Phenylpyridyl-Fused Boroles: A Unique Coordination Mode and Weak B-N Coordination-Induced Dual Fluorescence.
Using 4-phenylpyridine or 2-phenylpyridine in place of biphenyl, two electron-poor phenylpyridyl-fused boroles, [TipPBB1]4 and TipPBB2 were prepared. [TipPBB1]4 adopts a unique coordination mode and forms a tetramer with a cavity in both the solid state and solution. The boron center of TipPBB2 is 4-coordinate in the solid state but the system dissociates in solution, leading to 3-coordinate borole species. Compared to its borafluorene analogues, the electron-accepting ability of TipPBB2 is largely enhanced by the pyridyl group. TipPBB2 exhibits dual fluorescence in solution due to an equilibrium between free TipPBB2 and a weak intermolecular coordination adduct with a second molecule. This equilibrium was further investigated by low-temperature NMR spectroscopy and photophysical studies. Theoretical studies indicate that the highest occupied molecular orbital (HOMO) of TipPBB2 localizes at the Tip group, in contrast to its borafluorene derivatives, wherein the HOMOs are localized on the borafluorene cores.


Characterization of a calcitonin gene-related peptide (CGRP) receptor on mouse bone marrow cells.
Calcitonin gene-related peptide, (CGRP), a vasoactive neuropeptide, is found throughout the peripheral nervous system, and CGRP receptors are present on mature lymphocytes. The current studies describe a CGRP receptor on isolated mouse bone marrow cells. The affinity, distribution and specificity of CGRP receptors were analyzed using radioligand binding assays. [125I]CGRP binding in mouse bone marrow cells was dependent on cell concentration and was stable from 5 to 60 min at room temperature. The average Kd is 3.29 +/- 1.24 nM and the average receptor density is 2796 +/- 365 sites/cell. Competition binding analysis found rat alpha and beta CGRP to be the most inhibitory, (Ki values 0.899 and 0.711 nM, respectively), followed by human alpha CGRP and the antagonist human CGRP8-37. The neuropeptides human and salmon calcitonin did not inhibit [125I]CGRP binding to bone marrow cells. The presence of CGRP receptors on mouse bone marrow cells provides further evidence for a direct role for CGRP in modulating the function and differentiation of cellular components of the immune and inflammatory systems.


Cardiovascular impairment in children, adolescents, and young adults with type 1 diabetes mellitus (T1DM).
Left ventricular (LV) function was assessed in 42 patients (mean age +/- SD, 18.45 +/- 3.76 years; 17 males) with type I diabetes mellitus (T1DM; mean duration 9.89 years) and in 43 healthy controls (mean age +/- SD, 18.27 +/- 3.36 years; 18 males). Systolic, diastolic cardiac function and LV dimensions were assessed using M-mode and Doppler echocardiography. Neural autonomic function was assessed by measuring RR variation during deep breathing, Valsava maneuver, 30/15 ratio, and blood pressure response to standing. Fractional shortening, peak velocity of early ventricular filling (E wave), peak velocity of LV filling (A wave), E/A ratio, deceleration time, isovolumic relaxation time, LV dimensions (interventricular septum, posterior wall thickness, end diastolic diameter [EDD] and systolic diameter [ESD]) were all comparable between patients with T1DM and controls. However, in 11 T1DM patients with microalbuminuria and/or retinopathy, EDD, ESD, E/A ratio, and E wave were all lower (p = 0.0011, p = 0.019, p = 0.0011, and p = 0.030, respectively) while, A wave, heart rate, and diastolic blood pressure were all higher (p = 0.008, p = 0.0024 and p = 0.004, respectively) compared to matched for age and sex controls. Furthermore, in six of the 11 T1DM patients with microangiopathy who had E/A <1.12 (<2 SD of the control mean), significant and marginally significant correlations were found between E/A ratio and the duration of the disease as well as the mean HbA1c of the last year (r = -0.38, p = 0.011 and r = -0.287, p = 0.064, respectively). In conclusion, it has been found that impairment of diastolic, but not systolic, LV function can be detected early in young patients with T1DM and microangiopathy.


Pancreaticopleural fistula in a Thai boy with SPINK1 c.101A>G substitution variant-related chronic pancreatitis: a case report and literature review.
Chronic pancreatitis is the most common etiology of pancreaticopleural fistula (PPF) in children, and underlying genetic variations are now widely known, accounting for most chronic pediatric pancreatitis. We describe a case of previously undetected chronic pancreatitis and PPF with a SPINK1 variation in a 10-year-old Thai boy who presented with massive left pleural effusion. Magnetic resonance cholangiopancreatography (MRCP) revealed disruption of the pancreatic duct, which was communicating with a large pancreatic pseudocyst with mediastinal extension. The patient subsequently underwent endoscopic intervention with improved clinical symptoms. We also reviewed the imaging findings of 12 other reported cases of pediatric PPF. Massive pleural effusion due to PPF can be an atypical manifestation in children with chronic pancreatitis. MRCP is the preferable imaging study for PPF due to the production of highly detailed images of pancreatic duct disruptions and anatomy, and the imaging is helpful to guide for appropriate treatment. Tests for genetic variation are also recommended in a child with chronic pancreatitis.


Recurrent cardiac myxoma in a 25 year old male: a DNA study.
We present a 25 year old Caucasian male patient with multiple recurrences of cardiac myxomas after surgical removal of the original tumor. His mother was operated on for right ventricular myxoma. The genetic analyses disclosed an aneuploid DNA content by flow cytometry analysis. The familial form of the cardiac myxomas must be distinguished from Carney complex syndrome. A long- term echocardiographic follow up is recommended to patients and their first degree relatives with cardiac myxomas.


Cyclo[6]aramide-Tropylium Charge Transfer Complex as a Colorimetric Chemosensor for Differentiation of Intimate and Loose Ion Pairs.
Shape-persistent iso-C16-cyclo[6]aramide (1) was found to form a charge-transfer (CT) complex with aromatic carbonium tropylium (Tr(+)). The resulting CT complex was evidenced by both experimental results and theoretical calculations. Particularly, dibutylammonium salt with PF6(-) as the counterion can extrude Tr(+) from the CT complex, but it cannot do so with Cl(-), thereby offering a visual approach to identify organic intimate ion pairs and loose ion pairs.


Nurse-Led Programs to Facilitate Enrollment to Children's Oncology Group Cancer Control Trials.
The progress made over the past 50 years in disease-directed clinical trials has significantly increased cure rates for children and adolescents with cancer. The Children's Oncology Group (COG) is now conducting more studies that emphasize improving quality of life for young people with cancer. These types of clinical trials are classified as cancer control (CCL) studies by the National Cancer Institute and require different resources and approaches to facilitate adequate accrual and implementation at COG institutions. Several COG institutions that had previously experienced problems with low accruals to CCL trials have successfully implemented local nursing leadership for these types of studies. Successful models of nurses as institutional leaders and "champions" of CCL trials are described.


Wideband nonlinear spectral broadening in ultra-short ultra - silicon rich nitride waveguides.
CMOS-compatible nonlinear optics platforms with high Kerr nonlinearity facilitate the generation of broadband spectra based on self-phase modulation. Our ultra - silicon rich nitride (USRN) platform is designed to have a large nonlinear refractive index and low nonlinear losses at 1.55 μm for the facilitation of wideband spectral broadening. We investigate the ultrafast spectral characteristics of USRN waveguides with 1-mm-length, which have high nonlinear parameters (γ ∼ 550 W(-1)/m) and anomalous dispersion at 1.55 μm wavelength of input light. USRN add-drop ring resonators broaden output spectra by a factor of 2 compared with the bandwidth of input fs laser with the highest quality factors of 11000 and 15000. Two - fold self phase modulation induced spectral broadening is observed using waveguides only 430 μm in length, whereas a quadrupling of the output bandwidth is observed with USRN waveguides with a 1-mm-length. A broadening factor of around 3 per 1 mm length is achieved in the USRN waveguides, a value which is comparatively larger than many other CMOS-compatible platforms.


Visual appearance modulates motor control in social interactions.
The goal of new adaptive technologies is to allow humans to interact with technical devices, such as robots, in natural ways akin to human interaction. Essential for achieving this goal, is the understanding of the factors that support natural interaction. Here, we examined whether human motor control is linked to the visual appearance of the interaction partner. Motor control theories consider kinematic-related information but not visual appearance as important for the control of motor movements (Flash & Hogan, 1985; Harris & Wolpert, 1998; Viviani & Terzuolo, 1982). We investigated the sensitivity of motor control to visual appearance during the execution of a social interaction, i.e. a high-five. In a novel mixed reality setup participants executed a high-five with a three-dimensional life-size human- or a robot-looking avatar. Our results demonstrate that movement trajectories and adjustments to perturbations depended on the visual appearance of the avatar despite both avatars carrying out identical movements. Moreover, two well-known motor theories (minimum jerk, two-thirds power law) better predict robot than human interaction trajectories. The dependence of motor control on the human likeness of the interaction partner suggests that different motor control principles might be at work in object and human directed interactions.


Digital inequality in Austria: Empirical evidence from the survey of the OECD "Programme for the International Assessment of Adult Competencies".
Digitisation and rapidly emerging new technologies are transforming many aspects of life such as education, work, and leisure. These changes lead to a growing demand for new skills related to ICT use, computer literacy, internet use, or technical digital skills. However, the extensive literature on digital inequality provides evidence for significant differences in computer skills along the usual dimensions of social inequality. Due to the omnipresence of digital technologies in everyday life, it is all the more important to know the extent of digital inequality to be able to take appropriate measures to ensure that social participation does not degenerate into a question of social stratification in the Digital Age. In this paper, we provide empirical evidence for socio-economic digital inequality in Austria using survey data from the "Programme for the International Assessment of Adult Competencies" (PIAAC) conducted in 2011/2012. We show, for Austria, that higher socio-economic background is positively related to digital problem-solving while being female is negatively correlated. However, when controlling for ICT engagement in everyday life, the positive effect of the socio-economic background only remains significant for groups of people with a very high socio-economic background while the effect of gender becomes statistically insignificant. Furthermore, based on Eurostat data we cannot identify a uniform trend towards a decline of digital inequality since 2012. Our results indicate that disadvantaged population groups in Austria should be encouraged and enabled to integrate ICT usage in their everyday life to reduce digital inequality.


