Integrated plasma cortisol concentration in children with asthma receiving long-term inhaled corticosteroids.
We assessed the effect of long-term therapy with inhaled beclomethasone dipropionate (BDP) on the pituitary-adrenal axis, by measuring the integrated concentration (IC) of plasma cortisol in eight children with asthma (age, 6-16 years) who regularly used inhaled BDP in doses ranging from 8 to 26.5 micrograms/kg (200-450 micrograms/day) for 6 months to 4 years. The control group included six children (age, 6-16 years) who had the IC of plasma cortisol measured as part of an endocrinological evaluation and were found to be healthy. Cortisol concentration was measured in blood samples collected continuously over a 24-hr period. Mean IC of plasma cortisol in the study group was significantly lower than in the healthy controls (mean +/- SD, 4.9 +/- 3.3 vs 9.1 +/- 1.9 micrograms/mL; P less than 0.02). Cortisol response to 0.25 mg ACTH (iv) was abnormal in one of the eight BDP-treated patients. No correlation was found between IC of plasma cortisol and the BDP dose, severity of asthma, height percentile, or the Tanner stage. We conclude that long-term therapy, even with relatively conventional doses of inhaled BDP may cause reduction in the normal physiological secretion of cortisol. The clinical relevance of low IC of plasma cortisol is not clear, but it may reflect partial suppression of the pituitary-adrenal axis.


Neuronal correlates of personal space intrusion in violent offenders.
Personal space (PS) is defined as the imagery region immediately surrounding our body, which acts as safety zone. It has been suggested that PS is enlarged in violent offenders and that this group shows an enhanced sensitivity to the reduction of interpersonal distance. In the present fMRI study high-risk violent offenders and noncriminal controls were presented with photos of neutral facial expressions by men and women. All images were shown twice, as static photos, and animated (i.e., appearing to approach the subject) in order to simulate PS intrusion. Approaching faces generally provoked activation of a fronto-parietal network and the insula. Offenders responded with greater insula activation to approaching faces, especially when the person was male. Insular activation has been recognized before as a neuronal correlate of potential threat and harm detection in PS. The increased reactivity of violent offenders is possibly a result of their hostile attribution bias.


An unexpected loss of domains in the conservative evolution ninth complement component in a higher teleost, Miichthys miiuy.
The complement systems of fish are well developed and play an important role in the innate immune response. C9 is the ninth member of complement components, involved in creating the membrane attack complex (MAC). In the present study, a truncated C9 cDNA sequence encoding 461 amino acids was cloned and characterized in the miiuy croaker (Miichthys miiuy). Typical fish C9 molecules have five characteristic modular domains, i.e. TSP1, LDLRA, MACPF, EGF, and a second TSP domain which is absent in mammalian counterparts. While in miiuy croaker, this truncated C9 presents only TSP1, LDLRA and MACPF domains. It is the first time of finding a truncated C9 in teleost components. RT-PCR analysis detected these C9 transcripts among all tissues examined, demonstrating its constitutive expression pattern in healthy fish. The highest levels of transcripts were detected in liver of both healthy and pathogen-infected miiuy croaker. Its constitutive and inducible expression pattern of this truncated C9 in liver is similar to most complement components which belong to the type of acute-phase proteins and are in general of hepatic origin. We cannot exclude the possibility that miiuy croaker presents the typical C9 although it has not yet been found. The molecular evolutionary analysis showed that this truncated C9 of miiuy croaker had a significantly higher omega value comparing with other fish and the positive selection pressure had happened on it after its divergence with other fish.


Supportive relationships in childhood: Does it have a long Reach into health and depression outcomes for immigrants from Latin America?
This study examines how social support during childhood and adolescence is associated with self-rated good health and the incidence of depression among Latin American immigrants in the U.S. We focus on those who immigrated under age 18 (childhood arrivals) to understand the interplay between early social support and adult health outcomes. Data are from the 2012-2013 iteration of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC-III), which included a sample of 3441 immigrant respondents born in Latin America. Multivariable binomial logistic regression analyses indicated that childhood and interpersonal support in adulthood were negatively associated with lifetime major depressive disorder (LMDD) episodes. These associations differed between childhood arrival and adult arrival immigration samples. Findings from this study highlight the role that social support in critical developmental periods has on immigrant health and depression outcomes. Continued and more nuanced investigations are warranted to examine social resources across lifespans and their roles in mitigating adverse health outcomes among immigrants from Latin America.


Proteins immunologically related to erythrocyte anion transporter band 3 are altered in brain areas affected by Alzheimer's disease.
Proteins immunologically related to the human erythrocyte anion transporter band 3 are present in neurons of the human neocortex and hippocampus. Immunocytochemical studies show increased band 3 immunoreactivity in neurons in the brains of patients with Alzheimer's disease. Immunoblot studies show the presence of band 3-like molecules in brain membrane fractions, and suggest changes in expression and/or processing of band 3-like molecules in Alzheimer's disease-affected regions. We postulate that alterations in membrane-bound, band 3-like molecules may reflect termination of neuronal lifespan in Alzheimer's disease.


Restoration of sensory information via bionic hands.
Individuals who have lost the use of their hands because of amputation or spinal cord injury can use prosthetic hands to restore their independence. A dexterous prosthesis requires the acquisition of control signals that drive the movements of the robotic hand, and the transmission of sensory signals to convey information to the user about the consequences of these movements. In this Review, we describe non-invasive and invasive technologies for conveying artificial sensory feedback through bionic hands, and evaluate the technologies' long-term prospects.


Enhanced antibactericidal function of W4+-doped titania-coated nickel ferrite composite nanoparticles: a biomaterial system.
The study demonstrates a distinct enhancement of antimicrobial activity of W4+-doped titania that is coated on nickel ferrite nanoparticles in comparison to undoped titania. The composite nanoparticles were synthesized by uniquely combining reverse micelle and chemical hydrolysis synthesis methods [Rana S, Rawat J, Misra RDK, Acta Biomater 2005;1:691]. The superior antimicrobial activity of W4+-doped titania is related to the inhibition of electron-hole recombination and decrease in the band gap energy of titania. The function of the ferrite is to facilitate the removal of nanoparticles from the sprayed surface using a small magnetic field. The coating of ferrite nanoparticles with titania retains superparamagnetic character and magnetic strength of composite nanoparticles signifying non-deterioration of magnetic properties and promoting their use as removable antimicrobial photocatalyst nanoparticles.


Parental COVID-19 vaccine hesitancy: a cross-sectional survey in Italy.
Understanding parents' hesitancy against COVID-19 vaccination for their children is useful. A self-administered online survey was conducted among 394 parents with at least one child aged 12-18 years in Italy. The mean perceived risk that their child can be infected by the SARS-CoV-2, measured on a 10-point Likert-type scale, was 7.7 and it was higher if at least one parent/partner cohabitant have had COVID-19, in those who believed that COVID-19 is a serious illness, and in those who had not vaccinated their child. 82.1% respondents were willing to vaccinate their child and this was more likely among those who believed that this vaccine is useful and who did not need additional information. 12.4% were, according to the 5-item Parent Attitudes About Childhood Vaccines Survey (PACV-5) score, high-hesitant toward anti-COVID-19 vaccination. Respondents not graduated, those who did not believe that this vaccination was useful, those who did not get this vaccine, those who did not obtain information from physicians, and those who needed additional information were more likely to be high-hesitant. Communication and public health interventions must be intensified to enhance the attitude and to help parents in deciding on COVID-19 vaccination of their children.


Postural seated balance in children can be assessed with good reliability.
Seated postural stability can be measured using Tekscan, CONFORMat. Standing postural stability has gained great clinical and, research value by use of different force platforms with mostly good reliability. No reliability testing or biologic variation assessment has been documented regarding seated balance. This study determines the reliability of the parameters of seated balance in healthy children using the Tekscan CONFORMat equipment. Sixty-six healthy children completed six measurements of seating position the first three with the child seated in a relaxed normal back position and the next three with the child seated in a complete up-right back position. The SAM software calculated five default parameters of balance (area, distance, variability, antero-posterior (AP) excursion and left-right excursion). Reliability parameters were assessed by one-way analysis of variance intra-class correlation (ICC) proving excellent reliability for relaxed and up-right back position with respect to distance (0.75/0.84) and good reliability with respect to variability (0.61/0.62) and area (0.61/0.60). AP excursion (0.41/0.59) and left-right excursion (0.54/0.24) showed fair to poor reliability. In conclusion, two of the five default parameters of balance used in the Tekscan CONFORMat system are direction-independent parameters and have been found reproducible for measuring seated balance in children. This study can be used as reference for comparisons of seated balance in children with affected seated postural control and for evaluating a clinical treatment effect.


Interphase cytogenetic analysis of gliomas.
Interphase cytogenetics is the application of nonradioactive in situ hybridization with chromosome-specific DNA probes to interphase nuclei. The possibilities and limitations of this new technique for the study of chromosomal aberrations in gliomas are discussed.


Research update: The relation between ME/CFS disease burden and research funding in the USA.
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating, chronic, multisystem disease that affects an estimated 1 to 2.5 million Americans. It has no widely accepted biomarkers and no FDA-approved treatment. ME/CFS has traditionally been one of the lowest funded diseases by the United States National Institutes of Health (NIH). We provide here an update to our 2016 article, which estimated the disease burden of ME/CFS in the United States in 2013 and its relation to NIH's 2015 analysis of research funding and disease burden. This update incorporates more recent burden data from 2015 and funding data from 2017. We perform a regression analysis on funding versus disease burden to determine 2017 funding levels that would be commensurate with burden. Burden figures for 2017 are estimated using population-based extrapolations of earlier data. We find the disease burden of ME/CFS is double that of HIV/AIDS and over half that of breast cancer. We also find that ME/CFS is more underfunded with respect to burden than any disease in NIH's analysis of funding and disease burden, with ME/CFS receiving roughly 7% of that commensurate with disease burden. To be commensurate with disease burden, NIH funding would need to increase roughly 14-fold.


