An Initial Assessment of a Forgotten Minority Community: Key Informant's Perceptions of Environmental Health in Fresno, Texas.
Environmental hazards are increasingly being detected in minority and low-income communities. The Fresno, Texas community is located near Houston, Texas, and many of its residents are ethnic minorities and of low socioeconomic status. While Fresno residents have voiced concerns about long-standing undocumented environmental hazards, the extent to which the concerns were accurate was unclear. As an initial assessment of environmental exposure hazards, key informant interviews of residents and officials were conducted to examine the perceptions of environmental exposures and associated health effects in the Fresno community. The responses about perceived environmental exposures and the extent of access to primary healthcare were similar between residents and officials. The key informants identified inadequate public water supply and possible groundwater contamination as sources of potential environmental exposures and agreed that access to primary healthcare was a major problem in the Fresno area. However, Fresno residents and officials had contrasting perceptions about the overall health of the community, the existence of community-based organizations, strengths and barriers of the community, and how well environmental concerns were addressed. Qualitative methodology was used to conduct key informant interviews of seven residents and five elected or assigned officials who serve residents of Fresno. An interview guide designed to obtain information on potential environmental hazards and associated health effects was utilized to collect qualitative data that were then utilized to identify recurrent themes and dissimilarities of responses. The responses obtained in this study suggest that potential environmental exposures may be present in this community. However, although residents and officials identified access to primary healthcare as a barrier to residing in Fresno, residents and officials had differing perceptions of the overall heath status of the Fresno community. These findings must be further investigated to develop additional qualitative and quantitative studies that will validate the preliminary findings of this study and begin to accurately measure contaminant levels and health status in Fresno residents.


A microelectrode/microelectronic hybrid device for brain implantable neuroprosthesis applications.
We have designed, fabricated, and characterized a microminiaturized "neuroport" for brain implantable neuroprosthesis applications, using an analog CMOS integrated circuit and a silicon based microelectrode array. An ultra-low power, low-noise CMOS preamplifier array with integral multiplexing was designed to accommodate stringent thermal and electrophysiological requirements for implantation in the brain, and a hybrid integration approach was developed to fabricate a functional microminiaturized neuroprobe device. Measurements showed that our fully scalable 16-channel CMOS amplifier chip had an average gain of 44 dB, bandwidth from 10 Hz to 7.3 kHz, and an equivalent input noise of approximately 9 microVrms with an average power consumption per preamplifier of 52 microW, which is consistent with simulation results. As a proof-of-concept demonstration, we have measured local field potentials from thalamocortical brain slices of rats, showing oscillatory behavior with an amplitude about 0.5 mV and a period ranging 80-120 ms. The results suggest that the hybrid integrated neuroport can form a prime platform for the development of a next level microminiaturized neural interface to the brain in a single implantable unit.


A phospholipid-modified polystyrene-polyisobutylene-polystyrene (SIBS) triblock polymer for enhanced hemocompatibility and potential use in artificial heart valves.
Poly(styrene-block-isobutylene-block-styrene) ('SIBS') is selected for a novel tri-leaflet heart valve due to its high resistance to oxidation, hydrolysis, and enzyme attack. SIBS is modified using six different phospholipids and its mechanical properties characterized by tensile stress, peel strength, shear strength, contact angle, and surface energy, and then for hemocompatibility by studying the adhesion of fluorescently labeled platelets in a parallel plate chamber under physiological flow conditions. Phospholipid modification decreases SIBS tensile stress (at 45% strain) by 30% and reduces platelet adhesion by a factor of 10, thereby improving its hemocompatibility and its potential use as a synthetic heart valve.


Digital tomosynthesis for verifying spine position during radiotherapy: a phantom study.
Monitoring the stability of patient position is essential during high-precision radiotherapy such as spine stereotactic body radiotherapy (SBRT). We evaluated the combination of digital tomosynthesis (DTS) and triangulation for spine position detection, using non-clinical DTS software and an anthropomorphic pelvic phantom that includes a bone-like spine structure. Kilovoltage cone beam CT projection images over 2-16° gantry rotation were used to generate single slice DTS images. Each DTS slice was registered to a digitally reconstructed DTS derived from the planning CT scan to determine 2D shifts between actual phantom and treatment plan position. Two or more DTS registrations, central axes 4-22° apart, were triangulated to determine the 3D phantom position. Using sequentially generated DTS images, the phantom position can be updated every degree with a small latency of DTS and triangulation angle. The precision of position determination was investigated as function of DTS and triangulation angle. To mimic the scenario of spine SBRT, the effect on the standard deviation of megavoltage radiation delivery during kV image acquisition was tested. In addition, the ability of the system to detect different types of movement was investigated for a variety of small sudden and gradual movements during kV image acquisition.


Rooming-in: redesigning hospitals and motherhood in cold war America.
Rooming-in, a model of maternity care that placed newborns in their mothers' rooms instead of central nurseries, appeared in American hospitals in the early 1940s, advocated by physicians and mothers as an antidote to the emotional sterility of the modern maternity ward. It has been cited as a successful illustration of health-care reform, in which practitioners and patients redesigned postpartum care to make it more fulfilling. However, factors other than visionary leadership contributed to the establishment and popularity of rooming-in. First, wartime changes in the medical care of postpartum patients, including antibiotic therapy and early ambulation, paved the way for a system in which mothers played an active role. Second, rooming-in effectively solved two hospital crises: a nursing shortage, and an epidemic of infections in newborn nurseries. Finally, it achieved notoriety far beyond its actual prevalence because it resonated with trends in mass culture: a wariness of technology, interest in the causes and prevention of neurosis, and the "feminine mystique." This article suggests that changes in health care depend less on reasoned planning than on coincidental events inside and outside the hospital.


Energetic contribution of solvent-exposed ion pairs to alpha-helix structure.
Understanding the role of amino acid side-chain interactions in forming secondary structure in proteins is useful for deciphering how proteins fold and for predicting folded structures of proteins from their sequence. Analysis of the secondary structure as a function of pH in two designed synthetic peptides with identical composition but different sequences, affords a quantitative estimate of the free energy contribution of a single ion pair to the stability of an isolated alpha-helix. One peptide contains repeated blocks of Glu4Lys4. The second has repeated blocks of Glu2Lys2. The former contains significant helical structure at neutral pH while the latter has none, based on ultraviolet light circular dichroism measurements and 1H nuclear magnetic resonance spectroscopy. The difference is attributed to formation of helix-stabilizing salt-bridges between Glu- and Lys+ spaced at i, i + 4 intervals in the former peptide. The free energy of formation of a single Glu(-)-Lys+ salt-bridge can be evaluated by using a statistical model of the helix-coil transition that explicitly includes salt-bridges: the result is -0.50(+/- 0.05) kcal/mol at 4 degrees C and neutral pH in 10 mM salt, in agreement with a value derived for a single salt-bridge in a helix on the surface of a globular protein.


Introducing taxanes in the adjuvant treatment of breast cancer: expectations and reality.
Adjuvant chemotherapy in early breast cancer significantly improves disease-free and overall survival. However, a recent update of the world-wide overview indicated that improvements, though statistically significant, are of modest magnitude. Considering the results of individual clinical trials, further improvements in disease-free survival through introduction of new drugs as part of adjuvant treatment for breast cancer are expected to be small. Phase III studies in advanced, measurable disease, each involving several hundreds of patients, have been conducted with both paclitaxel and docetaxel and these results are now available. The high level of efficacy observed, especially with docetaxel, has led to their prompt introduction into adjuvant trials, and the results of one trial with paclitaxel are already available. In this trial, which included 3170 patients, paclitaxel was given every three weeks for four courses following an adjuvant treatment with four courses of doxorubicin and cyclophosphamide (AC) combination. The sequential use of the AC following by the taxane showed an early significant improvement of disease-free survival as compared to AC alone, but the difference observed was exclusively in the 40% of patients who had oestrogen receptor (OR)-negative disease. These patients, and a few of those with OR-positive primaries, did not receive tamoxifen following chemotherapy. Differences in duration of the entire adjuvant treatment programme might have influenced results leading to potentially the wrong conclusion being drawn that the taxane made the difference and other treatment variables had a negligible influence on outcome. Taxanes deserve a 'fair trial' in the adjuvant setting. Moreover, potential cardiotoxicity and long-term impact of high-dose steroids suggest that caution and longer follow-up are required before the definitive introduction of taxanes into the routine care of patients with early breast cancer.


Small-Molecule Host-Defense Peptide Mimetic Antibacterial and Antifungal Agents Activate Human and Mouse Mast Cells via Mas-Related GPCRs.
Host-defense peptides (HDPs) have an important therapeutic potential against microbial infections but their metabolic instability and cellular cytotoxicity have limited their utility. To overcome these limitations, we utilized five small-molecule, nonpeptide HDP mimetics (smHDPMs) and tested their effects on cytotoxicity, antimicrobial activity, and mast cell (MC) degranulation. None of the smHDPMs displayed cytotoxicity against mouse 3T3 fibroblasts or human transformed liver HepG2 cells. However, one compound had both antifungal and antibacterial activity. Surprisingly, all five compounds induced degranulation in a human MC line, LAD2, and this response was substantially reduced in Mas-related G protein-coupled receptor (GPCR)-X2 (MRGPRX2)-silenced cells. Furthermore, all five compounds induced degranulation in RBL-2H3 cells expressing MRGPRX2 but this response was abolished in cells expressing naturally occurring loss-of-function missense variants G165E (rs141744602) and D184H (rs372988289). Mrgprb2 is the likely mouse ortholog of human MRGPRX2, which is expressed in connective tissue MCs (CTMCs) such as cutaneous and peritoneal MCs (PMCs). All five smHDPMs induced degranulation in wild-type PMCs but not in cells derived from Mrgprb2⁻/⁻ mice. These findings suggest that smHDPMs could serve as novel targets for the treatment of drug-resistant fungal and bacterial infections because of their ability to harness CTMCs' host defense functions.


