Factors impacting on the decision of graduate entry medical school students to pursue a career in obstetrics and gynecology in Ireland.
Challenges in recruiting appropriately trained obstetricians and gynaecologists have been identified across the world. Given well documented staff shortages within obstetrics and gynaecology in Ireland, it is increasingly important to understand the factors which influence medical students to choose or reject a career in the speciality. The aim of this study was to ascertain the perceptions of final year graduate entry medical students of obstetrics and gynaecology, including the factors which may influence a student's decision to pursue in a career in the speciality. Paper-based surveys of graduate entry medical students (n = 146) were conducted at the beginning and end of a six week rotation in obstetrics and gynaecology in Ireland. Responses to the surveys pre- and post-rotation were matched and changes in career choices, merits and demerits over time were analysed. All analysis was conducted using SPSS for Windows version 25. The responses of 72 students to both questionnaires could be matched (response rate of 49.3%). No male students expressed an interest in obstetrics, gynaecology or both as a first choice of career in the pre rotation survey. Obstetrics as a first choice of career increased from 6.9% pre rotation to 19.4% post rotation (p = 0.04) and this increase was seen in male and female students. Gynaecology as a first choice increased slightly from 1.4 to 4.2% (p = 0.50) and the dual speciality increased from 6.9 to 13.9% (p = 0.23). Students identified many merits of obstetrics pre-rotation with more than 60% identifying it as exciting, interesting fulfilling and challenging. However, incompatibility with family life was cited as a demerit by 72% of respondents and 68.1% identified fear of litigation as a demerit. Participants were less positive overall about the merits of a career in gynaecology with less than 40% viewing it as exciting, fulfilling, and varied. While respondents were positive about the merits of a career in obstetrics and gynecology, concerns remain about work-life balance, career opportunities, and the high-risk nature of the specialty. These concerns should be addressed by the profession and policy makers if they wish to attract sufficient numbers to address anticipated need in the coming years. Gender differences in speciality choice were also evident. If males are to be recruited into obstetrics and gynaecology, consideration should be given to the positive impact of internship.


Severe acute respiratory syndrome (SARS): a review of the history, epidemiology, prevention, and concerns for the future.
During the first part of 2003, the world experienced the first epidemic of the 21st century with the emergence of a new and readily transmissible disease. The disease, severe acute respiratory syndrome (SARS), spread quickly and caused numerous deaths, as well as public panic. This article provides a brief review of the initial history of the epidemiology, as well as of the clinical definition, occurrence in the pediatric population, etiology, prevention, drug studies, and considerations for the future.


Neurenteric cysts with meningomyelocele or meningocele. Split notochord syndrome.
Two rare cases of neurenteric cysts with meningomyelocele and meningocele were treated. The mechanism of the development of these anomalies is discussed. It is considered that the terminal, dorsal part of the enteric fistula, which is produced between the endoderm and the ectoderm through a partially duplicated notochord in the development of the embryo, remains after obliteration of the fistula and, consequently, that the mucosa of the enteric remnant is inverted and projects through the skin of the back.


Diffusion tensor imaging of the extracorticospinal network in the brains of patients with Wilson disease.
To evaluate damage to the extracorticospinal tract in Wilson disease (WD) patients using diffusion tensor imaging (DTI). 70 patients with WD, including 50 with cerebral type and 20 with hepatic type, and 20 age-matched healthy controls were enrolled. Neurological symptoms were scored using the modified Young Scale. Patients with cerebral type WD were divided into four subgroups: those with (1) hypokinesia, (2) parkinsonism, (3) mouth and throat dystonia, and (4) psychiatric symptoms. All study subjects underwent DTI of the brain. Five regions of interest (ROIs) were chosen. Fractional anisotropy (FA) and fiber volumes between ROIs were determined, and the relationships between DTI metrics and clinical status were evaluated. FA values and fiber volumes between subcortical nuclei were lower in WD patients. Fiber volumes between the putamen (PU) and the globus pallidus (GP), substantia nigra (SN), and thalamus (TH); between the head of the caudate nucleus (CA) and the GP and TH; and between the TH and cerebellum were lower in group 1 than in the other groups of WD patients. Fiber volumes between the GP and the SN and TH were lower in group 2, and fiber volumes between the SN and TH were lower in group 3. DTI metrics differed between patients with the cerebral and hepatic types of WD. DTI can reconstruct the network of the extracorticospinal tract. Fiber projection between subcortical nuclei was abnormal in WD patients. Damage to fiber connections may correlate with neurological symptoms in WD patients.


Benzoquinoquinoxaline derivatives stabilize and cleave H-DNA and repress transcription downstream of a triplex-forming sequence.
Oligopyrimidine*oligopurine sequences with potential to form intramolecular triple helix structures (H-DNA) have been found mainly in high eukaryote genomes. However, the natural occurrence and function of H-DNA remains elusive largely because we lack appropriate reagents to demonstrate the formation of these structures in cells. We examined whether a triple-helix specific stabilizing compound, benzoquinoquinoxaline (BQQ), and its 1,10-phenanthroline derivative can be efficiently utilized to study the formation and stabilization of an intramolecular triple-helical DNA structure in growing Escherichia coli cells and in vitro. Cell uptake of BQQ was confirmed by fluorescence microscopy. A plasmid carrying an H-DNA forming sequence upstream of a reporter gene was used to assess the effects of H-DNA formation and stabilization in growing cells. The presence of the H-DNA forming sequence dramatically repressed beta-lactamase expression, and sub-growth-inhibitory doses of BQQ caused a further 40% reduction. Most importantly, repression was dependent on the triple-helix forming sequence and correlated with the addition of BQQ. As the abundance of the H-DNA forming plasmid was not affected by the addition of BQQ, the dose-dependent reduction at the protein level observed here is likely caused by repression of transcription. Finally, the triple-helix specific interaction of BQQ with the target DNA sequence was demonstrated using a triple-helix directed cleavage assay by BQQ-1,10-phenanthroline conjugate in vitro.


Genetic polymorphism in the DNA repair gene XRCC1 and susceptibility to schizophrenia.
The X-ray repair cross-complementation group 1 (XRCC1) protein plays an important role in base excision repair. A high level of XRCC1 mRNA and/or protein has been found in rat and baboon brains. An exon 10 variant at codon 399 of XRCC1 leads to an Arg to Gln amino acid change. The 399Gln allele is associated with an increased risk of several types of cancers, increased DNA adducts and chromosomal changes; therefore, it appears that the 399Gln allele may alter the role of the XRCC1 protein in DNA repair. The present case-control study was performed on 303 (223 males, 80 females) in-patients with chronic schizophrenia and 303 healthy blood donors matched to the patients by age (+/-5 years) and gender. The XRCC1 genotypes were determined using a PCR-based method. Heterozygosity (OR=1.48, 95% CI: 1.05-2.09) and homozygosity (OR=2.00, 95% CI: 1.17-3.42) for the Gln399 allele increased the risk of schizophrenia. There was a significant linear trend in risk associated with zero, one, and two 399Gln alleles. The present finding indicates that XRCC1 is a candidate gene for susceptibility to schizophrenia.


[Perparation and characterization of the monoclonal antibodies against listeriolysin O].
To prepare the monoclonal antibodies (mAbs) against listeriolysin O (LLO), which is the major virulence factor of Listeria monocytogenes. The BALB/c mice were immunized with the SDS-PAGE product of BL21(pGEX-6p-1-hly). The purified LLO-GST protein was used as antigen for detection. mAbs against LLO were prepared by using the lymphocyte hybridoma technique. The specificity of mAbs was characterized by Dot-ELISA and Western blot. Three hybridoma cell lines named 3B6, 4D1 and 5D10 secreting mAbs against LLO were obtained. The immunoglobulin subclasses of the mAbs were IgG1. The ELISA titer of the ascitic fluids of 3B6, 4D1 and 5D10 was 1:200,000, 1:200,000 and 1:100,000, respectively. Western blot analysis confirmed the three mAbs reacted on fusion protein LLO-GST but didn't react on protein GST. Dot-ELISA proved the three mAbs only react on the bacteria expressing LLO. The successful preparation of three mAbs specific to protein LLO lays a foundation for further study of the biological characteristics of LLO and the pathogenesis of Listeria monocytogenes.


Little known Orphninae (Coleoptera, Scarabaeidae) collected by the Madagascan expeditions of the California Academy of Sciences.
New locality records for Madecorphnusniger Frolov, 2010, Madecorphnusfalcatus Paulian, 1992, Madecorphnussimplex Frolov, 2010, and Triodontusitremoi Paulian, 1977, are given. Endophallus armature of Madecorphnusniger Frolov, 2010, is described and illustrated.


Endohedral metal-nitride cluster ordering in metallofullerene-NiII(OEP) complexes and crystals: a theoretical study.
The ordering of endohedral clusterfullerenes Sc3N@C80 and YSc2N@C80 co-crystallized with Ni(OEP) and isolated complexes with Ni(OEP) have been investigated theoretically. Having used multiple orientations of M3N clusters inside the cages with Fibonacci sampling, we describe the effect of intermolecular interactions on the orientation of the endohedral cluster.


Molecular, serological and in vitro culture-based characterization of Bourbon virus, a newly described human pathogen of the genus Thogotovirus.
In June of 2014, a previously healthy man from Kansas with a recent history of tick exposure died from complications related to an illness marked by fever, thrombocytopenia and leukopenia. An isolate was derived from the blood of this patient during the course of diagnostic testing. This isolate was subsequently identified as a novel orthomyxovirus of the genus Thogotovirus by next generation sequencing and was named Bourbon virus after the patient's county of residence. To support research and diagnostic aims, we provide a basic description of Bourbon virus at both the molecular and serological levels. Furthermore, to preliminarily identify potential host and vector range associations we have characterized the growth kinetics of Bourbon virus in a variety of vertebrate and invertebrate cell lines. Bourbon virus was subjected to next generation-high throughput sequencing, phylogenetic, and basic structural protein analyses as well as 2-way plaque reduction neutralization assays. Also, we inoculated a variety of cell types with Bourbon virus and evaluated the growth kinetics by determining viral titers in the supernatants taken from infected cells over time. Bourbon virus possesses 24-82% identity at the amino acid sequence level and low serological cross-reactivity with other Thogotoviruses. In vitro growth kinetics reveal robust replication of Bourbon virus in mammalian and tick cells. Molecular and serological characterizations identify Bourbon virus as a novel member of the genus Thogotovirus. Results from cell culture analyses suggest an association between Bourbon virus and mammalian and tick hosts.


