Timing of birth for women with a twin pregnancy at term: a randomised controlled trial.
There is a well recognized risk of complications for both women and infants of a twin pregnancy, increasing beyond 37 weeks gestation. Preterm birth prior to 37 weeks gestation is a recognized complication of a twin pregnancy, however, up to 50% of twins will be born after this time. The aims of this randomised trial are to assess whether elective birth at 37 weeks gestation compared with standard care in women with a twin pregnancy affects the risk of perinatal death, and serious infant complications. Multicentred randomised trial. women with a twin pregnancy at 366 weeks or more without contraindication to continuation of pregnancy. Trial Entry & Randomisation: Following written informed consent, eligible women will be randomised from 36+6 weeks gestation. The randomisation schedule uses balanced variable blocks, with stratification for centre of birth and planned mode of birth. Women will be randomised to either elective birth or standard care. Treatment Schedules: Women allocated to the elective birth group will be planned for elective birth from 37 weeks gestation. Where the plan is for vaginal birth, this will involve induction of labour. Where the plan is for caesarean birth, this will involve elective caesarean section. For women allocated to standard care, birth will be planned for 38 weeks gestation or later. Where the plan is for vaginal birth, this will involve either awaiting the spontaneous onset of labour, or induction of labour if required. Where the plan is for caesarean birth, this will involve elective caesarean section (after 38 and as close to 39 weeks as possible). Primary Study Outcome: A composite of perinatal mortality or serious neonatal morbidity. 460 women with a twin pregnancy to show a reduction in the composite outcome from 16.3% to 6.7% with adjustment for the clustering of twin infants within mothers (p = 0.05, 80% power). This is a protocol for a randomised trial, the findings of which will contribute information about the optimal time of birth for women with an uncomplicated multiple pregnancy at and beyond 37 weeks gestation.


On decomposing mixed-mode oscillations and their return maps.
Alternating patterns of small and large amplitude oscillations occur in a wide variety of physical, chemical, biological, and engineering systems. These mixed-mode oscillations (MMOs) are often found in systems with multiple time scales. Previous differential equation modeling and analysis of MMOs have mainly focused on local mechanisms to explain the small oscillations. Numerical continuation studies reported different MMO patterns based on parameter variation. This paper aims at improving the link between local analysis and numerical simulation. Our starting point is a numerical study of a singular return map for the Koper model which is a prototypical example for MMOs, which also relates to local normal form theory. We demonstrate that many MMO patterns can be understood geometrically by approximating the singular maps with affine and quadratic maps. Motivated by our numerical analysis we use abstract affine and quadratic return map models in combination with two local normal forms that generate small oscillations. Using this decomposition approach we can reproduce many classical MMO patterns and effectively decouple bifurcation parameters for local and global parts of the flow. The overall strategy we employ provides an alternative technique for understanding MMOs.


Current trends in stroke rehabilitation. A review with focus on brain plasticity.
Current understanding of brain plasticity has lead to new approaches in ischemic stroke rehabilitation. Stroke units that combine good medical and nursing care with task-oriented intense training in an environment that provides confidence, stimulation and motivation significantly improve outcome. Repetitive trans-cranial magnetic stimulation (rTMS), and trans-cranial direct current stimulation (tDCS) are applied in rehabilitation of motor function. The long-term effect, optimal way of stimulation and possibly efficacy in cognitive rehabilitation need evaluation. Methods based on multisensory integration of motor, cognitive, and perceptual processes including action observation, mental training, and virtual reality are being tested. Different approaches of intensive aphasia training are described. Recent data on intensive melodic intonation therapy indicate that even patients with very severe non-fluent aphasia can regain speech through homotopic white matter tract plasticity. Music therapy is applied in motor and cognitive rehabilitation. To avoid the confounding effect of spontaneous improvement, most trials are preformed ≥3 months post stroke. Randomized controlled trials starting earlier after strokes are needed. More attention should be given to stroke heterogeneity, cognitive rehabilitation, and social adjustment and to genetic differences, including the role of BDNF polymorphism in brain plasticity.


Spectral studies of tert-butyl isothiocyanate-inactivated P450 2E1.
Inactivation of cytochrome P450 2E1 by tert-butyl isothiocyanate (tBITC) resulted in a loss in the spectrally detectable P450-reduced CO complex. The heme prosthetic group does not appear to become modified, since little loss of the heme was observed in the absolute spectra or the pyridine hemochrome spectra, or in the amount of heme recovered from HPLC analysis of the tBITC-inactivated samples. Prolonged incubations of the inactivated P450 2E1 with dithionite and CO resulted in a recovery of both the CO complex and the enzymatic activity. Inactivated samples that were first reduced with dithionite for 1 h prior to CO exposure recovered their CO spectrum to the same extent as samples not pretreated with dithionite, suggesting that the major defect was an inability of the inactivated sample to bind CO. Spectral binding studies with 4-methylpyrazole indicated that the inactivated P450 2E1 had an impaired ability to bind the substrate. Enzymatic activity could not be restored with iodosobenzene as the alternate oxidant. EPR analysis indicated that approximately 24% of the tBITC-inactivated P450 2E1 was EPR-silent. Of the remaining tBITC-inactivated P450 2E1, approximately 45% exhibited an unusual low-spin EPR signal that was attributed to the displacement of a water molecule at the sixth position of the heme by a tBITC modification to the apoprotein. ESI-LC-MS analysis of the inactivated P450 2E1 showed an increase in the mass of the apoprotein of 115 Da. In combination, the data suggest that tBITC inactivated P450 2E1 by binding to a critical active site amino acid residue(s). This modified amino acid(s) presumably acts as the sixth ligand to the heme, thereby interfering with oxygen binding and substrate binding.


Sodium and potassium fluxes and compartmentation in roots of atriplex and oat.
K(+) and Na(+) fluxes and ion content have been studied in roots of Atriplex nummularia Lindl. and Avena sativa L. cv Goodfield grown in 3 millimolar K(+) with or without 3 or 50 millimolar NaCl. Compartmental analysis was carried out with entire root systems under steady-state conditions.Increasing ambient Na(+) concentrations from 0 to 50 millimolar altered K(+), in Atriplex, as follows: slightly decreased the cytoplasmic content (Q(c)), the vacuolar content (Q(v)), and the plasma membrane influx and efflux. Xylem transport for K(+) decreased by 63% in Atriplex. For oat roots, similar increases in Na(+) altered K(+) parameters as follows: plasma membrane influx and efflux decreased by about 80%. Q(c) decreased by 65%, and xylem transport decreased by 91%. No change, however, was observed in Q(v) for K(+). Increasing ambient Na(+) resulted in higher (3 to 5-fold) Na(+) fluxes across the plasma membrane and in Q(c) of both species. In Atriplex, Na(+) fluxes across the tonoplast and Q(v) increased as external Na(+) was increased. In oat, however, no significant change was observed in Na(+) flux across the tonoplast or in Q(v) as external Na(+) was increased. In oat roots, Na(+) reduced K(+) uptake markedly; in Atriplex, this was not as pronounced. However, even at high Na(+) levels, the influx transport system at the plasma membrane of both species preferred K(+) over Na(+).Based upon the Ussing-Teorell equation, it was concluded that active inward transport of K(+) occurred across the plasma membrane, and passive movement of K(+) occurred across the tonoplast in both species. Na(+), in oat roots, was actively pumped out of the cytoplasm to the exterior, whereas, in Atriplex, Na(+) was passively distributed between the free space, cytoplasm, and vacuole.


alpha-Hydroxy phosphinyl-based inhibitors of human renin.
The design and application of alpha-hydroxy phosphonates, a new class of transition state analogs, toward the discovery of novel and potent inhibitors of the aspartyl protease renin is described. Tripeptidic alpha-hydroxy diethyl phosphonate 3, the first example in this series, was found to be a good inhibitor of human renin (IC50 = 29 nM), and preliminary studies led to the choice of alpha-hydroxy dimethyl phosphonate 15 (IC50 = 16 nM) as a base-line compound for further structure-activity relationship study. Corresponding phosphinate (28-30) and phosphine oxide (23 and 24) analogs of 15 were prepared to assess the steric and electronic requirements around the phosphorus center. Evaluation of these analogs suggested that the presence of at least one alkoxy group on phosphorus was a critical requirement for good activity. Inhibitors with leucine at P2 possessed better in vitro activity than the corresponding P2 histidine analogs (15, IC50 = 16 nM vs 37, IC50 = 220 nM; 33, IC50 = 8.5 nM vs 40, IC50 = 41 nM). Compound 34 (IC50 = 31 nM), the P3 aminocaproic analog of 15, showed complete and long-lasting inhibition of plasma renin activity while eliciting a 10-15 mmHg drop in mean arterial pressure when administered intravenously at 1 mumol/kg in conscious, sodium-depleted, cynomolgus monkeys. In summary, the alpha-hydroxy phosphonates represent a promising and structurally novel class of transition state analog inhibitors of human renin.


High density lipoprotein cholesterol following anaerobic swimming in trained swimmers.
HDL-C, LDL-C, total cholesterol and glycerol were determined in venous blood of 10 male trained swimmers at rest and following 100-m anaerobic swimming. When compared to rest levels, the peak HDL-C and glycerol concentrations were significantly enhanced following anaerobic swim test (p < 0.01). However, peak LDL-C and total cholesterol after anaerobic swim were not significantly increased compared with the rest level. The present data demonstrated that the anaerobic swimming induces an increase in HDL-C metabolism, suggesting that the anaerobic exercise per se was one reason for the elevated HDL-C levels.


Stripe states with spatially oscillating d-wave superconductivity in the two-dimensional t-t'-J model.
We study the interplay between stripes and d-wave superconductivity in the two-dimensional t-t'-J model using a variational Monte Carlo method. The next-nearest-neighbor hopping t'<0 stabilizes the stripe states around 1/8 hole doping rate. We find that stripes and spatially oscillating superconductivity coexist depending on parameters. The superconducting orders are enhanced at the hole stripe regions. Although the energy differences are relatively small, the stripe state in which the phases between adjacent superconducting stripes are the opposite (antiphase) is also stabilized. We consider the possibility that the antiphase coexistence may explain the weakness of the c-axis Josephson couplings in the La1.6-xNd0.4SrxCuO4.


