Surface-enhanced Raman scattering for perchlorate detection using cystamine-modified gold nanoparticles.
Perchlorate (ClO4-) has recently emerged as a widespread environmental contaminant found in groundwater and surface water, and there is a great need for rapid detection and monitoring of this contaminant. This study presents a new technique using cystamine-modified gold nanoparticles as a substrate for surface-enhanced Raman scattering (SERS) detection of perchlorate at low concentrations. A detection limit of 5x10(-6) M (0.5 mg/L) has been achieved using this method without sample preconcentration. This result was attributed to a strong plasmon enhancement by gold metal surfaces and the electrostatic attraction of ClO4- onto positively charged, cystamine-modified gold nanoparticles at a low pH. The methodology also was found to be reproducible, quantitative, and not susceptible to significant interference from the presence of anions such as sulfate, phosphate, nitrate and chloride at concentrations <1 mM, making it potentially suitable for rapid screening and routine analysis of perchlorate in environmental samples.


A clinical evaluation of N-5' with perennial-type allergic rhinitis--a test by the multi-clinic, intergroup, double-blind comparative method.
N-(3,4-dimethoxycinnamoyl) anthranilic acid (N-5'), a new orally useable mast cell stabilizer, was investigated for its efficacy, safety and usefulness in the treatment of 302 patients with perennial nasal allergy by an intergroup, double-blind comparative test using disodium cromoglycate (DSCG) and an inactive placebo as control. The results indicated that N-5', as a mild mast cell stabilizer, was comparable to DSCG in efficacy and minimum in side effect.


Nanoscale Photocatalytic Activity of Gold and Gold-Palladium Nanostructures Revealed by Tip-Enhanced Raman Spectroscopy.
The new paradigm of solid-state catalysis is that coupling of plasmonic and catalytic metals can be used to achieve much higher catalytic efficiency relative to their counterparts. Chemical reactions on such bimetallic nanostructures are light-driven, which essentially enables "green catalysis" in organic synthesis. The catalytic efficiency of bimetallic platforms directly depends on their nanoscale structures, which remain poorly understood. We used tip-enhanced Raman spectroscopy (TERS) to investigate nanoscale plasmonic and photocatalytic properties of novel gold-palladium microplates (Au@PdMPs), along with their monometallic counterparts. We found that 4-nitrobenzenethiol (4-NBT) can be catalyzed to p,p'-dimercaptoazobisbenzene (DMAB) and 4-aminothiophenol (4-ATP) on Au@PdMPs, whereas monometallic AuMPs produce exclusively DMAB as a result of such photocatalytic reduction of 4-NBT. Using 4-NBT as a molecular reporter, we found that the efficiency of these catalytic reactions has strong correlation with the nanoscale structure of microplates. Coupling TERS to GC-MS, we also found that Au@PdMPs were capable of catalyzing the Suzuki-Miyaura coupling reaction.


[Duties, rights and activity monitoring of the head of a medical organization worldwide].
The quality of medical care in a medical organization is largely determined by the effectiveness of its Head. The article looks at current regulatory acts, main factors of healthcare organization process in developed countries (France, Switzerland, Australia and South Korea) and methods for assessing the quality of health services. This work analyzes the world practice of appointment, functioning and activity effectiveness of the heads of healthcare system.


Concise synthesis and antiangiogenic activity of artemisinin-glycolipid hybrids on chorioallantoic membranes.
Novel hybrids of non acetal and acetal-type derivatives at C-12 of artemisinin and glycolipids were synthesized via efficient coupling reactions. Some of these hybrids showed potent in vivo antiangiogenic activity on the chorioallantoic membrane (CAM) that was higher than or comparable to those of fumagillin and thalidomide at a concentration of 2.5 nmol.


Allelopathic effects of Pakistani weeds: Euphorbia granulata Forssk.
The aqueous extract of Euphorbia granulata Forssk., prepared in Hoagland's nutrient solution; and underlying soil significantly inhibited germination and radicle growth of Dichanthium annulatum, Cynodon dactylon, Setaria italica, Pennisetum americanum, Euphorbia pilulifera, Oxalis corniculata and Lactuca sativa invariably in laboratory bioassays. Artificially decomposed E. granulata litter in a nutrient medium significantly reduced germination and fresh and dry weight of the aforementioned test species. The toxins affected germination and growth independently. The local dominance of this weed over its counterparts was primarily due to allelopathy, and it is therefore suggested that its litter must be removed from the fields during weeding.


Differentiating between benign follicular nodules and follicular neoplasms in thyroid liquid-based cytology preparations.
The cytological morphology observed in liquid-based cytology (LBC) preparations is dissimilar to that of conventional preparations. The aim of this report is to clarify the cytological differences between benign follicular nodules (BFNs) and follicular neoplasms (FNs) in LBC preparations and identify novel diagnostic criteria for LBC preparations. A retrospective review of LBC preparations from 38 BFN and 74 FN (57 follicular adenomas and 17 follicular carcinomas) cases confirmed by histological examination was conducted. LBC samples were obtained from the washout fluid in aspiration needles, fixed with CytoRich-RED(TM) , and prepared using the SurePath(TM) method. Fibrin was observed in 43.2% of FNs and in 23.7% of BFNs. The incidences of intercellular spaces, distinct outer margin, and cytoplasmic process were significantly higher in BFNs (P < 0.01, P < 0.01, and P < 0.05, respectively). Elongated microfollicles were seen in 55.4% of FNs and 10.5% of BFNs (P < 0.01). Membranous materials encircling the outer edge of the follicles were observed only in BFN cases (5.8%). There were no significant differences between follicular adenoma and carcinoma. Intercellular spaces, distinct outer margins of the follicular clusters, cytoplasmic process, and membranous materials constitute indicators of BFN in LBC preparations. Fibrin and elongated microfollicles point to FN. We believe that these findings will improve the diagnostic accuracy of thyroid LBC preparations. Diagn. Cytopathol. 2016;44:659-664. © 2016 Wiley Periodicals, Inc.


Targeting focal adhesion kinase in fibrotic diseases.
Fibrotic diseases such as idiopathic pulmonary fibrosis or scleroderma (systemic sclerosis) are chronic fibroproliferative disorders for which there are currently no effective treatments. Dysregulated normal tissue repair process is considered to cause a fibrotic response culminating in compromised organ function due to excess extracellular matrix deposition. The mechanisms underlying the pathophysiology of fibrosis are poorly understood. Recent findings suggest that focal adhesion kinase (FAK) plays a key role in development of fibrotic disorders, and it appears to be an attractive target for antifibrotic therapy. Here, we review the emerging role of FAK as a key regulator of fibrotic signaling and its potential as a future therapeutic target to counteract fibrosis.


Escherichia coli cyclomodulin Cif induces G2 arrest of the host cell cycle without activation of the DNA-damage checkpoint-signalling pathway.
The cycle inhibiting factor (Cif) belongs to a family of bacterial toxins and effector proteins, the cyclomodulins, that deregulate the host cell cycle. Upon injection into HeLa cells by the enteropathogenic Escherichia coli (EPEC) type III secretion system, Cif induces a cytopathic effect characterized by the recruitment of focal adhesion plates and the formation of stress fibres, an irreversible cell cycle arrest at the G(2)/M transition, and sustained inhibitory phosphorylation of mitosis inducer, CDK1. Here, we report that the reference typical EPEC strain B171 produces a functional Cif and that lipid-mediated delivery of purified Cif into HeLa cells induces cell cycle arrest and actin stress fibres, implying that Cif is necessary and sufficient for these effects. EPEC infection of intestinal epithelial cells (Caco-2, IEC-6) also induces cell cycle arrest and CDK1 inhibition. The effect of Cif is strikingly similar to that of cytolethal distending toxin (CDT), which inhibits the G(2)/M transition by activating the DNA-damage checkpoint pathway. However, in contrast to CDT, Cif does not cause phosphorylation of histone H2AX, which is associated with DNA double-stranded breaks. Following EPEC infection, the checkpoint effectors ATM/ATR, Chk1 and Chk2 are not activated, the levels of the CDK-activating phosphatases Cdc25B and Cdc25C are not affected, and Cdc25C is not sequestered in host cell cytoplasm. Hence, Cif activates a DNA damage-independent signalling pathway that leads to inhibition of the G(2)/M transition.


Mixed-type autoimmune hemolytic anaemia presenting as multiple thromboses: A case report.
Autoimmune hemolytic anaemia (AIHA) is a heterogenous disorder characterised by the presence of IgG or IgM pathological autoantibodies that target antigens of erythrocytes resulting in active hemolysis. Case presentation: A 40-year-old gentleman presented to a medical centre with chest pain and right sided hemiparesis for a week. He was pale and jaundiced. The power of the right upper and lower limbs was 3/5. His spleen was palpable. His complete blood count revealed macrocytic anaemia of 7.6 g/dL. The brain Magnetic Resonance Imaging (MRI) showed left fronto-parietal infarction. The right cardiac and left carotid angiogram revealed thromboses involving the right coronary and left internal carotid artery respectively. At the cardiology department, he was transfused with two units of red blood cells without his anemia being investigated and a stent was deployed to the left internal carotid artery. He was referred to the hematology department in which his peripheral blood smear revealed hemolysis and his direct antiglobulin test was positive. He responded to a course of steroids and direct oral anticoagulation and is in complete remission for the past 18 months. Conclusion: It is always imperative to investigate the cause of anaemia and consider hemolysis in a patient presenting with multiple unexplained thromboses.


Association of Infant Feeding Characteristics With Dietary Patterns and Obesity in Korean Childhood.
Young children's feeding characteristics can play an important role in eating habits and health during later childhood. This study was conducted to examine the associations of feeding characteristics with dietary patterns and obesity in children. This study utilized data from the Korea National Health and Nutrition Examination Survey conducted between 2013 and 2017. In total, 802 toddlers were included, with information on their demographic characteristics, feeding practices and duration, and 24-hour recall obtained from their parents. Feeding characteristics were categorized into feeding type, duration of total breastfeeding, duration of total formula feeding, duration of exclusive breastfeeding, and age when starting formula feeding. Dietary patterns were identified based on factor loadings for the food groups for 3 major factors, with "vegetables & traditional," "fish & carbohydrates," and "sweet & fat" patterns. Overweight/obesity was defined as ≥85th percentile in body mass index based on the 2017 Korean National Growth charts for children and adolescents. Multiple regression analysis was conducted to examine associations between feeding characteristics and dietary patterns. The association between dietary patterns and obesity was analyzed using multivariable logistic regression analysis. The early introduction of formula feeding was inversely associated with the "vegetables & traditional" pattern (β=-0.18; 95% confidence interval [CI], -0.34 to -0.02). A higher "vegetables & traditional" intake was associated with a lower risk of obesity (odds ratio, 0.48; 95% CI, 0.24 to 0.95). Feeding characteristics are associated with dietary patterns in later childhood, and dietary patterns were shown to have a potential protective association against obesity.