The case test-negative design for studies of the effectiveness of influenza vaccine.
A modification to the case-control study design has become popular to assess vaccine effectiveness (VE) against viral infections. Subjects with symptomatic illness seeking medical care are tested by a highly specific polymerase chain reaction (PCR) assay for the detection of the infection of interest. Cases are subjects testing positive for the virus; those testing negative represent the comparison group. Influenza and rotavirus VE studies using this design are often termed "test-negative case-control" studies, but this design has not been formally described or evaluated. We explicitly state several assumptions of the design and examine the conditions under which VE estimates derived with it are valid and unbiased. We derived mathematical expressions for VE estimators obtained using this design and examined their statistical properties. We used simulation methods to test the validity of the estimators and illustrate their performance using an influenza VE study as an example. Because the marginal ratio of cases to non-cases is unknown during enrollment, this design is not a traditional case-control study; we suggest the name "case test-negative" design. Under sets of increasingly general assumptions, we found that the case test-negative design can provide unbiased VE estimates. However, differences in health care-seeking behavior among cases and non-cases by vaccine status, strong viral interference, or modification of the probability of symptomatic illness by vaccine status can bias VE estimates. Vaccine effectiveness estimates derived from case test-negative studies are valid and unbiased under a wide range of assumptions. However, if vaccinated cases are less severely ill and seek care less frequently than unvaccinated cases, then an appropriate adjustment for illness severity is required to avoid bias in effectiveness estimates. Viral interference will lead to a non-trivial bias in the vaccine effectiveness estimate from case test-negative studies only when incidence of influenza is extremely high and duration of transient non-specific immunity is long.


Mini-dystrophin expression down-regulates IP3-mediated calcium release events in resting dystrophin-deficient muscle cells.
We present here evidence for the enhancement, at rest, of an inositol 1,4,5-trisphosphate (IP3)-mediated calcium signaling pathway in myotubes from dystrophin-deficient cell lines (SolC1(-)) as compared to a cell line from the same origin but transfected with mini-dystrophin (SolD(+)). With confocal microscopy, the number of sites discharging calcium (release site density [RSD]) was quantified and found more elevated in SolC1(-) than in SolD(+) myotubes. Variations of membrane potential had no significant effect on this difference, and higher resting [Ca2+]i in SolC1(-) (Marchand, E., B. Constantin, H. Balghi, M.C. Claudepierre, A. Cantereau, C. Magaud, A. Mouzou, G. Raymond, S. Braun, and C. Cognard. 2004. Exp. Cell Res. 297:363-379) cannot explain alone higher RSD. The exposure with SR Ca(2+) channel inhibitors (ryanodine and 2-APB) and phospholipase C inhibitor (U73122) significantly reduced RSD in both cell types but with a stronger effect in dystrophin-deficient SolC1(-) myotubes. Immunocytochemistry allowed us to localize ryanodine receptors (RyRs) as well as IP3 receptors (IP3Rs), IP3R-1 and IP3R-2 isoforms, indicating the presence of both RyRs-dependent and IP3-dependent release systems in both cells. We previously reported evidence for the enhancement, through a Gi protein, of the IP3-mediated calcium signaling pathway in SolC1(-) as compared to SolD(+) myotubes during a high K(+) stimulation (Balghi, H., S. Sebille, B. Constantin, S. Patri, V. Thoreau, L. Mondin, E. Mok, A. Kitzis, G. Raymond, and C. Cognard. 2006. J. Gen. Physiol. 127:171-182). Here we show that, at rest, these regulation mechanisms are also involved in the modulation of calcium release activities. The enhancement of resting release activity may participate in the calcium overload observed in dystrophin-deficient myotubes, and our findings support the hypothesis of the regulatory role of mini-dystrophin on intracellular signaling.


Direct measurement of Stokes-Einstein diffusion of Cowpea mosaic virus with 19 µs-resolved XPCS.
Brownian motion of Cowpea mosaic virus (CPMV) in water was measured using small-angle X-ray photon correlation spectroscopy (SA-XPCS) at 19.2 µs time resolution. It was found that the decorrelation time τ(Q) = 1/DQ2 up to Q = 0.091 nm-1. The hydrodynamic radius RH determined from XPCS using Stokes-Einstein diffusion D = kT/(6πηRH) is 43% larger than the geometric radius R0 determined from SAXS in the 0.007 M K3PO4 buffer solution, whereas it is 80% larger for CPMV in 0.5 M NaCl and 104% larger in 0.5 M (NH4)2SO4, a possible effect of aggregation as well as slight variation of the structures of the capsid resulting from the salt-protein interactions.


The function of Dmrt genes in vertebrate development: it is not just about sex.
The Dmrt genes encode a large family of transcription factors whose function in sexual development has been well studied in invertebrates and vertebrates. Their expression pattern is not restricted to the developing gonads, indicating that Dmrt genes might regulate other developmental processes. Here we review the expression pattern of several members of this family across species and summarize recent findings on the function of a subset of these genes in non-gonadal tissues.


[Outcomes of early endoscopic realignment of post-traumatic posterior urethral ruptures].
Post-traumatic rupture of the posterior urethra is a serious injury that can compromise the micturition and erectile prognosis of the often-young patient. The management of this lesion is still controversial, leaving the choice between early endoscopic realignment or suprapubic catheterization with deferred urethroplasty. The objective of this study was to report our clinical experience and outcomes with early endoscopic realignment (EER) for patients with pelvic fracture urethral injury. We underwent a retrospective review of patients with pelvic fracture associated urethral injury who underwent EER from 2010 to 2020. Preoperative, perioperative, and postoperative outcome data were collected. Complications for the surgical procedure were analyzed, as well as postoperative stenosis, urinary incontinence and erectile dysfunction. The primary endpoint was success, defined as satisfying micturition with no urethral stricture at the time of last follow-up. Early endoscopic realignment was performed in 26 patients managed for complete post-traumatic posterior urethral rupture. The median age was 26 (16-39) years. The most common mechanism of urethral injury was road traffic accidents in 69.23% of cases. The most common urethral injury was grade 4 in 23 patients (88.46%). The median time to endoscopic realignment was 8 days (3-18). The median time to postoperative bladder catheterization was 22 (10-32) days. The median follow-up time was 34 (18-54) months. Ten patients developed urethral stricture during follow-up: 7 (26.92%) were treated with one or two internal cold blade urethrotomies, 3 required urethroplasty. There were no urethroplasty failures after a first endoscopic realignment. Two patients reported severe stress urinary incontinence. The median IIEF-5 score at the date of last news was 23 (17-25). Early endoscopic realignment allows some patients to avoid a heavier surgical treatment, and doesn't compromise the realization of a later urethroplasty.


The Impact of Hearing Loss and Its Treatment on Health-Related Quality of Life Utility: a Systematic Review with Meta-analysis.
Hearing loss significantly impacts health-related quality of life (QoL), yet the effects of current treatments on QoL utility remain uncertain. Our objective was to describe the impact of untreated and treated hearing loss on QoL utility to inform hearing healthcare policy. We searched databases for articles published through 02/01/2021. Two independent reviewers screened for articles that reported elicitation of general QoL utility values for untreated and treated hearing loss health states. We extracted data and quality indicators from 62 studies that met the inclusion criteria. Included studies predominately used observational pre/post designs (61%), evaluated unilateral cochlear implantation (65%), administered the Health Utilities Index 3 (HUI3; 71%), and were conducted in Europe and North America (84%). In general, treatment of hearing loss improved post-treatment QoL utility when measured by most methods except the Euro-QoL 5 dimension (EQ-5D). In meta-analysis, hearing aids for adult mild-to-moderate hearing loss compared to no treatment significantly improved HUI3-estimated QoL utility (3 studies; mean change=0.11; 95% confidence interval (CI): 0.07 to 0.14) but did not impact EQ-5D-estimated QoL (3 studies; mean change=0.0; 95% CI: -0.03 to 0.04). Cochlear implants improved adult QoL utility 1-year post-implantation when measured by the HUI3 (7 studies; mean change=0.17; 95% CI: 0.11 to 0.23); however, pediatric VAS-estimated QoL utility was non-significant (4 studies; mean change=0.12; 95% CI: -0.02 to 0.25). The quality of included studies was limited by failure to report missingness of data and low survey response rates. Our study was limited by heterogeneous study populations and designs. Treatment of hearing loss significantly improves QoL utility, and the HUI3 and VAS were most sensitive to improvements in hearing. Improved access to hearing healthcare should be prioritized. SYSTEMATIC REVIEW REGISTRATION: PROSPERO: CRD42021253314.


Immune dependence of schistosomicidal chemotherapy: an ultrastructural study of Schistosoma mansoni adult worms exposed to praziquantel and immune serum in vivo.
This study examines the immune-dependence of praziquantel (PZQ) for the treatment of Schistosomiasis mansoni in mice. We have shown elsewhere from worm recovery data that the efficacy of PZQ is significantly enhanced when mice are treated concomitantly with antisera raised against antigens released from adult schistosomes, even though such antisera show no intrinsic helminthotoxic activity (Doenhoff et al. 1987, Doenhoff, Modha & Lambertucci 1988). Moreover, indirect immunofluorescence assays have shown that male worms exposed to the dual treatment regime in vivo bind antiserum to their dorsal surfaces in a pattern that seems to follow the outline of the dorsal tubercles. Scanning and transmission electron microscopy have now been used to further define the features of damage inflicted upon worms through exposure to antiserum alone, drug alone, or the two treatments in combination. Such investigations revealed that the antiserum induces a classical membrane repair process in worms of both sexes, but little other damage. PZQ causes the formation of spherical protuberances on the dorsal tubercles of male worms, while the dual treatment regime induces both kinds of damage in male schistosomes, but with much enhanced severity. The protuberances show evidence of explosion and some regions of the tegument become completely destroyed. Regions other than the dorsal surfaces of the male worms do not exhibit comparable trauma, and neither do the females. These data are discussed in relation to the known schistosomicidal activity of PZQ, the notion that male and female worms exhibit regional and sexual differences in susceptibility, documented evasive strategies of the parasite and the interdependence of immuno- and chemotherapy.


Thymoma followed by paroxysmal nocturnal hemoglobinuria: a unique clinical association in the context of multiorgan autoimmunity with a potential role for CD8+ T lymphocytes.
Seven years after a surgically resected thymoma, a female patient affected by myasthenia gravis and Good's syndrome presented with paroxysmal nocturnal hemoglobinuria (PNH). Co-culture experiments and spectratyping analyses indicated that CD8+ lymphocytes were involved in damaging hematopoietic precursors. While PNH clones have been identified in various hematological disorders, the sequential association of thymoma and PNH has been unreported so far.