PD-L1 signaling in reactive astrocytes counteracts neuroinflammation and ameliorates neuronal damage after traumatic brain injury.
Tissue damage and cellular destruction are the major events in traumatic brain injury (TBI), which trigger sterile neuroimmune and neuroinflammatory responses in the brain. While appropriate acute and transient neuroimmune and neuroinflammatory responses facilitate the repair and adaptation of injured brain tissues, prolonged and excessive neuroimmune and neuroinflammatory responses exacerbate brain damage. The mechanisms that control the intensity and duration of neuroimmune and neuroinflammatory responses in TBI largely remain elusive. We used the controlled cortical impact (CCI) model of TBI to study the role of immune checkpoints (ICPs), key regulators of immune homeostasis, in the regulation of neuroimmune and neuroinflammatory responses in the brain in vivo. We found that de novo expression of PD-L1, a potent inhibitory ICP, was robustly and transiently induced in reactive astrocytes, but not in microglia, neurons, or oligodendrocyte progenitor cells (OPCs). These PD-L1+ reactive astrocytes were highly enriched to form a dense zone around the TBI lesion. Blockade of PD-L1 signaling enlarged brain tissue cavity size, increased infiltration of inflammatory Ly-6CHigh monocytes/macrophages (M/Mɸ) but not tissue-repairing Ly-6CLowF4/80+ M/Mɸ, and worsened TBI outcomes in mice. PD-L1 gene knockout enhanced production of CCL2 that is best known for its ability to interact with its cognate receptor CCR2 on Ly-6CHigh M/Mϕ to chemotactically recruit these cells into inflammatory sites. Mechanically, PD-L1 signaling in astrocytes likely exhibits dual inhibitory activities for the prevention of excessive neuroimmune and neuroinflammatory responses to TBI through (1) the PD-1/PD-L1 axis to suppress the activity of brain-infiltrating PD-1+ immune cells, such as PD-1+ T cells, and (2) PD-L1 intrinsic signaling to regulate the timing and intensity of astrocyte reactions to TBI. PD-L1+ astrocytes act as a gatekeeper to the brain to control TBI-related neuroimmune and neuroinflammatory responses, thereby opening a novel avenue to study the role of ICP-neuroimmune axes in the pathophysiology of TBI and other neurological disorders.


Effects of camptothecin conjugated to a somatostatin analog vector on growth of tumor cell lines in culture and related tumors in rodents.
Two CPT-SSA conjugates, JF-10-71 and JF-10-81, containing a chemically adjustable release-rate carbamate linker, have been reported previously by us to potently inhibit growth of human neuroblastoma IMR32 cells overexpressing somatostatin receptor type II (SSTR2) but are stable under buffer incubation conditions or in rat plasma. Further experiments now reveal that the conjugates performed well against many additional cell lines, particularly somatostatin receptor containing rat pancreatic CA20948 cells that were actually more sensitive to the conjugates than free camptothecin itself. JF-10-71 and JF-10-81 also were examined for their inhibitory effects on the growth of this and several other tumors transplanted into rats (CA20948) or nude mice. CA20948 tumors, known to overexpress SSTR2 and grown in Lewis rats, were treated, respectively, with nontoxic 400 nmol/kg intraperitoneal (i.p.) doses of JF-10-71 or JF-10-81. Also, SSTR2-positive human SCLC NCI-H69 tumors transplanted in nude mice were treated in a similar fashion. Human prostate PC-3 tumors, which do not contain high concentrations of SSTR2, also were grown in nude mice and treated with a 400 nmol/kg ip dose of JF-10-71. Both cytotoxic conjugates significantly inhibited growth of SSTR2-specific pancreatic and SCLC tumors, but JF-10-81 did not significantly affect PC-3 tumor growth. These experimental results suggested that CPT-SSA conjugates can effectively target and kill tumor cells growing in vivo and that the effect is mediated by somatostatin receptors resulting in either release of camptothecin at the cell surface or, more likely, after receptor-mediated cellular internalization.


What is the effect of school closures on learning in Canada? A hypothesis informed by international data.
Canadian lockdown response to the COVID-19 pandemic has included province-wide school shutdowns and frequent individual school closures to contain outbreaks. A number of scientists and political figures have shared their concerns about the medium- and long-term effects of school closures/shutdowns on student academic achievement, learning loss, and learning gaps. Unfortunately, there are no pan-Canadian studies to date to help define the scope of the problem. In this commentary, we report the results of a number of longitudinal research studies conducted in the Netherlands, Belgium, England, and the United States. Using these studies as a basis for comparison, we extrapolated a "Canadian" hypothesis on the unintended academic consequences of school closures, keeping in mind the unique nature of each province. We continue with recommendations on the types of research required to validate this hypothesis, and conclude with implications on public health and education should learning loss and gaps prove true.


Potential biomarkers for differentiation of benign prostatic hyperplasia and prostate cancer.
This study aims to evaluate the role of free/total prostate-specific antigen (PSA) ratio, serum total sialic acid level and cathepsin D activity in the differentiation of prostate cancer and benign prostatic hyperplasia (BPH). The study looked at 100 patients with BPH, 75 patients with organ-confined or locally advanced prostate cancer, and a control group of 50 healthy volunteers. Prostate cancer patients showed significantly higher total sialic acid level and cathepsin D activity and lower free/total PSA ratio than those in the BPH group. The results suggest that combined measurement of serum total sialic acid and/or cathepsin D activity with free/total PSA ratio could serve as a useful adjunct to conventional diagnostics for the differentiation of prostate cancer and BPH.


Optimal conditions for mycelial growth of Schizosaccharomyces japonicus cells in liquid medium: it enables the molecular investigation of dimorphism.
The non-pathogenic dimorphic fission yeast, Schizosaccharomyces japonicus, could be a suitable model organism for investigation of the genetic background of mycelial growth, as it has a haploid chromosome set and its genome is sequenced. Since earlier results have suggested that its morphological transition required solid substrates, but molecular biological experiments would require hyphae production in a liquid medium, we wanted to find circumstances which would enable hyphae production in liquid media. Several external conditions were investigated, but the strongest inducer was fetal bovine serum (FBS). Its positive effect could be hampered by heat and was dependent on pH, temperature and concentration of the serum. Other protein-containing compounds, such as peptone and bovine serum albumin or amino acids, proved to be ineffective or weak. Generally, the uninduced and induced mycelial growth of Sz. japonicus could be improved by lower external pH and higher temperature.


Examining the heterogeneity by employment status in dynamics between BMI and cognition: a longitudinal cohort study of the Korean aging population.
This study investigated the potential heterogeneity by employment status in the relationship between body mass index (BMI) trajectory and cognitive function among an aging population. We analyzed 2010-2018 cohort data from the Korean Longitudinal Study of Aging involving 4889 individuals aged over 45. We used statistical techniques of quadratic terms, interaction terms, time-invariant unobserved fixed effects, and time-lag effects to estimate the dynamic and interactive relationships among study variables. The effect of BMI on cognitive function was heterogeneous based on employment status. For the nonemployed group, the impact of BMI on cognitive function showed an inverted U-shape with a turning point (BMI 25); a higher BMI (up to 25) was associated with higher cognitive function, but further increases beyond this threshold led to decreased cognitive function. For the employed group, however, the impact of BMI on cognitive function was nonsignificant. The nonlinear effect of BMI on cognitive function for the nonemployed group was robust across various subgroups and specifications. The findings highlight the risk of obesity (BMI ≥ 25) on cognitive decline, particularly among nonemployed individuals. This illuminates the critical role of labor activity in regulating the impact of BMI on cognitive function among an aging population.


Nasal glioma.
Nasal gliomas are rare, benign, congenital neoplasms of the skin, occurring in infancy, and usually appearing over the bridge of the nose. A case of extra-nasal glioma in an eight-month-old girl is presented herein.


Recent advances in the understanding of genetic defects of neutrophil number and function.
Neutrophils are amongst the first immune cells to arrive at sites of infection and play an important role as the host's first line of defence against invading pathogens. Defects of neutrophil number or function are usually recognized clinically by recurrent infections that often are life-threatening. Over the last few years, a number of genetic mutations have been discovered to be the basis for congenital neutropenia, adding to our understanding of the molecular basis of these diseases. While many genetic mutations that cause severe congenital neutropenia result in a differentiation block at the promyelocyte stage, defects of neutrophil function are more heterogeneous on clinical, genetic and mechanistic levels. In this review we discuss recent advances in our understanding of the genetic and molecular basis of human neutrophil disorders.


Patients rarely detect breaches of confidence.
To measure the prevalence of patient reported breaches of confidence emanating from health services in South Australia. A community household survey with follow up telephone interviews of those reporting unauthorised disclosures. Recruitment interviews were conducted during October and November 2001 with 3037 South Australian residents over 15 years of age. South Australian households were selected randomly within a representative selection of census collection districts. Follow up telephone interviews were conducted with 18 respondents who reported unauthorised information releases in the twelve months prior to the initial survey. The one year prevalence of breaches of confidence reported by patients was 0.23 +/- 0.17% (1.96 x SE). This prevalence was significantly lower than a previously published estimate (Mulligan, 2001) of 1.1 +/- 0.4% (difference between proportions p= 0.003, z= 4.415) which relied upon reports of information disclosed without the patients permission as a proxy for breaches of confidence. An incidental finding was that 0.20+/- 0.16% (1.96x SE) of respondents reported exchanges of information amongst members of treating teams which had not been authorised by the patient. True breaches of confidence arising from health care interactions are rarely detected by patients. Ordinary information sharing within treating teams may be a more important source of misunderstandings between patients and health care providers. This issue can be addressed at the point of care by informing patients what will be done with their health information and who may later gain access to it.


Unhealthy changes in eating habits cause acute onset hypertension in the normotensive community-dwelling elderly-3 years cohort study.
The aim of this study was to determine what lifestyle changes can predict acute onset hypertension in the normotensive community-dwelling elderly.This study targeted elderly people enrolled in National Health Insurance in Fukushima Prefecture, Japan. The subjects were 24,490 people who took all of the specific health examination conducted by National Health Insurance in fiscal years 2013, 2014, and 2015 continuously and had a recorded systolic blood pressure (BP) <130 mm Hg and diastolic BP <85 mm Hg in the first 2 fiscal years. We examined their lifestyle changes for the first 2 fiscal years using the questionnaires given at the health examination. Multivariate Poisson regression analysis was conducted to examine the relationship between new-onset hypertension observed at the last examination and unhealthy lifestyle changes.The mean age of the subjects was 61.5 ± 8.2 years old at baseline. We observed new-onset hypertension in 1.062 subjects at the last examination. Of the study subjects, 12,027 (49.1%) answered to having at least one of the items of unhealthy lifestyle change in the questionnaire. In the multivariate logistic regression, eating supper before bedtime showed a significant increase in the risk ratio for acute onset hypertension (risk ratio 1.27, 95% confidence interval, 1.01-1.58).This study indicated that eating before bedtime is a risk factor of new-onset hypertension in the normotensive community-dwelling elderly. Adequate health guidance to avoid unhealthy lifestyle changes is required even in normotensive people as this hypertension is preventable.