A large-scale epidemiological study to identify bacteria pathogenic to Pacific oyster Crassostrea gigas and correlation between virulence and metalloprotease-like activity.
A 4-year bacteriological survey (2003-2007) of four molluscs cultivated in France and faced with mortality episodes was performed by the French shellfish pathology network. The more abundant bacteria isolated during 92 mortality episodes, occurring mainly in Pacific oyster Crassostrea gigas, were identified by genotyping methods. It allowed us both to confirm the representativeness of Vibrio splendidus and Vibrio aestuarianus bacterial strains and to identify both a large number of Vibrio harveyi-related strains mainly detected during 2007 oyster mortality outbreaks and to a lesser extent bacterial strains identified as Shewanella colwelliana. Because metalloprotease has been reported to constitute a virulence factor in a few Vibrio strains pathogenic for C. gigas, several bacterial strains isolated in this study were screened to evaluate their pathogenicity in C. gigas spat by experimental infection and their ability to produce metalloprotease-like activity in the culture supernatant fluids. A high level (84%) of concordant results between azocaseinase activities and virulence of strains was obtained in this study. Because bacterial metalloprotease activities appeared as a common feature of pathogenic bacteria strains associated with mortality events of C. gigas reared in France, this phenotypic test could be useful for the evaluation of virulence in bacterial strains associated with such mortality episodes.


Imprinted and genotype-specific expression of genes at the IDDM2 locus in pancreas and leucocytes.
One of the loci encoding susceptibility to insulin-dependent diabetes mellitus (IDDM) is IDDM2, mapped to a variable number of tandem repeats (VNTR) polymorphism situated 596 bp upstream of the insulin gene (INS). The shorter alleles (class I) predispose to IDDM, while the longer class III alleles are protective. Besides INS, it is possible that transcription levels of IGF2, the nearby gene encoding the insulin-like growth factor II, may be modulated by allelic forms of the VNTR. In an effort to define the pathophysiologic mechanism of the IDDM2 effect, we examined the effect, in cis, of VNTR genotype on steady-state mRNA levels of INS in samples of human fetal pancreas, and of IGF2 in leucocytes of diabetic children. Relative levels of mRNA transcripts derived from each chromosome carrying a defined VNTR allele were measured by RT-PCR, taking advantage of transcribed polymorphisms at the 3' untranslated region of each gene. In 10 samples of human fetal pancreas, INS transcripts from chromosomes carrying a class III VNTR were slightly but significantly (P = 0.015) lower than those from class I (13% lower, 95% confidence limits 3-21%). In 10 leucocyte samples, mRNA from both IGF2 alleles was seen, indicating relaxation of the parental imprinting of IGF2 in these cells. However, this relaxation was incomplete as maternal allele mRNA was systematically at a lower level than paternal. The paternal/maternal ratio varied widely among individual subjects. Two of the most extreme cases, demonstrating almost complete repression of the maternal allele, were identical twins, suggesting that this variable relaxation of imprinting is genotype-dependent. However, this genotype-dependence cannot be accounted for by the maternal VNTR, as the mean ratios of paternal/maternal IGF2 mRNA levels were not statistically different in individuals with a maternal VNTR of class I vs. class III (3.2 +/- 1.5 vs. 3.89 +/- 0.94). Thus, we present evidence that: (a) class III VNTR alleles are associated with lower INS mRNA in fetal pancreas than class I alleles. The biologic importance of this difference remains to be determined; and (b) the variable relaxation of IGF2 imprinting seen in human leucocytes is not dependent on the presence of a class I vs. a class III VNTR.


Advances in Perovskite Solar Cells.
Organolead halide perovskite materials possess a combination of remarkable optoelectronic properties, such as steep optical absorption edge and high absorption coefficients, long charge carrier diffusion lengths and lifetimes. Taken together with the ability for low temperature preparation, also from solution, perovskite-based devices, especially photovoltaic (PV) cells have been studied intensively, with remarkable progress in performance, over the past few years. The combination of high efficiency, low cost and additional (non-PV) applications provides great potential for commercialization. Performance and applications of perovskite solar cells often correlate with their device structures. Many innovative device structures were developed, aiming at large-scale fabrication, reducing fabrication cost, enhancing the power conversion efficiency and thus broadening potential future applications. This review summarizes typical structures of perovskite solar cells and comments on novel device structures. The applications of perovskite solar cells are discussed.


[Anti-arrhythmic effect of starfish sterol].
To study the effect of modified starfish sterol [C03, succinic acid (5-epiandroene-17-one-3beta-ol) diester] on experimental arrhythmias. Arrhythmias were induced by drugs (Aco, Oua, BaCl2 and adrenalin) i.v., ligating the left anterior descending coronary artery and electricity. C03 71.4 mg x kg(-1) (ig) was shown to increase the dose of Oua inducing VP, VT, VF and CA in guinea pigs (P < 0.01); C03 (26.8, 80.4 mg x kg(-1)) was found to increase the dose of Aco inducing VF and CA in rats (P < 0.01); C03 (8.9, 26.8, 80.4 mg x kg(-1)) increase the dose of barium chloride and delay the onset time of ventricular arrhythmias (P < 0.01); C03 (14.1, 42.3 mg x kg(-10) shorten time of recovering induced by adrenalin in rabbits (P < 0.01); C03 (80.4 mg x kg(-1)) was shown to reduce the number of ventricular arrhythmias induced by coronary artery ligation in rats (P < 0.05), C03 increase VFT induced by electricity in rabbits, VFT of C03 14.1 mg x kg(-1) increased from (5.1 +/- 2.5) V to (11.0 +/- 2.7) V (P < 0.01), 42.3 mg x kg(-1) increased from (6.1 +/- 1.7) V to (15 +/- 5) V (P < 0.01). Starfish sterol has anti-arrhythmic effect.


Flexure effects of double-thin zone toric soft contact lenses.
We use a new model for describing the flexure of hydrogel lenses in situ to evaluate toric hydrogel lenses. The mathematical development of the model precludes use of prism ballasted lenses (because of differential thickness in the vertical meridian and possible lenticulation in the midperiphery), and so double-thin zone lenses were used here. Our results suggest that such lenses (low-minus power) align almost perfectly with the anterior corneal surface creating minimal tear layers.


Personal changes, dispositional optimism, and psychological adjustment to bone marrow transplantation.
We investigated the number and direction of personal changes experienced by long-term survivors of bone marrow transplantation (BMT) and the relationships of those changes and dispositional optimism to psychological adjustment (current and future life satisfaction and mood). Surveys were returned by 86.0% (N = 135) of all eligible long-term survivors; respondents primarily were young males who were 6 to 149 months post-BMT. Subjects reported more positive changes in the relationship and existential/psychological domains and more negative changes in the physical health domain; there was no difference on the plans/activities domain. Negative changes were more strongly related to adjustment than were positive changes. The number of negative changes reported was significantly related to current and future life satisfaction and negative mood after controlling for demographic and illness variables and dispositional optimism. The interaction term for negative and positive changes was significantly related to future life satisfaction after controlling for all other variables.


Cancer Chemopreventive Potential of Procyanidin.
Chemoprevention entails the use of synthetic agents or naturally occurring dietary phytochemicals to prevent cancer development and progression. One promising chemopreventive agent, procyanidin, is a naturally occurring polyphenol that exhibits beneficial health effects including anti-inflammatory, antiproliferative, and antitumor activities. Currently, many preclinical reports suggest procyanidin as a promising lead compound for cancer prevention and treatment. As a potential anticancer agent, procyanidin has been shown to inhibit the proliferation of various cancer cells in "in vitro and in vivo". Procyanidin has numerous targets, many of which are components of intracellular signaling pathways, including proinflammatory mediators, regulators of cell survival and apoptosis, and angiogenic and metastatic mediators, and modulates a set of upstream kinases, transcription factors, and their regulators. Although remarkable progress characterizing the molecular mechanisms and targets underlying the anticancer properties of procyanidin has been made in the past decade, the chemopreventive targets or biomarkers of procyanidin action have not been completely elucidated. This review focuses on the apoptosis and tumor inhibitory effects of procyanidin with respect to its bioavailability.


The expression of interleukin-1 alpha, TNF and VEGF in corneal cells of patients with bullous keratopathy.
Bullous keratopathy (BK) is a chronic corneal edema with or without subepithelial bullae as a result of a loss of the endothelial cells. 15 patients with BK after cataract surgery with intraocular lens implantation, due to Fuchs dystrophy (n = 3) or corneal endothelial trauma (n = 12) were included in the study. All patients were treated by amniotic membrane transplantation (AMT). Corneal epithelial cells in patients suffering from BK secreted 3.91 +/- 3.09 pg/mL of IL-1 alpha, 4446 +/- 16.8 pg/mL of TNF and 81.43 +/- 37.81 pg/mL of VEGF-I. Levels of all 3 investigated cytokines were significantly higher as compared to controls (p < 0.005). Amniotic membranes that were used to treat investigated patients contained 638.98 +/- 613.98 pg/mL of IL-1ra, 0.026 +/- 0.009 pg/mL of sTNF and 81.39 +/- 21.01 pg/mL of VEGF-R. Beneficial clinical effect of the AMT in treating BK could be explained by its natural production of pro-inflammatory cytokine antagonists such as IL-ra, sTNF antagonist and VEGF-R.


Breaking the Binary: The Approach to Chest Masculinizing Gender-Affirming Surgery in Trangender Men.
The purpose of mastectomy for the transgender patient is to produce a masculine appearance of the chest. A number of algorithms have been proposed for selecting the surgical technique. A holistic and surgical approach to transgender men includes our experience-based classification system for selecting the correct surgical technique. To present and discuss the Transgender Standard of Care and our personal experience. Data were collected from the files of female-to-male transgender persons who underwent surgery during 2003-2019. Pictures of the patients were also analyzed. Until May 2021, 342 mastectomies were performed by the senior author on 171 patients. The 220 mastectomies performed on 110 patients until November 2019 were included in our cohort. Patient age was 13.5 to 50 years (mean 22.5 ± 6.1). The excision averaged 443 grams per breast (range 85-2550). A periareolar approach was performed in 14 (12.7%), omega-shaped resection (nipple-areola complex on scar) in 2 (1.8%), spindle-shaped mastectomy with a dermal nipple-areola complex flap approach in 38 (34.5%), and a complete mastectomy with a free nipple-areola complex graft in 56 (50.9%). Complications included two hypertrophic scars, six hematomas requiring revision surgery, three wound dehiscences, and three cases of partial nipple necrosis. A holistic approach to transgender healthcare is presented based on the World Professional Association for Transgender Health standard of care. Analysis of the data led to Wolf's classification for female-to-male transgender mastectomy based on skin excess and the distance between the original and the planned position of the nipple-areola complex.


