Effects of copper exposure on the hatching status and antioxidant defense at different developmental stages of embryos and larvae of goldfish Carassius auratus.
This study aims to assess the effects of copper exposure on hatching status and antioxidant defense at different stages of embryos and larvae of goldfish Carassius auratus. In this study, day-old embryos were randomly grouped after fertilization and then exposed to copper concentrations of 0, 0.1, 0.4, 0.7, and 1.0mgL(-1). Copper-exposed fish embryos were sampled every 24h to determine superoxide dismutase (SOD), and catalase (CAT) activities, as well as malondialdehyde (MDA) content. In addition, cumulative mortality and larval deformity were also investigated. The findings showed that cumulative mortality and larval deformity rate increased gradually with copper concentration increase. SOD and CAT activities were inhibited at higher copper concentrations. At a lower concentration (0.1mgL(-1)), SOD activity increased in larvae, whereas CAT activity showed no significant change (p>0.05). MDA, as the lipid peroxidation product, gradually accumulated in embryos and larvae with increasing copper concentration and the extension of exposure time. At 0.4mgL(-1) and more, copper toxicity was shown in embryos and larvae. In conclusion, copper-exposed effects on hatching status and antioxidant defense in C. auratus embryos and larvae showed concentration- and time-dependent patterns. The biochemical parameters in this study can be used as effective indicators for evaluating the responses of copper-exposed fish embryos. In addition, this study demonstrates that 0.4mgL(-1) copper (corresponding to 1mgL(-1) copper sulfate), used to kill parasites in aquaculture, is not safe concentration, because it can result in toxicity to larvae. Therefore, the copper concentration to kill pathogen should be less than 0.4mgL(-1) for C. auratus.


Nonsystem reasons for delay in door-to-balloon time and associated in-hospital mortality: a report from the National Cardiovascular Data Registry.
The goal of this study was to characterize nonsystem reasons for delay in door-to-balloon time (D2BT) and the impact on in-hospital mortality. Studies have evaluated predictors of delay in D2BT, highlighting system-related issues and patient demographic characteristics. Limited data exist, however, for nonsystem reasons for delay in D2BT. We analyzed nonsystem reasons for delay in D2BT among 82,678 ST-segment elevation myocardial infarction patients who underwent primary percutaneous coronary intervention within 24 h of symptom onset in the CathPCI Registry from January 1, 2009, to June 30, 2011. Nonsystem delays occurred in 14.7% of patients (n = 12,146). Patients with nonsystem delays were more likely to be older, female, African American, and have greater comorbidities. The in-hospital mortality for patients treated without delay was 2.5% versus 15.1% for those with delay (p < 0.01). Nonsystem delay reasons included delays in providing consent (4.4%), difficult vascular access (8.4%), difficulty crossing the lesion (18.8%), "other" (31%), and cardiac arrest/intubation (37.4%). Cardiac arrest/intubation delays had the highest in-hospital mortality (29.9%) despite the shortest time delay (median D2BT: 84 min; 25th to 75th percentile: 64 to 108 min); delays in providing consent had a relatively lower in-hospital mortality rate (9.4%) despite the longest time delay (median D2BT: 100 min; 25th to 75th percentile: 80 to 131 min). Mortality for delays due to difficult vascular access, difficulty crossing a lesion, and other was also higher (8.0%, 5.6%, and 5.9%, respectively) compared with nondelayed patients (p < 0.0001). After adjustment for baseline characteristics, in-hospital mortality remained higher for patients with nonsystem delays. Nonsystem reasons for delay in D2BT in ST-segment elevation myocardial infarction patients presenting for primary percutaneous coronary intervention are common and associated with high in-hospital mortality.


Facile synthesis of highly functionalized N-methyl amino acid esters without side-chain protection.
[reaction: see text] The facile, two-pot synthesis of N-methyl amino acid esters by way of reductive amination is presented. Side chain protection schemes are not required, the starting materials are all commercially available, and the synthetic method is straightforward and affords desired product in very high yield.


Imidazoline binding sites and receptors in cardiovascular tissue.
1. Imidazoline binding sites and receptors and their endogenous ligands have been identified in cardiovascular tissue of various species including human beings. 2. I2- (but only exceptionally I1-)imidazoline binding sites have been shown to exist on cardiac myocytes and vascular smooth muscle cells; at present, their functional role is unknown. 3. The sympathetic nerves supplying the cardiovascular system are endowed with presynaptic inhibitory imidazoline receptors that may become of therapeutic relevance as targets of drugs. 4. ATP-sensitive K+ channels present in heart and blood vessels can be blocked by several imidazolines and guanidines; hence, those drugs can interfere with the cardioprotective effects resulting from K(ATP) channel activation by a decrease in the endogenous ligand ATP or by drugs. 5. Imidazoline derivatives exhibit antiarrhythmic properties that are due to a reduction of sympathetic tone by central and peripheral mechanisms and to blockade of postsynaptic alpha2-adrenoceptors in the heart and coronary arteries. 6. Agmatine and clonidine-displacing substance, which are endogenous ligands at imidazoline and alpha2-receptors, are present in the blood serum and appear to participate in vascular smooth muscle proliferation and blood pressure regulation.


Optimization of bovine satellite cell-derived myotube formation in vitro.
Post-natal myogenic satellite cells, isolated from the sternomandibularis muscles of bovine at slaughter were used for primary culture studies. Isolated satellite cells tended to differentiate into multinucleated myotubes more efficiently if initially plated on to a fibronectin substratum. Bovine-derived satellite cells displayed greater fused cell numbers when exposed to Dulbecco's Modified Eagle's Medium (DMEM) supplemented with horse serum than similar supplementation with fetal calf serum (P less than 0.05) or sheep serum (P less than 0.05). In addition, differentiation appeared nearly complete after 4 days exposure to DMEM-1% horse serum as verified by beta-D-arabinofuranosyl-cytosine addition to cultures. Collectively, these data provide the first evidence that satellite cells can be isolated from a bovine skeletal muscle. Furthermore, these data indicate that bovine-derived satellite cells can be induced to undergo substantial morphological differentiation in vitro.


VErapamil plus antiarrhythmic drugs reduce atrial fibrillation recurrences after an electrical cardioversion (VEPARAF Study).
To evaluate the impact, on atrial fibrillation (AF) recurrences, of verapamil addition to a class IC or III antiarrhythmic drug in patients, with persistent AF, who underwent an electrical cardioversion (EC). Three hundred sixty-three patients were randomized to receive four different pre-treatment protocols: oral amiodarone (group A), oral flecainide (group F), oral amiodarone plus oral verapamil (group A+V), oral flecainide plus oral verapamil (group F+V). Patients who showed an AF recurrence within 3 months were assigned to the alternative group and underwent a second EC after 48h. During 3 months of follow-up, 89 patients (27.5%) had an AF recurrence. By univariate analysis, verapamil reduced AF recurrences if added to amiodarone or flecainide (from 35% to 20%, P=0.004). Applying Cox proportional hazards regression model, only the younger age, the shorter duration of AF, and the use of verapamil were predictor of maintenance of sinus rhythm after cardioversion. In patients with primary AF recurrence, verapamil addition to group A and F patients, significantly decreased secondary AF recurrence rate as compared to group A+V and F+V patients who stopped the verapamil therapy (68% vs 88%, P=0.03). The addition of verapamil to class IC or III antiarrhythmic drug significantly reduced the AF recurrences, that were more frequent in older patients and in patients with longer lasting AF; moreover, verapamil was effective in reducing the secondary AF recurrences, too.


The Plasticene: Time and rocks.
Plastics, "yesterday's hero... today's villain" or "the contemporary symbol of modernity," were invented in the early 20th century by Leo Hendrik Baekeland from macromolecules (resins, elastomers, and artificial fibres) of formaldehyde and phenol. This synthetic organic polymer took hold of daily human life and transformed the modern world with an ever-widening range of applications. Plastics are the third most-widely manufactured material in the world after cement and steel, and they have become widespread in our society with excessive production and consumption to meet demand. Plastics use is so dominant that they are inappropriately considered essential in the world consumers marketplace. Plastics are a clear indicator of the Anthropocene and can be considered the marker of the upper subdivision of this stage: the Plasticene.


Non-Hodgkin's lymphomas.
The non-Hodgkin's lymphomas, although sharing a common origin, often present physicians with wide variations in natural history and prognosis. The proper therapy of these diseases is based on an understanding of these differences and upon the information gained by pathologic review and staging, as well as the available chemotherapeutic and radiotherapeutic options.


Life expectancy change in perturbed communities: derivation and qualitative analysis.
Pollution, loss of habitat, and climate change are introducing dramatic perturbations to natural communities and affecting public health. Populations in perturbed communities can change dynamically, in both abundance and age structure. While analysis of the community matrix can predict changes in population abundance arising from a sustained or press perturbation, perturbations also have the potential to modify life expectancy, which adds yet another means to falsify experimental hypotheses and to monitor management interventions in natural systems. In some instances, an input to a community will produce no change in the abundance of a population but create a major shift in its mean age. We present an analysis of change in both abundance and life expectancy, leading to a formal quantitative assessment as well as qualitative predictions, and illustrate the usefulness of the technique through general examples relating to vector-borne disease and fisheries.


Exogenous malic acid alleviates cadmium toxicity in Miscanthus sacchariflorus through enhancing photosynthetic capacity and restraining ROS accumulation.
Malic acid (MA) plays an important role in the regulation of plant growth, stomatal aperture, nutrition elements homeostasis and toxic metals tolerance. However, little is known about the effects of exogenous MA on physiological and biochemical responses to toxic metals in plants. To measure the alleviation roles of exogenous MA against cadmium (Cd), we determined the effects of MA on plant growth, net photosynthetic rate (Pn), reactive oxygen species (ROS) accumulation and the activities of anti-oxidant enzymes in the leaves of Miscanthus sacchariflorus (M. sacchariflorus) under Cd stress. The Cd exposure alone significantly inhibited plant growth and Pn, but increased the accumulation of ROS even though the anti-oxidant enzymes were markedly activated in the leaves of M. sacchariflorus. Treatment with MA significantly enhanced plant growth and decreased Cd accumulation accompanied by increasing Pn under Cd stress as compared to Cd stress alone, especially when treatment with high concentration of MA (200μM) was used. In addition, Cd and MA indicated synergistic effects by further increasing the activities and genes expression of partial anti-oxidant enzymes, thus resulting in higher glutathione accumulation and reduction of ROS production. The results showed that application of MA alleviated Cd-induced phytotoxicity and oxidant damage through the regulation of both enzymatic and non-enzymatic anti-oxidants under Cd stress in M. sacchariflorus.


