Simultaneous Enhancement in Visible Transparency and Electrical Conductivity via the Physicochemical Alterations of Ultrathin-Silver-Film-Based Transparent Electrodes.
A methodology for the simultaneous modulation of the chemical and physical states of an amorphous TiOx layer surface and its impact on the subsequent deposition of a polycrystalline Ag layer are presented. The smoothened TiOx layer surface comprising chemically altered, oxygen-deficient states serves as a nucleating platform for Ag deposition, facilitating a marked increase (∼75%) in the nucleation number density, which strongly enhances the wettability of ultrathin Ag layers. The physically smoothened TiOx/Ag interface further reduces the optical and electrical losses. When the proposed methodology is applied to TiOx/Ag/ZnO transparent conductive electrodes (TCEs), exceptional TCE properties are yielded owing to the simultaneous improvement in visible transparency and electrical conductivity; specifically, a record-high 0.22 Ω-1 Haacke figure of merit is realized. TCEs are prepared on flexible substrates to verify their applicability as stand-alone flexible transparent heaters and as integrated heaters within electrochromic devices to enhance color-switching reactions.


Investigation of multiphase multicomponent aerosol flow dictating pMDI-spacer interactions.
The use of Pressurized metered dose inhalers (pMDIs) for the treatment of asthma and other chronic obstructive pulmonary diseases is frequently associated with breath-actuation synchronization problems and poor pulmonary delivery, particularly amongst the pediatric and geriatric population groups. Spacers, or Valved Holding Chambers (VHCs), are frequently used to address these problems. However, the performance of spacers with different pMDIs is also highly variable and needs to be investigated. The purpose of the current study is to develop a computational fluid dynamics (CFD) model which can characterize multiphase multicomponent aerosol flow issuing from a commercial suspension-based pMDI into a spacer. The CFD model was initially calibrated against published experimental measurements in order to appropriately model the spray characteristics. This model was subsequently used to examine several combinations of inhaler, spacer and USP Throat geometries under different discharge rates of coflow air. The CFD model predictions compared favorably with experimental measurements. In particular, the predictions show, in accordance with experimental determinations, a decrease of drug retained by the spacers with increasing coflow air. The recirculation observed near the obstructions in axial path of the spray within either spacer is considered to be central for increasing spray retention and drug deposition behavior. Fluid flow patterns within the spacers were correlated with drug deposition behavior through a dimensionless variable, the Recirculation index (RCI). Bigger particles were found to be selectively retained within the spacer.


Dental caries in Swedish 4-year-old children. Changes between 1967 and 1987.
The aim of the study was to examine the prevalence of dental caries in 4-year-olds in the town of Umeå in 1987, and compare that data with data from 4-year-olds examined in 1967, 1971, 1976 and 1980/81, using the same diagnostic methods and criteria. The reduction in the mean dmfs value amounting to 75% between 1967 and 1980/81 did not continue up to 1987, but there was an increase in the number of children without caries from 50% in 1980/81 to 58% in 1987. There was also an increase in the proportion of children with 10 or more dmf-surfaces during the same period. The mean value for dmfs remained the same in these years. An analysis was made of the correlation between the frequency of tooth-brushing, use of fluoride toothpaste, snack consumption and the dmfs-value in 1987. A statistically significant difference in mean values for dmfs was found between children who had their teeth brushed greater than or equal to 2/day and less than or equal to 1/day. When fluoride toothpaste was used, the difference was less pronounced. There was no statistically significant difference in the mean intake frequency of snack products among children with and without caries, but a higher proportion of caries-free children was found among those with a low intake frequency of such products.


Sexual Partner Concurrency Among Partners Reported by MSM with Recent HIV Infection.
We examined concurrency among sexual partners reported by men who have sex with men (MSM) with recent (acute or early) HIV infection in San Diego, California (2002-2015). Partners overlapping in time in the past 3 months were considered concurrent. Logistic generalized linear mixed models were used to identify factors associated with concurrency at the partner-level. 56% (388/699) of partners were concurrent to ≥1 other partner. The odds of concurrency were higher among partners >10 years younger than the participant (vs. within 10 years of age) [adjusted odds ratio (AOR) = 2.22, 95% confidence interval (CI) 1.09-4.52], longer term partners (AOR per month = 1.02, 95% CI 1.01-1.03), and partners met online (AOR = 1.56, 95% CI 0.98-2.48). Concurrency is common among partners of recently HIV-infected MSM. Tailored HIV prevention strategies for MSM with older partners, longer term partners, and partners met online may help minimize the potential impact of concurrency on HIV transmission.


Structural and functional properties of lengsin, a pseudo-glutamine synthetase in the transparent human lens.
Lengsin (LGS) is an abundant transcript in the human lens, encoding a predicted polypeptide similar to glutamine synthetase (GS). We show that a major alternatively spliced product of LGS codes for a 57kDa polypeptide that assembles into a catalytically inactive dodecamer, cross-reacts with anti-GS antibodies, and is expressed at high levels in transparent, but not cataractous, human lenses. Based on this characteristic oligomeric organization, preferential expression in the transparent lens, and amyloid-beta association previously reported for GS, a potential chaperone-like role of LGS has been investigated. We find that LGS has six binding sites for the hydrophobic surface probe bis-ANS and relieves cellular toxicity caused by amyloid-beta expression in a folding-impaired yeast mutant. While documenting the structural similarity between LGS and prokaryotic GS-I, the data rule out any involvement of lengsin in glutamine biosynthesis and suggest an unrelated role that may be important for lens homeostasis and transparency.


Hydroalumination reactions on acetylenes and nitriles in the synthesis of carbaalanes and imidoalanes: an overview.
Hydroalumination reactions play an important role in industry as well as from the point of view of academics. The area of carbaalane chemistry is in its infant stage whereas aluminium nitride chemistry has generated a lot of interest from the synthetic and material science perspective. In this overview, we address the simple way of carrying out the hydroalumination reactions on acetylenes and nitriles in the synthesis of carbaalane and imidoalane cluster compounds. A possible mechanism involved in the synthesis of these compounds is discussed. Heteronuclear carbaalane and imidoalane clusters containing transition metals have also been emphasized.


A matrix for DNA separation: genotyping and sequencing using poly(vinylpyrrolidone) solution in uncoated capillaries.
We report a new sieving matrix for DNA separation based on commercially available poly(vinylpyrrolidone). The new sieving matrix has a very low viscosity at moderate concentrations, e.g., 27 cP at 4.5%. Its excellent self-coating property can reduce electroosmotic flow to a negligible level. Column regeneration between runs is very simple and effective. Successful separations were achieved in uncoated capillaries. For genotyping, we show that D1S80 and amelogenin sex determination system can be baseline separated as double-stranded DNA, and vWF, TH01, TPOX, and CSF1PO short tandem repeats can be separated with single-base resolution as single-stranded DNA in this new matrix. Sequencing of M13mp18 showed good resolution up to 500 bases in a solution of high-molecular-weight fraction extracted from commercially available PVP. The feasibility of adaptation to a multicapillary array system is discussed.


The pharmacotherapy of male hypogonadism besides androgens.
Adulthood male hypogonadism (HG) is the most common form of HG. Although testosterone (T) replacement therapy (TRT) is the most common way of treating HG, other options are available depending on patient's needs and expectations. We analyze alternative options to TRT as a medical intervention in treating HG. Gonadotropin (Gn) therapy is the treatment of choice in men with secondary HG (sHG), who require fertility. Gonadotropin-releasing hormone therapy represents an alternative to Gn for inducing spermatogenesis in patients with sHG, however, its use is limited by the poor patient compliance and high cost. In obese HG men, lifestyle modifications and, in particular, weight loss should be the first step. Recent data suggest that antiestrogens represent a successful treatment for sHG. Other potential therapeutic options include the stimulation of hypothalamic activity (i.e., kisspeptin and neurokinin-B agonists). Conversely, the possibility of increasing Leydig cell steroid production, independently from Gn stimulation, seems unreliable. Understanding the nature of male HG and patient's needs are mandatory before choosing among treatment options. For primary HG only TRT is advisable, whereas for the secondary form several alternative possibilities can be offered.


[Laughter and depression: hypothesis of pathogenic and therapeutic correlation].
Laughter is a very common behaviour in everyday life, nevertheless scientific literature is lacking in studies which examine closely its nature. The study aims are: to summarise the present knowledge about laughter and its relation with depression and to make hypotheses on its possible therapeutic function. In the first part of the review the main data existing about encephalic structures involved in laughter genesis, which show participation of cortical and subcortical regions, are reported and the effects of laughter on the organism physiologic equilibrium, particularly on the neuroendocrine and immune systems, are described. In the second part, scientific evidence about the influence of depression on the ability to laugh are referred, which suggests that reduction of laughter frequency is a symptom of the disease and that its increase may be used as a marker of clinical improvement. Finally, the main assumptions supporting the hypothesis of the therapeutic action of laughter on depression are examined: first of all, it has been demonstrated that laughter is able to improve mood directly and to moderate negative consequences of stressful events on psychological well-being; in addition, it is possible that the stimulation of particular cerebral regions, involved in depression pathogenesis, and the normalisation of the hypothalamic pituitary adrenocortical system dysfunctions, both mediated by laughter, can counteract efficiently depressive symptoms; finally, the favourable effects of laughter on social relationships and physical health may have a role in influencing the ability of depressed patients to face the disease.


Abyssocladia vaceleti (Porifera, Cladorhizidae): a new deep-sea carnivorous sponge from Patagonia.
This study describes a new species of carnivorous sponge (Family Cladorhizidae) collected in Patagonia, SW Atlantic, off Argentinean waters and the North of the Falkland Islands (Malvinas). The species described here, belongs to the genus Abyssocladia and was collected by dredging and trawling during IEO (Spanish Institute of Oceanography) cruises in the South West Atlantic Ocean from 2007 to 2010 under the Atlantis Project. Abyssocladia vaceleti sp. nov. is characterised by the possession of a long peduncle and flat body with bilaterally symmetrical and apical filaments with a skeleton of tornotes (often polytylotes), styles, abyssochelae, arcuate chelae, sigmancistras and acanthotylostrongyles. This species lives at depths of 901-1547 m.


