Cooperation within the therapeutic relationship improves metacognitive functioning: preliminary findings.
Both clinical observations and empirical data suggest that metacognitive functioning is a factor strongly associated with a good psychotherapeutic outcome. It has been suggested that some interpersonal social motivations (i.e., attachment and cooperation) may be associated with different levels of metacognitive functioning also within the therapeutic relationship. The aim of this study was to explore the relationship between cooperation and metacognitive monitoring within 58 psychotherapy sessions from seven different patients. All patients were initially assessed through a detailed psychiatric interview. Patients' adult attachment styles were evaluated using the Attachment Style Questionnaire. The association between the activation of patients' interpersonal social motivations (e.g., cooperation and attachment) and the modifications of metacognitive abilities during sessions was investigated using the Assessing Interpersonal Motivations in Transcripts method and the Metacognition Assessment Scale have been used. Our results showed that the activation of the patient's cooperative system is positively associated with an increase in metacognitive functioning, while the activation of attachment is not. The results of the present study have important implications for clinicians: they give empirical support for the role of cooperation in fostering metacognition within the therapeutic relationship.


A closer look at rituximab induction on HLA antibody rebound following HLA-incompatible kidney transplantation.
Rituximab has been used to increase the efficacy of desensitization protocols for human leukocyte antigen (HLA)-incompatible kidney transplantation; however, controlled comparisons have not been reported. Here we examined 256 post-transplant HLA antibody levels in 25 recipients desensitized with and 25 without rituximab induction, to determine the impact of B-cell depletion. We found significantly less HLA antibody rebound in the rituximab-treated patients (7% of donor-specific antibodies (DSAs) and 33% of non-DSAs) compared with a control cohort desensitized and transplanted without rituximab (32% DSAs and 55% non-DSAs). The magnitude of the increase was significantly larger among patients who did not receive rituximab. Interestingly, in rituximab-treated patients, of the 39 HLA antibodies that increased post transplant, 34 were specific for HLA mismatches present in previous allografts or pregnancies, implying limited efficacy in memory B-cell depletion. Compared with controls, rituximab-treated patients had a significantly greater mean reduction in DSA (-2505 vs. -292 mean fluorescence intensity), but a similar rate of DSA persistence (52% in rituximab treated-and 40% in non-treated recipients). Thus, rituximab induction in HLA-incompatible recipients reduced the incidence and magnitude of HLA antibody rebound, but did not affect DSA elimination, antibody-mediated rejection, or 5-year allograft survival when compared with recipients desensitized and transplanted without rituximab.


Relapsed parasitaemia following chemotherapy of chronic T. brucei infections in mice and its relation to cerebral trypanosomes.
Mice infected with Trypanosoma brucei can be easily cured using the available trypanocidal drugs, provided treatment is given soon after the infection; however, if infection is allowed to continue for some time then it is extremely difficult to obtain a permanent cure, and after an aparasitaemic period the infection eventually relapses. It has been shown that a relatively small number of infective trypanosomes in the brain have escaped the action of the drug and these are able to replicate and eventually they re-establish a circulating parasitaemia. The number of infective trypanosomes remaining after chemotherapy varied according to the stabilate of T. brucei, but using the stabilate T. brucei GVR 35 there were up to, 5,000 infective trypanosomes 2 days after treatment, and this rapidly increased up to 50,000 trypanosomes at 7 days. Infected mice on histological examination exhibited a mild meningitis and this was exacerbated by Berenil therapy and 7 days posttreatment the mice had an acute meningoencephalitis. It would appear that if the infective trypanosomes are completely eliminated from the brain this exacerbated reaction does not occur. It has been found that combined treatment of chronic T. brucei infections with either diminazene aceturate or suramin followed by 5-substituted nitroimidazoles at appropriate dose levels will completely eliminate the infective trypanosomes from the brain and the mice are permanently cured.


Nuclear magnetic resonance in adrenoleukodystrophy: report of a case.
The nuclear magnetic resonance images obtained in a case of adrenoleukodystrophy are presented. The areas of demyelination are clearly seen. The T1 values of the affected areas are not specific and coincide with those previously recorded in the lesions of multiple sclerosis or cerebrovascular disease. A diagnosis of adrenoleukodystrophy should be considered in younger male patients presenting with behavioural disturbances, especially when these are associated with abnormalities of vision or gait. There may be no clinical evidence of the associated adrenocortical insufficiency.


Identification of higenamine in Radix Aconiti Lateralis Preparata as a beta2-adrenergic receptor agonist1.
To screen beta2-adrenergic receptor (beta2-AR) agonists from Radix Aconiti Lateralis Preparata (RALP) as potential drug leads for asthma using a sensitive cell-based agonist assay. The beta2-AR gene was stably expressed by Chinese hamster ovary (CHO) cells also stably expressing a cyclic adenosine monophosphate (AMP) response element-linked enhanced green fluorescent protein reporter gene. The cells were used to screen agonists from high-performance liquid chromatographic fractions of an extract of RALP. The fraction with the highest activity was selected for further compound isolation and the study of the structure-activity relationship. Its active compound was further identified by chromatography and mass spectrometry. Bioactivity-directed fractionation of the crude extract of RALP led to the isolation and characterization of the effective compound, namely hignamine. It could dose-dependently relax the isolated guinea pig trachea strip precontraction with acetylcholine with EC(50) value of (2.60+/-0.36)x10(-5) mol/L. Further in vivo studies also displayed that hignamine could protect experimental asthma model induced by histamine in guinea pigs to prolong the latent periods of asthma. Hignamine, as a beta2-AR agonist existing in the extract of RALP, is the key compound contributing to the successful relief of the bronchoconstriction.


A Trio-Rac1-Pak1 signalling axis drives invadopodia disassembly.
Rho family GTPases control cell migration and participate in the regulation of cancer metastasis. Invadopodia, associated with invasive tumour cells, are crucial for cellular invasion and metastasis. To study Rac1 GTPase in invadopodia dynamics, we developed a genetically encoded, single-chain Rac1 fluorescence resonance energy (FRET) transfer biosensor. The biosensor shows Rac1 activity exclusion from the core of invadopodia, and higher activity when invadopodia disappear, suggesting that reduced Rac1 activity is necessary for their stability, and Rac1 activation is involved in disassembly. Photoactivating Rac1 at invadopodia confirmed this previously unknown Rac1 function. We describe here an invadopodia disassembly model, where a signalling axis involving TrioGEF, Rac1, Pak1, and phosphorylation of cortactin, causes invadopodia dissolution. This mechanism is critical for the proper turnover of invasive structures during tumour cell invasion, where a balance of proteolytic activity and locomotory protrusions must be carefully coordinated to achieve a maximally invasive phenotype.


Density functional complexation study of metal ions with cysteine.
Metal complexes of cysteine have been studied using a density functional theory based method together with a continuum solvation model. Complexation geometries for metal complexes of cysteine with Zn(2+), Mg(2+), Ca(2+), Fe(3+), and Mn(2+) have been determined. Different coordination modes have been considered for MCys(2) and MCys(3) complexes. Complexation energies have been determined, and they have been corrected with (empirical) metal- and ligand-specific parameters, the latter of which was determined separately for Cys(N,O,S) and Cys(N,S) ligands. The results indicate that the preferred binding mode for Zn(2+) with cysteine is bidentate (N,S) type binding in tetrahedral or trigonal bipyramidal geometry while Mg(2+) and Ca(2+) prefer sulfur-free binding sites in octahedral geometry. Fe(3+) prefers binding via sulfur and nitrogen atoms, whereas for Mn(2+) several equally stable structures were found. The new correction parameters can be applied for other sulfur-containing ligands to evaluate the binding strength of a new ligand with metal ions. The observed preferences of metal ions in binding are in agreement with the previous knowledge of the behavior of metal ions.


Exposure to dehydroepiandrosterone in utero affects T-cell function in males only.
Maternal stress can affect the growth, behavior and immune function of the offspring. Some of these effects are thought to be mediated by maternal glucocorticoids secreted in response to stress. The purpose of the present study was to establish whether dehydroepiandrosterone (DHEA), a weak androgen that is also secreted in response to stress, contributes to the sequelae of prenatal stress in the offspring. Therefore, pregnant rats were treated with different doses of DHEA in the drinking water from day 8 of gestation until parturition, when DHEA treatment was discontinued. Body weights of prepubertal male and female offspring of DHEA-treated dams were significantly and dose responsively lower than those of controls. In contrast, thymic weights were significantly higher in the DHEA offspring. Prenatal DHEA treatment reduced the splenic lymphocyte proliferative response to the T cell mitogen concanavalin A in prepubertal males only, while decreasing the mRNA levels of interleukin-2 receptor alpha and gamma subunits. The anterior pituitary expression of pro-opiomelanocortin (POMC) mRNA was increased in prepubertal males only. These data suggest that decreased body weight seen after prenatal stress can be mediated by either DHEA or glucocorticoids. The persistent increase in thymus weight is a new finding that may be very specific to prenatal DHEA treatment. In conclusion, the decreased T cell function and increased POMC expression found in this study indicate that prenatal-stress-induced immune suppression and altered hypothalamic-pituitary-adrenal activity can be, at least in part, DHEA mediated.


Computer system for analysis of ST segment changes on 24 hour Holter monitor tapes: comparison with other available systems.
The accuracy of a computer system that was developed for the analysis of ST segment changes recorded on Holter ambulatory electrocardiographic monitoring tapes was compared with conventional visual scrutiny, beat by beat analog printouts and a commercial J point trend system. The program calculates and plots multiple electrocardiographically derived variables in a high temporal resolution trend format. Fifty tapes of good recording quality obtained from 19 patients (13 with chronic stable angina and 6 with variant angina) were assessed visually and with the computer system; of these, 20 were analyzed by all four techniques. In the 50 tapes, 629 episodes of diagnostic ST segment changes (all true positive results) were identified by using the computer system. In contrast, only 507 were identified by visual scrutiny; none of these 507 episodes was missed by computer analysis. On the 20 tapes assessed using computer, visual, beat by beat analog and J point trend system analysis, 268, 221, 230 and 178 episodes, respectively, were documented. For the four techniques, false negative and positive results were 0, 47, 38 and 90 and 0, 10, 6 and 24, respectively. The results indicate that, of the systems assessed in this study, the computer program provides the highest accuracy for detection of transient ST segment changes. This is probably accreditable to the compact presentation of multiple electrocardiographically derived variables, allowing a detailed quantitative assessment of 24 hour tapes. It is of particular value for pathophysiologic and pharmacologic studies.