Genetic risk modifies the effect of long-term fine particulate matter exposure on coronary artery disease.
Although both environmental and genetic factors were linked to coronary artery disease (CAD), the extent to which the association of air pollution exposure with CAD can be influenced by genetic risk was not well understood. A total of 41,149 participants recruited from the project of Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) were included. Genetic risk scores of CAD were constructed based on 540 genetic variants. Long-term PM2.5 exposures were assessed by adopting satellite-based PM2.5 estimations at 1-km resolution. We used stratified Cox proportional hazards regression model to examine the impact of PM2.5 exposure and genetic risk on CAD risk, and further analyzed modification effect of genetic predisposition on association between PM2.5 exposure and CAD risk. During a median of 13.01 years of follow-up, 1,373 incident CAD events were observed. Long-term PM2.5 exposure significantly increased CAD risk, and the hazard ratios (HRs) [95% confidence intervals (CIs)] were 1.27 (1.05-1.54) and 1.95 (1.57-2.42) among intermediate and high PM2.5 exposure groups compared to low PM2.5 exposure group. The relative risks of CAD were 40% (HR: 1.40, 95%CI: 1.18-1.66) and 133% (HR: 2.33, 95%CI: 1.94-2.79) higher among individuals at intermediate and high genetic risk than those at low genetic risk. Compared with individuals with both low genetic risk and low PM2.5 exposure, those with high genetic risk and high PM2.5 exposure had highest CAD risk, with HR of 4.37 (95%CI: 3.13-6.11). We observed significant multiplicative (P < 0.001) and additive interaction [relative excess risk due to interaction (95%CI): 2.75 (1.32-4.20); attributable proportion due to interaction (95%CI): 0.56 (0.42-0.70)] between genetic risk and PM2.5 exposure on CAD. This study provided evidence that long-term PM2.5 exposure might increase CAD risk, especially among people at high genetic risk. Our findings highlighted the importance of taking strategies on air quality improvement to cardiovascular disease prevention.


Developmental transformation of dendritic arbors in mouse whisker thalamus.
Neurons in slices though the somatosensory thalamus of postnatal day 6 and adult mice were injected with Lucifer yellow. Dendritic arbors on postnatal day 6 are confined to single barreloids (single whisker representations); in adults they are seven times longer, extending beyond their barreloid to adjacent barreloids. The postnatal transformation of dendritic arbors by total process growth and extension to adjacent barreloids suggests a developmental change in the role of these cells from instructing whisker pattern formation to integrating sensory information from more than one whisker.


Target trial emulation of aspirin after diagnosis of colorectal polyps.
Previous research on the potential chemoprotective effect of aspirin for colorectal cancer (CRC) shows conflicting results. We aimed to emulate a trial of aspirin intiation in individuals with incident polyps. We identified individuals registered with their first colorectal polyp in the nationwide gastrointestinal ESPRESSO histopathology cohort in Sweden. Individuals aged 45-79 years diagnosed with colorectal polyps 2006-2016 in Sweden without CRC or contraindications for preventive aspirin (cerebrovascular disease, heart failure, aortic aneurysms, pulmonary emboli, myocardial infarction, gastric ulcer, dementia, liver cirrhosis, or any other metastatic cancer) registered until the month of first polyp detection were eligible. Using duplication and inverse probability weighting, we emulated a target trial of aspirin initiation within 2 years of initial polyp detection. The main outcome measures were incident CRC, CRC mortality and all-cause mortality registered until 2019. Of 31,633 individuals meeting our inclusion criteria, 1716 (5%) initiated aspirin within 2 years of colon polyp diagnosis. Median follow-up was 8.07 years. The 10-year cumulative incidence in initiators versus non-initiators was 6% versus 8% for CRC incidence, 1% versus 1% for CRC mortality and 21% versus 18% for all-cause mortality. The corresponding hazard ratios were 0.88 (95% confidence interval, 95%CI = 0.86-0.90), 0.90 (95%CI = 0.75-1.06) and 1.18 (95%CI = 1.12-1.24). Aspirin initiation in individuals with polyp removal was linked to 2% lower cumulative incidence of CRC after 10 years but did not alter CRC mortality. We also observed a 4% increased risk difference of all-cause mortality at 10 years after the initiation of aspirin.


The long-term trend of PM2.5-related mortality in China: The effects of source data selection.
Quantification of PM2.5 exposure and associated mortality is critical to inform policy making. Previous studies estimated varying PM2.5-related mortality in China due to the usage of different source data, but rarely justify the data selection. To quantify the sensitivity of mortality assessment to source data, we first constructed state-of-the-art PM2.5 predictions during 2000-2018 at a 1-km resolution with an ensemble machine learning model that filled missing data explicitly. We also calibrated and fused various gridded population data with a geostatistical method. Then we assessed the PM2.5-related mortality with various PM2.5 predictions, population distributions, exposure-response functions, and baseline mortalities. We found that in addition to the well documented uncertainties in the exposure-response functions, missingness in PM2.5 prediction, PM2.5 prediction error, and prediction error in population distribution resulted to a 40.5%, 25.2% and 15.9% lower mortality assessment compared to the mortality assessed with the best-performed source data, respectively. With the best-performed source data, we estimated a total of approximately 25 million PM2.5-related mortality during 2001-2017 in China. From 2001 to 2017, The PM2.5 variations, growth and aging of population, decrease in baseline mortality led to a 7.8% increase, a 42.0% increase and a 24.6% decrease in PM2.5-related mortality, separately. We showed that with the strict clean air policies implemented in 2013, the population-weighted PM2.5 concentration decreased remarkably at an annual rate of 4.5 μg/m3, leading to a decrease of 179 thousand PM2.5-related deaths nationwide during 2013-2017. The mortality decrease due to PM2.5 reduction was offset by the population growth and aging population.


Limitations of the open loop gain concept in studies of respiratory control.
A steady state mathematical model was used to study the limitations of applying the open loop gain concept to the ventilatory control system. Open loop gain is a term used in the study of linear control systems and is an indicator of how well the controlled variable is regulated. The model contained descriptions of the O2 and CO2 control systems as well as their interactions. Disturbances to the system were modelled as occurring via inspired air, metabolic rate and ventilation. The ventilatory response to hypoxia was simulated for (a) hypocapnic hypoxia, (b) normocapnic hypoxia (PaCO2 = 40 torr) and (c) hypercapnic hypoxia (PaCO2 = 45 torr). The open loop gains of the O2 and CO2 loops were calculated at each operating point. In addition, the sensitivity of the controlled variable to disturbances to the loop were also compared. It was observed that open loop gain did not completely describe the characteristics of the ventilatory control system. This was due to the fact that the ventilatory system is nonlinear and the regulatory ability of the ventilatory system depends on the route of the disturbance, and (2) open loop gain ignores the interactions of the CO2 and O2 loops, which can be substantial.


The function of Glu338 in the catalytic triad of the carbamoyl phosphate synthetase amidotransferase domain.
The synthesis of carbamoyl phosphate by the mammalian multifunctional protein, CAD, involves the concerted action of the 40 kDa amidotransferase domain (GLN), that hydrolyzes glutamine and the 120 kDa synthetase (CPS) domain that uses the ammonia, thus produced, ATP and bicarbonate to make carbamoyl phosphate. The separately cloned GLN domain has very low activity due to a reduction in kcat and an increase in Km but forms a hybrid complex with the isolated Escherichia coli CPS subunit. The hybrid has full glutamine-dependent catalytic activity and a functional interdomain linkage. The mammalian-E. coli hybrid was used to investigate the functional consequence of replacing His336 and Glu338, two residues postulated to participate in catalysis as part of a catalytic triad. The mutant mammalian GLN domains formed stable complexes with the E. coli CPS subunit, but the catalytic activity was severely impaired. While the His336Asn mutant does not form measurable amounts of the gamma-glutamyl thioester, the steady state concentration of the intermediate with the Glu338Gly mutant was comparable to the wild type hybrid because both the rate of formation and breakdown of the thioester are reduced. This result is consistent with the postulated role of Glu338 in maintaining His336 in the optimal orientation for catalysis and suggests a mechanism for the GLN CPS functional linkage.


The health risks of smoking. The Framingham Study: 34 years of follow-up.
This study summarizes the effects of both the rate and the cumulative dose of cigarette smoking on the health of the original Framingham cohort, 5209 individuals aged 30 to 62 years at entry. After 34 years of follow-up, it was observed that cigarette smoking was the prime determinant of chronic cough, and reduced both forced vital capacity and the 1-second forced expiratory volume. A significant relationship was observed between cigarette smoking and the incidence of cancer of the lung, stroke and transient ischemic attacks, intermittent claudication, and total cardiovascular disease, and most especially the average annual death rate. Cigarette smoking was significantly related to coronary heart disease in men 45 to 64 years old, although not related in women or older men. The data confirm and extend the evidence of the detrimental influence of cigarette smoking on health.


Increased risk for ascending aortic dilatation in patients with complex compared to simple aortic coarctation.
Aortic coarctation (CoA) occurs as a "simple" isolated disorder, and in a more "complex" form, combined with associated congenital cardiac abnormalities. Long term outcome of all CoA patients may be complicated by dilatation of the thoracic aorta. The aim of this study was to quantify progressive aortic dilatation, and identify determinants for progressive aortic dilatation. Cardiovascular Magnetic Resonance Imaging (CMR) and echocardiographic data of 93 CoA patients were analyzed retrospectively on the progression, and determinants, of progressive thoracic aortic dilatation. Outcome of simple- versus complex CoA patients were compared. 93 CoA patients (mean age 39 ± 12 years, male 59%) were followed with CMR (follow-up 5.3 ± 1.8 years). Twenty-eight patients were classified as simple- and 68 as complex CoA. The mean progression rate of thoracic aortic dilatation was highest in the ascending aorta with 2.2 ± 2.0mm/5 years (range 0-7.2mm/5 years). History of VSD (β=1.77, P=0.004) and an increased left ventricular mass index (β=0.02, P=0.04) were associated with progressive ascending aortic dilatation. Complex CoA patients show an increased progression rate compared to simple CoA patients with 2.4mm/5 years versus 1.5mm/5 years respectively. (P=0.03). Adult post-coarctectomy patients show an increased mean progression rate of ascending aortic dilatation with 2.2mm/5 years. The progression rate of ascending aortic dilatation is increased in complex CoA patients, as compared to simple CoA patients. These findings point towards a more comprehensive genetic subset of patients with an increased risk for progressive ascending aortic dilatation.


The use of pilocarpine hydrochloride to prevent xerostomia in a child treated with high dose radiotherapy for nasopharynx carcinoma.
A case is presented of a 10-year-old male with carcinoma of the nasopharynx with involvement of neck nodes, treated with high dose radiotherapy after four cycles of chemotherapy. Because of concern about causing xerostomia with its attendant problems, pilocarpine hydrochloride, 5 mg orally three times daily, was initiated at the onset of radiotherapy. Radiotherapy was well tolerated and at 7 months postradiotherapy, there was no evidence of residual or recurrent tumour and no xerostomia. Pilocarpine hydrochloride should be considered in children who are to receive high dose radiotherapy to the head and neck region which would include the parotid glands.