Effect of ionic sites of surfactants on leukocyte metabolism.
The effect of ionic and nonionic surfactants on the metabolism of leukocytes was studied. Among anionic surfactants, sodium laurylsulfate, sodium laurate, and sodium lauroyllactate stimulated oxygen uptake and glucose oxidation through the hexose monophosphate pathway. The magnitude of the effect of anionic surfactants seemed to be related to the electrostatic strength of the ionic site of each compound. Cationic, amphoteric, and nonionic surfactants were inhibitory to leukocyte metabolism.


Diagnostic accuracy of multislice CT angiography in peripheral arterial disease.
A systematic search of the PubMed and Medline databases of English literature was performed to determine the diagnostic accuracy of multislice computed tomographic (CT; MSCT) angiography in peripheral arterial disease (PAD) compared with digital subtraction angiography (DSA). Studies comparing MSCT angiography with DSA in peripheral vascular disease were included, and the diagnostic value of MSCT angiography in terms of sensitivity, specificity, and diagnostic accuracy was compared and analyzed. Ten studies (19 comparisons) met the criteria and were included for analysis. The pooled sensitivity, specificity, and accuracy rates were 92%, 91%, and 91%, respectively, at all arterial levels; 92%, 94%, and 93%, respectively, at aortoiliac arteries; 96%, 85%, and 92%, respectively, at femoropopliteal arteries; and 91%, 85%, and 87%, respectively, at infrapopliteal arteries. A significant difference was found in the sensitivity of MSCT angiography in PAD between four-slice CT and 16-slice CT, between aortoiliac and femoropopliteal arterial segments, and between femoropopliteal and infrapopliteal arterial segments (P<.05). This review demonstrates that MSCT angiography has a high diagnostic value and could be a reliable alternative to DSA in the diagnosis of PAD.


Development of an inducible Cas9 nickase and PAM-free Cas12a platform for bacterial diagnostics.
Rapid, efficient, specific and sensitive diagnostic techniques are critical for selecting appropriate treatments for drug-resistant bacterial infections. To address this challenge, we have developed a novel diagnostic method, called the Dual-Cas Tandem Diagnostic Platform (DTDP), which combines the use of Cas9 nickase (Cas9n) and Cas12a. DTDP works by utilizing the Cas9n-sgRNA complex to create a nick in the target strand's double-stranded DNA (dsDNA). This prompts DNA polymerase to displace the single-stranded DNA (ssDNA) and leads to cycles of DNA replication through nicking, displacement, and extension. The ssDNA is then detected by the Cas12a-crRNA complex (which is PAM-free), activating trans-cleavage and generating a fluorescent signal from the fluorescent reporter. DTDP exhibits a high sensitivity (1 CFU/mL or 100 ag/μL), high specificity (specifically to MRSA in nine pathogenic species), and excellent accuracy (100%). The dual RNA recognition process in our method improves diagnostic specificity by decreasing the limitations of Cas12a in detecting dsDNA protospacer adjacent motifs (PAMs) and leverages multiple advantages of multi-Cas enzymes in diagnostics. This novel approach to pathogenic microorganism detection has also great potential for clinical diagnosis.


A procedure for the rapid, large-scall purification of Escherichia coli DNA-dependent RNA polymerase involving Polymin P precipitation and DNA-cellulose chromatography.
An improved method is described for the purification of the DNA-dependent RNA polymerase [ribonucleosidetriphosphate:RNA nucleotidyltransferase, EC 126.96.36.199] from Escherichia coli. The method involves lysozyme-sodium deoxycholate lysis, low-speed centrifugation, precipitation with Polymin P, elution from the Polymin P precipitate, ammonium sulfate precipitation, and chromatography on DNA-cellulose and Bio-Gel A 5m. RNA polymerase is purified to electrophoretic homogeneity in 2 days with a recovery of 45%, resulting in a yield of 250 mg of holoenzyme from 500 g of cells.


Hydroxylation of Compactin (ML-236B) by CYP105D7 (SAV_7469) from Streptomyces avermitilis.
Compactin and pravastatin are competitive cholesterol biosynthesis inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase and belong to the statin drugs; however, the latter shows superior pharmacokinetic characteristics. Previously, we reported that the bacterial P450, CYP105D7, from Streptomyces avermitilis can catalyze the hydroxylation of 1-deoxypentalenic acid, diclofenac, and naringenin. Here, we demonstrate that CYP105D7 could also catalyze compactin hydroxylation in vitro. In the presence of both bacterial and cyanobacterial redox partner systems with an NADPH regeneration system, the reaction produced two hydroxylated products, including pravastatin (hydroxylated at the C6 position). The steady-state kinetic parameters were measured using the redox partners of putidaredoxin and its reductase. The Km and kcat values for compactin were 39.1 ± 8.8 µM and 1.12 ± 0.09 min-1, respectively. The kcat/Km value for compactin (0.029 min-1·µM-1) was lower than that for diclofenac (0.114 min-1·µM-1). Spectroscopic analysis showed that CYP105D7 binds to compactin with a Kd value of 17.5 ± 3.6 µM. Molecular docking analysis was performed to build a possible binding model of compactin. Comparisons of different substrates with CYP105D7 were conclusively illustrated for the first time.


Attempt to assess the infiltration of enamel made with experimental preparation using a scanning electron microscope.
The resin infiltration technique, a minimally invasive method, involves the saturation, strengthening, and stabilization of demineralized enamel by a mixture of polymer resins without the need to use rotary tools or the risk of losing healthy tooth structures. To design and synthesize an experimental infiltrant with potential bacteriostatic properties.To compare the depth of infiltration of the designed experimental preparation with the infiltrant available in the market using a scanning electron microscope. Composition of the experimental infiltrant was established after analysis of 1H NMR spectra of the commercially available compounds that can penetrate pores of demineralized enamel. As the infiltrant should have bacteriostatic features by definition, an addition of 1% of monomer containing metronidazole was made. Thirty extracted human teeth were soaked in an acidic solution, which was to provide appropriate conditions for demineralization of enamel. Afterward, each tooth was divided along the coronal-root axis into two zones. One zone had experimental preparation applied to it (the test group), while the other had commercially available Icon (the control group). The teeth were dissected along the long axis and described above underwent initial observation with use of a Hitachi S-4200 scanning electron microscope. It was found that all samples contained only oxygen and carbon, regardless of the concentration of additions introduced into them. The occurrence of carbon is partially because it is a component of the preparation in question and partially because of sputtering of the sample with it. Hydrogen is also a component of the preparation, as a result of its phase composition; however, it cannot be detected by the EDS method. SEM, in combination with X-ray microanalysis, does not allow one to explicitly assess the depth of penetration of infiltration preparations into enamel.In order to assess the depth of penetration of infiltration preparations with use of X-ray microanalysis, it is recommended to introduce a contrast agent that is approved for use in dental materials, such as ytterbium III fluoride.


The role of the primary care clinician in the management of erectile dysfunction.
Although many medical problems commonly seen in the primary care clinician's office are associated with ED, the majority of men do not discuss sexual difficulties and activities with their clinician. Patients are, however, appreciative of the clinician's willingness to listen and initiate discussions. Often a new level of patient-doctor relationship is thereby reached, which provides for comanagement of sexual and other disorders. The acronym "ALLOW" defines a 5-step proactive management plan for the primary care clinician to follow in order to improve his or her flexibility and sensitivity of response to the patient's ED; at the same time, "ALLOW" helps the clinician to recognize possible limitations in managing sexual health problems. More overall communication has been related to greater patient satisfaction, which in turn results in patients who are more involved in following through on their care, who have increased confidence in their clinician, and who continue to see one physician for their health care needs.


Phospholipase C treatment of mitochondria.
Heavy beef heart mitochondria depleted of phospholipids by treatment with phospholipase C followed by removal of the by products by lipase treatment or sonication in pentane were analyzed by electron microscopy, chemical analysis and assays of enzymatic activities. The results indicate that diglycerides are present after phospholipase C treatment and are inhibitors of NADH-cytochrome c reductase. After removal of diglycerides with lipase treatment, a phospholipid requirement for NADH-cytochrome c reductase could be demonstrated.


The effects of gastric surgery on serum ferritin concentrations.
Changes in serum ferritin concentrations were monitored for three months after gastric operation, in 25 patients. In 23 patients, the serum ferritin concentration was seen to be increased, one week postoperatively, as compared with the preoperative level. Thereafter, in most patients, the serum ferritin concentration gradually decreased to the initial preoperative level. Preoperatively, 13 of the total 25 patients had low serum ferritin concentrations, indicating depleted iron stores. In eleven of these patients, the serum ferritin concentrations followed the above-mentioned course and normal values of serum ferritin concentration were seen postoperatively, indicating normal body iron stores. In six of the ten patients with normal preoperative serum ferritin concentrations, there was a temporary increase within the limits of the normal range. The temporary postoperative increase of serum ferritin concentration was more marked in the patients who underwent total or partial gastrectomy than highly selective vagotomy or fundoplication. We conclude that measurement of serum ferritin concentration may give a false impression of normal body iron stores in the postoperative state.


Tensile bond strength of dentin-resinous system interfaces conditioned with Er:YAG laser irradiation.
The aim of this in vitro study was to assess tensile bond strength of dentin-resinous system interfaces conditioned with Er:YAG laser irradiation. There are different results reported in the literature which relate to laser Er:YAG effects on dentin surface as a pretreatment during adhesives procedures. Forty-two surfaces of human dentin from third upper molar were used after being extracted and kept in the refrigerator in 0.5% chloramines aqueous solution and then divided into three experimental groups and three control groups. The chosen restorative systems were Alert (Jeneric/Penton), Prodigy (Kerr Co.), and Z-100 (3M Co.), with correspondent dental adhesives Bond 1, Optibond Solo, and Single Bond, respectively. To conduct tensile tests, a special system of pairs of rods aligned in a specific apparatus was used, in accordance with ISO/TR 11405 standard (1994). By means of statistical analysis, the Kruskal Wallis test, it was noticed that group IE (laser + acid + Alert), 18.89 MPa, differed considerably from group IC (acid + Alert), 8.03 MPa (p < 0.10), but did not differ from the other groups. Group IIC (acid + Prodigy), 19.88 MPa, differed from group IIE (laser + acid + Prodigy), 12.57 MPa (p < 0.05), but did not differ from groups IIIE (laser + acid + Z-100), 14.11 MPa, and IIIC (acid + Z-100), 19.58 MPa. Group IIIE did not differ statistically from group IIIC. It was concluded that previous Er:YAG laser treatment on the dentinal structure only improved the tensile bond resistance of the Alert restorative system.