Pharmacogenetics of antiplatelets and anticoagulants: a report on clopidogrel, warfarin and dabigatran.
Genetic polymorphisms are thought to contribute to the wide intraindividual variability in antiplatelet and anticoagulant drug response. Pharmacogenetics is the study of how genetic variants influence drug response and how the adoption of a more personalized approach in antiplatelet and anticoagulant therapy may help to minimize harmful drug effects and optimize care for individual patients. However, due to sometimes conflicting evidence, the uptake of pharmacogenetics in the clinical setting has been slow. In this article, we review the genetic mechanisms contributing to the variability in response to three commonly used and emerging antiplatelet and anticoagulant drug therapies, namely clopidogrel, warfarin and dabigatran. We will focus on common genetic variants that influence the absorption, metabolism and/or action of these agents, including CYP2C19 (*2, *3 and *17), CYP3A4, CYP3A5, CYP2C9, ABCB1, P2RY12, CYP2C9 (*2/*3), VKORC1 and CESI.


Microbial genome-enabled insights into plant-microorganism interactions.
Advances in genome-based studies on plant-associated microorganisms have transformed our understanding of many plant pathogens and are beginning to greatly widen our knowledge of plant interactions with mutualistic and commensal microorganisms. Pathogenomics has revealed how pathogenic microorganisms adapt to particular hosts, subvert innate immune responses and change host range, as well as how new pathogen species emerge. Similarly, culture-independent community profiling methods, coupled with metagenomic and metatranscriptomic studies, have provided the first insights into the emerging field of research on plant-associated microbial communities. Together, these approaches have the potential to bridge the gap between plant microbial ecology and plant pathology, which have traditionally been two distinct research fields.


Influences of knee flexion angle and portal position on the location of femoral tunnel outlet in anterior cruciate ligament reconstruction with anteromedial portal technique.
To evaluate the influences of knee flexion angle and portal position on the location of femoral tunnel outlet in anterior cruciate ligament (ACL) reconstruction with the anteromedial (AM) portal technique. We recruited 6 volunteers with 12 normal knees. Each knee was flexed 120° or 135° and scanned with an open MRI. A 3D knee model was created. Virtual femoral tunnels were created on the footprint of the AM bundle and the posterolateral (PL) bundle of the ACL from three arthroscopic portals: the standard AM portal, the far medial and low portal, and the far medial and high (FMH) portal. The location of the femoral tunnel outlet was evaluated by comparing to the dissected cadaveric knee. Both increased flexion angle and lowering the drilling portal have a similar influence on the femoral tunnel outlet by moving them anterior and distally. Medialization of the portal moves them posteriorly and distally. PL tunnels created on the 120° knee model are more likely to be located under the lateral head of the gastrocnemius especially when they are drilled through the AM or FMH portals. If the femoral tunnel outlet is located under the soft tissue such as gastrocnemius attachment, suspension fixation devices may lapse into fixation failure by sitting on the soft tissue rather than the cortex bone surface. It is more desirable to drill in 135° knee flexion rather than 120°, and through a lower portal, to avoid creating the femoral tunnel outlet under soft tissues.


Improvement in suicidal ideation after ketamine infusion: relationship to reductions in depression and anxiety.
Suicide is a psychiatric emergency. Currently, there are no approved pharmacologic treatments for suicidal ideation. Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist that rapidly reduces suicidal ideation as well as depression and anxiety, but the dynamic between these symptoms is not known. The aim of this analysis was to evaluate whether ketamine has an impact on suicidal thoughts, independent of depressive and anxiety symptoms. 133 patients with treatment-resistant depression (major depressive disorder or bipolar I/II disorder) received a single subanesthetic infusion of ketamine (0.5 mg/kg over 40 min). Post-hoc correlations and linear mixed models evaluated the relationship between suicidal ideation and depression and anxiety symptoms using the Hamilton Depression Rating Scale (HAMD), Scale for Suicidal Ideation (SSI), Beck Depression Inventory (BDI), and Hamilton Anxiety Rating Scale (HAMA) focusing on 230 min post-infusion. At 230 min post-infusion, correlations between changes in suicidal ideation and depression ranged from 0.23 to 0.44 (p < .05), accounting for up to 19% in the variance of ideation change. Correlations with anxiety ranged from 0.23 to 0.40 (p < .05), accounting for similar levels of variance. Ketamine infusion was associated with significant reductions in suicidal ideation compared to placebo, when controlling for the effects of ketamine on depression (F1,587 = 10.31, p = .001) and anxiety (F1,567 = 8.54, p = .004). Improvements in suicidal ideation after ketamine infusion are related to, but not completely driven by, improvements in depression and anxiety. Investigation of the specific effects of ketamine on suicidal thoughts is warranted.


Textbook outcomes after oesophagectomy: a single-centre observational study.
Textbook outcomes is a composite quality assurance tool assessing the ideal perioperative and postoperative course as a unified measure. Currently, its definition and application in the context of oesophagectomy in Australia is unknown. The aim of this study was to assess the textbook outcomes after oesophagectomy in a single referral centre of Australia and investigate the association between textbook outcomes and patient, tumour, and treatment characteristics. An observational study was retrospectively performed on patients undergoing open, laparoscopic, or hybrid oesophagectomy between January 2010 and December 2019 in a single cancer referral centre. A textbook outcome was defined as the fulfillment of 10 criteria: R0 resection, retrieval of at least 15 lymph nodes, no intraoperative complications, no postoperative complications greater than Clavien-Dindo grade III, no anastomotic leak, no readmission to the ICU, no hospital stay beyond 21 days, no mortality within 90 days, no readmission related to the surgical procedure within 30 days from admission and no reintervention related to the surgical procedure. The proportion of patients who met each criterion for textbook outcome was calculated and compared. Selected patient-related parameters (age, gender, BMI, ASA score, CCI score), tumour-related factors (tumour location, tumour histology, AJCC clinical T and N stage and treatment-related factor [neoadjuvant chemotherapy and surgical approach]) were assessed. Disease recurrence and one year survival were also evaluated. 110 patients who underwent oesophagectomy were included. The overall textbook outcome rate was 24%. The difference in rates across the years was not statistically significant. The most achieved textbook outcome parameters were 'no mortality in 90 days' (96%) and 'R0 resection' (89%). The least frequently met textbook outcome parameter was 'no severe postoperative complications' (58%), followed by 'no hospital stays over 21 days' (61%). No significant association was found between patient, tumour and treatment characteristics and the rate of textbook outcome. Tumour recurrence rate and overall long term survival was similar between textbook outcome and non-textbook outcome groups. Patients with R0 resection, no intraoperative complication and a hospital stay less than 21 days had reduced mortality rates. Textbook outcome is a clinically relevant indicator and was achieved in 24% of patients. Severe complications and a prolonged hospital stay were the key criteria that limited the achievement of a textbook outcome. These findings provide meticulous evaluation of oesophagectomy perioperative care and provide a direction for the utilisation of this concept in identifying and improving surgical and oncological care across multiple healthcare levels.


DNA barcoding unmasks overlooked diversity improving knowledge on the composition and origins of the Churchill algal flora.
Sampling expeditions to Churchill in the Canadian subarctic were completed with the aim of compiling a molecular-assisted survey of the macroalgal flora (seaweeds) for comparison to published accounts for this area, which are based on morphological identifications. Further, because the Churchill region was covered by ice until recently (~10,000 before present), the current algal flora has had to migrate from adjacent waters into that region. We used our DNA barcode data to predict the relative contribution of the North Atlantic and North Pacific floras (Likely Source Region) in repopulating the Churchill region following the most recent glacial retreat. We processed 422 collections representing ~50 morpho-species, which is the approximate number reported for this region, and generated DNA barcode data for 346 of these. In contrast to the morpho-species count, we recovered 57 genetic groups indicating overlooked species (this despite failing to generate barcode data for six of the ~50 morpho-species). However, we additionally uncovered numerous inconsistencies between the species that are currently listed in the Churchill flora (again as a result of overlooked species diversity, but combined with taxonomic confusion) and those identified following our molecular analyses including eight new records and another 17 genetic complexes in need of further study. Based on a comparison of DNA barcode data from the Churchill flora to collections from the contiguous Atlantic and Pacific floras we estimate that minimally 21% (possibly as much as 44%) of the Churchill flora was established by migration from the Pacific region with the balance of species arriving from the Atlantic (predominantly North American populations) following the last glacial retreat. Owing to difficulties associated with the morphological identification of macroalgae, our results indicate that current comprehension of the Canadian Arctic flora is weak. We consider that morphology-based field-identifications are ill-advised in carrying out floristic and ecological surveys for macroalgae and that much of the current data, at least for the Canadian Arctic, should be used with caution. Our efforts to use DNA barcode data to identify the most Likely Source Regions for macroalgal species currently found in Churchill suggests that migration from both the Atlantic and the Pacific have played important roles in establishing the Canadian Arctic flora. This result has significance for understanding both the current and future biodiversity and biogeography of macroalgae in these waters.


[Analysis of scientific production of nurses from Minas Gerais published in nursing journals].
This is a descriptive, exploratory and retrospective study on the scientific production by nurses from Minas Gerais in BDENF Nursing journals from 1989 to 1998. The main objective was to characterize the scientific production by nurses from Minas Gerais published in the national nursing journals which comprise the BDENF. The names of 5.613 nurses from the records of COREn/MG were included in the database in order to find authors and their writings. Fifty-four authors and 87 writings were found with an average of 1.6 writings per author. The authors and co-authors who produce and publish are university professors working in collaboration with their peers.


