per 1,000 people and can lead to severe joint damage and disability. However, the knowledge of pathogenesis and treatment for RA remains limited. Here, we found that histone demethylase inhibitor GSK-J4 relieved collagen induced arthritis (CIA) symptom in experimental mice model, and the underlying mechanism is related to epigenetic transcriptional regulation in macrophages. The role of epigenetic regulation has been introduced in the process of macrophage polarization and the pathogenesis of inflammatory diseases. As a repressive epigenetic marker, tri-methylation of lysine 27 on histone H3 (H3K27me3) was shown to be important for transcriptional gene expression regulation. Here, we comprehensively analyzed H3K27me3 binding promoter and corresponding genes function by RNA sequencing in two differentially polarized macrophage populations. The results revealed that H3K27me3 binds on the promoter regions of multiple critical cytokine genes and suppressed their transcription, such as IL6, specifically in M-CSF derived macrophages but not GM-CSF derived counterparts. Our results may provide a new approach for the treatment of inflammatory and autoimmune disorders.


Effect of the curing cycle on some properties of a polymethylmethacrylate denture base material.
The properties of a denture base material may be modified by altering both the temperature and the time of heating during the curing cycle. In this study a polymethylmethacrylate denture base containing no crosslinking agent was polymerised using four different curing cycles. The structure of the materials so obtained was investigated by an acid etching technique. The materials were characterized with respect to degree of cure, strength and water sorption. It was concluded that: 1. No correlation was observed between the curing cycles and polymer structure. 2. The curing cycle of 7 h at 70 degrees C plus 1 h at 100 degrees C produced best indentation strength and tensile strength. 3. A correlation was observed between residual monomer, indentation resistance, tensile strength and water sorption. This suggested that residual monomer concentration is the most important parameter in the determination of the properties of the material investigated in this study.


Kinetics, localization and characteristics of B- and T-cell responses to iscoms containing human influenza virus glycoproteins.
B- and T-cell responses have been studied after primary and secondary immunizations of mice with iscoms containing influenza virus envelope glycoproteins. After primary immunization both B- and T-cell responses were initiated in the draining lymph nodes. T-cells showed peak activity with respect to proliferation and cytokine production after five to eight days and the highest number of IgG secreting cells (IgG-SC) was recorded at day seven. The responses in the spleen developed slowly but were of longer duration. Cytokines produced by spleen cells included high levels of IFN-gamma and IL-2. After a secondary immunization the frequencies of IgG-SC were drastically increased in both LN and spleen, but decreased rapidly with time. At day eight after the secondary immunization high numbers of IgG-SC were detected in the bone marrow. High titres of IgG1 and IgG2a and substantial titres of IgG2b and IgG3 were detected in serum.


In Vitro Anti-Oxidant and Anti-Microbial Potentiality Investigation of Different Fractions of Caryota urens Leaves.
Caryota urens is a member of the Arecaceae family and a common plant in the Southeast Asian region. This plant has been reported as an anti-microbial agent in recent years. Thus, we aimed to find out the MIC (minimum inhibitory concentration) against different pathogenic microorganism. The leaves of C. urens were extracted and fractioned using different reagents (chloroform, n-hexane and carbon tetrachloride). Disc diffusion method was implemented for the assessment of in vitro anti-microbial potency (500 and 250 µg/disc). The entire fraction showed good effect (with the zone of inhibition 19-25 mm) against both gram positive (Bacillus subtilis, Bacillus megaterium, Bacillus cereus, Sarina lutea) and gram negative (Vibrio mimicus, Shigella boydii, Escherichia coli, Pseudomonas aeruginosa) bacterial pathogens and fungal strains (Aspergillus niger, Saccharomyces cerevisiae). The plants also possess effective free radical scavenging potency with an IC50 of 130.32 µg/mL. This finding reflects a link between the presence of anti-oxidative material and a substantial anti-microbial activity, and substantiates all previous claims against C. urens.


Unlocking Reactivity of TrpB: A General Biocatalytic Platform for Synthesis of Tryptophan Analogues.
Derivatives of the amino acid tryptophan (Trp) serve as precursors for the chemical and biological synthesis of complex molecules with a wide range of biological properties. Trp analogues are also valuable as building blocks for medicinal chemistry and as tools for chemical biology. While the enantioselective synthesis of Trp analogues is often lengthy and requires the use of protecting groups, enzymes have the potential to synthesize such products in fewer steps and with the pristine chemo- and stereoselectivity that is a hallmark of biocatalysis. The enzyme TrpB is especially attractive because it can form Trp analogues directly from serine (Ser) and the corresponding indole analogue. However, many potentially useful substrates, including bulky or electron-deficient indoles, are poorly accepted. We have applied directed evolution to TrpB from Pyrococcus furiosus and Thermotoga maritima to generate a suite of catalysts for the synthesis of previously intractable Trp analogues. For the most challenging substrates, such as nitroindoles, the key to improving activity lay in the mutation of a universally conserved and mechanistically important residue, E104. The new catalysts express at high levels (>200 mg/L of Escherichia coli culture) and can be purified by heat treatment; they can operate up to 75 °C (where solubility is enhanced) and can synthesize enantiopure Trp analogues substituted at the 4-, 5-, 6-, and 7-positions, using Ser and readily available indole analogues as starting materials. Spectroscopic analysis shows that many of the activating mutations suppress the decomposition of the active electrophilic intermediate, an amino-acrylate, which aids in unlocking the synthetic potential of TrpB.


3D Reconstruction in the Presence of Glass and Mirrors by Acoustic and Visual Fusion.
We present a practical and inexpensive method to reconstruct 3D scenes that include transparent and mirror objects. Our work is motivated by the need for automatically generating 3D models of interior scenes, which commonly include glass. These large structures are often invisible to cameras or even to our human visual system. Existing 3D reconstruction methods for transparent objects are usually not applicable in such a room-sized reconstruction setting. Our simple hardware setup augments a regular depth camera (e.g., the Microsoft Kinect camera) with a single ultrasonic sensor, which is able to measure the distance to any object, including transparent surfaces. The key technical challenge is the sparse sampling rate from the acoustic sensor, which only takes one point measurement per frame. To address this challenge, we take advantage of the fact that the large scale glass structures in indoor environments are usually either piece-wise planar or a simple parametric surface. Based on these assumptions, we have developed a novel sensor fusion algorithm that first segments the (hybrid) depth map into different categories such as opaque/transparent/infinity (e.g., too far to measure) and then updates the depth map based on the segmentation outcome. We validated our algorithms with a number of challenging cases, including multiple panes of glass, mirrors, and even a curved glass cabinet.


Excision margins for primary cutaneous melanoma: updated pooled analysis of randomized controlled trials.
To determine the effectiveness of wide vs narrow excision margins in the treatment of primary cutaneous melanoma. We conducted a search of MEDLINE and the Cochrane Controlled Trials Register as well as a manual search of the reference lists of all relevant papers. No language or date restrictions were applied. Only prospective randomized trials were included. Two reviewers independently extracted the data from each study. Outcomes evaluated were local and locoregional recurrences and overall mortality. Data were analyzed using Cochrane Collaboration Review Manager software. Five randomized trials comprising 3313 participants were retrieved and analyzed. Pooled data showed no statistically significant difference in overall mortality when comparing wide vs narrow excision margins (odds ratio, 0.98; 95% confidence interval, 0.72-1.22; and test for overall effect of P = .88). There was no statistically significant difference in the occurrence of locoregional recurrence between 2 groups of patients (odds ratio, 1.18; 95% confidence interval, 0.98-1.41; and test for overall effect not significant at P = .08). Although statistically significant heterogeneity was not detected among included trials, there was considerable clinical heterogeneity. Although this meta-analysis did not show any statistically significant difference between patients treated with wide or narrow excision margins insofar as overall mortality and locoregional and local recurrences, current evidence is insufficient to address the optimal excision margins for all types of melanomas. Further research is required to establish the appropriate local treatment for different types of primary melanoma and subgroups of patients.


