The effectiveness of interventions in managing treatment adherence in adult heart transplant patients: a systematic review.
Over the past 20 years, solid organ transplantation has evolved from experimental treatments to an effective alternative for the treatment of various diseases, including heart failure. Treatment non-adherence is a limiting factor for the success of heart transplants. A systematic review of the evidence is needed to examine the effectiveness of interventions for managing adherence to treatment in heart transplant patients. The primary objective of this systematic review was to synthesize the best available evidence regarding interventions for managing adherence to pharmacological and non-pharmacological treatments in heart/heart-lung transplant patients. This review considered primary studies that included patients 18 years old or older, who had undergone heart or heart-lung transplantation (regardless of gender, ethnicity, comorbidities or whether they had received other treatments or not) who were receiving pharmacological and non-pharmacological treatments.This review considered studies that evaluated the effectiveness of interventions in managing adherence to pharmacological or non-pharmacological treatments among adult heart/heart-lung transplant patients. Primary studies comparing standard care with any type of intervention to maintain treatment adherence were considered.This review considered any experimental study design including randomized controlled trials; other research designs, such as non-randomized controlled trials and before and after studies, were also considered for inclusion.The primary outcome considered was patient adherence to pharmacological or non-pharmacological treatments by means of objective or self-report assessment. Published and unpublished studies in English, Portuguese and Spanish were searched in electronic databases. Searches were completed in January 2014. Two independent reviewers, using the standardized critical appraisal instruments from the Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument, assessed methodological quality. Data were extracted using the standardized data extraction tool from Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument. Statistical pooling was not possible due to substantial heterogeneity of the studies; therefore data were presented as a narrative summary. Three quasi-experimental studies were included in this review. One study found that a dose reduction of immunosuppressive medications from a twice-daily to a once-daily regimen had a positive impact on treatment adherence; one found no significant difference in treatment adherence between patients who received educational intervention conducted in a teaching laboratory and those who received standard care; the third one also reported no significant difference in outcomes between a multifaceted intervention consisting of internet-based interactive workshops and standard care. The current best evidence to guide decisions regarding interventions to manage treatment adherence in heart transplant patients is limited. There is weak evidence that psycho-educational interventions (other than the standard care) has a positive impact on adherence and that decreasing the complexity of the treatment regimen by reducing the daily dose of the immunosuppressant drug improves adherence in heart transplant patients.


Dual-mode recognition of noncanonical tRNAs(Ser) by seryl-tRNA synthetase in mammalian mitochondria.
The secondary structures of metazoan mitochondrial (mt) tRNAs(Ser) deviate markedly from the paradigm of the canonical cloverleaf structure; particularly, tRNA(Ser)(GCU) corresponding to the AGY codon (Y=U and C) is highly truncated and intrinsically missing the entire dihydrouridine arm. None of the mt serine isoacceptors possesses the elongated variable arm, which is the universal landmark for recognition by seryl-tRNA synthetase (SerRS). Here, we report the crystal structure of mammalian mt SerRS from Bos taurus in complex with seryl adenylate at an atomic resolution of 1.65 A. Coupling structural information with a tRNA-docking model and the mutagenesis studies, we have unraveled the key elements that establish tRNA binding specificity, differ from all other known bacterial and eukaryotic systems, are the characteristic extensions in both extremities, as well as a few basic residues residing in the amino-terminal helical arm of mt SerRS. Our data further uncover an unprecedented mechanism of a dual-mode recognition employed to discriminate two distinct 'bizarre' mt tRNAs(Ser) by alternative combination of interaction sites.