Self-acceptance of stuttering: A preliminary study.
This study explored the relationship between self-acceptance of stuttering and (1) psychosocial factors (self-esteem, hostility towards others, emotional support, and perceived discrimination); (2) treatment history (support group participation, therapy duration, and perceived therapy success); and (3) previously reported variables in self-acceptance of stuttering, which include age and stuttering severity. Participants were 80 adults who stutter who were recruited with assistance from the National Stuttering Association and Board Certified Specialists in Fluency Disorders. Participants completed an electronic survey composed of an acceptance of stuttering scale, psychosocial scales, and a participant information questionnaire. Statistical analysis identified significant correlations between participants' reports of self-acceptance of stuttering and self-esteem, perceived discrimination, hostility towards others, and perceived therapy outcome. Self-esteem was positively correlated with self-acceptance, while hostility towards others and perceived discrimination was negatively correlated with self-acceptance. Participants who perceived their therapy outcome to be successful were significantly more likely to report higher levels of self-acceptance. No significant relationships were found between self-acceptance of stuttering and support group participation, emotional support, stuttering severity, and participant age. This exploratory investigation has provided a foundation for future studies on the self-acceptance of stuttering. The findings indicate common psychosocial variables in self-acceptance of stuttering and of other disabilities. The significant relationships between self-acceptance of stuttering and psychosocial and therapeutic variables found need to be further explored to identify its causalities and clinical implications. The reader will be able to (1) discuss the importance of assessing self-acceptance of stuttering, (2) summarize the literature on self-acceptance of disability, and (3) describe the significant findings related to self-acceptance of stuttering and psychosocial, therapeutic variables.


A wicked problem: early childhood safety in the dynamic, interactive environment of home.
Young children being injured at home is a perennial problem. When parents of young children and family workers discussed what influenced parents' perceptions and responses to child injury risk at home, both "upstream" and "downstream" causal factors were identified. Among the former, complex and interactive facets of society and contemporary living emerged as potentially critical features. The "wicked problems" model arose from the need to find resolutions for complex problems in multidimensional environments and it proved a useful analogy for child injury. Designing dynamic strategies to provide resolutions to childhood injury, may address our over-dependence on 'tame solutions' that only deal with physical cause-and-effect relationships and which cannot address the complex interactive contexts in which young children are often injured.


Biosynthesis of a repressor/nuclease hybrid protein.
The phage T7 endonuclease gene was fused to the 3' end of the lac repressor gene. The hybrid protein exhibits repressor and nuclease functions in a manner dependent on the conformation of the DNA. With supercoiled DNA, nuclease activity is directed to the major cruciform, whereas with linear DNA, the enzyme cleaves preferentially restriction fragments carrying the operator. These properties render the hybrid protein a unique probe of DNA conformation in vitro and in vivo.


Strategies for the development of amperometric enzyme electrodes.
There are now a number of distinct strategies which can be employed to make amperometric enzyme electrodes. These include the use of homogeneous mediators, modified electrodes and organic conducting salts. In this paper we review these strategies and discuss their application to NAD(P)H dependent dehydrogenase and flavoprotein based biosensors. In addition we discuss recent work on the immobilisation of glucose oxidase in polypyrrole, poly-N-methylpyrrole, polyaniline and polyphenol films electrochemically grown at the electrode surface and on the covalent attachment of redox mediators to glucose oxidase in order to achieve direct electron transfer to the electrode.


Synthesis, spectroscopic and structural elucidation of tyrosinamide hydrogensquarate monohydrate.
Synthesis, isolation, spectroscopic and structural elucidation of tyrosinamide hydrogensquarate monohydrate (I) is reported on the basis of quantum chemical DFT calculations, vibrational analysis and experimental linear-polarized IR-spectroscopy in solid state. These data are compared with those obtained using single crystal X-ray diffraction, which show that the molecules of (I) in the unit cell formed 3D network through moderate intermolecular (Tyr)OH...O = C(Sq) (2.727 A), O=C-NH2...OH(Tyr) (2.991 A), O=C-NH2...OH(Sq) (2.988 A), O=C-NH2...O=C-NH2 (3.068 A), N+H3...O=C(Sq) (2.737, 2.953, 2.954 A), OH2...O=C(Sq) (2.839 A) and (Sq)OH...OH2 (2.607 A) hydrogen bonds. The relationship between the structure and spectroscopic properties is studied.


Characterisation of a tamoxifen-resistant variant of the ZR-75-1 human breast cancer cell line (ZR-75-9a1) and ability of the resistant phenotype.
A 6-month exposure of ZR-75-1 human breast cancer cells to tamoxifen (1 microM rising to 2 microM). resulted in a fall in oestrogen receptor (ER) levels from 225 fmol mg protein-1 to 56 fmol mg protein-1 while progesterone receptor (PGR) concentration fell from 63 fmol mg protein-1 to undetectable levels. Sensitivity to the anti-proliferative effects of tamoxifen was unchanged. A further 6 months' exposure to 4 microM tamoxifen resulted in loss of detectable ER and PGR and development of resistance to tamoxifen. Resistant cells, designated ZR-75-9a1, displayed morphological changes consistent with the acquisition of a less well differentiated phenotype. Flow cytometric studies demonstrated that the cell cycle distribution pattern of the resistant variant growing in the presence of 8 microM tamoxifen was identical to that of the untreated parent line, which showed marked accumulation of cells in G0/G1 when exposed to 8 microM tamoxifen. The resistant phenotype was not stable if cells were transferred to complete drug-free medium, but remained stable for at least 3 months in the presence of medium lacking oestrogenic activity. ZR-75-9a1 cells differ from previously reported tamoxifen-resistant variants of the MCF-7 line which retain ER and may prove a valuable model for the study of the development and stability of tamoxifen resistance in human breast cancer.


SARS-CoV-2 and other respiratory pathogens are detected in continuous air samples from congregate settings.
Two years after the emergence of SARS-CoV-2, there is still a need for better ways to assess the risk of transmission in congregate spaces. We deployed active air samplers to monitor the presence of SARS-CoV-2 in real-world settings across communities in the Upper Midwestern states of Wisconsin and Minnesota. Over 29 weeks, we collected 527 air samples from 15 congregate settings and detected 106 SARS-CoV-2 positive samples, demonstrating SARS-CoV-2 can be detected in air collected from daily and weekly sampling intervals. We expanded the utility of air surveillance to test for 40 other respiratory pathogens. Surveillance data revealed differences in timing and location of SARS-CoV-2 and influenza A virus detection in the community. In addition, we obtained SARS-CoV-2 genome sequences from air samples to identify variant lineages. Collectively, this shows air surveillance is a scalable, cost-effective, and high throughput alternative to individual testing for detecting respiratory pathogens in congregate settings.


Axonal transport of nerve growth factor and serum albumin in the dystrophic mouse.
Specific (nerve growth factor, NGF) and non-specific (serum albumin, BSA) uptake followed by retrograde axonal transport was studied in the sciatic nerves of normal (C57BL/6J) and dystrophic (dy2J/dy2J) mice. In the dystrophic mouse there was a significant decrease in the amount of NGF transported to dorsal root ganglia or BSA accumulating at a ligature placed on the sciatic nerve.


Impairment of event schema in patients with schizophrenia: examination of script for shopping at supermarket.
The purpose of this study was to examine event schema, the conceptualization of past experience based on script theory, in Japanese patients with schizophrenia. Subjects comprised 25 patients meeting DSM-IV criteria for schizophrenia and 31 normal individuals who gave informed consent. This experiment used three script tasks measuring free recall, frequency judgment, and sequencing of events encountered when shopping at a supermarket. Patients with schizophrenia performed significantly worse than did control subjects on all tasks. In particular, patients committed more errors when judging the events that "occasionally happen" in the frequency judgment task. On the other hand, these patients judged "seldom occurring events" relatively well. Patients with schizophrenia made more errors than normal people in the free recall task. Specifically, patients made more intrusion errors and failed to close scripts. There was a negative correlation between scores the Scale for the Assessment of Positive Symptoms and performance on the free recall task. The results of the present study suggest that event schemas (semantic structure) in patients with schizophrenia are impaired which may be associated with positive symptoms and frontal lobe dysfunction.


Lower circulating zinc and selenium levels are associated with an increased risk of asthma: evidence from a meta-analysis.
Previous studies evaluating the associations of circulating Zn and Se levels with asthma have produced inconsistent results. Therefore, we conducted a meta-analysis to summarize and quantitatively synthesize the evidence from observational research. Meta-analysis. We searched PubMed, Web of Science and Scopus databases up to May 2019 for relevant available articles. Random-effects model was adopted to estimate the pooled standardized mean difference (SMD) with 95 % CI. Meta-regression analysis and 'leave-one-out' sensitivity analysis were used to assess heterogeneity. The meta-analysis focused on general populations. A total of twenty-six studies for Zn and forty studies for Se were included in the meta-analysis. The overall analyses identified that asthma patients had lower Zn (SMD = -0·40; 95 % CI -0·77, -0·03; I2 = 94·1 %) and Se (SMD = -0·32; 95 % CI -0·48, -0·17; I2 = 90·9 %) levels in serum or plasma compared with healthy controls. After removing the studies that contributed to the heterogeneity, the pooled SMD were -0·26 (95 % CI -0·40, -0·13; I2 = 37·42 %) for Zn and -0·06 (95 % CI -0·13, 0·02; I2 = 43·54 %) for Se. Lower circulating Zn and Se levels might be associated with an increased risk of asthma.


Uromodulin in renal transplant recipients: elevated urinary levels and bimodal association with graft failure.
Urinary uromodulin (UMOD) predicts renal prognosis in native kidneys, but data are conflicting. We investigated its prognostic impact for graft failure (GF) in renal transplant recipients (RTR; n = 600). UMOD concentration was measured cross-sectionally in RTR at 6.0 years [2.6-11.4] post-transplant, in matched patients with native chronic kidney disease (CKD) and healthy subjects. In 59 cases, RTR allograft biopsies were reviewed. During a follow-up of 5.3 years [4.5-5.7], GF had occurred in 7% of RTR. Median UMOD excretion (mg/24 h) was 20.4 in RTR, 11.6 in CKD and 5.7 in controls (p < 0.001). There was a curvilinear association between UMOD excretion and baseline renal function (p < 0.003) and death-censored GF, with 5.5, 11.5 and 4.0% of the cases in subsequent UMOD excretion tertiles, respectively (p = 0.002). On multivariate Cox regression analysis, hazard ratios for GF for the 1st and 3rd tertiles were 0.37 (p = 0.01) and 0.21 (p = 0.001), respectively. Interstitial fibrosis and tubular atrophy were more severe in the middle tertile (p = 0.007). Urinary UMOD is elevated in RTR and associated with graft function, morphology and outcome in a bimodal fashion. Dissection of the disparate mechanisms of GF prediction by urinary UMOD might provide new clues for its alleged pathogenetic significance in progressive renal function loss.