Effect of repeated heating and cooling cycles on the degree of conversion and microhardness of four resin composites.
This study evaluated the effect of repeatedly heating and cooling four resin-based composites (RBCs) for up to six cycles. Four commercial RBCs were heated to 68°C and cooled to room temperature for up to six cycles before photocuring at 30°C. Specimens spent a total of 0, 30, 60, 90, 120, 150 min, or 7 days at 68°C. The degree of conversion (DC) was measured at the bottom of the specimens immediately after photocuring. The Vickers microhardness was measured at the top and bottom of the RBC surfaces 24 h after photocuring. The data were analyzed using one-way analysis of variance, Dunnett's or Bonferroni post-hoc tests, and Spearman correlation analysis (α = 0.05). For two brands of RBC, the DC decreased at various time points; however, these decreases were small, and there was no correlation (negative or positive) between the number of heating cycles and the DC for any of the RBCs. Repeated heated and cooling resulted in small changes in the hardness (compared to the control) in both directions (Dunnett; p < 0.05). Two of the RBCs showed a significant, positive correlation between the number of heating cycles and their hardness at the bottom surface. Repeated heating, cooling, and then reheating the RBCs for up to 1 week had little overall effect on their DC and microhardness values. The 2 mm thick specimens of all four RBCs achieved a bottom: top hardness ratio exceeding 0.8 after a 20 s exposure to light from a commercial LED curing light CLINICAL SIGNIFICANCE: Six repeated dry heating and cooling cycles of up to 1 week in duration had little effect on the DC and the microhardness of four commercial resin-based composites.


Shift in Immune Parameters After Repeated Exposure to Nanoplastics in the Marine Bivalve Mytilus.
Bivalves are widespread in coastal environments subjected to a wide range of environmental fluctuations: however, the rapidly occurring changes due to several anthropogenic factors can represent a significant threat to bivalve immunity. The mussel Mytilus spp. has extremely powerful immune defenses toward different potential pathogens and contaminant stressors. In particular, the mussel immune system represents a significant target for different types of nanoparticles (NPs), including amino-modified nanopolystyrene (PS-NH2) as a model of nanoplastics. In this work, the effects of repeated exposure to PS-NH2 on immune responses of Mytilus galloprovincialis were investigated after a first exposure (10 μg/L; 24 h), followed by a resting period (72-h depuration) and a second exposure (10 μg/L; 24 h). Functional parameters were measured in hemocytes, serum, and whole hemolymph samples. In hemocytes, transcription of selected genes involved in proliferation/apoptosis and immune response was evaluated by qPCR. First exposure to PS-NH2 significantly affected hemocyte mitochondrial and lysosomal parameters, serum lysozyme activity, and transcription of proliferation/apoptosis markers; significant upregulation of extrapallial protein precursor (EPp) and downregulation of lysozyme and mytilin B were observed. The results of functional hemocyte parameters indicate the occurrence of stress conditions that did not however result in changes in the overall bactericidal activity. After the second exposure, a shift in hemocyte subpopulations, together with reestablishment of basal functional parameters and of proliferation/apoptotic markers, was observed. Moreover, hemolymph bactericidal activity, as well as transcription of five out of six immune-related genes, all codifying for secreted proteins, was significantly increased. The results indicate an overall shift in immune parameters that may act as compensatory mechanisms to maintain immune homeostasis after a second encounter with PS-NH2.


How composition methods are developed and validated.
Method validation is a critical prerequisite to performing analytical methods in the laboratory. A given analytical method is validated for a specific matrix or matrices. If the matrix to be tested is not included in the original scope of method validation, a validation must be performed to determine if the method is applicable to that particular matrix. A number of organizations, such as AOAC and ISO, publish peer-reviewed methods for cross-industry matrices, whereas others, such as AOCS and AACC, are focused on specific industry segments (fats/oils and cereal grains). When no validated method is available for the analyte of interest, method development and validation must first be performed to ensure that correct identification and quantification of the analyte are being observed and measured. Development of a new method requires an understanding of the chemistry and properties of the analyte to be tested, as well as the various types of instrumentation currently available. Method development and improvement is a continuous process, as technology advances and new instrumentation and techniques become available. This paper addresses some of the decisions related to method development but will primarily focus on validation as it applies to compositional testing of foods, crops, and commodities, the factors that determine method selection, and how extensive the validation need be.


Large variance in reproductive success and the Ne/N ratio.
The ratio of the effective population size to adult (or census) population size (Ne/N) is an indicator of the extent of genetic variation expected in a population. It has been suggested that this ratio may be quite low for highly fecund species in which there is a sweepstakes-like chance of reproductive success, known as the Hedgecock effect. Here I show theoretically how the ratio may be quite small when there are only a few successful breeders (Nb) and that in this case, the Ne/N ratio is approximately Nb/N. In other words, high variance in reproductive success within a generation can result in a very low effective population size in an organism with large numbers of adults and consequently a very low Ne/N ratio. This finding appears robust when there is a large proportion of families with exactly two progeny or when there is random variation in progeny numbers among these families.


Lithium niobate ridged waveguides with smooth vertical sidewalls fabricated by an ultra-precision cutting method.
This paper demonstrates the application of ultra-precision cutting to the fabrication of ridged LiNbO₃ waveguides for use in low-loss photonic integrated circuits. Ridged waveguides with sidewall verticality of 88° and ultra-smooth sidewalls were obtained in LiNbO₃ crystals using this technique. In addition, the possibility of fabricating bent ridged waveguides via this mechanical micromachining method was examined. The root mean square surface roughness of the machined sidewall was 4.5 nm over an area of 2.5 × 10 µm, which is sufficiently low so as to minimize scattering losses of guided light. The propagation loss of the ridged waveguide produced during this work was well below 1 dB/cm at a wavelength of 1550 nm. The present technique should have significant applicability to the micromachining of ferroelectric materials and the fabrication of highly confined optical waveguides such as ridged waveguides and photonic wires.


[Ultrasound guided interventional radiology].
Ultrasound is a valuable imaging technique for musculoskeletal pathology. It is increasingly used for image-guided procedures such as aspiration of superficial or deep collections, injection of drugs, or biopsies. Ultrasound guidance is an interesting alternative to procedures performed either blindly or under fluoroscopic or CT guidance. Advantages of US-guided procedures include the absence of ionizing radiation, real-time monitoring during needle placement, decreased risk of injury to neighboring structures (namely vessels and nerves), real time confirmation of procedure success (injection, drainage, biopsy). Minor inconveniences relate to the proper conditions for performance of ultrasound. Complications are rare and can be avoided by using proper sterile technique and evaluate for potential contra-indications to the procedure. As with any other image guided procedure, informed consent is required.


The hydroxycinnamic acid content of barley and brewers' spent grain (BSG) and the potential to incorporate phenolic extracts of BSG as antioxidants into fruit beverages.
The hydroxycinnamic acid (HA) content of starting barley for brewers' spent grains (BSG), whole BSG and phenolic extracts from BSG was measured using high performance liquid chromatography (HPLC) and correlated with antioxidant potential. The effect of BSG phenolic extracts on antioxidant activity of fruit beverages was also assessed (using the total phenolic content (TPC), 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays). The concentration of HA present in barley extract and BSG was in the order of ferulic acid (FA), p-coumaric acid (p-CA) derivatives, FA derivatives, p-CA, caffeic acid (CA) and CA derivatives. Results suggested that brewing and roasting decreased the HA content. Antioxidant activity was significantly (P<0.05) correlated with caffeic acid (R(2)=0.8309) and total HA (R(2)=0.3942) concentrations. Addition of extracts to fruit beverages resulted in a significant (P<0.05) increase in antioxidant activity of cranberry juice, measured by the FRAP assay. In vitro digestion significantly (P<0.05) reduced TPC, DPPH and FRAP activity of the fruit beverages.


Therapeutic defibrination and heparin therapy in the prevention and resolution of experimental venous thrombosis.
The application of phenol to the femoral veins of anesthetized dogs resulted in an occluding thrombus in 24 of 25 veins at 1 week. Serial venography and eventual histology showed that these veins remained occluded over a 5-week observation period, the thrombi undergoing organization. Therapeutic defibrination was achieved with administration of an enzyme from venom of the pit viper (Arvin). Arvin, administered for 1 week immediately following phenol application and before thrombus formation had occurred, prevented thrombosis in all 10 such veins, and serial venography for a further 4 weeks showed that the veins remained patent. Administration of Arvin was begun 24 hours postoperatively, when venography had demonstrated an occluding thrombus and failed to clear any of 11 veins after 3 weeks of treatment. Intravenous administration of heparin, 10,000 units, at 6, 6, and 12-hour intervals in a 24-hour period, was begun immediately after phenol application and continued for 1 week; 10 of 12 veins were blocked at 1 week. Following the same dose of heparin every 6 hours four of eight veins were blocked at 1 week. The results indicate that when the vascular endothelium is damaged, therapeutic defibrination is more effective than heparin therapy in preventing venous thrombosis. Arvin therapy has no significant thrombolytic effect even if the thrombus is less than 24 hours old.