[Reducing the Care-Related Burdens of a Family Caregiver of a Person With Mild Cognitive Impairment: A Home-Based Case Management Program].
The long-term care of cognitively impaired patients with concomitant behavioral problems brings great stress and burdens to family caregivers. The present article describes a family caregiver with multiple chronic diseases who concurrently shouldered primary care responsibilities for her husband, a patient with mild cognitive impairment, problematic behaviors, and medication non-adherence issues. The period of care was between September 23rd and December 29th, 2015. Data on physiological, psychological, and social burdens were collected based on a stress process model for family caregiving. We then applied a home-based, individually tailored intervention, which included nursing education, skills training, listening/counseling, and resource connecting, that effectively helped the family caregiver reduce her burdens. Our assessment identified nursing-care-related problems as the primary source of caregiver burden in this case, with identified stressors including a lack of knowledge regarding patient care, medication management problems, sleep disorders, and inadequate social resources. Using continuous care interactions, we established a trust relationship with the family caregiver, prioritized her needs, and provided dementia care knowledge and skills, which gradually improved her caregiving competence. Our instruction included increasing caregiver understanding of the disease course of dementia, related problematic behaviors, and medication management. Our intervention enhanced the disease awareness of the caregiver and helped her become more positive about her caregiving tasks. Therefore, the negative impacts on her family were reduced. Social support and long-term care resources further reduced her burden and improved her quality of life.


Predictors of survival in patients undergoing cardiac rehabilitation after transcatheter aortic valve implantation.
Cardiac rehabilitation may improve physical and functional recovery after transcatheter aortic valve implantation (TAVI), but outcome predictors in TAVI patients are usually based on assessments made before or at the time of TAVI without regard to cardiac rehabilitation referral. We aimed to assess exercise-based cardiac rehabilitation-derived parameters that may predict 3-year outcome in TAVI patients undergoing residential cardiac rehabilitation. In 95 consecutive TAVI patients (82.7 ± 4.9 years, 65% women) who underwent a 3-week cardiac rehabilitation program, at 3-year follow-up 35 deaths occurred. Compared with survivors, nonsurvivors had longer stay in cardiac rehabilitation (29.5 ± 12.3 vs. 21.6 ± 7.5 days, P = 0.0001), worse serum creatinine at admission/discharge (1.59 ± 0.86 vs. 1.26 ± 0.43 mg/dl, P = 0.0164; 1.52 ± 0.61 vs. 1.23 ± 0.44 mg/dl, P = 0.011), higher Cumulative Illness Rated State Comorbidity Index (5.4 ± 1.5 vs. 4.6 ± 1.8, P = 0.036) and Barthel Index at admission/discharge (51.8 ± 24.5 vs. 68.1 ± 23.2, P = 0.0016; 73.5 ± 27.2 vs. 88.6 ± 15.3, P = 0.0007), higher Morse Fall Risk score (35.6 ± 24 vs. 24.3 ± 14.1, P = 0.0056), and were less likely to train above the median exercise workload (fit) (11 vs. 35%, P = 0.008) or perform the 6-min walk test (6MWT) at admission/discharge (NO-6MWT: 34 vs. 12%, P = 0.008) and walked less distance on admission (6MWT: 129.6 ± 88.3 vs. 193.3 ± 69.8 m, P = 0.008). Univariate predictors of 3-year survival were cardiac rehabilitation duration, serum creatinine, Cumulative Illness Rated State Comorbidity Index, Barthel Index and NO-6MWT at admission/discharge, 6MWT at admission, Morse Fall Risk score at discharge and fit. Multivariate analysis confirmed exercise tolerance, Barthel Index and sCr at discharge as predictors. In TAVI patients who undergo cardiac rehabilitation, lower exercise tolerance, higher Barthel Index and sCr at discharge may predict 3-year mortality.