Gait Disorder Detection and Classification Method Using Inertia Measurement Unit for Augmented Feedback Training in Wearable Devices.
Parkinson's disease (PD) is a common neurodegenerative disease, one of the symptoms of which is a gait disorder, which decreases gait speed and cadence. Recently, augmented feedback training has been considered to achieve effective physical rehabilitation. Therefore, we have devised a numerical modeling process and algorithm for gait detection and classification (GDC) that actively utilizes augmented feedback training. The numerical model converted each joint angle into a magnitude of acceleration (MoA) and a Z-axis angular velocity (ZAV) parameter. Subsequently, we confirmed the validity of both the GDC numerical modeling and algorithm. As a result, a higher gait detection and classification rate (GDCR) could be observed at a higher gait speed and lower acceleration threshold (AT) and gyroscopic threshold (GT). However, the pattern of the GDCR was ambiguous if the patient was affected by a gait disorder compared to a normal user. To utilize the relationships between the GDCR, AT, GT, and gait speed, we controlled the GDCR by using AT and GT as inputs, which we found to be a reasonable methodology. Moreover, the GDC algorithm could distinguish between normal people and people who suffered from gait disorders. Consequently, the GDC method could be used for rehabilitation and gait evaluation.


Peripheral hearing loss following head trauma in children.
The purpose of this prospective study was to determine the incidence and type of hearing loss occurring in children who suffered head injuries. Fifty children admitted to the neurosurgical service after sustaining head trauma were studied. Neurologic, otologic, and audiologic evaluations were performed. Diagnostic studies included skull roentgenograms and computerized tomography scans. A 32% incidence of conductive hearing loss and a 16% incidence of high-frequency sensorineural hearing loss was found in this group. All patients with temporal bone fractures had conductive hearing losses, but the presence of a skull vault fracture did not correlate with the presence, type, or degree of hearing loss. In addition, there was no correlation between either cause of injury, loss of consciousness, or Glasgow Coma Scale scores and the presence, type, or degree of hearing loss. There was a significant incidence of both sensorineural and conductive hearing loss in this series of patients, which indicates that close audiologic and otologic follow-up is necessary for all head injury patients.


Endothelial cells dysfunction induced by silica nanoparticles through oxidative stress via JNK/P53 and NF-kappaB pathways.
Drug carriers are generally introduced into the body intravenously and directly exposed to endothelial cells. Silica nanoparticles could be promising delivery vehicles for drug targeting or gene therapy. However, few studies have been undertaken to determine the biological behavior of silica nanoparticles on endothelial cells. Here we measured reactive oxygen species (ROS) generation, apoptosis and necrosis, proinflammatory and prothrombic properties and the levels of the apoptotic signaling proteins and the transcription factors in human umbilical vein endothelial cells (HUVECs) after exposure to silica nanoparticles of different concentrations (25, 50, 100, and 200 microg/mL) for 24h. The results showed that silica nanoparticles, ranging from 50 microg/mL to 200 microg/mL, markedly induced ROS production, mitochondrial depolarization and apoptosis in HUVECs. At the highest concentration, the necrotic rate, LDH leakage, the expression of CD54 and CD62E, and the release of TF, IL-6, IL-8 and MCP-1 were significantly increased. Silica nanoparticles also activated c-Jun N-terminal kinase (JNK), c-Jun, p53, caspase-3 and NF-kappaB, increased Bax expression and suppressed Bcl-2 protein. Moreover, inhibition of ROS attenuated silica nanoparticles-induced apoptosis and inflammation and the activation of JNK, c-Jun, p53 and NF-kappaB. In summary, our findings demonstrated that silica nanoparticles could induce dysfunction of endothelial cells through oxidative stress via JNK, p53 and NF-kappaB pathways, suggesting that exposure to silica nanoparticles may be a significant risk for the development of cardiovascular diseases such as atherosclerosis and thrombus.


Invasive Candidiasis in Severe Acute Pancreatitis: Experience from a Tertiary Care Teaching Hospital.
Invasive candidiasis (IC) is associated with increased morbidity in severe acute pancreatitis (SAP). There is limited information regarding the predisposing factors, Candida species distribution and in vitro susceptibility. Current data have been derived from a larger prospective nonintervention study conducted on 200 critically ill patients which was done to study the antifungal prescription practices, collect epidemiological data, and perform an external validation of risk prediction models for IC under senior research associateship program of Council of Scientific and Industrial Research New Delhi. Of these critically ill patients, thirty had SAP and were included for analysis. There were 23 males and 7 females. Out of eight patients (27%) who developed IC, three had isolated candidemia, two had isolated deep-seated candidiasis while three had both candidemia and deep-seated candidiasis. SAP patients with IC had a longer duration of Intensive Care Unit stay, hospital stay, days on mechanical ventilation and duration of shock. Mortality was not different between SAP patients with or without IC. There is a high rate of Candida infection in SAP. More studies are needed to generate epidemiological data and develop antifungal stewardship in this subset of high-risk population.


Kinetic equilibrium of forces and molecular events in muscle contraction.
In biomolecular systems, the mechanical transfer of free energy occurs with both high efficiency and high speed. It is shown here that such a transfer can be achieved only if the participating free-energy-storing elements exhibit opposing relationships between their content of free energy and the force they exert in the transfer direction. A kinetic equilibrium of forces (KEF) results, in which the transfer of free energy is mediated essentially by thermal molecular motion. On the basis of present evidence, KEF is used as a guiding principle in developing a mechanical model of the crossbridge cycle in muscle contraction. The model allows the basic features of molecular events to be visualized in terms of plausible structures. Real understanding of the process will require identification of the elements that perform the functions described here. Besides chemomechanical energy transduction, KEF may have a role in other biomolecular processes in which free energy is transferred mechanically over large distances.


The radiation response of asynchronous cells at low dose: evidence of substructure.
Flow cytometry and cell sorting techniques have been used together with repeated measurement in an attempt to define better the radiation survival response of asynchronously dividing Chinese hamster V79-171 cells under aerobic and hypoxic conditions. Although the first two decades of cell inactivation have been examined, particular attention has been given to the low-dose range of a few grays, as used in individual radiation therapy treatments. A single linear-quadratic dose-response function was consistently unable to fit both the low-dose and high-dose data satisfactorily, suggesting a two-component response. Separate fitting of the low-dose and high-dose portions of the response yielded alpha and beta values which differed significantly (P = 0.001 to 0.002). The data are consistent with the hypothesis that the observed substructure simply reflects the presence of subpopulations of sensitive (G1-, G2-phase) and resistant (late S-phase) cells, which are resolved in these measurements. These results may have significance for certain situations in radiation therapy and in biophysical modeling of the radiation response.


Dielectrophoretic force on a sphere near a planar boundary.
The small gap distance separating a spherical colloidal particle in electrophoretic motion from a planar nonconducting surface is a required parameter for calculating its electrophoretic mobility. In the presence of an externally applied electric field, this gap distance is determined by balancing the van der Waals, electrical double layer interaction, and gravitational forces with a dielectrophoretic (DEP) force. Here, the DEP force was determined analytically by integration of the Maxwell stress over the surface of the particle. The account of this force showed that its previous omission from the analysis always resulted in underpredicted gap distances. Furthermore, the DEP force dominated under conditions of low particle density or high electric field strength and led to much higher gap distances on the order of a few microns. In one particular case, a combination of low particle density and small particle size produced two possible equilibrium gap distances for the particle. However, the particle was unstable in the second equilibrium position when subjected to small perturbations. In general, larger particles had smaller gap sizes. The effects of four other parameters on gap distance were studied, and gap distances were found to increase with lower particle density, higher electric field strength, higher particle and wall zeta potentials, and lower Hamaker constants. Retardation effects on van der Waals attraction were considered.


Selective Separation of Metal Ions via Monolayer Nanoporous Graphene with Carboxyl Groups.
Graphene-coated plastic substrates, such as polyethylene terephthalate (PET), are regularly used in flexible electronic devices. Here we demonstrate a new application of the graphene-coated nanoporous PET membrane for the selective separation of metal ions in an ion exchange manner. Irradiation with swift heavy ions is used to perforate graphene and PET substrate. This process could create graphene nanopores with carboxyl groups, thus forming conical holes in the PET after chemical etching to support graphene nanopores. Therefore, a monolayer nanoporous graphene membrane with a PET substrate is constructed successfully to investigate its ionic selective separation. We find that the permeation ratio of ions strongly depends on the temperature and H+ concentration in the driving solution. An electric field can increase the permeation ratio of ions through the graphene nanopores, but it inhibits the ion selective separation. Moreover, the structure of the graphene nanopore with carboxyl groups is resolved at the density functional theory level. The results show the asymmetric structure of the nanopore with carboxyl groups, and the analysis indicates that the ionic permeation can be attributed to the ion exchange between metal ions and protons on the two sides of graphene nanopores. These results would be beneficial to the design of membrane separation materials made from graphene with efficient online and offline bulk separation.


Membrane association and conformational change of palmitoylated G(o)alpha.
Bovine brain G(o)alpha was specifically palmitoylated in vitro. The apparent dissociation constant for depalmitoylated G(o)alpha (dG(o)alpha) was 0.273 microM, while that for palmitoylated G(o)alpha (pG(o)alpha) was 5.77 nM. The dissociation rate constant (K(21)) and dissociation half-life for dG(o)alpha were 8.4x10(-4) min and 825 min respectively, while no significant dissociation of pG(o)alpha was detected. The limiting membrane insertion pressures for pG(o)alpha and dG(o)alpha were 44.4 mN/m and 41.3 mN/m respectively. These data suggested that palmitoylation facilitated the membrane association of G(o)alpha. Conformational changes of dG(o)alpha and pG(o)alpha detected by monitoring fluorescence spectra and fluorescence quenching were significantly different after they were associated with the membrane. It was suggested that conformational changes of G(o)alpha upon membrane association might be related to regulation of G(o)alpha signaling by palmitoylation.


Pollinator-mediated gene flow fosters genetic variability in a narrow alpine endemic, Abronia alpina (Nyctaginaceae).
For rare and endemic plants that exist in small, isolated habitats, natural selection is expected to favor self-compatibility, which can result in low genetic diversity due to inbreeding and genetic drift. Using Abronia alpina, a rare alpine endemic of the California Floristic Province, we demonstrate that there are exceptions to these predictions. We present the results of both a pollination experiment and a genetic study using AFLPs (amplified fragment length polymorphisms). Using controlled hand-pollination and pollinator observations, we examined the breeding system, pollination ecology, and mechanism for self-incompatibility in A. alpina. Abronia alpina exhibits an allogamous mating system with probable self-incompatibility resulting from limited growth of pollen tubes originating from self-pollination. Only xenogamous crosses and open-pollinated controls produced seed, and only xenogamous crosses produced pollen tubes that reached the ovary. The molecular study shows that A. alpina has substantial genetic diversity for a rare, endemic species, evidenced by the high percentage of polymorphic loci and average expected heterozygosity. Gene flow among subpopulations, as inferred from AFLP markers, appears to be substantial, although the Kern River is an important physical barrier. Our results indicate that A. alpina is dependent on insects for both seed production and the maintenance of genetic diversity. This finding suggests that pollinators may be crucial to the long-term adaptive potential of rare, endemic plants and that conservation of rare endemics is, in part, dependent on community-level interactions such as plant-pollinator mutualisms.