Effects of combined and sequential addition of dual oxidants (H2O2/S2O8(2-)) on the aqueous carbofuran photodegradation.
Carbofuran (2,3-dihydro-2,2-dimethylbenzofuran-7-yl methylcarbamate) (CBF) is a widely used insecticide. Traditional methods like hydrolysis and direct photolysis cannot remove CBF effectively. In this study, the photodecay of 0.1 mM CBF in UV/H2O2, UV/S2O8(2-), and UV/H2O2/S2O8(2-) and sequential addition of a second oxidant were studied under UV light at 254 nm. The degradations of CBF follow pseudo-first-order decay kinetics. Direct photolysis was slow, but the corresponding degradation rate was increased with the addition of hydrogen peroxide (H2O2) or potassium peroxydisulfate (K2S2O8). In the UV/H2O2 reaction, the optimum reaction rate was 0.9841 min-1 at 10 mM H2O2 (pH 7); however, retardation is observed if H2O2 is overdosed. Such retardation is not observed in the UV/S2O8(2-) system, but a nonlinear increment of removal efficiency is identified. The UV/H2O2/S2O8(2-) process on the other hand shows the best performance in CBF degradation, but it has a less effective mineralization than that of the sole UV/S2O8(2-) reaction.


Comparison of the biological effects of four irreversible inhibitors of ornithine decarboxylase in two murine lymphocytic leukemia cell lines.
The effects of the enzyme-activated irreversible inhibitors of ornithine decarboxylase, alpha-difluoromethylornithine, alpha-(fluoromethyl)dehydroornithine, alpha-(fluoromethyl)dehydroornithine methyl ester, and (2R,5R)-6-heptyne-2,5-diamine (RR-MAP), on cell growth and parameters related to polyamine biosynthesis were compared in L5178Y and L1210 cells under identical culture conditions. The two lines are murine lymphocytic leukemia cells which differ in their ability to metabolize 5'-methylthioadenosine, the by-product of polyamine biosynthesis: L5178Y cells contain a specific 5'-methylthioadenosine phosphorylase; L1210 cells do not. In L1210 cells, the 50% inhibitory concentrations (lC50S) of the various analogues were 3.0 mM for alpha-difluoromethylornithine, 0.2 mM for alpha-(fluoromethyl)dehydroornithine, 0.1 mM for alpha-(fluoromethyl)dehydroornithine methyl ester, and 0.01 mM for RR-MAP. L5178Y cells were somewhat more sensitive to the inhibitors with lC50 values of 0.5 mM for alpha-difluoromethylornithine, 0.06 mM for alpha-(fluoromethyl)dehydroornithine, 0.03 mM for alpha-(fluoromethyl)dehydroornithine methyl ester, and 0.002 mM for RR-MAP. In all cases, growth inhibition was fully prevented by exogenous putrescine. The effects of the inhibitors on parameters related to polyamine metabolism were compared at drug concentrations approximating the average of lC50 values for the two cell lines. Under these treatment conditions, polyamine pools were similarly affected by the various inhibitors. Typically, putrescine and spermidine were depleted, but effects on spermine pools differed according to the cell line, increasing slightly in L1210 cells and decreasing by about 50% in L5178Y cells. Spermine pools in L1210 cells could be reduced by RR-MAP at concentrations higher than the lC50 (i.e., 0.1 mM). Clonogenicity in soft agar was decreased about 50% by putrescine and spermidine depletion and was not further affected by spermine depletion. The inhibitors elevated S-adenosylmethionine decarboxylase activity in both cell lines with a 2-fold greater increase in L5178Y cells than in L1210 cells. Finally, the inhibitors decreased S-adenosylmethionine pools in L1210 cells by about 50% but had little effect on these pools in L5178Y cells with the exception of RR-MAP, which decreased S-adenosylmethionine pools by about 40%. Whether the different polyamine responses of the two cell lines are related to their ability to metabolize 5'-methylthioadenosine is uncertain. It is apparent, however, that the presence or absence of methylthioadenosine phosphorylase does not substantially modulate the antiproliferative activity of ornithine decarboxylase inhibitors.(ABSTRACT TRUNCATED AT 400 WORDS)


Expression of the Arabidopsis Mg-chelatase H subunit alleviates iron deficiency-induced stress in transgenic rice.
The most common symptom of iron (Fe) deficiency in plants is leaf chlorosis caused by impairment of chlorophyll biosynthesis. Magnesium (Mg)-chelatase H subunit (CHLH) is a key component in both chlorophyll biosynthesis and plastid signaling, but its role in Fe deficiency is poorly understood. Heterologous expression of the Arabidopsis thaliana Mg-chelatase H subunit gene (AtCHLH) increased Mg-chelatase activity by up to 6-fold and abundance of its product, Mg-protoporphyrin IX (Mg-Proto IX), by 60-75% in transgenic rice (Oryza sativa) seedlings compared to wild-type (WT) controls. Noticeably, the transgenic seedlings showed alleviation of Fe deficiency symptoms, as evidenced by their less pronounced leaf chlorosis and lower declines in shoot growth, chlorophyll contents, and photosynthetic efficiency, as indicated by F v/F m and electron transport rate, compared to those in WT seedlings under Fe deficiency. Porphyrin metabolism was differentially regulated by Fe deficiency between WT and transgenic seedlings, particularly with a higher level of Mg-Proto IX in transgenic lines, showing that overexpression of AtCHLH reprograms porphyrin metabolism in transgenic rice. Leaves of Fe-deficient transgenic seedlings exhibited greater upregulation of deoxymugineic acid biosynthesis-related genes (i.e., NAS, NAS2, and NAAT1), YSL2 transporter gene, and Fe-related transcription factor genes IRO2 and IDEF2 than those of WT, which may also partly contribute to alleviating Fe deficiency. Although AtCHLH was postulated to act as a receptor for abscisic acid (ABA), exogenous ABA did not alter the phenotypes of Fe-deficient WT or transgenic seedlings. Our study demonstrates that modulation of porphyrin biosynthesis through expression of AtCHLH in transgenic rice alleviates Fe deficiency-induced stress, suggesting a possible role for CHLH in Fe deficiency responses.


Inducible nitric oxide synthase participates in cochlear damage after acoustic stimulation in Guinea pigs.
Inducible nitric oxide synthase (iNOS/NOS II) mediates cytotoxicity under pathological stimulation. The purpose of this study was to examine whether the blockade of NOS activity leads to a decrease in cochlear damage after intense acoustic stimulation. Guinea pigs were divided into 4 groups: (1) a noise group, (2) a NOS inhibitor (NG-nitro-L-arginine methyl ester [L-NAME]) + noise group (L-NAME/noise group), (3) an L-NAME group, and (4) a control group. Stimuli involved a pure tone at a frequency of 2 kHz for 5 hours. The sound pressure level was 120 dBSPL. In the L-NAME/noise group, 50 mg/kg body weight of L-NAME was injected 1 hour before acoustic stimulation. In the control group and the L-NAME group, acoustic stimulation was not performed. In the L-NAME group, the same dose of L-NAME was injected intraperitoneally. In the control group, only physiological saline was injected. Auditory brainstem responses (ABRs) were recorded before and immediately, 1 day, and 7 days after acoustic stimulation. The ABR threshold was significantly higher immediately after acoustic stimulation in both the noise group and the L-NAME/noise group. One day after acoustic stimulation, the threshold shift was decreased in the noise group. The threshold shift was still present 7 days after acoustic stimulation but was significantly lower in the L-NAME/noise group than in the noise group. In the L-NAME group and the control group, threshold shifts were not apparent. The lateral wall, the organ of Corti, and the spiral ganglion cells of the cochlea in both the L-NAME group and the control group did not display immunoreactivity for iNOS at any time. Immunoreactivity for iNOS was found in the lateral wall, the supporting cells (Hensen's cells, Deiters' cells, and pillar cells), and the spiral ganglion cells in both the noise group and the L-NAME/noise group. These immunoreactivities for iNOS were detected immediately, 1 day, and 7 days after acoustic stimulation. Immunoreactivity decreased over time in the stria vascularis, the organ of Corti, and the spiral ganglion cells in the noise group. The same phenomenon was observed in the L-NAME/noise group. In conclusion, iNOS was detected in cochlea damaged by acoustic stimulation. A NOS inhibitor (L-NAME) reduced the elevation of hearing thresholds. Our results suggest that the expression of iNOS participates in the pathogenesis of cochlear damage caused by acoustic trauma.