Development and single-laboratory validation of a pseudofunctional biosensor immunoassay for the detection of the okadaic acid group of toxins.
A rapid analytical optical biosensor-based immunoassay was developed and validated for the detection of okadaic acid (OA) and its structurally related toxins from shellfish matrix. The assay utilizes a monoclonal antibody which binds to the OA group of toxins in order of their toxicities, resulting in a pseudofunctional assay. Single-laboratory validation of the assay for quantitative detection of OA determined that it has an action limit of 120 microg/kg, a limit of detection of 31 microg/kg, and a working range of 31-174 microg/kg. The midpoint on the standard matrix calibration curve is 80 microg/kg, half the current regulatory limit. Inter- and intra-assay studies of negative mussel samples spiked with various OA concentrations produced average coefficient of variation (CV) and standard deviation (SD) values of 7.9 and 10.1, respectively. The assay was also validated to confirm the ability to accurately codetect and quantify dinophysistoxin-1 (DTX-1), DTX-2, and DTX-3 from shellfish matrix. Alkaline hydrolysis was not required for the detection of DTX-3 from matrix. Excellent correlations with the data generated by the biosensor method and liquid chromatography/tandem mass spectrometry (LC/MS/MS) were obtained using a certified reference material (R(2) = 0.99), laboratory reference material, and naturally contaminated mussel samples (R(2) = 0.97). This new procedure could be used as a rapid screening procedure replacing animal-based tests for DSP toxins.


Fluorescence-Amplified Detection of Redox Turnovers in Supported Lipid Bilayers Illuminates Redox Processes of α-Tocopherol.
Electron-transfer processes in lipid membranes are key to biological functions, yet challenging to study because of the intrinsic heterogeneity of the systems. Here, we report spectro-electrochemical measurements on indium tin oxide-supported lipid bilayers toward the selective induction and sensing of redox processes in membranes. Working at neutral pH with a fluorogenic α-tocopherol analogue, the dynamics of the two-electron oxidation of the chromanol to a chromanone and the rapid thermal decay of the latter to a chromoquinone are recorded as a rapid surge and drop in intensity, respectively. Continuous voltage cycling reveals rapid chromoquinone two-electron, two-proton reduction to dihydrochromoquinone at negative bias, followed by slow regeneration of the former at positive bias. The kinetic parameters of these different transitions are readily obtained as a function of applied potentials. The sensitivity and selectivity afforded by the reported method enables monitoring signals equivalent to femtoampere currents with a high signal-to-background ratio. The study provides a new method to monitor membrane redox processes with high sensitivity and minimal concentrations and unravels key dynamic aspects of α-tocopherol redox chemistry.


Time-domain digital pre-equalization for band-limited signals based on receiver-side adaptive equalizers.
We theoretically and experimentally investigate a time-domain digital pre-equalization (DPEQ) scheme for bandwidth-limited optical coherent communication systems, which is based on feedback of channel characteristics from the receiver-side blind and adaptive equalizers, such as least-mean-squares (LMS) algorithm and constant or multi- modulus algorithms (CMA, MMA). Based on the proposed DPEQ scheme, we theoretically and experimentally study its performance in terms of various channel conditions as well as resolutions for channel estimation, such as filtering bandwidth, taps length, and OSNR. Using a high speed 64-GSa/s DAC in cooperation with the proposed DPEQ technique, we successfully synthesized band-limited 40-Gbaud signals in modulation formats of polarization-diversion multiplexed (PDM) quadrature phase shift keying (QPSK), 8-quadrature amplitude modulation (QAM) and 16-QAM, and significant improvement in both back-to-back and transmission BER performances are also demonstrated.


The carboxy-terminus of the formin FMNL1ɣ bundles actin to potentiate adenocarcinoma migration.
The formin family of proteins contributes to spatiotemporal control of actin cytoskeletal rearrangements during motile cell activities. The FMNL subfamily exhibits multiple mechanisms of linear actin filament formation and organization. Here we report novel actin-modifying functions of FMNL1 in breast adenocarcinoma migration models. FMNL1 is required for efficient cell migration and its three isoforms exhibit distinct localization. Suppression of FMNL1 protein expression results in a significant impairment of cell adhesion, migration, and invasion. Overexpression of FMNL1ɣ, but not FMNL1β or FMNL1α, enhances cell adhesion independent of the FH2 domain and FMNL1ɣ rescues migration in cells depleted of all three endogenous isoforms. While FMNL1ɣ inhibits actin assembly in vitro, it facilitates bundling of filamentous actin independent of the FH2 domain. The unique interactions of FMNL1ɣ with filamentous actin provide a new understanding of formin domain functions and its effect on motility of diverse cell types suggest a broader role than previously realized.


Proportional spike-timing precision and firing reliability underlie efficient temporal processing of periodicity and envelope shape cues.
Temporal sound cues are essential for sound recognition, pitch, rhythm, and timbre perception, yet how auditory neurons encode such cues is subject of ongoing debate. Rate coding theories propose that temporal sound features are represented by rate tuned modulation filters. However, overwhelming evidence also suggests that precise spike timing is an essential attribute of the neural code. Here we demonstrate that single neurons in the auditory midbrain employ a proportional code in which spike-timing precision and firing reliability covary with the sound envelope cues to provide an efficient representation of the stimulus. Spike-timing precision varied systematically with the timescale and shape of the sound envelope and yet was largely independent of the sound modulation frequency, a prominent cue for pitch. In contrast, spike-count reliability was strongly affected by the modulation frequency. Spike-timing precision extends from sub-millisecond for brief transient sounds up to tens of milliseconds for sounds with slow-varying envelope. Information theoretic analysis further confirms that spike-timing precision depends strongly on the sound envelope shape, while firing reliability was strongly affected by the sound modulation frequency. Both the information efficiency and total information were limited by the firing reliability and spike-timing precision in a manner that reflected the sound structure. This result supports a temporal coding strategy in the auditory midbrain where proportional changes in spike-timing precision and firing reliability can efficiently signal shape and periodicity temporal cues.


Slivers of the journey: the use of photovoice and storytelling to examine female to male transsexuals' experience of health care access.
The purpose of this research project was to examine female to male transsexuals' (FTMs) experiences of accessing health care. This was accomplished by documenting and recording the experiences of five FTMs through the use of photography and interviews. It was hoped that such an inquiry would provide a starting point for future research about the health care needs of the transgender community, and document some of the health care needs of the FTM community that would lead to recommendations for policy changes and educating providers.


A case of Falciparum malaria presenting with features of functional bowel obstruction.
Malaria is the most common tropical disease in Sudan, which is caused by an infection with Plasmodium protozoa transmitted by an infective female Anopheles mosquito. Headache, fever, cough, fatigue, malaise, shaking chills, arthralgia and myalgia are the cardinal features of malaria, but occasionally, it has an atypical presentation. Intestinal obstruction as a complication is an extremely rare presentation. Here within, we describe a 28-year-old Sudanese man who has presented with of colicky abdominal pain, absolute constipation for two days and fever. Blood film for malaria was positive for Plasmodium falciparum. Intravenous artesunate injections have resulted in the resolution of symptoms of bowel obstruction. In conclusion, malaria should be suspected in any febrile patient with the features of bowel obstruction especially in an endemic area or if the patient has recently travelled to an endemic area with malaria. Treatment of malaria will result in the resolution of symptoms of functional bowel obstruction.


Determination and quantification of Escherichia coli by capillary electrophoresis.
Capillary electrophoresis (CE) is widely employed for the separation of nucleic acids or protein, but it is rarely applied in the quantification of Escherichia coli (E. coli). Here, we have analysed E. coli by CE with mercury lamp induced fluorescence, and demonstrated the relationship between its fluorescence intensity with the concentration of E. coli for the first time. The gradient concentration of E. coli was obtained by polymerase chain reaction (PCR) with different amplification cycles and dilution certain PCR products of E. coli, respectively. Results show that the peak area was linearly related to the logarithm of the concentration of E. coli and the logarithm of PCR replication numbers. The correlation coefficients R(2) are 0.957 and 0.966, respectively. The limit of detection (LOD) was found to be about 8.913 × 10(-15) mol μl(-1). The reproducibility of capillary electrophoresis may make this technique possible for quantitative measurement of bacteria in bio-analytical science.


Brillouin amplification in phase coherent transfer of optical frequencies over 480 km fiber.
We describe the use of fiber Brillouin amplification (FBA) for the coherent transmission of optical frequencies over a 480 km long optical fiber link. FBA uses the transmission fiber itself for efficient, bi-directional coherent amplification of weak signals with pump powers around 30 mW. In a test setup we measured the gain and the achievable signal-to-noise ratio (SNR) of FBA and compared it to that of the widely used uni-directional Erbium doped fiber amplifiers (EDFA) and to our recently built bi-directional EDFA. We measured also the phase noise introduced by the FBA and used a new and simple technique to stabilize the frequency of the FBA pump laser. We then transferred a stabilized laser frequency over a wide area network with a total fiber length of 480 km using only one intermediate FBA station. After compensating the noise induced by the fiber, the frequency is delivered to the user end with an uncertainty below 2 x 10(-18) and an instability sigma y(tau) = 2 x 10(-14) /(tau/s).


Antiplasmodial Activity and Phytochemical Constituents of Selected Antimalarial Plants Used by Native People in West Timor Indonesia.
To document traditional antimalarial plants used by Tetun ethnic people in West Timor Indonesia and evaluate the antiplasmodial activity and phytochemicals of several plants that are widely used as oral medicine. A field study to document antimalarial plants followed by laboratory works to test antiplasmodial activity and identify the phytochemical constituents of some selected plants extract were applied. The inhibitory potency of ethanolic extracts of Strychnos ligustrina wood, roots of Calotropis gigantea, Fatuoa pilosa, and Neoalsomitra podagrica, whole plant of Cleome rutidosperma and Physalis angulata, stem barks of Alstonia spectabilis, Alstonia scholaris, Jatropha curcas and Plumeria alba, and leaves of Melia azedarach on the Plasmodium falciparum 3D7 strain in vitro were tested. Gas chromatography-mass spectrometry instrument was used to analyze the phytochemicals of the extracts. The Tetun ethnic people use 50 plant species as antimalarials. P. angulata, J. curcas, and A. spectabilis extracts show strong antiplasmodial activity with IC50 values of 0.22, 0.22, and 1.23 μg/mL, respectively; N. podagrica, A. scholaris, F. pilosa, and P. alba were moderate antiplasmodials with IC50 values of 11.60, 15.46, 24.92, and 36.39 μg/mL, respectively; and C. rutidosperma, M. azedarach, S. ligustrina, and C. gigantea were weak antiplasmodials with IC50 values of 54.25, 63.52, 63.91, and 66.49 μg/mL, respectively. The phytochemicals identification data indicate that these 11 plants contain alkaloids, terpenoids, steroids, coumarins, alcohols, thiols, phenolics, aldehydes, fatty acids, esters, and so forth. Plants widely used as antimalarials by the Tetun ethnic people is proven to have antiplasmodial activity.