Intrinsic motivation as a predictor of work outcome after vocational rehabilitation in schizophrenia.
Intrinsic motivation is a construct commonly used in explaining goal-directed behavior. In people with schizophrenia, intrinsic motivation is usually subsumed as a feature of negative symptoms or underlying neurocognitive dysfunction. A growing literature reflects an interest in defining and measuring motivational impairment in schizophrenia and in delineating the specific role of intrinsic motivation as both an independent predictor and a mediator of psychosocial functioning. This cross-sectional study examined intrinsic motivation as a predictor of vocational outcomes for 145 individuals with schizophrenia and schizoaffective disorder participating in a 6-month work rehabilitation trial. Correlation and mediation analyses examined baseline intrinsic motivation and negative symptoms in relation to work hours and work performance. Data support a significant relationship between intrinsic motivation and negative symptoms and significant correlations with outcome variables, such that lower negative symptoms and greater intrinsic motivation were associated with better work functioning. Moreover, in this sample, intrinsic motivation fully mediated the relationships between negative symptoms, work productivity, and work performance. These results have significant implications on the design of work rehabilitation interventions for people with schizophrenia and support a role for targeting intrinsic motivation directly to influence vocational functioning. Future directions for research and intervention are discussed.


Rubber-Filler Interactions in Polyisoprene Filled with In Situ Generated Silica: A Solid State NMR Study.
In this paper we used high- and low-resolution solid state Nuclear Magnetic Resonance (NMR) techniques to investigate a series of polyisoprene samples filled with silica generated in situ from tetraethoxysilane by sol-gel process. In particular, ¹H spin-lattice and spin-spin relaxation times allowed us to get insights into the dynamic properties of both the polymer bulk and the bound rubber, and to obtain a comparative estimate of the amount of bound rubber in samples prepared with different compositions and sol-gel reaction times. In all samples, three fractions with different mobility could be distinguished by ¹H T₂ and ascribed to loosely bound rubber, polymer bulk, and free chain ends. The amount of bound rubber was found to be dependent on sample preparation, and it resulted maximum in the sample showing the best dispersion of silica domains in the rubber matrix. The interpretation of the loosely bound rubber in terms of "glassy" behaviour was discussed, also on the basis of ¹H T₁ and T1ρ data.


Diagnostic ileocolonoscopy: getting the basics right.
Proficient colonoscopy technique that optimises patient comfort while simultaneously enhancing the timely detection of pathology and subsequent therapy is an aspirational and achievable goal for every endoscopist. This article aims to provide strategies to improve colonoscopy quality for both endoscopists and patients.


Phylogeny, origin and dispersal of Saussurea (Asteraceae) based on chloroplast genome data.
Saussurea is one of the largest genera of the tribe Cardueae of Asteraceae, comprising about 460 species from the Northern Hemisphere with most species distributed in QTPss and adjacent areas. Here, we established a well-supported phylogenetic framework for Saussurea based on whole chloroplast genomes of 136 taxa plus 16 additional taxa of Cardueae using Bayesian inference and Maximum Likelihood. Our phylogenetic results are inconsistent with previous subgeneric classifications of Saussurea. We nearly completely delimited subgen. Eriocoryne, and found that subgen. Theodorea, subgen. Saussurea section Laguranthera and Rosulascentes are closely related to each other. Based on our phylogenetic results, we performed biogeographic analyses and inferred that the genus Saussurea arose during early-middle Miocene within the Hengduan Mountains. We expect that landscape heterogeneity within the QTPss and adjacent areas, such as the Hengduan Mountains, played an important role in the evolution of Saussurea. Following its evolutionary origin, the genus underwent rapid diversification in situs and dispersed northwards in several migrational patterns. Both continuous uplift of the QTPss and adjacent areas as well as global cooling since mid-Miocene probably led to geographic expansion and diffusion of Saussurea, with the latter, in particular, resulting in the northward dispersal.


Size, technology, complexity, and structural differentiation: toward a theoretical synthesis.
This paper proposes a theoretical synthesis of the concepts of organizational size, technology, complexity, and structural differentiation. It suggests and finds that the most important determinant of differentiation in the division of labor is the scope of an organization's task, a technological dimension, and not organizational size. Neither horizontal nor vertical differentiation is thought to be determined by size while the scope of the task is proposed as a determinant of horizontal differentiation. The findings, however, support only the inference of a moderate causal connection between either size or task scope and either form of differentiation. Throughout the analysis and discussion the contrast between causal inference based on associations of levels and change rates is discussed. When dealing with the organizational processes addressed in this paper, both associations must be examined to adequately portray the complexity of the causal processes inferred.


Guidelines for the conduct of human embryonic stem cell research.
This appendix provides a summary of and links to the ISSCR Guidelines for the Conduct of Human Embryonic Stem Cell Research and supporting documents.


Glioma targeted therapy: insight into future of molecular approaches.
Gliomas are the common type of brain tumors originating from glial cells. Epidemiologically, gliomas occur among all ages, more often seen in adults, which males are more susceptible than females. According to the fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5), standard of care and prognosis of gliomas can be dramatically different. Generally, circumscribed gliomas are usually benign and recommended to early complete resection, with chemotherapy if necessary. Diffuse gliomas and other high-grade gliomas according to their molecule subtype are slightly intractable, with necessity of chemotherapy. However, for glioblastoma, feasible resection followed by radiotherapy plus temozolomide chemotherapy define the current standard of care. Here, we discuss novel feasible or potential targets for treatment of gliomas, especially IDH-wild type glioblastoma. Classic targets such as the p53 and retinoblastoma (RB) pathway and epidermal growth factor receptor (EGFR) gene alteration have met failure due to complex regulatory network. There is ever-increasing interest in immunotherapy (immune checkpoint molecule, tumor associated macrophage, dendritic cell vaccine, CAR-T), tumor microenvironment, and combination of several efficacious methods. With many targeted therapy options emerging, biomarkers guiding the prescription of a particular targeted therapy are also attractive. More pre-clinical and clinical trials are urgently needed to explore and evaluate the feasibility of targeted therapy with the corresponding biomarkers for effective personalized treatment options.


False memories seconds later: the rapid and compelling onset of illusory recognition.
Distortions of long-term memory (LTM) in the converging associates task are thought to arise from semantic associative processes and monitoring failures due to degraded verbatim and/or contextual memory. Sensory-based coding is traditionally considered more prevalent than meaning-based coding in short-term memory (STM), whereas the converse is true of LTM, leading to the expectation that false memory phenomena should be less robust in a canonical STM task. These expectations were violated in 2 experiments in which participants were shown lists of 4 semantically related words and were probed immediately following a filled 3- to 4-s retention interval or approximately 20 min later in a surprise recognition test. Corrected false recognition rates, confidence ratings, and Remember/Know judgments reveal similar false memory effects across STM and LTM conditions. These results indicate that compelling false memory illusions can be rapidly instantiated and that, consistent with unitary models of memory, they originate from processes that are not specific to LTM tasks.


Antileishmanial Mechanism of Diamidines Involves Targeting Kinetoplasts.
Leishmaniasis is a disease caused by pathogenic Leishmania parasites; current treatments are toxic and expensive, and drug resistance has emerged. While pentamidine, a diamidine-type compound, is one of the treatments, its antileishmanial mechanism of action has not been investigated in depth. Here we tested several diamidines, including pentamidine and its analog DB75, against Leishmania donovani and elucidated their antileishmanial mechanisms. We identified three promising new antileishmanial diamidine compounds with 50% effective concentrations (EC50s) of 3.2, 3.4, and 4.5 μM, while pentamidine and DB75 exhibited EC50s of 1.46 and 20 μM, respectively. The most potent antileishmanial inhibitor, compound 1, showed strong DNA binding properties, with a shift in the melting temperature (ΔTm) of 24.2°C, whereas pentamidine had a ΔTm value of 2.1°C, and DB75 had a ΔTm value of 7.7°C. Additionally, DB75 localized in L. donovani kinetoplast DNA (kDNA) and mitochondria but not in nuclear DNA (nDNA). For 2 new diamidines, strong localization signals were observed in kDNA at 1 μM, and at higher concentrations, the signals also appeared in nuclei. All tested diamidines showed selective and dose-dependent inhibition of kDNA, but not nDNA, replication, likely by inhibiting L. donovani topoisomerase IB. Overall, these results suggest that diamidine antileishmanial compounds exert activity by accumulating toward and blocking replication of parasite kDNA.


Progress Toward Rice Seed OMICS in Low-Level Gamma Radiation Environment in Iitate Village, Fukushima.
Here, we present an update on the next level of experiments studying the impact of the gamma radiation environment, created post-March, 2011 nuclear accident at Fukushima Daiichi nuclear power plant, on rice plant and its next generation-the seed. Japonica-type rice (Oryza sativa L. cv. Koshihikari) plant was exposed to low-level gamma radiation (~4 μSv/h) in the contaminated Iitate Farm field in Iitate village (Fukushima). Seeds were harvested from these plants at maturity, and serve as the treated group. For control group, seeds (cv. Koshihikari) were harvested from rice grown in clean soil in Soma city, adjacent to Iitate village, in Fukushima. Focusing on the multi-omics approach, we have investigated the dry mature rice seed transcriptome, proteome, and metabolome following cultivation of rice in the radionuclide contaminated soil and compared it with the control group seed (non-radioactive field-soil environment). This update article presents an overview of both the multi-omics approach/technologies and the first findings on how rice seed has changed or adapted its biology to the low-level radioactive environment.