Two mammalian Sec16 homologues have nonredundant functions in endoplasmic reticulum (ER) export and transitional ER organization.
Budding yeast Sec16 is a large peripheral endoplasmic reticulum (ER) membrane protein that functions in generating COPII transport vesicles and in clustering COPII components at transitional ER (tER) sites. Sec16 interacts with multiple COPII components. Although the COPII assembly pathway is evolutionarily conserved, Sec16 homologues have not been described in higher eukaryotes. Here, we show that mammalian cells contain two distinct Sec16 homologues: a large protein that we term Sec16L and a smaller protein that we term Sec16S. These proteins localize to tER sites, and an N-terminal region of each protein is necessary and sufficient for tER localization. The Sec16L and Sec16S genes are both expressed in every tissue examined, and both proteins are required in HeLa cells for ER export and for normal tER organization. Sec16L resembles yeast Sec16 in having a C-terminal conserved domain that interacts with the COPII coat protein Sec23, but Sec16S lacks such a C-terminal conserved domain. Immunoprecipitation data indicate that Sec16L and Sec16S are each present at multiple copies in a heteromeric complex. We infer that mammalian cells have preserved and extended the function of Sec16.


Sustained transmission of nosocomial Legionnaires disease--Arizona and Ohio.
In 1996, two hospitals reported sustained transmission of nosocomial Legionnaires disease (LD). The hot water distribution systems in each hospital were implicated as the sources of infection. This report summarizes investigations in these two hospitals by hospital personnel, state and local health officials, and CDC and efforts to control transmission.


Binding modes of two novel non-nucleoside reverse transcriptase inhibitors, YM-215389 and YM-228855, to HIV type-1 reverse transcriptase.
YM-215389 and YM-228855 are thiazolidenebenzenesulfonamide (TBS) derivatives and novel non-nucleoside reverse transcriptase inhibitors (NNRTIs) that inhibit not only wild-type, but also the K103N- and Y181C-substituted reverse transcriptase (RT) of HIV type-1 (HIV-1). To characterize the binding modes of the TBS derivatives in detail, the anti-HIV-1 activities of YM-215389 and YM-228855 against various NNRTI-resistant clones were examined. Docking studies with HIV-1 RT were also performed. YM-215389, which effectively inhibits various NNRTI-resistant clones, interacted with L100, K103, V106 and Y318 through the benzene ring and with E138, V179, Y181, Y188 and W229 through the thiazole ring. A single amino acid substitution confers only moderate resistance to YM-215389; indeed, four amino acid substitutions (V106L, V108I, E138K and L214F) were necessary for high-level resistance. Although the activity of YM-228855, a derivative of YM-215389 that has two bulky and rigid cyano-moieties on the benzene ring, was 10x more potent against HIV-1 than YM-215389, its anti-HIV-1 activity was readily reduced with single substitutions as with Y181I and K103N. These results provide structural information for optimizing the TBS derivatives in an attempt to construct ideal NNRTIs that maintain anti-HIV-1 activity to various HIV-1 variants.


Tuning the Cathode-Electrolyte Interphase Chemistry with Multifunctional Additive for High-Voltage Li-Ion Batteries.
The utilization of layered oxides as cathode materials has significantly contributed to the advancement of the lithium-ion batteries (LIBs) with high energy density and reliability. However, the structural and interfacial instability triggered by side reactions when charged to high voltage has plagued their practical applications. Here, this work reports a novel multifunctional additive, id est, 7-Anilino-3-diethylamino-6-methyl fluoran (ADMF), which exhibits unique characteristics such as preferential adsorption, oxygen scavenging, and electropolymerization protection for high-voltage cathodes. The ADMF demonstrates the capability to ameliorate the growth of cathode-electrolyte interphase (CEI), effectively diminishing the dissolution of transition metal (TM) ions, reducing the interface impedance, and facilitating the Li+ transport. As a result, ADMF additive with side reaction-blocking ability significantly enhances the cycling stability of MCMB||NCM811 full-cells at 4.4 V and MCMB||LCO full-cells at 4.55 V, as evidenced by the 80% retention over 600 cycles and 87% retention after 750 cycles, respectively. These findings highlight the potential of the additive design strategy to modulate the CEI chemistry, representing a new paradigm with profound implications for the development of next-generation high-voltage LIBs.


Control of rabbit myxomatosis in Poland.
The authors present an epizootiological analysis of myxomatosis in Poland. The biological, physical and chemical properties of virus strains used for the production and control of 'Myxovac M' vaccine are discussed. The long-term stability, safety and efficacy of the vaccine are demonstrated. Laboratory experiments were confirmed in large-scale field observations.


The biology of Kit in disease and the application of pharmacogenetics.
C-kit encodes a transmembrane protein with intrinsic tyrosine kinase activity, which functions as the receptor for stem cell factor. It is expressed on a variety of cell types, including mast cells, hematopoietic progenitor cells, melanocytes, germ cells, and gastrointestinal pacemaker cells. Mutations resulting in alteration of Kit function are associated with diseases involving each of these cells. Recent development of tyrosine kinase inhibitors led to their evaluation as novel therapies for diseases associated with Kit activation. This review will discuss the pathobiology of Kit in human disease, with a particular emphasis on implications for potential targeted treatment strategies in mast cell disease.


Challenges to the measurement of estradiol: an endocrine society position statement.
The objective of the study was to evaluate the current state of clinical assays for estradiol in the context of their applications. The participants were appointed by the Council of The Endocrine Society and charged with attaining the objective using published data and expert opinion. Data were gathered from published sources via online databases (principally PubMed, Ovid MEDLINE, Google Scholar), and the clinical and laboratory experience of the participants. The statement was an effort of the committee and was reviewed by each member. The Clinical Affairs Committee, the Council of The Endocrine Society, and JCEM reviewers reviewed the manuscript and made recommendations. The measurement of estradiol in biological fluids is important in human biology from cradle to grave. In addition to its centrality in sexual development, it has significant effects on skin, blood vessels, bone, muscle, coagulation, hepatic cells, adipose tissue, the kidney, the gastrointestinal tract, brain, lung, and pancreas. Alterations in its plasma concentration have been implicated in coronary artery disease, stroke, and breast cancer. Although modern immunoassays and liquid chromatography/tandem mass spectrometry-based methods for estradiol are reasonably well suited to the diagnosis and management of infertility (nonetheless, imprecision and method-to-method differences remain problematic), the very low concentrations that appear to be crucial in nonreproductive tissues are a separate and more difficult issue. Such levels of estradiol are too low to be routinely measured accurately or precisely, and further evolution of analytical methods and the way in which estradiol is standardized is needed.


Novel SEPN1 Mutations in Exon 1 Are Common in Rigid Spine With Muscular Dystrophy Type 1 in Chinese Patients.
Congenital muscular dystrophy with early rigid spine, also known as the rigid spine with muscular dystrophy type 1 (RSMD1), is caused by SEPN1 mutation. We investigated the clinical manifestations, pathological features, and genetic characteristics of 8 Chinese RSMD1 patients in order to improve diagnosis and management of the disease. Eight patients presented with delayed motor development, muscle weakness, hypotonia, and a myopathic face with high palatine arches. All patients could walk independently, though with poor running and jumping, and most had a rigid spine, lordosis, or scoliosis. The symptoms of respiratory involvement were present early, and upper respiratory tract infections and pneumonia often occurred. Five patients had severe pneumonia, pulmonary hypertension, and respiratory failure. Lung function tests showed variable restrictive ventilation dysfunction. Polysomnography suggested hypoxia and hypoventilation. The serum creatine kinase (CK) level was normal or mildly increased. Muscle biopsy indicated chronic myopathic changes and minicores. Muscle magnetic resonance imaging (MRI) showed diffuse fatty infiltration of the gluteus maximus and thigh muscle. SEPN1 gene analysis revealed 16 compound heterozygous variants, 81.3% of which are unreported, including 7 exon 1 variants. Our study expands the spectrum of clinical and genetic findings in RSMD1 to improve diagnosis, management, and standards of care. SEPN1 mutations in exon 1 are common and easily missed, and exon 1 should be carefully analyzed when RSMD1 is suspected, which will provide valuable genetic counseling for the family and useful information for future natural history studies and clinical trials.