High amylase resistant starch to decrease stool output in people with short bowel syndrome: A pilot trial.
Short bowel syndrome (SBS) is defined as having less than 200 cm of functional small bowel. Malabsorptive diarrhoea and dehydration are difficult to manage despite medical therapy and dietary manipulations. Evidence shows that supplementing the diet with High Amylase Resistant Starch (HARS) can reduce diarrhoea from a number of causes including gastroenteritis. It is hypothesised HARS will decrease stool output via the production of short chain fatty acids and the resultant increased water reabsorption. This study aimed to determine if the addition of HARS can reduce diarrhoea in patients with SBS. Patients with SBS with colon in continuity were recruited from the intestinal rehabilitation clinic at Austin Health. The study was a 2 week crossover trial. Each participant completed the control and the intervention (addition of 50 g HARS to usual diet). Total daily stool weight and number of bowel actions per day were compared between groups using paired t-tests. Eight adults (58% male, mean age 55.7 yrs) were recruited. Five participants completed the trial. Total daily stool weight was reduced in all participants when consuming HARS. Mean daily stool output was significantly decreased 1049 ± 519 g/d to 804 ± 585 g/d (p = 0.023). Number of bowel actions per day showed a trend to reduction. This study gives some support to the hypothesis that the addition of HARS into the diet of patients with short bowel syndrome reduces stool output. Longer trials are required to confirm the effect on nutritional/hydration status.


Exploring crown ethers as shift reagents for ion mobility spectrometry.
A series of crown ethers, 12-crown-4, 15-crown-5, 18-crown-6, and dibenzo-30-crown-10, are examined as a possible means of shifting the mobilities of peptide ions. In this approach, a crown ether is added to a solution containing a mixture of peptides and is electrosprayed into the gas phase in order to create distributions of peptide-crown complexes. The ion complexes have different mobilities than the naked peptide ions, and the crown ether molecules appear to interact specifically with basic sites in the peptides thus providing some sequence selectivity. After the peptide-crown complexes are separated by ion mobility spectrometry, the ions can be collisionally activated to dissociate the complex (forming the naked peptide ions) prior to m/z analysis. The overall effect is that complex formation shifts peptide ions to different regions of the mobility spectrum, extending the ability to resolve components. The approach is illustrated by examining isobaric dipeptides as well as a combinatorial library containing 27 tripeptides. Cross sections for the series of crown ether ions and complexes that are observed are reported.


Short-run economic effects of the Scottish smoking ban.
We estimated the short-run economic impacts of the Scottish smoking ban on public houses. Previous findings on the effect of smoking bans on the hospitality sector have mainly focused on the United States. These studies have mostly found no negative economic effects of such legislation on the hospitality sector in the long run. However, differences in the social use of public houses in Great Britain in comparison with the United States may lead to different findings. We used a quasi-experimental research design that compared the sales and number of customers in public houses located in Scotland before and after the Scottish smoking ban was introduced, relative to a control group of establishments across the English border where no ban was imposed. To perform this analysis, we collected data on 2724 pubs, 1590 in Scotland and 1134 in Northern England by phone interviews using quota sampling. We found that the Scottish ban led to a 10% decrease in sales [P = 0.02, 95% confidence interval (CI) -19% to -2%] and a 14% decrease in customers (P = 0.02, 95% CI -26% to -2%). Our study suggests that the Scottish smoking ban had a negative economic impact on public houses, at least in the short run, due in part to a drop in the number of customers.


Lack of dynamic lipid changes after binding of interleukin 2 in chronic lymphatic leukemia lymphocytes indicates defective transmembrane signalling.
The role of membrane fluidity in the process of signal transduction after binding of Interleukin-2 (Il-2) to its specific cell-surface receptor was investigated in lymphocytes from normal donors and patients with Chronic Lymphocytic Leukemia (CLL). Membrane fluidity was assessed by fluorescence polarization analysis of the apolar fluorophor 1,6-diphenyl-1, 3, 5-hexatrien (DPH) incorporated in the lipid core of the cell membrane. Phytohemagglutinin (PHA) stimulation of lymphocytes for 72h disclosed marked membrane fluidization in normal lymphocytes without affecting lipid phase separation lacking in leukemic cells. Binding of Il-2 induced a significant decrease of the thermotropic transition temperature and overall membrane fluidization within 1h. These effects were not observed in CLL lymphocytes. Results are discussed in terms of defective transmembrane signalling in leukemic cells and pathogenetic implications for uncoupling from proliferation and differentiation signals in the development of leukemia.