Walking in postpoliomyelitis syndrome: the relationships between time-scored tests, walking in daily life and perceived mobility problems.
To compare walking test results with walking in daily life, and to investigate the relationships between walking tests, walking activity in daily life, and perceived mobility problems in patients with post-poliomyelitis syndrome. Twenty-four ambulant patients with post-poliomyelitis syndrome. Walking tests were performed at self-preferred and maximal speed. Walking activity was measured with an ambulatory activity monitor. Heart rate, step cadence and walking speed in the test and in daily life were compared. Walking speed in daily life was represented by the intensity of walking. Perceived mobility problems were assessed with the Nottingham Health Profile. Heart rate during walking was lower in the test at self-preferred speed than in daily life (mean difference: 11.3+/-10.4; p=0.001). Self-preferred walking speed in the test and in daily life correlated significantly (r=0.55; p=0.04). In a sub-group with a test performance below the median value, test performance correlated significantly with walking activity. No significant correlation was found between perceived mobility problems and walking activity. Walking in daily life may be more demanding than walking under standardized conditions. Patients with post-poliomyelitis syndrome with the lowest test performance walked less in daily life. Patients do not necessarily match their activity pattern to their perceived mobility problems.


Stem cells and nuclear reprogramming.
Derivation of human embryonic stem (ES) cells from preimplantation embryos ten years ago raised great hopes that they may be an excellent source of cells for cell replacement therapy. However, serious ethical concerns and the risk of immune rejection of allotransplanted cells have hindered the translation of ES cell-based therapies into the clinic. In an attempt to circumvent these barriers, a number of methods have been developed for converting adult somatic cells into a pluripotent state from which ethically acceptable patient-specific mature cells of interest could be derived. These efforts, backed by advances in elucidating the molecular basis of pluripotency, have culminated in successful reprogramming of fibroblasts into ES cell-like cells, termed induced pluripotent stem (iPS) cells, by ectopic expression of only a handful of "stemness" factors. iPS cells possess morphological, molecular and developmental features of conventional blastocyst-derived ES cells and have the potential to serve as a source of therapeutic cells for customized tissue repair, gene therapy, drug discovery, toxicological testing and for studying the molecular basis of human disease. The goal of this review is to provide the current state-of-the-art in this very exciting and dynamic field and to discuss barriers that remain to be removed before the therapeutic potential of iPS cells can be fully realized.


iTRAQ plus 18O: a new technique for target glycoprotein analysis.
A novel strategy combining iTRAQ with (18)O stable isotope labeling (iTRAQ plus (18)O) was established to identify N-glycosylation site, quantify the glycopeptides and non-glycosylated peptides, and obtain N-glycosylation site ratio on the target glycoprotein. In this approach, all peptides of four biological samples are labeled with four iTRAQ reagents in parallel, followed by PNGase F catalyzed labeling of N-glycosylation sites with H(2)(16)O and H(2)(18)O. Two sample groups are labeled with H(2)(16)O and the other two are labeled with H(2)(18)O. After the modification of MS precursor ion isolation window, tagged peptides are identified by LC-MS/MS, both glycopeptides and non-glycopeptides are quantified simultaneously using ProteinPilot™ Software. With four samples to be maximally analyzed in parallel, this workflow supports accurate identification and quantification of glycopeptides in a site-specific fashion. Furthermore, N-glycosylation site ratios on serum haptoglobin (Hp) β chain in healthy individuals as well as patients with hepatitis B virus (HBV), liver cirrhosis (LC) and hepatocellular carcinoma (HCC) were quantified to validate the novel 'iTRAQ plus (18)O' method. Glycosite ratios of VVLHPN#YSQVDIGLIK were observed to change significantly in HCC patients compared with LC and HBV patients. This novel approach supports the screening of the target glycoproteins as biomarkers in clinical application.


Strong Eu2+ light emission in Eu silicate through Eu3+ reduction in Eu2O3/Si multilayer deposited on Si substrates.
Eu2O3/Si multilayer nanostructured films are deposited on Si substrates by magnetron sputtering. Transmission electron microscopy and X-ray diffraction measurements demonstrate that multicrystalline Eu silicate is homogeneously distributed in the film after high-temperature treatment in N2. The Eu2+ silicate is formed by the reaction of Eu2O3 and Si layers, showing an intense and broad room-temperature photoluminescence peak centered at 610 nm. It is found that the Si layer thickness in nanostructures has great influence on Eu ion optical behavior by forming different Eu silicate crystalline phases. These findings open a promising way to prepare efficient Eu2+ materials for photonic application.


Giant and anisotropic many-body spin-orbit tunability in a strongly correlated kagome magnet.
Owing to the unusual geometry of kagome lattices-lattices made of corner-sharing triangles-their electrons are useful for studying the physics of frustrated, correlated and topological quantum electronic states1-9. In the presence of strong spin-orbit coupling, the magnetic and electronic structures of kagome lattices are further entangled, which can lead to hitherto unknown spin-orbit phenomena. Here we use a combination of vector-magnetic-field capability and scanning tunnelling microscopy to elucidate the spin-orbit nature of the kagome ferromagnet Fe3Sn2 and explore the associated exotic correlated phenomena. We discover that a many-body electronic state from the kagome lattice couples strongly to the vector field with three-dimensional anisotropy, exhibiting a magnetization-driven giant nematic (two-fold-symmetric) energy shift. Probing the fermionic quasi-particle interference reveals consistent spontaneous nematicity-a clear indication of electron correlation-and vector magnetization is capable of altering this state, thus controlling the many-body electronic symmetry. These spin-driven giant electronic responses go well beyond Zeeman physics and point to the realization of an underlying correlated magnetic topological phase. The tunability of this kagome magnet reveals a strong interplay between an externally applied field, electronic excitations and nematicity, providing new ways of controlling spin-orbit properties and exploring emergent phenomena in topological or quantum materials10-12.


Acute pancreatitis caused by Mycoplasma pneumoniae: an unusual etiology.
It is well known that the most important etiologies of acute pancreatitis are gallstones and alcohol consumption. Once these causes have been ruled out, especially in young adults, it is important to consider less frequent etiologic factors such as drugs, trauma, malformations, autoimmunity or systemic diseases. Other rare and less well studied causes of this pathology are infections, among which Mycoplasma pneumoniae has been reported to cause acute pancreatitis as an unusual extrapulmonary manifestation. Here, we report the case of a 21-year-old patient who had acute idiopathic pancreatitis associated with an upper respiratory tract infection. After an in-depth study, all other causes of pancreatitis were ruled out and Mycoplasma was established as the clinical etiology.


Calcitriol in the treatment of postmenopausal osteoporosis.
Calcitriol was compared with placebo in the treatment of postmenopausal osteoporosis in a double-blind, randomized, parallel clinical trial of 24 months' duration. Adjustment was made in dietary calcium to maximize the dose of calcitriol. The study was completed by 15 patients who received placebo and 12 patients who received calcitriol. The calcitriol group had positive slopes (compared with negative slopes for the placebo group) for total body calcium, bone mineral content of the radius, bone mineral density of the lumbar spine, and radiographic absorptiometry of the middle phalanges. The difference between the two groups was statistically significant for each of these measurements. The fracture rate in the treatment group was 250 per 1,000 patient-years as compared with 333 for the placebo group. The mean dose of calcitriol was 0.8 micrograms per day. Hypercalcemia, hypercalciuria, and perhaps nephrolithiasis were observed as complications of treatment. Calcitriol increased bone mineral density by decreasing bone resorption, but not by increasing bone formation. Future studies should concentrate on treatment with oral calcitriol in lower doses. It would also be of interest to examine parenteral administration of calcitriol. It is possible that bone formation can be increased by achieving higher serum levels of the drug, whereas complications may be avoided by using a non-oral route of administration.


The Role of Bone Marrow Aspirate in Osseous and Soft Tissue Pathology.
Bone marrow aspirate (BMA) is an emerging therapy that is gaining popularity for orthoplastic reconstruction. The stem cells collected are multipotent and regenerative in nature. In addition to stem cells, other biological components collected augment the mitogen of local cells, proliferation, and angiogenesis, and inhibit proinflammatory cytokine and bacteria to optimize an environment to heal. The most common site for harvest is the iliac crest. Techniques for harvesting BMA are simple to perform, financially modest, and associated with low morbidity. Additional research is needed to evolve and standardize the technology; however, BMA is proven to be advantageous for tissue repair.


Global study of viral diarrhea in hospitalized children in Spain: results of structural surveillance of viral gastroenteritis net work (VIGESS-net) 2006-2008.
Detection and characterization of gastroenteritis cases (viruses) was conducted during eleven years through the surveillance VIGESS-net, which was created in an effort to conduct a structured surveillance of rotavirus genotypes co-circulating in Spain. This phase includes the study of 2048 fecal samples from children <5 years old, hospitalized in fifteen different hospitals throughout Spain from March 2006 to March 2008. Of them, 821 (40.1%) samples were rotavirus positive. Rotavirus was identified as the only etiological agent in 694 (33.9%) cases and in 127 (6.2%) was found as coinfection with other enteric viruses, mainly with noroviruses. Predominant G genotypes detected were G1 (49.8%) followed by G9 (32.9%), G3 (2.6%), G8 (1.0%), G4 (0.4%), G6 (0.2%) and G12 (0.2%). The G2 was encountered in 3.2% of cases. Rotavirus mixed G-types infections occurred in 3.9% of cases. The main G/P combinations were G1P[8] (51.9%) and G9P[8] (35.6%), which predominates alternatively in the first and second period of the study. More rare combinations occur in less than 7.4% of cases. The diversity of rotavirus circulating strains suggests to maintain a surveillance system through different regions of the country.


Biofilm Attached Cultivation of Chlorella pyrenoidosa Is a Developed System for Swine Wastewater Treatment and Lipid Production.
This study showed the new potential of using soluble contents and heavy metals in swine wastewater as nutrient supplements for the algae Chlorella pyrenoidosa with biofilm attached method. Algae with biofilm attached cultivation grew well in unpasteurized wastewater reaching a biomass productivity of 5.03 g m-2 d-1, lipid content of 35.9% and lipid productivity of 1.80 g m-2 d-1. Chlorella grew in BG11 medium delivered lower values for each of the aforementioned parameters. The FAMEs compositions in the algae paste were mainly consisted of C16:0, C18:2, and C18:3. Algae removed NH4+-N, total phosphorus (TP), and COD by 75.9, 68.4, and 74.8%, respectively. Notably, Zn2+, Cu+, and Fe2+ were removed from wastewater with a ratio of 65.71, 53.64, and 58.89%, respectively. Biofilm attached cultivation of C. pyrenoidosa in swine wastewater containing heavy metals could accumulate considerable biomass and lipid, and the removal ratio of NH4+-N, TP, COD, and as well as heavy metal were high. Treatment of wastewater with biofilm attached cultivation showed an increasingly popular for the concentration of microalgae and environmental sustainability.