MDP SPECT/CT Demonstration of Baastrup Disease.
We report the MDP SPECT/CT findings of Baastrup disease in the interspinal region of L4 to L5 in a 76-year-old woman with a history of lung cancer. Baastrup disease, also known as "kissing" spine, is characterized by close contact of adjacent spinous processes with resultant enlargement, flattening, and reactive sclerosis of apposing interspinous surfaces. Knowledge regarding the appearance of Baastrup disease on 99mTc-MDP SPECT/CT is important to distinguish it from spinal bone metastasis.


A Systematic Review of Physical Examination Components Adapted for Telemedicine.
Introduction: The COVID-19 pandemic ushered in a rapid, transformative adoption of telemedicine to maintain patient access to care. As clinicians made the shift from in-person to virtual practice, they faced a paucity of established and reliable clinical examination standards for virtual care settings. In this systematic review, we summarize the accuracy and reliability of virtual assessments compared with traditional in-person examination tools. Methods: We searched PubMed, Embase, Web of Science, and CINAHL from inception through September 2019 and included additional studies from handsearching of reference lists. We included studies that compared synchronous video (except allowing for audio-only modality for cardiopulmonary exams) with in-person clinical assessments of patients in various settings. We excluded behavioral health and dermatological assessments. Two investigators abstracted data using a predefined protocol. Results: A total of 64 studies were included and categorized into 5 clinical domains: neurological (N = 41), HEENT (head, eyes, ears, nose, and throat; N = 5), cardiopulmonary (N = 5), musculoskeletal (N = 8), and assessment of critically ill patients (N = 5). The cognitive assessment within the neurological exam was by far the most studied (N = 19) with the Mini-Mental Status Exam found to be highly reliable in multiple settings. Most studies showed relatively good reliability of the virtual assessment, although sample sizes were often small (<50 participants). Conclusions: Overall, virtual assessments performed similarly to in-person exam components for diagnostic accuracy but had a wide range of interrater reliability. The high heterogeneity in population, setting, and outcomes reported across studies render it difficult to draw broad conclusions on the most effective exam components to adopt into clinical practice. Further work is needed to identify virtual exam components that improve diagnostic accuracy.


Common-path and compact wavefront diagnosis system based on cross grating lateral shearing interferometer.
A common-path and compact wavefront diagnosis system for both continuous and transient wavefronts measurement is proposed based on cross grating lateral shearing interferometer (CGLSI). Derived from the basic CGLSI configuration, this system employs an aplanatic lens to convert the wavefront under test into a convergent beam, which makes it possible for CGLSI to test the wavefront of collimated beams. A geometrical optics model for grating pitch determination and a Fresnel diffraction model for order selection mask design are presented. Then a detailed analysis about the influence of the grating pitch, the distance from the cross grating to the order selection mask and the numerical aperture of the aplanatic lens on the system error is made, and a calibration method is proposed to eliminate the system error. In addition, the differential Zernike polynomials fitting method is introduced for wavefront retrieval. Before our experiment, we have designed several grating pitches and their corresponding order selection mask parameters. In the final comparative experiment with ZYGO interferometer, the wavefront diagnosis system exhibits both high precision and repeatability.


Effects of the neurogranin variant rs12807809 on thalamocortical morphology in schizophrenia.
Although the genome wide supported psychosis susceptibility neurogranin (NRGN) gene is expressed in human brains, it is unclear how it impacts brain morphology in schizophrenia. We investigated the influence of NRGN rs12807809 on cortical thickness, subcortical volumes and shapes in patients with schizophrenia. One hundred and fifty six subjects (91 patients with schizophrenia and 65 healthy controls) underwent structural MRI scans and their blood samples were genotyped. A brain mapping algorithm, large deformation diffeomorphic metric mapping, was used to perform group analysis of subcortical shapes and cortical thickness. Patients with risk TT genotype were associated with widespread cortical thinning involving frontal, parietal and temporal cortices compared with controls with TT genotype. No volumetric difference in subcortical structures (hippocampus, thalamus, amygdala, basal ganglia) was observed between risk TT genotype in patients and controls. However, patients with risk TT genotype were associated with thalamic shape abnormalities involving regions related to pulvinar and medial dorsal nuclei. Our results revealed the influence of the NRGN gene on thalamocortical morphology in schizophrenia involving widespread cortical thinning and thalamic shape abnormalities. These findings help to clarify underlying NRGN mediated pathophysiological mechanisms involving cortical-subcortical brain networks in schizophrenia.


An open trial targeting emotional eating among adolescents with overweight or obesity.
Emotional eating is associated with obesity and disordered eating in adolescents, and thus, is an important target for treatment. We developed a program called PEER (Preventing Emotional Eating Routines), which incorporates emotion regulation skills with behavioral weight loss and parenting techniques for adolescents who are overweight or obese (OW/OB) and their parent. This open label trial evaluated the feasibility, acceptability, and initial efficacy of the PEER program. Thirty adolescents who were OW/OB (86.7% female; mean age = 14.6 years (SD = 1.2); Body Mass Index (BMI) = 34.0 kg/m2 (SD = 5.6); 33.3% White non-Hispanic) and their parent (66.7% biological mother) participated in a 4-month treatment and 3-month follow-up. The PEER program was well accepted. Initial efficacy showed significant decreases in emotional eating, and there were trends towards weight loss and a decrease in emotion dysregulation. This trial provides preliminary evidence for the feasibility, acceptability, and initial efficacy of the PEER program among adolescents who are OW/OB and their parent. Further treatment development and randomized controlled studies are needed.


Predicting the risks of venous thromboembolism versus post-pancreatectomy haemorrhage: analysis of 13,771 NSQIP patients.
The fear of an early post-pancreatectomy haemorrhage (PPH) may prevent surgeons from prescribing post-operative venous thromboembolism (VTE) chemoprophylaxis. The primary hypothesis of this study was that the national post-pancreatectomy early PPH rate was lower than the rate of VTE. The secondary hypothesis was that patients at high risk for post-discharge VTE could be identified, potentially facilitating the selective use of extended chemoprophylaxis. All elective pancreatectomies were identified in the 2005 to 2010 American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) database. Factors associated with 30-day rates of (pre- versus post-discharge) VTE, early PPH (transfusions > 4 units within 72 h) and return to the operating room (ROR) with PPH were analysed. Pancreaticoduodenectomies (PD) and distal pancreatectomies (DP) numbered 9140 (66.4%) and 4631 (33.6%) out of 13 771 pancreatectomies, respectively. Event rates included: VTE (3.1%), PPH (1.1%) and ROR+PPH (0.7%). PD and DP had similar VTE rates (P > 0.05) with 31.9% of VTE occurring post-discharge. Independent risk factors for late VTE included obesity [odds ratio (OR), 1.5], age ≥ 75 years (OR, 1.8), DP (OR, 2.4) and organ space infection (OR, 2.1) (all P < 0.02). Within current practice patterns, post-pancreatectomy VTE outnumber early haemorrhagic complications, which are rare. The fear of PPH should not prevent routine and timely post-pancreatectomy VTE chemoprophylaxis. Because one-third of VTE occur post-discharge, high-risk patients may benefit from post-discharge chemoprophylaxis.