Effect of electroacupuncture on TRPM7 mRNA expression after cerebral ischemia/reperfusion in rats via TrkA pathway.
The effect of electroacupuncture (EA) on TRPM7 mRNA expression of focal cerebral ischemia in rats and further the role of EA in the relationship between TRPM7 and trkA pathway was investigated. Thirty SD rats were randomly divided into 5 groups : normal group, ischemia/reperfusion group, EA treated group (ischemic rats with EA treatment), TE infusion group (ischemic rats with EA treatment and TE buffer infusion), AS-ODN group (ischemic rats with EA treatment and antisense trkA oligonucleotide infusion). The stroke animal model was established by the modified method of middle cerebral artery occlusion. Antisense trkA oligonucleotide that blocked NGFs effects was injected into cerebroventricle before EA. The TRPM7 mRNA was detected by RT-PCR method. The results showed that there were low TRPM7 mRNA levels in cortex and hippocampus in normal group. Compared with normal group, TRPM7 mRNA expression was increased significantly in ischemia/reperfusion group (P<0.05). A significant reduction in the expression of TR-PM7 mRNA was found in EA treated group in contrast to ischemia/reperfusion group (P<0.05). The expression of TRPM7 mRNA in AS-ODN group was remarkably increased compared with EA treated group and TE infusion group (P<0.05). The results indicated that TRPM7 channels in the ischemic cortex and hippocampus in rats might play a key role in ischemic brain injury. EA could reverse the overexpression of TRPM7 in cerebral ischemia/reperfusion rats. And the inhibitory effect of EA on TRPM7 channels might be through trkA pathway.


In vivo cholesterol kinetics in apolipoprotein E-deficient and control mice.
The in vivo total body cholesterol transport of homozygous apoE-deficient (-/-) and control (+/+) mice was evaluated by compartmental analysis of plasma cholesterol decay. Body cholesterol fractional catabolic rates of chow fed mutants were less (-/-, 0.17 +/- 0.02; +/+, 0.51 +/- 0.06 day-1) and body cholesterol contents greater (-/-, 68 +/- 5; +/+, 48 +/- 5 mumol) than controls. The body cholesterol expansion of the chow-fed mutant was extracellular with at least half in plasma. Cholesterol transport, i.e., the mass entering, moving through, and exiting the body each day, was similar (-/-, 6.9 +/- 0.7; +/+, 8.5 +/- 0.9 mumol/day) for homozygotes and controls on chow, and both tripled with cholesterol feeding. Differing from controls, however, mutants had considerable expansions of plasma and body cholesterol (-/-, 166 +/- 21; +/+, 59 +/- 11 mumol) with increments in peripheral tissue cholesterol contents. Cholesterol feeding increased control hepatic cholesterol without a change in plasma, whereas mutants had large increments in plasma cholesterol with no change in liver. Consistent with impaired hepatic uptake of cholesterol, mutants had much slower plasma clearance of lipoprotein cholesterol, as well as slower transfer to catabolic pools than normals. Treatment of homozygotes with lovastatin doubled both plasma cholesterol concentration and body cholesterol transport indicating the importance of apoE-dependent cell cholesterol transfer in synthetic down-regulation with this agent. These data indicate that mice lacking apoE have lower affinity hepatic uptake of plasma remnant cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)


Reversible inhibition of LCAT by penicillins. Kinetic and mechanistic investigations.
A simple and rapid method is described for labelling serum lipoproteins with 3H cholesterol. According to the tracer data as well as cholesterol analyses, the velocity of ester formation in rat sera and beta-lipoprotein-depleted human sera decreased during incubations as a first order reaction. This suggests a level of chemical activity for cholesterol far below the Km of the enzyme. The reversible inhibition by three different penicillins showed a dependency of the inhibitor concentration which supports this notion. 50 per cent inhibition of the rat enzyme was obtained with 0.1 mM dicloxacillin, 0.3 mM benzylpenicillin, and 1.4 mM methicillin (water phase concentrations). The human enzyme was about 10-fold less sensitive. The mechanism of penicillin inhibition, investigated by stripping-recombination experiments with the 20-fold purified rat enzyme chromatographed on penicillin-loaded Sephadex G-25 columns, was found to be a dissociation of the enzyme into two components, an inactive apoenzyme and a coenzyme with a molecular weight below 1000.


Significance of trough monitoring for tacrolimus blood concentration and calcineurin activity in adult patients undergoing primary living-donor liver transplantation.
Tacrolimus pharmacokinetics and calcineurin activity in peripheral blood mononuclear cells (PBMCs) were investigated in adult patients undergoing primary living-donor liver transplantation (LDLT) in order to clarify the significance of monitoring the tacrolimus blood trough concentration during the early post-transplantation period. Fourteen patients were enrolled in this study, and time-course data following the oral administration of a conventional tacrolimus formulation twice daily were obtained at 1 and 3 weeks post-transplantation. The concentration of tacrolimus in whole blood and calcineurin activity in PBMCs were measured. The apparent clearance of tacrolimus significantly increased at 3 weeks versus 1 week post-transplantation, although the trough concentration did not significantly differ at these time points. The concentration at each sampling time, except at 1 h post-dose, correlated well with the area under the concentration-time curve from 0 to 12 h (AUC(0-12)). Neither the concentration at the trough time point nor AUC(0-12) was correlated with the area under the calcineurin activity-time curve from 0 to 12 h; however, calcineurin activity at the trough time point was strongly correlated with the latter (r (2) > 0.92). Based on these results, trough concentration monitoring can be considered an appropriate procedure for routine tacrolimus dosage adjustment in adult LDLT patients. Monitoring of calcineurin activity at the trough time point was also found to be potentially useful for predicting the immunological status of the patient during the tacrolimus dosing interval.


[Scanning electron microscopy study of autologous vein and fascia lata before and one year after implantation into the arterial blood stream].
The present communication deals with scanning electronmicroscopical changes of autologous vein and autologous fascia lata, which were used as arterial implants. We examined material, which could be removed during reoperation for vascular occlusion. After one year, the surface exposed to the blood stream shows a homogenous layer of fibrin. Whilst the elastic fibers of fascia lata-transplants have nearly completely disappeared, we can still find them in the vein. This might be the essential reason for the longer survival of venous implants into the arterial blood stream.


Effort-reward imbalance and depression in Japanese medical residents.
The effort-reward imbalance is an important psychosocial factor which is related to poor health among employees. However, there are few studies that have evaluated effort-reward imbalance among medical residents. The present study was done to determine the association between psychosocial factors at work as defined by the effort-reward imbalance model and depression among Japanese medical residents. We distributed a questionnaire to 227 medical residents at 16 teaching hospitals in Japan at the end of August 2005. We asked participants to answer questions which included demographic information, depressive symptoms, effort-reward imbalance, over-commitment and social support. Depression was evaluated using the Japanese version of the Center for Epidemiologic Studies-Depression (CES-D) scale. The effort-reward imbalance and over-commitment were assessed by the Effort-Reward Imbalance (ERI) questionnaire which Siegrist developed. Social support was determined on a visual analog scale. Logistic regression analysis was performed to determine the associations between effort-reward imbalance and depressive symptoms. Depressive symptoms were found in 35 (29.2%) 1st-year residents and 21 (27.6%) 2nd-year residents. The effort-reward ratio >1 (OR, 8.83; 95% CI, 2.87-27.12) and low social support score (OR, 2.77, 95% CI, 1.36-5.64) were associated with depressive symptoms among medical residents. Effort-reward imbalance was independently related to depression among Japanese medical residents. The present study suggests that balancing between effort and reward at work is important for medical residents' mental health.


Primary central nervous system vasculitis and its mimicking diseases - clinical features, outcome, comorbidities and diagnostic results - A case control study.
To compare clinical features and outcome, imaging characteristics, biopsy results and laboratory findings in a cohort of 69 patients with suspected or diagnosed primary central nervous system vasculitis (PCNSV) in adults; to identify risk factors and predictive features for PCNSV. We performed a case-control-study including 69 patients referred with suspected PCNSV from whom 25 were confirmed by predetermined diagnostic criteria based on biopsy (72%) or angiography (28%). Forty-four patients turned out to have 15 distinct other diagnoses. Clinical and diagnostic data were compared between PCNSV and Non-PCNSV cohorts. Clinical presentation was not able to discriminate between PCNSV and its differential diagnoses. However, a worse clinical outcome was associated with PCNSV (p=0.005). Biopsy (p=0.004), contrast enhancement (p=0.000) or tumour-like mass lesion (p=0.008) in magnetic resonance imaging (MRI), intrathecal IgG increase (p=0.020), normal Duplex findings of cerebral arteries (p=0.022) and conventional angiography (p 0.010) were able to distinguish between the two cohorts. In a cohort of 69 patients with suspected PCNSV, a large number (64%) was misdiagnosed and partly received treatment, since mimicking diseases are very difficult to discriminate. Clinical presentation at manifestation does not help to differentiate PCNSV from its mimicking diseases. MRI and cerebrospinal fluid analysis are unlikely to be normal in PCNSV, though unspecific if pathological. Cerebral angiography and biopsy must complement other diagnostics when establishing the diagnosis in order to avoid misdiagnosis and mistreatment. German clinical trials register: http://drks-neu.uniklinik-freiburg.de/drks_web/, Unique identifier: DRKS00005347.


Stabilisation of human telomeric quadruplex DNA and inhibition of telomerase by a platinum-phenanthroline complex.
Two new mono-substituted phenanthroline ligands and their platinum(II) square planar complexes have been prepared; one of the complexes has been shown to induce a high degree of quadruplex DNA stabilisation and to inhibit telomerase.


Validation of the A&D BP UA-1200BLE device for home blood pressure measurement according to the ISO 81060-2: 2013 standard.
The aim of this study was to validate the UA-1200BLE device using the ISO 81060-2:2013 standard. Individuals aged more than 12 years were recruited from among the outpatients and volunteers of Jichi Medical University (Tochigi, Japan). Eighty-five patients were included in the final analyses. Validation was performed using the same-arm sequence protocol as per the ISO 81060-2:2013 standard. The device performed well against the standard; the mean and SD values for the differences between device and observed systolic and diastolic blood pressure values fulfilled both criterion 1 and criterion 2 of the standard (criterion 1: -2.62±6.89 and -0.90±6.63 mmHg, respectively; criterion 2: -2.65±5.36 and -0.91±6.12 mmHg, respectively). The Bland-Altman plots did not show any systematic variation in the error. The UA-1200BLE device had a high level of accuracy and fulfilled all ISO 81060-2:2013 standard requirements in adults with a wide range of arm circumference measurements. It is therefore suitable as a wireless blood pressure monitoring tool in patients with hypertension.