Topography of the pulp chamber in the maxillary primary molars of a Tunisian children.
Knowledge of the variations in pulp chamber topography is very useful to the dentist while performing endodontic access cavity in primary teeth. To determine the horizontal crown dimensions and the pulp chamber topography of shedding maxillary primary molars in a sample of Tunisian children. Forty two maxillary primary molars (24 first and 18 second molars) were used. Teeth were ultrasonically cleaned before taking morphometric measurements of the buccolingual and mesiodistal sizes. Statistical student test was used comparing the mean sizes. All the crown measurements were higher in the second molar. While the buccolingual dimension of the pulp chamber was higher in the second molar, the mesiodistal sizes were equivalent among the teeth. The thickest walls were in the buccal side of the first molar and in the mesial side of the second one. The ratio of several measurements indicate that the pulp cavity is more vestibularly and distally located in the second molar. Mesiodistal dimension of the pulp cavity is not proportional to that of the dental crown. Endodontic access cavity have to be shifted to the distal and vestibular sides from the first to the second upper molar.


Subcellular localization of glucose-6-phosphatase in animal tissues.
1. Glucose-6-phosphatase (EC 126.96.36.199 D-glucose-6-phosphate phosphohydrolase) was found to be localized mainly in the endoplasmic reticulum (microsomal fraction) of all species of vertebrate liver tissue examined. 2. Hepatopancreas tissue from gastropod molluscs was found to be unique in showing the localization of glucose-6-phosphatase in the cytosol (soluble fraction).


Phytoremediation of nitrate contamination using two halophytic species, Portulaca oleracea and Salicornia europaea.
Nitrate is a common form of nitrogen fertilizer, and its excess application combined with easy leaching from agricultural fields causes water and soil contamination, hazards on human health, and eutrophication of aquatic ecosystems. Compared to other pollutants, the application of phytoremediation technology for nitrate-contaminated sites has received less attention. Nitrophilous halophyte species are suitable candidates for this purpose particularly by application of additional treatments for assisting nitrate accumulation. In this work, two annual halophyte species, Portulaca oleracea and Salicornia europaea were studied for their phytoremediation capacity of nitrate-contaminated water and soils. Plants were treated with three nitrate levels (2, 14, and 50 mM) combined with either selenium (10 µM as Na2SeO4) or salt (100 mM NaCl) in the hydroponics and sand culture medium, respectively. A fast growth and production of higher biomass enables P. oleracea for higher nitrate removal compared with S. europaea in both experiments. In S. europaea, both selenium and salt treatments enhanced nitrate removal competence through increasing the biomass and nitrate uptake or assimilation capacity. Salt treatment, however, reduced these parameters in P. oleracea. Based on data, selenium-assisted phytoremediation of nitrate contamination is a feasible strategy for both species and S. europaea is better suited to nitrate-contaminated saline water and soils. Nitrate accumulation in both species, however, exceeds that of the permitted nitrate level in the forage crops suggesting that the phytoremediation byproducts could not be consumed and other management strategies should be applied to the residual biomass.


Measuring physical function in patients with complex medical and postsurgical conditions: a computer adaptive approach.
To examine whether the range of disability in the medically complex and postsurgical populations receiving rehabilitation is adequately sampled by the new Activity Measure--Post-Acute Care (AM-PAC), and to assess whether computer adaptive testing (CAT) can derive valid patient scores using fewer questions. Observational study of 158 subjects (mean age 67.2 yrs) receiving skilled rehabilitation services in inpatient (acute rehabilitation hospitals, skilled nursing facility units) and community (home health services, outpatient departments) settings for recent-onset or worsening disability from medical (excluding neurological) and surgical (excluding orthopedic) conditions. Measures were interviewer-administered activity questions (all patients) and physical functioning portion of the SF-36 (outpatients) and standardized chart items (11 Functional Independence Measure (FIM), 19 Standardized Outcome and Assessment Information Set (OASIS) items, and 22 Minimum Data Set (MDS) items). Rasch modeling analyzed all data and the relationship between person ability estimates and average item difficulty. CAT assessed the ability to derive accurate patient scores using a sample of questions. The 163-item activity item pool covered the range of physical movement and personal and instrumental activities. CAT analysis showed comparable scores between estimates using 10 items or the total item pool. The AM-PAC can assess a broad range of function in patients with complex medical illness. CAT achieves valid patient scores using fewer questions.


Capture and purification of Human Immunodeficiency Virus-1 virus-like particles: Convective media vs porous beads.
Downstream processing (DSP) of large bionanoparticles is still a challenge. The present study aims to systematically compare some of the most commonly used DSP strategies for capture and purification of enveloped viruses and virus-like particles (eVLPs) by using the same staring material and analytical tools. As a model, Human Immunodeficiency Virus-1 (HIV-1) gag VLPs produced in CHO cells were used. Four different DSP strategies were tested. An anion-exchange monolith and a membrane adsorber, for direct capture and purification of eVLPs, and a polymer-grafted anion-exchange resin and a heparin-affinity resin for eVLP purification after a first flow-through step to remove small impurities. All tested strategies were suitable for capture and purification of eVLPs. The performance of the different strategies was evaluated regarding its binding capacity, ability to separate different particle populations and product purity. The highest binding capacity regarding total particles was obtained using the anion exchange membrane adsorber (5.3 × 1012 part/mL membrane), however this method did not allow the separation of different particle populations. Despite having a lower binding capacity (1.5 × 1011 part/mL column) and requiring a pre-processing step with flow-through chromatography, Heparin-affinity chromatography showed the best performance regarding separation of different particle populations, allowing not only the separation of HIV-1 gag VLPs from host cell derived bionanoparticles but also from chromatin. This work additionally shows the importance of thorough sample characterization combining several biochemical and biophysical methods in eVLP DSP.


Determination of Platinum Group Elements in Particulate Matter by Inductively Coupled Plasma Mass Spectrometry.
This study examined a method for determination of rhodium (Rh), palladium (Pd) and platinum (Pt) in particulate matter using standard solutions, model samples and certified reference materials (NIST 1648a and ERM CZ120). The method was based on microwave digestion followed by inductively coupled plasma mass spectrometry (ICP-MS). The results showed that the stability of the standard solution mixture of Rh, Pd and Pt was better when chlorides were present in the solution. A membrane filter and one type of quartz filter were the most adequate for analyzing platinum group elements (PGE). Respective limits of detection for Rh, Pd and Pt were 0.028, 0.503 and 0.0265 pg/m3 with a membrane filter and 0.478, 4.530 and 0.070 pg/m3 for one type of quartz filters. The sample matrix had no significant effects on the determination of three PGEs.


Assessing alcohol abstinence self-efficacy in undergraduate students: psychometric evaluation of the alcohol abstinence self-efficacy scale.
Alcohol use is a major public health concern with respect to its impact on youth morbidity and mortality. Self-efficacy to abstain from alcohol use in young people is an important prevention and intervention strategy in future alcohol dependence. However, research on the assessment of self-efficacy to abstain from alcohol use among undergraduate students is almost non-existent in Ghana, apparently due to the unavailability of a standardised testing instrument. The purpose of this study was to examine the factor validity, structure, and reliability of the 20-item Alcohol Abstinence Self-efficacy Scale (AASES) in undergraduate students in Ghana. Two hundred and fifteen undergraduate students studying in a private university with a mean age of 23.5 years participated in the study by completing the AASES. Results of a confirmatory factor analysis showed that the data did not fit the initial four-factor AASES model. Subsequent exploratory factor analysis showed that the AASES is a unidimensional construct (in the total sample and a subsample of drinkers), contrary to findings found in western cultures. The AASES also had a high Cronbach's alpha. Although the AASES was unidimensional in this study, each of the original four-factor model also had high and acceptable Cronbach's alpha. The original AASES structure was not confirmed in this study but a unidimensional factor was found suggesting that the AASES could be used as an instrument for assessing alcohol abstinence self-efficacy in undergraduate students in Ghana, although further validation research is needed in larger as well as in different samples.


Oral vaccination with different antigens from Yersinia pestis KIM delivered by live attenuated Salmonella typhimurium elicits a protective immune response against plague.
The use of live recombinant Salmonella attenuated vaccine (RASV) encoding Yersinia proteins is a promising new approach for the vaccination against Yersinia pestis. We have tested the efficacy of 2 proteins, Psn and a portion of LcrV in protecting mice against virulent Yersinia pestis challenge. To remove the immunosuppressive properties of LcrV protein, the lcrV gene, without the TLR2 receptor sequence, was cloned into a beta-lactamase secretion vector. Immunizations were performed with RSAV expressing LcrV or Psn. Challenge with a virulent Y. pestis strain was performed 4 weeks after the last immunization. Our results show that the truncated LcrV protein delivered by RASV is sufficient to afford a full protective immune response in a mouse model of bubonic plague and the Psn protein afforded partial protection in a non-optimized system. This finding should facilitate the design and development of a new generation of vaccines against Y. pestis.


Epidemiology of pediatric tumors of the nervous system according to the WHO 2000 classification: a report of 1,195 cases from a single institution.
The purpose of this study is to determine the epidemiology of tumors of the nervous system diagnosed according to the WHO 2000 classification in a single Brazilian institution. One thousand one hundred ninety-five tumors in children between 0 and 21 years of age diagnosed between 1974 and 2003 were classified according the sex, topography, and age distribution. In all ages, males were slightly more affected. In the first 2 years, the prevalence for boys was higher (68.3%). In the whole series, 58.7% were supratentorial, 31.4% infratentorial, and 9.9% spinal (44% intra- and 56% extramedullary). Among these latter, ependymomas and schwannomas were the most frequent. In the cerebral compartment, pilocytic astrocytomas were the single most frequent tumors (18%), followed by diffuse astrocytomas (14%), medulloblastomas (11%), and craniopharyngiomas (11%). In the posterior fossa, there was an even distribution among medulloblastomas and pilocytic astrocytomas, but the former was much more frequent in the first 2 years of age. High-grade (III and IV) diffuse astrocytomas were slightly more frequent than low grades (II), and this difference becomes more evident as the child grows older. Due to the new development of the surgery of epilepsy, the frequency of neuronal and mixed neuronal-glial tumors is increasing (8%). Classified according to the latest WHO classification, by a single neuropathologist in a single institution, this large series of pediatric neurological tumors may reflect fairly well their real incidence. Our results obtained in a developing country do not differ substantially from other similar series reported in the literature from the First World.