MEF2C haploinsufficiency syndrome: Report of a new MEF2C mutation and review.
MEF2C haploinsufficiency syndrome is characterized by severe intellectual disability, epilepsy, stereotypic movements, minor dysmorphisms and brain abnormalities. We report the case of a patient with a new MEF2C mutation, comparing his clinical and imaging features to those previously reported in the literature. A 10 year-old boy first came to pediatric neurology clinic at the age of 11 months because of severe psychomotor delay, without regression. He presented generalized hypotonia, poor eye contact, hand-mouth stereotypies, strabismus and minor facial dimorphisms. Epileptic seizures started at 26 months of age and were refractory. Brain MRI showed a slight increase in periventricular white matter signal and globally enlarged CSF spaces. Molecular analysis revealed a de novo, pathogenic and causative MEF2C mutation. MEF2C haploinsufficiency syndrome was recently recognized as a neurodevelopmental disorder. Severe intellectual disability with inability to speak and epilepsy are universal features in patients with MEF2C mutations, although mild cognitive and speech disorders have been reported to occur in patients with duplications. Epilepsy might be absent in patients with partial deletions. Abnormal movement patterns are very common in patients with MEF2C haploinsufficiency. Delayed myelination seems to be more commonly observed in patients with MEF2C mutations, while malformations of cortical development were only reported in patients with microdeletions. Although MEF2C haploinsufficiency prevalence is yet to be determined, it should be considered in the differential diagnosis of patients with severe intellectual disability and Rett-like features.


Assessment of Mechanical Root Canal Preparation with Centric Reciprocating or Eccentric Rotary Kinematics: A Micro-computed Tomographic Study.
The aim of this study was to compare, using micro-computed tomographic imaging, the preparation of mesial canals of mandibular molars with the Reciproc (VDW GmbH, Munich, Germany) and XP-endo Shaper (FKG, La Chaux-de-Fonds, Switzerland) systems, evaluating changes in dentin and canal volume, the percentage of untouched walls, the volume of accumulated hard tissue debris, and root canal deviation in the apical third. Twenty-four mandibular molars with 2 mesial root canals and a single foramen were anatomically paired and divided into 2 experimental groups (n = 12) according to the system used. The specimens were scanned before and after preparation with the SkyScan 1176 microtomographic scanner (Bruker-microCT, Kontich, Belgium) at a resolution of 17.42 μm. The resulting data were statistically compared at a significance level of 5% using the Student t test and the Mann-Whitney test. A significant difference was observed in the untouched surface area for the total canal and the cervical and middle thirds, with the lowest untouched surface area in the XP-endo Shaper group (P < .05). The volume of accumulated hard tissue debris was significantly higher in the Reciproc group in the total canal as well as in the middle and apical thirds. There was no significant difference between the groups regarding the volume of dentin removed or the increase in canal volume and surface area (P > .05). The XP-endo Shaper touched more walls and left less accumulated hard tissue debris in the root canal system than the Reciproc group. Although the XP-endo Shaper showed superior results, neither system was able to fully prepare the root canal.


Burst discharge in mammalian neuroendocrine cells involves an intrinsic regenerative mechanism.
Intracellular recordings from mammalian neuroendocrine cells showed that steady, injected currents can modify and block periodic spike bursts previously associated with increased neurohormone release. Spike afterpotentials could sum to form plateau potentials, which generated bursts and did not depend on axonal conduction or chemical synapses. Therefore, bursting involves a spike-dependent, positive-feedback mechanism endogenous to single neuroendocrine cells.


[External respiratory function in patients with primary pulmonary emphysema etiologically related to alpha 1-antitrypsin deficiency].
To improve the diagnosis of primary lung emphysema etiologically linked with alpha-trypsin deficiency, the authors provide the results of a detailed clinico-functional study of 6 patients with an appreciable deficiency of this enzyme. According to the clinical and functional signs, all the patients were diagnosed to have a typical, pronounced lung emphysema. Therefore, the measurement of the alpha-antitrypsin content plays the crucial part in differential diagnosis of primary (hereditary determined) and secondary (obstructive) emphysema.


Anemia and its association with clinical outcome in heart failure patients undergoing cardiac resynchronization therapy.
Although a substantial proportion of patients with heart failure (HF) have anemia, there is a paucity of data evaluating the impact of anemia on clinical outcome in CRT patients. Our goal was to examine the ability of baseline hemoglobin (Hb) level and change in Hb level over time to predict clinical 2-year outcome and echocardiographic response to CRT. Three hundred consecutive CRT patients (median 72 years [interquartile range (IQR) 16 years], 19% female) with baseline and follow-up hematological profiles available were examined. Baseline anemia was defined as Hb <12 g/dL in women and <13 g/dL in men, and patients were grouped into equal quartiles based on change in Hb. Two-year clinical outcome was determined using a composite endpoint that included HF hospitalization, left ventricular assist device (LVAD) placement, heart transplantation, and all-cause mortality. Echocardiographic reverse remodeling was examined at 6-month follow-up. One hundred fifty-one anemic patients were compared to 149 non-anemic patients. Changes in left ventricular dimensions and ejection fraction were similar for both groups. Univariate predictors of 2-year clinical outcome included baseline creatinine level, diuretic usage, and anemia; in multivariable regression, baseline anemia was an independent predictor for outcome (hazard ratio [HR] 1.79, 95% confidence interval [CI] [1.22-2.63], p = 0.003). The quartile with the most negative change in Hb concentration over time (≤-1.00 g/dL) had poorer event-free 2-year survival (HR 1.84, CI [1.13-3.00], p = 0.014). Baseline anemia and early postimplantation decline in Hb levels are associated with a worse 2-year prognosis in CRT patients, even though the magnitude of left ventricular reverse remodeling is similar compared to non-anemic patients.


A novel DNA structure induced by the anticancer bisplatinum compound crosslinked to a GpC site in DNA.
The bifunctional platinum compound, [(trans-PtCI(NH)3)2)2(H2N(CH2)4NH2)]2+, forms a stable adduct with the self-complementary DNA oligomer CATGCATG, with the two platinum atoms coordinated at the N7 positions of the two symmetrical G4 nucleotides. The NMR-derived structure shows that the DNA octamer forms a novel hairpin structure with the platinated G4 residue adopting a syn conformation and the guanine base in the minor groove. Two such hairpins stack end-over-end and are linked together by the butanediamine tether to form a dumbbell structure. Such unusual structural distortion is different from that of the anticancer drug cisplatin-DNA adduct and may provide clues to explain the distinct biological activities of the two compounds.


Superconductivity phase diagram of Na(x)CoO2*1.3H2O.
The microscopic origin of superconductivity in the high-transition-temperature (high-T(c)) copper oxides remains the subject of active inquiry; several of their electronic characteristics are well established as universal to all the known materials, forming the experimental foundation that all theories must address. The most fundamental of those characteristics, for both the copper oxides and other superconductors, is the dependence of the superconducting T(c) on the degree of electronic band filling. The recent report of superconductivity near 4 K in the layered sodium cobalt oxyhydrate, Na(0.35)CoO2*1.3H2O, is of interest owing to both its triangular cobalt-oxygen lattice and its generally analogous chemical and structural relationships to the copper oxide superconductors. Here we show that the superconducting T(c) of this compound displays the same kind of behaviour on chemical doping that is observed in the high-T(c) copper oxides. Specifically, the optimal superconducting T(c) occurs in a narrow range of sodium concentrations (and therefore electron concentrations) and decreases for both underdoped and overdoped materials, as observed in the phase diagram of the copper oxide superconductors. The analogy is not perfect, however, suggesting that Na(x)CoO2*1.3H2O, with its triangular lattice geometry and special magnetic characteristics, may provide insights into systems where coupled charge and spin dynamics play an essential role in leading to superconductivity.


Role of coronary computed tomography angiography (CTA) post the ISCHEMIA trial: Precision prevention based on coronary CTA-derived coronary atherosclerosis.
The International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA) trial has been recently published and suggested the importance of the selection of patients at high risk for future cardiovascular disease events and the enhancing optimal medical therapy. In the ISCHEMIA trial, coronary computed tomography angiography (CTA) was performed in most of the patients to exclude high-risk patients and those without obstructive coronary artery disease (CAD) who should not be randomized. Coronary CTA has been widely used as a non-invasive diagnostic modality to assess patients with suspected CAD. Currently, the international guidelines allow use of coronary CTA as a class I recommendation for patients with chest pain. Besides, in the numerous multicenter trials, the emerging role of coronary CTA has proven that it could soon become the standard for monitoring CAD and identifying patients at high risk of future cardiovascular events. In this review article, we summarize the current evidence on coronary CTA and the potential role of coronary CTA after the ISCHEMIA trial for patients with CAD. Risk assessment using detailed CAD data obtained non-invasively and prevention of future cardiovascular events through improved medical care will become increasingly essential for the precision treatment and prevention of CAD in patients.


Depleted soil carbon and nitrogen pools beneath impervious surfaces.
Urban soils and vegetation contain large pools of carbon (C) and nitrogen (N) and may sequester these elements at considerable rates; however, there have been no systematic studies of the composition of soils beneath the impervious surfaces that dominate urban areas. This has made it impossible to reliably estimate the net impact of urbanization on terrestrial C and N pools. In this study, we compared open area and impervious-covered soils in New York City and found that the C and N content of the soil (0-15 cm) under impervious surfaces was 66% and 95% lower, respectively. Analysis of extracellular enzyme activities in the soils suggests that recalcitrant compounds dominate the organic matter pool under impervious surfaces. If the differences between impervious-covered and open area soils represent a loss of C and N from urban ecosystems, the magnitude of these losses could offset sequestration in other parts of the urban landscape.


Column-switching techniques for high-performance liquid chromatography of drugs in biological samples.
In recent years, an increasing number of publications have demonstrated the potential of column-switching techniques for the chromatographic separation, determination and preparative isolation of analytes from biological matrices. Column-switching systems greatly facilitate drug analysis, by on-line sample clean-up and trace enrichment, or by improving the analytical separative process. In this paper, the main applications of column-switching techniques to drug analysis in biological samples, are reviewed.