Investigation of Babesia spp. in sympatric populations of Dermacentor reticulatus and Ixodes ricinus ticks in Lithuania and Latvia.
The objectives of the present study were to investigate the presence of the Babesia parasites in Dermacentor reticulatus ticks along its current distribution range in Lithuania and Latvia, and Ixodes ricinus in Lithuania, to characterize the detected Babesia spp. using partial sequencing of 18S rRNR gene, and to determine the prevalence of the Babesia pathogens in ticks from different locations of Lithuania and Latvia. From 2013 to 2015, four D. reticulatus nymphs and 2255 questing adults were collected from 40 locations in Lithuania, and 181 questing adult D. reticulatus specimens from 11 locations in Latvia. In Lithuania, 16 questing I. ricinus nymphs and 354 questing adults were collected from 12 locations with the sympatric existence of D. reticulatus and I. ricinus. In Lithuania, Babesia spp. were detected in 1.2% (26/2259) of D. reticulatus and in 9.5% (35/370) of I. ricinus ticks. The overall prevalence of Babesia in D. reticulatus ticks from Latvia was 2.8% (5/181). Sequence analysis of partial 18S rRNA gene of positive samples indicated the presence of B. canis and B. venatorum in D. reticulatus ticks, whereas B. microti and B. venatorum were detected in I. ricinus ticks. Our study is the first investigation on the prevalence and molecular characterization of zoonotic B. canis, B. venatorum, and B. microti in ixodid ticks in Lithuania, and of B. canis in D. reticulatus ticks in Latvia. It is also the first report of B. venatorum in D. reticulatus ticks.


Relationship between matrix metalloproteinase-7 and pit pattern in early stage colorectal cancer.
The surface pit pattern of early stage colorectal cancer changes with tumor growth and invasion. It was postulated by us that the expression of matrix metalloproteinase-7 is related to tumor invasiveness and disturbance of the pit pattern. Sixty-eight colorectal epithelial tumors were examined, and the pit pattern was classified by stereoscopic microscopy. Immunostaining for matrix metalloproteinase-7 and its substrate laminin were performed. The rate of matrix metalloproteinase-7 positive staining was significantly higher for mucosal (70.6%) and submucosal cancer (80.0%) than for adenoma (18.6%) (p<0.0083). The rate of matrix metalloproteinase-7 positive specimens was significantly higher for type IV and type V compared with type III pit patterns. Where the tumor surface was positive for matrix metalloproteinase-7, expression of laminin was negative in 40% of specimens with a type IV pit pattern and 100% of those with the type V pit pattern. The results of this study indicate that expression of matrix metalloproteinase-7 is related to both the invasiveness of colorectal epithelial tumors and the disturbance of the pit pattern on the tumor surface.


Forgotten giants: Robust climate signal in pollarded trees.
Tree ring records are among the most valuable resources to create high-resolution climate reconstructions. Most climate reconstructions are based on old trees growing in inaccessible mountainous areas with low human activity. Therefore, reconstruction of climate conditions in lowlands is usually based on data from distant mountains. Albeit old trees can be common in humanized areas, they are not used for climate reconstructions. Pollarding was a common traditional management in Europe that enabled trees to maintain great vitality for periods exceeding the longevity of unmanaged trees. We evaluate the potential of pollarded deciduous oaks to record past climate signal. We sampled four pollarded woodlands in Central Spain under continental Mediterranean climate. We hypothesized that pollarded trees have a strong response to water availability during current period without pollarding management, but also in the period under traditional management if pruning was asynchronous among trees. Moreover, we hypothesized that if climate is a regional driver of oak secondary growth, chronologies from different woodlands will be correlated. Pollard oaks age exceeded 500 years with a strong response to Standardized Precipitation-Evapotranspiration Index (SPEI) from 9 to 11 months. Climate signal was exceptionally high in three of the sites (r2 = 0.443-0.655) during low management period (1962-2022). The largest fraction of this climate signal (≈70 %) could be retrieved during the traditional management period (1902-1961) in the three sites where pollarding was asynchronous. Chronologies were significantly correlated since the 19th century for all the studied period, highlighting a shared climate forcing. We identified critical points to optimize pollard tree sampling schema. Our results show the enormous potential of pollarded woodlands to reconstruct hydroclimate conditions in the Mediterranean with a fine spatial grain. Studying pollarded trees is an urgent task, since the temporal window to retrieve the valuable information in pollarded trees is closing as these giants collapse and their wood rots.


Psychiatric Multimorbidity in a Specialized Program for Severely Mentally Ill Veterans.
It has been suggested that psychiatric multimorbidity may better characterize severely impaired psychiatric patients than individual severe mental illness (SMI) diagnoses, and that these patients may be better served by centers offering integrated co-located, psychiatric and social services than in conventional clinics providing one-to-one care. We tested the hypothesis that multimorbidity is a critical characteristic of Veterans treated at a co-located multi-service Veteran's Health Administration (VHA) program originally established to treat Veterans living with SMI. Administrative data from the VA Connecticut Health Care System from fiscal year 2012 were used to compare veterans using diverse mental health and social services at the Errera Community Care Center (ECCC), an integrated "one-stop shop" for SMI veterans, and those seen exclusively at standard outpatient mental health clinics. Bivariate and multiple logistic regression analyses were used to compare groups on demographic characteristics, psychiatric and medical diagnoses, service utilization, and psychotropic medication fills. Results: Of the 11,092 veterans included in the study, 2281 (20.6%) had been treated at the ECCC and 8811 (79.4%) had not. Multivariable analysis highlighted the association of treatment in the ECCC and younger age, lower income, homelessness, and especially multimorbidity including both multiple substance use and multiple psychiatric diagnoses. Programs originally designed to address the diverse needs of patients living with SMI and homelessness may be usefully characterized as treating patients with psychiatric multimorbidity, a term of greater clinical relevance. Effectiveness research is needed to evaluate the one-stop shop approach to their treatment.


Toluene diisocyanate concentration investigation among TDI-related factories in Taiwan and their relations to the type of industry.
To determine nationwide 2,4- and 2,6-toluene diisocyanates (TDI) concentrations among polyurethane (PU) resin, PU foam, and other TDI-related industries in Taiwan. The ratios of 2,4-/2,6-TDI and the noncarcinogenic risk among these three industries were also investigated. Personal and fixed-area monitoring of TDI concentrations as well as questionnaires were performed for 26 factories in Taiwan. The modified OHSA 42 method was applied in sampling and analysis. Noncarcinogenic hazard index was estimated for these three industries based on the average concentration measurements. Significant differences of TDI concentrations were found among the three industry categories. For personal monitoring, PU foam was found to have the highest TDI levels [18.6 (+/-33.6) and 22.1 (+/-42.3) ppb for 2,4- and 2,6-TDI], Others average [8.3 (+/-18.9) and 10.2 (+/-17.2) ppb], and PU resin lowest [2.0 (+/-3.5) and 0.7 (+/-1.2) ppb]. The estimated average hazard indices were found to be 310-3310. A substantial percentage of airborne TDI concentrations among in Taiwan industries exceeded current TDI occupational exposure limit, and significant difference of TDI levels were found among the three industry categories. The control remedy for the tasks of charging and foaming should be enforced with the highest priority. A separate 2,6-TDI exposure standard is warranted.


Macrophage biology in development, homeostasis and disease.
Macrophages, the most plastic cells of the haematopoietic system, are found in all tissues and show great functional diversity. They have roles in development, homeostasis, tissue repair and immunity. Although tissue macrophages are anatomically distinct from one another, and have different transcriptional profiles and functional capabilities, they are all required for the maintenance of homeostasis. However, these reparative and homeostatic functions can be subverted by chronic insults, resulting in a causal association of macrophages with disease states. In this Review, we discuss how macrophages regulate normal physiology and development, and provide several examples of their pathophysiological roles in disease. We define the 'hallmarks' of macrophages according to the states that they adopt during the performance of their various roles, taking into account new insights into the diversity of their lineages, identities and regulation. It is essential to understand this diversity because macrophages have emerged as important therapeutic targets in many human diseases.


All Talk, No Assembly: Voltage-Gated Calcium Channels Do Not Mediate Active Zone Formation.
How synapses assemble remains unknown. In this issue of Neuron, Held et al. (2020) demonstrate that Cav2-type voltage-gated calcium channels do not mediate presynaptic assembly. Moreover, the channel-associated protein α2δ localizes independently, suggesting additional functions for this auxiliary protein.


High serum urate in HIV-infected persons: the choice of the antiretroviral drug matters.
Data with regard to serum uric acid levels in HIV-infected subjects are scarce. A high prevalence of hyperuricaemia was identified in a prospective analysis of urate levels in 2287 visits made by a cohort of 270 HIV-positive patients. In univariate and multivariate analysis, hyperuricaemia was associated with factors previously identified in HIV-uninfected individuals, but also with the use of some antiretroviral drugs, particularly with the use of stavudine.


Laparoscopic mesh explantation and drainage of sacral abscess remote from transvaginal excision of exposed sacral colpopexy mesh.
Sacral colpopexy may be complicated by mesh exposure, and the surgical treatment of mesh exposure typically results in minor postoperative morbidity and few delayed complications. A 75-year-old woman presented 7 years after a laparoscopic sacral colpopexy, with Mersilene mesh, with an apical mesh exposure. She underwent an uncomplicated transvaginal excision and was asymptomatic until 8 months later when she presented with vaginal drainage and a sacral abscess. This was successfully treated with laparoscopic enterolysis, drainage of the abscess, and explantation of the remaining mesh. Incomplete excision of exposed colpopexy mesh can lead to ascending infection and sacral abscess. Laparoscopic drainage and mesh removal may be considered in these patients.