Utility of Sonoclot in Prediction of Postoperative Bleeding in Pediatric Patients Undergoing Cardiac Surgery for Congenital Cyanotic Heart Disease: A Prospective Observational Study.
To assess the utility of Sonoclot in prediction of postoperative bleeding in pediatric patients undergoing cardiac surgery with cardiopulmonary bypass for congenital cyanotic heart disease. Prospective, observational study. Single university hospital. Eighty-seven pediatric patients undergoing cardiac surgery for congenital cyanotic heart disease. Laboratory coagulation parameters (prothrombin time, international normalization ratio, activated partial thromboplastin time, fibrinogen, D-dimer) as well as point-of-care Sonoclot glass bead activation time, clot rate, and platelet function (gbPF) were done before induction of anesthesia and following heparin reversal after termination of cardiopulmonary bypass (CPB) in all patients. Postoperative blood loss was monitored by the amount of chest tube drainage. The primary outcome was to define Sonoclot parameters for prediction of postoperative bleeding. Secondary outcomes studied were amount of postoperative blood loss, transfusion requirement of various blood products, incidence of surgical re-exploration, duration of postoperative mechanical ventilation, intensive care unit and hospital stay. Among studied subjects, 37.9% (33 of 87 patients) were designated as bleeders while 62.1% (54 of 87 patients) were non-bleeders. Lower age, D-dimer, and gbPF test after termination of CPB following heparin neutralization were predictive for postoperative bleeders. Among these, post-protamine gbPF had the highest area under the curve (0.725), 95% confidence interval (0.619-0.831) for prediction of postoperative bleeders. Duration of mechanical ventilation (26.41±36.44 v 8.25±6.36 h, respectively, p = 0.001), intensive care unit stay (7.36 ± 4.05 v 4.96 ± 2.49, p = 0.001), and hospital stay (11.69±4.82 v 8.63±3.48 p = 0.001) were higher in bleeders; however, incidence of re-exploration was comparable between both groups. Postoperative bleeders may be predicted independently by post-CPB gbPF, postoperative D-dimer, and lower age of patients. Among these, post-CPB gbPF has maximum predictive value.


Initiation of reflex glottic closure.
Review of the literature reveals scant information regarding the initiation of reflex glottic closure. Using the adult cat as our experimental model, we have attempted to analyze both the ipsilateral and crossed laryngeal adductor responses involved in reflex closure of the glottis. These ipsilateral and crossed reflexes are particularly well developed in the cat allowing their study with relative ease. From multifiber and single unit recurrent laryngeal nerve preparations, detailed descriptions of both peripheral and central neural organizations of these reflexes may be obtained. These data further elucidate the mechanism for initial incoordination of the glottic closure reflex, resulting from weak stimulus applied simultaneously to both superior laryngeal nerves, or from unilateral superior laryngeal denervation due to surgical trauma, metabolic neuropathy, or direct tumor involvement.


Brief Report: Developmental Trajectories of Adaptive Behavior in Children and Adolescents with ASD.
Research suggests that individuals with autism spectrum disorder (ASD) have significant difficulties with adaptive behavior skills including daily living and functional communication skills. Few studies have examined the developmental trajectory of adaptive behavior across childhood and adolescence. The present study examined longitudinal trajectories of adaptive behavior in a community-based clinic sample of 186 individuals with ASD. The overall pattern indicated an initial increase in adaptive behavior during early childhood followed by a plateau in skills during adolescence for individuals of all IQ groups. Given the importance of adaptive behavior for employment and quality of life, this study emphasizes the importance of targeting adaptive behavior during adolescence to insure continued gains.


Validity and Reliability of the Brazilian Version of the Weight Control Behaviors Scale.
To develop and validate the weight-control behaviors (WCBs) scale and to evaluate its psychometric properties. We made use of data from a cluster-randomized trial assessing the effectiveness of the Brazilian New Moves Program. The Brazilian New Moves Program was a multicomponent intervention aimed at preventing weight-related problems among adolescent girls in public schools in São Paulo, Brazil. Healthy and unhealthy WCBs were strongly associated. A 2-factor solution was the best model to explain the correlation across items, including following constructs: (1) healthy WCB: exercising, eating more fruits and vegetables, drinking less regular soda or sweetened drinks, eating fewer sweets, and paying attention to portion sizes; and (2) unhealthy WCB: skipping meals and the presence of any other, combined unhealthy weight-control behaviors, including fasting, eating little, going on a diet, vomiting, taking diet pills, using diuretics (water pills), using laxatives, using food substitutes (powder/special drinks), and smoking more cigarettes. The WCB scale was determined to be reliable (internally consistent) and valid, with high scores positively associated with body dissatisfaction and high body mass index values. Individual reliability values were high for factors representing healthy and unhealthy WCBs. Our findings support the use of the WCB scale as a screening tool for overall weight control behaviors among female adolescents. This assessment tool should be considered in future observational and experimental prospective studies. Brazilian Registry of Clinical Trials: RBR-6ddpb3.


[Purification of mammalian orthoreovirus serotype 3 Dearing Sigma1 protein and preparation of polyclonal antibody].
Objective To prepare T3Dsigma1 polyclonal antibody with purified sigma1 fusion protein of mammalian orthoreovirus (MRV) serotype 3 Dearing (T3D). Methods The recombinant plasmid T3DS1-pET28a was transformed into Rosetta (DE3) competent cells, and the isopropyl-β-D-thiogalactopyranoside (IPTG) was used to induce a large amount of target proteins which were subjected to purification by histidine-tagged Ni-IDA chromatography column to obtain the T3Dsigma1 fusion protein. New Zealand white rabbits were immunized with the purified protein to prepare polyclonal antibodies specific against sigma1 protein. The titer of polyclonal antibody was detected by indirect ELISA, and the specificity by Western blot analysis and indirect immunofluorescence assay (IFA). Results The relative molecular mass (Mr) of T3Dsigma1 fusion protein, mainly in the form of inclusion body, was about 32 000. The fusion protein was purified by denaturation and renaturation. The polyclonal antibody with the titer greater than 1:106 was prepared by immunizing New Zealand white rabbits and detected by Western blot analysis and IFA. Conclusion The T3Dsigma1 polyclonal antibody with high titer and sensitivity was prepared.


Measurement of the energy spectrum of cosmic-ray induced neutrons aboard an ER-2 high-altitude airplane.
Crews working on present-day jet aircraft are a large occupationally exposed group with a relatively high average effective dose from galactic cosmic radiation. Crews of future high-speed commercial aircraft flying at higher altitudes would be even more exposed. To help reduce the significant uncertainties in calculations of such exposures, the atmospheric ionizing radiation (AIR) project, an international collaboration of 15 laboratories, made simultaneous radiation measurements with 14 instruments on five flights of a NASA ER-2 high-altitude aircraft. The primary AIR instrument was a highly sensitive extended-energy multisphere neutron spectrometer with lead and steel shells placed within the moderators of two of its 14 detectors to enhance response at high energies. Detector responses were calculated for neutrons and charged hadrons at energies up to 100 GeV using MCNPX. Neutron spectra were unfolded from the measured count rates using the new MAXED code. We have measured the cosmic-ray neutron spectrum (thermal to >10 GeV), total neutron fluence rate, and neutron effective dose and dose equivalent rates and their dependence on altitude and geomagnetic cutoff. The measured cosmic-ray neutron spectra have almost no thermal neutrons, a large "evaporation" peak near 1 MeV and a second broad peak near 100 MeV which contributes about 69% of the neutron effective dose. At high altitude, geomagnetic latitude has very little effect on the shape of the spectrum, but it is the dominant variable affecting neutron fluence rate, which was eight times higher at the northernmost measurement location than it was at the southernmost. The shape of the spectrum varied only slightly with altitude from 21 km down to 12 km (56-201 g cm-2 atmospheric depth), but was significantly different on the ground. In all cases, ambient dose equivalent was greater than effective dose for cosmic-ray neutrons.


Regulation of cadherin stability and turnover by p120ctn: implications in disease and cancer.
The strength of cadherin based cell-cell adhesion is modulated by signaling events that control the amount of cadherin present at the cell surface, and the clustering of cadherins into strong adhesive junctions. p120ctn has been indirectly implicated in clustering for some time, but it now appears that its main function is to regulate cadherin turnover. Forced p120 downregulation (e.g., by siRNA targeting) results in a striking dose-dependant loss of endogenous cadherins, indicating that p120 is essential for cadherin stability. These data challenge some important paradigms and suggest novel interpretations of existing data. For example, most of the effects of DN-cadherin expression can be accounted for by sequestration of p120. Thus, DN-cadherins phenocopy p120-downregulation, and a significant literature exists already that suggests consequences of p120-deficiency in disease and cancer. Moreover, p120 downregulation occurs frequently in essentially all of the major carcinoma types. Thus, it is possible that the classic observation of E-cadherin-deficiency in metastatic cancer may in some cases be due to p120 downregulation rather than better understood mechanisms acting at the level of E-cadherin transcription.