Determination of trimethoprim in pediatric samples by high-performance liquid chromatography.
We describe and evaluate modifications to a known high-performance liquid chromatography assay of trimethoprim. The sensitivity, specificity and wide range of linearity (0.11-690 mumol/l) of this method make it suitable for analysing samples with large variations in volume and concentration. We have used it to study the pharmacokinetics of trimethoprim in children, including newborns. Automated injection is a useful option if the sample volume is not limited. The recovery (at 3.44 mumol/l) of the method was 99.8% with a coefficient of variation of 6.8% for manually injected samples. The corresponding results for automated injection were 97.9% and 12.8%.


Basophil Degranulation Assay.
Basophil degranulation assay has gained importance over the last decade in both diagnosis of food allergy and evaluation of progression of immunotherapy. This assay involves the identification and quantification of the expression of CD63 molecule on basophil membrane. CD63 is a marker of multivesicular bodies that is exposed to cell membrane during the process of degranulation in which the contents of basophil granules are released. This chapter describes the methodology for performing this assay.


Comparing memory and meta-memory abilities between children with acquired brain injury and healthy peers.
This study compared visual memory and meta-memory abilities of children with ABI to that of healthy peers. Participants included 16 children (aged 13.55 ± 3.29 years) with moderate or severe ABI and 16 healthy children (aged 12.44 ± 3.24 years) with typical development. Children completed the Contextual Memory Test for Children (CMT-CH). The study group showed significantly lower immediate and delayed recall abilities. While the controls used the context for better memorizing, most of the children with ABI used rehearsals. In both groups better delayed recall correlated with the use of a more efficient strategy. Meta-memory should be an integral part of the assessment for children with ABI. Therapists should enhance child's self-awareness to his/her abilities and encourage the use of strategies (e.g. context) for memorizing in daily life.


Chitosan-based siRNA delivery systems.
Recently, chitosan has attracted significant attention in the formulation of small interfering RNA (siRNA). Because of its cationic nature, chitosan can easily complex siRNA, thus readily forming nanoparticles. Moreover, chitosan is biocompatible and biodegradable, which make it a good candidate for siRNA delivery in vivo. However, chitosan requires further development to achieve high efficiency. This review will describe the major barriers that impair the efficiency of the chitosan-based siRNA delivery systems, including the stability of the delivery system in biological fluids and endosomal escape. Several solutions to counteract these barriers have been developed and will be discussed. The parameters to consider for designing powerful delivery systems will be described, particularly the possibilities for grafting targeting ligands. Finally, optimized systems that allow in vivo therapeutic applications for both local and systemic delivery will be reviewed. This review will present recent improvements in chitosan-based siRNA delivery systems that overcome many of these system's previous pitfalls and pave the way to a new generation of siRNA delivery systems.


JNK1/2 regulates ER-mitochondrial Ca2+ cross-talk during IL-1β-mediated cell death in RINm5F and human primary β-cells.
Elevated interleukin-1β (IL-1β) induces apoptosis in pancreatic β-cells through endoplasmic reticulum (ER) stress induction and subsequent c-jun-N-terminal kinase 1/2 (JNK1/2) activation. In earlier work we showed that JNK1/2 activation is initiated before ER stress and apoptotic induction in response to IL-1β. However, the detailed regulatory mechanisms are not completely understood. Because the ER is the organelle responsible for Ca(2+) handling and storage, here we examine the effects of IL-1β on cellular Ca(2+) movement and mitochondrial dysfunction and evaluate the role of JNK1/2. Our results show that in RINm5F cells and human primary β-cells, IL-1β alters mitochondrial membrane potential, mitochondrial permeability transition pore opening, ATP content, and reactive oxygen species production and these alterations are preceded by ER Ca(2+) release via IP3R channels and mitochondrial Ca(2+) uptake. All these events are prevented by JNK1/2 small interfering RNA (siRNA), indicating the mediating role of JNK1/2 in IL-1β-induced cellular alteration. This is accompanied by IL-1β-induced apoptosis, which is prevented by JNK1/2 siRNA and the IP3R inhibitor xestospongin C. This suggests a regulatory role of JNK1/2 in modulating the ER-mitochondrial-Ca(2+) axis by IL-1β in apoptotic cell death.


Treatment with targeted vesicular stomatitis virus generates therapeutic multifunctional anti-tumor memory CD4 T cells.
A generally applicable, easy-to-use method of focusing a patient's immune system to eradicate or prevent cancer has been elusive. We are attempting to develop a targeted virus to accomplish these aims. We previously created a recombinant replicating vesicular stomatitis virus (VSV) that preferentially infected Her2/neu expressing breast cancer cells and showed therapeutic efficacy in an implanted Balb/c mouse tumor model. The current work shows that this therapy generated therapeutic anti-tumor CD4 T cells against multiple tumor antigens. CD4 T cells transferred directly from cured donor mice could eradicate established tumors in host mice. T cells were transferred directly from donor mice and were not stimulated ex vivo. Both tumors that expressed Her2/neu and those that did not were cured by transferred T cells. Analysis of cytokines secreted by anti-tumor memory CD4 T cells displayed a multifunctional pattern with high levels of interferon-γ, interleukin (IL)-4 and IL-17. Anti-tumor memory CD4 T cells traveled to the mesenteric lymph nodes and were activated there. Treatment with targeted recombinant replicating VSV is a potent immune adjuvant that generates therapeutic, multifunctional anti-tumor memory CD4 T cells that recognize multiple tumor antigens. Immunity elicited by viral therapy is independent of host major histocompatibility complex or knowledge of tumor antigens. Virus-induced tumor immunity could have great benefit in the prevention and treatment of tumor metastases.


Patient-centered care during the last year of life: adaptation and validation of the German PACIC short form for bereaved persons as proxies (PACIC-S9-proxy).
Providing patient-centered care (PCC) during the last year of life (LYOL) can be challenging due to the complexity of the patients' medical, social and psychological needs, especially in case of chronic illnesses. Assessing PCC can be helpful in identifying areas for improvements. Since not all patients can be surveyed, a questionnaire for proxy informants was developed in order to retrospectively assess patient-centeredness in care during the whole LYOL. This study aimed to evaluate the feasibility and validity of an adapted version of the German Patient Assessment of Chronic Illness Care (PACIC) for surveying bereaved persons in order to assess PCC during the decedents' LYOL. The German PACIC short form (11 items) was adapted to a nine-item version for surveying bereaved persons on the decedent's LYOL (PACIC-S9-Proxy). Items were rated on a five-point Likert scale. The PACIC adaptation and validation was part of a cross-sectional survey in the region of Cologne. Participants were recruited through self-selection and active recruitment by practice partners. Sociodemographic characteristics and missing data were analyzed using descriptive statistics. An exploratory factor analysis was conducted in order to assess the structure of the PACIC-S9-Proxy. Internal consistency was estimated using Cronbach's alpha. Of the 351 informants who participated in the survey, 230 (65.52%) considered their decedent to have suffered from chronic illness prior to death. 193 of these informants (83.91%) completed ≥5 items of the questionnaire and were included in the analysis. The least answered item was item (74.09%) was item 4 (encouragement to group & classes for coping). The most frequently answered item (96.89%) was item 2 (satisfaction with care organization). Informants rated the item" Given a copy of their treatment plan" highest (mean 3.96), whereas "encouragement to get to a specific group or class to cope with the condition" (mean 1.74) was rated lowest. Cronbach's alpha was 0.84. A unidimensional structure of the questionnaire was found (Kaiser-Meyer-Olkin 0.86, Bartlett's test for sphericity p < 0.001), with items' factor loadings ranging from 0.46 to 0.82. The nine-item questionnaire can be used as efficient tool for assessing PCC during the LYOL retrospectively and by proxies. The study was registered in the German Clinical Trials Register ( DRKS00011925 ) on 13 June 2017.


Mental health rehabilitation services in Ireland: vision and reality.
The Irish national mental health policy document, A Vision for Change , included recommendations to develop specialist rehabilitation mental health services. This survey was conducted as part of a multicentre study to investigate current provision of mental health rehabilitation services in Ireland and factors associated with better clinical outcomes for users of these services. The aim was to carry out a detailed national survey of specialist rehabilitation services in order to describe current service provision. A structured questionnaire was sent to consultant rehabilitation psychiatrists in all mental health catchment areas of Ireland that had any rehabilitation services to gather data on various aspects of service provision. Twenty-six of the 31 mental health areas of Ireland had some form of rehabilitation service. Sixteen teams working in 15 of these areas fulfilled A Vision for Change criteria to be defined as specialist rehabilitation services and all 16 responded to the survey. The overall response rate was 73% (19/26). Most services lacked a full multidisciplinary team. Only one service had an assertive outreach team with acceptable fidelity to the assertive outreach model. Urban services were less well resourced than rural services. This is the first national survey to describe the provision of mental health rehabilitation services in Ireland. Although there has been an increase in the provision of consultant-led specialist rehabilitation services nationally, these services lack multidisciplinary input. There also appears to be a lack of planned provision of the facilities required to provide comprehensive rehabilitation services with unequal distribution of resources between urban and rural areas. This has potential cost implications for local mental health services in relation to 'out of area treatment' placements and perhaps more importantly to the overall quality of patient care.


[Correction of nose deformities after plastic surgery of unilateral cleft lip].
The author describes the method of operation for the elimination of the recurrent flat wing and tip of the nose after reconstructive chilorhinoplasty in unilateral cleft lips. The method of chilorhinoplasty was used in more than 500 patients. The symmetry of the nose tip was achieved in 85% of the cases which shows the prospects of introduction of the method into wide clinical practice.


Diagnostic evaluation of the infertile female: a committee opinion.
Diagnostic evaluation for infertility in women should be conducted in a systematic, expeditious, and cost-effective manner to identify all relevant factors with initial emphasis on the least invasive methods for detection of the most common causes of infertility. The purpose of this committee opinion is to provide a critical review of the current methods and procedures for the evaluation of the infertile female, and it replaces the document of the same name, last published in 2012 (Fertil Steril 2012;98:302–7).


Subacute cutaneous lupus erythematosus associated with radioiodine treatment.
Subacute cutaneous lupus erythematosus (SCLE) is characterized by nonscarring, photodistributed, annular or papulosquamous plaques with antibodies to Ro/SS-A antigen. We report a case of SCLE associated with radioiodine treatment.