Cucumis monosomic alien addition lines: morphological, cytological, and genotypic analyses.
Cucumis hystrix Chakr. (HH, 2n=24), a wild relative of the cultivated cucumber, possesses several potentially valuable disease-resistance and abiotic stress-tolerance traits for cucumber ( C. sativus L., CC, 2n=14) improvement. Numerous attempts have been made to transfer desirable traits since the successful interspecific hybridization between C. hystrix and C. sativus, one of which resulted in the production of an allotriploid (HCC, 2n=26: one genome of C. hystrix and two of C. sativus). When this genotype was treated with colchicine to induce polyploidy, two monosomic alien addition lines (MAALs) (plant nos. 87 and 517: 14 CC+1 H, 2n=15) were recovered among 252 viable plants. Each of these plants was morphologically distinct from allotriploids and cultivated cucumbers. Cytogenetic and molecular marker analyses were performed to confirm the genetic constitution and further characterize these two MAALs. Chromosome counts made from at least 30 meristematic cells from each plant confirmed 15 nuclear chromosomes. In pollen mother cells of plant nos. 87 and 517, seven bivalents and one univalent were observed at diakinesis and metaphase I; the frequency of trivalent formation was low (about 4-5%). At anaphase I and II, stochastic and asymmetric division led to the formation of two gamete classes: n=7 and n=8; however, pollen fertility was relatively high. Pollen stainability in plant no. 87 was 86.7% and in plant no. 517 was 93.2%. Random amplified polymorphic DNA analysis was performed using 100 random 10-base primers. Genotypes obtained with eight primers (A-9, A-11, AH-13, AI-19, AJ-18, AJ-20, E-19, and N-20) showed a band common to the two MAAL plants and C. hystrix that was absent in C. sativus, confirming that the alien chromosomes present in the MAALs were derived from C. hystrix. Morphological differences and differences in banding patterns were also observed between plant nos. 87 and 517 after amplification with primers AI-5, AJ-13, N-12, and N-20, suggesting that these plants may contain different C. hystrix chromosomes.


Decellularized human dermis to treat massive rotator cuff tears: in vitro evaluations.
Interest is increasing in biological scaffolds for tissue regeneration such as extracellular matrix membranes, developed through soft tissue decellularization. Extracellular matrix membranes were developed to heal different tendon and soft tissue lesions that are very frequent in the general population with high health-care costs and patient morbidity. The aim of this research was to evaluate a human dermal matrix (HDM) decellularized by a chemico-physical method. A primary culture of rat tenocytes was performed: tenocytes were seeded on HDM samples and on polystyrene wells as controls (CTR). Cell viability and synthetic activity were evaluated at 3 and 7 days. An in vitro microwound model was used to evaluate HDM bioactivity: after tenocyte expansion, artificial wounds were created, HDM extracts were added, and closure time and decorin synthesis were monitored histomorphometrically at 1, 4, 24, and 72 hr. A significant higher amount of collagen I was observed when cells were cultured on HDM in comparison with that on CTR (3 days: p < 0.0001; 7 days: p < 0.05). In HDM group, fibronectin synthesis was significantly higher at both experimental times (p < 0.0001). At 3 days, proteoglycans and transforming growth factor-β1 releases were significantly higher on HDM (p < 0.0001 and p < 0.005, respectively). The artificial microwound closure time and decorin expression were significantly enhanced by the addition of 50% HDM extract (p < 0.05). In vitro data showed that the decellularization technique enabled the development of a matrix with adequate biological and biomechanical properties.


Lack of association of group specific component haplotypes with lung function in smokers.
Airway inflammation may affect the decrease in lung function that occurs in response to cigarette smoke, and is an important pathological feature in chronic obstructive pulmonary disease (COPD). Group specific component (GC) can act as an inflammatory mediator and may therefore have important influences on the inflammatory reaction in the airway. Several reports have described associations between GC haplotypes and COPD but these remain controversial. In addition, most of these studies were based on a small number of subjects. We have studied the contribution of GC haplotypes to the level of lung function in a large cohort of smokers with high or low lung function (mean FEV(1) % predicted 91.8 and 62.6, respectively). The frequency of the three major GC haplotypes (1S, 1F and 2) was investigated in 537 individuals with high lung function and 533 with low lung function. No significant difference was found in the frequency of any GC haplotype between the high and low lung function groups. There was also no significant difference between the groups in genotype frequency of the two single nucleotide polymorphisms that underlie the haplotypes. The GC haplotype does not contribute to reduced lung function in this cohort of smokers.


Seawater acidification aggravated cadmium toxicity in the oyster Crassostrea gigas: Metal bioaccumulation, subcellular distribution and multiple physiological responses.
Mounting evidence has demonstrated the combined effects of ocean acidification (OA) and other environmental stressors on marine organisms. Although metal pollution is widely distributed in coasts and estuaries, the combined effects of OA and metal pollution have received little attention until recent years. In this study, the accumulation and subcellular distribution of cadmium (Cd) and the physiological responses of the oyster Crassostrea gigas were investigated after 31 days of exposure to OA and Cd, either alone or in combination. Increased Cd accumulation was found both in gills (about 57% increase at pH 7.8, 22% increase at pH 7.6) and digestive glands (about 38% increase at pH 7.8, 22% increase at pH 7.6) of C. gigas under elevated pCO2 exposure. Although a similar total Cd accumulation pattern was seen in oyster gills and digestive glands, a higher partition of Cd in the BIM (biologically inactive metal) fractions of gills (about 60%) was found in Cd-exposed treatments compared to the digestive glands (about 45%), which might correspond to the generally lower toxicity in gills. Moreover, synergetic effects of Cd and OA on the oxidative stresses, histopathological damage, and apoptosis of exposed oysters were observed in this study, which might be explained by significant interactions of these two factors on increased generation of ROS. These findings demonstrated that OA could aggravate the toxicity of metals in marine organisms, with significant implications for coastal benthic ecosystems regarding the widespread metal contamination and the concurrent increase of acidified seawater.


Dynamics of a novel centromeric histone variant CenH3 reveals the evolutionary ancestral timing of centromere biogenesis.
The centromeric histone H3 variant (CenH3) serves to target the kinetochore to the centromeres and thus ensures correct chromosome segregation during mitosis and meiosis. The Dictyostelium H3-like variant H3v1 was identified as the CenH3 ortholog. Dictyostelium CenH3 has an extended N-terminal domain with no similarity to any other known proteins and a histone fold domain at its C-terminus. Within the histone fold, α-helix 2 (α2) and an extended loop 1 (L1) have been shown to be required for targeting CenH3 to centromeres. Compared to other known and putative CenH3 histones, Dictyostelium CenH3 has a shorter L1, suggesting that the extension is not an obligatory feature. Through ChIP analysis and fluorescence microscopy of live and fixed cells, we provide here the first survey of centromere structure in amoebozoa. The six telocentric centromeres were found to mostly consist of all the DIRS-1 elements and to associate with H3K9me3. During interphase, the centromeres remain attached to the centrosome forming a single CenH3-containing cluster. Loading of Dictyostelium CenH3 onto centromeres occurs at the G2/prophase transition, in contrast to the anaphase/telophase loading of CenH3 observed in metazoans. This suggests that loading during G2/prophase is the ancestral eukaryotic mechanism and that anaphase/telophase loading of CenH3 has evolved more recently after the amoebozoa diverged from the animal linage.


Fibrinogen in equine pregnancy as a mediator of cell adhesion, an epigenetic and functional investigation.
Preimplantation equine embryos synthesize and secrete fibrinogen, which is a peculiar finding as fibrinogen synthesis almost exclusively occurs in the liver. This study investigated the hypothesis that conceptus-derived fibrinogen mediates cell adhesion during fixation. On day 21 of pregnancy, five integrin subunits, including ITGA5, ITGB1, ITGAV, and ITGB1, displayed significantly higher transcript abundance than on day 16 of pregnancy. Endometrial epithelial cells adhered to fibrinogen in an integrin-dependent manner in an in vitro cell adhesion assay. Bilaminar trophoblast and allantochorion expressed fibrinogen transcript, indicating that fibrinogen expression persists past fixation. Preimplantation-phase endometrium, conceptuses, and microcotyledonary tissue expressed components of the clotting cascade regulating fibrin homeostasis, leaving open the possibility that fibrinogen is converted to fibrin. Fibrinogen is likely to have functions beyond mediating cell adhesion, such trapping growth factors and triggering signaling cascades, and has remarkable parallels to the expression of fibrinogen by some tumors. The deposition of fibrinogen within tumor stroma is characteristic of breast carcinoma, and tumor-derived fibrinogen has been implicated in the metastatic potential of circulating tumor cells. DNA methylation of the fibrinogen locus in equine conceptuses was examined in comparison to liver and endometrium, and across the full gene cluster, was significantly higher for endometrium than liver and conceptus. DNA methylation of regulatory regions did not differ between liver and conceptus, and was significantly lower than in endometrium. These results, therefore, support the hypothesis of DNA methylation being a regulator of fibrinogen expression in the conceptus.


Co-administered Tag-Less Toxoid Fusion 3xSTaN12S-mnLTR192G/L211A and CFA/I/II/IV MEFA (Multiepitope Fusion Antigen) Induce Neutralizing Antibodies to 7 Adhesins (CFA/I, CS1-CS6) and Both Enterotoxins (LT, STa) of Enterotoxigenic Escherichia coli (ETEC).
Enterotoxigenic Escherichia coli (ETEC) bacteria remain a leading cause of children's diarrhea and travelers' diarrhea. Vaccines that induce antibodies to block ETEC bacterial adherence and to neutralize toxin enterotoxicity can be effective against ETEC-associated diarrhea. Recent studies showed that 6xHis-tagged CFA/I/II/IV multiepitope fusion antigen (MEFA) induced broad-spectrum antibodies to inhibit adherence of the seven most important ETEC adhesins (CFA/I, CS1 to CS6) (Ruan et al., 2014a) and 6xHis-tagged toxoid fusion antigen 3xSTaN12S-mnLTR192G/L211A (previously named as 3xSTaN12S-dmLT) elicited antibodies to neutralize both heat-labile toxin (LT) and heat-stable toxin (STa) produced by ETEC strains (Ruan et al., 2014b). In this study, we constructed two new genes to express tag-less toxoid fusion 3xSTaN12S-mnLTR192G/L211A and tag-less CFA/I/II/IV MEFA and then examined immunogenicity of each tag-less protein in mouse immunization. We further combined two tag-less proteins and investigated antigen co-administration in mice. Data showed that mice immunized with tag-less 3xSTaN12S-mnLTR192G/L211A or tag-less CFA/I/II/IV MEFA developed antigen-specific IgG antibody responses, and mice co-administered with two tag-less proteins induced neutralizing antibodies against seven adhesins and both toxins. These results indicated tag-less toxoid fusion 3xSTaN12S-mnLTR192G/L211A and tag-less CFA/I/II/IV MEFA administered individually or combined induced neutralizing antitoxin and/or anti-adhesin antibodies, and suggested the potential application of two tag-less proteins for ETEC vaccine development.