Antioxidant vitamin levels among preschool children with uncomplicated Plasmodium falciparum malaria in Sokoto, Nigeria.
To assess antioxidant vitamin levels among preschool children with plasmodium malarial infection. We assessed antioxidant vitamin levels by using a standard procedure in 130 malaria-parasitized preschool children. Packed cell volume and parasite density were also evaluated. Forty healthy age- and gender-matched nonparasitized children were included as controls. Plasmodium falciparum was the causative species in all subjects. The mean malaria parasitemia was 4529.45 ± 1237.5/μL. The mean antioxidant concentrations for vitamins A, C, and E among plasmodium-parasitized subjects were 33.15 ± 1.79 μg/dL, 0.51 ± 0.02 mg/dL, and 0.61 ± 0.02 mg/dL, respectively. The mean concentrations of vitamins A, C, and E among the non-malaria-parasitized controls were 69.72 ± 1.71 μg/dL, 1.25 ± 0.04 mg/dL, and 1.31 ± 0.04 mg/dL respectively. We observed that the mean antioxidant concentrations of vitamins A, C, and E were significantly lower among plasmodium-parasitized subjects compared with non-parasitized controls (P = 0.01). Malaria parasitemia correlated negatively with antioxidant concentrations and packed cell volume (r = -0.736 and -0.723, P = 0.001). We observed that the higher the level of parasitemia, the lower the antioxidant concentration. Our study has shown that the antioxidant levels in plasmodium-parasitized children in the North-West of Nigeria are low and that the more severe the malarial infection, the lower the antioxidant level and the packed cell volume. One key strategic intervention is the provision of early diagnosis and prompt effective treatment. We recommend that malaria-parasitized children, particularly those in the North-West of Nigeria, be placed routinely on antioxidant vitamins to manage the micronutrient deficiencies seen in these children. There is also the need for the promotion of insecticide-treated bed nets, intermittent preventive treatment, and effective case management of malarial illness among children.


Progression of Inflammatory Bowel Diseases Throughout Latin America and the Caribbean: A Systematic Review.
The incidence of inflammatory bowel diseases (IBD) is increasing in Latin America. We performed a systematic review to identify clinical and epidemiologic features of IBD in Latin America (including Mexico, Central America, and South America) and the Caribbean. We searched MEDLINE, EMBASE, and SciELO databases for clinical or epidemiologic studies of Crohn's disease (CD) or ulcerative colitis (UC) from Latin American and Caribbean countries and territories that reported incidence, prevalence, ratio of UC:CD, IBD phenotype, and treatment, through September 12, 2018. Data were extracted from 61 articles for analysis. The incidence and prevalence of IBD have been steadily increasing in Latin America and the Caribbean. The incidence of CD in Brazil increased from 0.08 per 100,000 person-years in 1988 to 0.68 per 100,000 person-years in 1991-1995 to 5.5 per 100,000 person-years in 2015. The highest reported prevalence of IBD was in Argentina, in 2007, at 15 and 82 per 100,000 person-years for CD and UC, respectively. The ratio of UC:CD exceeded 1 in all regions throughout Latin America and the Caribbean with the exception of Brazil. Treatment with tumor necrosis factor antagonists increased steadily for patients with CD (43.4% of all patients in Brazil were treated in 2014) but less so for patients with UC (4.5% of all patients were treated in 2014). Surgery for IBD decreased with time. In Chile, surgeries were performed on 57.0% of patients with CD and 18.0% of patients with UC during the period of 1990-2002; these values decreased to 38.0% and 5.0%, respectively, during the period of 2012-2015. In Peru, 6.9% of patients with UC received colectomies in the period of 2001-2003 and 6.2% in 2004-2014. In a systematic review, we found the incidence of IBD to be increasing throughout Latin America and the Caribbean. Population-based epidemiology studies are needed to evaluate the increase in IBD in these regions, which differ from other global regions in climate, culture, demographics, diet, healthcare delivery and infrastructure, and socioeconomic status.


Beta thalassemia minor is a beneficial determinant of red blood cell storage lesion.
Blood donor genetics and lifestyle affect the quality of red blood cell (RBC) storage. Heterozygotes for beta thalassemia (bThal+) constitute a non-negligible proportion of blood donors in the Mediterranean and other geographical areas. The unique hematological profile of bThal+ could affect the capacity of enduring storage stress, however, the storability of bThal+ RBC is largely unknown. In this study, RBC from 18 bThal+ donors were stored in the cold and profiled for primary (hemolysis) and secondary (phosphatidylserine exposure, potassium leakage, oxidative stress) quality measures, and metabolomics, versus sex- and age-matched controls. The bThal+ units exhibited better levels of storage hemolysis and susceptibility to lysis following osmotic, oxidative and mechanical insults. Moreover, bThal+ RBC had a lower percentage of surface removal signaling, reactive oxygen species and oxidative defects to membrane components at late stages of storage. Lower potassium accumulation and higher uratedependent antioxidant capacity were noted in the bThal+ supernatant. Full metabolomics analyses revealed alterations in purine and arginine pathways at baseline, along with activation of the pentose phosphate pathway and glycolysis upstream to pyruvate kinase in bThal+ RBC. Upon storage, substantial changes were observed in arginine, purine and vitamin B6 metabolism, as well as in the hexosamine pathway. A high degree of glutamate generation in bThal+ RBC was accompanied by low levels of purine oxidation products (IMP, hypoxanthine, allantoin). The bThal mutations impact the metabolism and the susceptibility to hemolysis of stored RBC, suggesting good post-transfusion recovery. However, hemoglobin increment and other clinical outcomes of bThal+ RBC transfusion deserve elucidation by future studies.


Therapeutic effectiveness of instrument-assisted soft tissue mobilization for soft tissue injury: mechanisms and practical application.
This article reviews the mechanism and effects of instrument-assisted soft tissue mobilization (IASTM), along with guidelines for its practical application. IASTM refers to a technique that uses instruments to remove scar tissues from injured soft tissues and facilitate healing process through formation of new extracellular matrix proteins such as collagen. Recently, frequent use of this instrument has increased in the fields of sports rehabilitation and athlete training. Some experimental studies and case reports have reported that IASTM can significantly improve soft tissue function and range of motion following sports injury, while also reducing pain. Based on the previous studies, it is thought that IASTM can help shorten the rehabilitation period and time to return to sports among athletes and ordinary people who have suffered sports injuries. However, few experimental studies of the mechanisms and effects of IASTM have examined, while case reports have accounted for the majority of articles. In the future, the scientific basis of IASTM and its reliability should be provided through well-designed experimental studies on humans. Moreover, IASTM studies that have mostly focused on tendons need to broaden their scope toward other soft tissues such as muscles and ligaments.


Automated "Bone Subtraction" Image Analysis Software Package for Improved and Faster CT Monitoring of Longitudinal Spine Involvement in Patients with Multiple Myeloma.
The study aimed to assess the diagnostic benefit of a novel computed tomography (CT) post-processing software generating subtraction maps of longitudinal non-enhanced CT examinations for monitoring the course of myeloma bone disease in the spine. The local institutional review board approved the retrospective data evaluation. Included were 82 consecutive myeloma patients (46 male; mean age, 65.08 ± 9.76) who underwent 188 repeated whole-body reduced-dose Multislice Detector Computed Tomography (MDCT) at our institution between December 2013 and January 2016. Lytic bone lesions were categorized as new or enlarging versus stable. Bone subtraction maps were read in combination with corresponding 1-mm source images comparing results to those of standard image reading of 5-mm axial and 2-mm multiplanar reformat reconstructions (MPR) scans and hematologic markers, and classified as either progressive disease (PD) or stable disease (SD or remission). The standard of reference was 1-mm axial CT image reading + hematologic response both confirmed at follow-up. For statistical purposes, we subgrouped the hematologic response categories similarly to those applied for CT imaging (progression vs stable/response). According to the standard of reference, 16 patients experienced PD and 66 SD at follow-up. Th sensitivity, specificity, and accuracy for axial 5 mm + 2 mm MPR image versus bone subtraction maps in a "lesion-by-lesion" reading were 97.6%, 92.3%, and 97.2% versus 97.8%, 96.7%, and 97.7%, respectively. The use of bone subtraction maps resulted in a change of response classification in 9.7% of the patients (n = 8) versus 5 mm + 2 mm MPR image reading from SD to PD. Bone sclerosis lesions were detected in 52 out of 82 patients (63.4%). The reading time was significantly lower with the software bone subtraction compared to standard reading (P < 0.01) and 1-mm image reading (P < 0.001). Accuracy of bone subtraction maps reading for monitoring multiple myeloma is slightly increased over that of conventional axial + MPR image reading and significantly speeds up the reading time.


Effect of n-3 fatty acids supplementation during life style modification in women with overweight.
The marine n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) exert numerous beneficial effects on health, but their potency to defend against development of peripheral insulin resistance of healthy person with overweight remains poorly characterized. We aimed to evaluate the effect of a combination intervention using EPA + DHA and the lifestyle modification (LSM) in women with overweight. In a parallel-group, three-arm, randomized trial (UMIN Clinical Trials Registry - R000031131), 34 women were assigned to a 12-week-intervention using corn oil (1.5 g/day; placebo); LSM and corn oil (1.5 g/day; LSM); or LSM and EPA + DHA concentrate (1.5 g/day, containing ~ 0.6 g EPA + DHA; LSM & n-3). At baseline and after intervention, anthropometric measurements including bioelectrical impedance analysis, spiroergometry, 24-hours dietary recall, and various metabolic markers, adiponectin and cytokines were evaluated in serum using standard procedures. Data from 29 women were used for the final evaluation. Wilcoxon two-sided rank-sum test was used to inspect the differences between LSM and LSM & n-3, and placebo groups, with a p-value of ≤ 0.05. All computations were performed with MATLAB Statistics Toolbox. In comparison with placebo, LSM and LSM & n-3 decreased body weight, waist circumference, and body fat, and increased VO2max/kg. LSM & n-3 increased adiponectin levels in comparison to LSM. Fasting insulin, IL8, and cholesterol were decreased by LSM, but were unchanged by LSM & n-3. IL6 was not affected in LSM & n-3, while it was increased in LSM. Other inflammatory markers, as well as leptin, LIF, follistatin, BDNF, and fasting triacylglycerol were not significantly affected by any of the interventions. Besides preventing a modest negative effect of LSM on IL6 and adiponectin level, the combination of LSM and EPA + DHA supplementation could be probably used to improve the functional capacity of adipose tissue in women with overweight.