The clinical effect of Nano micelles containing curcumin as a therapeutic supplement in patients with COVID-19 and the immune responses balance changes following treatment: A structured summary of a study protocol for a randomised controlled trial.
To investigates the effectiveness of curcumin-containing Nanomicelles as a therapeutic supplement in the treatment of patients with COVID-19 and its effect on immune responses balance changes following treatment. This study is conducted as a prospective, placebo-controlled with parallel group, single-center randomized clinical trial on COVID-19 patients. Patients are selected from the COVID-19 ward of Shahid Mohammadi Hospital in Bandar Abbas, Iran. 1. Real time PCR-approved positive COVID-19 test. 2. Both gender 3. Age between 18 and 75 years 4. Signing a written consent 5. Lack of participation in other clinical trials Exclusion criteria: 1. Pregnancy or lactation 2. Allergy to turmeric or curcumin 3. Smoking 4. Patient connected to the ventilator 5. SaO2 less than 90% or PaO2 less than 8 kPa 6. Having comorbidities (such as severe renal failure, Glomerular filtration rate less than 30 ml/min, liver failure, Congestive heart failure, or Chronic obstructive pulmonary disease) 7. History of gallstones 8. History of gastritis or active gastrointestinal ulcer INTERVENTION AND COMPARATOR: In addition to the routine standard treatments for COVID-19, in the intervention group, 40mg nanomicelles containing curcumin (SinaCurcumin Capsule, Exir Nano Sina Company, Iran), four times per day (after breakfast, lunch, dinner and before bedtime) and in the placebo group as the control group, capsules with the same appearance and characteristics (Placebo capsules, Exir Nano Sina Company, Iran) are prescribed for two weeks. The effectiveness of Nano micelles containing curcumin treatment will be evaluated as daily clinical examinations of patients in both groups and, on days 0, 7 and 14, complete clinical symptoms and laboratory findings including peripheral blood and serum parameters such as inflammatory markers will be measured and recorded. Moreover, in order to evaluate the balance of immune responses changes following treatments, serum level of IFN-γ, IL-17, Il-4 and TGF-β serum cytokines will be measured in both groups at time points of 0, 7 and 14 days post treatment. Gene expression of t-bet, GATA-3, FoxP3 and ROR- γT will also be measured at mentioned time points to assess the shift of T helper1, T helper2, T regulatory and T helper 17 immune responses following treatment. Randomized trials will be performed on 40 COVID-19 patients which will be randomized using encoded sealed boxes with computer generated random digits with 1:1 allocation ratio. In order to randomization, placebo and SinaCurcumin Capsules will be numbered first by computer generated random digits. SinaCurcumin and placebo will then be stored and numbered in sealed packages based on generated random numbers. Finally, according to the order in which patients enter the study, packages are given to patients based on their number. The present study will be blind for all patients, physicians and nurses, laboratory technicians and statisticians. A total of 40 patients will be included in the study, 20 of them will be randomly assigned to the intervention group and 20 to the placebo group. This is Version 1.0 of protocol dated 21 May 2020. The recruitment was started June 24, 2020 and is expected to be completed by October 31, 2020. This present clinical trial has been registered in the Iranian Registry of Clinical Trials (IRCT) with the registration code of "IRCT20200611047735N1", https://www.irct.ir/trial/48843 . Dated: 19 June 2020. The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Development of chalcone-based derivatives for sensing applications.
The sensing of various analytes including metal ions and anions is at an incredible speed due to their widespread use in biological processes. Various small molecular species have been reported for the detection of various analytes, with the advantage of low cost and high sensitivity. Among various classes of organic molecules, chalcones are suitable candidates for the design of new chemosensors for targeted ions. In this review, using extensive examples of chalcone-based chemosensors, we explore the design, mechanism, and performance of various chemosensors for the detection of different ions. We believe that this review will provide new insight for researchers in related areas to develop chemosensors for various targeted ions.


Reversible binding of ethacrynic acid to human serum albumin: difference circular dichroism study.
The reversible binding of ethacrynic acid was characterized by a difference circular dichroism method. A 2/1 stoichiometry was determined for the [drug]/[HSA] (human serum albumin) complex. The reversible binding of ethacrynic acid to HSA determines direct competition with ligands that selectivity bind to site II and to the fatty acid site. Furthermore, indirect competition was shown for ligands for site I (anti-cooperative) and to site III (cooperative).


The primary structure of the hemoglobin from the aardwolf (Proteles cristatus, Hyaenidae).
The hemoglobin of the aardwolf (Proteles cristatus) contains only one component. In this paper, we are presenting its primary structure. The globin chains were separated by high-performance liquid chromatography and the sequences determined by automatic liquid and gas-phase Edman degradation of the chains and their tryptic peptides. The alpha- as well as the beta-chains show 20 exchanges compared with the corresponding human chains. The difference to the masked palm civet (Paguma larvata) and the spotted hyaena (Crocuta crocuta) is marked by 16 and 4 replacements in the alpha-chains and by 10 and 1 in the beta-chains, thus supporting the hyaenid character of the aardwolf. The exchanges at contact positions are shared by other carnivoran hemoglobins.


Quality control of MHC class II associated peptides by HLA-DM/H2-M.
For many years the crucial components involved in MHC class II mediated antigen presentation have been thought to be known: polymorphic MHC class II molecules, the monomorphic invariant chain (li) and a set of conventional proteases that cleave antigenic proteins thereby generating ligands able to associate with MHC class II molecules. However, in 1994 it was found that without an additional molecule, HLA-DM (DM), efficient presentation of protein antigens cannot be achieved. Biochemical studies showed that DM acts as a molecular chaperone protecting empty MHC class II molecules from functional inactivation. In addition, it serves as a peptide editor: DM catalyzes not only the release of the invariant chain remnant CLIP, but of all sorts of low-stability peptides, and simultaneously favors binding of high-stability peptides. Through this quality control of peptide loading, DM enables APCs to optimize MHC restriction and to display their antigenic peptide cargo on the surface for prolonged periods of time to be scrutinized by T cells.


Adult orthodontic therapy: extraction versus non-extraction.
This study addresses the problem of randomization of subjects with respect to an irreversible aspect of treatment strategy, namely, the extraction of teeth. The investigation includes both prospective and retrospective components. The data presented focus on clinician decision-making. Of the 1321 potential subjects for whom records were taken, 250 met the inclusion criteria. Of these subjects, 82 declined to participate and 20 were dropped because of difficulty in obtaining five independent evaluations of their records within a reasonable time frame. Thus, the final sample contained 148 subjects. Approximately one-third of the subjects in the sample are adult, somewhat more than half are female, and Class I malocclusions outnumber Class II malocclusions by a count of 95 to 53. Patterns of agreement and disagreement among five clinicians include: a) agreement/disagreement on the primary decision whether or not to extract: the data reveal a strong tendency towards consensus among the clinicians; b) agreement/disagreement on extraction pattern in patients in whom the clinician believes that extraction is indicated: the clinicians tended strongly to agree on extraction pattern; c) agreement/disagreement on the need for adjunctive orthognathic surgery: decisions favoring surgery were more common and more 'definite' than 'probable' in the adult cohort than in the adolescent cohort but this tendency was not as strong as had been anticipated; d) agreement/disagreement concerning Angle classification: disagreements were more common than had been anticipated; and e) differences among the individual clinicians as to their ratios of extraction/non-extraction decisions: overall, clinicians opted for extraction less frequently in the adolescent cohort than in the adult cohort (55 vs. 66%). Because the data are drawn from actual clinical experience, the conclusions involve a number of assumptions and their generalizability should be evaluated.


Translation and Validation Study of the French Version of the eHealth Literacy Scale: Web-Based Survey on a Student Population.
eHealth literacy is emerging as a crucial concept for promoting patient self-management in an overloaded hospital system. However, to the best of our knowledge, no tool currently exists to measure the level of eHealth literacy among French-speaking people. The eHealth Literacy Scale (eHEALS) is an easy-to-administer 8-item questionnaire (5-point Likert scale, ranging from strongly disagree to strongly agree) that has already been translated into many languages. Currently, it is the most cited questionnaire in the literature. The aim of this study was to translate eHEALS to French and validate the French version of eHEALS (F-eHEALS). The validation of the F-eHEALS scale followed the 5 steps of the transcultural validation method: double reverse translation, validation by a committee of experts (n=4), pretest measurement to check the clarity of the items (n=22), administration of the scale in French via a web-based quantitative study combined with two other questionnaires (Health Literacy Survey-Europe-16 and Patient Activation Measure-13; N=328 students), and finally test-retest (n=78) to check the temporal stability of the measurements obtained from the scale. The results obtained for the measurement of factor structure, internal consistency, and temporal stability (intraclass correlation coefficient=0.84; 95% CI 0.76-0.9; F77,77=6.416; P<.001) prove the validity and fidelity of the proposed scale. The internal consistency of F-eHEALS was estimated by Cronbach α of .89. The factor analysis with varimax rotation used to validate the construct showed a 2-factor scale. The effect of the construct was analyzed using 3 hypotheses related to the theory. The F-eHEALS score was correlated with the Health Literacy Survey-Europe-16 score (r=0.34; P<.001) and the Patient Activation Measure-13 score (r=0.31; P<.001). F-eHEALS is consistent with the original version. It presents adequate levels of validity and fidelity. This 2D scale will need to be generalized to other populations in a French-speaking context. Finally, a version taking into account collaborative applications (ie, Health 2.0; eg, Digital Health Literacy Instrument scale) should be considered on the basis of this study.


Assessment of suitable porcine semen for freezing, according to the ejaculate characteristics in the Iberico x Landrace breed.
A total of 35 ejaculates were studied in order to assess the suitability of porcine semen for freezing according to the ejaculate characteristics. The effects of the freezing procedure were identified; a decrease in motility and acrosome quality was found after thawing. The best results on motility were linked to the ejaculates with a volume of less than 100 ml of the sperm-rich fraction, a concentration lower than 450 x 10(6) spermatozoa/ml and an agglutination score below 2. However, the best normal apical ridge (NAR) was found when the volume of the sperm-rich fraction was greater than 150 ml. For this reason, an intermediate volume of the sperm-rich fraction of the ejaculate for the best motility and the best NAR, a concentration lower than 450 x 106 spermatozoa/ml and a rate of agglutination below 2 should provide the best quality after freezing. This study also attempted to determine whether a positive effect of ejaculate selection on the overall freezing performance might be expected.