Genuine stress incontinence: pathophysiology and rationale for its medical management.
Genuine stress incontinence is a condition in which increments of intra-abdominal pressure produce involuntary urine loss. The condition occurs as a result of urethral sphincteric failure in the absence of involuntary detrusor contractility. Several aspects of this dysfunction are amenable to nonsurgical treatment. These interventions are worth trying prior to proceeding for surgery.


Resting-state functional connectivity of emotion regulation networks in euthymic and non-euthymic bipolar disorder patients.
Previous functional magnetic resonance imaging studies in bipolar disorder (BD) have evidenced changes in functional connectivity (FC) in brain areas associated with emotion processing, but how these changes vary with mood state and specific clinical symptoms is not fully understood. We investigated resting-state FC between a priori regions of interest (ROIs) from the default-mode network and key structures for emotion processing and regulation in 27 BD patients and 27 matched healthy controls. We further compared connectivity patterns in subgroups of 15 euthymic and 12 non-euthymic patients and tested for correlations of the connectivity strength with measures of mood, anxiety, and rumination tendency. No correction for multiple comparisons was applied given the small population sample and pre-defined target ROIs. Overall, regardless of mood state, BD patients exhibited increased FC of the left amygdala with left sgACC and PCC, relative to controls. In addition, non-euthymic BD patients showed distinctive decrease in FC between right amygdala and sgACC, whereas euthymic patients showed lower FC between PCC and sgACC. Euthymic patients also displayed increased FC between sgACC and right VLPFC. The sgACC-PCC and sgACC-left amygdala connections were modulated by rumination tendency in non-euthymic patients, whereas the sgACC-VLPFC connection was modulated by both the current mood and tendency to ruminate. Our results suggest that sgACC-amygdala coupling is critically affected during mood episodes, and that FC of sgACC play a pivotal role in mood normalization through its interactions with the VLPFC and PCC. However, these preliminary findings require replication with larger samples of patients.


Methotrexate and sulforaphane loaded PBA-G5-PAMAM dendrimers as a combination therapy for anti-inflammatory response in an intra-articular joint arthritic animal model.
L-sulforaphane (LSF), a natural product developed from cruciferous vegetables, have shown potent anti-inflammatory effect in cancer as well as arthritis. However, the stable delivery of LSF remains a major challenge. Methotrexate (MTX) is currently the first line treatment for managing RA and is most effective in patients when used in combination with other anti-inflammatory or anti-rheumatic drugs. Here we developed phenylboronic acid-PAMAM dendrimer (PBA-G5D) nanoparticles conjugated MTX (MTX-PBA-G5D), and L-sulforaphane (LSF/PBA-G5D) loaded dendrimers. The MTX and LSF drug loading and release kinetics was analyzed using HPLC. The lipopolysaccharide (LPS) stimulated macrophages were treated with the formulations to study the inflammatory response in vitro. For in vivo studies, arthritis was induced in five-week-old female Wistar rats, and the MTX- and LSF/PBA-G5-D were injected via intra-articular injection for treatment and the arthritis reduction was scored by weight, knee diameter, and serum cytokine level measurement. The average size of the drug-nanoparticle conjugates ranged from 135 to 250 nm, with mostly cationic surface charges. The encapsulation efficiency of the drugs to the modified dendrimer was more than 60% with a slow release of drugs from the nanoparticles within 24 h at pH 7.4. Drugs in the nanoparticle formulation were biocompatible, with promising anti-inflammatory effects in vitro against LPS-activated murine macrophages. Further in vivo studies on arthritis induced female Wistar rats, revealed significant anti-arthritic effects based on the arthritic scoring from the knee diameter reading, and anti-inflammatory effects based on the serum cytokine levels. This study provides a promising strategy for utilizing PAMAM dendrimers as a nanocarrier for LSF delivery for RA therapy.


Theta oscillatory dynamics of inhibitory control, error processing, and post-error adjustments: Neural underpinnings and alcohol-induced dysregulation in social drinkers.
Alcohol intoxication impairs inhibitory control, resulting in disinhibited, impulsive behavior. The anterior cingulate cortex (ACC) plays an essential role in a range of executive functions and is sensitive to the effects of alcohol, which contributes to the top-down cognitive dysregulation. This study used a multimodal approach to examine the acute effects of alcohol on the neural underpinnings of inhibitory control, inhibition failures, and neurobehavioral optimization as reflected in trial-to-trial dynamics of post-error adjustments. Adult social drinkers served as their own controls by participating in the Go/NoGo task during acute alcohol and placebo conditions in a multi-session, counterbalanced design. Distributed source modeling of the magnetoencephalographic signal was combined with structural magnetic resonance imaging to characterize the spatio-temporal dynamics of inhibitory control in the time-frequency domain. Successful response inhibition (NoGo) elicited right-lateralized event-related theta power (4 to 7 Hz). Errors elicited a short-latency increase in theta power in the dorsal (dACC), followed by activity in the rostral (rACC), which may underlie an affective "oh, no!" orienting response to errors. Error-related theta in the dACC was associated with subsequent activity of the motor areas on the first post-error trial, suggesting the occurrence of post-error output adjustments. Importantly, a gradual increase of the dACC theta across post-error trials closely tracked improvements in accuracy under placebo, which may reflect cognitive control engagement to optimize response accuracy. In contrast, alcohol increased NoGo commission errors, dysregulated theta during correct NoGo withholding, and abolished the post-error theta enhancement of cognitive control. Confirming the sensitivity of frontal theta to inhibitory control and error monitoring, the results support functional and temporal dissociation along the dorso-rostral axis of the ACC and the deleterious effects of alcohol on the frontal circuitry subserving top-down regulation. Over time, alcohol-induced disinhibition may give rise to compulsive drinking and contribute to alcohol misuse.


Endothelium determines flow-dependent dilation of the epicardial coronary artery in dogs.
The mechanisms of epicardial coronary artery dilation after reactive hyperemia were studied in instrumented conscious dogs. A pair of ultrasonic crystals, an electromagnetic flow probe and a cuff occluder were placed on the left circumflex coronary artery in 12 mongrel dogs under sterile conditions. Reactive hyperemia after 20 s of coronary occlusion dilated the epicardial coronary artery by 120 +/- 14 micron (3.8 +/- 0.6%, p less than 0.01) from 3.167 +/- 0.345 mm. This reactive dilation was abolished by flow-limiting coronary stenosis. However, vasodilation after nitroglycerin was 168 +/- 26 micron (5.1 +/- 0.5%) and 162 +/- 27 micron (4.9 +/- 0.6%), respectively, before and after flow limitation. After removal of the endothelium by a balloon catheter, dilation of the epicardial coronary artery after reactive hyperemia was markedly attenuated to 7 +/- 4 micron (p less than 0.01 versus before denudation), despite the presence of a similar degree of reactive hyperemia. The extent of coronary dilation after nitroglycerin was unchanged before and after de-endothelialization. Thus, the endothelium contributed to reactive dilation but not to the nitroglycerin-induced dilation. The negative feedback control of coronary diameter to changes in flow velocity may relate to the regulation of coronary artery tone.


Fitting models of carcinogenesis to a case-control study of breast cancer.
Data from a case-control study of breast cancer in 441 cases and matched controls aged less than or equal to 38 in Los Angeles is fitted to two models of carcinogenesis: the two-stage model of Moolgavkar and Knudson; and a multistage adaptation of the log/log model proposed by Pike et al. In the two-stage model, risk factors (here age at menarche, age at first pregnancy, abortion, regularity of cycling, benign breast disease, and use of oral contraceptives (OCs] are postulated to act either by increasing the rate of mutation of normal to intermediate or of intermediate to malignant stage cells, or by increasing the proliferation rates of such cells. In the multistage model, it is postulated that all transition rates are equally determined by the rate of cell turnover, which is in turn influenced by risk factors. In both models, positive family history is modelled in two ways: (1) all cells may have started in an intermediate stage at birth, with probability depending on the number and degree of affected family members; or (2) as an event rate modifier in the same way as other covariates. With only menarche or menarche and family history included, the multistage and two-stage models both produced likelihoods very similar to those from a simple logistic model, though both fit better than the logistic model as more covariates were added to the model. The two stage models offer greater flexibility in modelling the time at which each factor is most effective. We found irregular menstrual cycling to reduce the rate of proliferation of normal cells or their mutation rate to intermediate cells by 50% (p less than 0.025) and use of OCs to increase these rates by 3.25 fold (p less than 0.01). Having completed a pregnancy of more than 26 weeks gestation appeared to reduce the rate of intermediate cell proliferation by 5% (p less than 0.05) relative to a baseline rate of 14% per year. Benign breast disease was associated with a 1.60 fold increased rate of the second mutation (p less than 0.025). In all models, family history was by far the strongest risk factor (RR = 4.44 from the logistic model, p less than 0.0001). Covariates showed similar effects in the multistage model, though their magnitudes were slightly different.


Upregulation of lncRNA NONRATG019935.2 suppresses the p53-mediated apoptosis of renal tubular epithelial cells in septic acute kidney injury.
Although increasing evidence has confirmed that the apoptosis of renal tubular epithelial cells (RTECs) is a crucial contributor to the onset and development of septic acute kidney injury (AKI), the pathological mechanism by which RTEC apoptosis is upregulated during septic AKI is not entirely clear. In this study, a rat model of septic AKI was induced by a cecal ligation puncture procedure or lipopolysaccharide (LPS) injection. Four differentially expressed long noncoding RNAs (DE-Lncs) in the rat model of septic AKI were determined using RNA-sequencing and verified by qRT-PCR. Among the four DE-Lncs, the expression level of lncRNA NONRATG019935.2 (9935) exhibited the most significant reduction in both septic AKI rats and LPS-treated NRK-52E cells (a rat RTEC line). The overexpression of 9935 suppressed cell apoptosis and p53 protein level in LPS-treated NRK-52E cells, and retarded septic AKI development in the rat model of septic AKI. Mechanistically, 9935 decreased the human antigen R (HuR)-mediated Tp53 mRNA stability by limiting the combination of HuR and the 3'UTR region of Tp53 mRNA in RTECs. The overexpression of HuR abrogated the inhibitory effect of pcDNA-9935 on the LPS-induced apoptosis of NRK-52E and rat primary RTECs. In conclusion, 9935 exerts its role in septic AKI by suppressing the p53-mediated apoptosis of RTECs, and this essential role of 9935 relies on its destructive effect on HuR-mediated Tp53 mRNA stability.