Characterization of tick antigens inducing host immune resistance. II. Description of rabbit-acquired immunity to Amblyomma americanum ticks and identification of potential tick antigens by Western blot analysis.
Feeding by adult Amblyomma americanum ticks induced a level of immunity in rabbits to subsequent tick feeding that resulted in a significant decrease in tick feeding success and fecundity. Histological analysis of tick feeding sites in hosts expressing resistance revealed a predominant eosinophil response, with weak basophil and neutrophil infiltrates. While the basophil was never the dominant granulocyte at the tick feeding sites in resistant hosts, this cell exhibited the greatest increase in density (tenfold) over levels observed in hosts experiencing their first infestation; eosinophils and neutrophils exhibited increases of five- and twofold, respectively. Serum from animals that expressed resistance was tested for the presence of anti-tick antibodies to tick-derived salivary gland substances (SGA) by Western blotting. Western blot analysis of female-derived SGA compared to male-derived SGA, using the Avidin/Biotin technique, resulted in the identification of approximately 25 proteins from the female preparation, but only seven from the male. The use of 125I labeled protein-A as the probe for anti-tick antibody in Western blot analysis resulted in fewer recognized proteins. Serum from rabbits immunized with A. americanum-derived SGA emulsified with complete (CFA) Freund's adjuvant recognized most of the proteins identified by active serum, whereas serum from animals immunized with SGA in incomplete (IFA) Freund's adjuvant did not. Furthermore, both sera recognized a multiplicity of proteins from extracts of larval A. americanum Dermacentor variabilis and Boophilus microplus ticks, suggesting the presence of common antigens between these distantly related ticks. The results from this study demonstrate that rabbits acquire a strong immunity to A. americanum ticks characterized by the production of antibody. Furthermore, ticks secrete a number of substances into rabbits during feeding, as seen by Western blot analysis but only three may be crucial to the induction of host immunity; proteins at 41, 40 and 39 kDa. The purified anti-tick antibody will be used for subsequent isolation and characterization of crucial antigens.


Pathologic Correlation of Cellular Imaging Using Apparent Diffusion Coefficient Quantification in Patients with Brain Metastases After Gamma Knife Radiosurgery.
To evaluate the role of apparent diffusion coefficient (ADC) in differentiating radiation necrosis (RN) from recurrent tumor after Gamma Knife radiosurgery (GKRS) for brain metastases (BMs). Forty-one patients with BM who underwent surgical intervention after GKRS at Cleveland Clinic (2006-2017) were included in this retrospective study. The ADC values of the growing lesions and the contralateral hemisphere were calculated using picture archiving and communication system. These values were correlated to the percentage of RN identified on pathologic evaluation of the surgical specimen. The median age of the patients was 59 years (range, 25-86 years), and lung cancer (63.4%) was the most common malignancy. Median initial (pre-GKRS) target volume of the lesions was 5.4 cc (range, 0.135-45.6 cc), and median GKRS dose was 18.0 Gy. Surgical resection or biopsy was performed at a median of 176 days after GKRS. Two variables were statistically significant predictors of predominate RN (75%-100%) in the surgical specimen: 1) ADC of the lesion on the preresection magnetic resonance imaging (MRI) and 2) initial pre-GKRS target volume. ADC >1.5 × 10-3 mm2/s within the lesion on MRI predicted significant RN on pathologic evaluation of the lesion (P < 0.05). Similarly, when the target volume before GKRS was large (>10 cc), the risk of identifying significant necrosis in the pathologic specimen was elevated (P < 0.05). Our data suggest that the combination of lesion ADC on MRI prior to surgical intervention and the initial target volume can predict RN with reasonable accuracy.


Population genetic structure of the striped silverside, Atherinomorus endrachtensis (Atherinidae, Atheriniformes, Teleostei), inhabiting marine lakes and adjacent lagoons in Palau: marine lakes are "Islands" for marine species.
Although evidence for the evolution of terrestrial species on islands continues to rapidly accumulate, little is known about the evolution of marine species in geographically isolated environments such as islands as ocean currents often facilitate gene flow among populations. In this study, we focused on marine lakes of the Palau Islands, which are considered to be true analogues of terrestrial islands for marine species. To examine evolutionary processes in marine lakes, we conducted population genetic analyses on marine lake and lagoon populations of the striped silverside, Atherinomorus endrachtensis, using two mitochondrial DNA markers differing in evolutionary rate, the cytochrome b gene and the control region. The analyses revealed that the amount of genetic diversity of marine lake populations is much lower than that of lagoon populations and high levels of genetic differentiation occur among marine lake and lagoon populations. The present study has shown that marine lake populations have been completely isolated and have differentiated from lagoon populations, and each marine lake population is experiencing different evolutionary processes. These findings clearly demonstrate that marine lakes are excellent environments for the evolutionary study of marine species.


Mild ovarian stimulation with letrozole plus fixed dose human menopausal gonadotropin prior to IVF/ICSI for infertile non-obese women with polycystic ovarian syndrome being pre-treated with metformin: a pilot study.
Letrozole is widely employed as ovulation induction agent in women with PCOS, but its use in mild stimulation (MS) protocols for IVF is limited. Aim of the present study was to evaluate the feasibility of a MS protocol with letrozole plus hMG in non-obese PCOS women undergoing IVF after a metformin pre-treatment. We retrospectively evaluated the data of 125 non-obese PCOS undergoing MS with letrozole plus hMG, 150 IU as starting dose, (group 1, N = 80) compared to those undergoing a conventional IVF stimulation protocols (CS) (group 2, N = 45) prior to IVF. All patients had received metformin extended release 1200-2000 mg daily for three to six months before IVF. GnRH antagonist was administered in both groups when the leading follicles reached 14 mm. Both groups were comparable for age, BMI and ovarian reserve markers. Both groups showed lower than expected AFC and AMH values as a consequence of metformin pre-treatment. Letrozole-treated patients required a significantly lower amount of gonadotropins units (p < 0.0001), and showed significantly lower day 5, day 8 and hCG day E2 levels compared to patients undergoing the CS protocol (p < 0.0001, p < 0.0001 and p = 0.001 respectively). The oocyte yield, in terms of total (6, IQR 3, vs 6, IQR 4 respectively,) and MII oocytes (5, IQR 3, vs 5, IQR 3, respectively) number, did not differ among groups; the number of total (3, IQR 2, vs 3, IQR 1 respectively) and good quality embryos (2, IQR1 vs 2, IQR 1,5 respectively) obtained was comparable as well in the two groups. The number of fresh transfers was significantly higher in group 1 compared to group 2 (80% vs 60%, p = 0.016). A trend for higher cumulative clinical pregnancy rate was found in women undergoing MS compared to CS (42.5%vs 24,4%, p = 0.044), but the study was not powered to detect this difference. The present study suggests that the use of letrozole as adjuvant treatment to MS protocols for IVF may be an effective alternative to CS protocols for non-obese PCOS patients pre-treated with metformin, as it provides comparable IVF outcome without requiring high FSH dose, and avoiding supraphysiological estradiol levels.


Intravital measurement of arteriolar pressure and tangential wall stress in normotensive and spontaneously hypertensive rats (established hypertension).
Under intravital conditions, intravascular pressures of mesenteric resistance vessels were measured in normotensive (NR, mean blood pressure 92 mm Hg) and spontaneously hypertensive rats (SHR, 161 mm Hg) being elevated over all by about 75%; the tangential wall stress (sigma = p.r/h; p represents the intravascular pressure and r/h the ratio of internal radius to wall thickness) was found to be increased by 120-140% in SHR.


Circulating plasma NT-proBNP predicts subclinical coronary atherosclerosis on CT angiography among older adults in Uganda.
Phenotypes and mechanisms of cardiovascular disease (CVD) may differ across global populations. In sub-Saharan Africa (SSA), distinct environmental determinants may influence development and progression of atherosclerotic coronary artery disease (CAD). We investigated associations between 6 established markers of myocardial stress and subsequent subclinical CAD (sCAD), defined as presence of any atherosclerosis on coronary CT angiography (CCTA) in a 2-year prospective cohort of Ugandan adults enriched for cardiometabolic risk factors (RFs) and HIV. Six plasma biomarkers were measured baseline among 200 participants (50% with HIV) aged ≥ 45 years with ≥ 1 cardiovascular RF. At 2-year follow-up, 132 participants (52% with HIV) who returned underwent coronary CCTA. In logistic regression models adjusted for cardiovascular RFs (age, diabetes, hypertension, hyperlipidemia, smoking, obesity) and non-traditional RFs (HIV, chronic kidney disease), only NT-proBNP predicted subsequent subclinical CAD (p < 0.008, Bonferroni correction for multiple testing). In sensitivity analyses adjusted for ASCVD risk category (instead of individual RFs) in the baseline cohort with multiple imputation applied to missing year 2 CCTA data (n = 200), NT-proBNP remained significantly associated with subsequent CAD (p < 0.008). NT-proBNP consistently predicted subclinical CAD in Uganda in the absence of such an association among other markers of myocardial stress, suggesting a role for NT-proBNP in atherosclerosis independently of coronary microvascular dysfunction.


Development of ultrasonic investigations in medicine and biology in the U.S.S.R.
Ultrasonic research in biology and medicine, both fundamental and applied, has become so vast in scope, that a mere listing of specific subject-areas would take up too much space. This article is intended to give an overview of Soviet scientists' contribution to the field, with the emphasis on the most important and promising subject-areas which are now given priority in the U.S.S.R. Among specific subject-areas in ultrasonics are the studies of the biological action of ultrasound and ultrasonic safety in medicine, the effect of focused ultrasound, acoustic spectroscopy of solutions of biological media and acoustic specification of biological objects, acoustic visualization and microscopy and clinical ultrasonics.


Modification of cocaine sensitization by dopamine D1 and D2 receptor antagonists in terms of ambulation in mice.
The progressive enhancement in the ambulation increase caused by the repeated five-time dosings of cocaine (10 mg/kg SC) at 3- to 4-day intervals was dose dependently reduced by simultaneous administration with the selective dopamine D1 and D2 receptor antagonists, SCH 23390; R(+)-7-chloro-8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (0.01, 0.03, and 0.1 mg/kg SC) and YM-09151-2 (nemonapride); cis-N-(1-benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4- methylaminobenzamide (0.01, 0.03, and 0.1 mg/kg SC), respectively. However, the mice given cocaine with SCH 23390 (0.03 mg/kg) or YM-09151-2 (0.03 and 0.1 mg/kg) demonstrated significantly higher sensitivity than the mice given cocaine alone to challenge cocaine. Both 2-h and 24-h posttreatments with SCH 23390 (0.01-0.1 mg/kg) after each cocaine administration, at which the acute stimulant effect of cocaine had disappeared, significantly and dose dependently enhanced the cocaine sensitization. In contrast, 2-h, but not 24-h, posttreatment with YM-09151-2 (0.01-0.1 mg/kg), slightly retarded the induction of cocaine sensitization. The present results suggest that the blockade of dopamine D1 receptors is responsible for a significant enhancement in the cocaine sensitization, independent of the timings of its administration, whereas the blockade of dopamine D2 receptors elicits time-dependent alterations in the cocaine sensitization, a strong enhancement in the simultaneous administration schedule, but a slight retardation in the early posttreatment schedule.