Proximal tubular dysfunction in patients with COVID-19: what have we learnt so far?
Recent studies have reported a variety of urine abnormalities in patients hospitalized due to severe acute respiratory syndrome coronavirus 2 infection. In a single-center study from Belgium, Werion et al. present a concise investigation of tubular dysfunction in patients with coronavirus disease 2019, identifying potential risk factors for increased disease severity. These data complement current evidence regarding severe acute respiratory syndrome coronavirus 2 presence and potential infection in the kidney.


Distinctive ultrasonographic finding of complete uterine rupture in early mid-trimester.
In many cases of uterine rupture, diagnosis is often impossible when characteristic clinical symptoms are absent. We encountered a case of suspected peritoneal pregnancy in which we were able to make a definitive diagnosis by ultrasonography of complete uterine rupture in early mid-trimester. The possibly distinctive finding is the high-echo area that extends from the endometrium to the uterine serosa. This contiguous, highly echogenic finding should be recognized as characteristic of complete rupture of the uterus.


Primary cervico-uterine anastomosis in a patient with agenesis of the uterine isthmus: A case report and review.
Arrested caudal extension of the fused Müllerian ducts, either complete or segmental, causes obstruction of the outflow tract. We describe a case of agenesis of the uterine isthmus and the procedure to establish the continuity of the outflow tract. A 15-year-old girl with cyclic pelvic pain and amenorrhea was found to have a 3-cm gap between the uterine body and the cervix. After cervico-uterine anastomosis via laparotomy she menstruated normally and was pain-free. Selected cases of arrested Müllerian duct extension can be corrected by primary anastomosis, which establishes anatomical continuity and restores menstruation and, possibly, future fertility.


Mutation in hinge region of lactose repressor protein alters physical and functional properties.
A mutant of the Escherichia coli lactose repressor (BG124) in which serine at position 77 is replaced by leucine has been examined by physical methods. Consistent with the phenotypic character of this i-d mutant, BG124 protein did not bind lactose operator specifically, but did bind to DNA nonspecifically. Titration with inducer monitoring tryptophan fluorescence changes yielded a biphasic saturation curve, and Scatchard and Hill plots of the fluorescence and equilibrium dialysis data demonstrated heterogeneity of inducer binding sites. Although ultraviolet difference spectra and potassium iodide quenching of fluorescence indicated that BG124 repressor has structural distinctions from wild-type protein, circular dichroism spectra and acrylamide quenching of fluorescence for the two proteins were quite similar. A significantly greater increase of 1-anilino-8-naphthalenesulfonate fluorescence was observed in the presence of mutant versus wild-type repressor. Unlike wild-type behavior, changes in both 1-anilino-8-naphthalenesulfonate fluorescence intensity and maximum emission wavelength in response to inducer were found for the BG124 protein. These results are consistent with conformational alterations in the interface between NH2-terminal and core domains of this mutant repressor. The single amino acid alteration in the hinge between the core and NH2 terminus yields conformational effects which influence physical and functional properties associated with both domains.


Dynamic behavior of prosthetic aortic tissue valves as viewed by high-speed cinematography.
Using a valve testing apparatus of our own design and with a high-speed (600 to 800 frames per second) 16 mm movie camera, films were made of Hancock porcine, Carpentier-Edwards porcine, and Ionescu-Shiley bovine pericardial valves mounted in the aortic position and cycled under physiological conditions at 72 to 100 beats per minute. Fresh and explanted valves were observed using saline or 36.5% glycerol as the pumping solution. When fresh valves were studied using saline solution as the pumpint fluid, the Hancock and Carpentier-Edwards porcine valves showed high-frequency leaflet vibration, which increased in frequency with higher cycling rates. Abnormal leaflet motion was decreased when glycerol was used as the blood analogue. The Ionescu-Shiley bovine pericardial valve did not show abnormal leaflet motion under these conditions. Conclusions drawn from tissue valve testing studies that use excessively high pulsing rates and pressures (accelerated testing) and saline or water as pumping solutions cannot be transposed to predict the fate of tissue valves in a clinical setting.


Flavonoids in Lemon and Grapefruit IntegroPectin*.
Following the analysis of terpenes present in new lemon and grapefruit "IntegroPectin" pectins obtained via the hydrodynamic cavitation of industrial lemon and grapefruit processing waste, the HPLC-MS analysis of flavonoid and other phenolic compounds reveals the presence of eriocitrin, naringin, hesperidin and kaempferol typical of the respective citrus fruits. The pectic fibers rich in rhamnogalacturonan-I regions act as chemical sponges adsorbing and concentrating at their outer surface highly bioactive citrus flavonoids and terpenes. These findings, together with the unique molecular structure of these new whole citrus pectins, provide preliminary insight into the broad-scope biological activity of these new biomaterials. Numerous new biomedical applications are anticipated, including likely use in the prevention and treatment of microbial infections and neurodegenerative disease.


Operation rate is more than double the revision rate for periprosthetic femur fractures.
Periprosthetic femur fractures (PFFs) following hip arthroplasty can lead to significant morbidity due to their impact on mobility and the need for surgery. Its incidence often measured by the prosthesis revision rate reported in joint replacement registries. However, many PFFs are also treated with prosthesis retention and internal fixation. Minimally displaced and stable fractures may be treated without surgery. Knowledge of the difference between the number of femoral revisions for PFF (well reported in registries) and the number of surgeries for PFF overall would allow us to estimate the overall surgical burden. This study aims to determine the number of post-operative PFF in three hospitals and compare those treated with revision surgery to those PFF treated with internal fixation and femoral stem retention. By determining this difference, we can ascertain a more accurate estimate of the overall surgical burden of PFF. Patients 50 years and older who sustained a post-operative PFF between 1 January 2011 and 31 December 2017 at three public hospitals were extracted from hospital records. The number of revision procedures was compared to the number of re-operations of any type. There were 200 patients admitted for management of PFF. One hundred and forty-three (71.5%) required an operation of which 67 (47%) were revision arthroplasty. The overall surgical burden of PFF is approximately twice that represented by the revision rate.


Role of dopamine D1 receptor in the modulation of memory consolidation by passive and self-administered heroin and associated conditioned stimuli.
It has been proposed that opiates modulate memory consolidation, but recent work has indicated that this effect may be mediated by how the drug is experienced (i.e., passive injections vs. self-administration). Because the dopamine (DA) D1 receptor is involved in processing of learning signals and attribution of salience to events experienced by an organism, two studies in male Sprague-Dawley rats tested the effect of blocking this receptor on modulation of memory consolidation by passive and self-administered heroin, in addition to conditioned memory modulation by heroin-paired cues. Using the object location memory task, Study 1 employed SCH23390 (0, 0.05, 0.10 mg/kg, SC) to modulate enhancement of memory consolidation induced by post-training injections of heroin (1 mg/kg, SC) as well as by exposure to the environment paired with heroin injections (6 pairings, 1 h each, 1 mg/kg). Study 2 was conducted in rats that could self-administer heroin (0.05 mg/kg/infusion, IV) and tested whether SCH23390 (0 and 0.1 mg/kg, SC) could prevent memory modulation induced by a change in schedule of self-administration (from fixed to variable ratio). It was found that while repeated passive injections of heroin retained their enhancing effect on memory, when self-administered, heroin enhanced consolidation of object location memory only at the beginning of self-administration and after a change in schedule. Importantly, SCH23390 blocked memory modulation by heroin when passively administered and when the drug was self-administered on a novel schedule. SCH23390 also blocked conditioned memory modulation induced by post-training exposure to heroin-paired cues. Taken together, these results suggest that modulation of memory consolidation by unconditioned and conditioned opiate reinforcers involve a D1-dependent mechanism of salience attribution linked to the anticipation of drug effects.


Spinal CCL1/CCR8 signaling interplay as a potential therapeutic target - Evidence from a mouse diabetic neuropathy model.
Chemokine signaling has been implicated in the pathogenesis of diabetic neuropathy; however, the involvement of the chemokine CC motif ligand 1 (CCL1)-chemokine CC motif receptor 8 (CCR8) interaction remains unknown. The goal of this study was to examine the role of CCL1-CCR8 signaling interplay in the development of hypersensitivity and in opioid effectiveness in diabetic neuropathy. Primary glial cell cultures and a streptozotocin (STZ; 200mg/kg, intraperitoneal)-induced mouse model of diabetic neuropathy were used. Analysis of mRNA/protein expression of glial markers and CCL1/CCR8 was performed by qRT-PCR, Western blotting and/or protein arrays. The co-localization of CCL1/CCR8 with neural/glial cells was visualized by immunofluorescence. The pharmacological tools were injected intrathecally, and pain behavior was evaluated by von Frey/cold plate tests. Single STZ injection increased blood glucose levels and induced the development of hypersensitivity as measured on days 7-21. On day 7 after STZ, the protein levels of CCL1 and IBA1 but not of CCR8 or GFAP were elevated. Immunofluorescent staining revealed that CCR8 was predominantly localized in neurons, which are also the main source of spinal CCL1. Lipopolysaccharide stimulation of primary microglial cultures resulted in decreases in the levels of CCL1 and CCR8. Single intrathecal injection of CCL1 (10-500ng) induced the development of hypersensitivity, whereas on day 7 after STZ, a CCL1-neutralizing antibody dose-dependently (2-8μg) delayed pain behavior. Repeated administration of the CCL1-neutralizing antibody (4μg) also enhanced the effectiveness of morphine and buprenorphine (1μg). These results reveal that CCL1/CCR8 neuronal signaling plays an important role in the development of diabetic neuropathy and the effectiveness of opioids.


Feline cerebral veins and arteries: comparison of autonomic innervation and vasomotor responses.
1. The innervation of feline cerebral (pial) vessels by nerve fibres containing noradrenaline, substance P or vasoactive intestinal polypeptide (VIP) has been examined using the Falck-Hillarp histo-fluorescence method and immunohistochemical techniques. Cerebral veins were shown to be innervated by nerve fibres containing noradrenaline, substance P or VIP. Nerve fibres containing noradrenaline were the most numerous, while fibres containing substance P were observed least frequently in both types of vessel. For each putative neurotransmitter, the density of the innervation of the cerebral veins was less than that of cerebral arteries.2. The vasomotor responses of individual pial arteries and veins on the convexity of the cerebral cortex to perivascular micro-injection of noradrenaline, substance P and VIP were examined in twenty-five cats anaesthetized with alpha-chloralose.3. The perivascular micro-application of noradrenaline resulted in pronounced dose-dependent reductions in the diameter of pial veins (maximum calibre reduction: 32+/-3% noradrenaline 10(-5) M) and arteries (22+/-3% noradrenaline 10(-5) M). Pial veins were more sensitive to noradrenaline than were pial arteries tested under similar conditions. The reductions in the diameter of cerebral veins and arteries resulting from the administration of noradrenaline could be attenuated by the concomitant micro-application of phentolamine (10(-6) M).4. The perivascular micro-application of substance P effected significant dose-dependent increases in the calibre of pial veins (maximum calibre increase: 16+/-4% substance P 10(-7) M) which were of a similar magnitude to those observed in pial arteries in response to this peptide (21+/-4% substance P 10(-6) M).5. The perivascular micro-application of VIP resulted in small increases in the calibre of pial veins (maximum calibre increase: 9+/-2% VIP 10(-8) M) which were proportionately smaller than those observed in pial arteries in response to this peptide (23+/-5% VIP 10(-7) M).