Skeletal Muscle Hypertrophy with Concurrent Exercise Training: Contrary Evidence for an Interference Effect.
Over the last 30+ years, it has become axiomatic that performing aerobic exercise within the same training program as resistance exercise (termed concurrent exercise training) interferes with the hypertrophic adaptations associated with resistance exercise training. However, a close examination of the literature reveals that the interference effect of concurrent exercise training on muscle growth in humans is not as compelling as previously thought. Moreover, recent studies show that, under certain conditions, concurrent exercise may augment resistance exercise-induced hypertrophy in healthy human skeletal muscle. The purpose of this article is to outline the contrary evidence for an acute and chronic interference effect of concurrent exercise on skeletal muscle growth in humans and provide practical literature-based recommendations for maximizing hypertrophy when training concurrently.


Capturing the value and core concepts of the Clinical Research Nurse.
As nurses, we identify our profession as a caring one, but how does this identity translate from a conceptual definition, to real-world practice for the Clinical Research Nurse? To offer a novel, four-point conceptual model that encapsulates the Clinical Research Nurse's intrinsic value, active leadership, and direct contribution to high quality, person-centered, safe care, addressing current misperceptions of research nursing. This paper describes the provision of 'care', safely delivered by the Clinical Research Nurse through a four-point conceptual model and case-driven example. Clinical research nursing is conceptualized within the domains of Care and Trust, Role, Impact, and Integration. The case example demonstrates real-world application of these domains and the expertise required to balance the complexities of clinical needs and research demands in a healthcare environment. This paper offers a mechanism for understanding the importance of the Clinical Research Nurse and their role in maintaining safety and a high-level view of the care arena. These reflections are considered with an international application for the role.


Cervical endometriosis: facilitated diagnosis by fine needle aspiration cytologic testing.
Regarded as infrequent, endometriosis of the cervix probably occurs more commonly than is generally realized. The lesion's apparent rarity may be ascribed to limited awareness of the clinical appearance, combined with technical difficulty in obtaining suitable biopsy material for confirmation. A consequence of previous cervical trauma, endometriosis of the cervix can be expected to increase in incidence with more widespread use of invasive cervical procedures. Clinical recognition and tissue confirmation thus become essential. This paper refocuses attention on cervical endometriosis by documenting the clinical, colposcopic, and histopathologic findings in 16 cases seen at a single colposcopy clinic over a 6-month period. Diagnosis in these patients was facilitated and improved by fine needle aspiration cytologic testing. This technique, not previously used for documentation of endometriosis in this location, is outlined in detail, together with a full description and illustration of the cytologic features.


The Kluyveromyces lactis KEX1 gene encodes a subtilisin-type serine proteinase.
KEX1 is a chromosomal gene required for the production of the killer toxin encoded by the linear DNA plasmid pGKL-1 of Kluyveromyces lactis. The nucleotide sequence of the cloned KEX1 gene has been determined. The deduced structure of the KEX1 protein, 700 amino acids long, indicated that it contained an internal domain with a striking homology to the sequences of the subtilisin-type proteinases, and a probable transmembrane domain near the carboxyl terminus. The results confirm the hypothesis that the product of the gene KEX1 of K. lactis is a proteinase involved in the processing of the toxin precursor.


Altered protein expression in endometrial carcinogenesis.
We have discovered several protein biomarkers that are altered during carcinogenesis of the human uterine endometrium. Proteins prepared from 19 endometrial carcinomas (Group A), and 20 normal endometria obtained from benign gynecological conditions (Group B), were investigated by Surface Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (SELDI-TOF-MS). Two proteins, EC1 and EC2, were consistently expressed differentially. EC1 had an increased level of expression in carcinomas (P<0.001), while EC2 was expressed at a lower level (P=0.004). The isoelectric points of EC1 and EC2 were approximately pH 5.0 and 7.0, respectively. These proteins are thus potential biomarkers for detection of endometrial carcinoma.


Radioactive iodine therapy: effect on functioning metastases of adenocarcinoma of the thyroid.
A case of metastatic adenocarcinoma of the thyroid is reported in which treatment by means of radioactive iodine has been successful. The patient was completely thyroidectomized for "malignant adenoma" in 1923, with neither thyrotoxicosis then nor hypothyroidism postoperatively; 15 years later there developed classic symptoms of hyperthyroidism and severe pain in the lower back. In October 1939 a pulsating tumor removed from the level of the 12th thoracic vertebra proved to be metastatic thyroid adenocarcinoma (histologically well differentiated, with small follicles and colloid). In the next two years hyperthyroidism increased and roentgenograms revealed new metastases in the lungs, upper part of the right femur, second rib on the left side, left ilium, and skull. Roentgenologic irradiation of the metastases proved ineffectual. In March 1943 a tracer dose of radioactive iodine revealed iodine retention by all the known lesions and no evidence of residual thyroid tissue in the neck. Therapeutic amounts of radioactive iodine were administered orally between May and October 1943. Definite and lasting clinical improvement followed. In April 1944 and March 1945 additional I* was administered with a resultant disappearance of pain, increase in weight, and progressive change in all clinical criteria in the direction of hypothyroidism. Roentgenographic evidence pointed to an arrest if not a regression of the disease. No untoward effects followed this therapy. Radioactive iodine seems to be an effective therapeutic agent in the control of this type of tumor.


Role of porcine endometrial estrogen sulfotransferase in progesterone mediated downregulation of estrogen receptor.
Estrogen sulfotransferase (EST) is a progesterone (Pg) induced secretory endometrial enzyme which may effect estrogen receptor levels by esterifying estradiol-17 beta (E2) to an inactive, sulfate form. The effects of this enzyme were studied using specific inhibitors of EST that do not bind to estrogen receptor (ER): 4-nitroestrone 3-methyl ether and 4-fluoroestrone 3-methyl ether. A 1 h pulse with 4 nM E2 caused ERn (i.e. E2-bound, chromatin-bound receptor) to increase 40% in incubations of proliferative gilt endometrium (no EST activity), while the same E2 treatment of secretory endometrium (high EST activity) caused no increase in ERn. ERn accumulation was completely restored in these experiments by preincubating secretory endometrium with 4 microM 4-fluoroestrone 3-methyl ether. Gilt endometrial explants cultured 7 days with 1 nM E2 plus 1 microM Pg (which induced EST activity) possessed half the ERn as explants devoid of EST activity which were cultured in E2 alone. The addition of 10 microM 4-nitroestrone 3-methyl ester to the cultures of secretory endometrium restored ERn to the levels seen in minces cultured with E2 alone. Furthermore, ovariectomized gilts injected daily with 250 micrograms E2 plus 25 mg Pg had much lower ERn (0.06 fmol/micrograms DNA) than gilts injected with E2 only (0.21 fmol/microgram DNA). ERn was restored completely by supplementing the E2 plus Pg injections with 0.5 g 4-nitroestrone 3-methyl ether administered by vaginal suppositories.(ABSTRACT TRUNCATED AT 250 WORDS)


The histone demethylase Lsd1 regulates multiple repressive gene programs during T cell development.
Analysis of the transcriptional profiles of developing thymocytes has shown that T lineage commitment is associated with loss of stem cell and early progenitor gene signatures and the acquisition of T cell gene signatures. Less well understood are the epigenetic alterations that accompany or enable these transcriptional changes. Here, we show that the histone demethylase Lsd1 (Kdm1a) performs a key role in extinguishing stem/progenitor transcriptional programs in addition to key repressive gene programs during thymocyte maturation. Deletion of Lsd1 caused a block in late T cell development and resulted in overexpression of interferon response genes as well as genes regulated by the Gfi1, Bcl6, and, most prominently, Bcl11b transcriptional repressors in CD4+CD8+ thymocytes. Transcriptional overexpression in Lsd1-deficient thymocytes was not always associated with increased H3K4 trimethylation at gene promoters, indicating that Lsd1 indirectly affects the expression of many genes. Together, these results identify a critical function for Lsd1 in the epigenetic regulation of multiple repressive gene signatures during T cell development.


Multi-cycle recovery of lactoferrin and lactoperoxidase from crude whey using fimbriated high-capacity magnetic cation exchangers and a novel "rotor-stator" high-gradient magnetic separator.
Cerium (IV) initiated "graft-from" polymerization reactions were employed to convert M-PVA magnetic particles into polyacrylic acid-fimbriated magnetic cation exchange supports displaying ultra-high binding capacity for basic target proteins. The modifications, which were performed at 25 mg and 2.5 g scales, delivered maximum binding capacities (Qmax ) for hen egg white lysozyme in excess of 320 mg g(-1) , combined with sub-micromolar dissociation constants (0.45-0.69 µm) and "tightness of binding" values greater than 49 L g(-1) . Two batches of polyacrylic acid-fimbriated magnetic cation exchangers were combined to form a 5 g pooled batch exhibiting Qmax values for lysozyme, lactoferrin, and lactoperoxidase of 404, 585, and 685 mg g(-1) , respectively. These magnetic cation exchangers were subsequently employed together with a newly designed "rotor-stator" type HGMF rig, in five sequential cycles of recovery of lactoferrin and lactoperoxidase from 2 L batches of a crude sweet bovine whey feedstock. Lactoferrin purification performance was observed to remain relatively constant from one HGMF cycle to the next over the five operating cycles, with yields between 40% and 49% combined with purification and concentration factors of 37- to 46-fold and 1.3- to 1.6-fold, respectively. The far superior multi-cycle HGMF performance seen here compared to that observed in our earlier studies can be directly attributed to the combined use of improved high capacity adsorbents and superior particle resuspension afforded by the new "rotor-stator" HGMS design.


Skin testing with extracts of fungal species derived from the homes of allergy clinic patients in Toronto, Canada.
Airborne fungi in the homes of patients with allergic rhinitis or asthma, from a Toronto Allergy Clinic population, were isolated, quantified and identified to species. Allergen extracts were prepared from sixteen of these isolated species and used for skin-prick testing of twenty-six patients. Fourteen of the total patients reacted to one or more of these extracts at 1:10 (w/v) concentrations. The most common positive skin responses (8/14 to 6/14) were found for Cladosporium cladosporioides, Alternaria tenuis, C. sphaerospermum, and Fusarium sp. The two Cladosporium species were also most commonly isolated in homes, but A. tenuis and Fusarium sp. were found only in 4% and less than 1% of the air samples, respectively. Epicoccum purpurascens and C. herbarum, which were isolated on approximately 10% of the plates, showed fewer skin reactions compared with the above. Positive skin-test response to the other ten study extracts ranged from 5/14 for two species of Aspergillus and Phoma glomerata, to 1/14 for Penicillium viridicatum; of these species, Aspergillus fumigatus was isolated in 3% of the home samples, the others were less than 1%. The findings suggest that fungal antigens from species found in homes are commonly associated with skin sensitization in an allergy clinic population with upper or lower respiratory allergy. No specific relationships were found, however, between the prevalence of fungal species in the home environment and their prevalence as skin-test allergens.