Distribution of type VI collagen in the cartilaginous tissue of the proximal tibia in the domestic cat.
To investigate the distribution of the early stage chondrocytes during the formation and closure of epiphyseal growth plate (EGP) of the domestic cat, we examined the EGP of proximal tibiae by immunohistochemistry for type VI collagen. In the epiphyseal cartilage without the secondary ossification center (SOC) and EGP in newborn cats aged 1 and 10 days, type VI collagen-positive chondrocytes were located around the cartilage canals and articular surface. In the epiphyseal cartilage with the SOC and EGP in young cats aged 1 to 3 months, type VI collagen-positive chondrocytes were located in the upper resting zone of the EGP, and then increased throughout the resting zone along with maturation. In the adult cats with the partially closed EGP, type VI collagen-positive chondrocytes were distributed throughout the remaining EGP. These findings indicate that the early stage chondrocytes characterized with type VI collagen are continuously located in the EGP during maturation. In addition, the increase of the early stage chondrocytes and the decrease of the reserve chondrocytes in the EGP along with maturation may cause the cessation of the longitudinal growth of the EGP, and finally bring about the EGP closure.


Mimicking the first step of RNA splicing: an artificial DNA enzyme can synthesize branched RNA using an oligonucleotide leaving group as a 5'-exon analogue.
The 7S11 deoxyribozyme synthesizes 2',5'-branched RNA by mediating the nucleophilic attack of an internal 2'-hydroxyl group of one RNA substrate into the 5'-triphosphate of a second RNA substrate, with pyrophosphate as the leaving group. Here we comprehensively examined the role of the leaving group in the 7S11-catalyzed reaction by altering the 5'-phosphorylation state and the length of the second RNA substrate. When the leaving group is the less stabilized phosphate or hydroxide anion as provided by a 5'-diphosphate or 5'-monophosphate, the same 2',5'-branched product is formed as when pyrophosphate is the leaving group, but with an approximately 50- or approximately 1000-fold lower rate (Brønsted beta(LG) = -0.40). When the 5'-end of the RNA substrate that bears the leaving group is longer by one or more nucleotides, either the new 5'-terminal alpha-phosphate or the original alpha-phosphate can be attacked by the branch-site 2'-hydroxyl group; in the latter case, the leaving group is an oligonucleotide. The choice between these alpha-phosphate reaction sites is determined by the subtle balance between the length of the single-stranded 5'-extension and the stability of the leaving group. Because the branch-site adenosine is a bulged nucleotide flanked by Watson-Crick duplex regions, we earlier concluded that 7S11 structurally mimics the first step of natural RNA splicing. The observation of 7S11-catalyzed branch formation with an oligonucleotide leaving group strengthens this resemblance to natural RNA splicing, with the oligonucleotide playing the role of the 5'-exon in the first step. These findings reinforce the notion that splicing-related catalysis can be achieved by artificial nucleic acid enzymes that are much smaller than the spliceosome and group II introns.


Islamist insurgency and the war against polio: a cross-national analysis of the political determinants of polio.
There is widespread agreement that civil war obstructs efforts to eradicate polio. It is suggested that Islamist insurgents have a particularly negative effect on vaccination programmes, but this claim is controversial. We analyse cross-national data for the period 2003-14 using negative binomial regressions to investigate the relationship between Islamist and non-Islamist insurgency and the global distribution of polio. The dependent variable is the annual number of polio cases in a country according to the WHO. Insurgency is operationalized as armed conflict between the state and an insurgent organization resulting in ≥25 battle deaths per year according to the Uppsala Conflict Data Programme. Insurgencies are divided into Islamist and non-Islamist insurgencies. We control for other possible explanatory variables. Islamist insurgency did not have a significant positive relationship with polio throughout the whole period. But in the past few years - since the assassination of Osama bin Laden in 2011- Islamist insurgency has had a strong effect on where polio cases occur. The evidence for a relationship between non-Islamist insurgency and polio is less compelling and where there is a relationship it is either spurious or driven by ecological fallacy. Only particular forms of internal armed conflict - those prosecuted by Islamist insurgents - explain the current global distribution of polio. The variation over time in the relationship between Islamist insurgency and polio suggests that Islamist insurgent's hostility to polio vaccinations programmes is not the result of their theology, as the core tenets of Islam have not changed over the period of the study. Rather, our analysis indicates that it is a plausibly a reaction to the counterinsurgency strategies used against Islamist insurgents. The assassination of Osama bin Laden and the use of drone strikes seemingly vindicated Islamist insurgents' suspicions that immunization drives are a cover for espionage activities.