Acupuncture for diabetic neuropathic pain: A protocol for systematic review and meta analysis.
Diabetic neuropathic pain (DNP) is a common complication of diabetes mellitus, it severely affects the quality of life of Diabetic patients. Acupuncture is proofed to have favorable effects in treating DNP, however, evidence needs to be gathered and interpreted. We will make a comprehensive review of clinical trials concerning acupuncture in treating DNP and do meta-analysis if possible. The following databases will be searched from the inception to September 2020: PubMed, Embase, Web of Science, China National Knowledge Infrastructure, Wan-Fang Database, and Chinese Scientific Journal Database. RCTs that evaluated acupuncture for patients with DNP will be included. The primary outcome will be patient-reported pain intensity using validated scales or verbal reporting. The secondary outcomes including the Toronto clinical scoring system, Sensory Nerve Conduction Velocity, Motor Nerve Conduction Velocity, and quality of life. The study selection, data extraction, and study quality evaluation will be performed independently by 2 researchers. A meta-analysis will be performed using RevMan V5.3 statistical software if possible; otherwise, descriptive analysis or subgroup analysis will be conducted. The quality of evidence for outcomes will be assessed with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. This study will evaluate the effect and safety of acupuncture in treating DNP. The evidence we generated from the present study will provide more options for DNP management in clinical practice. INPLASY202090043.


Hydatid cyst excision using Dowling's technique of hydrodissection.
Neurohydatidosis is a rare zoonotic disease in nonendemic areas and a differential diagnosis of intracerebral cysts workup. Appropriate imaging modalities with serology are required for proper diagnosis. The gold standard surgical intervention is the Dowling-Orlando technique. We provide a detailed description, with key surgical steps, for total excision of hydatid cysts with intact capsules by hydrodissection. We also describe the relevant surgical anatomy, with indications, limitations, and possible complications. Hydrodissection allows safe resection of hydatid cysts without further damage to the surrounding parenchyma and reduces the risk of cystic wall rupture.


Risk Factors of Prolonged Nausea and Vomiting During Pregnancy.
Determination of the risk factors associated with prolonged nausea and vomiting during pregnancy (NVP) helps to develop prevention strategies. However, there is a lack of studies regarding risk factors of prolonged NVP. Thus, the potential risk factors of prolonged moderate and severe NVP were examined. This is a retrospective study among pregnant women in South of China. The Pregnancy-Unique Quantification of Emesis (PUQE) scale was used to evaluate NVP. Onset before 12 weeks and persistence after 20 weeks of gestation were defined as prolonged NVP. Data on NVP and other variables were collected by standard questionnaires and medical records. A finally sample of 1739 participants were analyzed. The incidence of prolonged moderate and severe NVP was 42.1% and 1.1%, respectively. Among those with NVP, the increased risk of prolonged moderate NVP was associated with lower gestational age (OR = 0.95 per SD increase, 95% CI=0.93-0.97), being a housewife (OR = 1.30, 95% CI=1.02-1.65), pre-pregnant longer sedentary time (OR = 2.02, 95% CI=1.16-1.83), pre-pregnant lower exercise frequency (OR = 1.84, 95% CI=1.20-2.82), and history of gastrointestinal (GI) diseases (OR = 2.21, 95% CI=1.61-3.03). Persons who were a housewife (OR = 6.39, 95% CI=1.90-21.47), with pre-pregnant high frequent (always) cold drinking (OR=11.12, 95% CI=1.24-100.73), and had a history of GI diseases (OR=10.10, 95% CI=2.63-38.86) were more likely to experience prolonged severe NVP. The results of the present study suggested that pregnant women unemployed, with lower gestational age, pre-pregnant longer sedentary time, less exercise, high frequent (always) cold drinking and history of GI diseases had a higher risk of prolonged NVP and should be taken more care.


Memristive Effect in Ti3 C2 Tx (MXene) Polyelectrolyte Multilayers.
The emerging novel class of two-dimensional materials - MХenes - have attracted significant research attention. However, there are only few reports on using the most prominent member of the MXene family, Ti3 C2 Tx , as an active material for memristive devices within a polyelectrolyte matrix and its deposition on inert electrodes like ITO and Pt. In this study, we systematically investigate Ti3 C2 Tx MXenes synthesized with two classical delamination agents, such as lithium chloride and tetramethylammonium hydroxide, to identify the most suitable candidate for memristive device applications. The characteristics of memristors based on the hybrid structures consisting of MXene-polyelectrolyte multilayers, specifically polyethyleneimine (PEI) and poly(sodium 4-styrenesulfonate) (PSS) are explored. The PEI(MXene)/PSS memristor exhibits a voltage threshold (VSET/RESET ) range of 1.5-2.0 V, enabling the transition from a high-resistive state (HRS) to a low-resistive state (LRS), along with a significant current switching ratio of approximately two orders of magnitude. The observed VSET/RESET difference of approximately 4 V is further supported by density functional theory (DFT) calculated redox potential. These findings underscore the potential of polyelectrolyte-based memristors, such as the in PEI-Ti3 C2 Tx -PSS system, in facilitating the development of highly functional, self-assembled memristive devices with diverse applications.


Exchange of free fatty acids and glucose in leg tissues before and immediately after surgery.
The present study was undertaken to investigate whether there is an augmented uptake of free fatty acids (FFA) in the leg tissues immediately after surgery when the energy expenditure of the leg is increased considerably. Eight patients were studied before and after cholecystectomy. Blood and plasma flow were determined in one leg, as well as arterio-venous concentration differences for oxygen, glycose, lactate and the total fraction of FFA. To determine uptake and release of FFA, 1-(14C)-oleic acid was infused intravenously and the arterio-venous differences for (14C)-FFA were determined. The mean oxygen uptake in the leg increased from 0.72+/-0.06 mmol/min to 1.78+/-0.41 mmol/min. The uptake of free fatty acids in the leg did not increase significantly after cholecystectomy when compared to before operation in spite of the marked increase in oxygen uptake. Postoperatively there was, however, a positive linear relationship between the uptake of FFA and that of oxygen in the leg. The glucose uptake, after correction for released lactate, corresponded to 7% of the oxygen uptake before surgery and 13% after surgery. The arterial FFA concentration did not change. This study indicates that the combined possible contribution of glucose and free fatty acids to the oxidative energy metabolism of the leg tissues exceeded the oxygen uptake before, but not after surgery. In the postoperative state there was a positive correlation between oxygen uptake and FFA uptake in the leg.


Spectrophotometric assay of the interaction between malaria erythrocyte lysates with methylene blue and neutral red dyes.
Changes of oxidative processes induced in mouse erythrocytes by Plasmodium berghei were studied in the presence of methylene blue, neutral red or of both cationic redox dyes. The results are discussed in terms of redox and metachromatic modifications of the dyes which are produced by malarial and normal erythrocyte lysates.


Prediction of all causes of death as a function of some factors commonly measured in cardiovascular population surveys.
A 20-year follow-up study for all causes of death has been conducted on two groups of men aged 40-59 at entry in two rural communities of northern and central Italy on a total of 1,712 subjects representing 98.9% of defined demographic samples. Personal characteristics or risk factors usually studied for coronary heart disease (CHD), as measured at entry, have been related to the risk of dying in 20 years (600 cases). By means of multivariate analysis, 11 out of 33 considered characteristics were shown to be significant predictors of any cause of death. These were mean blood pressure, age, arm circumference (protective), early death of parents, cigarette smoking, forced expiratory volume (protective), CHD, arcus senilis, vital capacity (protective), xanthelasma, and serum cholesterol. Discrimination between cases and noncases was satisfactory with about 40% of deaths in the upper quintile of the estimated distribution of risk and less than 7% in the lowest quintile (relative risk = 6.20).


Three-dimensional anatomy of the left atrium by magnetic resonance angiography: implications for catheter ablation for atrial fibrillation.
Pulmonary vein isolation (PVI) has become one of the primary treatments for symptomatic drug-refractory atrial fibrillation (AF). During this procedure, delivery of ablation lesions to certain regions of the left atrium can be technically challenging. Among the most challenging regions are the ridges separating the left pulmonary veins (LPV) from the left atrial appendage (LAA), and the right middle pulmonary vein (RMPV) from the right superior (RSPV) and right inferior (RIPV) pulmonary veins. A detailed anatomical characterization of these regions has not been previously reported. Magnetic resonance angiography (MRA) was performed in patients prior to undergoing PVI. Fifty consecutive patients with a RMPV identified by MRA were included in this study. Ridges associated with the left pulmonary veins were examined in an additional 30 patients who did not have a RMPV. Endoluminal views were reconstructed from the gadolinium-enhanced, breath-hold three-dimensional MRA data sets. Measurements were performed using electronic calipers. The width of the ridge separating the LPV from the LAA was found to be 3.7 +/- 1.1 mm at its narrowest point. The segment of this ridge with a width of 5 mm or less was 16.6 +/- 6.4 mm long. The width of the ridges separating the RMPV from the RSPV and the RIPV was found to be 3.0 +/-1.5 mm and 3.1 +/-1.8 mm, respectively. There were no significant differences between LPV ridges for patients with versus without a RMPV. The width of the ridges of atrial tissue separating LPV from the LAA and the RMPV from its neighboring veins may explain the technical challenge in obtaining stable catheter positions in these areas. A detailed assessment of the anatomy of these regions may improve the safety and efficacy of catheter ablation at these sites.


Trichalasins C and D from the plant endophytic fungus Trichoderma gamsii.
Two new cytochalasans, trichalasins C (1) and D (2) together with known cytochalasans aspochalasins D (3), M (4) and P (5) were isolated from one endophytic fungus Trichoderma gamsii inhabiting in traditional medicinal plant Panax notoginseng (BurK.) F.H.Chen. The structures for the new compounds 1 and 2 were determined by NMR and HRESIMS, and their relative configurations were established by analysis of coupling constants and NOESY correlations. Compound 3 displaying inhibitory activity with EC₅₀ value 5.72 μM, whereas the EC₅₀ values for compounds 1, 2 and 4, 5 are more than 40 μM.


Biocompatibility and biological activity of C70 fullerene adduct with L-threonine (C70(C4H9NO3)2).
The aim of this work is to synthesise and study the biocompatibility and biological activity of the C70 fullerene adduct with l-threonine (C70-Thr). The obtained adduct was identified using a complex of physicochemical methods, namely, 13C NMR spectroscopy, IR spectroscopy, thermogravimetric analysis, electron spectroscopy, elemental analysis, and high-performance liquid chromatography. The study of biocompatibility and biological activity of the C70-Thr adduct included the study of haemocompatibility (haemolysis, platelet aggregation, plasma coagulation haemostasis, binding to human serum albumin, esterase activity), antiradical activity, cytotoxicity, cell proliferation, and interaction with DNA (determination of the DNA binding constant and genotoxicity).