The mitochondrial genome of the endophyte Edenia gomezpompae CRI Eg3 isolated from sweet potato.
Edenia gomezpompae CRI Eg3 was isolated from the leaves of sweet potato. Its complete mitogenome contains 37,226 bp, with a G + C content of 26.1%. A total of 51 genes were annotated, including 16 protein-coding genes, 33 tRNA genes, and 2 rRNA (s-rRNA, L-rRNA) genes. The most significant character of this mitogenome is its free of group I introns in the CDS regions. Phylogenetic analysis using the mitogenomes of relative fungal species indicated that CRI Eg3 is closely related to Shiraia bambusicola, and they clustered in the Pleosporales lineage. This is the first genome reported in the genus Edenia.


Nuclear localization of a novel human syntaxin 1B isoform.
The syntaxins are proteins associated with various intracellular membrane compartments. They are major participants in a large variety of physiological processes where membrane fusion occurs, including exocytosis. We have identified a novel syntaxin isoform generated by alternative splicing of the human STX1B gene. In contrast with the canonical syntaxins, this isoform (STX1B-DeltaTMD) lacked the classical C-terminal transmembrane domain and localized to the nucleus of various tumoral and non-tumoral cell types including human brain cortical neurons in vivo. The reversible blockade of STX1B-DeltaTMD nuclear import demonstrated that nuclear import occurred via a Ran-dependent pathway. A specific and glycine-rich C-terminus of 15 amino acids served as an unconventional nuclear localization signal. STX1B-DeltaTMD colocalized with Lamin A/C and NuMA (NUclear Mitotic Apparatus protein) in interphasic nuclei, and with NuMA and gamma-tubulin in the pericentrosomal region of the mitotic spindle in dividing cells. In a series of 37 human primary brain tumors, the ratio of STX1B-DeltaTMD to Lamin A/C transcripts was a significant prognostic marker of survival, independent of tumor staging. The characterization of STX1B-DeltaTMD as the first nucleoplasmic syntaxin with no transmembrane domain, illustrates the importance of alternative splicing in the emergence of unsuspected properties of the syntaxins in human cells, in both physiological and pathological conditions.


A Cuvette Design for Measurement of Ethylene Production and Carbon Dioxide Exchange by Intact Shoots under Controlled Environmental Conditions.
A cuvette is described for simultaneous measurement of ethylene production and CO(2) fixation by intact shoots under controlled environmental conditions. This design overcomes potential problems associated with closed systems conventionally used for studies on ethylene production, allowing accurate determination of rates of ethylene production in plants exposed to different environmental conditions.


The Indiana Cancer Pain and Depression (INCPAD) trial Design of a telecare management intervention for cancer-related symptoms and baseline characteristics of study participants.
Pain and depression are two of the most prevalent and treatable cancer-related symptoms, each present in at least 20-30% of oncology patients. Both symptoms are frequently either unrecognized or undertreated, however. This article describes a telecare management intervention delivered by a nurse-psychiatrist team that is designed to improve recognition and treatment of pain and depression. The enrolled sample is also described. The Indiana Cancer Pain and Depression study is a National Cancer Institute-sponsored randomized clinical trial. Four hundred five patients with cancer-related pain and/or clinically significant depression from 16 urban or rural oncology practices throughout Indiana have been enrolled and randomized to either the intervention group or to a usual-care control group. Intervention patients receive centralized telecare management coupled with automated home-based symptom monitoring. Outcomes will be assessed at 1, 3, 6 and 12 months by research assistants blinded to treatment arms. Of 4465 patients screened, 2185 (49%) endorsed symptoms of pain or depression. Of screen-positive patients, about one-third were ineligible (most commonly due to pain or depression not meeting severity thresholds or to pain that is not related to cancer). Of the 405 patients enrolled, 32% have depression only, 24% have pain only and 44% have both depression and pain. At baseline, participants reported an average of 16.8 days out of the past 4 weeks during which they were confined to bed or had to reduce their usual activities by > or =50% due to pain or depression. Also, 176 (44%) reported being unable to work due to health reasons. When completed, the Indiana Cancer Pain and Depression trial will test whether centralized telecare management coupled with automated home-based symptom monitoring improves outcomes in cancer patients with depression and/or pain. Findings will be important for both oncologists and mental health clinicians confronted with oncology patients' depression or pain.


Rapid Formation of Acrylated Microstructures by Microwave-Induced Thermal Crosslinking.
We present a rapid and highly efficient method to form microstructure of poly(ethylene glycol) (PEG)-based acrylates by microwave-induced thermal crosslinking. PEG-based polymeric microstructures such as polymer microarrays and microwells were fabricated on 3-(trimethoxysilyl)propyl methacrylate (TMSPMA)-coated glass slides that were placed on top of a silicon wafer. In comparison to ultraviolet (UV) irradiation curing, microwave-induced thermal crosslinking could be completed within 10 s, without thermal degradation or oxygen inhibition in the presence of ambient oxygen. Furthermore, the activation of surviving free radical impurities by microwave-induced heating enabled crosslinking even without an exogenous radical initiator (e.g., 2,2'-azoisobutyronitrile (AIBN)). This approach can be beneficial for fabricating various PEG-based microstructures for high-throughput screening assays, cell-based biosensors, and biomedical microdevices.


Prosodic Entrainment in Conversations of Verbal Children and Teens on the Autism Spectrum.
Unusual speech prosody has long been recognized as a characteristic feature of the speech of individuals diagnosed with Autism Spectrum Disorders (ASD). However, research to determine the exact nature of this difference in speech prosody is still ongoing. Many individuals with verbal autism perform well on tasks testing speech prosody. Nonetheless, their expressive prosody is judged to be unusual by others. We propose that one aspect of this perceived difference in speech prosody in individuals with ASD may be due to a deficit in the ability to entrain-or become more similar-to their conversation partners in prosodic features over the course of a conversation. In order to investigate this hypothesis, 24 children and teens between the ages of 9 and 15 years participated in our study. Twelve of the participants had previously been diagnosed with ASD and the other 12 participants were matched to the ASD participants in age, gender, and non-verbal IQ scores. All participants completed a goal-directed conversation task, which was subsequently analyzed acoustically. Our results suggest (1) that youth diagnosed with ASD entrain less to their conversation partners compared to their neurotypical peers-in fact, children and teens diagnosed with ASD tend to dis-entrain from their conversation partners while their neurotypical peers tend to converge to their conversation partners' prosodic features. (2) Although age interacts differently with prosodic entrainment in youth with and without ASD, this difference is attributable to the entrainment behavior of the conversation partners rather than to those with ASD. (3) Better language skill is negatively correlated with prosodic entrainment for both youth with and without ASD. The observed differences in prosodic entrainment in children and teens with ASD may not only contribute to the perceived unusual prosody in youth with ASD but are also likely to be indicative of their difficulties in social communication, which constitutes a core challenge for individuals with ASD.


[Prevalence of chronic urticaria of autoimmune origin at the Regional Hospital Adolfo López Mateos].
Chronic urticaria is a common skin disorder characterized by recurrent, transitory, itchy wheals with individual lesions lasting less than 24 hours and affecting patients for six weeks or longer. In adults it has been shown that approximately 40% of the patients with chronic urticaria have autoimmune urticaria. To determine the prevalence of autoimmune urticaria in adults with chronic urticaria. We studied adult patients with chronic urticaria by means of autologous serum skin test (ASST), and by antinuclear and antithyroid (antityroglobulin, antiperoxidase) antibodies. We compared them with a group matched by sex and age. We included 68 patients: 34 cases (patients with chronic urticaria) and 34 controls (healthy individuals). In the cases we found high levels of TSH (p = 0.003) and positive autologous serum skin test (p = 0.04), while in the controls we observed a statistically significant difference of the levels of antithyroid antibodies (p = 0.002). The prevalence of autoantibodies (antithyroid or by autologous serum) was present in 55 and 44% of the patients with chronic urticaria. Autoimmunity is one of the most common causes of chronic urticaria; it may explain the pathogenesis in half of the studied cases.


Serous macular detachment secondary to distant retinal vascular disorders.
To report tomographic features of macular edema associated with distant retinal vascular disorders. Six eyes with macular edema (three with extramacular branch retinal vein occlusion and three with Coats disease) underwent fluorescein angiography to detect dye leakage and optical coherence tomography to evaluate the macular features and measure the foveal height (distance between inner retinal surface and retinal pigment epithelium) and the retinal thickness (thickness of neurosensory retina) at the central fovea. Fluorescein angiography showed widespread nonperfusion and retinal vein staining in the eyes with a branch retinal vein occlusion not involving the macula. In eyes with Coats disease, nonperfused areas, telangiectatic retinal vessels, and aneurysms were seen in the peripheral fundus on fluorescein angiography. In one eye with Coats disease, telangiectatic vessels and aneurysms were seen in the nasal mid periphery of the optic disk. There was no dye leakage in the macular area in any eyes. Optical coherence tomography showed subretinal fluid and retinal swelling at the fovea in all eyes. The foveal height ranged from 300 to 697 microm (mean, 478 microm) and retinal thicknesses ranged from 170 to 280 microm (mean, 233 microm). Distant retinal vascular leakage causes serous retinal detachment in the macula. The macula is predisposed to collect subretinal fluid although retinal vascular leakage is far from the macula.