Onyx embolization of a ruptured anterior inferior cerebellar artery in a neonate.
Aneurysmal subarachnoid hemorrhage (SAH) is rare in neonates. The authors present a unique report of a neonate with SAH from anterior inferior cerebellar artery (AICA) aneurysm rupture that was successfully treated with Onyx embolization. This case report demonstrates the utility of Onyx embolization for posterior circulation aneurysms in neonates and the successful management of SAH in this population.


Prevalence of resistance mechanisms against macrolides and lincosamides in methicillin-resistant coagulase-negative staphylococci in the Czech Republic and occurrence of an undefined mechanism of resistance to lincosamides.
High occurrence of the non-macrolide-lincosamide-streptogramin B resistance genes msrA (53%) and linA/linA' (30%) was found among 98 methicillin-resistant coagulase-negative staphylococci additionally resistant to macrolides and/or lincosamides. The gene msrA predominated in Staphylococcus haemolyticus (43 of 62 isolates). In Staphylococcus epidermidis, it was present in 7 of 27 isolates. A novel mechanism of resistance to lincosamides appears to be present in 10 genetically related isolates of S. haemolyticus in the absence of ermA, ermC, msrA, and linA/linA'.


[The Historical Collection of the Institut universitaire en santé mentale de Montreal: from the Quill to the Electronic Record, 140 Years of Mental Health Records].
Few institutions have kept the vast majority of their records. It is the enviable position of l'IUSMM. The article describes the collection, the challenges of preserving and sharing with limited budget within a legal context protecting confidentiality.


Mechanisms of cross-resistance to methotrexate and 5-fluorouracil in an A2780 human ovarian carcinoma cell subline resistant to cisplatin.
Some properties of the human ovarian carcinoma line A2780 and a subline three times more resistant than the parent line to cisplatin are compared in this report. The rates of uptake and release of cisplatin were similar in the two cell lines. Resistance to cisplatin was associated with: (a) cross-resistance to 5-fluorouracil and methotrexate; (b) a 2.5-fold increase in thymidylate synthase, as measured by both enzyme activity and the capacity to complex 5-fluorodeoxyuridylate; and (c) an increase in the intracellular pools of 5,10-methylenetetrahydrofolate and tetrahydrofolate. These data suggest that cross-resistance to 5-fluorouracil and methotrexate in A2780 cells may be a consequence of increases in their respective target enzymes.


A pilot study of chemo-radiotherapy in advanced carcinoma of the vulva.
Advanced squamous cell carcinoma of the vulva (FIGO stages III and IV) has a poor cure rate even with exenterative surgery. We report a pilot study of combined pre-operative chemo-radiotherapy (CHT/RT) in all patients with advanced vulval carcinoma presenting to St Bartholomew's Hospital between July 1987 and March 1989. Twelve patients have been treated, of whom nine had primary lesions (four FIGO stage III and five stage IV) and three had recurrent disease after simple or radical vulvectomy. Seven patients were treated with an initial split course of CHT/RT: there was one treatment-related death and the others have all died following recurrence with a median disease-free survival of 5 months (range 3-12) and a median survival of 7 months (range 3-16). Five patients have received a continuous course of CHT/RT: one died before operation with pulmonary metastases, three patients are disease free at 6 to 9 months, and another patient has been treated with only palliative intent. Toxicity was acceptable in the continuous regimen and this treatment seems to have a promising role in the management of advanced carcinoma of the vulva. A review of the literature on combined therapy is presented.


Nonpulmonary vein foci: do they exist?
Though the majority of foci triggering atrial fibrillation (AF) have been mapped to the pulmonary veins (PV), recurrence of paroxysmal AF after isolation of all four pulmonary veins indicates the presence of other foci. In a series of 160 consecutive patients who underwent PV ablation, endocardial mapping of AF and ectopy recurring after PV isolation was performed. Thirty-six patients (24%) had a total of 85 non-PV foci; 39 were mapped to the ostia of ablated PVs, 30 to the posterior left atrium (LA), 5 to other parts of the LA, 5 to the right atrium (RA), 4 to the coronary sinus (CS), and 3 to the superior vena cava (SVC) (including one persistent left SVC). Mapping was confirmed by successful ablation. At least 16 foci could not be localized and after a follow-up of 8 +/- 6 months, 68% of patients were free of AF without any antiarrhythmic treatment. The occurrence of non-PV foci correlated with recurrence of AF, perhaps as a correlate of insufficient ostial ablation. These data reinforce the requirement for more proximal disconnection of the PVs by performing ablation within the LA. In patients with non-PV foci that are difficult to map conventionally, the use of surface ECG data, or multielectrode contact or noncontact mapping arrays, or substrate modifying/excluding ablation may be helpful in ablating these foci and therefore eliminating AF.


Quantitative analysis of a deeply sequenced marine microbial metatranscriptome.
The potential of metatranscriptomic sequencing to provide insights into the environmental factors that regulate microbial activities depends on how fully the sequence libraries capture community expression (that is, sample-sequencing depth and coverage depth), and the sensitivity with which expression differences between communities can be detected (that is, statistical power for hypothesis testing). In this study, we use an internal standard approach to make absolute (per liter) estimates of transcript numbers, a significant advantage over proportional estimates that can be biased by expression changes in unrelated genes. Coastal waters of the southeastern United States contain 1 × 10(12) bacterioplankton mRNA molecules per liter of seawater (~200 mRNA molecules per bacterial cell). Even for the large bacterioplankton libraries obtained in this study (~500,000 possible protein-encoding sequences in each of two libraries after discarding rRNAs and small RNAs from >1 million 454 FLX pyrosequencing reads), sample-sequencing depth was only 0.00001%. Expression levels of 82 genes diagnostic for transformations in the marine nitrogen, phosphorus and sulfur cycles ranged from below detection (<1 × 10(6) transcripts per liter) for 36 genes (for example, phosphonate metabolism gene phnH, dissimilatory nitrate reductase subunit napA) to >2.7 × 10(9) transcripts per liter (ammonia transporter amt and ammonia monooxygenase subunit amoC). Half of the categories for which expression was detected, however, had too few copy numbers for robust statistical resolution, as would be required for comparative (experimental or time-series) expression studies. By representing whole community gene abundance and expression in absolute units (per volume or mass of environment), 'omics' data can be better leveraged to improve understanding of microbially mediated processes in the ocean.


Haemophilus urethritis in males: A series of 30 cases.
Pathogens such as Haemophilus spp. have been associated with non-gonococcal urethritis, but their role is unproven. To describe the clinical characteristics and therapeutic outcomes in male patients diagnosed with Haemophilus spp. urethritis. We carried out a retrospective study of all patients who presented to our hospital (in either the emergency department or the outpatient clinic) between July 2016 and April 2018 in whom Haemophilus spp. was isolated in the urethral samples. We enrolled 30 men with Haemophilus spp.-positive urethritis, including coinfections with Neisseria gonorrhoeae and Chlamydia trachomatis. Clinical, laboratory, demographic, and behavioral data were obtained by reviewing medical histories. The mean age of the patients was 36.6 years (range 21-87). Seventeen patients (63%) reported being exclusively heterosexual. Three patients (10%) were HIV infected, all of them with an undetectable viral load. The most common clinical presentation was mucopurulent urethral discharge, in 13 patients (43%). The antibiotic treatment achieved a complete clinical resolution in 73%. Haemophilus urethritis affected men regardless of their sexual orientation or HIV status. Unprotected oral sex may play a role in its transmission. The limitations of the study preclude verification of the pathogenic role of Haemophilus spp. in acute urethritis, but clinical response after antibiotic treatment suggests that Haemophilus spp. can play such a role.


Bacteriophage T4 late gene expression: overlapping promoters direct divergent transcription of the base plate gene cluster.
Eight 5' ends of RNA molecules which encompass the bacteriophage T4 base plate late genes 51 to 26 region have been mapped by S1 nuclease protection and reverse transcription within a 246-bp DNA segment. Two of eight 5' ends are initiated at two absolutely conserved late promoter sites, P51 and P26a, that direct RNA synthesis on opposite strands. These two promoters share four of eight promoter sequence base pairs. A third 5' end arises from another promoter, P26b, which shows one base pair mismatch with respect to the absolutely conserved -10 sequence. All the other 5' ends arise from RNA processing and/or degradation. Since no other late transcription promoter sites were found within the base plate cluster sequence, we propose that the two overlapping late promoters, P51 and P26a, direct the expression of the T4 base plate gene cluster, included between map coordinates 114,000 and 121,038: P51 directs the transcription of genes 51, 27, 28, 29, 48, and 54 on the rDNA strand and P26a the transcription of genes 26 and 25 on the /DNA strand. This peculiar promoter configuration might account for the low level of transcription of these late genes.


"Simple febrile seizures plus (SFS+)": more than one febrile seizure within 24 hours is usually okay.
This study aimed to investigate whether children with recurrent febrile seizures within a 24-hour period need to be worked up differently from children with simple febrile seizures. Inclusion criteria included the following: (i) children with first seizure cluster between 4 months and 3 years of age, (ii) children who had more than one febrile seizure within 24 hours, and (iii) children who returned to baseline between and after each event. Thirty-two patients met the inclusion criteria over a 3-year period. All patients underwent brain CT and/or MRI and EEG. All head CTs were normal. Two children had abnormal MRI findings - both benign: one is thought to represent postictal changes, and the other one is an incidental arachnoid cyst. Of the 4 abnormal EEGs, one showed epileptiform discharges, while the others showed generalized ictal or postictal features. We propose the term "simple febrile seizures plus (SFS+)" to describe children who have more than one seizure within 24 hours but who are otherwise not different in presentation from children with SFS.


On the biomechanics of human shoulder complex--II. Passive resistive properties beyond the shoulder complex sinus.
In multi-segmented total-human-body models the most difficult and the least successful modeling of a major articulating joint has been the shoulder complex because of the lack of appropriate biomechanical data as well as the anatomical complexity of the region. In this paper, quantitative results on the three-dimensional passive resistive properties beyond the voluntary shoulder complex sinus are presented by applying the methodology developed in part I. Constant-restoring-force(moment) contours are established for the shoulder complex and the numerical results are presented for the three subjects tested. In addition, functional expansions are presented for the voluntary and restoring force(moment) contours using spherical coordinates.