Successful behavior change in obesity interventions in adults: a systematic review of self-regulation mediators.
Relapse is high in lifestyle obesity interventions involving behavior and weight change. Identifying mediators of successful outcomes in these interventions is critical to improve effectiveness and to guide approaches to obesity treatment, including resource allocation. This article reviews the most consistent self-regulation mediators of medium- and long-term weight control, physical activity, and dietary intake in clinical and community behavior change interventions targeting overweight/obese adults. A comprehensive search of peer-reviewed articles, published since 2000, was conducted on electronic databases (for example, MEDLINE) and journal reference lists. Experimental studies were eligible if they reported intervention effects on hypothesized mediators (self-regulatory and psychological mechanisms) and the association between these and the outcomes of interest (weight change, physical activity, and dietary intake). Quality and content of selected studies were analyzed and findings summarized. Studies with formal mediation analyses were reported separately. Thirty-five studies were included testing 42 putative mediators. Ten studies used formal mediation analyses. Twenty-eight studies were randomized controlled trials, mainly aiming at weight loss or maintenance (n = 21). Targeted participants were obese (n = 26) or overweight individuals, aged between 25 to 44 years (n = 23), and 13 studies targeted women only. In terms of study quality, 13 trials were rated as "strong", 15 as "moderate", and 7 studies as "weak". In addition, methodological quality of formal mediation analyses was "medium". Identified mediators for medium-/long-term weight control were higher levels of autonomous motivation, self-efficacy/barriers, self-regulation skills (such as self-monitoring), flexible eating restraint, and positive body image. For physical activity, significant putative mediators were high autonomous motivation, self-efficacy, and use of self-regulation skills. For dietary intake, the evidence was much less clear, and no consistent mediators were identified. This is the first systematic review of mediational psychological mechanisms of successful outcomes in obesity-related lifestyle change interventions. Despite limited evidence, higher autonomous motivation, self-efficacy, and self-regulation skills emerged as the best predictors of beneficial weight and physical activity outcomes; for weight control, positive body image and flexible eating restraint may additionally improve outcomes. These variables represent possible targets for future lifestyle interventions in overweight/obese populations.


Reducing the risk of HIV transmission through blood transfusion by donor self-deferral.
A cross sectional study was conducted to evaluate the validity of implementing a blood donor self-deferral form for reducing the risk of HIV transmission through blood transfusion. The self-deferral form which was given to all blood donors, included questions about HIV risk factors in the three month period prior to blood donation. Donors were asked to declare confidentially whether their blood was safe for transfusion or not. Blood was collected and examined for HIV antigen, anti-HIV antibodies, HBsAg and syphilis antibodies. All of the serological markers detected among high risk donors and general donors were compared and analysed by Yates corrected X2 test and one-tailed Fisher's exact test with a significance level of 0.05. There were 401 self-deferred high risk donors and 15,523 general donors. The HIV antigen was found as a single marker in only one male high risk individual. The prevalence of anti-HIV antibodies, HBsAg and syphilis antibodies among the general donors was 0.61%, 5.29% and 1.17%, respectively. The anti-HIV, HBsAg and syphilis antibodies in the high risk donors were 1.99%, 7.98% and 1.25%, respectively. In comparison with the general donors, the high risk donors demonstrated statistically significant higher prevalence rates of HIV antigen (p < 0.05), anti-HIV (p < 0.005) and HBsAg (p < 0.05). In conclusion, donor self-deferral is valid for reducing the risk of HIV transmission through blood transfusion and its implementation should be encouraged when recruiting blood donors.


Locally acquired Dengue--Key West, Florida, 2009-2010.
Dengue is the most common vector-borne viral disease in the world, causing an estimated 50-100 million infections and 25,000 deaths each year. During 1946-1980, no cases of dengue acquired in the continental United States were reported. Since 1980, a few locally acquired U.S. cases have been confirmed along the Texas-Mexico border, temporally associated with large outbreaks in neighboring Mexican cities. On September 1, 2009, a New York physician notified the Monroe County (Florida) Health Department (MCHD) and the Florida Department of Health (FDOH) of a suspected dengue case in a New York state resident whose only recent travel was to Key West, Florida. CDC confirmed the diagnosis, and a press release was issued to notify the public and Key West physicians of the potential risk for locally acquired dengue infections. In the next 2 weeks, two dengue infections in Key West residents without recent travel were reported and confirmed. Subsequently, enhanced and active surveillance identified 24 more Key West cases during 2009. On April 13, 2010, another Key West dengue case was reported to FDOH, bringing the total to 28. This report describes the first three dengue cases reported in 2009, briefly summarizes the 2010 case, highlights preliminary findings from the ongoing investigation, and outlines measures used to mitigate and control the outbreak. Clinicians should include dengue in the differential diagnosis of acute febrile illnesses in patients who live in or have recently traveled to subtropical areas of the United States or to the tropics.


Liver-specific loss of lipin-1-mediated phosphatidic acid phosphatase activity does not mitigate intrahepatic TG accumulation in mice.
Lipin proteins (lipin 1, 2, and 3) regulate glycerolipid homeostasis by acting as phosphatidic acid phosphohydrolase (PAP) enzymes in the TG synthesis pathway and by regulating DNA-bound transcription factors to control gene transcription. Hepatic PAP activity could contribute to hepatic fat accumulation in response to physiological and pathophysiological stimuli. To examine the role of lipin 1 in regulating hepatic lipid metabolism, we generated mice that are deficient in lipin-1-encoded PAP activity in a liver-specific manner (Alb-Lpin1(-/-) mice). This allele of lipin 1 was still able to transcriptionally regulate the expression of its target genes encoding fatty acid oxidation enzymes, and the expression of these genes was not affected in Alb-Lpin1(-/-) mouse liver. Hepatic PAP activity was significantly reduced in mice with liver-specific lipin 1 deficiency. However, hepatocytes from Alb-Lpin1(-/-) mice had normal rates of TG synthesis, and steady-state hepatic TG levels were unaffected under fed and fasted conditions. Furthermore, Alb-Lpin1(-/-) mice were not protected from intrahepatic accumulation of diacylglycerol and TG after chronic feeding of a diet rich in fat and fructose. Collectively, these data demonstrate that marked deficits in hepatic PAP activity do not impair TG synthesis and accumulation under acute or chronic conditions of lipid overload.


Laparoscopic pyeloplasty: the updated McMaster University experience.
The open Anderson-Hynes procedure has an overall success rate of 90% for ureteropelvic junction obstruction. Laparoscopic pyeloplasty (LP) was developed to reduce morbidity and hospital stay while preserving the excellent results. We report on the results of our experience with laparoscopic pyeloplasty. Between January 2001 and May 2006, 77 consecutive patients underwent LP performed by one of 4 surgeons at our institution. Patients were reassessed with ultrasound (U/S) or intravenous pyelogram (IVP) at 6 weeks. Diuretic renal scan and U/S or IVP were performed at 6 months, and subsequent follow-up included a U/S or IVP as well as clinical assessment. Patients were assessed for pain and hydronephrosis on radiologic imaging, clearance on diuretic renal scan (T(1/2)) and differential renal function. We evaluated 73 patients. The mean patient age was 38 years (range 16-71 yr), the mean operating time was 218 minutes (range 110-409 min), and the mean blood loss was 57 mL (range 25-250 mL). Mean hospital stay was 3.0 days (range 2-7 d). The success rate was 90.4%, and failures were mainly due to poor function after surgery (3 patients). Pyelolithotomy was performed concomitantly on 6 patients, which on average extended operative time by 36 minutes. Our success rates are consistent with the LP experience of other centres and are comparable with rates for the open technique. Patients had short hospital stays, and complications were negligible. With experienced surgeons, LP should be the first-line treatment for ureteropelvic junction obstruction.


Deep Learning-Assisted Intelligent Artificial Vision Platform Based on Dual-Luminescence Eu(III)-Functionalized HOF for the Diagnosis of Breast and Ovarian Cancer.
Developing an advanced analytical method to detect spermine (Spm) and N-acetylneuraminic acid (NANA), the biomarkers of breast and ovarian cancers, respectively, is critical for the early diagnosis of the two cancers, which is very meaningful for women's health. Here, a deep learning-assisted artificial vision platform based on a dual-emission ratiometric fluorescence sensor is first constructed to monitor Spm and NANA. The ratiometric fluorescence sensor (Eu@TCBP-HOF, 1) can selectively detect Spm with high sensitivity based on "Turn-on" mode. After adding Spm, the new ratiometric fluorescence sensor (1-Spm, named 2) shows high sensitivity for NANA with "Turn-off" mode. Moreover, the fluorescence sensors can achieve an obvious fluorescence color response to Spm and NANA. Even in real saliva and serum samples, 1 and 2 still show high sensitivity and color responsiveness with limit of detection (LODs) of 0.5 μM for Spm and 0.96 μM for NANA. In virtue of different fluorescence responses, the DenseNet algorithm of deep learning assists the fluorescence sensors, which can simulate the human visual systems to identify fluorescence images and distinguish the concentration of Spm and NANA within 1 s with over 99% recognition accuracy. The intelligent artificial vision platform developed in this work may provide a prospective analytical method for the early diagnosis of female malignant tumors.


HLA-DRB1, DQA1, and DQB1 alleles associated with giant cell arteritis in northern Italy.
To evaluate by molecular typing the possible associations of HLA-DRB1, DQA1, and DQB1 alleles with biopsy proven giant cell arteritis (GCA) in a Mediterranean country, and to examine possible relationships between these alleles and GCA clinical subsets. Thirty-nine patients from the Reggio Emilia area diagnosed over a 12 year period with biopsy proven GCA were studied. The clinical findings at diagnosis and during the followup were evaluated through interviews and by reviewing the medical records. HLA-DRB1, DQA1, and DQB1 alleles were determined in the 39 patients and in 250 healthy controls from the same geographic area by polymerase chain reaction amplification using sequence-specific primers. No associations were found between GCA and the shared epitope, the DRYF epitope, or the DRB1*04 or DQA1 alleles. The only significant association was with DQB1*0302 allele (p = 0.03, RR = 2.2). However, the association was weak and the significance was lost when corrected for the number of antigens tested. The frequencies of DQB1*0301 and 0302 in DR4 patients were not significantly different from those observed in DR4 positive controls. Significant associations were found between DRB1*04 allele and the presence of systemic signs and/or symptoms (p = 0.04, RR = 1.5) and between DRB1*07 allele and the male patients (p = 0.04, RR = 2.6). Our data showed no associations of biopsy proven GCA with HLA-DRB1*04 and HLA-DRB1*01 alleles, rheumatoid epitope, or DRYF epitope. Discrepancies with other studies may be related to the different ethnic backgrounds of the populations studied and to differences in the referral patterns of patients with GCA.