Cellular and subcellular localization of kainic acid in the marine red alga Digenea simplex.
Polyclonal antibodies specific for the excitatory amino acid, kainic acid (KA), were raised in rabbits. The antibody recognized KA but did not cross-react with other structurally related amino acids, including glutamate. We used this anti-KA antibody to localize KA immunohistochemically in the KA-producing red alga Digenea simplex. KA immunoreactivity was most dense in the fine cylindrical thallus, which covers the middle to upper part of the alga. The cortical cells, but not the inner layers of the main axis, and cells of the rhizoid were also stained with this antibody. The presence of KA in cells that cover the surface of the alga might reflect its role in chemical defense. At the subcellular level, KA immunoreactivity was most intense in the nucleus, pit plugs, and the electron-dense areas denoted as "granule bodies", which were found only in the pericentral cells of the thallus.


Purification of beta-N-acetyl-D-glucosaminidase of the horseshoe crab by affinity chromatography.
An affinity column has been synthesized consisting of p-aminophenyl 1-thio-beta-L-fucopyranoside residues attached to Sepharose 4B through succinylated diaminodipropylamine bridges. Surprisingly, it has been found to bind beta-N-acetylglucosaminidase in the serum of Limulus polyphemus (horseshoe crab). The enzyme is eluted with N-acetyl-D-glucosamine at a concentration of 2 mg/ml and with other sugars at higher concentrations. A highly purified enzyme free from other glycosidases is obtained. The enzyme is not eluted by solutions of salt.


Concentration-detection functions for the odor of homologous n-acetate esters.
Using air-dilution olfactometry, we measured concentration-response functions for the odor detection of the homologous esters ethyl, butyl, hexyl, and octyl acetate. Stimuli were delivered by means of an 8-station vapor delivery device (VDD-8) specifically designed to capture odor detection performance by humans under environmentally realistic conditions. Groups of 16-17 (half female) normosmic (i.e., having a normal olfaction) non-smokers (ages 18-38) were tested intensively. The method involved a three-alternative forced-choice procedure against carbon-filtered air, with an ascending concentration approach. Delivered concentrations were confirmed by gas chromatography before and during actual testing. A sigmoid (logistic) model provided an excellent fit to the odor detection functions both at the group and individual levels. Odor detection thresholds (ODTs) (defined as the half-way point between chance and perfect detection) decreased from ethyl (245 ppb by volume), to butyl (4.3 ppb), to hexyl acetate (2.9 ppb), and increased for octyl acetate (20 ppb). Interindividual threshold variability was near one and always below two orders of magnitude. The steepness of the functions increased slightly but significantly with carbon chain length. The outcome showed that the present thresholds lie at the very low end of those previously reported, but share with them a similar relative trend across n-acetates. On this basis, we suggest that a recent quantitative structure-activity relationship (QSAR) for ODTs can be applied to these and additional optimized data, and used to describe and predict not just ODTs but the complete underlying psychometric odor functions.


Postvaccination increase in serotype 19A pneumococcal disease in Norway is driven by expansion of penicillin-susceptible strains of the ST199 complex.
Serotype replacement in invasive pneumococcal disease has been observed after widespread use of the 7-valent pneumococcal conjugate vaccine (PCV7). Replacement is dominated by penicillin-nonsusceptible serotype 19A in several countries. Antibiotic selection pressure has been proposed to interact with immunization, leading to rapid replacement. In Norway, where prescription of antibiotics is limited, post-PCV7 replacement by serotype 19A is dominated by penicillin-susceptible clones. Hence, serotype 19A replacement occurs, although it is not driven by antibiotic selection pressure.


Cost Effectiveness of HIV Prevention Interventions in the U.S.
The purpose of this study was to assess and compare the cost effectiveness of current HIV prevention interventions in the U.S. using a consistent, standardized methodology. The cost effectiveness of common and emerging HIV biomedical and behavioral prevention interventions as delivered to men who have sex with men, injection drug users, and sexually active heterosexuals was estimated. Data on program costs, intervention efficacy, risk behaviors, and per contact transmission probabilities were collected from peer-reviewed papers and health department reports. These data were combined with 2010 national HIV incidence and prevalence surveillance data in a Bernoulli process model to estimate the reduced annual risk of HIV transmission or acquisition associated with these interventions. The cost per prevented case of HIV and the cost per saved quality-adjusted life year were then calculated. Analyses were conducted between 2014 and 2015. Interventions to diagnose HIV and provide ongoing care and treatment had the lowest cost per prevented case. Among interventions targeted at specific risk groups, interventions for men who have sex with men were the most cost effective. The least cost-effective interventions typically addressed people at risk of acquiring HIV rather than those at risk of transmitting the disease. HIV prevention interventions targeted at high-risk populations, those associated with the care continuum, and those that reduce the transmission risk of HIV-infected people are typically the most cost effective. Decision makers can consider these results in planning an efficient allocation of HIV prevention resources.


Factitious pain and swelling of the upper arm. Case report.
After a trivial injury, a 16-year-old girl had pain, disability and oedema in her right arm. In a first operation the suspectedly entrapped ulnar nerve was anteposed, and in a second--because symptoms worsened--it was retroposed. The condition proved to be self-induced, by compression of the arm with a bandage.


Primary echocardiographic results of the Carpentier-Edwards Perimount Magna.
The aim of this study was to investigate the primary echocardiographic results of aortic valve replacement using 21- and 19-mm Carpentier-Edwards Perimount Magna bioprosthesis aortic xenografts in patients with small aortic annulus. Twenty patients (mean body surface area 1.63 ± 0.16 m(2)) underwent aortic valve replacement between June 2008 and December 2009. Eight and 12 patients received 21- and 19-mm Magna bioprostheses, respectively. After 12 months, hemodynamic data were obtained by echocardiography to estimate the prosthesis-patient mismatch. At follow-up, significant decreases in peak and mean left ventricular aortic pressure gradients were observed in the 12 patients with aortic stenosis (P < 0.05). Regression of the left ventricular mass was observed in all the patients (P < 0.05). The mean measured effective orifice area (EOA) and EOA index (EOAI) were 1.61 ± 0.28 cm(2) and 0.99 ± 0.16 cm(2)/m(2), respectively. Prosthesis-patient mismatch (EOAI ≤0.85) was documented in three patients. The primary echocardiographic findings suggested that the hemodynamic performance of the 19- and 21-mm Carpentier-Edwards Perimount Magna bioprostheses was satisfactory in the patients with a small aortic annulus.


Left gastric artery as an alternative for arterial reconstruction in orthotopic liver transplantation.
The hepatic arterial blood supply is indispensable for the survival of the graft during liver transplantation. Inadequacies in the recipient hepatic artery mandate arterial reconstruction different from the preferred method of direct anastomosis. We report the use of the left gastric artery as an attractive alternative for reconstructing the arterial blood supply of a transplanted liver.


Sulcozoa revealed as a paraphyletic group in mitochondrial phylogenomics.
Recently, phylogenomic analyses have been used to assign the vast majority of eukaryotes into only a handful of supergroups. However, a few enigmatic lineages still do not fit into this simple picture. Such lineages may have originated early in the history of eukaryotes and are therefore of key importance in deduction of cellular evolution. In this study, we focus on two deeply diverging lineages, Diphyllatea and Thecamonadea. They are classified in the same phylum, Sulcozoa, but previous multigene phylogenetic analyses have included only one of these two lineages. It is therefore unclear whether they constitute one group or two distinct lineages. The study of rare genomic changes reveals that both have the fused dihydrofolate reductase (DHFR) and thymidylate synthase (TS) genes (i.e. DHFR-TS), which are separated in all other unikonts that have been investigated, indicating a possible close relationship. Their phylogenetic positions have implications for the classification of Sulcozoa and the early eukaryote evolution. Here we present a phylogenomic analysis of these species that include Illumina and 454 transcriptome data from two Collodictyon strains. A total of 42 mitochondrial proteins, which correspond to orthologs published from Thecamonas trahens (Thecamonadea), were used to reconstruct their phylogenies. In the resulting trees, Collodictyon appears as sister to Amoebozoa, whereas Thecamonas branches as the closest relative of Opisthokonta (i.e. the animal, fungi and unicellular Choanozoa). In contrast, the position of another early diverging eukaryote, Malawimonas, is unresolved. The separation of Collodictyon and Thecamonas in our studies suggests that the recently proposed Sulcozoa group is most likely paraphyletic. Furthermore, the data support the hypothesis that the two supergroups Opisthokonta and Amoebozoa, which comprise a great diversity of eukaryotes, have originated from a sulcozoan ancestor.


Attitude towards computer-based learning: determinants as revealed by a controlled interventional study.
Curriculum-wide implementation of computer-based learning (CBL) in undergraduate medical education remains elusive. Unlike many pilot tests of singular learning programmes, dropout rates are high and acceptance seems low in the long run. We studied the effect of a new CBL programme, suitable for curriculum-wide implementation, on Year 3 medical students' attitudes towards CBL. Students from 2 universities participating in a mandatory pharmacology course were given access to a CBL programme covering cardiovascular drug therapy in a controlled randomised study (n = 167). Learner properties and attitude towards CBL were measured using psychometric scales, and knowledge by multiple-choice questions (pre- and post-test). Attitude towards CBL worsened in the CBL group (n = 70). Individual learners' properties did not explain this effect. The perceived programme quality was rated only 'average', which may contribute to the lower post-test values of attitude towards CBL. Learning outcomes were similar between the control group (n = 97) and students using CBL (n = 44). Learning efforts were shifted from self-study towards CBL. The initial enthusiasm of students was not maintained when using a programme designed to complement or even replace traditional teaching. Curriculum-wide implementation of CBL might be hampered by the discouragement of users.


Effects of Maillard reaction on physicochemical and functional properties of walnut protein isolate.
In this study, the Maillard reaction (MR) of glucose was applied to improve the physicochemical and functional properties of walnut protein isolate (WNPI). The MR products (MRPs) were prepared with glucose at 0 h (MRP0), 1 h (MRP1), 2 h (MRP2) and 3 h (MRP3) heating at 95 °C. The Infra-Red spectrum showed reduction of amide and S-H functionalities in MRPs with complete intermixing of glucose in MRP3. Scanning electron microscopy indicated changes in the morphology of MRP3 which also exhibited promising antioxidant effect. Significant decrease (P < 0.05) in hydrophobicity values (Ho) and increase (P < 0.05) in emulsifying activity/emulsifying stability indexes values were observed for MRPs. Uniform droplet distribution was observed in microscopy of emulsions while an increase in the interfacial protein concentration ( Г) was obtained for MRPs. These results suggest that MR is useful in improving the utilization of this protein in food product development.