Imprinting: expanding the extra-pharmacological model of psychedelic drug action to incorporate delayed influences of sets and settings.
Psychedelic drug experiences are shaped by current-moment contextual factors, commonly categorized as internal (set) and external (setting). Potential influences of past environments, however, have received little attention. To investigate how previous environmental stimuli shaped the experiences of patients receiving ketamine for treatment-resistant depression (TRD), and develop the concept of "imprinting" to account for such time-lagged effects across diverse hallucinogenic drugs. Recordings of treatment sessions and phenomenological interviews from 26 participants of a clinical trial investigating serial intravenous ketamine infusions for TRD, conducted from January 2021 to August 2022, were retrospectively reviewed. A broad literature search was undertaken to identify potentially underrecognized examples of imprinting with both serotonergic and atypical psychedelics, as well as analogous cognitive processes and neural mechanisms. In naturalistic single-subject experiments of a 28-year-old female and a 34-year-old male, subjective ketamine experiences were significantly altered by varying exposures to particular forms of digital media in the days preceding treatments. Higher levels of media exposure reduced the mystical/emotional qualities of subsequent psychedelic ketamine experiences, overpowering standard intention-setting practices and altering therapeutic outcomes. Qualitative data from 24 additional patients yielded eight further spontaneous reports of past environmental exposures manifesting as visual hallucinations during ketamine experiences. We identified similar examples of imprinting with diverse psychoactive drugs in past publications, including in the first-ever report of ketamine in human subjects, as well as analogous processes known to underly dreaming. Past environmental exposures can significantly influence the phenomenology and therapeutic outcomes of psychedelic experiences, yet are underrecognized and understudied. To facilitate future research, we propose expanding the contextual model of psychedelic drug actions to incorporate imprinting, a novel concept that may aid clinicians, patients, and researchers to better understand psychedelic drug effects. ClinicalTrials.gov, identifier NCT04701866.


Plant-derived nanoparticle treatment with cocc 30c ameliorates attention and motor abilities in sleep-deprived rats.
Sleep is an essential physiological process that underlies crucial cognitive functions as well as emotional reactivity. Thus, sleep deprivation (SD) may exert various deleterious effects. In this study, we aimed to examine the adverse behavioral and hormonal effects of SD and a potential treatment with Plant-derived nanoparticle treatment - cocc 30c. The study was a 4-arm trial with randomization and double-blinding of verum and placebo treatments. SD was induced by using the Multiple Platform Method for 48 h. The effects of SD were evaluated behaviorally (pre-pulse inhibition (PPI), startle response and rotor-rod) at baseline as well as at 6, 12, 24h, and 14 days post deprivation. cocc 30c treatment was administrated Per Os every three hours starting immediately after baseline tests and for a period of 24h. On day 14, blood samples were taken and serum levels of corticosterone, testosterone, serotonin and leptin were tested. We found that cocc 30c improved PPI 12 and 24h post deprivation, likewise, cocc 30c improved motor learning. On day 14 SD led to increased startle response that was ameliorated by cocc 30c. Likewise, SD led to increased levels of corticosterone and serotonin while decreasing testosterone and leptin. Interestingly, cocc 30c treatment has moderated these hormonal alterations. We conclude that the treatment with cocc 30c recovers both short-term behavioral and the long-term hormonal modulations following SD.


Determination of the spatial structure of glutathione by residual dipolar coupling analysis.
The approach based on analysis of the residual 1H-13C dipolar couplings in molecules partially aligned in a lyotropic liquid crystalline medium was used in the NMR investigation of the reduced glutathione (Glu-Cys-Gly; GSH) structure in a lyotropic medium (cetylpyridinium chloride-n-hexanol). The spatial structure of GSH in solution was established on the basis of the experimental data for observed couplings only.


Cordycepin augments the chemosensitivity of osteosarcoma to cisplatin by activating AMPK and suppressing the AKT signaling pathway.
Osteosarcoma is the most common primary bone tumor in children and adolescents. However, some patients with osteosarcoma develop resistance to chemotherapy, leading to a poor clinical prognosis. Hence, effective therapeutic agents that can improve the response to chemotherapy drugs to improve the prognosis of patients with osteosarcoma are urgently needed. Cordycepin has recently emerged as a promising antitumor drug candidate. This study aims to explore the effect of cordycepin in suppressing osteosarcoma in vivo and in vitro and the synergistic effect of cordycepin combined with cisplatin and to demonstrate the underlying molecular mechanism. CCK-8 assay was performed to investigate the inhibition effect of cordycepin combined with cisplatin in osteosarcoma cell lines. The colony formation and invasion abilities were measured by colony formation assay and Transwell assay. Osteosarcoma cells apoptosis was detected by flow cytometry. Western blot analysis were used to detect the expression of cell apoptosis-related proteins and AMPK and AKT/mTOR signaling pathway-related proteins. Finally, we performed the in vivo animal model to further explore whether cordycepin and cisplatin exert synergistic antitumor effects. Notably, we found that treatment with cordycepin inhibited cell proliferation, invasion, and induced apoptosis in osteosarcoma cells in vitro and in vivo. Moreover, the combination of cordycepin and cisplatin led to marked inhibition of osteosarcoma cell proliferation and invasion and promoted osteosarcoma cell apoptosis in vitro and in vivo. Mechanistically, we demonstrated that cordycepin enhanced the sensitivity of osteosarcoma cells to cisplatin by activating AMPK and inhibiting the AKT/mTOR signaling pathway. In brief, this study provides comprehensive evidence that cordycepin inhibits osteosarcoma cell growth and invasion and induces osteosarcoma cell apoptosis by activating AMPK and inhibiting the AKT/mTOR signaling pathway and enhances the sensitivity of osteosarcoma cells to cisplatin, suggesting that cordycepin is a promising treatment for osteosarcoma.


Finding All Longest Common Segments in Protein Structures Efficiently.
The Local/Global Alignment (Zemla, 2003), or LGA, is a popular method for the comparison of protein structures. One of the two components of LGA requires us to compute the longest common contiguous segments between two protein structures. That is, given two structures A = (a1, ... ,a(n)) and B = (b1, ... ,b(n)) where a(k), b(k) ∈ ℝ(3), we are to find, among all the segments f = (a(i), ... ,a(j)) and g = (b(i), ... ,b(j)) that fulfill a certain criterion regarding their similarity, those of the maximum length. We consider the following criteria: (1) the root mean squared deviation (RMSD) between f and g is to be within a given t ∈ ℝ; (2) f and g can be superposed such that for each k, i ≤ k ≤ j, ||a(k) - b(k)|| ≤ t for a given t ∈ ℝ. We give an algorithm of O(n log n + nl) time complexity when the first requirement applies, where l is the maximum length of the segments fulfilling the criterion. We show an FPTAS which, for any ϵ ∈ ℝ, finds a segment of length at least l, but of RMSD up to (1 + ϵ)t, in O(n log n + n/ϵ) time. We propose an FPTAS which for any given ϵ ∈ R, finds all the segments f and g of the maximum length which can be superposed such that for each k, i ≤ k ≤ j, ||a(k) - b(k)|| ≤ (1 + ϵ)t, thus fulfilling the second requirement approximately. The algorithm has a time complexity of O(n log(2) n/ϵ(5)) when consecutive points in A are separated by the same distance (which is the case with protein structures). These worst-case runtime complexities are verified using C++ implementations of the algorithms, which we have made available at http://alcs.sourceforge.net/.


Cystatin A and B in the development of human squamous epithelia.
The expression of cystatin A (Acid cysteine proteinase inhibitor) and B (Neutral cysteine proteinase inhibitor) during human embryogenesis was studied immunohistochemically by using the PAP-complex method. Both inhibitors were visible first in the developing mucosal tissue at the age of about 9 weeks. In the fetal epidermis (periderm), cystatin B was demonstrated at the age of 11 weeks and cystatin A at 12 weeks. In these young fetuses, the staining was visible in the basal cells, whereas in fetuses older than 17 weeks the staining of both inhibitors diminished in the basal cells. In the skin of 17 to 25 weeks old fetuses, the epidermal staining of cystatin B become weaker than that of cystatin A, and at the age of about 26 weeks, cystatin B disappeared totally. At this stage, cystatin A was localized in the cytoplasm of the middle to upper cell layers of the epidermis. In the squamous epithelia of the mucosal tissues, the staining of the both inhibitors reached their maximal intensity when the fetuses were about 16 weeks old. At the mature fetuses, infants as well as adults, both cystatin A and B seemed to be present in wet squamous epithelia while in the epidermis only cystatin A was expressed.


Intestinal helminths and protozoan infections in patients with colorectal cancer: prevalence and possible association with cancer pathogenesis.
The purpose of the present study was to determine the prevalence of intestinal helminths and protozoa in colorectal cancer (CRC) patients and to evaluate the possible association between the prevalence and CRC pathogenesis. A total of 200 CRC patients and 200 residents of Tashkent, who had no complaints related to the gastrointestinal tract, were examined by triple coproscopy using a concentration method and estimations of protozoan infection intensity. Of the CRC patients tested, 144 were classified as T1-4N0M0 (without metastases) and 56 were classified as T1-4N1-2M0-1 (with metastases). Parasitological examination was performed during CRC diagnosis before and after surgery and chemotherapy. A significantly higher prevalence of Blastocystis sp., Chilomastix mesnili, Jodamoeba butschlii, and Endolimax nana was found in CRC patients than in the control population (p < 0.0001), amounting to 80, 20, 22.5, and 11.5%, respectively. The high prevalence of Blastocystis sp., as well as the patterns of infection intensity, was stable at all stages of examination. The ratio of the number of CRC patients with and without Blastocystis sp. in the T1-4N0M0 and T1-4N1-2M0-1 groups amounted to 3.3 and 7.0, respectively. The ratios for C. mesnili, E. coli, J. butschlii, and E. nana in both groups were 0.2 and 0.2, 0.07 and 0.07, 0.3 and 0.16, and 0.18 and 0.01, respectively. The prevalence of helminths and Giardia lamblia in CRC patients and the control population was not significantly different. Taken together, these data indicate a possible role for Blastocystis sp. in CRC pathogenesis. Diagnosis, treatment, and further observation of patients with Blastocystis sp. are necessary at all stages of CRC, including during diagnosis and before and after surgery and chemotherapy.


A study of interference with the activities of schizophrenics by auditory hallucinations.
Interference with self-care, occupation, social activities and leisure time activities by auditory hallucinations was examined in 30 schizophrenics. 9 Patients did not experience interference with their activities. Psychoticism scores, neuroticism scores, presence of advising voices and presence of known living 'speakers' were related to interference with activities by the voices.