Ventricular arrhythmias in heart failure.
In the management of patients with chronic heart failure, our attention is shifting from just improving left ventricular function and abolishing ventricular arrhythmias to improving personal longevity. Importantly, sudden cardiac death is a pattern of death in as many as a half of patients with chronic heart failure. Arrhythmias are common in this disorder, but may possibly be a marker of diseased heart rather than a predictor of sudden cardiac death. The mechanisms and triggers of rapid ventricular tachycardia or fibrillation responsible for sudden cardiac death have not been well established. At present, it is important to be reminded that pharmacologic augmentation of cardiac contractility or suppression of asymptomatic ventricular arrhythmias is not an effective approach to preventing sudden cardiac death, but may even be deleterious. Three groups of drugs that have shown efficacy in preventing sudden cardiac death in patients with chronic heart failure are amiodarone, beta-blockers, and angiotensin-converting enzyme (ACE) inhibitors. Although how these drugs improve prognosis of heart failure are not clear at present, myocardial protection by these agents appears to be most important.


Release characteristics of microspheres prepared by co-spray drying Actinobacillus pleuropneumoniae antigens and aqueous ethyl-cellulose dispersion.
Using formalin inactivated Actinobacillus pleuropneumoniae antigens and aqueous ethylcellulose dispersions, microspheres of oral vaccines were developed by a co-spray drying process. The present study attempted to determine whether the dosage formulations of microspheres could form enteric matrices. To assess the enteric characteristics, an in vitro dissolution test was performed with the AQ6-AP microspheres; 95% of the A. pleuropneumoniae protein was released within 3 h at pH 7, but there was no release at pH 1.5. The scanning microscopy revealed that the surface structure of AQ6-AP microspheres became porous at neutral pH. The SDS-PAGE analysis showed that the release rate of proteins from the microspheres was pH dependent not only for the AQ6-AP formulation but also when antigens of A. pleuropneumoniae were replaced with porcine serum. The results suggest that the A. pleuropneumoniae antigens were entrapped in the AQ6 microspheres under the acidic conditions. In a mouse model, oral immunization with AQ6-AP microspheres containing A. pleuropneumoniae evoked systemic IgG and mucosal IgA responses against A. pleuropneumoniae antigens. Thus, the present method may further provide an opportunity to develop oral vaccines and mucosal immunity.


Population structure and pathotype diversity of the wheat blast pathogen Magnaporthe oryzae 25 years after its emergence in Brazil.
Since its first report in Brazil in 1985, wheat blast, caused by Magnaporthe oryzae (anamorph: Pyricularia oryzae), has become increasingly important in South America, where the disease is still spreading. We used 11 microsatellite loci to elucidate the population structure of the wheat blast pathogen in wheat fields in central-western, southeastern, and southern Brazil. No subdivision was found among the wheat-infecting populations, consistent with high levels of gene flow across a large spatial scale. Although the clonal fraction was relatively high and the two mating type idiomorphs (MAT1-1 and MAT1-2) were not at similar frequencies, the clone-corrected populations from Distrito Federal and Goiás, Minas Triangle, and São Paulo were in gametic equilibrium. Based on these findings, we propose that populations of the wheat blast pathogen exhibit a mixed reproductive system in which sexual reproduction is followed by the local dispersal of clones. Seedling virulence assays with local wheat cultivars differentiated 14 pathotypes in the current population. Detached head virulence assays differentiated eight virulence groups on the same wheat cultivars. There was no correlation between seedling and head reactions.


Deep Sea Microplastic Pollution Extends Out to Sediments in the Northeast Atlantic Ocean Margins.
Microplastics are ubiquitous emerging contaminants found in every habitat surveyed, building upon international databases globally. Costs and accessibility often correlate to few deep sea sediment surveys, restricting the number of stations within a given sampling area. An extensive survey of the Porcupine Seabight, Porcupine Bank, the Goban Spur, and south-western canyons resulted in identifying microplastics in deep sea sediment surface layers from 33 of the 44 stations sampled (75%), with a total of 83 particles (74 synthetic and 9 natural) recorded. No microplastic hotspots were identified, and abundances (kg d.w.-1) were not correlated with distance from land, depth, or the presence of macrolitter on the seafloor. Understanding the sources of deep sea microplastics, such as marine traffic, is crucial to developing effective mitigation strategies as well as further monitoring campaigns targeting microplastic pollution in areas with significant deep sea biodiversity such as the Porcupine Seabright.


Cochrane Rehabilitation: 2020 annual report.
During its fourth year of existence, Cochrane Rehabilitation went on to promote evidence-informed health decision-making in rehabilitation. In 2020, the outbreak of the COVID-19 pandemic has made it necessary to alter priorities. In these challenging times, Cochrane Rehabilitation has firstly changed its internal organisation and established a new relevant project in line with pandemic needs: the REH-COVER (Rehabilitation - COVID-19 evidence-based response) action. The aim was to focus on the timely collection, review and dissemination of summarised and synthesised evidence relating to COVID-19 and rehabilitation. Cochrane Rehabilitation REH-COVER action has included in 2020 five main initiatives: 1) rapid living systematic reviews on rehabilitation and COVID-19; 2) interactive living evidence map on rehabilitation and COVID-19; 3) definition of the research topics on "rehabilitation and COVID-19" in collaboration with the World Health Organization (WHO) rehabilitation programme; 4) Cochrane Library special collection on Coronavirus (COVID-19) rehabilitation; and 5) collaboration with COVID-END for the topics "rehabilitation" and "disability." Furthermore, we are still carrying on five different special projects: Be4rehab; RCTRACK; definition of rehabilitation for research purposes; ebook project; and a prioritization exercise for Cochrane Reviews production. The Review Working Area continued to identify and "tag" the rehabilitation-relevant reviews published in the Cochrane library; the Publication Working Area went on to publish Cochrane Corners, working more closely with the Cochrane Review Groups (CRGs) and Cochrane Networks, particularly with Cochrane Musculoskeletal, Oral, Skin and Sensory Network; the Education Working Area, the most damaged in 2020, tried to continue performing educational activities such as workshops in different online meetings; the Methodology Working Area organized the third and fourth Cochrane Rehabilitation Methodological (CRM) meetings respectively in Milan and Orlando; the Communication Working Area spread rehabilitation evidences through different channels and translated the contents in different languages.


Arthropathies in Inflammatory Bowel Disease: A Review for Clinicians.
Inflammatory bowel disease (IBD) is a systemic, chronic autoimmune disease of the digestive tract. The etiology and pathophysiology of IBD is not fully understood, though it is believed to be due to a complex interaction among the patient's genotype, immune system, and environmental factors. Inflammatory bowel disease is frequently accompanied by extraintestinal manifestations that occur in almost half of all patients. The most common extraintestinal manifestation that occurs is joint disease, collectively termed the arthropathies of IBD. While epidemiological studies have estimated that the arthropathies of IBD occur in over 46% of the IBD population, there is a paucity of nursing literature concerning the extraintestinal manifestations of IBD and the role of nurses in patient care. Thus, the purpose of this article is to facilitate a greater understanding for nurses and nurse clinicians regarding the arthropathies associated with IBD including classifications, pathophysiology, diagnosis, and management.


Analytical and numerical design of a hybrid Fabry-Perot plano-concave microcavity for hexagonal boron nitride.
An efficient single-photon emitter (SPE) should emit photons at a high rate into a well-defined spatio-temporal mode along with an accessible numerical aperture (NA) to increase the light extraction efficiency that is required for effective coupling into optical waveguides. Based on a previously developed experimental approach to fabricate hybrid Fabry-Perot microcavities (Ortiz-Huerta et al. Opt. Express 2018, 26, 33245), we managed to find analytical and finite-difference time-domain (FDTD) values for the, experimentally achievable, geometrical parameters of a hybrid plano-concave microcavity that enhances the spontaneous emission (i.e., Purcell enhancement) of color centers in two-dimensional (2D) hexagonal boron nitride (hBN) while simultaneously limiting the NA of the emitter. Paraxial approximation and a transfer matrix model are used to find the spotsize of the fundamental Gaussian mode and the resonant modes of our microcavity, respectively. A Purcell enhancement of 6 is found for a SPE (i.e., in-plane dipole) hosted by a 2D hBN layer inside the hybrid plano-concave microcavity.


Atomistic Origins of Surface Defects in CH3NH3PbBr3 Perovskite and Their Electronic Structures.
The inherent instability of CH3NH3PbX3 remains a major technical barrier for the industrial applications of perovskite materials. Recently, the most stable surface structures of CH3NH3PbX3 have been successfully characterized by using density functional theory (DFT) calculations together with the high-resolution scanning tunneling microscopy (STM) results. The two coexisting phases of the perovskite surfaces have been ascribed to the alternate orientation of the methylammonium (MA) cations. Notably, similar surface defect images (a dark depression at the sites of X atoms) have been observed on surfaces produced with various experimental methods. As such, these defects are expected to be intrinsic to the perovskite crystals and may play an important role in the structural decomposition of perovskite materials. Understanding the nature of such defects should provide some useful information toward understanding the instability of perovskite materials. Thus, we investigate the chemical identity of the surface defects systematically with first-principles density functional theory calculations and STM simulations. The calculated STM images of the Br and Br-MA vacancies are both in good agreement with the experimental measurements. In vacuum conditions, the formation energy of Br-MA is 0.43 eV less than the Br vacancy. In the presence of solvation effects, however, the formation energy of a Br vacancy becomes 0.42 eV lower than the Br-MA vacancy. In addition, at the vacancy sites, the adsorption energies of water, oxygen, and acetonitrile molecules are significantly higher than those on the pristine surfaces. This clearly demonstrated that the structural decomposition of perovskites are much easier to start from these vacancy sites than the pristine surfaces. Combining DFT calculations and STM simulations, this work reveals the chemical identities of the intrinsic defects in the CH3NH3PbX3 perovskite crystals and their effects on the stability of perovskite materials.