Slack Reducing Band Improves Combat Application Tourniquet Pressure Profile and Hemorrhage Control Rate.
The Combat Application Tourniquet (CAT) is the tourniquet of choice in the Israeli defense forces. Applying the device loosely before windlass twisting is a main pitfall in CAT application. This study objective is to assess the effectiveness of a novel design modification of the CAT, aiming to prevent loose applications, by minimizing the slack. Using the HapMed leg tourniquet trainer, an above the knee traumatic amputation was simulated. Active duty combatants and Special Forces basic medics were randomly assigned to apply the modified (n = 67) or conventional CAT (n = 65) once. Applied pressure, hemorrhage control status, time to stop the bleeding, and estimated blood volume loss were measured. Using the modified CAT, the mean (±SD) pressure applied was significantly higher compared to the conventional one (231.49 ± 37.84 mm Hg vs. 213.31 ± 45.51 mm Hg, p < 0.05). Hemorrhage control rate was 86.6% in the modified CAT group versus 67.7% in the conventional CAT group (p < 0.05). Analyzing only the applications that succeeded in hemorrhage control, blood loss (171.12 ± 72.43 mL vs.187.75 ± 91.72 mL, p > 0.05) and time to stop bleeding (27.27 ± 13.15 seconds vs. 27.5 ± 11.25 seconds, p > 0.05) were similar. The modified CAT demonstrated an upgraded pressure profile and hemorrhage control rate, potentially indicating its improved efficacy.


Acute and subacute oral toxicity assessment of the oil extracted from Attalea phalerata Mart ex Spreng. pulp fruit in rats.
Attalea phalerata Mart. ex Spreng., popularly known as "bacuri", is a native plant from the brazilian Cerrado and used in folk medicine as a pulmonary decongestant, an anti-inflammatory for joints and antipyretic. There is an expectation about the use in chronic disease of the Attalea phalerata oil since its composition is high in carotenoids and beneficial fatty acids. The aim of the study was to evaluate the toxicological profile of the oil extracted from Attalea phalerata Mart. ex Spreng. pulp (APO). Acute and subacute toxicity studies were performed in male and female Wistar rats according to the OECD - Guidelines 425 and 407. For the acute toxicity, one single dose of the APO (2000mg/kg) was administered by gavage to five female rats. In the subacute toxicity, four different doses (125, 250, 500 and 1000mg/kg) of the APO were administered to male and female rats for 28 consecutive days. No deaths or behavioral changes were observed during both experiments as well as no changes in organ weights, hematological, histopathological parameters. The biochemical parameters showed changes in phosphatase alkaline and albumin levels, however these values are within the normal range for the species. A significant reduction in cholesterol and triglycerides was also observed in some of the animals treated with the APO. Therefore, the LD50 is higher than 2000mg/kg and the APO oil can be considered safe at the doses tested in rats. However, further assessments are required in order to proceed to clinical studies in humans.


Impact of vaccine platform and BCG vaccination on antibody responses to COVID-19 vaccination.
Multiple factors, including vaccine platform and prior vaccinations, influence vaccine responses. We compared antibody responses to CoronaVac (Sinovac) and ChAdOx1-S (AstraZeneca-Oxford) vaccination in 874 healthcare workers in Brazil. As participants were randomised to BCG vaccination or placebo in the preceding 0-6 months as part of the BCG vaccination to reduce the impact of COVID-19 in healthcare workers (BRACE) trial, we also investigated the influence of recent BCG vaccination on antibody responses to these COVID-19 vaccines. Twenty-eight days after the second dose of each vaccine, ChAdOx1-S induced a stronger anti-spike IgG response than CoronaVac vaccination. Recent BCG vaccination did not impact IgG antibody responses to ChAdOx1-S or CoronaVac.


A case of epirubicin-associated cardiotoxicity progressing to life-threatening heart failure and splenic thromboembolism.
We present the case of a 42-year-old Japanese woman who developed acute heart failure after chemotherapy with epirubicin for breast cancer. Echocardiography revealed a cardiac dysfunction with left ventricular thrombus. Serial serum troponin T tests were positive over a 5-week period, and an endomyocardial biopsy demonstrated ultrastructural lesions which were similar to those caused by cardiotoxicities due to doxorubicin. Although the patient developed splenic thromboembolism, her cardiac function recovered gradually, and she regained full range of her activities. This case report demonstrates that epirubicin-associated cardiotoxicity causes life-threatening heart failure and supportive care is important until the patient recovers from acute intoxication.


Collaborating to conserve large mammals in Southeast Asia.
Depressed mammal densities characterize the interior of many Southeast Asian protected areas, and are the result of commercial and subsistence hunting. Local people are part of this problem but can participate in solutions through improved partnerships that incorporate local knowledge into problem diagnosis. The process of involving local people helps build a constituency that is more aware of its role (positive and negative) in a protected area and generates site-specific conservation assessments for management planning. We illustrate the practical details of initiating such a partnership through our work in a Thai wildlife sanctuary. Many protected areas in Southeast Asia present similar opportunities. In local workshops, village woodsmen were led through ranking exercises to develop a spatially explicit picture of 20-year trends in the abundance of 31 mammal species and to compare species-specific causes for declines. Within five taxonomic groups, leaf monkeys (primates), porcupines (rodents), tigers (large carnivores), civets (small carnivores), and elephants (ungulates) had declined most severely (37-74%). Commercial hunting contributed heavily to extensive population declines for most species, and subsistence hunting was locally significant for some small carnivores, leaf monkeys, and deer. Workshops thus clarified which species were at highest risk of local extinction, where the most threatened populations were, and causes for these patterns. Most important, they advanced a shared problem definition, thereby unlocking opportunities for collaboration. As a result, local people and sanctuary managers have increased communication, initiated joint monitoring and patrolling, and established wildlife recovery zones. Using local knowledge has limitations, but the process of engaging local people promotes collaborative action that large mammals in Southeast Asia need.


Ultrathin Space-Shift Phase-Coherent Cancellation Metasurface for Broadband Sound Absorption.
A space-shift phase-coherent cancellation acoustic metasurface is developed, which can achieve broadband low-frequency sound absorption via ultra-thin integrated structure composed of multiple units with weak absorption capability. Through a space-shift design of the channel length, the large-size required in the thickness direction for low-frequency absorption is transferred into an extremely ultra-thin space layer. The units with gradient channel length are compactly arranged in an ultra-thin layer through space folding, a coplanar sound absorption metasurface component with working bandwidth exceeding an octave and thickness of only λ/25 to λ/57 is obtained. As the construction of a special double-hole "bridge" layout, even if the elements are sparsely distributed, strong coupling interactions between the units can sustain. When a certain local phase relationship is satisfied, the coherent cancellation of sound energy can be achieved, so as to reduce the sound reflection and scattering, and enhance the absorption performance. Therefore, from the perspective of phase relationship among units, the present work provides more clear physical image and intuitive theoretical explanation for achieving excellent broadband sound absorption through parallel superposition of multiple units with weak absorption capability. The proposed ultra-thin sound absorbing metasurface can satisfy the thickness limitations and absorption performance requirements in most equipment.


Changing prevalence of severe congenital heart disease: Results from the National Register for Congenital Heart Defects in Germany.
To assess the prevalence of congenital heart disease (CHD) in Germany in relation to phenotypes, severity and gender. Cross-sectional registry study. We analyzed data from patients with CHD born between 1996 and 2015. A total of 26 630 patients, registered with the NRCHD, were born between 1996 and 2015. 10 927 patients were excluded from the current analysis due to prior registration with the NRCHD under the German PAN Prevalence Study, which showed a potential bias in the inclusion of this patient population (proportion of mild cardiac lesions was comparatively high due to improved diagnostic capability for earlier identifying minor lesions). At least 15 703 patients with demographic data and detailed medical information were included in the current study. None. Prevalence of CHD in Germany differentiated into gender, severity, and phenotype. In total, 15 703 patients with CHD (47.1% female) were included in this study. The five most common phenotypes were found to be ventricular septal defect (19.2%), atrial septal defect (13.0%), Tetralogy of Fallot (9.3%), univentricular heart (9.4%), and coractation of the aortae (7.0%). The prevalence of CHD in regard to severity changed over the duration of the observation period. From 1996 to 2007, the number of simple CHD rose steadily (P < .001), whereas the number of severe CHD has grown significantly since 2008/2009 (P < .001). In regard to gender, the prevalence of simple CHD was higher in females, whereas complex lesions were more common in males (P < .001). Our study shows a growing number of registered severe CHD in the recent decade in Germany. This development is noteworthy as it implicates a growing demand for first intensive hospital care, expert pediatric cardiologic aftercare, and consequently higher economic impact for this patient population.


The repopulation of lymph nodes of dogs after 1200 R whole-body x-irradiation and intravenous administration of mononuclear blood leukocytes.
Fresh and cryopreserved autologous or allogeneic mononuclear blood cells (MBCs) intravenously injected in 1200 R total-body x-irradiated dogs repopulated lymph nodes within 10 days after tranfusion. Several parameters of the lymphopoietic regeneration were correlated with the number of cells transfused and with the number of colony-forming units contained in the cell suspension when they were cultured in agar (CFUc). Values within the normal or close to normal range were reached in the mesenteric nodes of most of the animals transfused with 10 X 10(9) MBC or more. These values were obtained when 5 X 10(5) CFUc or more were transfused. Axillary nodes showed lower values than mesenteric nodes. They were mostly under the normal range but well over those of the irradiated controls. Frozen and thawed MBCs seem to be as effective as fresh cells for lymphopoietic restoration. The mesenteric nodes of dogs transfused with allogeneic MBCs showed higher cellularity and larger cortical-paracortical areas than those of dogs tranfused with approximately the same number of autologous cells. The repopulation of lymph nodes parallels that of the marrow.