The impact of fall-related loading rate on the formation of micro-damage in human cortical bone fracture.
The quest for better predictive tools as well as new preventative and therapeutic measures for bone fragility and fracture has highlighted the need for greater mechanistic understanding of the bone fracture process. Cortical bone, the major load bearing part of the bone, employs different toughening mechanisms to either inhibit or slow down crack growth which leads to fracture. Among these toughening mechanisms, is the formation of a micro-damage process zone (MDPZ) around the region of the propagating crack. Investigations into the MDPZ to date have primarily been based on quasi-static or cyclic loading rate experiments which do not necessarily replicate physiological fracture rates. Consequently, the impact of fall-related loading rates on the formation of the micro-damage process zone was investigated comparing these to quasi-static loading rate equivalents. The size of MDPZ was found to be 42% smaller in the high-rate group compared to the quasi-static rate group. The smaller MDPZ size was associated with a brittle, unstable fracture behaviour and an overall smaller fracture resistance measure (Jmax). This result points to the possibility of a strain rate hardening mechanism at the heart of micro-damage formation, which is hampered under high loading rates, resulting in lower overall fracture resistance.


Students' reports of athletic involvement as predictors of drinking: a pilot study.
54 undergraduates' reports indicated that the amount of alcohol consumed per week did not differ among university athletes, intramural athletes, and non-athletes, but it was positively related to male gender and to reported smoking.


Modelling the PKPD of oxycodone in experimental pain - Impact of opioid receptor polymorphisms.
Polymorphisms in the opioid receptor genes may affect the pharmacodynamics (PD) of oxycodone and be part of the reason behind the diversity in clinical response. The aim of the analysis was to model the exposure-response profile of oxycodone for three different pain variables and search for genetic covariates. Model simulations were used to predict how population and effect-size impact the power to detect clinical significant SNPs. The population pharmacokinetic-pharmacodynamic (PKPD) model of oral single-dosed oxycodone was based on pooled data from three published studies in healthy volunteers. Pain tolerance data from muscle pressure (n=36), visceral pressure (n=54) and skin pinch (n=34) were included. Genetic associations with 18 opioid-receptor SNPs were explored using a stepwise covariate approach. Model simulations were performed using the estimated model parameters. None of the selected SNPs were associated with analgesic response of oxycodone at P<0.001. Baseline response in muscle cuff pressure was associated with OPRK1 rs7016778 and rs7824175 (P<0.001). Simulations indicated that large differences in drug response between genotypes (>50% for similar population sizes) or large populations (n>200 for a 20% response difference) are necessary to identify clinical significant SNP effects due to high population variability. A population PKPD model has been developed for oral oxycodone using three different pain variables to explore impact of genetic covariates and study design. None of the selected polymorphisms were significantly associated with analgesic response of oxycodone, but an association of baseline response in muscle cuff pressure with two OPRK1 SNPs was identified.


Diode laser photocoagulation of intraoral (and perioral) venous malformations: Cases series.
Vascular anomalies are subdivided into vascular tumors (hemangiomas) and vascular malformations. They are frequently located in the head, neck, and oral cavity. They are common complaints reported in patients seeking treatment for aesthetic or functional issues. However, recent advances in the diagnosis and management of these lesions are improving treatment strategies. This review provides both basic and up-to-date knowledge on the most common vascular anomalies encountered by practitioners. Due to the wide variability of treatment options which often generates debate, this paper work aims to provide a comprehensive approach of these lesions based upon current concepts and practical clinical experience. Our article is about 4 patients who had consulted for one or several purplish, elevated, well limited and soft lesion. These lesions was not painful, but worrying for patients. Therapies for VAs continue to generate a dilemma for oral surgeons. Several treatment options were reported, including conventional surgery with or without adjunctive preoperative embolization, and drug therapies, such corticosteroids, intralesional injection of corticosteroids and intralesional injections of sclerosing agents. All of these therapeutic approaches carry a high risk of severe side effects such as scars, pain, and bleeding [7]. Nowadays, advances in the use of lasers have allowed doctors an effective treatment with minimal side effects [9]. All our cases described in this article were done by Pr Haitami, using the 980 nm Diode laser, and a complete healing was observed in about 8 months at the most. The laser is therefore a great help in the management of this type of lesion.


Comparing the clinical impact of pancreatic cyst surveillance programs: A trial of the ECOG-ACRIN cancer research group (EA2185).
The optimal surveillance strategy for pancreatic cysts, which occur in up to 20% of the adult population, is ill defined. The risk of malignant degeneration of these cysts is low, however the morbidity and mortality associated with pancreatic cancer are high. Two clinical surveillance guidelines are in regular use. Both the Fukuoka and American Gastroenterological Association (AGA) guidelines rely on radiographic and endoscopic imaging. They differ primarily in their recommended frequencies of interval surveillance imaging. While evidence driven clinical guidelines should promote higher quality care, competing guidelines on the same topic may provide discordant recommendations and potential reduction in the quality and/or value of care. The primary objective is to compare the clinical effectiveness of the two surveillance guidelines to identify patients most likely to benefit from pancreatic resection. Secondary objectives include comparison of resource utilization, patient reported outcomes, incidental findings are other clinical outcomes. 4606 asymptomatic patients with newly identified pancreatic cysts ≥1 cm in diameter will be randomized 1:1 to high intensity (Fukuoka) or low intensity (AGA) surveillance. All participants will be followed prospectively for 5 years. Differing guidelines confuse providers, patients and policymakers. This large, prospective, randomized trial will compare the clinical effectiveness and resource allocation requirements of two guidelines addressing a common clinical entity. CLINICALTRIALS. NCT04239573.


Multistep tumorigenesis and the microenvironment.
Early-stage cancers have long been considered to be less aggressive than late-stage cancers because it is assumed that they have accumulated fewer of the mutations that are required for full metastatic potential. For breast cancer, recent gene expression profiling data have challenged this paradigm by identifying early-stage cancers with similar gene expression profiles to fully metastatic cancers. In this review, multistep carcinogenesis is reconsidered in light of these new data. The concept that the tumor stroma plays a key role in determining whether a metastatic tumor cell will remain dormant or become invasive is discussed. Recent studies demonstrating the feasibility of targeting tumor stroma for cancer prevention and treatment are presented.


PCR primers with enhanced specificity for nematode-trapping fungi (Orbiliales).
Nematode-trapping fungi, a monophyletic lineage within the Orbiliales (Ascomycota), use specialized structures to capture and consume nematodes in soil, leaf litter, and other substrates. These fungi have been studied both because of their unique predatory life history and because they are potential control agents of important plant- and animal-parasitic nematodes. Ecological studies of nematode-trapping fungi have primarily used culture-based methods, but molecular detection techniques are now available and should be useful for studying this group. We developed Orbiliales-specific PCR primers for the ITS and 28s rDNA to directly detect nematode-trapping fungi without culturing and also to screen fungal isolates for phylogenetic placement in the Orbiliales. We used these primers to selectively amplify, clone, and sequence Orbiliales DNA extracted from soil, litter, and wood, and we compared the results of molecular detection with those obtained using a culture-based method. Of the eight species of nematode-trapping Orbiliales detected with the culture-based assay, only three were detected with PCR. The molecular assay, however, detected 18 species of uncultured Orbiliales, many of which are closely related to nematode-trapping fungi and fungal parasites of nematode eggs. Our results suggest that the combined use of Orbiliales-specific primers and culture-based techniques may benefit future studies of nematophagous fungi.


What are the functions of psychiatric classifications?
Faced with clinical, methodological, conceptual and modeling challenges, psychiatric nosology turned forty years ago towards a descriptive approach, with the third edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III). More recently, the discipline has sought answers in precision medicine and biomarkers, e.g., with the Research Domain Criteria project of the National Institute for Mental Health, towards statistical and dimensional approaches, e.g., the Hierarchical Taxonomy of Psychopathology, or towards dynamic (e.g., staging models) and computational approaches (e.g., symptom network in psychopathology). However, despite these attempts to guardedly move away from a descriptive perspective, the functions of classifications have remained the same in psychiatry over time. These functions could be seen as the guarantee of a stable ground for psychiatry, and it seems necessary that they be made explicit from methodological and deontological points of view.


A graphene electrode functionalized with aminoterephthalic acid for impedimetric immunosensing of Escherichia coli.
A screen-printed electrode prepared from graphene oxide (GO) has been functionalized with 2-aminoterephthalic acid, followed by the exploitation of this functional material in an electrochemical immunoassay for Escherichia coli (E. coli) by immobilizing the antibody on its surface. The functionalization steps followed a straightforward approach and were proven by various instrumental techniques. The detection of E. coli with antibody immobilized electrodes was performed using electrochemical impedance spectroscopy. The analyses were carried out using the hexacyanoferrate redox couple as the electrochemical probe. The present method has a wide analytical range (from 2.2 × 102 to 2.2 × 108 cfu.mL-1), a low limit of detection (2 cfu.mL-1), fast response (4 min), and good stability (up to 2 months). The analytical performance of the biosensor was comparable to the previously reported electrochemical biosensors for E. coli. As such, the approach of functionalization of graphene with 2-aminoterephthalic acid should be useful to allow the development of other similar sensing systems for other environmentally and clinically important analytes. Graphical abstractSchematic representation of the preparation and the function of an amino-functionalized graphene oxide (NH2-GO) based impedimetric biosensor for the electrochemical detection of E. coli.


Quantitative analysis of electrical properties of dendritic spines.
Several suggestions have been made with regard to the functional significance of dendritic spines in connection with synaptic plasticity. We have shown that for a constant synaptic current, when the synaptic resistance is large compared to the spine-stem resistance, a morphological change in the spine does not produce a marked change in the postsynaptic potential (PSP). When the synaptic resistance is comparable to the spine-stem impedance a morphological change in the spine can induce changes in the synaptic current and the PSP due to the so-called nonlinear effect to the synapse (Kawato and Tsukahara, 1983, 1984). Consequently, in a study of the electrical properties of dendritic spines the input impedance of the parent dendrite, the spinestalk conductance and the conductance change associated with synaptic activity must be considered. We quantitatively estimated all three factors. By comparing electrophysiological data with morphological data, we estimated the synaptic conductance which causes corticorubral EPSP. Its maximum amplitude was 43 nS with a time-to-peak value of 0.3 ms. With this value, the effects of the spine were examined using an improved algorithm based on that of Butz and Cowan (1974). It uses a three-dimensional morphology of the rubrospinal (RS) neurons, which was reconstructed from serial sections containing HRP-filled RS cells. As the spine shortens, the amplitude of the EPSP becomes considerably larger, but its time-to-peak value does not markedly change. Moreover, if unitary EPSP in the RS cell is produced by the activation of several synaptic terminals a morphological change of the spine has a smaller effect on the EPSPs.