Dynamic event-driven neural network-based adaptive fault-attack-tolerant control for wheeled mobile robot system.
In this article, the fault-attack control problem is investigated for wheeled mobile robot (WMR) systems subjected to actuator faults, disturbances, communication attacks, and limited communication resources. An event-observer based compensation controller is presented. With the help of the observer estimation values and the attack sleep/active instant trigger information, the tracking control performance is realized for the robot system with the assistance of the neural network approximation technology. Concretely, first, the robot system dynamic model with actuator faults, disturbances, and attacks is established. Then, an event-based proportional-integral observer (PIO) is established. In the observer framework, a state estimator, an actuator fault efficiency estimator, and a disturbance estimator are embedded. Based on the observer outputs, a second-order adaptive sliding mode fault-compensation reliable controller is presented. In this controller framework, the fault compensation, disturbance attenuation, and the attack sleep/active time instant information are contained to guarantee the reliability and performance recoverability of the robot system. Furthermore, a dynamic even condition and an adaptive trigger scheme are constructed in the sensor and actuator channel to achieve the communication-efficient purpose. Finally, two cases of the robot system are performed to verify the system recoverability of the presented approach.


Safety and outcome of hepatitis B core antibody-positive donors in right-lobe living donor liver transplantation.
We studied the safety of right-lobe donor hepatectomy in living donors with a positive serological test result for antibody against hepatitis B core antigen (anti-HBc). Of 54 right-lobe living liver donors, serum anti-HBc was positive in 29 donors (54%) and negative in 25 donors (46%). None had a history of hepatitis and all had normal liver biochemistry test results before surgery. Surgical data, postoperative liver function, and outcome of donors were compared according to anti-HBc status. Donors positive for anti-HBc were significantly older (median age, 42 v 31 years; P <.001), but there was no difference in other demographics and liver size. Median blood loss was greater in anti-HBc-positive donors (600 v 350 mL; P =.007). Histological examination showed no difference in degree of portal fibrosis or fatty change in liver grafts. There was no significant difference in postoperative serum transaminase levels or prothrombin times; however, anti-HBc-positive donors had greater serum bilirubin levels day 6 (26 v 21 micromol/L; P =.01) and day 7 (22 v 15 micromol/L; P =.004) after surgery. Postoperative complications developed in 10 anti-HBc-positive and 6 anti-HBc-negative donors (P =.4). All donors who developed cholestasis were positive for anti-HBc, aged 45 years or older, and had mild fatty changes of the liver. Hospital stays were similar. All donors had completely normal liver function at a median follow-up of 31 months (range, 21 to 76 months). A positive serological test result for anti-HBc should not be regarded as a contraindication for right-lobe liver donation.


Transition from cMyc to L-Myc during dendritic cell development coordinated by rising levels of IRF8.
During dendritic cell (DC) development, Myc expression in progenitors is replaced by Mycl in mature DCs, but when and how this transition occurs is unknown. We evaluated DC development using reporters for MYC, MYCL, and cell cycle proteins Geminin and CDT1 in wild-type and various mutant mice. For classical type 1 dendritic cells (cDC1s) and plasmacytoid DCs (pDCs), the transition occurred upon their initial specification from common dendritic cell progenitors (CDPs) or common lymphoid progenitors (CLPs), respectively. This transition required high levels of IRF8 and interaction with PU.1, suggesting the use of EICEs within Mycl enhancers. In pDCs, maximal MYCL induction also required the +41kb Irf8 enhancer that controls pDC IRF8 expression. IRF8 also contributed to repression of MYC. While MYC is expressed only in rapidly dividing DC progenitors, MYCL is most highly expressed in DCs that have exited the cell cycle. Thus, IRF8 levels coordinate the Myc-Mycl transition during DC development.


Fractures of the Humeral Shaft with Primary Radial Nerve Palsy: Do Injury Mechanism, Fracture Type, or Treatment Influence Nerve Recovery?
Adult humeral shaft fractures are associated with primary radial nerve palsy in up to 18% of cases. The purpose of this study was to assess the influence of injury mechanism, fracture type, and treatment on nerve recovery in patients with humeral shaft fractures and primary nerve palsy. Data of fifty patients (age-43.5 ± 21.3; female: male-1:1.8) with humeral shaft fractures and concomitant grade I-II primary radial nerve palsy, who underwent either open reduction and internal fixation (ORIF) or intramedullary nailing at an academic level I trauma center between 1994 and 2013, were evaluated. Factors potentially influencing the time to onset of recovery or full nerve recovery (injury mechanism, fracture type, fracture location and treatment) were analyzed in detail. Thirty patients were treated with ORIF and twenty patients with closed unreamed intramedullary nailing of the humeral shaft, respectively. The mean time to onset of recovery was 10.5 ± 3.4 weeks (2-17 weeks). Twenty-six (52%) patients reported significant clinical improvement within the first 12 weeks. Mean time to full recovery was 26.8 ± 8.9 weeks (4-52 weeks). Twenty-five (50%) patients regained full manual strength within the first six months following the injury. Forty-nine (98%) patients regained full manual strength within the first 52 weeks. Trauma mechanism, fracture type, fracture location, and treatment modality did not influence the time to onset of nerve recovery or time to full recovery following humeral shaft fractures with grade I-II primary radial nerve palsy.


M4 B6 X6 as a New Family of High-Efficient Electrocatalysts: The Role of Surface Reconstruction in Water Oxidization.
Searching for highly-efficient electrocatalysts for water splitting has been greatly endowed due to the huge demand for green energy sources. Two-dimensional (2D) materials are widely explored for the purpose because of their unique physical and chemical properties, abundant active sites, and easy fabrication. Here, we present a new family of 2D M4 B6 X6 (2D Boridenes) and investigate their physical and chemical properties for their potential applications into electrocatalysis based on first-principles calculations. We demonstrate that 2D M4 B6 X6 (M=Cr, Mo, and W; X=O and F) are dynamically, thermodynamically, and mechanically stable, and show intriguing electronic and catalytic properties. Importantly, we find that M4 B6 O6 are intrinsically active for oxygen evolution reaction (OER). Our results demonstrate that: (1) the adsorbate-escape mechanism dominates the OER process with a low overpotential of 0.652 V on Cr4 B6 O6 ; (2) the partial surface-oxidization can improve the catalytic performance of M4 B6 F6 dramatically; and (3) the surface reconstruction greatly affects the OER performance of M4 B6 X6 . Our findings illustrate that the surface reconstruction is critical to the OER activity, which may provide a new strategy on the design of 2D materials for electrocatalysis and offer theoretical insight into the catalytic mechanism.


Perinatal depression and serum vitamin D status: A cross-sectional study in urban China.
Although vitamin D has been found to be associated with perinatal depression, the results are inconsistent. The aim of this cross-sectional study was to examine the association between vitamin D and PND in Chinese pregnant women and lactating women. A total of 1773 participants were included, including 907 lactating women and 866 pregnant women. The Edinburgh Postnatal Depression Scale (EPDS) was used to screen for PND, and those with scores ≥13 were considered to have PND. Serum 25-hydroxyvitamin D concentrations were assessed with high-performance liquid chromatography. The prevalence of postpartum depression (PPD) and antenatal depression (AD) were 15.9 % and 9.8 %, respectively. Compared with individuals with sufficient vitamin D, those with vitamin D deficiency were associated with a higher prevalence of PPD in lactating women (OR = 1.71, 95%CI: 1.01-2.88, p = 0.044). The serum 25(OH)D of lactating women was inversely associated with the scores of the factor "depressive mood" of the EPDS (ORper 5 ng/mL = -0.10, 95%CI: -0.19 to -0.01, p = 0.032). No significant association between serum 25-hydroxyvitamin D and AD was observed. First, this study is a cross-sectional design, which can only determine associations but not causality. Secondly, this study only included participants from urban areas. Thirdly, there are still some possible confounding factors that have not been considered. In conclusion, this study suggested a significant association between vitamin D status and PPD; however, the association between vitamin D status and AD was not significant.


Fitness Beats Truth in the Evolution of Perception.
Does natural selection favor veridical percepts-those that accurately (if not exhaustively) depict objective reality? Perceptual and cognitive scientists standardly claim that it does. Here we formalize this claim using the tools of evolutionary game theory and Bayesian decision theory. We state and prove the "Fitness-Beats-Truth (FBT) Theorem" which shows that the claim is false: If one starts with the assumption that perception involves inference to states of the objective world, then the FBT Theorem shows that a strategy that simply seeks to maximize expected-fitness payoff, with no attempt to estimate the "true" world state, does consistently better. More precisely, the FBT Theorem provides a quantitative measure of the extent to which the fitness-only strategy dominates the truth strategy, and of how this dominance increases with the size of the perceptual space. The FBT Theorem supports the Interface Theory of Perception (e.g. Hoffman et al. in Psychon Bull Rev https://doi.org/10.3758/s13423-015-0890-8 , 2015), which proposes that our perceptual systems have evolved to provide a species-specific interface to guide adaptive behavior, and not to provide a veridical representation of objective reality.


Laboratory diagnosis of alpha1-antitrypsin deficiency.
The laboratory diagnosis of alpha(1)-antitrypsin (AAT) deficiency (AATD) has evolved over the last 40 years since the first cases of the disorder were reported. It is currently performed in specialized centers, and it requires a combination of different biochemical methods: nephelometric AAT concentration, isoelectric focusing, genotyping, and sequencing. The availability of matrices such as the dried blood spot have facilitated the implementation of laboratory analyses for AATD, but they have also challenged laboratories to develop more reliable and reproducible techniques starting from dried blood. In this article, we describe the protocols we have optimized for AATD diagnosis from dried blood spot, in an attempt to hopefully provide useful information for physicians and scientists involved in this diagnostic line. We also describe the diagnostic flowchart for AATD detection that we have developed accordingly.


12 years' experience with intraoperative radiotherapy (IORT) of malignant gliomas.
Even after surgery and radiotherapy, malignant gliomas still have a poor prognosis. The authors report on their experience with IORT in 71 patients. From May 1992 to February 2004, 71 patients with malignant gliomas were treated with IORT. 26 patients suffered from grade III gliomas, 45 patients from glioblastomas (GBM). IORT was carried out using a standard electron tube and 9- to 18-MeV electrons. 52/71 patients who were primarily treated received 20 Gy IORT + 60 Gy postoperative radiotherapy, 19/71 patients with recurrences only received IORT (20-25 Gy). The complication rates were 1.4% for wound infections and 5.6% for hemorrhage. Median disease-specific survival amounted to 14.9 months (gliomas III) and 14.2 months (GBM). The 2-year survival rates amounted to 26.9% (gliomas III) and 6.8% (GBM; p = 0.0296). Total versus subtotal resection had no significant influence on survival (p = 0.0741), nor had age, sex, tumor site, performance status, size, primary versus recurrence, and radiation dose. A comparison to a conventionally treated patient group did not show a significant survival improvement. 3 months after treatment, initial symptoms had improved in 59% (hemiparesis), 50% (aphasia), 50% (hemianopsia), and 60% (convulsions). IORT has been shown to be feasible; perioperative complication rates were not increased. Survival was generally not improved compared to a historical control group. Recurrences achieved the same survival as primary tumors, and GBM also had a slightly increased survival, thus being possible indications for IORT.