Sensitivity of drug-resistant mutants of hepatitis B virus to poly-IC.
The long-term benefits of antiviral treatment are limited by the resistance of hepatitis B virus (HBV). However, the effect of interferon (IFN)α treatment on drug-resistant HBVs is so far unknown. We, therefore, investigated the effects of IFN-α inducer poly-IC on the replication of HBV mutants resistant to drugs such as lamivudine (LAM), adefovir dipivoxil (ADV) and entecavir (ETV) in mice. HBV DNA and HBV DNA intermediate (RI) were employed as markers of the virus replication and 2',5'-oligoadenylate synthase (OAS) mRNA as a marker of IFN-α/β induction. Poly-IC inhibited wtHBV replication and increased levels of OAS mRNA. Compared to the wt virus, the capacity of virus replication was reduced in most LAMr and ETVr mutants except those with mutations rtM(204V+L180M+V173L), and was similary in the ADVr mutants except rt(A121V+N236T). The virus replication was reduced after poly-IC treatment with LAMr and ADVr mutants similary to the wt virus. In contrast, ETVr mutants were resistant to the poly-IC treatment. In conclusion, the capacity of HBV replication and the sensitivity to IFN therapy are influenced by drug-resistant mutations. The IFN therapy may effectively inhibit HBV replication in particular in patients with LAMr or ADVr mutations but not in patients with ETVr mutations.


Analysis of a new human parechovirus allows the definition of parechovirus types and the identification of RNA structural domains.
Human parechoviruses (HPeV), members of the Parechovirus genus of Picornaviridae, are frequent pathogens but have been comparatively poorly studied, and little is known of their diversity, evolution, and molecular biology. To increase the amount of information available, we have analyzed 7 HPeV strains isolated in California between 1973 and 1992. We found that, on the basis of VP1 sequences, these fall into two genetic groups, one of which has not been previously observed, bringing the number of known groups to five. While these correlate partly with the three known serotypes, two members of the HPeV2 serotype belong to different genetic groups. In view of the growing importance of molecular techniques in diagnosis, we suggest that genotype is an important criterion for identifying viruses, and we propose that the genetic groups we have defined should be termed human parechovirus types 1 to 5. Complete nucleotide sequence analysis of two of the Californian isolates, representing two types, confirmed the identification of a new genetic group and suggested a role for recombination in parechovirus evolution. It also allowed the identification of a putative HPeV1 cis-acting replication element, which is located in the VP0 coding region, as well as the refinement of previously predicted 5' and 3' untranslated region structures. Thus, the results have significantly improved our understanding of these common pathogens.


The present status of rabies vaccine development and clinical experience with rabies vaccine.
Attempts to control human rabies have a long history: animal and human vaccines provide efficient weapons for prevention. In this presentation, we would like to consider the different rabies vaccines available for human use, and particularly the modern vaccines produced in cell culture. Rabies virus is considered as an unique virus, but in fact, 5 groups of rabies fixed strains are used throughout the world to produce human rabies vaccines: Pasteur, Beijing, Flury, Fuenzalida and SAD strains. The Pasteur-derived strains, designated PV or PM, are the most widely used for the production of traditional vaccines of the Semple or Suckling Mouse Brain (SMB) types, but also for the production of modern cell culture vaccines: Human Diploid and Purified Vero Cell vaccines (HDCV and PVRV). The different rabies vaccines should be classified according to the cell system used to cultivate the virus: animal systems are still employed to produce the old traditional vaccines-Semple and SMB-which continue to be produced in several countries; Primary cell systems, particularly Hamster Kidney and Chick embryo cells, are used; Cell lines are presently the most interesting approach for vaccine production. The use of the human diploid cell system permitted the development of the HDCV, the most widely distributed cell culture rabies vaccine, and today considered as the reference vaccine. The heteroploid VERO cell line was introduced in 1982 to the production of inactivated rabies vaccine; it retained all the advantages of the Human Diploid Cell system, while offering the possibility of the large scale industrial production of PVRV. For both HDCV and PVRV, production security is guaranteed by the existence of a master cell seed and working cell bank, with a complete history of the cell, a limited number of passages and permanent and total quality control of the cell substrate. The principal human rabies vaccines produced worldwide at present using cell culture are compared, in terms of their technical characteristics and their capacity economically to face worldwide vaccine needs. The greatest needs are today in tropical countries, where only a limited amount of modern cell culture vaccines are used.


Lymphocyte proliferation in response to Brucella abortus 2308 or RB51 antigens in mice infected with strain 2308, RB51, or 19.
Lymphocyte proliferation to 22 protein fractions (106 to 18 kDa) of Brucella abortus 2308 or the lipopolysaccharide O-antigen-deficient mutant of 2308, strain RB51, was measured for 20 weeks after infection of mice with strain 2308, RB51, or 19. Throughout the 20-week study, the 22 protein fractions of 2308 and RB51 induced a similar pattern of proliferation when they were incubated with lymphocytes from the infected mice. In addition, during the 20 weeks, lymphocytes from all groups of infected mice exhibited the highest proliferation when the lymphocytes were incubated with 18-kDa or smaller proteins from either 2308 or RB51. Lymphocytes obtained from mice at 6 weeks after infection with strain RB51 or 19 exhibited similar proliferation to the 18-kDa proteins of S2308 or SRB51. Lymphocytes from strain 2308-infected mice did not proliferate to these proteins until 10 weeks after infection, and the responses were similar to those in strain RB51-infected mice but lower than those in strain 19-infected mice. Lymphocytes obtained from mice at 20 weeks after infection with strain 19 or 2308 proliferated to most of the 22 fractions of 2308 or RB51, which contained 106- to 18-kDa proteins. However, lymphocytes obtained from strain RB51-infected mice at 20 weeks did not proliferate to any of these fractions. These results indicate that mice infected with RB51 have less-persistent lymphocyte proliferative responses to 2308 proteins than do mice infected with 2308 or 19. In addition, all 2308 proteins that stimulate lymphocyte proliferation appear to be present in RB51.


'When I am together with them I feel more ill.' The stigma of multiple sclerosis experienced in social relationships.
We explored the stigma that people with multiple sclerosis (MS) experienced in social relationships. Informed by the symbolic integrationist paradigm, this sociological study focuses on the creation of personal identity through interaction with others. The symbolic interactionist account of stigma examines the meaning and reality being negotiated in communication with others. Fourteen people with MS and their relatives were interviewed. The unstructured interviews were tape-recorded, transcribed and coded in accordance with the procedure of grounded theory. Informants reported being ignored or, in contrast, having people overemphasize MS in interpersonal encounters. Although people tried to act tactfully, these acts were experienced as crucial stigmatizing. Informants were coping to counteract stigmatizing experiences in social relationships. People with MS perceive that their bodily performance and impression management is being judged in interpersonal encounters. Being ignored or perceiving that MS is overemphasized indicates the dilemma of managing stigma in social networks. Consequently, during interaction and in social relationships, people with MS experience a sense of 'feeling more ill'. This paper describes strategies of networking to affirm self and identity.


Heart failure and anti tumor necrosis factor-alpha in systemic chronic inflammatory diseases.
Tumor necrosis factor alpha (TNF-alpha) antagonists have emerged as an effective therapy for patients with diseases as Crohn's disease, rheumatoid arthritis, and other chronic systemic inflammatory diseases. In the last years, there has been a growing interest in the role that inflammatory cytokines, which sustain the pathogenesis of these diseases, plays in regulating cardiac structure and function, particularly in the progression of chronic heart failure. In fact there is an increase of anti-TNF alpha levels in advanced heart failure but the treatment with anti-TNF alpha has been shown to worsen the prognosis of heart failure in randomized controlled trials. Patients with rheumatoid arthritis have an increased risk for cardiovascular disease and anti-TNF alpha therapy seems to be beneficial on the risk of cardiovascular disease. In Crohn's disease the increased risk of cardiovascular disease is controversial and therefore it is impossible to demonstrate an effect in reduction of the risk; however, heart failure in patients treated with anti-TNF alpha, despite in a small proportion, has been observed. On the basis of this observation, anti-TNF alpha therapy is contraindicated in patients with Crohn's disease and III-IV New York Heart Association heart failure class.


The emerging relationship of psychology and the Internet: proposed guidelines for conducting Internet intervention research.
The Internet is rapidly developing into an important medium of communication in modern society, and both psychological research and therapeutic interventions are being increasingly conducted using this new communication medium. As therapeutic interventions using the Internet are becoming more prevalent, it is becoming increasingly important to conduct research on psychotherapeutic Internet interventions to assist in the development of an appropriate standard of practice regarding interventions using this new medium. In this article, we examine the Internet and the current psychological uses which are being initiated using this medium. Ethical concerns related to the psychological use of the Internet are discussed, and guidelines are proposed for the conduct of Internet intervention research.


Barriers and facilitators of pediatric shared decision-making: a systematic review.
Shared decision-making (SDM) is rarely implemented in pediatric practice. Pediatric health decision-making differs from that of adult practice. Yet, little is known about the factors that influence the implementation of pediatric shared decision-making (SDM). We synthesized pediatric SDM barriers and facilitators from the perspectives of healthcare providers (HCP), parents, children, and observers (i.e., persons who evaluated the SDM process, but were not directly involved). We conducted a systematic review guided by the Ottawa Model of Research Use (OMRU). We searched MEDLINE, EMBASE, Cochrane Library, CINAHL, PubMed, and PsycINFO (inception to March 2017) and included studies that reported clinical pediatric SDM barriers and/or facilitators from the perspective of HCPs, parents, children, and/or observers. We considered all or no comparison groups and included all study designs reporting original data. Content analysis was used to synthesize barriers and facilitators and categorized them according to the OMRU levels (i.e., decision, innovation, adopters, relational, and environment) and participant types (i.e., HCP, parents, children, and observers). We used the Mixed Methods Appraisal Tool to appraise study quality. Of 20,008 identified citations, 79 were included. At each OMRU level, the most frequent barriers were features of the options (decision), poor quality information (innovation), parent/child emotional state (adopter), power relations (relational), and insufficient time (environment). The most frequent facilitators were low stake decisions (decision), good quality information (innovation), agreement with SDM (adopter), trust and respect (relational), and SDM tools/resources (environment). Across participant types, the most frequent barriers were insufficient time (HCPs), features of the options (parents), power imbalances (children), and HCP skill for SDM (observers). The most frequent facilitators were good quality information (HCP) and agreement with SDM (parents and children). There was no consistent facilitator category for observers. Overall, study quality was moderate with quantitative studies having the highest ratings and mixed-method studies having the lowest ratings. Numerous diverse and interrelated factors influence SDM use in pediatric clinical practice. Our findings can be used to identify potential pediatric SDM barriers and facilitators, guide context-specific barrier and facilitator assessments, and inform interventions for implementing SDM in pediatric practice. PROSPERO CRD42015020527.