Parvalbumin-expressing interneurons can act solo while somatostatin-expressing interneurons act in chorus in most cases on cortical pyramidal cells.
Neural circuits in the cerebral cortex consist primarily of excitatory pyramidal (Pyr) cells and inhibitory interneurons. Interneurons are divided into several subtypes, in which the two major groups are those expressing parvalbumin (PV) or somatostatin (SOM). These subtypes of interneurons are reported to play distinct roles in tuning and/or gain of visual response of pyramidal cells in the visual cortex. It remains unclear whether there is any quantitative and functional difference between the PV → Pyr and SOM → Pyr connections. We compared unitary inhibitory postsynaptic currents (uIPSCs) evoked by electrophysiological activation of single presynaptic interneurons with population IPSCs evoked by photo-activation of a mass of interneurons in vivo and in vitro in transgenic mice in which PV or SOM neurons expressed channelrhodopsin-2, and found that at least about 14 PV neurons made strong connections with a postsynaptic Pyr cell while a much larger number of SOM neurons made weak connections. Activation or suppression of single PV neurons modified visual responses of postsynaptic Pyr cells in 6 of 7 pairs whereas that of single SOM neurons showed no significant modification in 8 of 11 pairs, suggesting that PV neurons can act solo whereas most of SOM neurons may act in chorus on Pyr cells.


Cloning of two putative Giardia lamblia glucosamine 6-phosphate isomerase genes only one of which is transcriptionally activated during encystment.
The biosynthesis of the carbohydrate component of the cyst wall of the protozoan parasite Giardia lamblia, a polymer of N-acetylgalactosamine (GalNac), is by a pathway that is initiated with the conversion of fructose 6-phosphate to glucosamine 6-phosphate by an aminating isomerase, glucose 6-phosphate isomerase. This enzyme appears only after Giardia trophozoites are induced to start the production of cyst wall components after bile is added. To investigate whether induction of glucosamine 6-phosphate isomerase is by protein modification or by transcription activation, its gene was cloned and sequenced. Two genes, gpi1 and gpi2, encoding putative glucosamine 6-phosphate isomerases were identified but one, gpi1 was expressed. The transcript for gpi1 appeared not earlier than 6 h after cells were induced with bile salts. These results show that the first enzyme in the pathway leading to GalNac synthesis in encysting Giardia cyst wall biosynthesis is under transcriptional control.


Phagocytosis of Escherichia coli mediated by mannose resistant non-fimbrial haemagglutinin (NFA-1).
We examined the interaction between a urinary isolate of E. coli carrying non-fimbrial MR adhesin (NFA-1) and human polymorphonuclear leukocytes (PMN). We found that the organisms attach to PMN and the attachment was dose dependent and saturable. It was inhibited by isolated NFA-1, but not by mannoside. Recombinant plasmid encoding NFA-1 adhesin conferred binding capacity on a non-adhesive strain. The attachment of the bacteria carrying NFA-1 to PMN was associated with oxidative burst and inhibited by isolated NFA-1. The data taken together suggest that NFA-1 mediates the attachment of the bacteria to PMN. The attachment is followed by ingestion and killing of the organisms, but at a slower rate than with bacteria bound via type 1 fimbriae.


Significance of exercise-induced ST segment elevation in Q leads in patients with a recent myocardial infarction and an open infarct-related artery Analysis with angiography, intracoronary myocardial contrast echocardiography and cardiac magnetic resonance.
The significance of exercise-induced ST segment elevation in Q leads in patients with a recent myocardial infarction and without significant residual stenosis in the infarct-related artery has not been defined. We aimed to elucidate the role of myocardial perfusion and viability in this scenario. Sixty-six patients with a first myocardial infarction, single-vessel disease and an open artery were studied. Myocardial perfusion was assessed with angiographic blush, intracoronary myocardial contrast echocardiography and magnetic resonance. Myocardial viability was quantified by means of magnetic resonance (transmural extent of necrosis). Exercise-induced ST elevation in Q leads was observed only in 13 cases (20%); 53 patients (80%) did not show this finding. The group with ST elevation had fewer cases with normal perfusion: Blush 3 (15% vs. 74%, p=0.001), myocardial contrast echocardiography score >0.75 (8% vs. 81%, p=0.001) and magnetic resonance score >0.75 (31% vs. 68%, p=0.03). Similarly, myocardial viability (necrosis <50%) was less frequent in patients with ST elevation (8% vs. 72%, p=0.001). In patients with a first myocardial infarction and without residual ischemia, exercise-induced ST segment elevation in Q leads is an uncommon finding and it is related to a more damaged coronary microcirculation and to less viable myocardium.


Plants are visited by more pollinator species than pollination syndromes predicted in an oceanic island community.
The pollination syndrome concept has provided powerful utility in understanding the evolution and adaptation of floral traits. However, the utility of this conception has been questioned on the grounds that flowers usually attract a broader spectrum of visitors than one might expect. Furthermore, the relationship between plant specialization and floral traits is poorly understood. Here, we examined the applicability of using the pollination syndrome to predict the pollinators of plants on Yongxing Island. We used the species-level specialization of pollination networks to compare the difference of plant ecological specialization among floral traits. The result of full model was not significant, indicating that floral traits did not affect the pollinator functional groups. The five floral traits explained only 22.5% of the pollinator's visitation preference. Our results showed that plants were visited by more pollinator species than pollination syndromes predicted. Plants with restrictive flowers showed higher specialization than those with unrestrictive flowers, while other floral traits exhibited no significant effect on plant specialization. Generalized pollination system on oceanic island might influence the predictive accuracy of pollination syndromes and the relationship between floral traits and plant ecological specialization. Our findings highlighted the utility and limitations of pollination syndromes concept in oceanic island communities.


Metal-Organic Framework-Derived Co3O4/Au Heterostructure as a Catalyst for Efficient Oxygen Reduction.
Porous nanostructures with a yolk-shell complex interior will provide lots of virtues to construct advanced catalysts. In our work, the preparation of novel yolk-shell Au nanocrystal-loaded Co3O4 nanocages (Co3O4/Au heterostructure) from a metal-organic framework-derived composite was reported. Scanning electron microscopy, energy-dispersive X-ray spectroscopy, transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, Brunauer-Emmett-Teller analysis, and so forth were used to analyze the morphology, structure, and composition of the heterostructures. Most importantly, Co3O4/Au heterostructures are a kind of low-cost, good performance catalysts for the oxygen reduction reaction to replace the noble-Pt catalysts. The high surface area of the porous structure and the excellent electron transfer properties of well-dispersed Au nanocrystals and also the electronic coupling effect between Co3O4 and Au in the composites are attributed to the good performance.


Immunosuppressive therapy in the nephrotic syndrome in children.
The high incidence of remission and prevention of relapse of minimal change nephrotic syndrome (MCNS) in children, produced by corticosteroids is reviewed. With the introduction of corticosteroids over 30 years ago and the increased expertise in their use, the mortality rate has been reduced to less than 5%. There is no justification for a clinical trial to test the effect of corticosteroids in inducing remission, but the need remains to evaluate methods of administration in order to achieve therapeutic benefit with minimum toxicity. Children with frequently relapsing, steroid-dependent MCNS will usually enter remission following treatment with an alkylating agent such as cyclophosphamide. In about 50% no further relapse in experienced. The results of recent experience using cyclosporin A immunosuppression suggest a beneficial effect associated with steroid responsiveness. Approximately 30% of children with focal segmental glomerulosclerosis enter remission following treatment with corticosteroids. Some 30% require dialysis and transplantation within 5 years of diagnosis and immunosuppressive therapy to prevent deterioration of renal function is probably justified.


Language spoken at home and the association between ethnicity and doctor-patient communication in primary care: analysis of survey data for South Asian and White British patients.
To investigate if language spoken at home mediates the relationship between ethnicity and doctor-patient communication for South Asian and White British patients. We conducted secondary analysis of patient experience survey data collected from 5870 patients across 25 English general practices. Mixed effect linear regression estimated the difference in composite general practitioner-patient communication scores between White British and South Asian patients, controlling for practice, patient demographics and patient language. There was strong evidence of an association between doctor-patient communication scores and ethnicity. South Asian patients reported scores averaging 3.0 percentage points lower (scale of 0-100) than White British patients (95% CI -4.9 to -1.1, p=0.002). This difference reduced to 1.4 points (95% CI -3.1 to 0.4) after accounting for speaking a non-English language at home; respondents who spoke a non-English language at home reported lower scores than English-speakers (adjusted difference 3.3 points, 95% CI -6.4 to -0.2). South Asian patients rate communication lower than White British patients within the same practices and with similar demographics. Our analysis further shows that this disparity is largely mediated by language.


A dual-targeting nanocarrier based on poly(amidoamine) dendrimers conjugated with transferrin and tamoxifen for treating brain gliomas.
A pH-sensitive dual-targeting drug carrier (G4-DOX-PEG-Tf-TAM) was synthesized with transferrin (Tf) conjugated on the exterior and Tamoxifen (TAM) in the interior of the fourth generation PAMAM dendrimers for enhancing the blood-brain barrier (BBB) transportation and improving the drug accumulation in the glioma cells. It was found that, on average, 7 doxorubicine (DOX) molecules, over 30 PEG(1000) and PEG(2000) chains and one Tf group were bonded on the periphery of each G4 PAMAM dendrimer, while 29 TAM molecules were encapsulated into the interior of per dendrimer. The pH-triggered DOX release was 32% at pH 4.5 and 6% at pH 7.4, indicating a comparatively fast drug release at weak acidic condition and stable state of the carrier at physiological environment. The in vitro assay of the drug transport across the BBB model showed that G4-DOX-PEG-Tf-TAM exhibited higher BBB transportation ability with the transporting ratio of 6.06% in 3 h. The carrier was internalized into C6 glioma cells upon crossing the BBB model by the coactions of TfR-mediated endocytosis and the inhibition effect of TAM to the drug efflux transports. Moreover, it also displayed the in vitro accumulation of DOX in the avascular C6 glioma spheroids made the tumor volume effectively reduced.