Anti-hepatitis B virus activity of lithospermic acid, a polyphenol from Salvia miltiorrhiza, in vitro and in vivo by autophagy regulation.
Salvia miltiorrhiza (the roots of S. miltiorrhiza Bunge, Danshen in Chinese), a traditional Chinese medicine, has been clinically used to prevent and treat various diseases, such as cardiovascular and cerebrovascular diseases, diabetes, and hepatitis B, in China and some other Asian countries. Lithospermic acid (LA), a polyphenol derived from S. miltiorrhiza, has been reported to exhibit multiple pharmacological properties, such as anti-inflammatory, anti-HIV, and anti-carbon tetrachloride-induced liver injury activities. However, little is known about the anti-hepatitis B virus (HBV) activity of LA. The study was projected to investigate the anti-HBV activity of LA in vitro (HepG2.2.15 and pHBV1.3-transfected HepG2 cells) and in vivo (pAAV-HBV1.2 hydrodynamic injection [HBV-HDI] mice) and explore the potential mechanism as well. Hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) contents were detected by ELISA kits. HBV DNA and hepatitis B core antigen (HBcAg) levels were evaluated by quantitative real-time polymerase chain reaction and immunohistochemistry assay, respectively. The proteins in autophagy process, lysosomal acidic function, and autophagy-related signaling pathways were examined by Western blot. Transmission electron microscopy was used to observe the number of autophagosomes and autolysosomes. Confocal microscopy was applied to analyze the autophagic flux and lysosomal acidification, using mCherry-enhanced green fluorescent protein (EGFP)-microtubule-associated protein light chain (LC)3 and lysosomal probes, respectively. LA exhibited anti-HBV activity by inhibiting HBV DNA replication in HepG2.2.15 and pHBV-transfected HepG2 cells in dose- and time-dependent manners and hampering HBsAg and HBeAg levels in HepG2.2.15 cells to a certain extent. LA reduced HBV DNA, HBsAg/HBeAg, and HBcAg levels in the serum/liver tissues of HBV-HDI C57BL/6 mice during the 3-week treatment and suppressed the withdrawal rebound of HBV DNA and HBsAg in the mice serum. LA increased LC3-II protein expression and the number of autolysosomes/autophagosomes and promoted the degradation of sequestosome 1(p62) protein in vitro and in vivo. LA enhanced the co-localization of LC3 protein with autolysosomes, further confirming the ability of LA to induce a complete autophagy. Knockdown of autophagy-related gene (Atg) 7 or 5 in vitro and administration of 3-methyladenine (an autophagic inhibitor) in vivo disabled the inhibitory efficacy of LA on HBV DNA replication, suggesting that the anti-HBV efficacy of LA depended on its ability of inducing autophagy. LA could enhance lysosomal acidification and improve the function of lysosomes by promoting the protein expression of lysosomal-associated membrane protein (LAMP)-1, LAMP-2, and mature cathepsin D, which may contribute to the autophagic induction of LA. LA inhibited the activation of AKT and mammalian target of rapamycin (mTOR) induced by HBV, which was reversed by IGF-1 (an agonist of the PI3K/AKT/mTOR signaling pathway), indicating that LA elicited autophagy through hampering the PI3K/AKT/mTOR signaling pathway. We revealed the anti-HBV activity and mechanism of LA in vitro and in vivo. This study facilitates a new understanding of the anti-HBV potent components of S. miltiorrhiza and sheds light on LA for further development as an active constituent or candidate used in the therapy against HBV infection.


Massive pericardial effusion causing cardiac tamponade accompanied by elevated CA-125 and thoracic lymphadenopathy in sarcoidosis: a case report.
Pericardial effusion and cardiac tamponade are rare manifestations of cardiac sarcoidosis. This is a first case report that describes a patient with severe pericardial effusion and signs of cardiac tamponade with elevated carbohydrate antigen 125 (CA-125) levels, enlarged pericardial (PLN) and mediastinal lymph nodes (MLN), histologically confirmed as sarcoidosis. A 51-year-old female patient was admitted with complaints of sickness, shortness of breath on minimal exertion, swelling in lower extremities, and heaviness in right upper abdomen. Patient had diminished heart sounds, peripheral edema and hepatomegaly. She had elevated CA-125 level without gynecologic pathology. There were QRS alternation on ECG and water-bottle configuration on chest-X-ray, severe pericardial effusion, and signs of cardiac tamponade on echocardiography. CT demonstrated massive pericardial effusion, pericardial mass and enlargement of anterior MLN. The patient underwent pericardial drainage with removal of 850 mL of pericardial fluid and excision of enlarged PLN. Histological examination of PLN revealed non-caseating epithelioid cell granulomas. The diagnosis of cardiac sarcoidosis was established. Patient was discharged and 6-month follow-up was uneventful. There are no reports on association of pericardial effusion, with increased CA-125 level in sarcoidosis, as we established in our patient. Our case is notable by incidental finding of enlarged PLN, mimicking pericardial mass and mediastinal lymphoadenopathy on CT, further confirmed by histological examination of PLN specimen as cardiac sarcoidosis. It should be kept in mind that sarcoidosis may present as massive pericardial effusion, with signs of tamponade and pericardial lymphoadenopathy mimicking pericardial mass, mediastinal lymphoadenopathy and elevated CA-125, mimicking malignancy.


Author Correction: T-cell tolerance and exhaustion in the clearance of Echinococcus multilocularis: role of inoculum size in a quantitative hepatic experimental model.
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.


Inhibition of ACAT as a Therapeutic Target for Alzheimer's Disease Is Independent of ApoE4 Lipidation.
APOE4, encoding apolipoprotein E4 (apoE4), is the greatest genetic risk factor for Alzheimer's disease (AD), compared to the common APOE3. While the mechanism(s) underlying APOE4-induced AD risk remains unclear, increasing the lipidation of apoE4 is an important therapeutic target as apoE4-lipoproteins are poorly lipidated compared to apoE3-lipoproteins. ACAT (acyl-CoA: cholesterol-acyltransferase) catalyzes the formation of intracellular cholesteryl-ester droplets, reducing the intracellular free cholesterol (FC) pool. Thus, inhibiting ACAT increases the FC pool and facilitates lipid secretion to extracellular apoE-containing lipoproteins. Previous studies using commercial ACAT inhibitors, including avasimibe (AVAS), as well as ACAT-knock out (KO) mice, exhibit reduced AD-like pathology and amyloid precursor protein (APP) processing in familial AD (FAD)-transgenic (Tg) mice. However, the effects of AVAS with human apoE4 remain unknown. In vitro, AVAS induced apoE efflux at concentrations of AVAS measured in the brains of treated mice. AVAS treatment of male E4FAD-Tg mice (5xFAD+/-APOE4+/+) at 6-8 months had no effect on plasma cholesterol levels or distribution, the original mechanism for AVAS treatment of CVD. In the CNS, AVAS reduced intracellular lipid droplets, indirectly demonstrating target engagement. Surrogate efficacy was demonstrated by an increase in Morris water maze measures of memory and postsynaptic protein levels. Amyloid-beta peptide (Aβ) solubility/deposition and neuroinflammation were reduced, critical components of APOE4-modulated pathology. However, there was no increase in apoE4 levels or apoE4 lipidation, while amyloidogenic and non-amyloidogenic processing of APP were significantly reduced. This suggests that the AVAS-induced reduction in Aβ via reduced APP processing was sufficient to reduce AD pathology, as apoE4-lipoproteins remained poorly lipidated.


Correlation and Crosswalks Between Patient-Reported Functional Outcomes and PROMIS Physical Function Among Medically Ill Patients.
To develop scoring crosswalks between a new multidomain patient-reported outcome measure, the Functional Assessment in Acute Care (FAMCAT), with a Patient-Reported Outcomes Measurement (PROMIS) measure of physical function, and examine correlations with existing legacy instruments. Cross-sectional, single-group design study. Large, Midwestern academic teaching hospital. A sample of patients (N=1885; 53% men; average age, 62±16y) hospitalized on the general medical services between May 2016 and June 2017. Not applicable. Scores from the FAMCAT administered via computerized adaptive testing were compared with scores on the 8-item PROMIS Physical Function (PROMIS PF) short form. Correlations with the FAMCAT and the PROMIS PF were strong for initial scores (MCAT_Mobilty: r=0.78, P<.0001; MCAT_DailyAct: r=0.81, P<.0001). The Applied Cognition scale did not demonstrate adequate correlations and thus was not a candidate for crosswalk scores. Although the MCAT_Mobility scale could be initially linked, subsequent analysis did not support a valid crosswalk. Linking criteria were applied with the Daily Activity scale to developing a final concordance table. The FAMCAT Daily Activity scale yielded robust correlations to develop crosswalk scores with the PROMIS PF. The resulting crosswalk conversion metric may be useful to compare outcomes across these constructs for assessing functional abilities among patients on general medical services. The Applied Cognition and Basic Mobility scales did not meet the criteria; therefore, alternate legacy instruments are needed to develop additional crosswalks.


What Do I Do if There is No Distal Nerve Stump for Inferior Alveolar Nerve Reconstruction?
This technical note describes an innovation that addresses a clinical problem in inferior alveolar nerve (IAN) reconstruction. In some cases of mandibular resection, there is a need to resect a significant amount of the IAN along with the pathologic lesion and this may result in a lack of a distal nerve stump for completion of the neural anastomosis. This technical note offers the option to perform the distal neurorrhaphy into the residual soft tissues with the expectation that axonal sprouting will occur and result in lower lip and chin sensory reinnervation. There are no inherent risks or additional costs. The significance of this technique is that it permits IAN reconstruction in cases where the actual nerve stump is not available and improves patient care. There should be no challenges or delays to implementing this innovation for surgeons who reconstruct the IAN during ablative mandibular resection.