Abscisic acid promotion of arbuscular mycorrhizal colonization requires a component of the PROTEIN PHOSPHATASE 2A complex.
Legumes can establish intracellular interactions with symbiotic microbes to enhance their fitness, including the interaction with arbuscular mycorrhizal (AM) fungi. AM fungi colonize root epidermal cells to gain access to the root cortex, and this requires the recognition by the host plant of fungus-made mycorrhizal factors. Genetic dissection has revealed the symbiosis signaling pathway that allows the recognition of AM fungi, but the downstream processes that are required to promote fungal infection are poorly understood. Abscisic acid (ABA) has been shown to promote arbuscule formation in tomato (Solanum lycopersicum). Here, we show that ABA modulates the establishment of the AM symbiosis in Medicago truncatula by promoting fungal colonization at low concentrations and impairing it at high concentrations. We show that the positive regulation of AM colonization via ABA requires a PROTEIN PHOSPHATASE 2A (PP2A) holoenzyme subunit, PP2AB'1. Mutations in PP2AB'1 cause reduced levels of AM colonization that cannot be rescued with permissive ABA application. The action of PP2AB'1 in response to ABA is unlinked to the generation of calcium oscillations, as the pp2aB'1 mutant displays a normal calcium response. This contrasts with the application of high concentrations of ABA that impairs mycorrhizal factor-induced calcium oscillations, suggesting different modes of action of ABA on the AM symbiosis. Our work reveals that ABA functions at multiple levels to regulate the AM symbiosis and that a PP2A phosphatase is required for the ABA promotion of AM colonization.


Expression of proteolytic activity by cultures of Trichophyton rubrum.
Trichophyton rubrum parasitizes the keratinized tissues of humans and proteinases secreted by this organism could function to allow this fungus to metabolize and invade host tissues. The effect of culture medium and glucose on the production of proteinases by cultures of T. rubrum was studied and the expression of these enzymes as a function of time in culture was followed. The fungus was grown to stationary-phase in Sabouraud's glucose broth and the original broth was then replaced with neopeptone, elastin salts, or keratin salts medium. The culture medium was assayed for azocollytic, elastinolytic and keratinolytic activity. Proteolytic activity was also analysed by electrophoresis of culture medium on gelatin and elastin substrate gels. T. rubrum expressed relatively high levels of azocoll-, elastin- and keratin-degrading activity in all of the types of media tested. Glucose partially repressed expression of proteolytic activity, the effect being dependent on the time and conditions of culture. Generally, expression of azocollytic activity peaked in the third week of culture, expression of elastinolytic activity peaked in the first or second week of culture, and expression of keratinolytic activity peaked at different times depending on the composition of the medium. These proteinases probably function to provide the fungus with a source of carbon, nitrogen, and sulfur and may also be responsible for the invasion of host tissues by T. rubrum in the rare cases of disseminated disease.


NCA-Net for Tracking Multiple Objects across Multiple Cameras.
Tracking multiple pedestrians across multi-camera scenarios is an important part of intelligent video surveillance and has great potential application for public security, which has been an attractive topic in the literature in recent years. In most previous methods, artificial features such as color histograms, HOG descriptors and Haar-like feature were adopted to associate objects among different cameras. But there are still many challenges caused by low resolution, variation of illumination, complex background and posture change. In this paper, a feature extraction network named NCA-Net is designed to improve the performance of multiple objects tracking across multiple cameras by avoiding the problem of insufficient robustness caused by hand-crafted features. The network combines features learning and metric learning via a Convolutional Neural Network (CNN) model and the loss function similar to neighborhood components analysis (NCA). The loss function is adapted from the probability loss of NCA aiming at object tracking. The experiments conducted on the NLPR_MCT dataset show that we obtain satisfactory results even with a simple matching operation. In addition, we embed the proposed NCA-Net with two existing tracking systems. The experimental results on the corresponding datasets demonstrate that the extracted features using NCA-net can effectively make improvement on the tracking performance.


Effects of high-intensity isokinetic exercise on salivary cortisol in athletes with different training schedules: relationships to serum cortisol and lactate.
Physical exercise is associated with increases of serum and salivary levels of cortisol. The concomitant increase in serum lactate has been implicated as one of the mechanisms responsible for adrenocortical activation. We evaluated the responses of serum lactate and serum and salivary cortisol to an acute bout of high-intensity isokinetic exercise in eleven non-competitive and twenty competitive athletes (NCA and CA, respectively). The latter group was composed of endurance- and power-trained athletes (EA and PA, respectively). Aims of the study were to determine interindividual differences in the lactate and cortisol responses as a function of type and intensity of training and to search for relationships both between lactate and cortisol production and between serum and salivary cortisol levels. The isokinetic exercise test elicited significant cortisol and lactate responses. No difference was evident in the lactate responses between NCA and CA, while the PA showed a higher response during and after the exercise in comparison to EA (peak levels immediately after the exercise: PA 15.0 +/- 1.5 mmol/l vs. EA 11.1 +/- 2.6 mmol/l, p < 0.01). Serum cortisol was higher in the CA in comparison to the NCA group at 30 and 120 minutes after the termination of the exercise, while no differential response was evident between EA and PA groups. Salivary cortisol response was higher in the CA group in comparison to NCA immediately after the exercise and at 90 and 120 minutes after the termination and was higher in PA in comparison to EA at 60, 90, and 120 minutes after the termination (peak levels at 60 minutes: PA 51.2 +/- 18.5 nmol/l vs. EA 27.5 +/- 20.8 nmol/l, p < 0.05). No significant correlations were found between serum or salivary cortisol and lactate levels. The relationship between serum and salivary cortisol was markedly non-linear, the slope of the serum-saliva regression line being lower for serum cortisol concentrations over 500 nmol/l than for concentrations below that value (0.019 and 0.037, respectively, p < 0.01). We have confirmed in this particular setting the existence of an important adrenocortical response that can be reliably and non invasively assessed by a serial saliva sampling and have supported the concept that cortisol and lactate responses to a high-intensity isokinetic exercise are independent. The interindividual differences in cortisol changes are likely to be related to the training status and mode as well as to the correspondence between the evaluation protocol and the discipline individually performed.


The dementia diagnosis: a literature review of information, understanding, and attributions.
This review examines how people understand and make sense of a dementia diagnosis. The review explores how lay frameworks and information presented at diagnosis may inform a caregiver's understanding of dementia in a family member. Existing qualitative research exploring how caregivers understand and make sense of dementia is reviewed. A literature search was conducted, and the results indicated that family carers often receive little or unclear information about dementia, with diagnostic information often delivered in euphemistic terms. Lack of clarity regarding diagnosis and prognosis creates uncertainty for caregivers and impacts future care planning. Caregiver's understandings of the condition vary, with some symptoms often not attributed to the condition. The literature highlights significant gaps and misconceptions in public knowledge regarding dementia, which raises questions about how family caregivers understand the condition. Further research is required to explore how information is presented to family carers at the time of diagnosis and how this is used to understand the condition.


[Prenatal diagnosis of hemophilia A by DNA analysis].
Hemophilia A caused by defect in the gene of factor VIII is an inherited bleeding disorder most commonly seen in man. Prenatal diagnosis and carrier detection of hemophilia have been done through RFLP analysis in recent years. By use of Bc1I/FVIII-i18, XbaI/FVIII-i22, Bc1I/St14, TaqI/St14 and Bg1II/DX 13 RFLP analysis, prenatal diagnosis of 16 cases at risk of hemophilia A were performed. The results of gene diagnosis showed that two out of 16 pregnant women were normal and therefore prenatal diagnosis was not needed. Among the 14 fetuses at risk four normals and 4 carriers were found in the 8 female fetuses, while in the 6 male fetuses 3 were identified as normal and 3 affected.


Minimally invasive resection of cervical schwannoma (C1-C2 level) using tubular retractors.
Cervical schwannoma excision usually involves laminectomy and violation of the facet joints that necessitates the need for fusion with consequent loss of cervical mobility. The authors present the first video demonstration of an excision of the cervical schwannoma at the C1-2 level using minimally invasive spine tubular retractors, which allows direct access to the lesion and prevents the need for any bony removal. It also preserves the paraspinal muscles, which are important for spinal stability, especially at the C2 level. Special attention is given to incision planning and preoperative image analysis for preventing injury to critical neurovascular structures at this level.


The proportion of individuals with alcohol-induced hypertension among total hypertensives in a general Japanese population: NIPPON DATA90.
Japanese men consume more alcoholic beverages than men in many other developed countries. The high consumption rate of alcoholic beverages among Japanese men may contribute to the high prevalence of hypertension in Japan. In the present study, we calculated the odds ratio for hypertension in alcohol drinkers based on recent criteria using data from a nationwide survey conducted in Japan in 1990, and estimated, among total hypertensives in a general Japanese population, the percentage of hypertensives whose condition was due to alcohol consumption. Of 3,454 male participants, 64.8% were drinkers (1 gou/day, 28.9%; 2 gou/day, 20.1%; 3 gou/day or more, 8.7%; ex-drinkers, 7.0%) and 49.8% were hypertensive, whereas 7.6% of 4,808 female participants were drinkers (1 gou/day, 5.2%; 2 gou/day or more, 1.3%; ex-drinkers, 1.1%) and 43.1% were hypertensive (1 gou=23.0 g of alcohol). In both sexes, drinkers had a higher odds ratio for hypertension than never drinkers, and there was a significant dose-response relationship between the amount of alcohol consumed and the odds ratio for hypertension. Among all hypertensives, the percentage whose hypertension was due to alcohol consumption was 34.5% (95% confidence interval, 10.9%-51.9%) for men and 2.6% (0.8%-5.8%) for women. The corresponding proportion based on daily alcohol intake was 12.7% for 1 gou/day, 11.1% for 2 gou/day, 5.8% for 3 gou/day or more, and 4.8% for ex-drinkers in men, and 1.8% for 1 gou/day, 0.7% for 2 gou/day or more, and -0.1% for ex-drinkers in women. In conclusion, we found that a large percentage of the hypertensives in a general Japanese male population had alcohol-induced hypertension.