Role of free fatty acids on cardiac autonomic nervous system in noninsulin-dependent diabetic patients: effects of metabolic control.
Decreased heart rate variability (HRV) is a risk factor for cardiovascular mortality. Elevated plasma free fatty acid (FFA) levels decrease HRV in healthy subjects. Thus, we investigated the effect of changes in plasma FFA levels on HRV, in non-insulin-dependent diabetes (NIDDM) patients. Thirty NIDDM patients free from diabetic neuropathy volunteered for a study made by two phases. In study A, changes in HRV along a 10% lipid emulsion infusion + heparin (n = 15) or saline infusion (control study; n = 15) were investigated. In study B, all patients (n = 30) underwent further determination of HRV after 3 months of improved metabolic control achieved by intensified insulin treatment. In study A, lipid emulsion infusion increased plasma FFA (P < 0.001) and catecholamine concentrations (P < 0.005), mean arterial blood pressure (P < 0.005), low frequency/high frequency (LF/HF) ratio (P < 0.001). Delta plasma FFA levels correlated with delta LF/HF ratio (r = 0.57; P < 0.02). Along with saline infusion, metabolic and cardiovascular parameters remained unchanged throughout the test. In study B, improved metabolic control lowered fasting plasma glucose (P < 0.005), FFA (P < 0.001), norepinephrine (P < 0.02), epinephrine (P < 0.04), and glycosylated hemoglobin levels (P < 0.001), mean arterial blood pressure(P < 0.05), and LF/HF ratio (P < 0.001). Again percent decline in plasma FFA correlated with the percent change in LF/HF ratio (r = 0.72; P < 0.001). In a multivariate analysis, percent changes in LF/HF ratio were associated with percent changes in plasma FFA independently of gender and percent changes in body mass index, waist/hip ratio, plasma norepinephrine, epinephrine, glycosylated hemoglobin, and daily insulin therapy. Our study demonstrates that changes in plasma FFA levels may have a parallel effect on cardiac sympathetic/parasympathetic nervous system balance in NIDDM patients.


MUC1 and survivin combination tumor gene vaccine generates specific immune responses and anti-tumor effects in a murine melanoma model.
MUC1 and survivin are ideal tumor antigens. Although many cancer vaccines targeting survivin or MUC1 have entered clinical trials, no vaccine combining MUC1 and survivin have been reported. Due to tumor heterogeneity, vaccines containing a combination of antigens may have improved efficacy and coverage of a broader spectrum of cancer targets. Here, cellular responses and anti-tumor activities induced by a combination of DNA vaccine targeting MUC1 and survivin (MS) were evaluated. Results showed that CTL activity and inhibition of tumor growth were obviously enhanced in mice immunized with the combined vaccine in a protection assay. However, in order to enhance the therapeutic effect in the treatment assay, a recombinant adenovirus (rAd) vaccine expressing MUC1 and survivin (Ad-MS) was used as a booster following the DNA vaccine prime. Meanwhile, IL-2 promoting T cell proliferation was used as an immunoadjuvant for the DNA vaccine. Results showed that the CTL activity response to the DNA vaccine was enhanced nearly 200% when boosted by the rAd vaccine and was further enhanced by nearly 60% when combined with the IL-2 adjuvant. Therefore, DNA prime combined with rAd boost and IL-2 (MS/IL2/Ad-MS) adjuvant was considered as the best strategy and further evaluated. Multiple cytokines promoting cellular immune responses were shown to be greatly enhanced in mice immunized with MS/IL2/Ad-MS. Moreover, in the treatment assay, the tumor inhibition rate of MS/IL2/Ad-MS reached up to 50.1%, which may be attributed to the enhancement of immune responses and reduction of immunosuppressive factors in tumor-bearing mice. These results suggested that immunization with the combination vaccine targeting MUC1 and survivin using a DNA prime-rAd boost strategy along with IL-2 adjuvant may be an effective method for breaking through immune tolerance to tumors expressing these antigens with potential therapeutic benefits in melanoma cancer.


Chondrosarcoma in a patient with McCune-Albright syndrome. Report of a case.
A case of McCune-Albright syndrome with acromegaly and chrondrosarcoma is reported. The potential role of chronic growth hormone overproduction in the occurrence of malignant transformation and the possible value of bisphosphonates in the treatment of bone fibrous dysplasias are discussed.


The effect of precooling on cardiovascular and metabolic strain during incremental exercise.
The purpose of this study was to investigate the effect of precooling on the chronotropic index defined as the slope of the heart rate (HR) and oxygen uptake during incremental exercise. Ten men performed incremental exercise following 2 conditions: control (rest in a thermoneutral laboratory, 21.5 ± 0.7 °C; performed first) and precooling (cold-water immersion, 23.1 ± 0.2 °C). Prior to exercise, core temperature was significantly lower for precooling (36.6 ± 0.3 °C) compared with control (37.1 ± 0.4 °C; p < 0.001) and remained lower throughout exercise (p < 0.05). Time to volitional fatigue during the incremental exercise test was significantly longer in the control (914 ± 97 s) compared with precooling (889 ± 97 s; p = 0.015). Precooling reduced HR by 8-10 beats·min(-1) compared with control throughout exercise (peak HR: precooling, 178 ± 9 beats·min(-1); control, 188 ± 6 beats·min(-1); p = 0.001). Oxygen uptake did not differ between conditions (p > 0.05). The chronotropic index did not differ between conditions (p = 0.301); however, the y intercept was significantly lower (p = 0.009) for precooling (53.6 ± 11.0) compared with control (67.3 ± 11.0). Thus, the benefit of precooling was a lower HR that was maintained throughout exercise rather than a reduced rate of rise in HR. These results suggest the potential use of precooling to mitigate cardiovascular strain in individuals working at elevated metabolic rates. However, the reduced exercise time warrants consideration.


Increase In Hepatic Quinolinic Acid Concentrations In Alcohol Withdrawn Rats.
Behavioral associated disturbance involves excitotoxic quinolinate in alcohol withdrawal syndrome in man due to increase availability of tryptophan. In present study we investigated alcoholism related clinical features in relation to tryptophan and 5-HT levels in rat's model. Locally bred male Wistar rats, weighing 200-250 g were housed separately into 6 animals/ group with 12 h light: dark cycle at room temp 22±3 °C. They were given diet ad libitum, for three days then alcohol 8% (v/v) was added into the liquid diet. Matched control rats of each group were given maltose-dextrin as a substitute of alcohol. Alcohol withdrawal syndrome was assessed after 7 hours by replacing the alcohol-containing liquid diet with tap water. Alcohol withdrawal group showed significant increase (p<0.001) in holo, apo, and total tryptophan 2, 3 dioxygenase enzyme activities, no significant change in brain tryptophan and 5HIAA however significant decrease (p<0.001) in brain 5HT was observed when compared with chow controls. Both alcohols administered and withdrawal groups showed significant rise in serum corticosterone by p<0.05 and p<0.001 respectively. Liver quinolinic acid concentrations were increased significantly (p<0.01) with robust increase in alcohol withdrawn rats. We conclude that the excitotoxin tryptophan metabolite quinolinic acid of peripheral origin plays significant role in the behavioral manifestation of the alcohol withdrawal syndrome. Tryptophan metabolites should be targeted to develop new strategies in the progress of pharmacological interventions related to alcoholism.


Primary endodermal sinus (yolk sac) tumor of the anterior mediastinum: a report of a successfully treated eleven-year-old boy.
An asymptomatic 11-year-old Japanese boy with an endodermal sinus (yolk sac) tumor of the anterior mediastinum was successfully treated with cisplatinum-based combination chemotherapy and subsequent surgical excision. The patient is alive and in good health 60 months from diagnosis.


The herpes simplex virus latency-associated transcript is spliced during the latent phase of infection.
The herpes simplex virus type 1 latency-associated transcript (LAT) is expressed as a major species 2,100 to 2,200 bases in length and a less abundant one ca. 730 bases shorter in latently infected mouse and rabbit neurons. RNA blot hybridization experiments using 20- to 22-base synthetic oligonucleotides and mung bean nuclease protection assays have demonstrated that the smaller LAT species is colinear with the larger one, except for a 730-base intron. On the basis of Northern blot analysis, the spliced species which comprises as much as 50% of the total LAT in latent infections of mice with several strains of herpes simplex virus type 1 and latent infections of rabbits with either the McKrae or the KOS(M) strains of virus is not present in the acute phase of infection. Further and rather surprisingly, in mice latently infected with the KOS(M) strain of virus, the spliced LAT species is considerably less abundant. This suggests that both the strain of virus and the animal in which the latent infection occurs are important in either the processing or stability of spliced LAT. Finally, an exhaustive series of experiments failed to provide convincing evidence that a unique, poly(A)+ species of LAT exists in the latent phase of infection.


Gender, division of unpaid family work and psychological distress in dual-earner families.
Epidemiological studies have only recently begun to address the consequences of unpaid family work (ie., housework and child rearing) for mental health. Although research is suggestive of an association between the division of unpaid family work and psychological health, especially for women, additional research is required to clarify the conditions under which such a relationship holds. The purpose of the present study was to examine more nuanced relationships between the division of family work and psychological distress by disaggregating the family work construct according to type (housework/child rearing), control over scheduling, and evaluations of fairness. Analysis of data obtained from a cross-sectional telephone survey conducted in a Canadian city. Analyses were based on 293 employed parents (182 mothers and 111 fathers), with at least one preschool child, living in dual-earner households. Several multiple linear regression models were estimated with psychological distress as the outcome, adjusting for confounders. For mothers, more perceived time spent in child rearing (particularly primary child care) and high-schedule-control housework tasks (e.g. yard work) relative to one's partner, were associated with greater distress. For fathers, perceived unfairness in the division of housework and child rearing were associated with greater distress. Although methodological limitations temper firm conclusions, these results suggest that the gendered nature of household work has implications for the psychological well-being of both mothers and fathers of preschool children in dual-earner households. However, more longitudinal research and the development of theoretically-informed measures of family work are needed to advance the field.


The anchor cell initiates dorsal lumen formation during C. elegans vulval tubulogenesis.
Tubulogenesis and lumen formation are critical to the development of most organs. We study Caenorhabditis elegans vulval and uterine development to probe the complex mechanisms that mediate these events. Development of the vulva and the ventral uterus is coordinated by the inductive cell-signaling activity of a gonadal cell called the anchor cell (AC). We demonstrate that in addition to its function in specifying fate, the AC directly promotes dorsal vulval tubulogenesis. Two types of mutants with defective anchor cell behavior reveal that anchor cell invasion of the vulva is important for forming the toroidal shape of the dorsal vulval cell, vulF. In fos-1 mutants, where the AC cannot breakdown the basement membranes between the gonad and the vulva, and in mutants in unc-6 netrin or its receptor unc-40, which cause AC migration defects, the AC fails to invade the vulva and no lumen is formed in vulF. By examining GFP markers of dorsal vulval cell fate, we demonstrate that fate specification defects do not account for the aberrant vulF shape. We propose that the presence of the AC in the center of the developing vulF toroid is required for dorsal vulval lumen formation to complete vulval tubulogenesis.


Hypopyon in the context of tuberculous uveitis.
An 86-year-old man presented with blurred vision and pain in the left eye. A slitlamp examination revealed anterior uveitis with hypopyon. During the investigation of the uveitis, the diagnosis of tuberculosis was confirmed. Hypopyon is a rare manifestation of uveitis due to tuberculosis.