Serum carbonic anhydrase III in neuromuscular disorders and in healthy persons after a long-distance run.
A radioimmunosorbent technique was used for the assay of the skeletal muscle specific enzyme, carbonic anhydrase III (CA III). The usefulness of serum CA III determinations for detecting skeletal muscle damage was evaluated by comparing the serum levels of this enzyme and of myoglobin and creatine kinase in 64 patients with neuromuscular disorders and in 13 healthy volunteers before and after a long-distance run. Increased serum CA III levels were found in all patients with muscular dystrophy, chronic polymyositis and amyotrophic lateral sclerosis and in many with myasthenia gravis. In patients with polymyositis who were followed up with repeated blood sampling, the time courses of serum CA III levels, myoglobin levels and clinical symptoms were closely related. In all the runners the serum CA III level immediately after the run was increased. In the present study serum CA III and myoglobin seemed to be equally sensitive as biochemical markers of muscular damage and more sensitive than creatine kinase.


Surgery for early breast cancer.
Optimal surgery for breast cancer demands effectiveness in local disease control, minimal physical and psychosocial morbidity, and efficient use of resources for assessment, diagnosis, treatment, and follow-up. These issues are addressed below with particular emphasis on the biologic relevance of tumor recurrence for planning local treatment, the management of subclinical radiographic abnormalities, the degree of importance of the timing of surgery in the menstrual cycle, and the value of axillary dissection.


Allogeneic NK cells induce monocyte-to-dendritic cell conversion, control tumor growth, and trigger a pro-inflammatory shift in patient-derived cultures of primary and metastatic colorectal cancer.
Natural killer (NK) cells are innate lymphocytes with a key role in the defense against tumors. Recently, allogeneic NK cell-based therapies have gained interest because of their ability to directly lyse tumor cells without inducing graft-versus-host disease. As NK cells are also able to influence the function of other immune cells (most notably dendritic cells (DC)), a better understanding of the effects of allogeneic NK cell products on the host immune system is required. In this study, we analyzed the effects of an allogeneic off-the-shelf NK cell product, on the tumor microenvironment (TME) of primary and metastatic colorectal cancer (pCRC and mCRC, respectively). Moreover, we explored if the combination of NK cells with R848, a toll-like receptors 7/8 ligand, could further enhance any pro-inflammatory effects. Ex vivo expanded umbilical cord blood stem cell derived NK cells were co-cultured with pCRC or mCRC single-cell suspensions in the presence or absence of R848 for 5 days, during and after which flow cytometry and cytokine release profiling were performed. NK cells efficiently induced lysis of tumor cells in both pCRC and mCRC single-cell suspensions and thereby controlled growth rates during culture. They also induced differentiation of infiltrating monocytic cells to an activated DC phenotype. Importantly, this NK-mediated myeloid conversion was also apparent in cultures after tumor cell depletion and was further enhanced by combining NK cells with R848. Moreover, NK cells, and to a greater extent, the combination of NK cells and R848, triggered CD8+ and CD4+ T-cell activation as well as a reduction in activated regulatory T cell rates. Finally, the combination of NK cells and R848 induced a pro-inflammatory shift in the cytokine release profile resulting in higher levels of interferon (IFN)-γ, interleukin (IL)-2, IL-12p70, and IFN-α as well as a reduction in IL-6, in both pCRC and mCRC cultures. Allogeneic NK cells engaged in favorable myeloid crosstalk, displayed effective antitumor activity and, when combined with R848, induced a pro-inflammatory shift of the CRC TME. These findings prompt the investigation of NK cells and R848 as a combination therapy for solid tumors.


A cost-utility and budget impact analysis of allogeneic hematopoietic stem cell transplantation for severe thalassemic patients in Thailand.
Hematopoietic stem cell transplantation (HSCT) is the only curative treatment available to severe thalassemic patients. The treatment, however, is very costly, particularly in the context of low and middle income countries, and no studies have been carried out to explore its economic justifiability. This study aimed to estimate the cost-utility of HSCT compared with blood transfusions combined with iron chelating therapy (BT-ICT) for severe thalassemia in Thailand, and to investigate the affordability of HSCT using a budget impact analysis. A Markov model was used to estimate the relevant costs and health outcomes over the patients' lifetimes taking a societal perspective as recommended by Thailand's health technology assessment guidelines. All future costs and outcomes were discounted at a rate of 3% per annum. Primary outcomes of interest were lifetime costs, quality adjusted life years (QALYs) gained, and the incremental cost-effectiveness ratio (ICER) in Thai baht (THB) per QALY gained. Compared to BT-ICT, the incremental cost-effectiveness ratio increased with patient age from 80,700 to 183,000 THB per QALY gained for related HSCT and 209,000 to 953,000 THB per QALY gained for unrelated HSCT among patients aged 1 to 15 years (US$1= 34 THB). The governmental budget impact analysis showed that providing 200 related HSCT to patients aged 1 to 10 years, in accordance with the current infrastructure limitations, would initially require approximately 90 million additional THB per year. At a societal willingness to pay of 100,000 THB per QALY gained, related HSCT was likely to be a cost-effective and affordable treatment for young children with severe thalassemia in Thailand.


In vitro uptake of [3H]alpha-tocopherol from low density lipoprotein by cultured human fibroblasts.
Studies were performed to determine the mechanism of entry of [3H]alpha-tocopherol from low density lipoprotein into cultured human fibroblasts. The cellular uptake of alpha-tocopherol at 37 degrees C was significantly different in time- and concentration-dependent experiments between normal fibroblasts and mutant fibroblasts that lack the membrane receptor for low density lipoprotein. The uptake by normal cells of both 125I-labeled low density lipoprotein and [3H]alpha-tocopherol was significantly lower at 4 degrees C where endocytosis does not occur, compared to 37 degrees C where it does occur. Also, the cellular uptake of both [3H]vitamin E and 125I-labeled low density lipoprotein was much lower when the lipoprotein was modified by methylation, which prevented its binding by the receptor, than when the native lipoprotein was measured. Although passive transfer and exchange cannot be excluded as mechanisms of entry, these data indicate that the majority of the alpha-tocopherol enters the cell with the intact lipoprotein particle. This finding is in contrast to several other hydrophobic compounds which reportedly transfer from the lipoprotein into the cell even in the absence of the lipoprotein receptor.


Safety, tolerability, and pharmacokinetics of oral (S)-oxiracetam in Chinese healthy volunteers: A randomized, double-blind, controlled phase I study.
(S)-oxiracetam is the major active enantiomer of oxiracetam, which is being developed for dementia. This trial was designed to evaluate the safety, tolerability, and pharmacokinetics of oral (S)-oxiracetam in healthy Chinese volunteers. A randomized, controlled, double-blind and dose-escalation design was used in this Phase I trial, which consisted of a single-ascending-dose (SAD) study (400-2000 mg) and a multiple-ascending-dose (MAD) study (400-1600 mg). Blood, urine and feces samples were collected for pharmacokinetic analysis. Safety was evaluated by monitoring adverse events (AEs). AEs in both studies were mild or moderate in severity and dose-independent. In the SAD study, no chiral transformation was observed. 55.03% and 36.16% of (S)-oxiracetam was excreted unchanged in urine and feces, respectively. Exposures exhibited dose-proportional increases over the range of 400 to 1600 mg but almost unchanged from 1600 to 2000 mg. (S)-oxiracetam was absorbed rapidly, reaching a peak at 0.75-1.00 h, and t1/2 was 6.12-6.60 h. Food had no effect on AUC, but prolonged Tmax to 3.00 h. In the MAD study, steady-state was observed on day 5. Mild accumulations were observed after 7 days of repeated dosing. (S)-oxiracetam was safe and tolerated with favorable pharmacokinetic profiles at all study doses, providing dosing evidence for further efficacy evaluation.


The trabecular pattern of the calcaneum as an index of osteoporosis.
Radiographs of the foot and hip in 61 patients with fractures of the upper end of femur have been studied, noting the progressive loss of bone trabeculae with age. The trabecular pattern in the calcaneum (expressed as the calcaneal index) closely parallels that in the upper end of the femur (Singh's index) and is easier to assess. Both indices have a significant correlation with age.


The management of diabetes mellitus by mangiferin: advances and prospects.
Diabetes mellitus has become one of the most challenging public health problems today. There are still various deficiencies that remain in existing therapeutic drugs. With increasing prevalence and mortality rates, more effective therapeutic agents are required for treatment clinically. As a kind of polyphenol and as a natural product, mangiferin has numerous pharmacological and excellent effects. In this review, the underlying mechanisms of mangiferin on diabetes mellitus and complications will be summarized. Moreover, mangiferin belongs to the BSC IV class and the clinical application and development of mangiferin are limited due to its poor aqueous solubility and fat solubility as well as low bioavailability. Our review also elaborated on improving the solubility of mangiferin by changing the dosage form and introduced the existing results, which hope to provide useful reference for mangiferin for further treating diabetes. In conclusion, mangiferin might be a potential adjuvant therapy for the treatment of diabetes mellitus and complications in the future.


Comfort and Attitudes Towards Robots Among Young, Middle-Aged, and Older Adults: A Cross-Sectional Study.
To explore the social impact of, comfort with, and negative attitudes towards robots among young, middle-aged, and older adults in the United States. Descriptive, cross-sectional. Conducted in 2014-2015 in an urban area of the western United States using a purposive sample of adults 18 years of age or older. Respondents completed a survey that included the Negative Attitudes Toward Robots Scale (NARS) and two questions taken or modified from the European Commission's Autonomous System 2015 Report. Analyses were conducted to compare perceptions and demographic factors by age groups (young adults:18-44, middle-aged adults: 45-64, and older adults: >65 years old). Sample included 499 individuals (n = 322 age 18-44 years, n = 50 age 45-64 years, and n = 102 age 65-98 years). There were no significant differences between age groups for 9 of the 11 items regarding social impact of robots and comfort with robots. There were no significant differences by age groups for 9 of the 14 items in the NARS. Among those items with statistically significant differences, the mean scores indicate similar sentiments for each group. Older, middle-aged, and younger adults had similar attitudes regarding the social impact of and comfort with robots; they also had similar negative attitudes towards robots. Findings dispel current perceptions that older adults are not as receptive to robots as other adults. This has implications for nurses who integrate supportive robots in their practice. Nurses working in clinical and community roles can use these findings when developing and implementing robotic solutions. Understanding attitudes towards robots can support how, where, and with whom robots can be used in nursing practice.