A Genome-Wide Association Study Identifies Novel Susceptibility loci in Chronic Chagas Cardiomyopathy.
Chagas disease is an infectious disease caused by the parasite Trypanosoma cruzi and is endemic from Latin American countries. The goal of our study was to identify novel genetic loci associated with chronic Chagas cardiomyopathy development in Chagas disease patients from different Latin American populations. We performed a cross-sectional, nested case-control study including 3 sample collections from Colombia, Argentina, and Bolivia. Samples were genotyped to conduct a genome-wide association study (GWAS). These results were meta-analyzed with summary statistic data from Brazil, gathering a total of 3413 Chagas disease patients. To identify the functional impact of the associated variant and its proxies, we performed an in silico analysis of this region. The meta-analysis revealed a novel genome-wide statistically significant association with chronic Chagas cardiomyopathy development in rs2458298 (OR = 0.90, 95%CI = 0.87-0.94, P-value = 3.27 × 10-08), nearby the SAC3D1 gene. In addition, further in silico analyses displayed functional relationships between the associated variant and the SNX15, BAFT2, and FERMT3 genes, related to cardiovascular traits. Our findings support the role of the host genetic factors in the susceptibility to the development of the chronic cardiac form of this neglected disease.


[Care under pressure, carers under pressure: in the shadow of zero risk].
Clinical care cannot ignore the environment in which it takes place. In recent years, we have witnessed a rise in coercive care. We are then required to question this phenomenon with the intention of not becoming "treatment machines". How can the creativity of nursing practice be preserved? Perhaps the nursing discourse within the health institution could be rehabilitated.


Androgenic/Anabolic steroid-induced toxic hepatitis.
Athletes and bodybuilders often misuse androgenic/anabolic steroids. When used in therapeutic doses, these drugs produce clinical jaundice in just a small number of recipients. We present a 26-year-old male bodybuilder who self-administered high doses of androgenic/anabolic steroids that induced liver damage. One month before admission to the hospital, he used testosterone enanthate (500 mg intramuscularly, twice weekly), stanozolol (40 mg/d), and methylandrostenediol (30 mg/d by mouth, for 5 weeks). On admission, his bilirubin level was 470 micromol/L (direct, 360 micromol/L), his aspartate aminotransferase (AST) level was 5,870 IU/L, his alanine aminotransferase (ALT) level was 10,580 IU/L, his alkaline phosphatase (ALP) level was 152 IU/L, his gamma-glutamyl-transpeptidase level was 140 IU/L, his albumin level was 27.6 g/L, and his prothrombin time was 29%. During the patient's prolonged hospitalization, multiple tests and liver biopsy were performed, showing only toxic hepatic lesions. The patient was provided with supportive medical treatment. Clinical signs and laboratory findings improved substantially 12 weeks after the patient discontinued androgenic/anabolic steroids. The reasons for presenting this case were the much higher values of AST and ALT levels than reported in other studies, although the values of bilirubin and ALP were similar to those found in the literature. To our knowledge, it is the first case of toxic hepatitis induced by androgenic/anabolic steroids with predominantly hepatocellular necrosis instead of intrahepatic cholestasis.


The excellence of turnip mitochondrial fraction.
Several mitochondrial fractions were screened for suitability in practical experiments designed for students, with the following issues in mind: avoiding the use of animals; minimal expenditure of labour and time; high enzyme activities; accessible instruments and low-cost materials. Turnips and potato tubers were identified as the best materials from which to extract purified mitochondria according to these criteria, with high respiratory activities and integrity maintained during five consecutive days. Mitochondrial respiration was assayed for succinate, exogenous NADH, malate/pyruvate and alpha-ketoglutarate oxidations with excellent results. At the fifth day, the respiratory control was still about 3, the integrity of the outer mitochondrial membrane maintained at values higher than 80%, and the enzymes retained more than 55% of the initial activities.


N-terminal chimaeras with signal sequences enhance the functional expression and alter the subcellular localization of heterologous membrane-bound inorganic pyrophosphatases in yeast.
Expression of heterologous multispanning membrane proteins in Saccharomyces cerevisiae is a difficult task. Quite often, the use of multicopy plasmids where the foreign gene is under the control of a strong promoter does not guarantee efficient production of the corresponding protein. In the present study, we show that the expression level and/or subcellular localization in S. cerevisiae of a heterologous type of multispanning membrane protein, the proton-translocating inorganic pyrophosphatase (H+-PPase), can be changed by fusing it with various suitable N-terminal signal sequences. Chimaeric proteins were constructed by adding the putative N-terminal extra domain of Trypanosoma cruzi H+-PPase or the bona fide signal sequence of S. cerevisiae invertase Suc2p to H+-PPase polypeptides of different organisms (from bacteria to plants) and expressed in a yeast conditional mutant deficient in its cytosolic PPi hydrolysis activity when grown on glucose. Chimaeric constructs not only substantially enhanced H+-PPase expression levels in transformed mutant cells, but also allowed functional complementation in those cases in which native H+-PPase failed to accomplish it. Activity assays and Western blot analyses demonstrated further the occurrence of most H+-PPase in internal membrane fractions of these cells. The addition of N-terminal signal sequences to the vacuolar H+-PPase AVP1 from the plant Arabidopsis thaliana, a protein efficiently expressed in yeast in its natural form, alters the subcellular distribution of the chimaeras, suggesting further progression along the secretory sorting pathways, as shown by density gradient ultracentrifugation and in vivo fluorescence microscopy of the corresponding GFP (green fluorescent protein)-H+-PPase fusion proteins.


Chondroitinase ABC enhances pericontusion axonal sprouting but does not confer robust improvements in behavioral recovery.
Traumatic brain injury (TBI) results in enduring functional deficits. Strategies aimed at promoting plasticity within the injured brain may aid in enhancing functional outcome. We have previously shown that spontaneous pericontusional axon sprouting occurs within 7-14 days after controlled cortical impact injury in the adult rat, but ultimately fails due to an increasingly growth-inhibitory environment. We therefore sought to determine whether acute infusion of chondroitinase ABC into the site of the cortical contusion, to further reduce pericontusional growth-inhibitory chondroitin sulfate proteoglycans (CSPGs), would enhance and prolong the sprouting response. We also wanted to determine if chondroitinase-enhanced sprouting would ameliorate the behavioral deficits in forelimb function that occur in this model. Acute chondroitinase infusion decreased intact CSPGs and significantly increased pericontusional cortical grey and white matter growth-associated protein 43 (GAP43)-positive axon sprouting at 7 days post-injury. A return of intact CSPGs at later time points likely contributed to the absence of persistently increased levels of axon sprouting by 14-21 days post-injury. There was no overall benefit on forelimb function during the time of maximal sprouting or at any subsequent times in three of four behavioral outcome measures. However, there was a chondroitinase-induced improvement in recovery from unskilled limb use deficits on the staircase forelimb reaching test toward sham-injured values at 28 days, which was not achieved by the vehicle-treated rats, indicating that there is some minor functional benefit of the increased sprouting induced by chondroitinase treatment. The current results, together with data from spinal cord injury models after chondroitinase intervention, suggest that a combinatorial approach with the addition of neurotrophins and rehabilitation would result in more robust axon sprouting and consequently improve behavioral outcome.


Interleukin-18 promoter polymorphism in patients with rheumatoid arthritis.
Rheumatoid arthritis (RA) is a chronic inflammatory disease in which interleukin (IL)-18 plays an important role. However, there are controversial reports on IL-18 promoter polymorphism as an independent marker of RA susceptibility. The aim of present study was to examine the IL-18 promoter polymorphism in patients with RA, and its association with disease susceptibility, activity and severity. We examined 309 patients with RA from a Polish population diagnosed according to the criteria of American College of Rheumatology. An allele-specific polymerase chain reaction was used for analysis of the polymorphisms in positions - 137 and - 607 in promoter region of IL-18 gene. A significantly decreased number of subjects with AC/AC and AG/AG diplotypes was observed among RA patients as compared with healthy controls (OR - 0.51, 95%CI 0.28-0.95, P = 0.045) and (OR - 0.12, 95% CI 0.02-0.97, P = 0.042), respectively. Nevertheless, there was no significant association with disease activity, joint erosions, extra-articular manifestations, rheumatoid factor. Above results suggest that IL-18-137 and - 607 promoter polymorphisms are not the significant factors influencing RA course and severity in a Polish population.


[Progressive complications associated with the use of a bovine heterograft for vascular access].
Three bovine carotid heterografts, used for vascular access, were analysed after removal following the development of aneurysms in two cases and thrombosis in one. The first prosthesis was implanted in a 17-year-old man who suffered from myasthenia gravis and was undergoing plasmapheresis. It became notably dilated several months after implantation, and resection was necessary 14 months after insertion. The second graft was placed in a 31-year-old woman being treated for a severe chronic potassium insufficiency. It was removed 16 months after insertion because of thrombosis. The third bovine carotid heterograft was inserted in a 48-year-old patient on long-term hemodialysis and was removed 3.5 months later because of aneurysmal dilatation adjacent to the arterial anastomosis. These evolutionary and degenerative changes associated with the bovine carotid heterograft illustrate the limitations of this material as an interpositional limb for arteriovenous fistulas in angioaccess therapy. Small weaknesses have sometimes been noted in the microstructure of the graft material studied before implantation.


Evaluation of the potential exposure of butterflies to genetically modified maize pollen in protected areas in Italy.
Environmental impacts of genetically modified crops are mandatorily assessed during their premarket phase. One of the areas of concern is the possible impact on nontarget organisms. Crops expressing Cry toxins might affect Lepidoptera larvae living outside cultivated fields, through pollen deposition on wild plants, which constitute their food source. While pollen toxicity varies among different events, possible exposure of nontarget species depends on the agro-environmental conditions. This study was conducted in two protected areas in Italy, characterized by different climatic conditions, where many Lepidoptera species thrive in proximity to maize cultivations. To estimate the possible exposure in absence of the actual stressor (e.g., Cry1-expressing maize plants), we conducted a two-year field survey of butterflies and weeds. Indicator species were selected-Aglais (Inachis) io in the Northern site and Vanessa cardui in the Southern site-and their phenology was investigated. Pollen dispersal from maize fields was measured by collection in Petri dishes. Duration and frequency of exposure was defined by the overlap between pollen emission and presence of larvae on host plants. Different risk scenarios are expected in the two regions: highest exposure is foreseen for A. io in the Northern site, while minimal exposure is estimated for V. cardui in the Southern site. In the latter case, locally grown maize cultivars flower in mid-summer in coincidence with an aestivation period for several butterfly species due to hot and dry conditions. Moreover, host plants of V. cardui are at the end of their life cycle thus limiting food availability.