Electroacupuncture in the treatment of post-traumatic sympathetic dystrophy (Sudeck's atrophy).
Twenty patients with established post-traumatic sympathetic dystrophy were treated with electroacupuncture after physical therapy with or without oral medication had failed to produce satisfactory relief of symptoms. Of these patients 14 (70%) experienced marked and permanent improvement. No complications were encountered. The possible mechanisms involved are discussed.


Impact of browning reactions and bran pigments on color of parboiled rice.
Rice color changes from white to amber during parboiling (soaking and steaming). Color parameters indicated that, during soaking, yellow bran pigments leached out in the water. The levels of the Maillard precursors (i.e., reducing sugars (RS) and free alpha-amino nitrogen (FAN)) depended on soaking temperature and time: leaching of RS was compensated by enzymic formation for long soaking times (>60 min), while proteolytic activity was too low to compensate for FAN leaching. Rice soaking under nitrogen, oxygen, or ambient conditions and determination of polyphenol oxidase activity allowed us to conclude that the effect of enzymic color changes on the soaked rice color was rather small. Color measurements of brown and milled mildly, intermediately, and severely parboiled rice samples showed that both brown and milled rice samples were darker and more red and yellow after parboiling and that the effect depended on the severity of parboiling conditions. Furthermore, steaming affected the rice color more and in a way opposite to that observed in soaking. The changes in RS and the loss of FAN during parboiling suggested that Maillard type reactions occur during brown rice steaming. Analyses of furosine levels confirmed Maillard browning of outer bran layers and endosperm during steaming. The level of this Maillard indicator increased with the severity of parboiling conditions in both brown and milled parboiled rice. Measurements of the levels of bran pigments indicated that bran pigments diffuse into the endosperm during parboiling and contribute to the parboiled rice color.


[Chronic pulmonary heart disease and its risk factors among a worker population in Teheran].
Because of the high frequency of chronic cor pulmonale in workers admitted to the cardiology department of the Khazaneh Hospital in Teheran, we studied the clinical aspect and the risk factors of this disease in 66 male patients. The average age of patients was 56.1 years and they often had a long history of bronchitis isolated or associated with emphysema. The ECG analysis showed that most abnormalities were localized on the QRST wave. Tobacco and a polluted working environment were the factors most frequently met in our patients. The opium habit probably acted as a risk factor for chronic bronchopneumopathy, but further studies are necessary to ascertain the fact.


Highly Hydrophobic Films of Engineered Silk Proteins by a Simple Deposition Method.
Molecular engineering of protein structures offers a uniquely versatile route for novel functionalities in materials. Here, we describe a method to form highly hydrophobic thin films using genetically engineered spider silk proteins. We used structurally engineered protein variants containing ADF3 and AQ12 spider silk sequences. Wetting properties were studied using static and dynamic contact angle measurements. Solution conditions and the surrounding humidity during film preparation were key parameters to obtain high hydrophobicity, as shown by contact angles in excess of 120°. Although the surface layer was highly hydrophobic, its structure was disrupted by the added water droplets. Crystal-like structures were found at the spots where water droplets had been placed. To understand the mechanism of film formation, different variants of the proteins, the topography of the films, and secondary structures of the protein components were studied. The high contact angle in the films demonstrates that the conformations that silk proteins take in the protein layer very efficiently expose their hydrophobic segments. This work reveals a highly amphiphilic nature of silk proteins and contributes to an understanding of their assembly mechanisms. It will also help in designing diverse technical uses for recombinant silk.


POPULATION GENETIC STRUCTURE OF CECROPIA OBTUSIFOLIA, A TROPICAL PIONEER TREE SPECIES.
Theoretical analyses of the genetic organization of pioneer species have postulated two very different scenarios. Some models have predicted that such species would show strong population substructuring, whereas other models have suggested that extinction and recolonization can augment gene flow and reduce interpopulation differentiation. We tested these alternative scenarios by analyzing the genetic structure of eight loci from populations of the pioneer dioecious tree, Cecropia obtusifolia, in the tropical rain forest region of Los Tuxtlas, México. The populations studied exhibit low overall FST values, no clear pattern of isolation by distance, and high estimates of gene flow. These results suggest either that the species is not at a genetic equilibrium under present levels of gene flow with populations derived from each other in the recent past, or that pollen and seed dispersal in this species occur over long distances (up to more than 100 km). Mating among relatives appears higher than expected by chance based on significantly positive fixation indices (F) and FIS values at some loci. However, no direct evidence for biparental inbreeding was found. The multilocus and single-locus outcrossing rates for C. obtusifolia were estimated at tm = 0.974 (SE = 0.024) and ts = 0.980 (SE = 0.035), respectively. These are not significantly different from 1, and the difference, tm - ts = - 0.006 (SE = 0.018), is not significantly different from 0. These estimates, however, could be biased because in all enzymes, except PGM-1, we found statistically significant departures from the mixed-mating model used to estimate them. Two rare alleles were found only in seeds collected from the soil, and the greatest number of different alleles were found also in soil seeds. It is hypothesized that the seed bank may play an important role in the genetic buffering of C. obtusifolia. Significantly positive or negative fixation indices in adults at some loci and significantly different heterozygosities among different life stages (from seeds to adults) suggest the action of selection at some loci.


Biochemical analysis of HIV-1 integrase variants resistant to strand transfer inhibitors.
In this study, eight different HIV-1 integrase proteins containing mutations observed in strand transfer inhibitor-resistant viruses were expressed, purified, and used for detailed enzymatic analyses. All the variants examined were impaired for strand transfer activity compared with the wild type enzyme, with relative catalytic efficiencies (k(p)/K(m)) ranging from 0.6 to 50% of wild type. The origin of the reduced strand transfer efficiencies of the variant enzymes was predominantly because of poorer catalytic turnover (k(p)) values. However, smaller second-order effects were caused by up to 4-fold increases in K(m) values for target DNA utilization in some of the variants. All the variants were less efficient than the wild type enzyme in assembling on the viral long terminal repeat, as each variant required more protein than wild type to attain maximal activity. In addition, the variant integrases displayed up to 8-fold reductions in their catalytic efficiencies for 3'-processing. The Q148R variant was the most defective enzyme. The molecular basis for resistance of these enzymes was shown to be due to lower affinity binding of the strand transfer inhibitor to the integrase complex, a consequence of faster dissociation rates. In the case of the Q148R variant, the origin of reduced compound affinity lies in alterations to the active site that reduce the binding of a catalytically essential magnesium ion. Finally, except for T66I, variant viruses harboring the resistance-inducing substitutions were defective for viral integration.


Formation of a Cubic Liquid Crystalline Nanostructure with π-Conjugated Fluorinated Rods on the Gyroid Minimal Surface.
Bicontinuous cubic phases are of significant importance for numerous applications, for example, for the crystallization of membrane proteins, as photonic materials and as templates for porous silica. A new variant of bicontinuous cubic liquid crystalline phase with Ia3‾ d lattice is reported herein for X-shaped bolapolyphiles. It was shown that in this class of compounds, cubic-phase induction can be achieved by proper aromatic core fluorination; in addition, the first cubic phases having π-conjugated oligo(phenylene ethynylene) rods on the gyroid minimal surface were obtained. These new structures composed of 3D folded layers of parallel arranged π-conjugated rods should allow charge transport in all three dimensions, which is of interest for organic semiconductor applications.