Microangiographic study of spinal cord injury and myelopathy.
Post-mortem microangiography has been performed in 12 patients with traumatic cervical cord injury, 2 patients with myelopathy, and one patient with post-traumatic syringomyelia. Microangiography defined 4 zones in the injured spinal cord. In traumatic injury, the size and extent of the non-filling area (Zone 1) was directly related to the injury force. Subsequently these areas became cavitated. Surrounding the non-filling area, widely extending areas demonstrated filling of capillaries but showed damaged neurons and axons (Zone 2). In the chronic stage, Zone 2 replaced by gliomesenchymal tissue. The capillaries in the gliomesenchymal scars revealed a distorted abnormal arrangement (Zone 3). In a case with myelopathy, the hypervascular areas (Zone 4) were observed just around the chronically compressed area. The vascular increases were considered to be a reaction against chronic compression. In a patient with post-traumatic syringomyelia, the vascular network of the posterior grey matter disappeared and the central arteries were distorted by the distending forces of the syrinx. The microangiographs suggested that vascular factors might play a significant role in original cavity formation; but in cavity extension, these factors were not primary.


Fat grafting accelerates revascularisation and decreases fibrosis following thermal injury.
Fat grafting has been shown clinically to improve the quality of burn scars. To date, no study has explored the mechanism of this effect. We aimed to do so by combining our murine model of fat grafting with a previously described murine model of thermal injury. Wild-type FVB mice (n=20) were anaesthetised, shaved and depilitated. Brass rods were heated to 100°C in a hot water bath before being applied to the dorsum of the mice for 10s, yielding a full-thickness injury. Following a 2-week recovery period, the mice underwent Doppler scanning before being fat/sham grafted with 1.5cc of human fat/saline. Half were sacrificed 4 weeks following grafting, and half were sacrificed 8 weeks following grafting. Both groups underwent repeat Doppler scanning immediately prior to sacrifice. Burn scar samples were taken following sacrifice at both time points for protein quantification, CD31 staining and Picrosirius red staining. Doppler scanning demonstrated significantly greater flux in fat-grafted animals than saline-grafted animals at 4 weeks (fat=305±15.77mV, saline=242±15.83mV; p=0.026). Enzyme-linked immunosorbent assay (ELISA) analysis in fat-grafted animals demonstrated significant increase in vasculogenic proteins at 4 weeks (vascular endothelial growth factor (VEGF): fat=74.3±4.39ngml(-1), saline=34.3±5.23ngml(-1); p=0.004) (stromal cell-derived factor-1 (SDF-1): fat=51.8±1.23ngml(-1), saline grafted=10.2±3.22ngml(-1); p<0.001) and significant decreases in fibrotic markers at 8 weeks (transforming growth factor-ß1(TGF-ß): saline=9.30±0.93, fat=4.63±0.38ngml(-1); p=0.002) (matrix metallopeptidase 9 (MMP9): saline=13.05±1.21ngml(-1), fat=6.83±1.39ngml(-1); p=0.010). CD31 staining demonstrated significantly up-regulated vascularity at 4 weeks in fat-grafted animals (fat=30.8±3.39 vessels per high power field (hpf), saline=20.0±0.91 vessels per high power field (hpf); p=0.029). Sirius red staining demonstrated significantly reduced scar index in fat-grafted animals at 8 weeks (fat=0.69±0.10, saline=2.03±0.53; p=0.046). Fat grafting resulted in more rapid revascularisation at the burn site as measured by laser Doppler flow, CD31 staining and chemical markers of angiogenesis. In turn, this resulted in decreased fibrosis as measured by Sirius red staining and chemical markers.


Regulation of human leukocyte antigen expression in human conjunctival epithelium.
To demonstrate that interferon-gamma (IFN-gamma) is the key cytokine responsible for the upregulation of HLA-DR antigen in conjunctival epithelial cells of Sjogren syndrome (SS) patients. Flow cytometry of conjunctival epithelial cells from SS and non-SS dry eye patients was performed for the quantification of HLA-DR surface expression. With a conjunctival epithelial cell line (ChWK), HLA-DR regulation by various cytokines was evaluated, and confocal immunocytochemical and western blot analyses were performed to evaluate the activation of nuclear factorkappa B (NF-kappaB) and signal transducers and activators of transcription 1 and 3 (STAT1 and STAT3, respectively). HLA-DR expression was upregulated in conjunctival epithelial cells of SS patients but not in non-SS dry eye patient or healthy control subject. IFN-gamma was the only cytokine that effectively upregulated HLA-DR expression in ChWK, which was synergistically enhanced by tumor necrosis factor-alpha (TNF-alpha). IFN-gamma induced the nuclear translocation of NF-kappaB, but did not activate STAT1 or STAT3 in ChWK. Upregulation of HLA-DR antigen in the conjunctival epithelium of SS patients may be regulated by IFN-gamma through the activation of NF-kappaB.


A radiochemical procedure for the assay of fatty acid binding by proteins.
Protein-bound and unbound fatty acids can be efficiently separated at 0 degree C using a hydrophobic column-packing material (Lipidex 1000) similar to the separation of protein-bound and unbound steroids (E. Dahlberg, M. Snochowski, and J.-A. Gustafsson (1980) Anal Biochem. 106, 380-388). Protein-bound fatty acids are also removed by Lipidex 1000 when treatment is performed at 37 degrees C. Lipidex 1000 does not exhibit binding properties for soluble proteins at 0 and 37 degrees C, in contrast to dextran-coated charcoal. Lipidex 1000 appeared to be useful for the delipidation of protein samples at 37 degrees C and for a radiochemical assay of fatty acid-binding by microgram amounts of protein at 0 degree C. With this assay we obtained results on palmitate binding to serum albumin similar to those reported on the basis of equilibrium dialysis. Delipidated proteins from dealbuminized rat liver cytosol maximally bind about 4 nmol palmitate/mg protein.


The shortest isoform of dystrophin (Dp40) interacts with a group of presynaptic proteins to form a presumptive novel complex in the mouse brain.
Duchenne muscular dystrophy (DMD) causes cognitive impairment in one third of the patients, although the underlying mechanisms remain to be elucidated. Recent studies showed that mutations in the distal part of the dystrophin gene correlate well with the cognitive impairment in DMD patients, which is attributed to Dp71. The study on the expression of the shortest isoform, Dp40, has not been possible due to the lack of an isoform specific antibody. Dp40 has the same promoter as that found in Dp71 and lacks the normal C-terminal end of Dp427. In the present study, we have raised polyclonal antibody against the N-terminal sequence common to short isoforms of dystrophin, including Dp40, and investigated the expression pattern of Dp40 in the mouse brain. Affinity chromatography with this antibody and the consecutive LC-MS/MS analysis on the interacting proteins revealed that Dp40 was abundantly expressed in synaptic vesicles and interacted with a group of presynaptic proteins, including syntaxin1A and SNAP25, which are involved in exocytosis of synaptic vesicles in neurons. We thus suggest that Dp40 may form a novel protein complex and play a crucial role in presynaptic function. Further studies on these aspects of Dp40 function might provide more insight into the molecular mechanisms of cognitive impairment found in patients with DMD.


Activation of spinal ERK signaling pathway contributes to pain-related responses induced by scorpion Buthus martensi Karch venom.
It has been demonstrated that spontaneous nociceptive behaviors, cutaneous hyperalgesia and paw edema can be induced by intraplantar injection of scorpion Buthus martensi Karch (BmK) venom in rats. In the present study, activation of spinal extracellular signal-regulated kinase (ERK) signaling pathway and its contribution to pain-related responses induced by scorpion BmK venom were investigated. It was found that ERK was activated not only in the superficial layers but also in deep layers of L4-L5 spinal cord dorsal horn, which started at 2 min, peaked at 30-60 min and almost disappeared at 4h following intraplantar injection of BmK venom. Intrathecal injection of U0126 (0.1, 1.0 and 10 microg), a widely used specific MAP kinase kinase (MEK) inhibitor, suppressed spontaneous nociceptive responses and reduced primary heat hyperalgesia and bilateral mechanical hyperalgesia induced by BmK venom. In addition, BmK venom-induced spinal c-Fos expression could be inhibited by U0126 dose-dependently. Intrathecal delivery of NMDA receptor antagonist (5R, 10S)-(+)-5-methyl-10, 11-dihydro-5H-dibenzo [a,d]-cyclohepten-5-10-imine hydrogen maleate (MK-801) and the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) could partially inhibit activation of spinal ERK induced by BmK venom at 30 min. Thus, activation of ERK in spinal cord dorsal horn, partially mediated by NMDA and non-NMDA receptor, potentially contributes to BmK venom-induced pain-related behaviors.


Evaluation of real-time polymerase chain reaction for the diagnosis of protozoal myeloencephalitis in horses using cerebrospinal fluid.
Equine protozoal myeloencephalitis (EPM) caused by Sarcocystis neurona remains an antemortem diagnostic challenge in some horses. Recent work suggested the use of real-time PCR (rtPCR) on cerebrospinal fluid (CSF) as a promising diagnostic tool. To evaluate the sensitivity and specificity of S. neurona rtPCR on CSF for EPM diagnosis using horses with EPM and S. neurona-seropositive horses with other neurologic conditions. Ninety-nine horses with neurologic disease that underwent complete neurologic examination, CSF collection, and, if euthanized, necropsy including the central nervous system (CNS). Retrospective case-control study using banked CSF samples. Samples from horses with neurologic abnormalities and necropsy-confirmed EPM diagnosis, presumptive EPM diagnosis using strict criteria (SnSAG2/4/3 ELISA serum:CSF titer ratios <50) and horses diagnosed with other neurologic diseases were used. Fifty-two horses had EPM; 23 were confirmed on necropsy, and 29 were presumptive clinical diagnoses. The other 47 horses all had necropsy-confirmed diagnoses. Four of the 47 horses had normal neurologic findings on necropsy and the remaining 43 horses had neurologic diseases including equine degenerative myeloencephalopathy (EDM), cervical vertebral stenotic myelopathy, trauma, and other miscellaneous conditions. One CSF sample was weakly positive for S. neurona by rtPCR, this sample was obtained from a horse with confirmed EDM. Samples from the other 98 horses were negative for S. neurona by rtPCR. Our study contradicts previous conclusions that S. neurona rtPCR is potentially useful for EPM diagnosis, because our results indicate that the assay has a low sensitivity (0%) for EPM.


Studies on tissue factor activity and production by leukocytes of human umbilical cord and adult origin.
Human adult and umbilical cord-derived leukocytes were shown to be capable of generating tissue factor activity on exposure to endotoxin and to reduced pH. Blood for leukocyte separation was collected from normal adults and from newly delivered sections of umbilical cord and mixed leukocyte preparations were obtained by separation over methyl cellulose Hypaque. The coagulant activity of the cell suspension was assayed using a one-stage or two-stage method. Cord-derived leukocytes were shown to develop greater coagulant activity than adult-derived leukocytes when stimulated by endotoxin in vitro at 2,000 cells/mm-3. This response to endotoxin was partially inhibited by prior exposure of the cells to prostaglandin (PG) E1 an to L-epinephrine. Acetylcholine stimulated the production of coagulant activity in the absence of endotoxin. Both cord and adult-derived leukocytes (20,000/mm-3) developed coagulant activity when exposed to pH reduction by lactic or hydrochloric acids and this activity was shown to be tissue factor.