Phased-array intracardiac echocardiography for guiding transseptal catheter placement: utility and learning curve.
The utility of a new intracardiac 64-element, phased-array, longitudinal ultrasound imaging system for guiding transseptal catheterization was assessed during 69 crossing attempts in 45 dogs because of the inherent limitations of fluoroscopy and mechanical ultrasound. Multifrequency (7.5-8.5 MHZ) imaging of the membranous fossa ovalis, posterior left atrium, and left atrial appendage was conducted from the right atrium. Contact of the Brockenbrough needle with the interatrial septum as reflected by membranous fossa ovalis "tenting" was uniformly identified. Transseptal crossing and advancement of the dilator and sheath were adequately imaged because of deeper ultrasound tissue penetration. Transseptal catheterization was successfully accomplished in 44 of 45 dogs: on the first attempt in 40 and with additional attempts in 4 and confirmed by direct far-field imaging of nonagitated saline injection via the sheath. Total transseptal catheterization time was 3.0 +/- 1.8 minutes. Unsuccessful first attempts and/or subsequent sheath pullback into the right atrium with catheter manipulation were also readily recognized. Insertion of the transseptal needle beyond the ultrasound imaging plane resulted in perforation of the posterior left atrial wall in three attempts. Accompanying effusions in these animals and three others related to subsequent intracardiac ablation catheter manipulation were readily identified and monitored echocardiographically. In conclusion, phased-array intracardiac imaging provides a highly reliable means of guiding transseptal access to the left atrium. In addition, inadvertent complications such as perforation and pericardial effusion development can be readily recognized.


[N-nitrosodiethylamine-induced changes in the liver of syrian hamster with superinvasive opistorchiasis].
Trematoda O. felinius-induced hepatic lesions were investigated in Syrian golden hamsters with superinvasive opistorchiasis. One hundred hamsters were divided into 4 groups: (1)--control; (2) N-nitrosodiethylamine (DENA), i.p., twice a week, 3 weeks, total dose 72 mg/kg; (3) metacercariae O. felinius, with drinking water, 3 injections per day, once in 2 weeks, and (4) metacercariae O. felinius, as in group 3, followed by DENA, as in group 2. Animals were sacrificed 12 months after the beginning of the study. No changes in the liver were found in group 2. Reddish protrusions, up to 4 cm in diameter, appeared on liver surfaces in groups 3 and 4. Group 4 featured the highest relative and absolute weights of liver as well as clusters of oval cells and cholangiocellular tubules and cholangiofibrosis (in group 3, they were less visible). Electron microscopic examination identified hepatocytes with destructive changes to plasmalemma, nucleus and cytoplasmic organelles. Also, perisinusoidal cells (Ito cells) occurred. Tumor-bearing animals showed low hepatic cytochrome P-450. It is suggested that proliferative growth in the liver was stimulated by opistorchis invasion.


Academic Achievement in Primary School in Offspring Born to Mothers With Type 1 Diabetes (the EPICOM Study): A Register-Based Prospective Cohort Study.
This study examined the effect of maternal pregestational type 1 diabetes on offspring primary school performance. We performed a prospective combined clinical and register-based cohort study comparing primary school performance in offspring (n = 707) of women with pregestational type 1 diabetes with matched control offspring (n = 60,341). We also examined the association between HbA1c levels during pregnancy and later school performance among offspring born to women with pregestational type 1 diabetes. Offspring of mothers with pregestational type 1 diabetes obtained similar school grades as control offspring when finishing primary school (regression coefficient [β] = -0.13; 95% CI = -0.30 to 0.03; P = 0.12). Adjusting for parental education also resulted in an insignificant difference between the two groups (β = -0.07; 95% CI = -0.23 to 0.09; P = 0.37). Among offspring of women with type 1 diabetes, increasing maternal HbA1c pregestationally and throughout the pregnancy was associated with lower average school grades. Offspring born to mothers with good glycemic control in the third trimester obtained higher average school grades compared with control offspring. The opposite applied to offspring born to mothers with inadequate glycemic control, who obtained significantly lower average school grades compared with control offspring. Offspring of mothers with pregestational type 1 diabetes obtained similar average grades when finishing primary school compared with matched control offspring. Among offspring of women with type 1 diabetes, we found a consistent negative association between maternal HbA1c in pregnancy and primary school grades. However, whether this association reflects a direct causal influence of intrauterine hyperglycemia is uncertain.


Cerebral sinovenous thrombosis. Neuroimaging diagnosis and clinical management.
Cerebral sinovenous thrombosis (CSVT) is an uncommon disorder that affects the dural venous sinus and cerebral vein. In our study, thirty- four patients were examined. Pre and/or post contrast-enhanced CT was done in 28 patients. MRI studies were done in 24 patients. 2-D TOF MR venography (MRV) and contrast-enhanced MRV (CEMRV) were done in 19 cases. Digital subtraction angiography (DSA) was done in 18 patients. Sixteen patients received systemic intravenous heparinization, and 12 received endovascular thrombolytic treatment with urokinase combined with anticoagulant therapy. Neuroimages of CSVT can be acquired by direct visualization of the thrombus within the dural sinus or by parenchymal changes secondary to venous occlusion. As there are some pitfalls to MRI in the diagnosis of CSVT, the combination of MRI and MRV is now the gold standard in the diagnosis of CSVT. Usually, accuracy can be improved by applying 2-D TOF MRV and CE MRV. Furthermore, the source image of MRV is critical in differentiating between normal sinus variations and diseased ones. DSA is the best tool for demonstrating dynamic intracranial circulation in CSVT and mostly is used for endovascular treatment. Systemic intravenous anticoagulant therapy with heparin is accepted as a first line treatment. Except for clinical manifestations after systemic heparinization, abnormal MR findings of parenchymal change can be used to determine when to initiate thrombolytic treatment. Endovascular therapy can be finished at the antegrade flow within the dural sinus and continuous anticoagulation is sufficient to facilitate clinical improvement. Clinical suspicion and excellent neuroimaging are crucial in making the diagnosis of CSVT. Proper management with anticoagulants and/or endovascular thrombolytic therapy is mandatory in preventing propagation of the thrombosis and improving the clinical outcome.


Medical waste management in Turkey: A case study of Istanbul.
The objective of this study was to analyze the present status of medical waste management in the light of the Medical Waste Control Regulation (MWCR) in Istanbul, the largest city in Turkey. About 17% of the hospitals, 20% of bed capacity, and 54% of private hospitals in Turkey are located in Istanbul. The first regulation about medical waste management in Turkey was published in 1993, and as a candidate state, it was changed in 2005 in accordance with EU Environmental Directives. In this work, a survey of 14 questions about the amount, collection, and temporary storage of medical wastes was applied to 192 hospitals in Istanbul through face-to-face interviews. It was found that the estimated quantity of medical waste from the hospitals is about 22tons/day and the average generation rate is 0.63kg/bed-day. Recyclable materials are collected separately at a rate of 83%. Separate collection of different types of wastes is consistently practiced, but 25% of the hospitals still use inappropriate containers for medical waste collection. Almost 77% of the hospitals use appropriate equipment for the medical waste collection personnel. The percentage of the hospitals that have temporary storage depots is 63%. Medical waste management in Istanbul is carried out by applying the MWCR.


Pathway-based classification of breast cancer subtypes.
Cancer heterogeneity represents a major hurdle in the development of effective theranostic strategies, as it prevents to devise unique and maximally efficient diagnostic, prognostic and therapeutic procedures even for patients affected by the same tumor type. Computational techniques can nowadays leverage the huge and ever increasing amount of (epi)genomic data to tackle this problem, therefore providing new and valuable instruments for decision support to biologists and pathologists, in the broad sphere of precision medicine. In this context, we here introduce a novel cancer subtype classifier from gene expression data and we apply it to two different Breast Cancer datasets, from TCGA and GEO repositories. The classifier is based on Support Vector Machines and relies on the information about the relevant pathways involved in breast cancer development to reduce the huge variable space. Among the main results, we show that the classifier accuracy is preserved at excellent values even when the variable space is reduced by a 20-fold, hence providing a precious tool for cancer patient profiling even in case of limited experimental resources.


The Use of Botulinum Toxin Injection for Brachial Plexus Birth Injuries: A Systematic Review of the Literature.
Most brachial plexus birth injuries (BPBIs) are caused by traction on the brachial plexus during a difficult delivery. Fortunately, the possibility of complete recovery from such an incident is relatively high, with only 10% to 30% of patients having prolonged and persistent disability. These patients have muscle imbalances and co-contractions typically localized around the shoulder and elbow. These imbalances and co-contractures cause abnormal motor performances and bone/joint deformities. Typically, physical/occupational therapies are the conventional therapeutic modalities but are often times inadequate. Botulinum toxin A (BTX-A) injections into targeted muscles have been used to combat the muscular imbalances and co-contractions. With compliance to PRISMA guidelines, a systematic review was performed to identify studies published between 2000 and 2017 that used BTX-A to treat neonatal brachial plexus palsies. Ten studies were included, involving 325 patients. Three groups of indications for the use of BTX-A were identified: (1) internal rotation/adduction contracture of the shoulder; (2) elbow flexion lag/elbow extension lag; and (3) forearm pronation contracture. The included studies show an overall beneficial effect of BTX-A in treating co-contractures seen in patients with BPBI. Specifically, BTX-A is shown to reduce internal rotation/adduction contractures of the shoulder, elbow flexion/extension contractures, and forearm pronation contractures. These beneficial effects are blunted when used in older patients. Nevertheless, BTX-A is a useful treatment for BPBIs with a relatively low-risk profile.


Telehealth follow-up consultations for melanoma patients during the COVID-19 pandemic: Patient and clinician satisfaction.
The COVID-19 pandemic caused rapid implementation of telehealth for melanoma follow-up care in Australia. This study explores Australian melanoma patients and clinicians' level of satisfaction with telehealth. A cross-sectional study was conducted across three specialist melanoma centres in Sydney, Australia. Melanoma patients (all stages) and clinicians completed mixed methods surveys seeking socio-demographic and clinical information and questionnaires to assess satisfaction with telehealth. Additionally, patients completed measures of quality of life, fear of cancer recurrence and trust in their oncologist. Patients and clinicians provided open-ended responses to qualitative questions about their perceptions of telehealth. One hundred and fifteen patients and 13 clinicians responded to surveys. Telephone was used by 109 (95%) patients and 11 (85%) clinicians. Fifty-seven (50%) patients and nine (69%) clinicians preferred face-to-face consultations, 38 (33%) patients and 3 (23%) clinicians preferred a combination of face-to-face and telehealth consultations. Five (4%) patients and nil clinicians preferred telehealth consultations. Patients diagnosed with early-stage melanoma, using telehealth for the first time, who have lower trust in their oncologist, and having higher care delivery, communication and supportive care concerns were likely to report lower satisfaction with telehealth. Open-ended responses were consistent between patients and clinicians, who reported safety, convenience and improved access to care as major benefits, while identifying personal, interpersonal, clinical and system-related disadvantages. While telehealth has been widely implemented during COVID-19, the benefits identified by patients and clinicians may extend past the pandemic. Telehealth may be considered for use in conjunction with face-to-face consultations to provide melanoma follow-up care.