Long term results of diaphragmatic plication for unilateral diaphragm paralysis.
To examine whether diaphragmatic plication is an effective and lasting treatment option for non-malignant diaphragmatic paralysis. Nineteen patients who had undergone diaphragm plication (1983-1990) were recalled for interview, pulmonary function testing and chest X-ray. There were 13 men and six women aged 24-73 (mean 55). Diaphragm paralysis was idiopathic (n=9), postsurgical (n=3), related to cervical spondylosis (n=4) and neck injury (n=2). Patients presented with breathlessness (18/19) or orthopnoea (1/19). Symptoms had lasted 3-60 months (mean 24 months). All patients had a raised hemidiaphragm on chest X-ray with paradoxical movement on ultrasound. Mean preoperative FVC was 71% predicted (range 38-93, SD 12.9) and mean FEV(1) was 67% predicted (range 33-90, SD 10.8). Supine lung volumes were 81% (mean) of sitting values. There were six right plications and 13 left. There were no postoperative deaths. One patient required re-plication. Follow-up (18/19 of original operated patients) ranged from 7-14 years (mean 10 years). Three patients had died of unrelated causes and one patient failed to attend long term follow-up, leaving 15 patients of the original 19 operated on. Positional change in lung volumes was not affected by surgery at early (6 week) or late (>5 year) follow-up. FVC, FEV(1), FRC and TLC improved by 10.1*, 11.8*, 16.9* and 9.2*%, respectively, at early follow-up and 11.8*, 15.4*, 26 and 13.3*% at late follow-up (*P<0.005 signed rank). Dyspnoea scores at long term follow-up improved 1 point (n=5), 2 points (n=5) and 3 points (n=2), remained unchanged (n=1) or dropped 1 point (n=2). Of the 15 patients followed up all but one who had been employed returned to work. 14/15 patients expressed satisfaction with their surgery. Diaphragm plication is an effective procedure with lasting results.


Uptake and distribution of doxorubicin in hormone-manipulated human breast cancer cells in vitro.
Kinetic resistance to cytotoxic drugs may account for the moderate responsiveness of breast cancer to chemotherapy. In the present study the in vitro effects of estradiol-mediated DNA stimulation on the cellular uptake of the DNA intercalating drug doxorubicin (DOX) were examined in MCF-7 human breast cancer cells. Using the fluorescent properties of the drug, the cellular uptake was investigated by high performance liquid chromatography (HPLC), and by flow cytometry. The uptake of DOX (0.01-2 microg/ml) by MCF-7 cells in suspension, incubated for 1 and 6 h, showed a strong correlation between the incubation concentration of DOX and the cellular uptake of the drug as measured by HPLC and flow cytometry. Simultaneous exposure of MCF-7 cells, in monolayer culture, to DOX (0.04-0.2 microg/ml) and estradiol (1 nM) for 1-24 h showed no significant difference in uptake of the drug compared to control cultures exposed to DOX in the absence of estradiol. Neither was there a significant difference in uptake of DOX when MCF-7 cells were pretreated with estradiol (1 nM) for 16-24 h followed by a 0.5, 1, 6, and 21/23 h incubation with DOX (0.01-2 microg/ml). Pretreatment with estradiol did not affect the retention of DOX as measured 24 h after a 0.5 h incubation with DOX (2 microg/ml). Furthermore, fluorescence microscopy revealed no difference in the cellular DOX distribution pattern of estradiol-stimulated MCF-7 cultures compared to unstimulated cultures. From this study we can conclude that, for the human MCF-7 breast cancer cells in vitro, the uptake, retention, and cellular distribution of DOX are not influenced by estrogenic manipulation.


Three-dimensional virtual reality in surgical planning for breast cancer with reconstruction.
Breast surgery is performed to achieve local control in patients with breast cancer. Visualization of the anatomy with a virtual reality software platform reconstructed from magnetic resonance imaging data improves surgical planning with regards to volume and localization of the tumor, lymph nodes, blood vessels, and surrounding tissue to perform oncoplastic tissue rearrangement. We report the use and advantages of virtual reality added to the magnetic resonance imaging assessment in a 36-year-old woman with breast cancer who underwent nipple sparing mastectomy with tissue expander reconstruction.


Maternal and embryonic signals cause functional differentiation of luminal epithelial cells and receptivity establishment.
Embryo implantation requires temporospatial maternal-embryonic dialog. Using single-cell RNA sequencing for the uterus from 2.5 to 4.5 days post-coitum (DPC) and bulk sequencing for the corresponding embryos of 3.5 and 4.0 DPC pregnant mice, we found that estrogen-responsive luminal epithelial cells (EECs) functionally differentiated into adhesive epithelial cells (AECs) and supporting epithelial cells (SECs), promoted by progesterone. Along with maternal signals, embryonic Pdgfa and Efna3/4 signaling activated AECs and SECs, respectively, enhancing the attachment of embryos to the endometrium and furthering embryo development. This differentiation process was largely conserved between humans and mice. Notably, the developmental defects of SOX9-positive human endometrial epithelial cells (similar to mouse EEC) were related to thin endometrium, whereas functional defects of SEC-similar unciliated epithelial cells were related to recurrent implantation failure (RIF). Our findings provide insights into endometrial luminal epithelial cell development directed by maternal and embryonic signaling, which is crucial for endometrial receptivity.


Dielectric breakdown of the erythrocyte membrane enhances transbilayer mobility of phospholipids.
Dielectric breakdown of erythrocytes is shown to result in a loss of asymmetry of phosphatidylethanolamine and in a markedly enhanced transbilayer mobility of exogenous lysophosphatidylcholine. The effect is much more pronounced in non-resealed cells than in cells resealed after the breakdown. A casual relationship between the structural defects in the lipid phase, indicated by these results, and fusion by dielectric breakdown is discussed.


Rat liver ischemia-reperfusion-induced apoptosis and necrosis are decreased by FK506 pretreatment.
The aim of this study was to demonstrate that tacrolimus (FK506) has a hepatoprotective effect by reducing ischemia-reperfusion-induced apoptosis and necrosis, both of which lead to post-surgical liver dysfunction. An ischemia-reperfusion model and primary cultured rat hepatocytes subjected to hypoxic and reoxygenation phases, mimicking the surgical process, were used. c-Jun N-terminal kinase 1/stress-activated protein kinase 1 (JNK1/SAPK1) activation leads to caspase 3 activation, a trigger of apoptosis. The activation status of JNK1/SAPK1 was evaluated by immunoprecipitation or Western-blotting experiments. Apoptosis was assessed by measuring caspase activation and by TUNEL (terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate-biotin nick-end labeling) reaction. Necrosis was assessed histologically. Tacrolimus improved the survival rate of rats subjected to ischemia-reperfusion. After FK506 pretreatment, the liver necrosis rate was reduced, and ischemia-reperfusion-induced JNK1/SAPK1 activation and apoptosis were significantly decreased. In hypoxia-reoxygenation-subjected hepatocytes, tacrolimus reduced JNK1/SAPK1 and caspase 3 activation. In the liver, tacrolimus prevented ischemia-reperfusion-induced apoptosis and necrosis.


Renal azotemia and associated clinical and laboratory findings in dogs with Babesia rossi infection.
The occurrence of acute kidney injury in canine babesiosis is not well documented. Furthermore, interpretation of urine specific gravity (USG) to assess renal concentrating ability is hampered by the frequent presence of hemoglobinuria in this disease. This cross-sectional study aimed to test the hypothesis that renal azotemia (RA) is underdiagnosed according to current canine babesiosis literature by determining its occurrence at presentation, using urine osmolality instead of USG to measure urinary concentration. The second objective was to examine potential associations between the presence of RA and selected clinical and laboratory variables at presentation. Medical records available from 3 previously performed prospective data collections were reviewed retrospectively. Client-owned dogs that were diagnosed with babesiosis caused by Babesia rossi, were included if a complete blood count, biochemistry profile, and urinalysis was performed at admission. Urine osmolality was measured to identify dogs with RA. Differences between dogs with RA and dogs without RA were assessed by nonparametric statistics. One hundred and fifty-two dogs were included, of which 26 (17%) were azotemic at admission. The occurrence of RA was 14% (21/152), hence 81% (21/26) of all azotemic dogs were diagnosed with RA. In contrast, when diagnosis of RA was based on an admission USG < 1.030, only 23% (6/26) of the azotemic dogs would have been considered to have RA. Several signalment and clinicopathological findings were found to be associated with the presence of RA, including older age, and the presence of collapse, hypoglycemia, hyperphosphatemia, cerebral babesiosis, and acute respiratory distress syndrome. Lastly, survival at discharge was significantly lower in dogs diagnosed with RA at presentation. Our results clarified that RA is more common than previously reported in B. rossi. This study also demonstrated that USG determination is not a reliable method to evaluate renal concentrating ability in azotemic dogs with babesiosis. Thus, if available, urine osmolality should be part of the diagnostic work-up of dogs infected with B. rossi to avoid misclassification of dogs with RA as having prerenal azotemia. If urine osmolality cannot be measured, clinicians should realize that most azotemic dogs with B. rossi infection have RA.


COVID-19: Poor outcomes in patients with zinc deficiency.
Zinc is a trace element with potent immunoregulatory and antiviral properties, and is utilized in the treatment of coronavirus disease 2019 (COVID-19). However, we do not know the clinical significance of serum Zinc levels in COVID-19 patients. The aim of this study was to determine the clinical significance of serum zinc in COVID-19 patients and to establish a correlation with disease severity. This was a prospective study of fasting zinc levels in COVID-19 patients at the time of hospitalization. An initial comparative analysis was conducted between COVID-19 patients and healthy controls. COVID-19 patients with zinc deficiency were compared to those with normal zinc levels. COVID-19 patients (n = 47) showed significantly lower zinc levels when compared to healthy controls (n = 45): median 74.5 (interquartile range 53.4-94.6) μg/dl vs 105.8 (interquartile range 95.65-120.90) μg/dl (p < 0.001). Amongst the COVID-19 patients, 27 (57.4%) were found to be zinc deficient. These patients were found to have higher rates of complications (p = 0.009), acute respiratory distress syndrome (18.5% vs 0%, p = 0.06), corticosteroid therapy (p = 0.02), prolonged hospital stay (p = 0.05), and increased mortality (18.5% vs 0%, p = 0.06). The odds ratio (OR) of developing complications was 5.54 for zinc deficient COVID-19 patients. The study data clearly show that a significant number of COVID-19 patients were zinc deficient. These zinc deficient patients developed more complications, and the deficiency was associated with a prolonged hospital stay and increased mortality.