Predictors of quality of life in inpatients with schizophrenia.
Shortening hospital stays has become a key focus in psychiatric care in recent years. However, patients with schizophrenia account for about 60% of inpatients in psychiatry departments in Japan. This study was designed to investigate the relationship between quality of life (QOL) and key indicators for long-term hospital stays among schizophrenia inpatients. A further aim was to elucidate the clinical determinants of QOL among long-stay inpatients. The study sample consisted of 217 inpatients with schizophrenia. Age, duration of illness, duration of hospitalization, years of education, body mass index, neurocognitive function, drug-induced extrapyramidal symptoms, involuntary movements, psychiatric symptoms, and dose equivalents of antipsychotics and anticholinergic agents were used as index factors. Pearson linear correlation and regression analyses were performed to examine the associations between QOL and the above-mentioned factors. Negative symptoms, psychological discomfort, and resistance as rated on the Brief Psychiatric Rating Scale (BPRS) were correlated with all subscale scores of the Japanese version of the Schizophrenia Quality of Life Scale (JSQLS). Stepwise regression showed that negative symptoms, psychological discomfort, and resistance predicted the dysfunction of psycho-social activity score and the dysfunction of motivation and energy score on the JSQLS. This study shows that active treatment for negative symptoms, psychological discomfort, and resistance should be recommended to improve QOL among inpatients with schizophrenia.


Salvage chemoradiation therapy for recurrence after radical surgery or palliative surgery in esophageal cancer patients: a prospective, multicenter clinical trial protocol.
Currently, adjuvant therapy is not recommended for patients with thoracic esophageal squamous cell cancer (TESCC) after radical surgery, and a proportion of these patients go on to develop locoregional recurrence (LRR) within 2 years. Besides, there is no evidence for salvage chemoradiation therapy (CRT) in patients with residual tumor after esophagectomy (R1/R2 resection). In addition, factors like different failure patterns and relationship with normal organs influence the decision for salvage strategy. Here, we aimed to design a modularized salvage CRT strategy for patients without a chance of salvage surgery according to different failure patterns (including R1/R2 resection), and further evaluated its efficacy and safety. Our study was designed as a one arm, multicenter, prospective clinical trial. All enrolled patients were stratified in a stepwise manner based on the nature of surgery (R0 or R1/2), recurrent lesion diameter, involved regions, and time-to-recurrence, and were further assigned to undergo either elective nodal irradiation or involved field irradiation. Then, radiation technique and dose prescription were modified according to the distance from the recurrent lesion to the thoracic stomach or intestine. Ultimately, four treatment plans were established. This prospective study provided high-level evidence for clinical salvage management in patients with TESCC who developed LRR after radical surgery or those who underwent R1/R2 resection. Prospectively Registered. ClinicalTrials.gov NCT03731442 , Registered November 6, 2018.


Rat prolactin-like protein A partial gene and promoter structure: promoter activity in placental and pituitary cells.
Rat prolactin-like protein A (rPLP-A) is a member of a rapidly expanding family of prolactin-related proteins that are expressed during pregnancy by the rat placenta according to specific developmental patterns. Although the factors involved in the pituitary-specific expression of the prolactin and growth hormone genes themselves have been extensively studied, essentially nothing is known of the factors responsible for the placental expression of these new family members. In this paper we describe the isolation of rPLP-A genomic clones, analyze a portion of the 5' flanking sequence of this gene and use the recently described rat choriocarcinoma cell line, Rcho, in transient transfection studies to show that a 975 base-pair (bp) fragment of 5' flanking sequence is sufficient to specify placental expression of the rPLP-A gene.


Needle core biopsy guided with mammography: a study of cost-effectiveness.
To analyze the cost-effectiveness of needle core biopsy (NCB) in a breast cancer screening program. A computer model was used to compare two hypothetical groups of women: those who undergo annual mammographic screening and those observed without screening. All clinically significant outcomes for each group were included in the model, which reflected the state of a woman's health each year beginning at age 40 years and ending at age 85 years. The marginal cost per year of life saved by screening was reduced a maximum of 23% (from $20,770 to $15,934) with use of NCB instead of surgical biopsy. The cost of NCB had less effect on cost-effectiveness than the number of women who underwent NCB. When used for the same indications as surgical biopsy, NCB substantially reduces the cost of a breast cancer screening program.


Immunohistologic characterization and quantitation of leukocyte subpopulations in human semen.
Various major leukocyte subpopulations (granulocytes, monocytes/macrophages, B lymphocytes, helper and suppressor/cytotoxic T lymphocytes) were detectable in human semen by applying monoclonal antibodies (MAbs) specific for pan-leukocyte and leukocyte subpopulation markers. MAb-labeled cells in smears of washed human semen were visualized by a standard streptavidin-biotin immunoperoxidase method. This approach was validated by testing the MAb panel against sections of human testis and epididymis to rule out cross-reactivity with immature germ cells or other reproductive tract cells, and against peripheral blood leukocytes that had been incubated in human semen to ascertain leukocyte marker stability in seminal plasma. When the immunoperoxidase technique was applied to semen smears from 17 proven fertile men and 51 randomly selected infertility patients, the authors found highly varying total leukocyte numbers, ranging from 8970 to 20,520,000 per ejaculate among fertile men (median, 170,000), and from 43,120 to 104,580,000 among infertility patients (median, 1,035,000). Higher means and medians of granulocytes, monocytes/macrophages, and lymphocyte subsets were seen in the infertility group. These results warrant further investigation on the diagnostic utility of semen leukocyte profiles and the possible role of seminal leukocytes in male infertility.


The mechanics of predation by the shore crab, Carcinus maenas (L.), on the edible mussel, Mytilus edulis L.
Mechanical aspects of predation by the shore crab, Carcinus maenas, on the edible mussel, Mytilus edulis, were examined. The shore crabs from the population studied utilized five distinct, largely size-related, mussel-opening techniques. Crushing the mussel umbone appeared the most successful opening method for medium-sized prey. Small mussels were crushed outright and large mussels could be opened by a slow, uneconomical, boring technique. The strengths of mussels, from an exposed shore, were tested under compression in four separate planes to determine the loads a crab would need to apply to crush the shells outright and the mechanical properties of mussels. Little inter-plane variability in compressive strength was observed, although intra-plane variability appeared high. The compressive strengths of mussels from a sheltered shore were found to be significantly higher than those from the exposed shore in the plane tested. A strain gauge was embedded in a mussel shell enabling the pattern and magnitude of forces produced by crab chelae in opening a mussel to be studied. The crab's chelae did not appear overwhelmingly strong when compared directly to the compressive strength of the crab's preferred mussel sizes. It is, therefore, postulated that crabs usually seek out and exploit weak spots in the umbone of mussels by trial and error, eventually breaking through the shell by a cumulative process of extending minute fractures in the shell substructure.


Exogenous Amylase Reverses Cerebral Ischemia Induced by Selective Intraarterial Injection of Degradable Starch Microspheres: An Angiographic and Histological Study in a Novel in Vivo Animal Model.
To validate a new particulate embolization method using degradable starch microspheres (DSM) and intraarterial exogenous amylase administration, which allow for regulated temporary cerebral arterial embolization without compromising tissue perfusion. Twenty-four male New Zealand rabbits were randomly divided into three groups. All animals underwent routine angiography. The control group received no additional intervention. In the ischemia group, 0.2ml DSM was administered to the animals via the right carotid artery with pulsed, gentle injections to induce ischemia in the cerebral microcirculation. Animals in the reperfusion group received 0.05 ml of exogenous amylase along with DSM administration. Six hours after the procedure, the animals were sacrificed and histopathological analysis was performed. The ischemia group was the most adversely affected group by embolization, with the highest number of pyknotic neurons. The reperfusion group, which received exogenous amylase, had lower pyknotic neurons than the ischemia group. The pyknotic neuron count was similar in some regions between reperfusion and control groups. Exogenous amylase can rapidly attenuate cerebral ischemia caused by microembolization with DSM.


Host sexual dimorphism and parasite adaptation.
In species with separate sexes, parasite prevalence and disease expression is often different between males and females. This effect has mainly been attributed to sex differences in host traits, such as immune response. Here, we make the case for how properties of the parasites themselves can also matter. Specifically, we suggest that differences between host sexes in many different traits, such as morphology and hormone levels, can impose selection on parasites. This selection can eventually lead to parasite adaptations specific to the host sex more commonly encountered, or to differential expression of parasite traits depending on which host sex they find themselves in. Parasites adapted to the sex of the host in this way can contribute to differences between males and females in disease prevalence and expression. Considering those possibilities can help shed light on host-parasite interactions, and impact epidemiological and medical science.


Molecular structures of centromeric heterochromatin and karyotypic evolution in the Siamese crocodile (Crocodylus siamensis) (Crocodylidae, Crocodylia).
Crocodilians have several unique karyotypic features, such as small diploid chromosome numbers (30-42) and the absence of dot-shaped microchromosomes. Of the extant crocodilian species, the Siamese crocodile (Crocodylus siamensis) has no more than 2n = 30, comprising mostly bi-armed chromosomes with large centromeric heterochromatin blocks. To investigate the molecular structures of C-heterochromatin and genomic compartmentalization in the karyotype, characterized by the disappearance of tiny microchromosomes and reduced chromosome number, we performed molecular cloning of centromeric repetitive sequences and chromosome mapping of the 18S-28S rDNA and telomeric (TTAGGG)( n ) sequences. The centromeric heterochromatin was composed mainly of two repetitive sequence families whose characteristics were quite different. Two types of GC-rich CSI-HindIII family sequences, the 305 bp CSI-HindIII-S (G+C content, 61.3%) and 424 bp CSI-HindIII-M (63.1%), were localized to the intensely PI-stained centric regions of all chromosomes, except for chromosome 2 with PI-negative heterochromatin. The 94 bp CSI-DraI (G+C content, 48.9%) was tandem-arrayed satellite DNA and localized to chromosome 2 and four pairs of small-sized chromosomes. The chromosomal size-dependent genomic compartmentalization that is supposedly unique to the Archosauromorpha was probably lost in the crocodilian lineage with the disappearance of microchromosomes followed by the homogenization of centromeric repetitive sequences between chromosomes, except for chromosome 2.