MLML: consistent simultaneous estimates of DNA methylation and hydroxymethylation.
The two major epigenetic modifications of cytosines, 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC), coexist with each other in a range of mammalian cell populations. Increasing evidence points to important roles of 5-hmC in demethylation of 5-mC and epigenomic regulation in development. Recently developed experimental methods allow direct single-base profiling of either 5-hmC or 5-mC. Meaningful analyses seem to require combining these experiments with bisulfite sequencing, but doing so naively produces inconsistent estimates of 5-mC or 5-hmC levels. We present a method to jointly model read counts from bisulfite sequencing, oxidative bisulfite sequencing and Tet-Assisted Bisulfite sequencing, providing simultaneous estimates of 5-hmC and 5-mC levels that are consistent across experiment types. http://smithlab.usc.edu/software/mlml


Autoradiographic localization of [3H]-L-glutamate binding sites in a model of cerebellar granule cell ectopia generated by methylazoxymethanol treatment.
The distribution of [3H]glutamate binding sites was studied in a model of altered cerebellar development obtained by injecting methylazoxymethanol (MAM) in 5-day-old mice. In these mice, at the 25th postnatal day, cerebella were smaller than normal, stratification was normal except for the presence in some lobes of a thin ectopic granule cell layer in the middle of the molecular layer, the proportion of the distribution of [3H]glutamate binding sites between molecular and internal granule cell layers was maintained but site density of both quisqualate- and NMDA-sensitive types was increased in the two layers. In the molecular layer, this increase was uniform in spite of the presence of the ectopic cell layer. In the internal granular layer, the increase of quisqualate-sensitive and NMDA-sensitive [3H]glutamate binding sites is topographically segregated and the first corresponds to areas of lesser cellular density. These results show that MAM treatment induces persistent alterations of the cerebellar glutamatergic system, which consist of receptor over-expression, possibly due to deficit of innervation, reactive gliosis and immaturity of surviving granule cells.


Single voxel magnetic resonance spectroscopy at 3 Tesla in a memory disorders clinic: early right hippocampal NAA/Cr loss in mildly impaired subjects.
In this study, we use magnetic resonance spectroscopy (MRS) at 3 Tesla to measure N-acetyl aspartate (NAA), myo-inositol (mI) and choline (Cho) to creatine (Cr) ratios in R (right) and L (left) hippocampi (H) in 8 mildly memory impaired (MMI), 6 probable Alzheimer's Disease (PRAD), and 17 control subjects. NAA/Cr was significantly reduced in the RH in the MMI group and bilaterally in the PRAD group vs. controls. No other metabolite differences were noted between the three groups. Five MMI subjects have converted to PRAD in follow-up. These findings suggest that RH NAA/Cr ratios measured at 3 Tesla may be a sensitive marker of future progression to dementia in a clinically defined population with isolated memory complaints.


Engineering microbial cell morphology and membrane homeostasis toward industrial applications.
Microbial cell factory performance is significantly affected by the cell morphology and membrane homeostasis. It is important to ensure that cell factories are able to regulate cell morphology and maintain membrane homeostasis. Cell morphology can be controlled by regulating the formation of elongasomes and divisomes, which change the shapes of cells from rods to fibers, large spheres, or mini-cells. Membrane homeostasis can also be controlled by regulating the homeostasis of membrane lipids and proteins, thereby improving the robustness of microbes in toxic environments. In the present review, we discuss promising developments in cell morphology and membrane homeostasis engineering that have improved microbial cell factory performance.


[Chinese herbs for shen invigorating and blood activating activated MMP-9 signaling pathway to mobilize rats' bone marrow EPCs: a molecular mechanism research].
To explore the effect of Chinese herbs for Shen invigorating and blood activating (CHSIBA) on the number of endothelial progenitor cells (EPCs) in the bone marrow and the peripheral blood and the signaling pathway of bone marrow matrix metalloproteinase 9 (MMP-9) of the myocardial infarction (MI) model rats. The MI rat model was established by ligation. Thirty successfully modeled rats were randomly divided into the high dose CHSIBA group, the low dose CHSIBA group, and the model group, 10 in each group. Besides, another 10 normal rats were recruited as the blank group. Rats in the high dose CHSIBA group and the low dose CHSIBA group were administered with CHSIBA at 3 g/kg and 1.5 g/kg body weight by gastrogavage (by adding them in 4 mL physiological saline), once daily. Rats in the model group and the blank group were administered with 4 mL physiological saline once daily. The EPCs were collected from the bone marrow and the peripheral blood 4 weeks later. Seven days later the CD34/CD133 phenotype was identified in collected sticking wall cells using flow cytometry. The MMP-9 and water soluble Kit ligand (sKitL) were detected using Western blot. The expressions of vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1alpha (SDF-1alpha) were detected using ELISA. The CD34/CD133 positive rate and the EPC quantity in the bone marrow and the peripheral blood were higher in the high dose CHSIBA group and the low dose CHSIBA group than in the model group (P < 0.05, P < 0.01). Besides, the expressions of VEGF, SDF-1alpha, MMP-9, and sKitL in the bone marrow and the peripheral blood were also higher in the high dose CHSIBA group and the low dose CHSIBA group than in the model group (P < 0.05, P < 0.01). CHSIBA could activate MMP-9 signaling pathway, increase its upstream and downstream signal expression levels, and mobilize EPCs in the bone marrow to enter the blood circulation.


SDF-1 expression and tumor-infiltrating lymphocytes identify clinical subtypes of triple-negative breast cancer with different responses to neoadjuvant chemotherapy and survival.
In this study, we investigated the prediction and prognostic value of SDF-1 for triple-negative breast cancer (TNBC) patients who underwent neoadjuvant chemotherapy (NAC) following standard radical surgery. A total of 303 TNBC patients were included in this study. The NAC regimen was weekly paclitaxel plus carboplatin (PC) for all patients. SDF-1 and CXCR4 expression were measured at baseline and surgery via enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC), respectively. Correlations between variables and treatment response were studied, and Cox proportional hazards regression analysis was implemented for prognostic evaluation. Of the 303 patients, 103 (34.0%) experienced pathological complete response (pCR) after completion of NAC. Serum SDF-1 expression before NAC was significantly correlated with the abundance of TILs. A higher pCR rate was more likely to be observed in patients with lower serum SDF-1 levels before NAC (P=0.001, OR=0.997, 95% CI: 0.996-0.999) and higher levels of TILs (P=0.005). In the multivariate survival model for nonpCR patients, serum SDF-1 expression at surgery served as an independent prognostic value for survival (high level, HR=1.980, 95% CI: 1.170-3.350, low level was used as a reference; P=0.011). Additionally, the predictive and prognostic value of serum SDF-1 expression was significant in patients with high abundance of TILs but not in patients with low abundance of TILs. This study contributes to the clarification of the value of serum SDF-1 to predict pCR and survival for TNBC patients who underwent NAC. This new serum marker, together with TILs, might help identify clinical subtypes of TNBC with different treatment responses and survival and play an important role in tailoring and modifying the NAC strategy for advanced TNBCs in the future.


Development of a novel intraoperative difficulty score for minimally invasive cholecystectomy.
The rate of biliary injuries from minimally invasive cholecystectomy has remained high for over two decades. To improve outcomes there are multiple bail-out methods described, including aborting the procedure, converting to open, or performing a sub-total cholecystectomy. However, the intraoperative difficulty threshold for when a bail-out method should be implemented is poorly understood. From 1/2014 to 2/2019 cholecystectomy videos were collected, de-identified, edited to include the 2-3 minutes when the gallbladder was first visualized, and accelerated. They were then rated on a 5-point difficulty scale. Inter-coder reliability was evaluated using Krippendorff's alpha and regression models were used to evaluate the scores ability to predict the need for a bail-out technique. 62 videos were analyzed with a median length after editing of 37.5 (29.0-43.3) seconds. A median time of 46.2 (38.3-53.4) seconds was required for grading. The bail-out rate was 42.9%. The inter-coder reliability between 2 surgeons and 8 non-clinical reviewers was 0.675 with an average difficulty score of 3.0 (SD = 1.01). Regression models showed that the scale was able to significantly predict conversion (β=0.56,p<.01). This novel difficulty score was able to predict conversion to a bail-out technique early in the course of minimally invasive cholecystectomy.


Effect of six Korean plants on glucagon like peptide-1 release.
Glucagon like peptide-1 (GLP-1) plays a major role in the regulation of energy homeostasis as it causes satiety and suppresses appetite. Angelica dahurica, Coreanomecon hylomeconoides, Chrysanthemum morifolium, Portulaca oleracea, Stellaria alsine, and Stellaria media have traditionally been used as famine relief foods in Korea. The aim of the present study was to determine whether the aqueous ethanolic extracts of the six plants stimulate GLP-1 secretion. The results demonstrated that each extract of the plants stimulated GLP-1 secretion from enteroendocrine NCI-H716 cells, respectively. Among the extracts examined, the extract of Portulaca oleracea showed the highest activity on GLP-1 release. The results may suggest that the GLP-1 secretion induced by the six plants is a possible mechanism for the six plants exerting effects on satiety increase and appetite suppression.


Determination of Actual Friction Factors in Metal Forming under Heavy Loaded Regimes Combining Experimental and Numerical Analysis.
Tribological conditions can change drastically during heavy loaded regimes as experienced in metal forming; this is especially critical when lubrication can only be applied at the early stage of the process because the homogeneous lubricant layer can break along the die-workpiece interface. In these cases, adopting a constant friction factor for the lubricant-surface pair may not be a valid assumption. This paper presents a procedure based on the use of dual friction factor maps to determine friction factors employed in heavy loaded regimes. A finite element (FE) simulation is used to obtain the friction factor map for the alloy UNS A96082. Experiments were conducted using four lubricants (aluminum anti-size, MoS₂ grease, silicone oil, and copper paste) to determine the actual friction curves. The experimental procedure is based on the application of lubricant only at the beginning of the first stage of ring compression, and not at intermediate stages as is usual in typical ring compression tests (RCTs). The results show that for small reductions (rh < 20%), the conventional RCT can be applied because the tribological conditions remain similar. For large reductions (rh > 20%), it is recommended to obtain an average value of the friction factor for every lubricant-surface pair in the range of deformation considered.