Renal neurohormonal and vascular responses to dynamic exercise in humans.
Effects of graded supine dynamic exercise (30, 60, and 80-90% of maximal physical capacity, i.e., work loads of 69, 132, and 188 W) on renal vascular resistance (RVR); renal sympathetic nerve activity [assessed by the renal venous overflow of norepinephrine (NE)]; renal overflows of dopamine (DA), immunoreactive neuropeptide Y (NPY-LI), and renin; as well as plasma concentrations of angiotensin-(1-8)-octapeptide (ANG II) were evaluated in eight healthy male volunteers. Exercise evoked stimulus-dependent and marked elevations of RVR, arterial NE, epinephrine (Epi), and DA. RVR increased by 140% and the renal overflows of NE and DA increased by 1,331 and 179%, respectively, at 188 W. A net removal of NPY-LI at rest turned into a small net renal overflow, which correlated with increases in RVR at 188 W. Increases in renin release (+1,200% at 188 W) correlated with increases in renal NE and DA overflows and with arterial Epi levels. Arterial ANG II levels increased stimulus dependently (by 264% at 188 W) and correlated more closely with increases in RVR than did other variables. Thus dynamic exercise is a potent stimulus for renal nerve activation in humans, and renal sympathetic nerve activity may contribute to increased RVR both directly (NE and, at exhaustive work loads, possibly NPY) and indirectly (via renin-mediated ANG II formation).


Transforming growth factor beta signaling is disabled early in human endometrial carcinogenesis concomitant with loss of growth inhibition.
Transforming growth factor beta (TGF-beta), a potent ubiquitous endogenous inhibitor of epithelial cell growth, is secreted as a latent molecule (LTGF-beta)requiring activation for function. TGF-beta signals through the type I(TbetaRI) and type II (TbetaRII) receptors, which cooperate to phosphorylate/activate Smad2/3, the transcriptional regulators of genes that induce cell cycle arrest. That carcinomas grow in vivo suggests that they are refractory to TGF-beta. However, this has been difficult to prove because of an inability to analyze the functional status of TGF-beta in vivo as well as lack of close physiological paradigms for carcinoma cells in vitro. The current studies demonstrate that whereas primary cultures of endometrial epithelial cells derived from normal proliferative endometrium (PE; n = 10) were dose-dependently and maximally growth inhibited by 55% +/- 5.3% with 10 pM TGF-beta1, endometrial epithelial cells derived from endometrial carcinomas (ECAs; n = 10) were unresponsive (P < or = 0.0066). To determine the mechanism of TGF-beta resistance in ECAs, we analyzed the TGF-beta signaling pathway in vivo by immunohistochemistry using specific antibodies to TbetaRI and TbetaRII, Smads, and to the phosphorylated form of Smad2 (Smad2P), an indicator of cells responding to bioactive TGF-beta. Smad2P was expressed in all of the normal endometria (n = 25), and was localized to the cytoplasm and nucleus in PE, and only nuclear in the secretory endometrium. In marked contrast, Smad2P immunostaining was weak or undetectable in ECA (n = 22; P < or = 0.001) and reduced in glandular hyperplasia (n = 25) compared with normal endometrium. However, total Smad2 and Smad7 (which inhibits Smad2 activation) levels were identical in ECA and normal tissue. Consistent with loss of downstream signaling, both TbetaRI (n = 19) and TbetaRII (n = 22) protein expression were significantly reduced in ECA compared with PE (n = 11; P < or = 0.05). By in situ hybridization, the mRNA levels of TbetaRI and TbetaRII were decreased in the carcinoma cells compared with normal PE glands, suggesting that receptor down-regulation occurs at the transcriptional level. Furthermore, a somatic frameshift mutation in the polyadenine tract at the 5' end of the TbetaR-II gene was detected in two of six cases examined. Finally, the ability of explants of ECA to activate endogenous LTGF-beta was deficient compared with normal tissue (23.5% versus 7.4%). Therefore, our results suggest that loss of Smad2 signaling in ECA may be because of down-regulation of TbetaRI and TbetaRII, and/or decreased activation of LTGF-beta. Because disruption of TGF-beta signaling occurred independent of grade or degree of invasion and was evident in premalignant hyperplasia, we conclude that inactivation of TGF-beta signaling leading to escape from normal growth control occurs at an early stage in endometrial carcinogenesis, thereby defining novel molecular targets for cancer prevention.


Biological and pharmacological aspects of borderline personality disorder.
Biological and psychopharmacological research focusing on patients with a DSM-III-R diagnosis of borderline personality disorder suggests that the disorder may encompass three clusters of symptoms--affective instability, transient psychotic phenomena, and impulsive aggressive behavior--that have different underlying biological substrates that respond to different classes of pharmacological agents. Affective instability, which may be related to abnormalities in the brain's adrenergic and cholinergic systems, appears to respond to agents such as lithium and carbamazepine that are effective in treating major affective disorders. Abnormalities in central dopaminergic systems may underlie transient psychotic symptoms. This relationship is consistent with reports of beneficial effects of low-dose neuroleptics in treating some borderline patients. Abnormalities in central nervous system serotonergic functioning appear to underlie impulsive aggressive behaviors. These behaviors may respond to serotonergic agents such as fluoxetine.


Culinary happiness.
Nutritional and dietary advice is the foundation of diabetes management. Unfortunately, such advice is seen in terms of intrusion and restriction of lifestyle, rather than as a health promoting intervention. This can be corrected by incorporating happiness into dietary modification. Culinary happiness can be defined as the process of sharing dietary, nutritional, and cooking advice, while ensuring the happiness associated with eating remains intact. The concept of culinary happiness includes all domains of culinary science: the procurement, preparation, plating and preservation of food.


Influence of growing season, tannin content and autoclave treatment on the nutritive value of near-isogenic lines of faba beans (Vicia faba L.) when fed to leghorn chicks.
1. The objective of this study was to determine the influence of heat-treatment (autoclaving) on the utilisation by chicks of near-isogenic lines of faba beans that were either tannin-free (Winter-white or Spring-white) or had tannins in the seed coat (Winter-coloured or Spring-coloured). The effect of heat treatment on a common tannin-containing cultivar, Diana, was also studied. 2. The nitrogen-corrected apparent metabolisable energy (AMEn) values of diets containing 600 g faba beans/kg diet were affected by tanning content and autoclave treatment of faba beans, with 59% of total variance in AMEn being attributable to the effect of autoclaving. The AMEn values were 9% higher for chicks fed on the autoclaved compared with those fed on diets containing the raw faba beans, 5% higher for the near-isogenic faba beans with no tannins compared with those with tannins, and 4% higher for the Winter compared with the Spring cultivars. 3. The above study was carried out on droppings obtained by total collection. Similar but not identical trends were obtained when AMEn was calculated using the chromic oxide index method (r = 0.91). 4. Both autoclaving and the use of tannin-free faba beans improved the apparent protein digestibility (APD) of the diets by similar amounts (4% as determined by the total collection method and 6% as determined by the chronic oxide index method). 5. The digestibility of most amino acids either alone or together was affected by a cultivar x tannin x processing interaction. The cultivar by tannin interaction demonstrated that autoclaving increased the digestibility of amino acids to a greater degree when the tannin-containing (for example, 9% for lysine) than when the tannin-free faba beans (4% for lysine) were used in the diets. 6. The improvements in AMEn, APD and total amino acid digestibilities of faba beans following heat treatments ranged from 18% to 33%, 5% to 16% and 5% to 11%, respectively. The results demonstrate that the method of analysis can affect the values obtained but that they do not change the overall pattern of results. The results also suggest that, in most cases, more than half of the response to heat treatment is associated with the inactivation of tannins while the balance of the response is attributable to an effect of heat treatment on the non-tannin-containing factors. In summary, heat treatment can improve the utilisation of faba bean by chickens especially when they contain tannins. 7. Chicks, unlike rats, do not seem to adapt to tannins as the excretion of 3 amino acids that are the main constituents of a proline-rich protein were not affected by dietary tannins.


Surgical retrieval of a guide wire lost during central venous catheterization in a dog.
To report a case of successful surgical removal of a guide wire lost during central venous catheterization. A 28 kg, 4-year-old female neutered mixed breed dog presented to the primary care veterinarian with diabetic ketosis. During the process of central venous catheterization, the guide wire was accidently released and the entire length of the guide wire slipped into the jugular vein. Due to the absence of nearby interventional radiology facilities, surgical intervention was proposed. An ultrasound was used to determine that the guide wire was located in the caudal vena cava extending caudally into the right internal iliac vein. Rommel tourniquets were placed around the iliac vein cranial to the bifurcation of the common iliac vein into the external and internal iliac veins. A venotomy was performed in the right common iliac vein and the guide wire was grasped with hemostats and gently removed while alternately relaxing the cranial then caudal tourniquets. During anesthesia, ventricular premature contractions were noted that varied in frequency with the dog's positioning. Postoperative color flow Doppler ultrasound evaluation of the caudal vena cava, right common, internal and external iliac veins, and right femoral vein was normal with no evidence of thrombosis. Several days postoperative the dog's diabetic ketosis and ventricular premature contractions had resolved and color flow Doppler ultrasound evaluation was normal with no evidence of thrombosis. To the authors' knowledge, this is the first reported veterinary case of loss and subsequent surgical retrieval of a central venous catheter guide wire.


Preparation and antioxidant activity of phosphorylated polysaccharide from purple sweet potato.
Purple sweet potato polysaccharide was extracted via hot water, and it was chemically modified by phosphorus oxychloride-pyridine to obtain phosphorylated polysaccharide from purple sweet potato (P-PPSP) with certain degrees of substitution. Furthermore, the structure and antioxidant activity in vitro of PPSP and phosphorylated derivative were compared. The result indicated that the phosphorylation modification product of polysaccharide from purple sweet potato could improve the scavenging effect on hydroxyl radical and superoxide anion of PPSP, significantly. It also could improve the anti-lipid peroxidation ability while fail to improve the reducing ability of PPSP.


ANCA Associated Vasculitis and Renal Failure Related to Propylthiouracil and Hyperthyroidism Induced Cholestasis in the Same Case.
Introduction. Liver involvement due to hyperthyroidism and also ANCA positive vasculitis related renal failure cases were reported separately several times before. However, to our knowledge, these two complications together in the same case had never been observed before. Case Presentation. The case of an ANCA positive 71-year-old Caucasian male with renal failure and lung involvement, subclinical hyperthyroidism, and intrahepatic cholestatic jaundice was presented in this paper. After exclusion of all of the other possibilities, cholestatic hepatitis was explained by subclinical hyperthyroidism; renal failure and lung involvement were interpreted as ANCA related vasculitis which might be a side effect of propylthiouracil use. Conclusion. The coexistence of these rare conditions in the same patient deserves emphasis and it is worth reporting. This case demonstrates that following the clinical course of the patient is essential after prescribing any medications to see whether any complication occurs or not. If the complications of this case were noticed earlier, it would be possible to treat and to prevent the permanent damages.