Cost-effectiveness for KTE-X19 CAR T therapy for adult patients with relapsed/refractory mantle cell lymphoma in the United States.
The objective of this study is to estimate the cost-effectiveness of KTE-X19 versus standard of care (SoC) in the treatment of relapsed/refractory (R/R) mantle cell lymphoma (MCL) patients from a US healthcare perspective. A three-state partitioned-survival model (pre-progression, post-progression, and death) with a cycle length of 1 month was used to extrapolate progression-free and overall survival (OS) over a lifetime horizon. Due to the long tail of the OS curve, OS was modeled applying a mixture-cure methodology, using the assumption that patients whose disease had not progressed after 5 years experienced long-term remission. Population inputs were derived from the ZUMA-2 trial. This was also the source of KTE-X19 efficacy and safety data, while this data was obtained from the literature for SoC. Costs and resource use inputs were derived from the published literature and publicly available data sources. Health state utilities were derived from the ZUMA-2 trial (NCT02601313), applying the US tariff. Adverse event disutilities were derived from the published literature. Costs and health outcomes were discounted at 3% per year. The model estimated expected life years (LY), quality-adjusted life years (QALY), and total costs for KTE-X19 vs SoC. Deterministic and probabilistic sensitivity analyses were performed. Median survival was 9.71 years for KTE-X19 and 2.13 for SoC. Discounted LYs, QALYs, and lifetime costs were 8.99, 7.39, and $693,832 for KTE-X19 vs 4.47, 3.65, and $574,263 for SoC, respectively. The KTE-X19 vs SoC cost per QALY was $31,985. The most influential model parameter was the utility for patients with long-term remission. At a willingness-to-pay threshold of $150,000 per QALY, the probability that KTE-X19 was cost-effective was 99%. The treatment of R/R MCL with KTE-X19 presents a potentially cost-effective alternative to the current SoC, deriving its value from incremental survival and health-related quality-of-life benefits.


Whole-body vibration training effect on physical performance and obesity in mice.
The purpose of this study was to verify the beneficial effects of whole-body vibration (WBV) training on exercise performance, physical fatigue and obesity in mice with obesity induced by a high-fat diet (HFD). Male C57BL/6 mice were randomly divided into two groups: normal group (n=6), fed standard diet (control), and experimental group (n=18), fed a HFD. After 4-week induction, followed by 6-week WBV of 5 days per week, the 18 obese mice were divided into 3 groups (n=6 per group): HFD with sedentary control (HFD), HFD with WBV at relatively low-intensity (5.6 Hz, 0.13 g) (HFD+VL) or high-intensity (13 Hz, 0.68 g) (HFD+VH). A trend analysis revealed that WBV increased the grip strength in mice. WBV also dose-dependently decreased serum lactate, ammonia and CK levels and increased glucose level after the swimming test. WBV slightly decreased final body weight and dose-dependently decreased weights of epididymal, retroperitoneal and perirenal fat pads and fasting serum levels of alanine aminotransferase, CK, glucose, total cholesterol and triacylglycerol. Therefore, WBV could improve exercise performance and fatigue and prevent fat accumulation and obesity-associated biochemical alterations in obese mice. It may be an effective intervention for health promotion and prevention of HFD-induced obesity.


Differences in xanthotoxin metabolites in seven mammalian liver microsomes.
Xanthotoxin, abundantly occurring in fruits, vegetables, grapefruit juice and oils, is widely used in medicine for the treatment of psoriasis and vitiligo. Xanthotoxin possesses the ability to inhibit mechanism-based cytochrome P450 (CYP450)-mediated activities in rats and mice. Furthermore, it time-dependently obstructs a number of CYP450-mediated functions in humans. CYP450 enzymes are most abundant in the liver and induce metabolic activation of numerous xenobiotic compounds. The present study aimed to identify the similarities and differences in xanthotoxin metabolism in liver microsomes of 7 mammalian species, including human liver microsomes (HLM), Rhesus monkey liver microsomes (RMLM), Cynomolgus monkey liver microsomes (CMLM), Sprague Dawley rat liver microsomes (RLM), mouse liver microsomes (MLM), Dunkin Hartley guinea pig liver microsomes (PLM) and Beagle dog liver microsomes (DLM). Ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometric analysis was used to determine the metabolites. A total of 3 metabolites were detected in RMLM, CMLM and RLM. Furthermore, two metabolites were observed in MLM, HLM, PLM and DLM. By analyzing the type and quantity of metabolites, the metabolism of xanthotoxin in MLM was indicated to be most similar to that in HLM. The metabolic transformations of xanthotoxin in the liver microsomes of the 7 species were analyzed in further detail. On the whole, the results of the present study provide a deeper understanding of the metabolic patterns of xanthotoxin in liver microsomes of different species, which may prove to be advantageous regarding the metabolic mechanisms of action of xanthotoxin. Further insight into drug metabolism with respect to different species will also aid in the selection of appropriate animal models for further research.


Children's problems predict adults' DSM-IV disorders across 24 years.
The goal of this study was to determine continuities of a broad range of psychopathology from childhood into middle adulthood in a general population sample across a 24-year follow-up. In 1983, parent ratings of children's problems were collected with the Child Behavior Checklist (CBCL) in a general population sample of 2,076 children and young adolescents aged 4 to 16 years. In 2007, 24 years later, 1,339 of these individuals were reassessed with the CIDI, a standardized DSM-IV interview. We used univariate logistic regression analyses to determine the associations between children's problems and adults' psychiatric disorders. Parent reported total problems scores in the deviant range (>85th percentile) predicted disruptive disorders in adulthood (odds ratio [OR] = 1.7, 95% confidence interval [95% CI] = 1.1-2.8). Adjusted for sex, age, and socioeconomic status in all analyses, deviant levels of parent-reported childhood anxiety predicted anxiety disorders in middle adulthood (OR = 1.6, 95% CI = 1.0-2.5). Conduct problems (i.e., cruelty to animals, lies) predicted both mood disorders (OR = 2.3, 95% CI = 1.1-4.8) and disruptive disorders (OR 2.1, 95% CI = 1.3-3.4), whereas oppositional defiant problems predicted only mood disorders (OR = 2.3, 95% CI = 1.0-5.2). Attention-deficit/hyperactivity problems did not predict any of the DSM-IV disorders in adulthood (OR = 0.8, 95% CI = 0.5-1.2). Children with psychopathology are at greater risk for meeting criteria for DSM-IV diagnoses in adulthood than children without psychopathology, even after 24 years. Moreover, different types of continuities of children's psychopathology exist across the lifespan. We found that anxious children, oppositional defiant children, and children with conduct problems are at greater risk for adult psychopathology. Effective identification and treatment of children with these problems may reduce long-term continuity of psychopathology.


Butyrivibrio spp. and other xylanolytic microorganisms from the rumen have cinnamoyl esterase activity.
High concentrations of hydroxycinnamic acids in the hemicellulosic fraction of dry season tropical grasses may influence the rate of microbial degradation of arabinoxylans by ruminant animals. The ability of 22 strains of Butyrivibrio fibrisolvens, other ruminal bacteria (Ruminococcus albus SY3, Ruminococcus flavefaciens RF1,Prevotella ruminicola AR20) and the ruminal phycomycete Neocallimastix patriciarum CX to digest the tropical grass Heteropogon contortus(spear grass) and hydrolyse esterified ferulic and p-coumaric acid was examined. Significant digestion (8-36%) of spear grass occurred with the B. fibrisolvens strains H17c, A38, LP92-1-1, 49,R. albus SY3 and N. patriciarum. Hydrolysis of ester-linked ferulic and p-coumaric acid occurred with all organisms except B. fibrisolvens strains GS113, OB156 and LP1028 and P. ruminicola AR20. The ratio of ferulic to p-coumaric acid hydrolysed by different strains of Butyrivibrio spp. varied markedly from 0.96 for AR 51 to 0.16 for A38. Butyrivibrios which were fibrolytic (H17c and A38) had higher extracellular cinnamoyl esterase activity than bacteria that did not digest spear grass fibre (LP 91-4-1 and AR 20) which had low activities or only produced cell associated enzyme. Cell associated and extracellular esterase activity were induced when Butyrivibrio spp. strains H17c, A38 and E14 and the Ruminococcus spp. were grown on birchwood xylan but induction did not occur to the same extent with N. patriciarum. This is the first reported observation of cinnamoyl esterase activity in the genus Ruminococcus. The fungus N. patriciarum had significantly higher digestibility of spear grass and solubilisation of phenolic acids than the bacteria. The study shows that high levels of extracellular cinnamoyl esterases are characteristic of a selection of fibre-degrading ruminal bacteria and fungi which probably indicates that these enzymes are common amongst xylanolytic ruminal microorganisms.


(-)-Epicatechin Improves Vasoreactivity and Mitochondrial Respiration in Thermoneutral-Housed Wistar Rat Vasculature.
Cardiovascular disease (CVD) is a global health concern. Vascular dysfunction is an aspect of CVD, and novel treatments targeting vascular physiology are necessary. In the endothelium, eNOS regulates vasodilation and mitochondrial function; both are disrupted in CVD. (−)-Epicatechin, a botanical compound known for its vasodilatory, eNOS, and mitochondrial-stimulating properties, is a potential therapy in those with CVD. We hypothesized that (−)-epicatechin would support eNOS activity and mitochondrial respiration, leading to improved vasoreactivity in a thermoneutral-derived rat model of vascular dysfunction. We housed Wistar rats at room temperature or in thermoneutral conditions for a total of 16 week and treated them with 1mg/kg body weight (−)-epicatechin for 15 day. Vasoreactivity, eNOS activity, and mitochondrial respiration were measured, in addition to the protein expression of upstream cellular signaling molecules including AMPK and CaMKII. We observed a significant improvement of vasodilation in those housed in thermoneutrality and treated with (−)-epicatechin (p < 0.05), as well as dampened mitochondrial respiration (p < 0.05). AMPK and CaMKIIα and β expression were lessened with (−)-epicatechin treatment in those housed at thermoneutrality (p < 0.05). The opposite was observed with animals housed at room temperature supplemented with (−)-epicatechin. These data illustrate a context-dependent vascular response to (−)-epicatechin, a candidate for CVD therapeutic development.


Morphologic changes in pulmonary vasculature with arteriographic correlation.
During fetal life the pulmonary circulation is one of high resistance. Soon after birth with the onset of breathing and thereafter, sequential structural changes in pulmonary vasculature take place. Several authors have reported differently on this structural remodeling. This study describes the changes in the pulmonary vasculature occurring following birth. Twenty-five cases submitted to autopsy with ages ranging from newborns up to fourteen years were studied. Postmortem arteriography was undertaken in most of the cases and arterial morphology was quantitated by histomorphometry. It was found that the thick-walled pulmonary arteries of the newborn show a reduction in medial thickness over a period of one month, the reduction being most rapid in the first three days. After one month there is no significant change in medial thickness until fourteen years of age.