Identify the key amino acid of BAFF binding with TACI.
B-cell activating factor (BAFF) has been used as a therapeutic target. To develop BAFF-specific small molecular inhibitors, it is necessary to know the key amino acid in the BAFF binding with its receptor. The key binding amino acid of BAFF interacting with its receptor TACI (trans-membrane activator and calcium modulator and cyclophilin ligand interactor) was analyzed based on the computer-guided molecular modeling method. According to theoretical prediction, a series of key amino acid mutants of BAFF, including M204 (Lys(204) to Ala), M208 (Met(208) to Ala), M209 (Gly(209) to Ala), M210 (His(210) to Ala), M234 (Gln(234) to Ala), M236 (Met(236) to Ala), and M237 (Pro(237) to Ala) were designed and evaluated with biological experiments. The results show that M208, M209, M236, and M237 of BAFF were the key amino acids and in accord with the theoretical results. The results highlight clues for the further development of BAFF-specific small molecular inhibitors.


Identification of Botryosphaeriaceae associated with stem-end rot of mango (Mangifera indica L.) in Malaysia.
To identify Botryosphaeriaceae fungal species that are associated with stem-end rot of mango, and to study their pathogenicity on mango fruit. Based on the sequences of internal transcribed spacer (ITS), TEF1-α and β-tubulin, as well as on the phylogenetic analysis of combined sequences, four species of Lasiodiplodia (L. theobromae,L. pseudotheobromae, L. iranensis, L. mahajangana) and two species of Neofusicoccum (N. ribis, N. parvum) were identified. Pseudofusicoccum violaceum, Neoscytalidium dimidiatum and three species of Botryosphaeria (B. scharifii, B. dothidea, B. ramosa) were identified based on sequences of ITS and TEF1-α. Pathogenicity test of selected isolates were tested on Chok Anan, Waterlily and Falan mango cultivars. Generally, all species were observed to be pathogenic on the three tested mango cultivars on wounded fruits, except for N. ribis and N. parvum, which were pathogenic on both wounded and unwounded fruits. However, N. ribis was only pathogenic on cultivar Falan, whereas B. ramosa were pathogenic on cultivars Waterlily and Falan. Eleven species of Botryosphaeriaceae were associated with mango stem-end rot in Malaysia. To the best of our knowledge, four species, namely L. mahajangana, B. ramosa, N. ribis and P. violaceum are the first recorded Botryosphaeriaceae fungi associated with stem end rot of mango. The identification of Botryosphaeriaceae fungi is important to establish suitable control measures and quarantine requirements. Many species have a wide host range, which means that there is a possibility of cross infection from other infected plants.


New Variant of mcr-3 in an Extensively Drug-Resistant Escherichia coli Clinical Isolate Carrying mcr-1 and blaNDM-5.
A colistin- and carbapenem-resistant Escherichia coli clinical isolate was found to carry two plasmid-borne colistin-resistant genes, mcr-1 and the newly identified mcr-3, and a carbapenemase gene, blaNDM-5mcr-3 is a new variant (mcr-3.5) in the isolate and encodes three amino acid substitutions compared with the original MCR-3. mcr-3 was carried by a TnAs3-like transposon on a self-transmissible IncP plasmid in the isolate, highlighting that mcr-3 may have widely spread.


Novel, disposable, self-inserted, vaginal device for the non-surgical management of pelvic organ prolapse: efficacy, safety, and quality of life.
We evaluated a novel disposable, collapsible, ring-shaped vaginal device that is self-inserted within an applicator and removed with a string. The device was developed to overcome the drawbacks of existing ring pessaries for non-surgical pelvic organ prolapse management (POP). The primary objective efficacy endpoint of this prospective, interventional, multicenter, self-controlled, and home-use study was the proportion of subjects with improved staging on the Pelvic Organ Prolapse Quantification (POP-Q) scale. Subjective efficacy was assessed using the POP symptoms alleviation score. Safety was evaluated by recording the rate and incidence of adverse events (AEs) in a daily diary, and quality of life (QoL) was evaluated using the modified Pelvic Floor Impact (PFIQ-7) and Pelvic Floor Disability Index (PFDI-20) questionnaires. A total of 94 usage cycles were observed in a group of 52 participants (mean age 60.2 ± 10.5 years, 81.1% postmenopausal) who used the device for 3558 days. Of these, 24 participants completed one usage cycle, 14 completed two usage cycles, and 14 completed three usage cycles with 28-45 days of ProVate use in each usage cycle. All patients experienced greater than two POP-Q stage reductions. The descent was completely reduced to POP-Q stage 0 in 97.8% of participants. The POP symptom alleviation questionnaire showed significant subjective efficacy (P < 0.0001). The modified PFDI-20 and PFIQ-7 scores also improved substantially (P < 0.0001 for both). There were 91 nonserious device-related AEs: 98.9% were mild and 87.9% anticipated, with no vaginal infection, and one case of urinary tract infection. The novel device substantially reduces prolapse and provides significant subjective POP symptom relief and QoL improvement, with minimal AEs. The device may enable women to self-manage their prolapse with a small, disposable device that minimizes self-touching and frequent dependency on the clinic. Clinical. gov , NCT02239133 , posted September 12, 2014 (retrospectively registered).


Rapid detection of Shiga toxin type II using lateral flow immunochromatography test strips of colorimetry and fluorimetry.
Two types of lateral flow immunochromatographic test strips (LFITS) using gold nanoparticles and fluorescent CdTe quantum dots (QDs) as signal labels, respectively, were developed for Shiga toxin type II (STX2) assays. Under optimal conditions, the corresponding visual detection limits were 25 ng mL-1 and 5 ng mL-1, respectively. The test results of gold based LFITS can be recognized directly by the naked eye, whereas the visualized results of CdTe QDs based LFITS can be observed by the aid of a UV lamp. Both assays showed good specificity and stability. The inexpensive LFITS were promising for the rapid clinical detection of STX2.


Catheter-Directed Therapy is Safe and Effective for the Management of Acute Inferior Vena Cava Thrombosis.
The management of acute thrombosis of inferior vena cava (AT-IVC) has evolved to catheter-based therapies, the results of which remain uncertain. We report our institution's experience treating AT-IVC using endovascular methods. A 10-year retrospective review of patients presenting with symptomatic IVC thrombosis between the years 2005 and 2014 was performed. Demographic data, treatment modalities, and outcomes were reviewed. Twenty-five patients (44% men) underwent treatment for acute (<2 weeks) symptomatic IVC thrombosis. Presenting symptoms included pain and limb swelling in 23 (92%), motor dysfunction in 16 (64%), sensory loss in 14 (56%), and pulmonary embolism (PE) in 2 (8%) patients. Phlegmasia cerulea dolens was present in 5 patients, a history of malignancy was identified in 7 patients, and 21 patients had an IVC filter at presentation (Trapease 12, G2X 3, Option 2, Eclipse 2, Meridian 2). Four patients had a documented hypercoagulable state, 21 patients underwent venous angioplasty, and 7 (28%) patients underwent venous stenting of the IVC or iliofemoral veins. Significant (>50% luminal gain) angiographic resolution of venous thrombus was achieved in all 25 patients. Twenty-one (84%) patients reported moderate-to-complete symptomatic improvement immediately after completion of the procedures. Two patients had a clinically symptomatic PE and 1 patient underwent an above-knee amputation secondary to venous gangrene. Other complications included 6 minor bleeding complications (2 local hematoma, 4 hematuria) all of which resolved spontaneously. There were 2 major bleeding complications (1 disseminated intravascular coagulation, 1 retroperitoneal hematoma). Endovascular treatment of AT-IVC, regardless of etiology, is safe and effective with excellent short-term clinical results. An aggressive endovascular approach to treatment of AT-IVC is warranted even in the presence of a thrombosed vena cava filter.


Effects of metoclopramide on the urethral pressure profile of healthy dogs.
The purpose of the present work was to study the effect of metoclopramide on urethral pressure since urethral relaxation is an important factor in vesical voiding. Urethral pressure was measured in 6 dogs, anesthetized with propofol before and 1, 5 and 10 minutes after the administration of metoclopramide (0.5 mg/kg.) or placebo. A single injection of metoclopramide induced a large decrease in maximal urethral closure pressure (53 to 90%; mean 71%, p < 0.001--Anova). The decrease with placebo, 5 to 44% (mean 26%), was not significant (Anova test: p = 0.06). It is argued that a central dopaminergic action most probably accounts for this effect of metoclopramide on urethral pressure.


Basophil chemotaxis under agarose: variability among guinea pig donors and response to sera of different species.
Guinea pig basophils were tested against chemotactic factor(s) generated from homologous and heterologous sera. An "under agarose" method of quantitating leukocyte chemotaxis was adapted to measure serum-derived basophil chemotactic factor(s) (BCF). The method was found to be simple, reproducible, and sparing of time and reagents and it provided simultaneous controls. Because of the economy of reagents compared with the Boyden chamber technique, basophils from individual guinea pigs could be studied and were found to be variable in responsiveness. A definite difference in the response of guinea pig basophils to zymosan-activated sera of various other species was demonstrated. Guinea pig basophils responded to zymosan-activated serum from guinea pig and rat but failed to respond to zymosan-activated serum from human, hamster, rabbit, or cow. Optimal conditions were determined for cell numbers, serum activation and dilution, and migration times for studies of guinea pig BCF. The under agarose technique provides a practical alternative to chamber methods for the study of basophil chemotaxis. Although guinea pig basophils do not respond to human serum-derived BCF, the economy of reagents with this technique gives promise toward adaptation of the method to studies of human basophil chemotaxis.


Genotoxic effect of 2,4,6-trichlorophenol on p53 gene in zebrafish liver.
Trichlorophenol (2,4,6-trichlorophenol [TCP]), a probable human carcinogen, is widely present in the environment. Employing denaturing high-performance liquid chromatography and DNA sequencing analyses, we demonstrated that 10-d exposure of zebrafish to TCP at 5 microg/L resulted in elevated point mutations of p53 gene in the liver genome. The result suggests that TCP might be involved in carcinogenesis by inducing point mutations in the somatic genome.


Quantum dot assisted precise and sensitive fluorescence-based formaldehyde detection in food samples.
Formaldehyde has an extremely reactive carbonyl group, commonly used as an antibacterial agent to sterilize and prevent food to spoil. This article describes an efficient and rapid detection method of formaldehyde from an aqueous solution by synthesizing 3-Aminopropyltriethoxysilane (APTES) quantum dots (Nano A) which react with formaldehyde to generate a Schiff base reaction. The photoinduced electron transfer produced by the quantum dots themselves results in fluorescence quenching to detect formaldehyde. The detection limit can reach 10-9 M, and it can further be used to detect formaldehyde content in foods, such as baby vegetables, mushrooms, and vermicelli among other daily foods.