Photic regulation of c-fos expression in neural components governing the entrainment of circadian rhythms.
The rapid and transient induction of the proto-oncogene c-fos in mature neurons within the brain occurs in response to a variety of extracellular stimuli. To determine whether lighting conditions influence c-fos gene expression in the primary neural structures mediating the photoentrainment and generation of mammalian circadian rhythms, the expression of the c-fos protein (Fos) and related proteins in the retina and suprachiasmatic nuclei (SCN) of the anterior hypothalamus was examined immunohistochemically in rats exposed to a light-dark cycle of 12 h of light and 12 h of darkness (LD 12:12), constant light (LL), or constant dark (DD). The retina exhibited clear light-dark differences in the expression of Fos protein(s), such that immunopositive nuclei were readily evident during exposure to light (i.e., during the day of diurnal lighting or in LL), but were absent during exposure to darkness. In the SCN, the distribution of Fos immunoreactivity within specific subfields was differentially affected by photic conditions. Following exposure to light, a dense population of Fos-immunopositive cells was found in close association with the immunohistochemically distinct cell and fiber populations distinguishing the ventrolateral subfield of the SCN. In dark-exposed animals, Fos-immuno-reactive profiles were distributed throughout the SCN in areas coextensive with the immunohistochemical localization of peptidergic neural elements in both the ventrolateral and dorsomedial subfields. As a consequence of this light-dark difference in the distribution of Fos immunoreactivity, the density of labeled cells was increased within the ventrolateral SCN, but was decreased within the dorsomedial subfield, as a result of exposure to light versus darkness.(ABSTRACT TRUNCATED AT 250 WORDS)


Deep brain stimulation: new directions.
The role of deep brain stimulation (DBS) in the treatment of movement disorders is well established, but there has recently been a proliferation of additional indications that have been shown to be amenable to this technology. The combination of innovative approaches to neural interface technology with novel target identification based on previously discovered clinical effects of lesioning procedures has led to a fundamental paradigm for new directions in the application of DBS. The historical use of neurosurgical lesioning procedures in the treatment of psychiatric diseases such as obsessive compulsive disorder provided an initial opportunity to expand the use of DBS. The list is rapidly expanding and now includes major depressive disorder, Tourette's syndrome, addiction disorders, and eating disorders. Keen observations by neurosurgeons using these devices have lead to the incidental discovery of treatments for diseases without previous neurosurgical treatments. These discoveries are breaking new ground in the treatment of disorders of cognition, headache syndromes, disorders of consciousness, and epilepsy. Two features of DBS make it well-suited for treatment of disorders of nervous system function. First, the reversible, non-lesional nature of DBS allows for investigation of new targets without the morbidity of permanent side effects. Second, the programmable nature of DBS allows practitioners to alter stimulation patterns to minimize side effects and potentially improve efficacy through reprogramming. More importantly, proper scientific evaluation of new targets is aided by the ability to turn stimulation on and off with evaluators blinded to the stimulation status. Knowledge of these emerging therapies is important for practitioners, as there are many situations where a single target can effectively treat the symptoms of more than one disease. The intersection of advances in neuromodulation, neurophysiology, neuroimaging, and functional neuroanatomy has created an environment rife with new therapeutic possibilities.