Electrically stimulated Krebs-Henseleit buffer does not relax precontracted human bronchi in vitro.
Electric field stimulation (EFS) causes a non-adrenergic relaxation of precontracted human airways. Only 10-20% of this response can be blocked with the nervous conductance blocker tetrodotoxin (TTX). Therefore, 80-90% of the non-adrenergic relaxation is not neurally mediated. The mechanism of this non-neural component is unclear. We examined whether EFS induces the generation of muscle relaxing substances in oxygenated Krebs-Henseleit buffer. Strips of central airways of 6 patients were precontracted with methacholine (10(-5) M) and exposed to Krebs buffer that had previously been stimulated with EFS (50 V, 0.3 ms, 30 s, 1-50 Hz). Results were compared to those obtained with unstimulated buffer. The contractile state of the airways did not change significantly with either EFS-stimulated or unstimulated buffer. We conclude that in oxygenated Krebs buffer EFS does not cause generation of substances that change the contractile state of prestimulated human airways.


In vivo transfection of bovine leukemia provirus into sheep.
Bovine leukemia virus is horizontally transmitted mainly through infected cells by direct blood transfer. In this report, a cloned bovine leukemia virus (BLV) provirus was examined for its infectivity by direct inoculation into sheep. One hundred micrograms of plasmid DNA containing a complete provirus was mixed with a cationic liposome solution and injected intradermally into five sheep at three different locations. Seroconversion occurred 1 to 2 months after injection as demonstrated by immunodiffusion, indirect ELISA (for the gp51 envelope protein), and blocking ELISA (for gp51 and the major capsid protein, p24). These results demonstrate that BLV infection can be efficiently initiated by direct transfection into sheep. This approach should thus facilitate investigation of the involvement of BLV genetic determinants in the induction of leukemia in ruminants.


Broad scale functional connectivity for Asian elephants in the Nepal-India transboundary region.
The Nepal-India transboundary region hosts one of Asia's most complex large mammal assemblages, including a small (but growing) population of Asian elephants (Elephas maximus). These elephants occur in four widespread and geographically disjunct subpopulations, and some of them undergo seasonal transboundary movements. We conducted a broad-scale evaluation of the amount and quality of elephant habitat available in the region and of functional landscape connectivity between and within subpopulations using Maxent, circuit theory, and least-cost path analysis. Habitat suitability was highly influenced by abiotic geographical factors (altitude and precipitation) and less by ecological factors (habitat heterogeneity, plant productivity) and human disturbance (distance to settlements). The region had a relatively small amount of high and optimal suitability habitat (12.6% out of 93,700 km2) but all subpopulations seem to be far from carrying capacity, suggesting ample potential for further population growth. Landscape connectivity was higher between and within the west and far-west subpopulations, which should be considered a single subpopulation. The central and ea st subpopulations, however, had low to very low between-subpopulation connectivity. Conservation priorities include maintaining the current connectivity in the west subpopulation and across the border in the east, and protecting high-quality habitats in eastern Nepal. Restoring connectivity between the central and other subpopulations is possible if the number of elephants continues growing, and it should be a long-term conservation aspiration. Maintaining and enhancing landscape connectivity in this region requires transboundary cooperation and coordination between Nepali and Indian authorities. If successful, it will bring considerable benefits for the conservation of elephants and other wildlife.


Tissue limited mosaicism for unbalanced autosomal translocation in a child with congenital anomalies and mental retardation.
We studied a patient with a sporadic mental retardation/multiple congenital anomalies syndrome. Chromosome analysis showed a 46,XX, inv(9)(p 11;q13) karyotype in all lymphocytes. Fibroblasts from two separate skin biopsies revealed a mosaic karyotype. Some 22.5% of fibroblasts had a karyotype like that of the lymphocytes, while 77.5% of fibroblasts had a karyotype 46,XX,inv(9)(p11;q13),der(12),t(12;?)(P13;?). The data in this case emphasize the drawbacks of confining cytogenetic analysis to lymphocytes.


Contributing factors to postoperative length of stay in laparoscopic cholecystectomy.
Laparoscopic cholecystectomy for gallbladder disease is a common surgical procedure performed in hospitals throughout the world. This study evaluates the major factors that contribute to postoperative length of stay for patients undergoing laparoscopic cholecystectomy. We analyzed data for patients undergoing laparoscopic cholecystectomy in a 5-hospital community health system from December 1, 2008 to January 31, 2009. The natural logarithm of postoperative length of stay was modeled to evaluate significant factors and contributions. Included in the analysis were 232 patients. Three preoperative patient factors were significant contributors: body mass index was associated with decreased postoperative length of stay, while white blood cell count and the presence of biliary pancreatitis were associated with increased postoperative length of stay. The operative factors of fluids administered and ASA class were significant contributors to increased postoperative length of stay, with an increasing contribution with a higher ASA class. The utilization factor of nonelective status was a significant contributor to increased postoperative length of stay. Several factors were major contributors to postoperative length of stay, with ASA class and nonelective status having the most significant increased contribution. Efforts to optimize efficient elective care delivery for patients with symptomatic gallbladder disease may demonstrate a benefit of decreased hospital utilization.


MEG measures of covert orienting and gaze processing in children.
We investigated developmental differences in the cortical attention processing network using magnetoencephalography (MEG) and a spatial cueing task in 7-8 and 12-13 year old children. The cueing paradigm consisted of a centrally presented face with left or right averted eye-gaze in the gaze cue condition, and a central face with straight gaze presented with a cue stimulus to the left or right of the face in the peripheral cue condition. Cue congruency was 50 %. MEG was recorded during the two conditions and event-related beamforming was used to determine the timing and location of the brain activity related to target detection with the two types of cueing. The MEG data showed no age differences in the eye-gaze condition, but a developmental difference characterised by slower and more diffuse activations for peripheral cues in the younger versus the older age group. In the 7-8 year olds activation peaked around 300 ms, and was localised to left inferior frontal gyrus as well as posterior areas related to visuo-spatial processing. The 12-13 year olds showed a temporoparietal pattern of activation characteristic of spatial reorientation which resembled that seen for adult participants using the same paradigm (Nagata et al. 2012). The activation peaked around 200 ms and was localised to the left superior frontal gyrus, middle frontal gyrus but bilaterally near the temporoparietal junction. The data indicate maturational changes in brain activity for peripheral cueing.


Concurrent treatment planning for outpatient high dose rate prostate template implants.
Since November of 1991, we have treated locally advanced (B2-C) prostate cancer using external beam radiotherapy integrated with outpatient high dose rate interstitial implant boost as part of a Phase II clinical trial. This required (a) rapid, automated planning; (b) incorporation of image data and (c) dose optimization. A treatment planning system was designed which integrates imaging and needle guidance with source reconstruction and dose display. All components of treatment planning (reconstruction, optimization, dose prescription, dose display) are largely automated. A rectal reference point was defined which was reproducible and easily verified. No pretreatment planning was required. As of November 1992, 83 treatments were delivered using this system. Intra-operative treatment decisions were made possible due to the speed and ease of interpretation of the system. The system has proven satisfactory in the operating room. Rectal doses were calculated for all patients, and ranged from 35-79% of the prescribed dose, with a mean of 58%. The first echelon of a Phase II escalating dose trial has been completed, with 22 patients treated over a period of 1 year. Outpatient high dose rate brachytherapy appears to be a practical means of boosting locally advanced prostate cancer patients. Rapid treatment planning is possible incorporating on-line ultrasound images to allow immediate dose optimization to be performed during and after implant placement.


Motion after-effects and word contingency.
Stimulus-selectivity in phenomena such as the McCollough effect and other contingent after effects are controversial. Word specific McCollough effects have been reported (Allan et al., Percept Psychophys 1989;45:104-113) that suggest an associative model rather then a neural one. However, failures to replicate make this finding controversial (Humphrey et al., J Exp Psychol: Gen 123:86-90). We applied the same contingency to the motion after-effect. Moving words, words paired with sine wave gratings and words composed of sine wave gratings failed to generate text contingent after-effects in stimulus situations that normally evoke motion after-effects. Thus, there was little evidence that motion adaptation can be made textually contingent.


Enhanced effect of modified Zika virus E antigen on the immunogenicity of DNA vaccine.
It has been reported worldwide that the Zika virus (ZIKV) could be transmitted through placentas and sexual contact. ZIKV can also cause Guillain-Barre syndrome, microcephaly and neurological abnormalities. However, there are no approved vaccines available. We constructed six DNA vaccine candidates and tested the immunogenicity. Tandem repeated envelope domain Ⅲ (ED Ⅲ × 3) induced highly total IgG and neutralization antibody, as well as CD8+ T cell responses. Also, stem region-removed envelope (E ΔSTEM) elicited a robust production of IFN-γ in mice. To examine in vivo protection, we used mice treated with an IFNAR1 blocking antibody before and after the challenge. Vaccination with the two candidates led to a decline in the level of viral RNAs in organs. Moreover, the sera from the vaccinated mice did not enhance the infection of Dengue virus in K562 cells. These findings suggest the potential for the development of a novel ZIKV DNA vaccine.


Antibody elbow angles are influenced by their light chain class.
We have examined the elbow angles for 365 different Fab fragments, and observe that Fabs with lambda light chains have adopted a wider range of elbow angles than their kappa chain counterparts, and that the lambda light chain Fabs are frequently found with very large (>195 degrees ) elbow angles. This apparent hyperflexibility of lambda chain Fabs may be due to an insertion in their switch region, which is one residue longer than in kappa chains, with glycine occurring most frequently at the insertion position. A new, web-based computer program that was used to calculate the Fab elbow angles is described.


[A clinical study of non-erosive reflux disease].
[corrected] To investigate the differences and similarities between non-erosive reflux disease (NERD) and reflux disease (RE). This study covered 30 patients who were grouped by endoscopy into the cases of NERD (n=17) or RE (n=13). The two groups' symptom, mentality, and damage to life quality were compared. Biopsy was performed at 3 cm above LES in oesophagus. The patients were placed under ambulatory 24-h oesophageal pH and Bilitec2000 monitoring. And their responses to the same anti-reflux treatment were evaluated. (1) The proportion of female (58.82%) in NERD group was much higher than that (15.38%) in RE group (P<0.05). (2) There was no remarkable difference in symptom, damage to life quality between the NERD and RE groups (P>0.05). But in respect to mentality, the NERD group had significantly higher anxiety and depression scores than did the RE group (P<0.05). (3) No noticeable difference in the pathological results of biopsy was seen between the NERD and RE groups (P>0.05). (4) The NERD group had less abnormal reflux, compared with the RE group (P<0.05). (5) The NERD group gave less response to treatment, compared to the RE group (P<0.05). NERD may be a kind of reflux disease different from RE.