Positivity rates of antithyroid antibody, antinuclear antibody and thyroid peroxidase antibody in different types of vitiligo.
Vitiligo is associated with various autoimmune disorders, and organ-specific autoantibodies are frequently found in patients with this disorder. Vitiligo is classically divided into segmental vitiligo (SV) and nonsegmental vitiligo (NSV), and it is believed that the pathogenesis differs between these two types. As the NSV type is related to an autoimmune mechanism, autoantibody detection rates are likely to be higher in the NSV type than in the segmental type; however, no comparative studies have been performed. To analyse the rates of autoantibody positivity according to the clinical features in patients with vitiligo. Rates of antithyroid antibody (Tg Ab), antinuclear antibody (ANA) and thyroid peroxidase antibody (TPO Ab) positivity were analysed and compared according to the sex, clinical type and age of onset of 807 patients with vitiligo. There were 106 patients with SV (13.1%) and 701 patients with NSV (86.9%). Tg Ab and ANA positivity did not differ between the SV and NSV types. A positive TPO Ab result was obtained in 16 patients with SV (15.1%) and 173 patients with NSV (24.7%). The TPO Ab positivity rate was significantly higher in NSV (χ² = 4.14, P < 0.05). The positivity rates of the three autoantibodies differed significantly according to age of onset (P = 0.001, P = 0.02 and P < 0.001 for Tg Ab, ANA and TPO Ab positivity, respectively). The TPO Ab positivity rate also showed a sex difference (P < 0.001). The positivity rates for the three autoantibodies showed differences according to age of onset and sex. The rates of Tg Ab and ANA positivity showed no significant differences according to clinical type, but the TPO Ab positivity rate was significantly different between SV and NSV. It appears likely that an autoimmune mechanism contributes to the pathogenesis of SV.


Insight into the neuroproteomics effects of the food-contaminant non-dioxin like polychlorinated biphenyls.
Recent studies showed that food-contaminant non-dioxin-like polychlorinated biphenyls (NDL-PCBs) congeners (PCB52, PCB138, PCB180) have neurotoxic potential, but the cellular and molecular mechanisms underlying neuronal damage are not entirely known. The aim of this study was to assess whether in-vitro exposure to NDL-PCBs may alter the proteome profile of primary cerebellar neurons in order to expand our knowledge on NDL-PCBs neurotoxicity. Comparison of proteome from unexposed and exposed rat cerebellar neurons was performed using state-of-the-art label-free semi-quantitative mass-spectrometry method. We observed significant changes in the abundance of several proteins, that fall into two main classes: (i) novel targets for both PCB138 and 180, mediating the dysregulation of CREB pathways and ubiquitin-proteasome system; (ii) different congeners-specific targets (alpha-actinin-1 for PCB138; microtubule-associated-protein-2 for PCB180) that might lead to similar deleterious consequences on neurons cytoskeleton organization. Interference of the PCB congeners with synaptic formation was supported by the increased expression of pre- and post-synaptic proteins quantified by western blot and immunocytochemistry. Expression alteration of synaptic markers was confirmed in the cerebellum of rats developmentally exposed to these congeners, suggesting an adaptive response to neurodevelopmental toxicity on brain structures. As such, our work is expected to lead to new insights into the mechanisms of NDL-PCBs neurotoxicity.


Is there association between chronic kidney disease and dental caries? A case-controlled study.
The purpose of this study was to assess the association between chronic kidney diseases (CKD) and dental caries. 107 patients with CKD and 107 with no systemic alteration were randomly included. DMFT (decayed, missing, and filled teeth), plaque index, colony-forming units (CFU) of Streptococcus mutans and salivary composition (IgA total, IgA anti- Streptococcus mutans, calcium and urea) were evaluated. McNemar and Wilcoxon tests were used to compare test and control groups. Spearman test was used to correlate time of hemodialysis and variables studied. Associations between variables were evaluated by logistic regression analysis. The number of filled teeth, the amount of IgA anti-Streptococcus mutans, salivary urea, education level, monthly income and the amount of CFU of Streptococcus mutans were statistically different between groups. There was a positive correlation between the duration of hemodialysis (Hd) and the amount of IgA anti-Streptococcus mutans, urea in saliva, and the number of CFU of Streptococcus mutans. In the adjusted model, a higher incidence of CFU mutans streptococci, elevated salivary urea, smaller number of filled teeth, lower DMFT, and less calcium salivary were associated with CKD. Programs to prevent and treat oral problems and regular follow-up at the beginning of dialysis are necessary to increase patients' awareness of their condition.


Computed Tomography-guided Pericardiocentesis: An alternative approach for accessing the pericardium.
Pericardial effusions compress the heart, decrease cardiac output, and lead to haemodynamic collapse. Ultrasound (US)-guided pericardiocentesis is the gold standard for treating pericardial effusions. Recently, the incorporation of computed tomography (CT) guidance has increased patient safety while entering the pericardium. Despite the superior performance of CT-guided pericardiocentesis in smaller, complex effusions, this procedure is not routinely performed by cardiologists and surgeons. Unlike those with an intact pericardium, patients with mediastinal trauma, pericardial adhesions, temporary pacing wires, and vascular conduits are high risk for pericardiocentesis. Tamponade physiology also increases patient susceptibility to the hypotensive effects of anaesthesia during surgical drainage. Here we illustrate the technique of CT-guided pericardiocentesis and demonstrate its application in specific clinical scenarios. We conclude that CT-guided pericardiocentesis provides a useful, alternative strategy for treating cardiac tamponade in high risk patients.


Reusing electronic patient data for dental clinical research: a review of current status.
The reuse of electronic patient data collected during clinical care has received increased attention as a way to increase our evidence base. The purpose of this paper was to review studies reusing electronic patient data for dental research. 1527 citations obtained by searching MEDLINE and Embase databases, hand-searching seven dental and informatics journals, and snowball sampling. We included studies reusing electronic patient data for research on dental and craniofacial topics, alone or in combination with medical conditions, medications and outcomes. Studies using administrative or research databases and systematic reviews were excluded. Three reviewers extracted data independently and performed analysis jointly The 60 studies reviewed covered epidemiological (32 studies), outcomes (16), health services research (10) and other (2) topics; were primarily retrospective (58 studies); varied significantly in sample size (9-153,619 patients) and follow-up period (1-12 years); often drew on other data sources in addition to electronic ones (25); but rarely tapped electronic dental record (EDR) data in private practices (3). Type of research was not associated with data sources used, but research topics/questions were. The most commonly reported advantages of reusing electronic data were being able to study large samples and saving time, while data quality and the inability to capture study-specific data were identified as major limitations. Dental research reusing electronic patient data is nascent but accelerating. Future EDR design should focus on enhancing data quality, begin to integrate research data collection and implement interoperability with electronic medical records to facilitate oral-systemic investigations. Measuring and improving the quality of dental care requires that we begin to reuse electronic patient data collected in practice for clinical research. Practice data can potentially serve as a useful complement to data collected in traditional research studies.


[Survey on deoxynivalenol, zearalenone, and HT-2/T-2 contamination of cereals and products derived from cereals].
Since February 2004 in Germany maximum limits forFusarium toxins do exist, while harmonised legislation within the EU was recently published and will come into force in July 2006. Meanwhile, the problematic nature ofFusarium mycotoxins is perceived by all participants of the processing chain of cereals. In this study the presence of deoxynivalenol and zearalenone in comparison to the rarely investigated type A-trichothecenes (HT-2, T-2 toxin) in different cereal-products is discussed. About 1000 cereal-based samples have been analysed using a recently developed multitoxin method based on HPLC-MS/MS technique. Despite, up to now no concrete limit for HT-2/T-2 toxin is discussed, the degree of contamination is of special concern for food products dedicated to be placed on the market, to avoid possible risks for consumers. The used method proved to be extremely sensitive for T-2 toxin with a LOD below 1 μg/kg, therefore a comprehensive data set was achieved.


Biochemical parameters in the anterior pituitary during the course of tumorigenesis induced by diethylstilbestrol treatment.
Treatment of F344 rats with diethylstilbestrol (DES) for 1-2 months induces a prolactin (PRL)-secreting pituitary adenoma. After 8 weeks of DES treatment, we have shown that the ratio of regulatory subunits of the cAMP-dependent protein kinase (RI/RII) increased in the tumors. Presently we report the variations in RI/RII ratio, pituitary weight, DNA content, serum PRL, nuclear estrogen receptor (E2R) and of ornithine decarboxylase (ODC) activity from the time of DES pellet implantation until 8 weeks. Pituitary weight, DNA content and serum PRL rose significantly at 4 weeks with a maximum at 6-8 weeks, and significantly correlated with each other. E2R and ODC activity increased from week 1 onwards, with a maximum at 2 weeks and decreased at 8 weeks. Both variables showed a positive correlation but neither E2R nor ODC activity correlated with pituitary weight, DNA or serum PRL. Values for RI remained stable with time, but RII decreased progressively. The RI/RII ratio was maintained around unity between 1-4 weeks, increasing to 1.6-2 thereafter. This ratio positively correlated with pituitary weight and DNA. It is suggested that during tumor induction by estrogen in a sensitive strain of rats, growth signals with different time-courses become activated. Increases in pituitary weight and DNA content, indicators of mammotroph hypertrophy and hyperplasia, were preceded by early rises in E2R and ODC activity. Increases in the RI/RII ratio accompanied the adenomatous change, suggesting their role in cell transformation after 6 weeks of estrogen exposure.