Lack of emotional support from parents early in life and alcohol abuse later in life.
The purpose of this study is to examine the association between lacking emotional support from parents early in life and adult alcohol abuse. A series of logistic regression models were run with data collected from a nationally representative sample of over 2500 adults ages 25-74. The findings reveal a linear relationship between level of deficiency in early maternal support and odds of alcohol abuse during adulthood, with even moderate deficiencies being associated with elevated risk. Further examination suggests that this association persists throughout adulthood. This association does not appear to be explained by the early initiation of alcohol use, but poor psychological well-being during adulthood does account for a large portion of this association. These findings expand our understanding of the risks associated with poor parental support during childhood, and underscore the importance of adopting a life course perspective in studying the social determinants of alcohol problems among adults.


Uncoupling protein-2 contributes significantly to high mitochondrial proton leak in INS-1E insulinoma cells and attenuates glucose-stimulated insulin secretion.
Proton leak exerts stronger control over ATP/ADP in mitochondria from clonal pancreatic beta-cells (INS-1E) than in those from rat skeletal muscle, due to the higher proton conductance of INS-1E mitochondria [Affourtit and Brand (2006) Biochem. J. 393, 151-159]. In the present study, we demonstrate that high proton leak manifests itself at the cellular level too: the leak rate (measured as myxothiazol-sensitive, oligomycin-resistant respiration) was nearly four times higher in INS-1E cells than in myoblasts. This relatively high leak activity was decreased more than 30% upon knock-down of UCP2 (uncoupling protein-2) by RNAi (RNA interference). The high contribution of UCP2 to leak suggests that proton conductance through UCP2 accounts for approx. 20% of INS-1E respiration. UCP2 knock-down enhanced GSIS (glucose-stimulated insulin secretion), consistent with a role for UCP2 in beta-cell physiology. We propose that the high mitochondrial proton leak in beta-cells is a mechanism which amplifies the effect of physiological UCP2 regulators on cytoplasmic ATP/ADP and hence on insulin secretion.


Technological Microbiology: Development and Applications.
Over thousands of years, modernization could be predicted for the use of microorganisms in the production of foods and beverages. However, the current accelerated pace of new food production is due to the rapid incorporation of biotechnological techniques that allow the rapid identification of new molecules and microorganisms or even the genetic improvement of known species. At no other time in history have microorganisms been so present in areas such as agriculture and medicine, except as recognized villains. Currently, however, beneficial microorganisms such as plant growth promoters and phytopathogen controllers are required by various agricultural crops, and many species are being used as biofactories of important pharmacological molecules. The use of biofactories does not end there: microorganisms have been explored for the synthesis of diverse chemicals, fuel molecules, and industrial polymers, and strains environmentally important due to their biodecomposing or biosorption capacity have gained interest in research laboratories and in industrial activities. We call this new microbiology Technological Microbiology, and we believe that complex techniques, such as heterologous expression and metabolic engineering, can be increasingly incorporated into this applied science, allowing the generation of new and improved products and services.


Acceleration of the rate of fluorescence decrease by high concentrations of ATP under the condition of accumulation of ADP-sensitive phosphoenzyme in Na+,K+-ATPase.
Addition of up to 300 microM ATP in the presence of 2 M NaCl with MgCl2 to pig kidney Na+,K+-ATPase treated with N-[p-(2-benzimidazolyl)phenyl]maleimide seemed to be insufficient to saturate the rate of the fluorescence decrease. However, both the extent of the decrease and the amount of phosphoenzyme at a steady state were saturated below 20 microM ATP. Addition of Mg2+ with Na+ to the enzyme preincubated with 20 to 600 microM ATP gave nearly the same rate constant, which was below 50% of that obtained by adding 300 microM ATP to the Na+-form enzyme in the presence of Mg2+. High concentrations of ATP affected neither the rate of light-scattering change (Taniguchi, K. et al. (1986) J. Biol. Chem. 261, 3272-3281) after ADP-sensitive phosphoenzyme formation (E1P) nor that of the breakdown of E1P. A stoichiometric amount of [32P]Pi was liberated from [32P]E1P. The data suggested that ATP did not bind to E1P in such a way as to increase the extent of phosphorylation further or to accelerate dephosphorylation. The data also suggested that the reason for the large difference in the apparent affinity of ATP as evaluated from the rate and the extent of fluorescence change is the large dissociation constant for ATP of a Michaelis complex.