Closed Mitral Valvotomy Reenvision.
In developing countries, like the Indian subcontinent, population overload, malnutrition, poor socio-economic status of affected groups, and health care facilities affect the treatment outcome. Nowadays procedures such as percutaneous balloon mitral valvotomy (PBMV) and open heart mitral valve replacement are offered to patients with mitral stenosis. Whenever PBMV is unavailable due to financial constraints and open surgical management cannot be offered due to overburdened healthcare facilities, closed mitral valvotomy (CMV) provides an excellent choice for patients with favorable mitral valve pathology. Many centers do not practice CMV and thus this procedure is dying out. The young generation of surgeons are not been trained in CMV. The purpose of our study is to reenvision CMV and emphasize its vital role in mitral stenosis patient subsets like pregnant women and young adults. We reviewed the literature for various valvotomy techniques done for mitral valve stenosis and restenosis. Immediate and late outcomes were compared between the patients receiving Percutaneous balloon mitral valvotomy and closed mitral valvotomy. The immediate and late-term results are comparable for PBMV and CMV and no statistically significant difference exists. The post-PBMV Mitral valve area (MVA) ranged from 2.1 +/- 0.7 cm^2 to 2.3 +/-0.94 cm^2 and post CMV MVA ranged from 1.3+/-0.3 cm^2 to 2.2+/-0.85 cm^2. Complications developing in both techniques are also nearly similar. Operative mortality in CMV patients ranged from 1% to 4.2%, also observed in PBMV patients in various studies. Mitral Regurgitation occurred in both groups equally and ranged from 0.3% to 14%. Restenosis was observed in both groups in the range of 4% to 5%. High fetal loss of around 20% mortality was witnessed in pregnant mitral stenosis patients undergoing open heart surgery. It's time to re-envision CMV since it is providing substantial outcomes and remitting the need for open-heart surgery at a very low cost in patients with mitral stenosis with a pliable valve.


[Estimates of natural fertility in rural Tokugawa Japan].
"This paper estimates the value of [natural fertility] and [the degree of parity-specific fertility control] in rural Tokugawa Japan mainly using [the Coale-Trussell model]. What we gained through this analysis is 1) the level of natural fertility in rural Tokugawa Japan was very low compared to the pre-transition level of England, [and] 2) in spite of this low level fertility, parity-specific fertility control was not practiced.... We can say that rural Tokugawa Japan since the second half of [the] seventeenth-century was in a 'natural fertility regime'...." (SUMMARY IN ENG)


Evaluation of right-to-left shunt on contrast-enhanced transcranial Doppler in patent foramen ovale-related cryptogenic stroke: Research based on imaging.
Cardiogenic embolism caused by patent foramen ovale (PFO) is a common etiology of cryptogenic stroke (CS), particularly in young and middle-aged patients. Studies about right-to-left shunt (RLS) detection using contrast-enhanced transcranial Doppler (c-TCD) are numerous. According to the time phase and number of microbubbles detected on c-TCD, RLS can be classified and graded. We hypothesized that the characteristics of an infarction lesion on diffusion-weighted imaging differs when combining the type and grade of RLS on c-TCD in patients with PFO-related CS. To explore the characteristics of infarction lesions on diffusion-weighted imaging when combining the RLS type and grade determined by c-TCD. We retrospectively evaluated CS patients from August 2015 to December 2019 at a tertiary hospital. In total, 111 PFO-related CS patients were divided according to whether RLS was permanent (microbubbles detected both at resting state and after the Valsalva maneuver) or latent (microbubbles detected only after the Valsalva maneuver) on c-TCD. Each group was subdivided into small, mild and large RLS according to the grade of shunt on c-TCD. A normal control group was composed of 33 patients who suffered from simple dizziness. Intragroup and intergroup differences were analyzed in terms of clinical, laboratory and diffusion-weighted imaging lesion characteristics. The correlation between RLS grade evaluated by c-TCD and size of PFO determined by transesophageal echocardiography were also analyzed. In 111 patients with PFO-related CS, 68 had permanent RLS and 43 had latent RLS. Clinical characteristics and laboratory tests were not significantly different among the permanent RLS, latent RLS and normal control groups. The proportion of patients with multiple territory lesions in the permanent RLS group (50%) was larger than that in the latent RLS group (27.91%; P = 0.021). Posterior circulation was more likely to be affected in the latent RLS group than in the permanent RLS group (30.23% vs 8.82%, P = 0.004). Permanent-large and latent-large RLS were both more likely to be related to multiple (P trend = 0.017 and 0.009, respectively), small (P trend = 0.035 and 0.006, respectively) and cortical (P trend = 0.031 and 0.033, respectively) lesions. The grade of RLS evaluated by c-TCD was correlated to the size of PFO determined by transesophageal echocardiography (r = 0.758, P < 0.001). Distribution of the infarct suggested the possible type of RLS. Multiple, small and cortical infarcts suggest large RLS induced by a large PFO.


[Ascites and extreme lipid abnormalities as initial symptoms of cystic fibrosis in a 5-years-old girl--case report].
Cystic fibrosis is the most common, multiorgan inherited autosomal recessive disorder. The gene associated with this disease encodes the CF transmembrane conductance regulator (CFTR). The aim of this article is a presentation of 5-years-old girl with cystic fibrosis and associated liver disease as the only manifestation of CF. We described the case of a 5.5-years-old girl with ascites and peripheral edema without of the symptoms. Laboratory tests revealed hepatic cell damage with cholestasis, extreme lipid abnormalities and hypocholesterolemia. Based on positive sweat test (CI: 122 mEq/l) and genetic analysis (homozygote deltaF508) the diagnosis of cystic fibrosis was confirmed. Patient was successfully treated with nutritional treatment and pancreatic enzymes.


Modified Carbon Fiber Paper-Based Electrodes Wrapped by Conducting Polymers with Enhanced Electrochemical Performance for Supercapacitors.
An easy approach to fabricating carbon fiber paper (CFP) based electrodes has been developed. This method can be mainly divided into two steps, for which the mixture of cellulose nanofibers (CNFs) and carbon nanotubes (CNTs) was first deposited on the surface of carbon fiber paper through a vacuum filtration device followed by immersing the hybrid paper into concentrated aniline solution to polymerize polyaniline (PANI). Compared to carbon fiber paper, the acid-treated carbon fiber paper (A-CFP)-based electrode provides more active sites, which are beneficial for the polymerization of polyaniline. The mixture of CNFs and CNTs could coat on the A-CFP by vacuum-filtration due to the high hydrophilicity of A-CFP improved by acid-treatment. PANI with different polymerization time was in-situ synthesized on the surface of the hybrid paper to form a three-dimensional cross-linked structure that greatly enhanced the electrochemical performance of the electrode by improving high capacitance, high rate-capability, and long cycle-life. Moreover, the assembled symmetrical supercapacitor showed a high area capacitance of 626 mF·cm-2 and an energy density of 87 µWh·cm-2. This facile, easy performed, and low-cost strategy may provide a feasible method for the production of supercapacitor electrodes.


Post-transplant cyclophosphamide in one-antigen mismatched unrelated donor transplantation versus haploidentical transplantation in acute myeloid leukemia: a study from the Acute Leukemia Working Party of the EBMT.
Whether to choose Haploidentical (Haplo) or one-antigen mismatched unrelated donor (1Ag-MMUD) hematopoietic cell transplantation (HCT) with post-transplant cyclophosphamide (PTCy) remains an unanswered question. We compared PTCy- Haplo-HCT to PTCy-1Ag-MMUD-HCT for acute myeloid leukemia (AML) in complete remission (three groups: 1Ag-MMUD using peripheral blood (1Ag-MMUD-PB; n = 155); Haplo using bone marrow (Haplo-BM; n = 647) or peripheral blood (Haplo-PB; n = 949)). Haplo-BM and Haplo-PB had a higher non-relapse mortality (NRM) compared to 1Ag-MMUD-PB (HR 2.28, 95% CI 1.23-4.24, p < 0.01; HR 2.65, 95% CI 1.46-4.81, p < 0.01, respectively). Haplo groups experienced a lower leukemia-free survival (LFS) compared to 1Ag-MMUD-PB (Haplo-BM: HR 1.51, 95% CI 1.06-2.14, p = 0.02; Haplo-PB: 1.47, 95% CI 1.05-2.05, p = 0.02); overall survival (OS) was also lower in Haplo-HCT (Haplo-BM: HR 1.50, 95% CI 1.02-2.21, p = 0.04; Haplo-PB: HR 1.51, 95% CI 1.05-2.19, p = 0.03). No differences were observed for graft-versus-host/relapse-free survival (GRFS) and relapse incidence (RI). Haplo-BM was associated with a lower risk of grade III-IV acute graft-versus-host disease (GVHD) (HR 0.44, 95% CI 0.24-0.81; p < 0.01), while no statistical differences were observed between groups for grade II-IV aGVHD and for cGVHD. Use of PTCy in 1Ag-MMUD-HCT is a valid alternative to consider when using alternative donors. Larger analysis of 1Ag-MMUD versus Haplo-HCT are warranted.


Jatropha curcas L., a multipurpose stress resistant plant with a potential for ethnomedicine and renewable energy.
Jatropha curcas is a stress--resistant perennial plant growing on marginal soils. This plant is widespread throughout arid and semiarid tropical regions of the world and has been used as a traditional folk medicine in many countries. J.curcas is a source of several secondary metabolites of medicinal importance. The leaf, fruits, latex and bark contain glycosides, tannins, phytosterols, flavonoids and steroidal sapogenins that exhibit wide ranging medicinal properties. The plant products exhibit anti-bacterial and anti-fungal activities. The paper highlights the ability of various metabolites present in the plant to act as therapeutic agents and plant protectants. The plant is designated as an energy plant and use of J.curcas oil as biodiesel is a promising and commercially viable alternative to diesel oil. The seeds of the plant are not only a source of biodiesel but also contain several metabolites of pharmaceutical importance. Commercial exploitation for biopharmaceuticals and bio-energy production are some of the prospective future potential of this plant. Further reclamation of wastelands and dry lands is also possible with J.curcas cultivation.