Polymyalgia rheumatica and breast cancer.
Polymyalgia rheumatica is infrequently the initial manifestation of underlying malignancy. A patient is described with infiltrating ductal carcinoma of the breast presenting with left breast mass and polymyalgia rheumatica (PMR)-like symptoms. Physicians should consider an associated malignancy in PMR when patients present with atypical features such as young age, modest elevation of the sedimentation rate, and incomplete response to corticosteroids.


Oxidative stress markers: specificity and measurement techniques.
With time, increasing evidence has been obtained of the involvement of oxidative stress in the pathophysiology of several diseases and ageing. Likewise, a large number of epidemiological studies have suggested that some pathologies can be prevented or delayed to some extent by dietary changes such as increased consumption of fruits, grains and vegetables. The above mentioned studies have suggested that the measurement of oxidative stress status, coupled to measurement of antioxidant status, may serve a role in diagnosis and/or treatment. The objective of this paper is to provide a review which, owing to the extent of the available literature, is obviously not exhaustive of current and most recent methods employed for the determination of the most specific markers of DNA, lipid and protein oxidative damage.


Women's multiple uses of an overdose prevention technology to mitigate risks and harms within a supportive housing environment: a qualitative study.
North America is amidst an opioid overdose epidemic. In many settings, particularly Canada, the majority of overdose deaths occur indoors and impact structurally vulnerable people who use drugs alone, making targeted housing-based interventions a priority. Mobile applications have been developed that allow individuals to solicit help to prevent overdose death. We examine the experiences of women residents utilizing an overdose response button technology within a supportive housing environment. In October 2019, we conducted semi-structured qualitative interviews with 14 residents of a women-only supportive housing building in an urban setting where the overdose response button technology was installed. Data was analyzed thematically and framed by theories of structural vulnerability. While participants described the utility and disadvantages of the technology for overdose response, most participants, unexpectedly described alternate adoptions of the technology. Participants used the technology for other emergency situations (e.g., gender-based violence), rather than its intended purpose of overdose response. Our findings highlight the limitations of current technologies while also demonstrating the clear need for housing-based emergency response interventions that address not just overdose risk but also gender-based violence. These need to be implemented alongside larger strategies to address structural vulnerabilities and provide greater agency to marginalized women who use drugs.


(+)-Podocarpic Acid as Chiral Template in the Synthesis of Aphidicolane, Stemodane and Stemarane Diterpenoids †.
In this review the synthetic work in the field of aphidicolane, stemodane and stemarane diterpenoids, in which readily available (+)-podocarpic acid (4) was used as chiral template for the construction of their polycyclic structures, is described as it developed along the years. In the frame of this work (+)-podocarpic acid (4) was a very useful tool in a model study leading to the syntheses of tetracyclic ketones 7 and 8, models of key intermediates 5a and 6 in the syntheses of (+)-aphidicolin (1) and (+)-stemodin (2a), respectively. (+)-Podocarpic acid (4) was also converted into (+)-2-deoxystemodinone (2d), allowing confirmation of the stemodane diterpenoids absolute configuration, into (+)-aphidicol-15-ene (36) and into Stemodia chilensis tetracyclic diterpenoid (+)-19-acetoxystemodan-12-ol (2f), allowing confirmation of its structure. (+)-Podocarpic acid (4) was then extensively used in the work which led to the synthesis of (+)-stemar-13-ene (57) and (+)-18-deoxystemarin (3b). Finally, (+)-4 was converted into (+)-2-deoxyoryzalexin S (66), which made it possible to demonstrate that the structure of (+)-66 could not be attributed to a Chilean Calceolaria isolated diterpenoid to which this structure had been assigned.


Precision cancer genome testing needs proficiency testing involving all stakeholders.
To implement precision oncology, analytical validity as well as clinical validity and utility are important. However, proficiency testing (PT) to assess validity has not yet been systematically performed in Japan. To investigate the quality of next-generation sequencing (NGS) platforms and cancer genome testing prevalent in laboratories, we performed pilot PT using patient samples. We prepared genomic DNA from the cancer tissue and peripheral blood of 5 cancer patients and distributed these to 15 laboratories. Most participating laboratories successfully identified the pathogenic variants, except for two closely located KRAS variants and 25 bp delins in EGFR. Conversely, the EGFR L858R variant was successfully identified, and the allele frequency was similar for all the laboratories. A high DNA integrity number led to excellent depth and reliable NGS results. By conducting this pilot study using patient samples, we were able to obtain a glimpse of the current status of cancer genome testing at participating laboratories. To enhance domestic cancer genome testing, it is important to conduct local PT and to involve the parties concerned as organizers and participants.


Radical retropubic prostatectomy for prostate carcinoma; first results of the Clinic of Urology in Skopje.
The aim of this retrospective study is to present our experience and results in the management of prostate carcinoma, with radical retropubic prostatectomy, for a period of seven years. From December 1997 to April 2005, 61 radical retropubic prostatectomies for prostate carcinoma were performed at the Clinic of Urology in Skopje. Mean age of the treated patients was 66.4 years. Mean serum PSA level was 32.75 ng/ml. None of the patients had distant or bone metastases. Mean operative time was 160 minutes and from 2 to 4 units of blood were transfused intra and postoperatively. Mean follow up time was 39 months. In all of 61 patients, the RRP was performed for adenocarcinoma of the prostate. The pathological findings postoperatively showed the following pTNM grade: pT2a in 8, pT2b in 10, pT3a in 10, pT3b in 27and pT4 in 6 patients. Positive lymph nodes were found in 14 cases. Intraoperative complications occurred in 6 patients. Early postoperative complications were seen in 12 patients. Urine leakage was seen in 2 patients, incontinence (day and night) in 8 and pulmonary embolia in 2 patients. Late postoperative complications occurred in 11 patients. Stenosis of the vesicourethral anasthomosis was seen in 3 patients and incontinence (during the night only) in 8 patients. The rate of potency was not evaluated but in the last 30 cases we insisted on preservation of the neurovascular bundles in the cases that it was possible. Radical retropubic prostatectomy is the method of choice and the golden standard for treatment of organ confined prostate carcinoma in patients with long life expectancy, no neither local nor distant metastases and good overall status. With this technique complication rates are minimal, the cure rate is very big and the patients have high quality of life. The experience of the surgeon is very important since the learning curve is crucial for diminishing operative time, postoperative complications and blood transfusions.


Cytoprotection by inhaled carbon monoxide before cardiopulmonary bypass in preclinical models.
Although a potentially toxic gaseous molecule, carbon monoxide recently gains rising scientifically and clinical interest as its beneficial effects and mechanisms of action are defined substantially in various in vitro and in vivo experiments. Its anti-inflammatory, anti-apoptotic and anti-proliferative properties but its increasing impact concerning numerous disease models in means of protection, well describe this gas as a new and challenging therapeutic alternative. In this review, we focus on the extensively analyzed advantageous value of pre- and postconditioning with inhaled carbon monoxide in the context of lung and kidney injury, induced by the low perfusion during and after cardiopulmonary bypass. Mechanisms like the heat shock response as well as an expanded view regarding toxicity and side effects are described broadly.


Assessing the 'relative value' of diabetic patients treated through an incentivized, corporate compliance model.
Primary Care clinics in the United States continue to incentivize doctors to adhere to clinical guidelines regarding record keeping and managing specific patient disorders. This paper offers a case study of a US physician working in a system of total compliance. This narrative will illustrate how a specific system has emerged that pays doctors an end-of-year bonus for achieving compliance in four specific areas: record keeping, service hours, customer satisfaction surveys, and maintaining tight control of diabetic patients. In particular, special attention is paid to the emphasis on 'the numbers' within the corporate compliance model, and specifically, the relative value units (RVUs) used for structuring billing, labeling patients, and organizing the day-to-day activities of doctors. Although incentivized models of compliance have proved effective in managing both doctors and patients, especially in the UK, 'gaming' the system can occur. This paper identifies one example of how patients assume a hidden risk within this model by potentially being labeled noncompliant by having the wrong numbers, even when receiving good clinical care and acting medically compliant.


Characterization of an exception to the 'even-electron rule' upon low-energy collision induced decomposition in negative ion electrospray tandem mass spectrometry.
Electrospray-generated precursor ions usually follow the 'even-electron rule' and yield 'closed shell' fragment ions. We characterize an exception to the 'even-electron rule.' In negative ion electrospray mass spectrometry (ES-MS), 2-(ethoxymethoxy)-3-hydroxyphenol (2-hydroxyl protected pyrogallol) easily formed a deprotonated molecular ion (M-H)(-) at m/z 183. Upon low-energy collision induced decomposition (CID), the m/z 183 precursor yielded a radical ion at m/z 124 as the base peak. The radical anion at m/z 124 was still the major fragment at all tested collision energies between 0 and 50 eV (E(lab)). Supported by computational studies, the appearance of the radical anion at m/z 124 as the major product ion can be attributed to the combination of a low reverse activation barrier and resonance stabilization of the product ions. Furthermore, our data lead to the proposal of a novel alternative radical formation pathway in the protection group removal of pyrogallol.


Dual anti-platelet therapy after coronary drug-eluting stent implantation and surgery-associated major adverse events.
Surgery may necessitate interruption of dual antiplatelet therapy (DAPT) within the first year after coronary drug-eluting stent (DES) implantation. We conducted a population-based cohort study to assess the rate of surgery within the first year after DES implantation, surgery-associated major adverse cardiac events (MACE), reoperation for bleeding within 30 days after surgery, and two nested case-control analyses to explore any association between preoperative antiplatelet therapy, MACE, and reoperation for bleeding. In the cohort of 22,654 patients treated with DES, 1,944 patients (8.6 %) underwent moderate- to high-risk surgery within 12 months. Of these, 62 (3.2 %) experienced MACE and 54 (2.8 %) needed reoperation for bleeding within 30 days. In the nested case-control analyses of 458 cases and controls, where 70 % (n=324) had a first generation DES, absence of preoperative antiplatelet therapy was associated with an increased MACE rate (OR 2.36, 95 % CI 1.02-5.48) compared to single antiplatelet therapy (SAPT) or DAPT. Preoperative SAPT versus DAPT showed no difference in MACE rates (OR 0.85, 95 % CI 0.30-2.40). Surgery within the first month was associated with increased MACE rate (OR 4.67, 95 % CI 2.22-9.83) compared to surgery 2-12 months after DES implantation. Absence of preoperative antiplatelet therapy did not reduce reoperation for bleeding as compared to patients on SAPT or DAPT (OR 1.32, 95 % CI 0.56-3.12). In conclusion, absence of preoperative antiplatelet therapy and surgery within the first month after DES implantation were associated with increased MACE rates.