18F-FDG-PET/CT localizes intervertebral disc space infection following posterior lumbar interbody fusion surgery leading to successful retention of percutaneously inserted pedicle screws: a case report.
Postoperative infection is a potentially devastating complication of spine surgery and an appropriate strategy and timely decision-making are essential for successful treatment of deep surgical site infection (SSI) after spinal instrumentation surgeries. However, there is a lack of consensus on implant removal or retention. We report on a case of deep SSI after posterior lumbar interbody fusion (PLIF) surgery in which we achieved clinical cure by debridement and removal of the interbody fusion cage without removing the percutaneously inserted pedicle screws (PPS). A case was a 53-year-old woman with deep SSI after PLIF surgery using the PPS system at the L4-5 level. Computed tomography (CT) showed no clear radiolucent line around the screws and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET)/CT demonstrated abnormal FDG uptake around the cages and no uptake around the pedicle screws. Intervertebral cages were removed and iliac bone grafts were inserted between the vertebral bodies, without removing the pedicle screws. The infection was cleared and bone fusion was achieved after the revision surgery. Targeting active infection using FDG-PET/CT is considered useful in narrowing the surgical margins and determining whether to preserve instrumentation in revision surgery after SSI. PLIF using the PPS system could be useful in preventing the easy spread of infection from the intervertebral space to the insertion point of PPS through the interstitial space.


Laboratory-scale study of the suppression of PCDD/F emission during coal and MSW co-incineration.
The experimental test of co-incinerating Chinese raw municipal solid waste (MSW) and coal in a laboratory-scale tubular reactor was first reported in present study, and the emission of normal gas components and the effects of the S/C1 molar ratio or coal mixing percentages on polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs/Fs) emission were investigated and discussed. The results indicated that OCDD was the only PCDD homologues since others like TCDD-HpCDD was hardly detected, while as the categories of PCDF homologues were comparatively much more general. The amount of PCDD was much larger than that of PCDF in all operating conditions. Since sigma PCDF/sigma PCDD<<1, the dominant role of the precursor formation was proven in our experimental conductions. With increasing the coal addition to MSW (from 0 to 16%), PCDD and PCDF were reduced considerably. Coal and MSW may suppress the PCDD/F emissions efficiently (over 95%) during the MSW incineration process. The PCDD/F suppression results of the present study could be helpful guidance to the industrial application of Chinese MSW and auxiliary coal co-incineration processes. The PCDD/F stack emission data of two industrial incinerators using co-incineration technology in China seem to have a great positive reduction of PCDDs/Fs.


Surface modification-mediated biodistribution of ¹³C-fullerene C₆₀ in vivo.
Functionalization is believed to have a considerable impact on the biodistribution of fullerene in vivo. However, a direct comparison of differently functionalized fullerenes is required to prove the hypothesis. The purpose of this study was to investigate the influences of surface modification on the biodistribution of fullerene following its exposure via several routs of administration. (13)C skeleton-labeled fullerene C60 ((13)C-C60) was functionalized with carboxyl groups ((13)C-C60-COOH) or hydroxyl groups ((13)C-C60-OH). Male ICR mice (~25 g) were exposed to a single dose of 400 μg of (13)C-C60-COOH or (13)C-C60-OH in 200 μL of aqueous 0.9% NaCl solution by three different exposure pathways, including tail vein injection, gavage and intraperitoneal exposure. Tissue samples, including blood, heart, liver, spleen, stomach, kidneys, lungs, brain, large intestine, small intestine, muscle, bone and skin were subsequently collected, dissected, homogenized, lyophilized, and analyzed by isotope ratio mass spectrometry. The liver, bone, muscle and skin were found to be the major target organs for C60-COOH and C60-OH after their intravenous injection, whereas unmodified C60 was mainly found in the liver, spleen and lung. The total uptakes in liver and spleen followed the order: C60 > > C60-COOH > C60-OH. The distribution rate over 24 h followed the order: C60 > C60-OH > C60-COOH. C60-COOH and C60-OH were both cleared from the body at 7 d post exposure. C60-COOH was absorbed in the gastrointestinal tract following gavage exposure and distributed into the heart, liver, spleen, stomach, lungs, intestine and bone tissues. The translocation of C60-OH was more widespread than that of C60-COOH after intraperitoneal injection. The surface modification of fullerene C60 led to a decreased in its accumulation level and distribution rate, as well as altering its target organs. These results therefore demonstrate that the chemical functionalization of fullerene had a significant impact on its translocation and biodistribution properties. Further surface modifications could therefore be used to reduce the toxicity of C60 and improve its biocompatibility, which would be beneficial for biomedical applications.


Thymectomy as an effective treatment in myasthenia.
The paper describes a patient case with early diagnosed myasthenia introduced, who after thymectomy and postsurgical pharmacology achieved a total remission of the disease within six years.


Incidental intrathorcic schwannoma post upper respiratory tract infection associated with Horner's syndrome: A case report.
Schwannomas may remain asymptomatic, and may be discovered incidentally. Here we describe a case of a young female complaining of upper respiratory tract symptoms who was incidentally found to have an intrathoracic neurogenic tumor consistent with schwannoma associated with Horner's syndrome. Biopsy of the tumor revealed S100, BCL-2 and CD 99+ compatible with schwannoma. Patient had brachial plexus exploration and dissection of thoracic inlet tumor resected through video assisted thoracoscopic surgery (VATS). Patient did exceptionally well afterwards with no documented Horner's symptoms. Characterized as a rare case, this patient presented post viral infection and found to have a rare tumor. Successful surgical treatment alleviated her symptoms.


New directions in library design and analysis.
The high costs associated with high-throughput screening (HTS) coupled with the limited coverage and bias of current screening collections is such that diversity analysis continues to be an important criterion in lead generation. Whereas early approaches to diversity analysis were based on traditional descriptors such as two-dimensional fingerprints a recent emphasis has been on assessing scaffold coverage to ensure that a variety of different chemotypes are represented. Moreover, whether designing diverse or focused libraries, it is widely recognised that designs should aim to achieve a balance in a number of different properties and multiobjective optimisation provides an effective way of achieving such designs.


Configurational Entropy Driven High-Pressure Behaviour of a Flexible Metal-Organic Framework (MOF).
Flexible metal-organic frameworks (MOFs) show large structural flexibility as a function of temperature or (gas)pressure variation, a fascinating property of high technological and scientific relevance. The targeted design of flexible MOFs demands control over the macroscopic thermodynamics as determined by microscopic chemical interactions and remains an open challenge. Herein we apply high-pressure powder X-ray diffraction and molecular dynamics simulations to gain insight into the microscopic chemical factors that determine the high-pressure macroscopic thermodynamics of two flexible pillared-layer MOFs. For the first time we identify configurational entropy that originates from side-chain modifications of the linker as the key factor determining the thermodynamics in a flexible MOF. The study shows that configurational entropy is an important yet largely overlooked parameter, providing an intriguing perspective of how to chemically access the underlying free energy landscape in MOFs.


[Body mass index and triceps skinfold correlation in children from Paulínia city, São Paulo, SP].
Body mass index (BMI) has been considered a criterion to define and analyse obesity in adults and children. the purpose of this study was to evaluate the correlation between BMI and triceps skinfold (TSF). there were studied 4,236 children (3.1-10.9y); 48.3%M:51.6%F, from four studies made in Paul nia, SP-Brazil. Height, weight and TSF (Holtain caliper) were measured. For each children BMI was calculated and transformed in SDS, according to North American data (Frisancho, 1993). Multiple linear regression analysis (stepwise) was used for the whole population and in three groups according to BMI: A) SDS < or = -1.0; B) -1.0 < SDS< 1.0) SDS(3) 1.0. Data were processed with SPSS software. in group A, the TSF (7.8 +/- 2.3) variability was lower when compared with the groups B (10.1 +/- 4.0) and C (17.8 +/- 6.2). In multiple linear regression with the whole population, R = 0.478 for TSF. In groups B and C, R = 0.364 and 0.368 respectively for TSF, and in group A it was only 0.032. these observations demonstrated a height correlation between BMI and TSF in children with obesity risk (group C). Therefore, we conclude that, in Brazil BMI can be used for children's research of obesity in population studies, instead of TSF.


Afferent hyperexcitability in neuropathic pain and the inconvenient truth about its degeneracy.
Neuropathic pain, which arises from damage to the nervous system, is a major unmet clinical challenge. Reversing the neuronal hyperexcitability induced by nerve damage is a logical treatment strategy but has proven frustratingly difficult. Here, we propose a novel explanation for that difficulty. Changes in several different ion channels are individually sufficient to cause hyperexcitability in primary somatosensory neurons. Despite offering multiple drug targets, this scenario is problematic: if multiple sufficient changes are triggered by nerve injury, then no single change is necessary for hyperexcitability. This so-called degeneracy compromises therapeutic interventions because drug effects on any one ion channel can be circumvented by changes occurring in other ion channels. Overcoming degeneracy demands a more integrative approach to drug discovery.


Immobilized pH gradient-driven paper-based IEF: a new method for fractionating complex peptide mixtures before MS analysis.
The vast difference in the abundance of different proteins in biological samples limits the determination of the complete proteome of a cell type, requiring fractionation of proteins and peptides before MS analysis. We present a method consisting of electrophoresis of complex mixtures of peptides using a strip of filter paper cut into 20 sections laid end to end over a 24-cm-long IPG strip, the pH gradient of which would drive the electrophoresis. Peptides absorbed onto individual paper pads after electrophoresis are subsequently recovered into a buffer solution, thus dividing a complex peptide mixture according to pI into 20 liquid fractions. This paper-based IEF method (PIEF) was compared side-by-side with a similar but liquid-based Offgel electrophoresis (OGE) by analyzing iTRAQ-labeled peptide mixtures of membrane proteins from four different cell types. PIEF outperformed OGE in resolving acidic peptides, whereas OGE did a better job in recovering relatively basic peptides. OGE and PIEF were quite comparable in their coverage, identifying almost equal number of distinct proteins (PIEF =1174; OGE = 1080). Interestingly, however, only 675 were identified by both of them, each method identifying many unique proteins (PIEF = 499; OGE = 415). Thus, the two methods uncovered almost 40% more proteins compared to what is obtained by only one method. This initial investigation demonstrates the technical feasibility of PIEF for complementing OGE. PIEF uses standard IPG IEF equipment, requires no specialized apparatus (e.g., OGE fractionator) and may be integrated into peptide mapping strategies for clinical samples.


Greek gods and the double-edged sword of liver regeneration.
In the current issue of the Biomedical Journal we gain an insight into the regeneration of liver tissue and how an over-the-counter supplement, stem cells and two plant extracts counteract liver damage. Furthermore the advances against hepatitis C virus are presented, the role of long non-coding RNA elucidated as well as the potential of an adhesion G protein-coupled receptor. In another contribution, the definition and evolutionary impact of copy number variants is clarified. Also, the polymorphism of a scaffolding caspase is investigated. We furthermore learn about the relation between SARS-CoV2 mutants in dependence of geography and explore the challenges of telemedicine in a complex healthcare field. A novel approach to engineering artificial grafts is presented, the challenges of total knee arthroplasty discussed as well as a possible mean of sinus floor elevation for dental implants. At last the concept of flipped classroom is scrutinized in terms of usefulness for a hospital in Taiwan.