Rituximab therapy in idiopathic membranous nephropathy: a 2-year study.
It was postulated that in patients with membranous nephropathy (MN), four weekly doses of Rituximab (RTX) would result in more effective B cell depletion, a higher remission rate, and maintaining the same safety profile compared with patients treated with RTX dosed at 1 g every 2 weeks. This hypothesis was supported by previous pharmacokinetic (PK) analysis showing that RTX levels in the two-dose regimen were 50% lower compared with nonproteinuric patients, which could potentially result in undertreatment. Twenty patients with MN and proteinuria >5 g/24 h received RTX (375 mg/m(2) × 4), with re-treatment at 6 months regardless of proteinuria response. PK analysis was conducted simultaneously with immunological analyses of T and B cells to ascertain the effect of RTX on lymphocyte subpopulations. Baseline proteinuria of 11.9 g/24 h decreased to 4.2 and 2.0 g/24 h at 12 and 24 months, respectively, whereas creatinine clearance increased from 72.4 ml/min per 1.73 m(2) at baseline to 88.4 ml/min per 1.73 m(2) at 24 months. Of 18 patients who completed 24-month follow-up, 4 are in complete remission, 12 are in partial remission, 1 has a limited response, and 1 patient relapsed. Serum RTX levels were similar to those obtained with two doses of RTX. Four doses of RTX resulted in more effective B cell depletion, but proteinuria reduction was similar to RTX at 1 g every 2 weeks. Baseline quantification of lymphocyte subpopulations did not predict response to RTX therapy.


Are SERMs safe and effective for the treatment of hypogonadism in men?
YES. For both normal-weight and obese men with low testosterone levels and hypogonadal symptoms, selective estrogen receptor modulators (SERMs), such as clomiphene citrate (CC) and enclomiphene citrate (EC), appear to be effective and safe for improving serum testosterone levels (strength of recommendation [SOR]: C, disease-oriented outcomes from randomized controlled trials [RCTs] and cohort studies). Studies also show that symptom improvement is comparable to that with exogenous testosterone replacement and similar to eugonadal men (SOR: B, patient-oriented outcomes from retrospective cohort studies).


In vitro selection and characterization of cellulose-binding RNA aptamers using isothermal amplification.
We sought to create new cellulose-binding RNA aptamers for use as modular components in the engineering of complex functional nucleic acids. We designed our in vitro selection strategy to incorporate self-sustained sequence replication (3SR), which is an isothermal nucleic acid amplification protocol that allows for the rapid amplification of RNAs with little manipulation. The best performing aptamer representative was chosen for reselection and further optimization. The aptamer exhibits robust binding of cellulose in both the powdered and paper form, but did not show any significant binding of closely related polysaccharides. The minimal cellulose-binding RNA aptamer also can be grafted onto other RNAs to permit the isolation of RNAs from complex biochemical mixtures via cellulose affinity chromatography. This was demonstrated by fusing the aptamer to a glmS ribozyme sequence, and selectively eluting ribozyme cleavage products from cellulose using glucosamine 6-phosphate to activate glmS ribozyme function.


Synchronous double tumor of breast cancer and gastrointestinal stromal tumor in a patient with neurofibromatosis type 1: report of a case.
We report a rare case of synchronous double tumor formation of breast cancer and gastrointestinal stromal tumor (GIST) in a patient with neurofibromatosis type 1(NF-1). A 76-year-old woman with a history of NF-1 who had undergone left modified mastectomy for breast cancer seven years previously was admitted to our hospital because of a right breast tumor and abdominal discomfort. Computed tomography revealed an enhanced irregular tumor in the right breast and peripheral enhanced tumors in the abdomen. The patient underwent right modified mastectomy and laparoscopic tumor resection combined with small intestine surgery. Histopathological examination revealed the presence of invasive lobular carcinoma in the right breast and GIST in the abdomen. The synchronous development of breast cancer and GIST in a patient with NF-1 is extremely rare, with this being the second case ever reported.


Stereochemical plasticity modulates cooperative binding in a CoII12L6 cuboctahedron.
Biomolecular receptors are able to process information by responding differentially to combinations of chemical signals. Synthetic receptors that are likewise capable of multi-stimuli response can form the basis of programmable molecular systems, wherein specific input sequences create distinct outputs. Here we report a pseudo-cuboctahedral assembly capable of cooperatively binding anionic and neutral guest species. The binding of pairs of fullerene guests was observed to effect the all-or-nothing cooperative templation of an S6-symmetric host stereoisomer. This bis-fullerene adduct exhibits different cooperativity in binding pairs of anions from the fullerene-free parent: in one case, positive cooperativity is observed, while in another all binding affinities are enhanced by an order of magnitude, and in a third the binding events are only minimally perturbed. This intricate modulation of binding affinity, and thus cooperativity, renders our new cuboctahedral receptor attractive for incorporation into systems with complex, programmable responses to different sets of stimuli.


Mesenchymal Stem Cells Decrease M1/M2 Ratio and Alleviate Inflammation to Improve Limb Ischemia in Mice.
BACKGROUND Limb ischemia (LI) is the underlying pathology of peripheral artery disease (PAD). Macrophages play a critical role in inflammation and can contribute to the exacerbation or reduction of inflammation. Transplantation of mesenchymal stem cells (MSCs) is an emerging therapeutic strategy for PAD. However, the mechanism by which human placenta-derived mesenchymal stem cells (PMSCs) regulate macrophage differentiation in ischemic tissue remains unclear. MATERIAL AND METHODS Placentas were obtained from healthy donors with normal 38- to 40-week gestation, and PMSCs were isolated from the placentas and cultured. A mouse model of hind-limb ischemia was established. Ischemic limbs were injected intramuscularly with about 5×10⁶ PMSCs in the PMSCs group or a placebo solution (phosphate-buffered saline) in the control group at 4 different sites 1 day after the procedure. The blood perfusion of hind-limbs and the histological morphology were observed at day 1, 7, and 14 after the surgical procedure. Macrophages were detected by flow cytometry. The expression of serum tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, and IL-10 were detected by enzyme-linked immunosorbent assay (ELISA). The expression of CD31 and smooth muscle alpha-actin (alpha-SMA) in frozen muscle samples were detected by immunofluorescence staining. RESULTS In the PMSCs group, blood perfusion was gradually recovered and ischemic injury was markedly alleviated. The percentage of M2-like macrophages was increased dramatically, while the M1/M2 macrophage ratio was reduced. The expression of TNF-alpha and IL-6 was reduced, while the IL-10 level was elevated. The expression and density of CD31- and alpha-SMA-positive vessels were both significantly increased. CONCLUSIONS Transplanted PMSCs alleviated inflammation, promoted neovascularization, and improved hind limb ischemia through regulating macrophage differentiation toward the M2 phenotype and cytokine secretion. Cytokine manipulation of macrophage phenotypes may have potential therapeutic benefits in injured ischemic limbs.


From contagious to chronic: a life course experience with leprosy in Taiwanese women.
This study used the narrative analysis method to explore stories told by Taiwanese women who had suffered from leprosy. Twenty-one women from a leprosarium, a long-term care centre, and the community participated in either focus group discussions or individual interviews. The age range for the participants was 54-88, with an average of 68 years old. Physical impairments and disabilities of the participants included skin scars, claw fingers, drop feet, amputated legs, and facial disfigurement. Their stories were analysed in two phases: structural and holistic content analyses. Structural analysis identified four life stages: before being diagnosed, after being diagnosed, living with leprosy, and the future. Holistic content analysis uncovered common themes in each life stage. Findings indicated that stigma was experienced throughout the life course of these women. At this stage of life, these women were facing not only physical impairments and disabilities from the leprosy, but also the usual chronic health problems of the elderly. This study suggests that prevention and treatment of leprosy-related physical impairments and chronic diseases are important.


[Therapeutic effect of chlorhexidine combined with mechanical debridement on peri-implantitis and its influence on patients' SF-36 score].
To study the effect of chlorhexidine combined with mechanical debridement on peri-implant inflammation and the influence on SF-36 score of patients. One hundred patients with peri-implantitis admitted to Zhejiang Provincial People's Hospital from January 2015 to January 2019 were selected and randomly divided into control group and combined group with 50 cases in each group according to random number table method.Patients in both groups were treated with mechanical debridement, and patients in the combined group were gargled with chlorhexidine gargle apart from mechanical debridement. Plaque biofilm average activity and modified plaque index (mPLI), bleeding on probing (BOP), modified sulcus bleeding index (mSBI), probing the depth (PPD), clinical attachment level(AL) were measured before and after treatment. Sf-36 scale and VAS visual pain score were used to evaluate the quality of life and pain degree of patients, and the therapeutic effect and incidence of complications were assessed. The data were analyzed with SPSS 20.0 software package. There was no significant difference in average activity, mPLI, mSBI, AL, PPD, BOP, VAS and SF-36 scores between the two groups before treatment(P>0.05); after treatment, the average activity, mPLI, mSBI, AL, PPD, BOP and VAS scores of plaque biofilm in the combined group were significantly lower than those of the control group, and the total effective rate of SF-36 score was significantly higher than that of the control group. The total effective rate of the combined group was significantly higher than that of the control group(P<0.05). The incidence of complications in the combined group was significantly lower than that in the control group(P<0.05). Chlorhexidine combined with mechanical debridement is an effective treatment of peri-implantitis, which can effectively inhibit plaque biofilm activity and plaque formation, alleviate pain and improve the quality of life of patients.


Complementation of the host range restriction of southern cowpea mosaic virus in bean by southern bean mosaic virus.
Vigna unguiculata (cowpea) and Phaseolus vulgaris (common bean) are permissive hosts for southern cowpea mosaic virus (SCPMV) and southern bean mosaic virus (SBMV), respectively. Neither of these two sobemoviruses systemically infects the permissive host of the other. Although bean cells are permissive for SCPMV RNA synthesis, they do not support the assembly of this virus. Thus, the host range restriction of SCPMV in bean may occur at the level of movement and may involve the inability of SCPMV to assemble in this host. In this study, it was demonstrated that SCPMV accumulates in an encapsidated form in the inoculated and systemic leaves of bean plants following coinoculation with SBMV. No evidence was observed that the SCPMV that accumulated in coinoculated bean plants had an altered host range relative to wild-type SCPMV. These results suggested that SBMV complemented the host range restriction of SCPMV in bean. Additional experiments demonstrated that cowpea protoplasts are permissive for SBMV RNA synthesis and assembly. It was concluded from these results that the host range restriction of SBMV in cowpea occurs at the level of movement. In mixed infections of cowpea with SCPMV and SBMV, the latter was recovered from the inoculated but not the systemic leaves. Its recovery from the inoculated leaves, however, was not dependent on the presence of SCPMV in the inoculum. From these results, it was concluded that SCPMV did not complement the host range restriction of SBMV in cowpea.