All together now: Simultaneous feature integration and feature retrieval in action control.
Accounts of human action control assume integration of stimulus and response features at response execution and, upon repetition of some of those features, retrieval of other previously integrated features. Even though both processes contribute sequentially to observed binding effects in studies using a sequential prime-probe design, integration and retrieval processes theoretically affect human action simultaneously. That is, every action that we execute leads to bindings between features of stimuli and responses, while at the same time these features also trigger retrieval of other previously integrated features. Nevertheless, the paradigms used to measure binding effects in action control can only testify for integration of stimulus and response features at the first (R1, n-1, or prime) and retrieval of the past event via feature repetition at the second (R2, n, or probe) response. Here we combined two paradigms used in the action control literature to show that integration and retrieval do indeed function simultaneously. We found both significant stimulus-response and significant response-response binding effects, indicating that integration of responses must have occurred at the same time as response retrieval due to feature repetition and vice versa.


Ultrasound Evaluation in Female Infertility: Part 1, the Ovary and the Follicle.
Infertility is defined by failure to achieve a pregnancy after 12 months or more of appropriate timed unprotected intercourse or therapeutic donor insemination. Ultrasound has now become an essential component of the modern investigation of female infertility and the management of assisted conception. Scans are predominantly performed transvaginally and recent technological advances such as 3D and Doppler imaging enhance our understanding of ovarian function such as ovarian reserve, follicular maturity and the assessment of polycystic morphology in the identification of polycystic ovarian syndrome. This chapter describes these latest advances in the context of infertility treatment.


Indigenous microbes and their soluble factors differentially modulate intestinal glycosylation steps in vivo. Use of a "lectin assay" to survey in vivo glycosylation changes.
It has been shown that Bacteroides thetaiotaomicron, a representative member of the gut microflora, signals intestinal epithelial cells both in vivo and in vitro and modulate specific glycosylation processes that may mediate intestinal functions. However it is not known whether these modulations depend on the presence of live bacteria or may be elicited by soluble factors produced in vitro by this bacterium. We used lectins and an histochemical approach to survey tissue sections prepared from various cellular compartments of the small and large intestine of NRMI/KI mice grown under gnotobiotic conditions. We compared the results obtained with bacterial culture supernatant and live B. thetaiotaomicron to those obtained from germ-free mice or mice having a conventional microflora. This approach allowed us to conclude that (1) a small but specific number of glycan patterns were restored after treatment with bacterial culture supernatant and (2) the B. thetaiotaomicron associated mice restored a larger number of patterns, however, the complete conventional mice pattern must be a function of the whole microflora in the gut. The possibility to modulate this complex glycosylation pattern by introducing exogenous bacteria and bacterial products should be considered as a promising approach towards understanding the molecular basis of microbial-host interactions.


Structure elucidation of two new unusual monoterpene glycosides from Euphorbia decipiens, by 1D and 2D NMR experiments.
Two new unusual monoterpene glycosides, (Z)-3,6-dimethyl-3-(β-D-O-glucosylmethylene)cyclohept-4-ene-1-one (1) and 3,6-dimethyl-3-(β-D-O-glucosylmethylene)cycloheptanone (2) have been isolated along with five known compounds, 3-hydroxy-4-methoxybenzoic acid, 6,7-dihydroxycoumarin, luteolin, apigenin 5-O-αl-L-rhamnoside, and pinocembrin-7-O-rutinoside from ethyl acetate extract of Euphorbia decipiens. The structures of the isolated compounds were elucidated by extensive 1D- and 2D-NMR, and mass spectroscopic analyses.


Humans, Fish, and Whales: How Right Whales Modify Calling Behavior in Response to Shifting Background Noise Conditions.
This study investigates the role of behavioral plasticity in the variation of sound production of southern right whales (Eubalaena australis) in response to changes in the ambient background noise conditions. Data were collected from southern right whales in Brazilian waters in October and November 2011. The goal of this study was to quantify differences in right whale vocalizations recorded in low background noise as a control, fish chorus noise, and vessel noise. Variation in call parameters were detected among the three background noise conditions and have implications for future studies of noise effects on whale sound production.


Effects of nonselective cation channels and PI3K on endothelin-1-induced PYK2 tyrosine phosphorylation in C6 glioma cells.
We recently demonstrated that endothelin-1 (ET-1) activates two types of Ca2+-permeable nonselective cation channels (designated NSCC-1 and NSCC-2) in C6 glioma cells. In the present study, we investigated the effects of NSCCs on the ET-1-induced proline-rich tyrosine kinase 2 (PYK2) phosphorylation in C6 glioma cells. In addition, we examined the effects of phosphoinositide 3-kinase (PI3K) on the ET-1-induced NSCCs activation and PYK2 phosphorylation. The PI3K inhibitors wortmannin and LY-294002 inhibited ET-1-induced Ca2+ influx through NSCC-2 but not NSCC-1. On the other hand, addition of these inhibitors after stimulation with ET-1 failed to suppress Ca2+ influx through NSCC-2. PYK2 phosphorylation was abolished by blocking Ca2+ influx through NSCCs. The PI3K inhibitors blocked the NSCC-2-dependent part of ET-1-induced PYK2 phosphorylation. These results indicate that 1) NSCC-2 is stimulated by ET-1 via a PI3K-dependent cascade, whereas NSCC-1 is stimulated via a PI3K-independent cascade; 2) PI3K seems to be required for the activation of the Ca2+ entry, but not for its maintenance; 3) Ca2+ influx through NSCC-1 and NSCC-2 plays an essential role in ET-1-induced PYK2 phosphorylation; and 4) PI3K is involved in the ET-1-induced PYK2 phosphorylation that depends on the Ca2+ influx through NSCC-2.


Ca(2+)/CREB/CBP-dependent gene regulation: a shared mechanism critical in long-term synaptic plasticity and neuronal survival.
CREB is a transcription factor critical for long-term synaptic plasticity. Intriguingly, recent work has elucidated a role for CREB, as well as upstream CREB kinases, in the control of activity-dependent neuronal survival. Additionally, analysis of the molecular pathology of polyglutamine-repeat diseases suggest that alteration of pCREB-CBP function may underlie, at least in part, the neurodegenerative process. Taken together, these new findings support the idea that Ca(2+)/CREB/CBP-dependent gene regulation might be a shared mechanism critical in both long-term synaptic plasticity and neuronal survival.


Free radicals mediate postshock contractile impairment in cardiomyocytes.
Previous studies demonstrated myocardial dysfunction after electrical shock and indicated it may be related to free radicals. Whether the free radicals are generated after electrical shock has not been documented at the cellular level. This study was to investigate whether electrical shock generates intracellular free radicals inside cardiomyocytes and to evaluate whether reducing intracellular free radicals by pretreatment of ascorbic acid would reduce the contractile dysfunction after electrical shock. Randomized prospective animal study. University affiliated research laboratory. Sprague-Dawley rats. Cardiomyocytes isolated from adult male rats were divided into four groups: (1) electrical shock alone; (2) electrical shock pretreated with ascorbic acid; (3) pretreated with ascorbic acid alone; and (4) control. Ascorbic acid (0.2 mM) was administrated in the perfusate of the ascorbic acid + electrical shock and ascorbic acid groups. A 2-J electrical shock was delivered to the electrical shock and ascorbic acid + electrical shock groups. DCFH-DA-loaded cardiomyocytes showed increased intracellular free radicals after electrical shock. The contractions and Ca2+ transients were recorded optically with fura-2 loading. Within 4 mins after electrical shock in the electrical shock group, the length shortening decreased from 8.4% +/- 2.5% to 5.6% +/- 3.4% (p = 0.000) and the Ca2+ transient decreased from 1.15 +/- 0.13 au to 1.08 +/- 0.1 au (p = 0.038). Compared with control, a significant difference in length shortening (p = 0.001) but not Ca2+ transient (p = 0.052) was noted. In the presence of ascorbic acid, electrical shock did not affect length shortening and Ca2+ transient. Electrical shock generates free radicals inside the cardiomyocyte, and causes contractile impairment and associated decrease of Ca transient. Administering ascorbic acid may improve such damage by eliminating free radicals.


Formulation, characterization and in vitro anti-leishmanial evaluation of amphotericin B loaded solid lipid nanoparticles coated with vitamin B12-stearic acid conjugate.
Despite the advancement of new anti-leishmanials, amphotericin B (AmB) prevails as one of the most potent agent in the treatment of visceral leishmaniasis (VL), a neglected tropical disease affecting mostly poverty ridden and underdeveloped regions of the globe. Nonetheless, many patients display intolerance to parenteral AmB, notably at higher dosages. Also, conventional AmB presents an apparently poor absorption. Therefore, to improve AmB bioavailability and overcome multiple barriers for oral delivery of AmB, we fabricated a promising vitamin B12-stearic acid (VBS) conjugate coated solid lipid nanoparticles (SLNs) encapsulated with AmB (VBS-AmB-SLNs) by a combination of double emulsion solvent evaporation and thermal sensitive hydrogel techniques. VBS-AmB-SLNs showed a particle size of 306.66 ± 3.35 nm with polydispersity index of 0.335 ± 0.08 while the encapsulation efficiency and drug loading was observed to be 97.99 ± 1.6% and 38.5 ± 5.6% respectively. In vitro drug release showed a biphasic release pattern and chemical stability of AmB was ensured against simulated gastrointestinal fluids. Cellular uptake studies confirmed complete internalization of the formulation. Anti-leishmanial evaluation against intramacrophage amastigotes showed an enhanced efficacy of 94% which was significantly (P < 0.01) higher than conventional AmB without showing any toxic effects on J774A.1 cells. VBS-AmB-SLNs could serve as a potential therapeutic strategy against VL.


A Prospective Study of Minimally Invasive Paravaginal Repair of Cystocele and Associated Pelvic Floor Defects: Our Experience.
To assess the outcome of minimally invasive paravaginal repair of symptomatic cystocele and to correlate postoperative outcome with preoperative presentation. The primary outcome was the anatomical outcome measured by postoperative physical examination and the functional outcome was assessed by subjective symptoms and questionnaires. The secondary outcomes were perioperative and postoperative complications. In this longitudinal prospective observational study, 44 women underwent laparoscopic or robotic paravaginal cystocele repair from January 2016 to July 2016 and they were followed up to 1 year after surgery in a tertiary advanced laparoscopic center. All patients had a symptomatic lateral cystocele ≥ grade 2 according to Baden-Walker classification. Other coexisting defects like apical cystocele or combined defects were corrected concomitantly. The anatomical outcome was measured by physical examination and functional outcome was assessed by questionnaires-Pelvic Organ Prolapse Distress Inventory 6 and Urinary Distress Inventory 6 preoperatively and during postoperative follow-up. All 44 patients were followed up to 12 months after surgery. The anatomical cure rate for cystocele was 97.7%. There were no major complications. All subjective symptoms and quality of life scores improved significantly during postoperative follow-up. The anatomical recurrence rate in our study was 2.3%. Minimally invasive paravaginal repair of cystocele is an effective advanced laparoscopic procedure. It can be concomitantly performed with other surgical procedures to correct coexisting defects. The anatomical and functional results were outstanding with minimum perioperative morbidity and encouraging long-term outcome.