Differential effects of halothane, enflurane, and isoflurane on Ca2+ transients and papillary muscle tension in guinea pigs.
These studies were designed to examine the effects of inhalational anesthetics on rapid changes in myocardial intracellular Ca2+ and Ca2+ sensitivity of the contractile apparatus. The effects of halothane, enflurane, and isoflurane on rapid changes in intracellular Ca2+ (Ca2+ transients as measured with bioluminescent protein aequorin) and contractile characteristics were compared in guinea pig right ventricular papillary muscles. In addition to examination of their potencies at equianesthetic concentrations, the effects of these agents on alterations in Ca2+ sensitivity at myofilaments were also investigated. The negative inotropic effects of halothane (0.65 and 1.15%) and enflurane (1.0 and 2.2%) were dose-dependent and closely related to a decrease in Ca2+ transients. In the presence of isoflurane (0.77 and 1.6%), the contractile force decreased in a dose-dependent manner, but the decrease was significantly less as compared to that with equianesthetic concentrations of halothane and enflurane. An additional feature observed in the presence of isoflurane was a dissociation between intracellular Ca2+ availability and contractile force. Although the magnitude of the Ca2+ transients did not change when the percentage of isoflurane was increased from 0.77 to 1.6, the contractile force decreased. Because of these findings, the effects of halothane (1.2%), enflurane (2.2%), and isoflurane (1.6%) on the relationship between intracellular Ca2+ and tension developed in the papillary muscle were examined in order to assess myofibrillar responsiveness to Ca2+. The results indicate that only isoflurane slightly but significantly shifted the Ca2+/isometric tension curve toward higher intracellular Ca2+ concentrations; no differences were observed in the absence and presence of equianesthetic concentrations of halothane and enflurane.(ABSTRACT TRUNCATED AT 250 WORDS)


[Clinical evaluation of chemoradiotherapy for advanced cervical cancer].
Locally advanced cervical cancer has a poor prognosis, poor survival rate, and high local failure rate. A number of questions regarding the optimal agents and schedule of concurrent chemoradiation remain unanswered. To improve the cure rate for advanced or recurrent cervix cancer, we studied intra-arterial infusion chemotherapy (IAIC) with or without radiotherapy. We analyzed 52 cases of advanced or recurrent cervical cancer treated by IAIC with or without radiotherapy. IAIC regimen was separated into two groups: group I consisted of 5-FU + MMC+/-ADM (30 cases) and group II of CDDP + MMC+/-5-FU (22 cases). The tip of the catheter was placed in the bifurcation of abdominal aorta or the bilateral internal iliac arteries (7 cases). The overall response rate (CR + PR) was 71%, 87% in patients receiving radiotherapy, 50% in those without radiotherapy, and 100% in primary cases. The five-year survival rate was 20% in primary cases, 14% in recurrent cases, 3% in group I and 38% in group II by chemotherapy regimen. Severe (more than grade III) hematological acute side effects were found in 48% of all cases, but recovered by interruption of drugs. In 7 cases in which the tip of the catheter was placed in internal iliac arteries, there were severe skin ulcers in 2 cases and severe pain of leg or gluteal region which need narcotics in 2 cases. These data suggest that IAIC mainly with cisplatin with or without radiotherapy is one of the effective treatments for advanced or recurrent cervical cancer. But we should check blood flow distribution periodically, and control the concentration of drugs. To improve the survival rate for advanced or recurrent cervical cancer, we should discuss neoadjuvant chemotherapy followed by chemoradiotherapy and maintenance systemic chemotherapy.


Image-based Abuse: Debate and Reflections on the "Iveco Case" in Spain on Twitter.
The instance of image-based abuse that ended in the victim's suicide, known as the "Iveco case," had an unprecedented social impact in Spain in 2019. This case provoked a great social reaction and became particularly viral on social networks such as Twitter. The present research investigates how this case has been dealt with through Twitter discourse. In particular, this study aimed to identify the main elements that could explain how people engaged with the problem of nonconsensual sharing of sexually explicit images in general, and with this case in particular. In total, 1,895 tweets with the word "Iveco" written in Spain were selected by streaming API, and their content was analyzed by lexical analysis using Iramuteq software (Reinert method). This software carries out an automatic lexical classification cluster analysis that groups the most significant words and text segments according to their co-occurrence. The results revealed that, on Twitter, it was stressed that the victim was a married woman with children who had practiced sexting. However, in response to this initial description, many voices also emerged that labelled this image-based abuse as gender-based online violence. Criticism was aimed at both the passivity of the company, and the attitude of hundreds of thousands of people who share the sexting video by WhatsApp groups without permission. Consequently, several feminist mobilizations emerged, framing this case within a sexist and patriarchal society and asking for accountability. However, in contrast, countermovements such as the #NotAllMen also emerged.


The preparation of tissue-type Plasminogen Activator (t-PA) containing liposomes: entrapment efficiency and ultracentrifugation damage.
In this study, a method was developed for the efficient entrapment of active tissue-type Plasminogen Activator (t-PA) into liposomes. Experimental conditions were varied to optimize t-PA entrapment: different buffer solutions were used (pH 4 and 7.5), the effect of the incubation concentrations of phospholipid (PL) and t-PA was monitored and the influence of liposome-size was examined. Furthermore, the effect of ultracentrifugation on t-PA containing liposomes was determined in the presence and absence of Tween 80. t-PA entrapment strongly depended on experimental conditions and ranged from 30 up to 90%. Almost quantitative+ (90%) entrapment (entrapment percentage defined as absolute entrapment (IU t-PA/mumol PL) divided by total incubation ratio (IU t-PA/mumol PL), times 100%) was obtained in Hepes buffer pH 7.5, devoid of arginine, with low ionic strength. Ultracentrifugation, used for removal of non-entrapped t-PA, was shown to have a damaging effect on the liposomes (especially in the presence of 0.05% Tween 80), leading to t-PA loss. However, because acceptable alternatives were not available, ultracentrifugation was used during this study. Therefore, the encapsulation-percentage values shown in this study are in fact underestimates for the true entrapment of t-PA. almost quantitative t-PA entrapment in liposomes can be achieved by selecting the proper milieu and inducing a strong interaction between t-PA and bilayer.


Implications of chemical and physical properties of desflurane for longer surgery.
Increased duration of anaesthetic administration has implications for recovery from anaesthesia, has cardiovascular effects, and potential for toxicity through metabolism and breakdown of the anaesthetics. Recovery of function after desflurane or sevoflurane anaesthesia, because of the low blood gas and tissue solubilities of these agents, is more rapid than after halothane, isoflurane or enflurane, with recovery being most rapid after desflurane. Increased duration of anaesthesia amplifies the differences in rate of recovery because of the additional anaesthetic (greater with more soluble agents) dissolved in tissues. Increased duration of anaesthesia lessens the cardiovascular depression associated with most halogenated inhaled anaesthetics including desflurane, but not isoflurane. Increased duration of anaesthesia allows for greater metabolism of anaesthetics and greater exposure to metabolites and potentially toxic breakdown products. Desflurane is the least metabolised of the available anaesthetics and is stable in soda lime and Baralyme. Thus, it has exceedingly low potential for toxicity. Sevoflurane undergoes considerable metabolism, producing free fluoride ion, with plasma concentrations proportional to dose and duration of anaesthesia exceeding 50 microM in approximately 7% of patients. In rats, the effects of a toxic breakdown product of sevoflurane, CF2 = C(CF3)OCH2F (compound A), are also dose- and duration-dependent, with lower concentrations producing toxic effects as duration of exposure increases. The clinical importance of the metabolism and in vitro breakdown of sevoflurane has still to be adequately tested.


Interprofessional and peer criticism: a side-effect of litigation?
Claims about a rising litigation rate, particularly in obstetrics, have allegedly fuelled fears of worsening relationships between obstetricians and midwives. Interviews with a number of practitioners, and others concerned with medical litigation, provided differing views about these assertions. While the fear of litigation is one element, it is probable that other often personal-factors may play a part. The overall tone of the interviews, however, suggested a significant degree of tension between obstetric and midwifery practitioners. The changing role of the midwife in contemporary maternity care also brings fresh challenges in developing healthy inter-professional relationships. At a time when litigation is believed to be ever-increasing, the existence of poor work relationships in this multi-disciplinary field may be critical.


Evaluation of Pointing Ray Techniques for Distant Object Referencing in Model-Free Outdoor Collaborative Augmented Reality.
Referencing objects of interest is a common requirement in many collaborative tasks. Nonetheless, accurate object referencing at a distance can be challenging due to the reduced visibility of the objects or the collaborator and limited communication medium. Augmented Reality (AR) may help address the issues by providing virtual pointing rays to the target of common interest. However, such pointing ray techniques can face critical limitations in large outdoor spaces, especially when the environment model is unavailable. In this work, we evaluated two pointing ray techniques for distant object referencing in model-free AR from the literature: the Double Ray technique enhancing visual matching between rays and targets, and the Parallel Bars technique providing artificial orientation cues. Our experiment in outdoor AR involving participants as pointers and observers partially replicated results from a previous study that only evaluated observers in simulated AR. We found that while the effectiveness of the Double Ray technique is reduced with the additional workload for the pointer and human pointing errors, it is still beneficial for distant object referencing.


Is it LDL particle size or number that correlates with risk for cardiovascular disease?
The role of low-density lipoprotein cholesterol (LDL-C) in the pathogenesis of cardiovascular disease (CVD) and the clinical benefit of lowering LDL-C in high-risk patients is well established. What remains controversial is whether we are using the best measure(s) of LDL characteristics to identify all individuals who are at CVD risk or if they would benefit from specific therapies. Despite the successful LDL-C reduction trials, substantial numbers of patients continue to have clinical events in the treatment groups. The size of LDL particles and assessment of the number of LDL particles (LDL-Num) have been suggested as a more reliable method of atherogenicity. Each LDL particle has one apoprotein B-100 measure attached; therefore, determination of whole plasma apoprotein B can be considered the best measure of LDL-Num. Because the cholesterol content per LDL particle exhibits large interindividual variation, the information provided by LDL-C and LDL-Num is not equivalent. Individuals with the same level of LDL-C may have higher or lower numbers of LDL particles and, as a result, may differ in terms of absolute CVD risk. LDL particle size and number provide independent measures of atherogenicity and are strong predictors of CVD.