Exosomes derived from neural progenitor cells preserve photoreceptors during retinal degeneration by inactivating microglia.
Retinal degeneration (RD) is one of the most common causes of visual impairment and blindness and is characterized by progressive degeneration of photoreceptors. Transplantation of neural stem/progenitor cells (NPCs) is a promising treatment for RD, although the mechanisms underlying the efficacy remain unclear. Accumulated evidence supports the notion that paracrine effects of transplanted stem cells is likely the major approach to rescuing early degeneration, rather than cell replacement. NPC-derived exosomes (NPC-exos), a type of extracellular vesicles (EVs) released from NPCs, are thought to carry functional molecules to recipient cells and play therapeutic roles. In present study, we found that grafted human NPCs (hNPCs) secreted EVs and exosomes in the subretinal space (SRS) of RCS rats, an RD model. And direct administration of mouse neural progenitor cell-derived exosomes (mNPC-exos) delayed photoreceptor degeneration, preserved visual function, prevented thinning of the outer nuclear layer (ONL), and decreased apoptosis of photoreceptors in RCS rats. Mechanistically, mNPC-exos were specifically internalized by retinal microglia and suppressed their activation in vitro and in vivo. RNA sequencing and miRNA profiling revealed a set of 17 miRNAs contained in mNPC-exos that markedly inhibited inflammatory signal pathways by targeting TNF-α, IL-1β, and COX-2 in activated microglia. The exosomes derived from hNPC (hNPC-exos) contained similar miRNAs to mNPC-exos that inhibited microglial activation. We demonstrated that NPC-exos markedly suppressed microglial activation to protect photoreceptors from apoptosis, suggesting that NPC-exos and their contents may be the mechanism of stem cell therapy for treating RD.


Telomere metabolism and diagnostic demonstration of telomere measurement in the human esophagus for distinguishing benign from malignant tissue by tissue quantitative fluorescence in situ hybridization.
We have developed a novel method for evaluating telomere length in four different cell types in non-cancerous and cancerous mucosal tissue from 15 cases of squamous cell carcinoma of the esophagus using tissue quantitative fluorescence in situ hybridization (Q-FISH). We hypothesized that the very rapid cell proliferation observed in esophageal squamous cell carcinomas might accelerate the telomere shortening and chromosomal instability associated with carcinogenesis. Tissue Q-FISH and the telomere to centromere intensity ratio (TCR) were used to compare telomere shortening in tissue sections taken from esophageal squamous cell carcinomas and adjacent non-cancerous esophageal tissues. The peak percentage of TCR was <1 for esophageal squamous carcinoma cells and >1 for the non-cancerous esophageal cell types. Basal layer cells had the longest telomeres in comparison with prickle, cancer, and stromal cells, and strongly expressed hTERT, cytokeratin 14 and CD49f, but not MIB-1. These results suggest the presence of stem cells in the basal layer of the esophagus. Esophageal squamous cell carcinomas also display anaphase bridges, evidencing chromosomal instability. In conclusion, our TCR method can be used to distinguish between benign and malignant tissue in esophageal lesions. In order to apply this approach clinically to individual cases, further studies are in progress.


Characterization of a human hematopoietic progenitor cell capable of forming blast cell containing colonies in vitro.
A hematopoietic cell (CFU-B1) capable of producing blast cell containing colonies in vitro was detected using a semisolid culture system. The CFU-B1 has the capacity for self-renewal and commitment to a number of hematopoietic lineages. Monoclonal antibody to the human progenitor cell antigen-1 (HPCA-1) and a monoclonal antibody against the major histocompatibility class II antigen (HLA-DR) were used with fluorescence activated cell sorting to phenotype the CFU-B1. The CFU-B1 was found to express My10 but not HLA-DR antigen; experiments using complement-dependent cytotoxicity to eliminate DR positive cells confirmed this finding. Pretreatment of marrow cells with two chemotherapeutic agents, 5-fluorouracil and 4-hydroperoxycyclophosphamide facilitated detection of CFU-B1 derived colonies, while diminishing or totally inhibiting colony formation by other hematopoietic progenitor cells. CFU-B1-derived colony formation was dependent upon the addition of exogenous hematopoietic growth factors. Media conditioned either by the human bladder carcinoma cell line 5637 or lectin stimulated leukocytes, as well as recombinant granulocyte-macrophage colony stimulating factor, interleukin 3 or interleukin 1 alpha promoted blast cell colony formation. By contrast, neither recombinant erythropoietin, recombinant interleukin 4, purified macrophage colony stimulating factor or recombinant granulocyte colony-stimulating factor alone promoted blast cell colony formation.


A comprehensive investigation on pan-cancer impacts of constitutive centromere associated network gene family by integrating multi-omics data: A CONSORT-compliant article.
The constitutive centromere associated network (CCAN) complex played a critical role in connecting the centromere with the mitotic spindle during mitosis and meiosis. Many studies have indicated that CCAN is related to the tumorigenesis and cancer development. Nonetheless, the overview of CCAN gene family in pan-cancer remain incompletely understood. We performed a comprehensive investigation on pan-cancer impacts of CCAN by integrating multi-omics data. We comprehensively investigated the expression profile, kyoto encyclopedia of genes and genomes (kegg) pathway, mutation, copy number variation, tumor microenvironment, immune cells infiltration, and drug sensitivity of CCAN in pan-cancer. MRNA expression profiles were collected from the cancer genome atlas, oncomine and ccle, the differential expression and various relevance analysis were performed with R or Perl. The results showed that the expression of CCAN was different in 33 tumors. Intriguingly, the poor survival in adrenocortical carcinoma, cholangiocarcinoma, kidney chromophobe, mesothelioma, kidney renal clear cell carcinoma, brain lower grade glioma, pheochromocytoma and paraganglioma, prostate adenocarcinoma, thyroid carcinoma, uveal melanoma was most likely related to the kegg single transduction pathway including one carbon pool by folate, proteasome, arachidonic acid metabolism and so on. CENPC, ITGB3BP, APITD1, CENPU, and CENPW were more involved in tumor microenvironment, which more likely related to NK cells resting, T cells follicular helper, T cells CD8, neutrophils, macrophages M0, T cells CD4 memory activated. The relationship of CCAN expression with drug sensitivity showed that chelerythrine, nelarabine, and hydroxyurea maybe be potential drugs. This multidimensional study provides a valuable resource to assist mechanism research and clinical utility about CCAN.


Antiplatelet therapy after percutaneous coronary intervention.
Antiplatelet therapy is key to reducing local thrombotic complications and systemic ischaemic events among patients undergoing percutaneous coronary interventions (PCI), but it is inevitably associated with increased bleeding. The continuous refinement in stent technologies, together with the high incidence of ischaemic recurrences after PCI and the understanding of prognostic implications associated with bleeding, have led to a substantial evolution in antiplatelet treatment regimens over the past decades. Numerous investigations have been conducted to better stratify patients undergoing PCI according to their ischaemic and bleeding risks and to implement antithrombotic regimens accordingly. Evidence from these investigations have resulted in a number of antithrombotic treatment options as recommended by recent guidelines. In this State-of-the-Art review we provide the rationale, summarise the evidence, and discuss current and future directions of antiplatelet treatment regimens after PCI.


Conscience and conscientious actions in the context of MCOs.
Managed care organizations can produce conflicts of obligation and conflicts of interest that may lead to problems of conscience for health care professionals. This paper provides a basis for understanding the notions of conscience and conscientious objection and offers a framework for clinicians to stake out positions grounded in personal conscience as a way for them to respond to unacceptable pressures from managers to limit services.


Effects of scaling and root planing and subantimicrobial dose doxycycline on gingival crevicular fluid levels of matrix metalloproteinase-8, -13 and serum levels of HsCRP in patients with chronic periodontitis.
This study evaluates the efficacy of subantimicrobial dose doxycycline (SDD) in conjunction with scaling and root planing (SRP) on gingival crevicular fluid (GCF) levels of matrix metalloproteinase (MMP)-8 and -13 and on serum levels of high-sensitivity C-reactive protein (HsCRP) in patients with chronic periodontitis (CP). A total of 41 patients with CP and 17 healthy individuals were included in this randomized controlled trial. CP patients were randomly distributed into two groups. Study groups were established as Group I with SRP+placebo, Group II with SRP+SDD, and Group III as control. All CP patients received two regimens of SRP and Group II patients also received SDD for 6 weeks. At baseline and 6 weeks, GCF and blood were collected and clinical indices were recorded. The HsCRP level was assayed in the plasma on a nephelometer. The GCF levels of MMPs were assayed by an enzyme-linked immunosorbent assay. Statistically significant differences in plaque index, gingival index (GI), probing depth (PD), GCF volumes, GCF MMP levels, and serum levels of HsCRP between pre-treatment and post-treatment were noted in both groups. Between groups there was a statistically significant decrease in PD, GI, and GCF levels of MMP-8 favoring the group receiving SDD adjunctive to SRP (P <0.05). In this study, greater improvement was detected for PD, GI, and GCF levels of MMP-8 when using SRP+SDD compared to SRP+placebo.