[South African family doctor's contribution to public health during the period 1900-1950].
During the period 1900-1950 the general or family practitioners made significant contributions to the health care in South Africa. The historical details of these contributions were not always documented and are difficult to trace. The Department of Family Medicine is anxious to preserve this part of South African medical history and a research project to further this effort was carried out. All possible sources of information were used. Chairs of medical history should be established in our medical faculties.


Leaf-level plasticity of Salix gordejevii in fixed dunes compared with lowlands in Hunshandake Sandland, North China.
To cope with adverse environments, the majority of indigenous plants in arid regions possess adaptive plasticity after long-term evolution. Leaf-level morphology, anatomy, biochemical properties, diurnal water potential and gas exchange of Salix gordejevii distributed in fixed dunes and lowlands in Hunshandake Sandland, China, were compared. Compared to plants growing in lowlands, individuals of S. gordejevii in fixed dunes displayed much smaller leaf area (0.26 vs 0.70 cm(2)) and thicker leaves (leaf total thickness 148.59 vs 123.44 mum), together with heavier crust wax, denser hairs, and more compacted epidermal cells. Moreover, those growing in fixed dunes displayed stronger drought-resistance properties as evidenced by higher levels of proline (3.68 vs 0.20 mg g(-1) DW) and soluble sugar (17.24 vs 14.49%). Furthermore, S. gordejevii in fixed dunes demonstrated lower water potential and lower light compensation point (28.8 vs 51.9 micromol m(-2) s(-1)). Our findings suggest that morphological and/or anatomical plasticity in leaves has had great adaptive value for Salix in responding to deteriorating environments. The evidence provided here may facilitate the prediction of plant adaptation in community succession in sandy habitats.


Metatarsal strains are sufficient to cause fatigue fracture during cyclic overloading.
Human in vivo tibial strains during vigorous walking have not been found to exceed 1200 microstrains. These values are below those found in ex vivo studies (>3000 microstrains) to cause cortical bone fatigue failure, suggesting that an intermediate bone remodeling response may be associated with tibial stress fractures. Metatarsal stress fractures, however, often develop before there is time for such a response to occur. Simultaneous in vivo axial strains were measured at the mid diaphysis of the second metatarsal and the tibia in two subjects. Peak axial metatarsal compression strains and strain rates were significantly higher than those of the tibia during treadmill walking and jogging both barefoot and with running shoes and during simple calisthenics. During barefoot treadmill walking metatarsal compression strains were greater than 2500 microstrains. During one- and two-leg vertical jumps and broad jumping, both metatarsal compression and tension strains were >3000 microstrains. Compression and tension strains in the metatarsus unlike those of the tibia may be sufficiently high even during moderate exertional activities to cause fatigue failure of bone secondary to the number of loading cycles without an intermediate bone remodeling response.


[Cancer screening and early diagnosis. Why? How? Where? Which ones? At what cost?].
Cancer is fighting with cardiovascular diseases for the first place as the number one killer of humans living in industrialized countries. Several factors contribute to the high incidence of cancers. The spectacular increase in life expectancy of individuals living in these areas is certainly one of the major causes that explain the steady rise of the number of patients suffering and dying from cancer. For most cancers, when the issue is fatal, it is usually after a long morbidity period often very difficult for the patient and with heavy public health consequences. Thus, a major challenge that the health professionals are facing is the reduction of malignant disease incidence. Primary prevention would be certainly the most successful strategy. However, its implementation is of extreme difficulty. Secondary prevention, non-exclusive to the primary one, represents probably the best approach to decrease morbidity and mortality linked to these diseases. Screening and early diagnosis are the two axes of such a strategy. The first one concerns the detection of a malignant lesion in an asymptomatic patient. Early diagnosis implies to consider with attention and explore any signs or symptoms that can be easily missed by the patient or the doctor and, hence, could be the first indication of a progressing cancer. The impact of cancer screening on the mortality rate due to cancer is still the subject of intense debates, while the efficacy of early diagnosis is unanimously recognized. Still, it is cancer screening that is the center of most attentions....


Whole embryo culture, transcriptomics and RNA interference identify TBX1 and FGF11 as novel regulators of limb development in the mouse.
Identifying genes involved in vertebrate developmental processes and characterizing this involvement are daunting tasks, especially in the mouse where viviparity complicates investigations. Attempting to devise a streamlined approach for this type of study we focused on limb development. We cultured E10.5 and E12.5 embryos and performed transcriptional profiling to track molecular changes in the forelimb bud over a 6-hour time-window. The expression of certain genes was found to diverge rapidly from its normal path, possibly reflecting the activation of a stress-induced response. Others, however, maintained for up to 3 hours dynamic expression profiles similar to those seen in utero. Some of these resilient genes were known regulators of limb development. The implication of the others in this process was either unsuspected or unsubstantiated. The localized knockdown of two such genes, Fgf11 and Tbx1, hampered forelimb bud development, providing evidence of their implication. These results show that combining embryo culture, transcriptome analysis and RNA interference could speed up the identification of genes involved in a variety of developmental processes, and the validation of their implication.


The perception of speech signals.
A brief outline of the mechanism of speech production is given. It is shown that the motion of the articulators is encoded in changes in the spectra of speech waveforms. Parameters derived from these spectra form the basis of a method of speech synthesis. The perception of speech is seen as a decoding of the acoustic features of the speech wave. The organs of the hearing system which are involved in this process are briefly described. An attempt is made to relate the results of auditory psychophysics to the physiology of the hearing mechanism. The acoustic features which are relevant for the perception of the various classes of speech sounds are described. These have mostly been obtained by experiments involving synthesized speech. Finally the results of some experiments in dichotic listening are presented which emphasize the differences in the perception of speech and other sounds.


Peripheral serotonin enhances lipid metabolism by accelerating bile acid turnover.
Serotonin is synthesized by two distinct tryptophan hydroxylases, one in the brain and one in the periphery. The latter is known to be unable to cross the blood-brain barrier. These two serotonin systems have apparently independent functions, although the functions of peripheral serotonin have yet to be fully elucidated. In this study, we have investigated the physiological effect of peripheral serotonin on the concentrations of metabolites in the circulation and in the liver. After fasting, mice were ip injected with 1 mg serotonin. The plasma glucose concentration was significantly elevated between 60 and 270 min after the injection. In contrast, plasma triglyceride, cholesterol, and nonesterified fatty acid concentrations were decreased. The hepatic glycogen synthesis and concentrations were significantly higher at 240 min. At the same time, the hepatic triglyceride content was significantly lower than the basal levels noted before the serotonin injection, whereas the hepatic cholesterol content was significantly higher by 60 min after the injection. Furthermore, serotonin stimulated the contraction of the gallbladder and the excretion of bile. After the serotonin injection, there was a significant induction of apical sodium-dependent bile acid transporter expression, resulting in a decrease in the concentration of bile acids in the feces. Additionally, data are presented to show that the functions of serotonin are mediated through diverse serotonin receptor subtypes. These data indicate that peripheral serotonin accelerates the metabolism of lipid by increasing the concentration of bile acids in circulation.


Long-Term Prognosis of Low-Risk Women Presenting to the Emergency Department with Chest Pain.
Prognosis of low-risk women presenting to the emergency department (ED) with chest pain has not been clarified. We assessed early and long-term outcomes of such patients and determined the need for predischarge testing. Retrospective assessment of consecutive low-risk women presenting to the ED with chest pain evaluated in a chest pain unit (CPU). Criteria of low risk: age ≤51 years; no history of cardiovascular disease, diabetes, or smoking; negative initial electrocardiogram (ECG); and cardiac troponin. Predischarge testing (treadmill or stress imaging) was performed at the discretion of the CPU attending physician. The study group comprised 214 consecutive women. Predischarge testing was performed in 142 patients (66%, age 43.9 years) and 72 patients (34%, age 43.1 years) had no predischarge testing. Predischarge testing comprised exercise treadmill (n = 102, 72%) or stress imaging (n = 40, 28%). Length of stay with no predischarge testing was 4.1 hours, compared with 8.6 hours with predischarge testing (P = .04). There were no cardiovascular events in the index presentation; during a 5-year interval (100% follow-up), there were 2 cardiovascular events (fatal heart failure, 1 patient; fatal stroke, 1 patient [total, 2/214, 0.93%]). Low-risk women presenting to the ED with chest pain have an excellent short- and long-term prognosis. A majority of patients did not receive predischarge testing, and their length of stay was reduced by >50% compared with those with predischarge testing. These findings suggest that such patients may not require predischarge testing for disposition from a CPU, which can reduce length of stay, decrease cost, and improve resource utilization.


Comparing Health Care Financial Burden With an Alternative Measure of Unaffordability.
Health insurance plans with high deductibles increase exposure to health care costs, raising concerns about how the growth in these plans may be impacting both the financial burden of health care expenditures on families and their access to health care. We find that foregoing medical care is common among low-income, privately insured families, occurring at a greater rate than those with higher incomes or Medicare coverage. To better understand the relationship between out-of-pocket (OOP) spending and access, we used the 2011-2014 Medical Expenditure Panel Survey (MEPS) data and a logistic model to analyze the likelihood of avoiding or delaying needed medical care based on health insurance design and other individual and family characteristics. We find that avoiding or delaying medical care is strongly correlated with coverage under a high-deductible health plan, and with depression, poor perceived health, or poverty. However, it is relatively independent of the percent of income spent on OOP costs, making the percent of income spent on OOP costs by itself a poor measure of health care unaffordability. Individuals who spend a small percentage of their income on health care costs may still be extremely burdened by their health plan when financial concerns prevent access to health care. This work emphasizes the importance of insurance design as a predictor of access and the need to expand the definition of financial barriers to care beyond expenditures, particularly for the low-income, privately insured population.