Preparation of monoclonal antibodies against Epstein-Barr virus glycoprotein 350.
Epstein-Barr virus (EBV) is the first identified human oncogenic herpesvirus infecting over 90% of the adults worldwide. However, the safe and effective prophylactic vaccine has not been licensed. The major glycoprotein 350 (gp350) on the EBV envelope is the main target for neutralizing antibodies, and gp350 (aa15-320) was used for the development of monoclonal antibodies in present study. The purified recombinant gp35015-320aa with an estimated molecular weight of 50 kDa was used to immunize six-week-old BALB/c mice, and the hybridoma cell lines that stably secreted monoclonal antibodies (mAbs) were obtained. The ability of developed mAbs for capturing and neutralizing EBV was evaluated, and mAb 4E1 presented better performance to block the infection of EBV in cell line Hone-1. The mAb 4E1 recognized the epitope. Its sequence of variable region genes (VH and VL) presented a unique identity which hadn't been reported. The developed mAbs might benefit the antiviral therapy and immunologic diagnosis for EBV infection.


TMSOTf-Promoted Intermolecular Cascade Reaction of Aromatic Diazo Ketones with Olefins: Selective Synthesis of 3-Arylethylideneoxindoles.
A simple trimethylsilyl trifluoromethanesulfonate (TMSOTf)-promoted intermolecular cascade reaction of aromatic diazo ketones with olefins has been developed. This method directly gave 3-phenylethylideneoxindoles from 3-diazooxindoles and styrenes with exclusive regioselectivity, chemoselectivity, and E-stereoselectivity. The key to the success of the reaction and higher yields is the elegant use of TMSOTf, which gradually released the active triflic acid promoter in situ. The reaction tolerates a wide substrate scope of 3-diazooxindoles and styrenes with electron-donating and electron-withdrawing groups and works well on the gram scale.


A nitrogen-vacancy spin based molecular structure microscope using multiplexed projection reconstruction.
Methods and techniques to measure and image beyond the state-of-the-art have always been influential in propelling basic science and technology. Because current technologies are venturing into nanoscopic and molecular-scale fabrication, atomic-scale measurement techniques are inevitable. One such emerging sensing method uses the spins associated with nitrogen-vacancy (NV) defects in diamond. The uniqueness of this NV sensor is its atomic size and ability to perform precision sensing under ambient conditions conveniently using light and microwaves (MW). These advantages have unique applications in nanoscale sensing and imaging of magnetic fields from nuclear spins in single biomolecules. During the last few years, several encouraging results have emerged towards the realization of an NV spin-based molecular structure microscope. Here, we present a projection-reconstruction method that retrieves the three-dimensional structure of a single molecule from the nuclear spin noise signatures. We validate this method using numerical simulations and reconstruct the structure of a molecular phantom β-cyclodextrin, revealing the characteristic toroidal shape.


Popliteal artery branching patterns -- an angiographic study.
To analyse the variations in branching patterns of the popliteal artery and infrapopliteal vessels using angiography. Femoral angiograms of 1037 lower limbs in 568 patients were examined to assess the popliteal artery branching pattern. Variations of the infrapopliteal vessels supplying the foot were assessed in 662 limbs from the same cohort of patients. Nine hundred and forty-one (90.7%) limbs had the usual branching pattern with anterior tibial artery (AT) arising first followed by the tibial-peroneal trunk (TPT), which then gives rise to the posterior tibial (PT) and peroneal (PR) arteries. Variations in popliteal branching pattern were seen in 96 (9.3%) limbs. The commonest variation is high origin of the AT in 47 (4.5%) limbs or trifurcation of the popliteal artery in 33 (3.2%) limbs with AT, PT and PR arising together with no true TPT. The course of AT with high origin either anterior or posterior to popliteus was almost equal [25 (2.4%) or 22 (2.1%) limbs, respectively]. Eleven limbs (1.1%) had high origin of PT and two (0.2%) had a high origin of the PR. Six hundred and fifty-five (99%) limbs had normal infrapopliteal vessels. Seven (1%) had hypoplasia-aplasia of the infrapopliteal vessels. Five (0.8%) limbs had a hypoplastic PT with the remaining 2 (0.2%) having either a hypoplastic-aplastic AT or hypoplasia-aplasia of both AT and PT. Variations in the branching of the popliteal artery occur in about 10% of patients. Knowledge of these variations is important because of the potential consequences for the management of peripheral vascular disease.


Predicting better performance on a college preparedness test from narrative comprehension at the age of 6 years: An fMRI study.
To investigate whether high performance on college preparedness tests at 18 years of age can be predicted from brain activation patterns during narrative comprehension at 5-7 years of age. In this longitudinal study, functional MRI data during an auditory narrative-comprehension task were acquired from 15 children (5-7 years of age) who also provided their American College Testing (ACT) scores at the age of 18 years. Active voxels during the narrative-comprehension task were correlated with both composite ACT scores and the reading-comprehension component of the exam. Higher composite ACT scores and behavioral scores for reading comprehension were positively correlated with greater activation in frontal and anterior brain regions during the narrative-comprehension task. Our results suggest that neural circuits supporting higher ACT performance are predictable from a narrative-comprehension task at the age of 5-7 years. This supports a critical role for the anterior cingulate cortex, which is a part of the cingulo-opercular cognitive-control network early in development, as a facilitator for better ACT scores. This study highlights that shared neural circuits that support overall ACT performance and neural circuits that support reading comprehension both rely on neural circuits related to narrative comprehension in childhood, suggesting that interventions involving narrative comprehension should be considered for individuals with reading and other academic difficulties.


Monitoring and predicting community mental health centre utilization in Auckland, New Zealand.
Deinstitutionalization of mental health care has been in progress in many countries for over a quarter of a century. A comprehensive and detailed literature has evolved focussing on this process and its implications for alternative forms of combatting the incidence of mental illness. Most notably, literature has concentrated on the need for community-based mental health services both to prevent hospitalization in the first place and to ease the return of the hospital patient into the outside environment. In this paper the evolution of such a community-based system in metropolitan Auckland, New Zealand is discussed. More specifically, the focus is on the utilization of four community-based centres, with a view to plan better growth or reduction of service provision. Two dimensions of centre use, spatial and sociodemographic, are analysed and incorporated into four predictive models that, with appropriate refinement, can be used to determine the likely level of centre use in unserviced parts of the metropolitan area. Distance of individuals from centre locations is shown to be a significant factor in affecting use for three suburban primary prevention and intervention centres, whilst distance is non-significant for an inner-city aftercare facility. Also, various combinations of socio-demographic variables, reflecting service-specific needs for specific groups in the population, are shown to contribute significantly to predicting centre use. The paper presents the results against a policy backdrop in New Zealand where community mental health services are very much experimental in nature. The results reaffirm the importance of community mental health care in fulfilling an important need in society that health care administrators should take seriously in future policy developments.


Clinical validation of the isothermal RT-LAMP test for rapid diagnosis of SARS-CoV-2
Introducción. Desde el primer reporte en la provincia de Wuhan (China) en el año 2019, el SARS-CoV-2 se ha diseminado por todo el mundo, provocando un enorme impacto en la salud pública. Para su diagnóstico, la Organización Mundial de la Salud ha incentivado el desarrollo de pruebas rápidas, de simple ejecución, sensibles y específicas, que complementan la RT-qPCR como prueba de referencia. La prueba RT-LAMP ha mostrado ser una excelente alternativa para la detección del SARS-CoV-2 en diferentes biofluidos. Validar la técnica RT-LAMP colorimétrica en muestras de hisopado nasofaríngeo previamente confirmadas por RT-qPCR, usando el protocolo Charité, Berlín, Alemania. Materiales y métodos. Un total de 153 muestras de hisopado nasofaríngeo de individuos con sospecha de COVID-19 se sometieron a RT-qPCR y RT-LAMP, usando un estuche comercial colorimétrico (NEB, Germany). La RT-LAMP se practicó con las muestras de ARN extraídas del hisopado nasofaríngeo y con muestras crudas sin previa extracción de ARN. El resultado fue evaluado por un simple cambio de color en la reacción. La sensibilidad y especificidad de la técnica RT-LAMP para detectar el gen N del SARS-CoV-2 mediante un set de cebadores previamente reportados (set de Broughton), arrojó valores de 0,97 (0,85-1,00) y 0,81 (0,65-0,92), respectivamente, con un intervalo de confianza del 95%. Otro set de cebadores dirigidos contra otra región del mismo gen (set de Lalli) arrojó valores de sensibilidad y especificidad de 0,96 (0,78-1,00) y 0,77 (0,55-0,92), respectivamente. Sin previa extracción de ARN, se encontró que la sensibilidad fue del 0,95 (0,74-1,00) y la especificidad del 0,88 (0,64-0,99). Estos resultados evidencian que la técnica RT-LAMP podría considerarse una prueba diagnóstica rápida, de fácil ejecución, libre de equipos sofisticados, sensible y específica, para el diagnóstico del SARS-CoV-2 en muestras de hisopados nasofaríngeos.


Sudden death and myocardial infarction in first degree relatives as predictors of primary cardiac arrest.
The hypothesis that family history (FH) of myocardial infarction (MI) and FH of sudden death (SD) are both independent risk factors for primary cardiac arrest (PCA) was examined in a case-control study. PCA cases were attended by paramedics (1988-1994) and community-based age and sex matched controls were identified. Subjects (25-74 years) were free of prior clinically-recognized heart disease and major co-morbidity. Interviewers obtained a detailed history of MI and SD in first-degree relatives from spouses of 235 cases and 374 control subjects. A parental history of early-onset SD (age <65) was associated with an increased risk of PCA (odds ratio (OR)=2.69, 95% CI=1.35-5.36), after adjustment for parental history of MI and other risk factors. A parental history of late-onset SD was not associated with PCA risk (OR=0.94, 95% CI=0.55-1.62). Additionally, parental history of SD was related to early-onset PCA (OR=1.89, 95% CI=1.08-3.30) but not to late-onset PCA (OR=0.89, 95% CI=0.49-1.61). In contrast, parental MI (early/late) was related to PCA (early/late), after adjustment for other risk factors and parental history of SD. Similar results were observed in first-degree relatives. Findings suggest a potential role of familial factors related to both MI and SD in PCA. Stronger findings for a familial patterning of PCA were noted for early onset disease in cases and their relatives.