The effect of surface charge density on valinomycin-K+ complex formation in model membranes.
The model membrane approach was used to investigate the surface charge effect on the ion-antibiotic complexation process. Mixed monolayers of valinomycin and lipids were spread on subphases containing K+ or Na+. The surface charge density was modified by spreading ionizable valinomycin analogs on aqueous subphases of different pH or by changing the nature of the lipid (neutral, negatively charged) in the mixed film. Surface pressure and surface potential measurements demonstrated that a neutral lipid (phosphatidylcholine) or positively charged valinomycin analogs didn't enhance the anti-biotic complexing capacity. However, a maximal complexation is reached for a critical lipid concentration in the valinomycin-phosphatidylserine mixed film. The role of the surface charge on the valinomycin complexing properties was examined in terms of the Gouy-Chapman theory. As a consequence of the negative charge of the lipid monolayer, the K+ concentration near the surface is larger than the bulk concentration, by a Boltzmann factor. A good agreement was observed between the experimental results and the theoretical predictions. Conductance measurements of asymmetric bilayers containing a neutral lipid (egg lecithin) on one side and a negatively charged lipid (phosphatidyl-serine) on the other, confirm the role of the surface charge. Indeed, addition of K+ to the neutral side of the bilayer containing valinomycin had no effect on the conductance whereas addition of K+ to the charged side of the bilayer caused a 80-fold conductance increase.


Cholesterol deficiency carriers have lowered serum cholesterol and perform well at an elite cattle show.
Cholesterol deficiency (CD) in Holstein cattle results from an insertion in the APOB gene, which traces to the bull Maughlin Storm and was spread to elite show cattle largely through his grandson Braedale Goldwyn. Calves that are homozygous for CD can neither transport dietary fat from the gut nor synthesize low-density lipoproteins, and they perish before 6 mo of age. The mutation may have a partially dominant effect, with lowered cholesterol in heterozygous animals. Our aims were to evaluate serum cholesterol in heterozygous animals, evaluate daily phenotypic records of lactating CD carriers, and determine whether CD carrier status is associated with show ring success. Blood was collected on a single date in May 2018 from 12 carriers and 14 controls and 1 yr later from 17 carriers (7 repeated for 2018) and 27 controls (6 repeated from 2018); animals ranged in age from 14 to 84 mo and varied in stage of lactation and pregnancy status. Serum samples were analyzed for cholesterol concentration (mg/dL) and results were analyzed using mixed models that included linear and quadratic effects of days in milk and days carried calf. Daily phenotypic records of milk yield, milking time, milk conductivity, activity, and body weight were compared between carriers and controls. Additionally, the CD carrier status of cows that were sired by known CD carriers and had available genotypes was recorded. Cows placing in the top 5 and top 10 of their classes at World Dairy Expo between the years of 2006 and 2019 were included in our analysis. Chi-squared tests for equal proportions were evaluated to determine whether the following were associated with CD status: placing in the top 10 with repeated placings from the same cow included, placing in the top 5 with repeated placings, top 10 cows considering individuals only once, and top 5 cows considering individuals only once. Control animals (noncarriers) had significantly higher serum cholesterol (116.21 ± 6.45 mg/dL) than CD carriers (90.15 ± 7.49 mg/dL). There was no difference between carriers and controls in milk yield, milk conductivity, or activity. However, CD carriers had shorter milking times and lower body weights than their herdmates. Further, there were more CD carriers in the top 5 and more carriers tended to place in the top 10 at World Dairy Expo when repeated placings were included. These data support observations that CD is partially dominant and indicate that CD carriers display other phenotypic differences from their herdmates that may give them a small advantage at elite cattle shows.


Post-operative budesonide irrigations for patients with polyposis: a blinded, randomized controlled trial.
To compare normal saline (NS) vs. NS+budesonide irrigations in post- functional endoscopic sinus surgery (FESS) patients with chronic rhinosinusitis with polyposis (CRSwNP). Currently, no evidence exists for NS+budesonide irrigation over NS irrigation alone. Prospective, single-blind, randomized controlled trial. Subjects were prospectively enrolled to NS or NS+budesonide arms. Patients were evaluated at pre-operative and three post-operative visits (POV): POV1 (1-2 weeks post-op), POV2 (3-8 weeks post-op), and POV3 (3-6 months post-op). Patients were evaluated by three quality of life (QOL) questionnaires (SNOT-22, RSOM-31, and RSDI) and two olfaction scores (UPSIT and the PEA test). Fifty patients were randomized, with 25 patients in the NS arm and 25 patients in the NS+budesonide arm. Two patients had unexpected pathology and were excluded from the study. By POV2 and POV3, patients experienced a significant improvement in all three QOL surveys, although the degree of improvement between arms was not significant up through POV3. Neither arm experienced significant olfactory improvement up through POV3. While both NS and NS+budesonide treatments improve QOL for post-FESS patients, neither intervention significantly increases QOL as compared to the other. Olfaction was not significantly improved in either treatment group.


Peptidyl sulfonium salts. A new class of protease inhibitors.
The possibility has been examined that peptidylmethyl sulfonium salts might affinity label proteases by an alkyl transfer from sulfur to an active center residue. The synthesis of a number of agents of this type is described as well as initial results of their effect on cysteinyl proteases, papain and cathepsin B. These are readily inactivated by reagents in which the peptidyl portion contains features that promote binding to the proteases such as a penultimate phenylalanine residue. Irreversible inactivation ensues by transfer of the peptidyl portion, not methyl groups. Peptidylmethyl sulfonium salts lose a proton to form an ylide structure which may be the prevalent form at physiological pH values. The ylide may also be the active affinity labeling form of the reagent since the rate of inactivation of cathepsin B increases with pH. In contrast, the action of another affinity labeling reagent for cathepsin B, benzyloxycarbonyl-Phe-AlaCHN2, a diazomethyl ketone, is relatively independent of pH.


Visualization of risk of radiogenic second cancer in the organs and tissues of the human body.
Radiogenic second cancer is a common late effect in long term cancer survivors. Currently there are few methods or tools available to visually evaluate the spatial distribution of risks of radiogenic late effects in the human body. We developed a risk visualization method and demonstrated it for radiogenic second cancers in tissues and organs of one patient treated with photon volumetric modulated arc therapy and one patient treated with proton craniospinal irradiation. Treatment plans were generated using radiotherapy treatment planning systems (TPS) and dose information was obtained from TPS. Linear non-threshold risk coefficients for organs at risk of second cancer incidence were taken from the Biological Effects of Ionization Radiation VII report. Alternative risk models including linear exponential model and linear plateau model were also examined. The predicted absolute lifetime risk distributions were visualized together with images of the patient anatomy. The risk distributions of second cancer for the two patients were visually presented. The risk distributions varied with tissue, dose, dose-risk model used, and the risk distribution could be similar to or very different from the dose distribution. Our method provides a convenient way to directly visualize and evaluate the risks of radiogenic second cancer in organs and tissues of the human body. In the future, visual assessment of risk distribution could be an influential determinant for treatment plan scoring.


Isolation of bacteriocinogenic Lactobacillus plantarum strains from ben saalga, a traditional fermented gruel from Burkina Faso.
A collection of lactic acid bacteria isolated from ben saalga, a traditional fermented gruel from Burkina Faso, was screened for bacteriocin production. Seven isolates were selected for their broad antimicrobial spectra, which overall included strains of Bacillus cereus, Bacillus licheniformis, Enterococcus faecalis, Listeria innocua, Listeria monocytogenes, Staphylococcus aureus, Escherichia coli and Salmonella enterica. Cluster analysis of RAPD-PCR patterns revealed that six of the isolates represent different strains. The six selected strains were identified as Lactobacillus plantarum by 16S rDNA sequencing, species-specific PCR and multiplex PCR of the recA gene. PCR amplification revealed the presence of genes of the plantaricin cluster described in L. plantarum C11. Among them, strain 5.2.2 carried the largest number of genes from this cluster.


4-Phenylbutyric acid regulates CCl4-induced acute hepatic dyslipidemia in a mouse model: A mechanism-based PK/PD study.
Endoplasmic reticulum (ER) stress and associated protein aggregation are closely associated with human diseases, including alterations in hepatic lipid metabolism. Inhibition of ER stress can have a significant effect on the prevention of hepatic dyslipidemia. Here, we studied the role of 4-phenylbutyric acid (4-PBA), a chemical chaperone, on ER stress-induced hepatic lipid accumulation. We studied ER stress induction following CCl4 exposure and delineated mechanisms of the CCl4-induced ER stress response in liver tissue from mice. CCl4 affected the formation of disulfide bonds through excessive hyper-oxidation of protein disulfide isomerase (PDI). Increased complex formation between PDI and its client proteins persisted in CCl4-exposed samples. Conversely, 4-PBA inhibited ER stress via secretion of apolipoprotein B and prevention of hepatic lipid accumulation. We also studied the mechanism-based pharmacokinetic and pharmacodynamic profiles and identified the ER stress-related proteins GRP78 and CHOP, along with plasma apolipoprotein B and triglyceride levels, as novel biomarkers of ER stress-induced hepatic lipid accumulation. ER stress and its clinical relevance for therapeutic approaches were well correlated with the activity of the ER stress regulator 4-PBA, which may be a promising drug candidate for the treatment of hepatic lipid accumulation, such as hepatic steatosis.


Efficacy and Safety of Vibegron for the Treatment of Overactive Bladder in Women: A Subgroup Analysis From the Double-Blind, Randomized, Controlled EMPOWUR Trial.
The international phase 3 EMPOWUR trial demonstrated efficacy and safety of vibegron, a newer β 3 -adrenergic receptor agonist, in adults with overactive bladder (OAB). Women are disproportionately affected by OAB, especially those with bothersome symptoms, such as urge urinary incontinence (UUI). This subgroup analysis from EMPOWUR assessed efficacy and safety of vibegron in women. In EMPOWUR, patients with OAB were randomized 5:5:4 to 12 weeks of treatment with once-daily vibegron 75 mg, placebo, or tolterodine 4-mg extended release. Efficacy end points included change from baseline at week 12 in mean daily number of micturitions, UUI episodes, and urgency episodes. Safety was assessed through adverse events (AEs). Of the patients included in the analysis, 1286 (84.9%) were women (vibegron, n = 463; placebo, n = 459; tolterodine, n = 364). At week 12, women receiving vibegron showed significant reductions (95% confidence intervals of least squares mean differences does not include 0) from baseline versus placebo in mean daily micturitions, UUI episodes, and urgency episodes, with least squares mean differences (95% confidence intervals) of -0.5 (-0.8 to -0.2), -0.7 (-1.0 to -0.4), and -0.8 (-1.3 to -0.4), respectively. Treatment-emergent AE incidence was similar with vibegron (39%) and placebo (35%); the most common AE with incidence higher with vibegron (4.3%) than placebo (2.6%) was headache. In this subgroup analysis, women receiving vibegron showed significant reductions in key efficacy end points versus placebo and favorable safety profile, consistent with the overall results from EMPOWUR, suggesting that vibegron is efficacious and safe for the treatment of OAB in this patient population.