A novel super-potent neurokinin A receptor antagonist containing dehydroalanine.
We report here the synthesis and preliminary pharmacological characterization of a novel Neurokinin A receptor antagonist. This molecule contains a dehydroalanine residue. It displays a high conformational rigidity and possesses very high activity. Its pharmacological properties as a neurokinin A receptor antagonist were assessed in in vitro experiments on rat vas deferens and were compared to those of Neuronorm and MEN10627.


Improved survival of surgery for acute type A aortic dissection: impact of noninvasive diagnosis and hemostatic surgical management.
In the past decade, progress in cardiovascular technology has been incorporated into the surgical treatment of acute type A dissection resulting in remarkable improvement. Factors in this progress encompass rapid noninvasive diagnosis, intraoperative introduction of aprotinine, surgical glue, sealed grafts, and refined surgical technique. The objective of this study is to identify which factors contributed to the improvement of the surgical outcome of acute type A dissections. Between January 1989 and February 2001, 78 consecutive patients had emergency surgeries for acute type A dissection. The initial 31 patients (group I) received preoperative angiography, when possible. Since 1996, the next 47 patients (group II) have received noninvasive rapid diagnosis with hemostatic surgical management. This included aggressive proximal resection and judicious use of gelatin resorcine formol glue and felt strips. Between the two groups, in-hospital mortality and morbidity, incidence of neurological complications, late survival and cardiovascular events were compared. Risk factors for in-hospital death were investigated with univariate and multivariate analysis. The in-hospital mortality was significantly improved in group II (4.3%) compared with group I (29.0%). Overall mortality was 14.1%. Multivariate analysis revealed preoperative limb ischemia and delayed timing of operation (> 3 hours after arrival) as independent risk factors for in-hospital death. Late survival at 5 years was 61.5+/-7.5%. Between the two groups there was no significant difference in late survival or cardiovascular events. Immediate surgical intervention, using rapid noninvasive diagnosis with hemostatic management, substantially improves the surgical outcome of acute aortic dissection.


Chitosan-montmorillonite biocomposite as an adsorbent for copper (II) cations from aqueous solutions.
Chitosan-montmorillonite (KSF-CTS) beads were prepared by crosslinking with pentasodium tripolyphosphate (TPP). Montmorillonite (KSF-Na), CTS and KSF-CTS biocomposite were used to remove Cu(II) from aqueous solutions. These materials were characterized before and after copper adsorption by XRD, FTIR and thermogravimetry (TG). The data indicated that the adsorption process proceeds kinetically according to a pseudo-second-order model. The adsorption processes were adjusted to the Langmuir model for KSF-Na and CTS and to the Temkin model for KSF-CTS. The maximum adsorption capacity followed the order CTS>KSF-CTS>KSF-Na. Percentages desorption of copper ions from the KSF-CTS composite after three desorption cycles were 86%, 85% and 84%, respectively, using EDTA as regeneration agents.


Analysis of biogenic volatile organic compounds in zucchini flowers: identification of scent sources.
An analytical method has been applied to determine volatile organic compounds in zucchini flowers. In a first step, the analytical method was applied to characterize the main scents emitted by whole male and female living flowers of three main commercial cultivars of zucchini (Tosca, Chapin, and Consul). In a second step, the compounds were quantified in different parts of the living flowers to identify the contribution of nectar, petals, anther, and stigma to the aroma profile of the flower. The analytical method is based on headspace solid-phase microextraction coupled on-line with GC and tandem MS detection (HS-SPME-GC-MS/MS). A reference compound is added to samples as part of the field quality control procedure to check for likely analyte losses or sample decomposition. The reference compound also acts as an internal standard for quantification purposes. Results have been statistically studied applying principal component analysis (PCA), which shows that three components explain more than 91% of the variance. PCA emphasizes the great importance of nectar as being the main source of 1,4-dimethoxybenzene and 1,2,4-trimethoxybenzene, which influence the aroma profile of flowers. The remaining components can be accounted for by emissions from petals and sexual organs (adroecium and gynoecium anthers or stigmas).


A multicenter phase II study on the safety of rho-kinase inhibitor (ripasudil) with needling for the patients after trabeculectomy.
There is no established method of maintaining or reducing intra ocular pressure after the needling procedure for failing blebs post trabeculectomy. Regarding newer antihypertensive medications, ripasudil, which is a rho-associated protein kinase inhibitor ophthalmic solution, was able to prevent excessive scarring in vitro. This study aims to evaluate the safety of glaucoma patients submitted to the needling procedure and administered ripasudil for preventing scarring after the procedure. We also investigate the efficacy of ripasudil after needling for bleb failure through suppression of fibrosis to the bleb. This study is a multicenter, open-label, single-arm, phase II trial to evaluate the safety and efficacy of ripasudil in glaucoma patients after the needling procedure. Forty patients who will undergo needling at least 3 months after trabeculectomy will be recruited in Hiroshima university hospital and Hiroshima eye clinic. All the patients will instill ripasudil two times per day for three months after the needling procedure. The primary endpoint is the safety of ripasudil. We plan to establish the safety of ripasudil and to collect information involving the efficacy of ripasudil widely in this study.


Potential risks of calcium channel blockers in chronic kidney disease.
Antihypertensive therapy remains the most effective strategy for slowing the progression of chronic kidney disease (CKD). However, in proteinuric nephropathies, calcium channel blockers (CCBs) are less effective than other antihypertensives unless normotension is achieved. This is because the glomerular capillaries, rather than larger vessels, are the primary site of hypertensive injury in proteinuric nephropathies. CCBs impair renal autoregulation, which protects glomerular capillaries against the transmission of systemic pressures. CCBs' renoprotective inferiority in the comparator group likely accounts for the greater renoprotection observed with renin-angiotensin system blockade rather than blood pressure (BP)-independent renoprotective superiority. Nevertheless, CKD patients are at greater absolute risk for cardiovascular events rather than end-stage renal disease. Therefore, if the needed BP reductions cannot be achieved with other agents, it may be appropriate to use CCBs because of their antihypertensive effectiveness, provided care is taken to ensure normotension and to closely monitor proteinuria and renal disease progression.


p21-activated kinases: three more join the Pak.
The p21-activated kinases (Paks) are serine/threonine protein kinases that bind to and, in some cases, are stimulated by activated forms of the small GTPases, Cdc42 and Rac. With the recent discovery of several novel isoforms, Paks are now categorized into two subgroups based on architectural similarities. The Group I Paks (Pak1, Pak2, Pak3) have been studied in greater detail and shown to be involved in the regulation of cellular processes such as gene transcription, cell morphology, motility, and apoptosis. Here we summarize recent findings that shed light on the newly recognized Group II Paks (Pak4, Pak5, Pak6) and review both similarities and differences between kinases of the two Pak subgroups.


Antihemolytic and antioxidant properties of pearl powder against 2,2'-azobis(2-amidinopropane) dihydrochloride-induced hemolysis and oxidative damage to erythrocyte membrane lipids and proteins.
Pearl powder, a well-known traditional mineral medicine, is reported to be used for well-being and to treat several diseases from centuries in Taiwan and China. We investigated the in vitro antihemolytic and antioxidant properties of pearl powder that could protect erythrocytes against 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced oxidative damage to membrane proteins/lipids. Human erythrocytes were incubated with different concentrations of pearl powder (50-200 μg/mL) for 30 minutes and then exposed to AAPH for 2-6 hours. We found that AAPH alone time dependently increased the oxidative hemolysis of erythrocytes, while pearl powder pretreatment substantially inhibited the hemolysis in a concentration-/time-dependent manner. AAPH-induced oxidative damage to erythrocyte membrane lipids was evidenced by the elevated malondialdehyde (MDA) levels. However, pearl powder remarkably inhibited the malondialdehyde formation, and the 200 μg/mL concentration showed almost similar malondialdehyde values to the control. Furthermore, pearl powder suppressed the AAPH-induced high-molecular-weight protein formation and concomitantly increased the low-molecular-weight proteins in erythrocytes. Antioxidant potential that was measured as superoxide dismutase activity and glutathione content was significantly dropped by AAPH incubation, which suggests the vulnerability of erythrocytes to AAPH-induced oxidative stress. Noteworthy, erythrocytes pretreated with pearl powder showed restored superoxide dismutase activity and glutathione levels against AAPH-induced loss. Our findings conclude that pearl powder attenuate free radical-induced hemolysis and oxidative damage to erythrocyte membrane lipids/proteins. The potent antioxidant property of pearl powder may offer protection from free radical-related diseases.


Formation, properties and antimicrobial activities of cotton xanthate-Cu(II)-homosulfamine complex.
To develop a cotton derivatives with prolonged antimicrobial activities, homosulfamine (Hs) was coupled to cotton xanthate (CX) via chelate bond in the presence of Cu(II) ion by one- and two-bath processes. In one-bath process, CX was treated with Cu(II)-Hs solution. In two-bath process, CX was treated with Cu(II) ion solution to produce CX-Cu(II) complex, which was isolated and treated in turn with Hs solution. Effects of concentration, Cu(II)/Hs ratio, and pH on the binding of Hs were investigated at 10 degrees C. In one-bath process, binding of Hs took place readily with optimum pH around 5-6. The amount of binding increased to give a maximum within 5 min and decreased slowly to establish an equilibrium within an hour. In two-bath process, binding of Hs was much lower than that of one-bath process. Release of Hs from CX-Cu(II)-Hs was investigated by batch and flow method. Antimicrobial activities of CX-Cu(II)-Hs were tested against Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa and Escherichia coli and it showed prolonged activity compared to that of free Hs.


Closing the Type 1 Diabetes gap in South-East Asia through government partnership working with non-government organisations.
This will be the first publication of Type 1 diabetes(T1D) outcomes in five low-middle-income countries (LMICs)-Laos, Malaysia, Vietnam, Cambodia and Myanmar in the Southeast Asia (SEA) region. The information obtained has been possible due to partnership programmes of non-government organisationAction4Diabetes (A4D) with defined local hospitalsthrough a Memorandum of Understandingsigned with the governments in SEAthat guarantees ongoing supplies of free insulin, blood glucose meter supplies, HbA1c tests and hospital emergency funds. Between 2020 and 2021, 383 children and young people with T1D who were active in the A4D supported programmes were reviewed including information on health coverage, multidisciplinary team management, diabetic ketoacidosis (DKA) on admission and insulin regimen. Mean HbA1c between 2020 and 2021 for patients in these LMICs arereported for the first time. The average glycaemic index in the five SEAcountries reviewed between 2020 and 2021 were high at 83 mmol/mol (9.7%). Government partnership working with non-government organisationsto support T1D from diagnosis to adulthood are the first steps to closing thegaps in many LMICs. Further epidemiological studies are needed to identify the glycaemic outcomes and DKA rates on admission for many of these countries.