The treatment of adult supratentorial high grade astrocytomas.
From 1 January, 1982 until 31 December, 1987 260 adult patients were referred to the Cancer Control Agency of B.C. with high grade supratentorial astrocytomas. Multifocal disease on presentation was present in 17 cases (6.5%). Their survival is poor and whole brain radiotherapy is required. All other cases had unifocal disease, but eight did not receive radiotherapy. The 235 cases who received radiotherapy were subject to univariate and multivariate analyses according to extent of surgery, age, Kernohan and WHO grading, Karnofsky performance status, whole brain treatment, partial brain treatment, total dose and neuroret. Age is an extremely important predictor of survival (P approximately equal to 0). The pathologic appearance of glioblastoma (WHO grade) as well as the Karnofsky performance status were also important independent factors in predicting survival (P = 0.016, 0.027 respectively) on Cox multivariate analysis. Dose and neurorets were significant factors only in cases where the performance status was not recorded, suggesting that dose was selected according to the patient's condition and age. In this analysis it was found that localized radiation fields may be used rather than whole brain without jeopardizing survival.


Manganese-Catalyzed β-Methylation of Alcohols by Methanol.
We report an earth-abundant-metal-catalyzed double and single methylation of alcohols. A manganese catalyst, which operates at low catalyst loadings and short reaction times, mediates these reactions efficiently. A broad scope of primary and secondary alcohols, including purely aliphatic examples, and 1,2-aminoalcohols can be methylated. Furthermore, alcohol methylation for the synthesis of pharmaceuticals has been demonstrated. The catalyst system tolerates many functional groups among them hydrogenation-sensitive examples and upscaling is easily achieved. Mechanistic investigations are indicative of a borrowing hydrogen or hydrogen autotransfer mechanism involving a bimetallic K-Mn catalyst. The catalyst accepts hydrogen as a proton and a hydride from alcohols efficiently and reacts with a chalcone via hydride transfer.


Intravenous cholangiography by bolus injection of meglumine iotroxamate and meglumine iodoxamate: a comparative trial of two new contrast media.
The meglumine salts of iodoxamic and iotroxamic acids are recently developed intravenous cholangiographic media. In several studies these two media have been shown to be significantly better than meglumine iodipamide and meglumine ioglycamate for opacification of the biliary tree and incidence of adverse effects. As part of a multi-centre double-blind trial 100 patients were given iodoxamate or iotroxamate. Comparisons of opacification, side effects and renal excretion of contrast were made. The results showed no statistically significant difference in biliary tree opacification; more frequent renal excretion of contrast with iodoxamate; and contrary to previous reports a slightly higher incidence of side effects with iotroxamate.


Effects of the first wave of COVID-19 pandemic on implied stock market volatility: International evidence using a google trend measure.
This paper investigates the relationship between investors' attention, as measured by Google search queries, and equity implied volatility during the COVID-19 outbreak. Recent studies show that search investors' behavior data is an extremely abundant repository of predictive data, and investor-limited attention increases when the uncertainty level is high. Our study using data from thirteen countries across the globe during the first wave of the COVID-19 pandemic (January-April 2020) examines whether the search "topic and terms" for the pandemic affect market participants' expectations about future realized volatility. With the panic and uncertainty about COVID-19, our empirical findings show that increased internet searches during the pandemic caused the information to flow into the financial markets at a faster rate and thus resulting in higher implied volatility directly and via the stock return-risk relation. More specifically for the latter, the leverage effect in the VIX becomes stronger as Google search queries intensify. Both the direct and indirect effects on implied volatility, highlight a risk-aversion channel that operates during the pandemic. We also find that these effects are stronger in Europe than in the rest of the world. Moreover, in a panel vector autoregression framework, we show that a positive shock on stock returns may soothe COVID-related Google searches in Europe. Our findings suggest that Google-based attention to COVID-19 leads to elevated risk aversion in stock markets.


Bacteraemia in surgical patients with intravenous devices: a European multicentre incidence study. The European Working Party on Control of Hospital Infections.
A survey of the incidence of bacteraemia and the use of intravenous (IV) devices among 10,616 surgical patients was performed in 42 hospitals in eight countries. It was found that 63 per cent of the patients surveyed had an IV device inserted at some time during their hospital stay, with national variations between 40 and 99 per cent. The incidence of device-related thrombophlebitis was 10.3 per cent, with national variations between 7.8 and 28.4. Among the surgical patients not given IV therapy, 1.5/1000 had a bacteraemia, 0.5/1000 of them hospital-acquired. The corresponding figures for patients with a peripheral but no central IV device were 6.9 and 3.7, and for patients with a central venous catheter (CVC) 59.0 and 44.8, respectively. Even though there was a strong correlation between the incidence of bacteraemia and certain diagnoses there was also an independent correlation between it and CVCs or peripheral IV lines. No correlation was demonstrated between the number of catheter days per site for patients with a peripheral IV device, and hospital-acquired bacteraemia. This may be due to the low mean number of catheter days per site that was observed. There was a large and not easily explained national variation in the incidence of bacteraemia in patients with CVCs of between 16 and 108/1000.


Effect of sex hormones on plasma cholesterol in castrated and noncastrated male rats.
The administration of estradiol to both castrated and noncastrated male rats was associated with significantly increased plasma cholesterol levels as compared to controls, the estradiol in the noncastrated rats overriding the tendency of testosterone to lower plasma cholesterol.


Prevalence and predictors of PTSD and depression among adolescent victims of the Summer 2016 tornado in Yancheng City.
The aim of this study was to investigate the prevalence rate of probable posttraumatic stress disorder (PTSD) and depression in the adolescents who experienced the 2016 Yancheng tornado 3 months ago, as well as to analyze the related risk factors. A total of 247 tornado adolescent survivors were recruited to complete child PTSD symptom scale and Center for Epidemiologic Studies Depression Scale for Children. Results showed that 57.5% and 58.7% of the participants reported suspected symptoms of PTSD and depression respectively. PTSD is highly comorbid with depression. Risk factors of these two disorders were age and tornado exposure. Finally, the implications of intervention and prevention of mental health problems among adolescents who experienced tornado were discussed.


Disturbed urinary transport in the pelvi-calyceal system in calcium-oxalate stone patients.
This study is intended to elucidate the process of urinary transport through the pelvi-calyceal system (PCS). PCS-motility of a total of 28 PCS was qualitatively and quantitatively determined in 9 stone patients and 14 control persons by examination of contrast medium excretion. From X-ray videograms recorded by means of Siemens urography, four different urinary transport types could be distinguished as well as the duration of the contraction periods and the intervals between the PCS-contractions. In stone patients physiological types of urinary transport are less common (33%) than in control subjects (81.25%). In stone patients the PCS is often characterized by reduced or even absent motility. Calyceal reflux is usually found in the systolic phase of PCS-contractions, which may apparently be regarded as a physiological process.


Somatostatin-14 blocks the hepatotrophic effects of insulin in the rat.
We hypothesized that somatostatin-14 (SS-14) might inhibit insulin-stimulated hepatic growth. Rat hepatocytes were isolated by a two-step collagenase perfusion technique and cultured on Matrigel. Differentiated hepatocyte function was documented by albumin synthesis. Hepatocytes were incubated with insulin in the presence or absence of SS-14. Hepatocyte proliferation was assessed by tritiated thymidine ([3H]thy) incorporation into DNA. [3H]thy incorporation was increased by 230% in the presence of insulin and was essentially abolished by the addition of SS-14. Insulin-stimulated cyclic-AMP accumulation was also decreased from 190 to 108% of control levels (P less than 0.05) by the addition of SS-14. Pretreatment with pertussis toxin, which inactivates the inhibitory G-protein, Gi, blocked the effect of SS-14. (i) In the rat, SS-14 effectively blocks insulin-stimulated [3H]thy incorporation into DNA, possibly by blocking intracellular cAMP accumulation. (ii) Pertussis toxin blocks the growth inhibitory effects of SS-14, suggesting that inhibitory G proteins are involved in the mechanism of SS-14 action. Somatostatin may be useful in studying the role of second messengers in cell growth.


Surfactant administration by transient intubation in infants 29 to 35 weeks' gestation with respiratory distress syndrome decreases the likelihood of later mechanical ventilation: a randomized controlled trial.
To assess, among premature infants with early respiratory distress syndrome (RDS), the effect of one dose of intratracheally administered surfactant followed by extubation to nasal continuous positive airway pressure (NCPAP) on subsequent mechanical ventilation (MV), when compared with NCPAP alone. Randomized, blinded trial in infants 29 to 35 weeks' gestation with mild-to-moderate RDS requiring supplemental oxygen and NCPAP. Infants were randomized to intubation, surfactant treatment, and immediate extubation (surfactant group N=52), or to no intervention (control group N=53). All infants were subsequently managed with NCPAP. Need for later MV was 70% in the control group and 50% in the surfactant group. Surfactant group subjects had lower inspired oxygen fraction (FiO(2)) after study intervention and were less likely to require subsequent surfactant. Overall surfactant use, duration of O(2) therapy, length of stay, and bronchopulmonary dysplasia were unaffected. Among premature infants with mild-to-moderate RDS, transient intubation for surfactant administration reduces later MV.


The paracellular pathway in toad urinary bladder: permselectivity and kinetics of opening.
Determination of serosa-to-mucosa fluxes of Na, K, and Cl yields information about the properties of the shunt pathway in toad urinary bladder. We show that measurement of these fluxes at 30-sec intervals following an abrupt increase in mucosal osmolality yields evidence on the rate of opening of the path and of its permselectivity. The relationship between the fluxes of any pair of these ions indicates that the shunt is paracellular both before and after the increase in conductance effected by hyperosmolality and that the transepithelial PD affects the permselectivity properties (at 0 mV, PK/PNa/PCl=1:0.71:0.57; at + 25 mV, Pk/PNaPCl=1:0.71:0.99). The relationship between any of the fluxes and the total transepithelial conductance is linear and yields an estimate of cellular conductance (the intercept of this regression on the conductance axis) which is in accord with that measured electrically. These studies provide information on tight junction permeability to nonelectrolytes, as well. Finally, they provide new information about the role of the shunt path as a controlling influence on transepithelial sodium transport and raise the possibility that, in both leaky and tight epithelia, differences in transepithelial conductance from tissue to tissue, organ to organ, and species to species may be due, in the absence of edge damage, to changes in conductance of the paracellular pathway.