The role of pyroptosis in incomplete immune reconstitution among people living with HIV:Potential therapeutic targets.
Globally, HIV infection causes significant morbidity and mortality, and is a major public health problem. Despite the fact that widespread use of antiretroviral therapy (ART) has substantially altered the natural history of HIV infection from originally being a universally lethal disease to now being a chronic medical condition for those taking appropriate treatment, approximately 10-40% of people living with HIV (PLWH) who take effective ART and maintain long-term viral suppression fail to achieve normalization of CD4 + T-cell counts. This phenomenon is referred to as incomplete immune reconstitution or immunological non-response. Although the precise mechanisms underlying this outcome have not been elucidated, recent evidence indicates that excessive pyroptosis may play a crucial role in the development of incomplete immune reconstitution. Pyroptosis is characterized by the formation of pores in the cell membrane, cell rupture, and secretion of intracellular contents and pro-inflammatory cytokines, including IL-1β and IL-18. This excessive inflammation-induced programmed cell death leads to a massive loss of CD4 + T-cells, and inflammatory consequences that may promote and sustain incomplete immune reconstitution. Herein, we review the possible pathways activated in HIV infection by inflammasomes that act as switches of pyroptosis, and the role of pyroptosis in HIV, as well as the relevance of CD4 + T-cells in incomplete immune reconstitution. We also highlight the possible mechanisms of pyroptosis involved in incomplete immune reconstitution, thus paving the way for the development of potential targets for the treatment of incomplete immune reconstitution.


The bacteriophage-associated ehly1 and ehly2 determinants from Escherichia coli O26:H- strains do not encode enterohemolysins per se but cause release of the ClyA cytolysin.
This report presents evidence that the bacteriophage-associated proteins Ehlyl and Ehly2 (enterohemolysin) of non-verotoxigenic E. coli O26:H- are not hemolysins per se. Ehly1 and Ehly2 conferred a hemolytic phenotype on wild-type but not on clyA knockout strains of E. coli K-12 when introduced in trans on plasmids. According to immunoblot analyses, and studies of the expression from a chromosomal clyA::luxAB fusion, the production of cytolysin A (ClyA) was not enhanced by the expression of Ehly1 or Ehly2. However, the analysis provided evidence that there was a low basal level expression of ClyA by E. coli K-12 strains that could be detected phenotypically when the bacteria were subject to lytic effects by bacteriophages or their gene products. In experiments when lysis of the bacteria was caused deliberately either by using lytic bacteriophages (P1 or phiW), or by triggering the SOS response with mitomycin C treatment, sufficient amounts of ClyA were released to cause detectable lysis on blood agar plates. Taken together, our findings support a model where Ehlyl and Ehly2 cause a hemolyric phenotype on blood agar as a result of their lytic and lethal effects on the bacterial hosts.


[Development and evaluation of determination methods for boric acid in agar using ICP-AES and ICP-MS].
A new test method for boric acid in agar was developed. After digestion with nitric acid, the concentration of boron was measured by ICP-AES or ICP-MS with internal standards. Collaborative studies involving 5 laboratories were conducted to evaluate the new method by using a finely powdered agar sample and a standard sample (NIST SRM SRM1570a). The repeatability and reproducibility were very good. Moreover, HORRAT(R) values were less than 2. Therefore, it was considered that the new method is acceptable for the determination of boric acid in agar.


Inhibition of cyclin-dependent kinase activity exacerbates H2 O2 -induced DNA damage in Kindler syndrome keratinocytes.
Kindler syndrome (KS) is an autosomal recessive skin disorder characterized by skin blistering and photosensitivity. KS is caused by loss of function mutations in FERMT1, which encodes Kindlin-1. Kindlin-1 is a FERM domain containing adaptor protein that is found predominantly at cell-extracellular matrix adhesions where it binds to integrin β subunits and is required for efficient integrin activation. Using keratinocytes derived from a patient with KS, into which wild-type Kindlin-1 (Kin1WT) has been expressed, we show that Kindlin-1 binds to cyclin-dependent kinase (CDK)1 and CDK2. CDK1 and CDK2 are key regulators of cell cycle progression, however, cell cycle analysis showed only small differences between the KS and KS-Kin1WT keratinocytes. In contrast, G2/M cell cycle arrest in response to oxidative stress induced by hydrogen peroxide (H2 O2 ) was enhanced in KS keratinocytes but not KS-Kin1WT cells, following inhibition of CDK activity. Furthermore, KS keratinocytes were more sensitive to DNA damage in response to H2 O2 and this was exacerbated by treatment with the CDK inhibitor roscovitine. Thus, in Kindlin-1 deficient keratinocytes, CDK activity can further regulate oxidative damage induced cell cycle arrest and DNA damage. This provides further insight into the key pathways that control sensitivity to oxidative stress in KS patients.


Isotropic-nematic phase equilibria in the Onsager theory of hard rods with length polydispersity.
We analyze the effect of a continuous spread of particle lengths on the phase behavior of rodlike particles, using the Onsager theory of hard rods. Our aim is to establish whether "unusual" effects such as isotropic-nematic-nematic (I-N-N) phase separation can occur even for length distributions with a single peak. We focus on the onset of I-N coexistence. For a log-normal distribution, we find that a finite upper cutoff on rod lengths is required to make this problem well posed. The cloud curve, which tracks the density at the onset of I-N coexistence as a function of the width of the length distribution, exhibits a kink; this demonstrates that the phase diagram must contain a three-phase I-N-N region. Theoretical analysis shows that in the limit of large cutoff, the cloud point density actually converges to zero, so that phase separation results at any nonzero density; this conclusion applies to all length distributions with fatter-than-exponentail tails. Finally, we consider the case of a Schulz distribution, with its exponential tail. Surprisingly, even here the long rods (and hence the cutoff) can dominate the phase behavior, and a kink in the cloud curve and I-N-N coexistence again result. Theory establishes that there is a nonzero threshold for the width of the length distribution above which these long-rod effects occur, and shows that the cloud and shadow curves approach nonzero limits for a large cutoff, both in good agreement with the numerical results.


Time/frequency-domain characterization of a mid-IR DFG frequency comb via two-photon and heterodyne detection.
Mid-infrared frequency combs are nowadays well-appreciated sources for spectroscopy and frequency metrology. Here, a comprehensive approach for characterizing a difference-frequency-generated mid-infrared frequency comb (DFG-comb) both in the time and in the frequency domain is presented. An autocorrelation scheme exploiting mid-infrared two-photon detection is used for characterizing the pulse width and to verify the optimal compression of the generated pulses reaching a pulse duration (FWHM) as low as 196 fs. A second scheme based on mid-infrared heterodyne detection employing two independent narrow-linewidth quantum cascade lasers (QCLs) is used for frequency-narrowing the modes of the DFG-comb down to 9.4 kHz on a 5-ms timescale.


Emerging immunotherapies for malignant glioma: from immunogenomics to cell therapy.
As immunotherapy assumes a central role in the management of many cancers, ongoing work is directed at understanding whether immune-based treatments will be successful in patients with glioblastoma (GBM). Despite several large studies conducted in the last several years, there remain no FDA-approved immunotherapies in this patient population. Nevertheless, there are a range of exciting new approaches being applied to GBM, all of which may not only allow us to develop new treatments but also help us understand fundamental features of the immune response in the central nervous system. In this review, we summarize new developments in the application of immune checkpoint blockade, from biomarker-driven patient selection to the timing of treatment. Moreover, we summarize novel work in personalized immune-oncology by reviewing work in cancer immunogenomics-driven neoantigen vaccine studies. Finally, we discuss cell therapy efforts by reviewing the current state of chimeric antigen receptor T-cell therapy.


Estrogen inhibits renal cell carcinoma cell progression through estrogen receptor-β activation.
Renal cell carcinoma (RCC) originates in the lining of the proximal convoluted tubule and accounts for approximately 3% of adult malignancies. The RCC incidence rate increases annually and is twofold higher in males than in females. Female hormones such as estrogen may play important roles during RCC carcinogenesis and result in significantly different incidence rates between males and females. In this study, we found that estrogen receptor β (ERβ) was more highly expressed in RCC cell lines (A498, RCC-1, 786-O, ACHN, and Caki-1) than in breast cancer cell lines (MCF-7 and HBL-100); however, no androgen receptor (AR) or estrogen receptor α (ERα) could be detected by western blot. In addition, proliferation of RCC cell lines was significantly decreased after estrogen (17-β-estradiol, E2) treatment. Since ERβ had been documented to be a potential tumor suppressor gene, we hypothesized that estrogen activates ERβ tumor suppressive function, which leads to different RCC incidence rates between males and females. We found that estrogen treatment inhibited cell proliferation, migration, invasion, and increased apoptosis of 786-O (high endogenous ERβ), and ERβ siRNA-induced silencing attenuated the estrogen-induced effects. Otherwise, ectopic ERβ expression in A498 (low endogenous ERβ) increased estrogen sensitivity and thus inhibited cell proliferation, migration, invasion, and increased apoptosis. Analysis of the molecular mechanisms revealed that estrogen-activated ERβ not only remarkably reduced growth hormone downstream signaling activation of the AKT, ERK, and JAK signaling pathways but also increased apoptotic cascade activation. In conclusion, this study found that estrogen-activated ERβ acts as a tumor suppressor. It may explain the different RCC incidence rates between males and females. Furthermore, it implies that ERβ may be a useful prognostic marker for RCC progression and a novel developmental direction for RCC treatment improvement.


Branchial cysts. A report of 4 cases.
Cysts presented in the lateral aspect of the neck are relatively uncommon anomalies. Many theories have been proposed to explain the aetiology of these cysts, grouped in two main categories: the congenital and the cervical lymph nodes cystic transformation hypotheses. In this paper we present 4 patient-cases documented in the department of Maxillofacial Surgery, and try to trace the profile of these lesions and investigate their origin. All lesions were well circumscribed by Computed Tomography, and prior to surgery they were assessed by means of fine needle aspiration cytology. Neutrophils, debris and mature squamous epithelial cells including degenerate forms, were the key-features in the cytological diagnosis. Histologic examination of the excised surgical specimen established the diagnosis in all cases. Our findings, compatible with the congenital theory lead us to the conclusion that the branchial cysts are the result of imperfect obliteration of the branchial clefts, arches, and pouches.