Evaluation of groundwater quality for drinking and irrigation purposes using proxy indices in the Gunabay watershed, Upper Blue Nile Basin, Ethiopia.
Evaluation of groundwater potential and its quality assessment for drinking and irrigation has recently become a major concern, especially in developing countries due to various constraints. The primary aim of this study is to evaluate the quality of groundwater and establish whether they are safe for domestic and agricultural usage. 78 samples were collected during dry and wet seasons from 39 locations in the Gunabay district of the upper Blue Nile, Ethiopia. The following physicochemical parameters were evaluated successfully (T, pH, EC, TDS, Na+, K+, Ca2+, Mg2+, Fe, Cl-, F-, SO4 2-, PO4 3-, CO3 2-, HCO3 -, and NO3 --N). Then, Entropy Weight Water Quality Index (EWQI) and irrigation water quality indices (SAR, %Na, MAR, RSC, PS, KI, PI, and IWQI) were used to assess the distribution of groundwater quality in the study area. The Piper diagram used to characterize the groundwater types revealed that Ca-HCO3 is dominant in the area and rock-water interaction regulates the chemical characteristics of groundwater. Wilcox diagram was used to analyze the salinity level in the groundwater. The findings showed that the groundwater had higher nitrate levels relative to the permissible level of WHO standards due to excessive use of fertilizers in rural areas. Depending on the EWQI approach, the study area was categorized as excellent, good, and medium zones, covering 84.6%, 12.8%, and 2.6%, respectively. The results depict that high-quality drinking water was available in rural areas, n high to medium in the urban regions. The comparative irrigation water indices record 85% of water wells are suitable for irrigation, but some well sites are unsuitable due to higher salinity hazards and deep rock interaction. These integrated water quality indices were effective in validating drinking and irrigation water quality in the study area.


The silent transition from curative to palliative treatment: a qualitative study about cancer patients' perceptions of end-of-life discussions with oncologists.
The aims of the study were to examine patients' experiences of end-of-life (EOL) discussions and to shed light on patients' perceptions of the transition from curative to palliative care. This study was based on a qualitative methodology; we conducted semi-structured interviews with advanced cancer patients admitted to the palliative care unit (PCU) of the Medical University of Vienna. Interviews were recorded digitally and transcribed verbatim. Data were analyzed based on thematic analysis, using the MAXQDA software. Twelve interviews were conducted with patients living with terminal cancer who were no longer under curative treatment. The findings revealed three themes: (1) that the medical EOL conversation contributed to the transition process from curative to palliative care, (2) that patients' information preferences were ambivalent and modulated by defense mechanisms, and (3) that the realization and integration of medical EOL conversations into the individual's personal frame of reference is a process that needs effort and information from different sources coming together. The results of the present study offer insight into how patients experienced their transition from curative to palliative care and into how EOL discussions are only one element within the disease trajectory. Many patients struggle with their situations. Therefore, more emphasis should be put on repeated offers to have EOL conversations and on early integration of aspects of palliative care into the overall treatment.


Adjuvant chemotherapy with a nitrosourea-based protocol in advanced malignant melanoma.
173 patients with regional lymphatic metastases (n = 139) or distant disease (n = 34) were prospectively randomised, following resection of all clinically detectable tumour, to observation (n = 88) or adjuvant chemotherapy (n = 85). The treatment group received 1, 3-bis(2-chloroethyl)-1-nitrosourea (BCNU) 80 mg/m2 intravenously (i.v.) every 4 weeks, and actinomycin-D 10 micrograms/kg, vincristine 1.0 mg/m2 i.v. every 2 weeks for 6 months. The disease-free survival curves between the two groups were significantly different (P = 0.03). The estimated 5-year disease-free survival rate for the observation group was 9% and for the treatment group 29%. However, the overall survival curves were not significantly different for the two groups. Nitrosoureas may have a weak effect as adjuvant treatment in malignant melanoma.


Dysregulation of cardiovascular and neuroendocrine responses to stress in premenstrual dysphoric disorder.
Twelve women with prospectively confirmed premenstrual dysphoric disorder (PMDD or PDD) were compared with 12 healthy control subjects for cardiovascular and neuroendocrine responses to speech and mental arithmetic (Paced Auditory Serial Addition Task) stressors during both the follicular and luteal phases of the menstrual cycle. Structured clinical interview was used to assess psychiatric and abuse histories, and standardized questionnaires were administered to assess current life stress. Results revealed that PMDD women had significantly lower stroke volume, cardiac output and cortisol levels but significantly elevated norepinephrine and total peripheral resistance at rest and also during mental stressors compared with control subjects. These effects were evident in both cycle phases. Significantly more women with PMDD had histories of sexual abuse, and they also reported greater current life stress than control subjects. Consistent with a history of trauma, the PMDD women exhibited significantly greater ratios of norepinephrine to cortisol at rest and during stress. These results are interpreted as reflecting dysregulation of the stress response and may be related to histories of severe and/or chronic exposure to stress for a subgroup of PMDD women.


A mentalization-based approach to common factors in the treatment of borderline personality disorder.
In this paper we conceptualize borderline personality disorder as a disorder of mentalizing, social cognition, and loss of resilience. Several treatment approaches are effective, and meta-analyses suggest that there are few substantive differences in effectiveness between them and between specialized and non-specialized approaches. We propose that these findings arise because of shared mechanisms of change, congruent with current thinking both about the existence of a general 'p' factor of psychopathology and a reconceptualization of personality disorders as involving a lack of resilience resulting from problems with epistemic trust and salutogenesis, the capacity to derive benefit from the social environment. Effective treatments share the characteristics of consistency, coherence and continuity, qualities particularly relevant to borderline personality disorder. They create the conditions for the reopening of epistemic trust, an essential component in therapeutic change, as it enables the individual to use the experience of being mentalized, to learn mentalizing of others, and then apply and develop these experiences in day-to-day life, which is the basis for meaningful therapeutic change.


Increased expression of valosin-containing protein (p97) is correlated with disease recurrence in follicular thyroid cancer.
Valosin-containing protein (VCP) is involved in the ubiquitin/proteasome-degradation pathway, which works in proliferation and antiapoptosis in human cancer cells. Our previous study showed that VCP expression levels correlated with the recurrence and prognosis of several human cancers, such as hepatocellular carcinoma, gastric carcinoma, and colorectal carcinoma. In this study, the correlation of VCP expression with the prognosis of differentiated thyroid carcinoma was examined. VCP expression in 332 patients who underwent operation for differentiated thyroid carcinoma--257 with papillary thyroid carcinoma and 75 with follicular thyroid carcinoma (FTC)--was analyzed by immunohistochemistry. The staining intensity in tumor cells was categorized as weaker than (low expression), equal to (intermediate expression), or stronger than (high expression) that in endothelial cells in noncancerous tissue. One hundred ten (33.5%) cases showed low VCP expression, 117 (28.0%) showed intermediate expression, and 101 (30.8%) showed high expression. VCP expression significantly correlated with histological subtype (P < .05) and lymph node metastasis (P < .01). However, it correlated with neither any clinicopathologic factor nor prognosis in papillary thyroid carcinoma. VCP expression correlated with extrathyroidal extension (P < .05), pT classification (P < .05), and lymph node metastasis (P < .01) in FTC. Patients with low VCP expressing FTC showed better disease-free and overall survival rates than those with intermediate or high expression (P < .01 and P < .05, respectively). Multivariate analysis revealed VCP expression and extracapsular extension to be independent prognostic factors for disease-free survival in cases of FTC. The prognostic utility of VCP expression in FTC was demonstrated.


The impact of passive hyperthermia on human attention networks: an fMRI study.
An attention network test (ANT) provides a behavioral measure of the efficiency of the three attention networks (alerting, orienting and executive networks) within a single task. In the present study, we investigated the effect of passive hyperthermia on the attention network with event-related functional magnetic resonance imaging (fMRI). The behavioral results showed that passive hyperthermia of 50 °C and 40% relative humidity impaired the executive function, but showed no effect on the alerting and orienting networks. The fMRI results showed that: (i) passive hyperthermia enhanced the activity in the right superior frontal gyrus and depressed the activity in the right middle occipital gyrus, left inferior parietal lobule and left culmen in the alerting network, (ii) passive hyperthermia enhanced the activity in the temporal lobe and depressed the activity in the frontal lobe, parietal lobe and occipital lobe in the orienting network, and (iii) passive hyperthermia enhanced the activity in the dorsolateral prefrontal cortex but did not affect the activity in the anterior cingulate. We concluded that passive hyperthermia impaired executive function, especially the efficiency of resolving conflict and the negative effects of passive hyperthermia on alerting and orienting were overcome through variant regional brain activation.


A deep learning-based method for detecting and classifying the ultrasound images of suspicious thyroid nodules.
The incidence of thyroid cancer has significantly increased in the last few decades. However, diagnosis of the thyroid nodules is labor and time intensive for radiologists and strongly depends on the personal experience of the radiologists. In this pursuit, the present study envisaged to develop a deep learning-based computer-aided diagnosis (CAD) method that enabled the automatic detection and classification of suspicious thyroid nodules in order to reduce the unnecessary fine-needle aspiration biopsy. The CAD method consisted of two main parts: detecting the location of thyroid nodules using a multiscale detection network and classifying the detected thyroid nodules by an attention-based classification network. The performance of the proposed method was evaluated and compared with that of other state-of-the-art deep learning methods and experienced radiologists. The proposed detection method outperformed three other detection architectures (average precision, 82.1% vs. 78.3%, 77.2%, and 74.8%). Moreover, the classification method showed a superior performance compared with four other state-of-the-art classification networks (accuracy, 94.8% vs. 91.2%, 85.0%, 80.8%, and 72.1%) and that by experienced radiologists (mean value of area under the curve, 0.941 vs. 0.833). Our study verified the high efficiency of the proposed detection method. The findings can help improve the diagnostic performance of radiologists. However, the developed CAD system requires more training and evaluation in a large-population study.