Atorvastatin decreases elevated soluble CD40L in subjects at high cardiovascular risk. Atorvastatin on inflammatory markers study: a substudy of ACTFAST.
The CD40/CD40 ligand plays a role in the inflammatory and prothrombotic processes in atherosclerosis. We analyzed whether short-term treatment with atorvastatin affects soluble CD40 ligand (sCD40L) plasma levels in subjects at high cardiovascular risk. sCD40L plasma concentrations were measured in 852 subjects from the Atorvastatin on Inflammatory Markers (AIM) Study, a 12-week prospective multicenter, open-label trial which enrolled statin-free subjects with coronary heart disease (CHD), CHD-equivalent (diabetes, peripheral vascular disease, or cerebrovascular disease), or a 10-year CHD risk >20%. Subjects were assigned to atorvastatin (10-80 mg/day) based on LDL-C at screening. Overall, sCD40L levels were not different in patients at high cardiovascular risk compared with healthy subjects. When sCD40L levels were divided in quartiles, patients in the highest quartile (N=213) had higher sCD40L concentrations than age- and gender-matched healthy subjects (N=29) (P<0.0001). Interestingly, all doses of atorvastatin significantly diminished sCD40L levels in subjects at the highest quartile. Furthermore, atorvastatin treatment decreased sCD40L more markedly in subjects with metabolic syndrome compared with those without metabolic syndrome. In conclusion, atorvastatin diminishes sCD40L plasma levels, more markedly so in subjects with metabolic syndrome. Our results indicate that short-term treatment with atorvastatin exhibits anti-inflammatory and antithrombotic effects in subjects at high cardiovascular risk.


INTER- AND INTRASPECIFIC VARIATION OF MOSSES IN TOLERANCE TO COPPER AND ZINC.
Bryophytes are often viewed as slowly evolving with little genetic variation within and among populations. A study of heavy-metal tolerance was initiated to test the capacity of bryophytes to undergo genetic differentiation in response to natural selection. Tolerance of Funaria hygrometrica to copper and zinc was greater in populations that originated on soil with high concentrations of these metals. Protonemal growth was more inhibited by the metals than was germination, and copper was more toxic than zinc. Zinc and copper tolerances were correlated, but so were the zinc and copper concentrations of native substrates. The pattern of population differentiation for heavy-metal tolerance in this species is much like that of flowering plants. Five populations of Physcomitrium pyriforme, which does not occur on metal-contaminated soil, were all highly tolerant of zinc but extremely intolerant of copper. This species seems to have an inherent tolerance to the former. Significant variation in tolerance to copper and zinc occurred among populations, but tolerance did not correlate with metal contents in native substrates. This pattern differs from that of flowering plants. Normal populations of species that colonize contaminated sites tended to be more tolerant than populations of species that do not colonize such sites. The extensive population differentiation in Funaria hygrometrica augments the evidence from electrophoretic data that there is genetic variation among populations of mosses and liverworts.


2D/2D heterojunction of g-C3N4/SnS2: room-temperature sensing material for ultrasensitive and rapid-recoverable NO2 detection.
Heterojunction engineering plays an indispensable role in improving gas-sensing performance. However, rational heterojunction engineering to achieve room-temperature NO2 sensing with both high response and rapid recovery is still a challenge. Herein, a 2D/2D heterojunction of g-C3N4/SnS2 is designed to improve the sensing performance of SnS2 and used for ultrasensitive and rapid-recoverable NO2 detection at room temperature. The pristine SnS2 fails to work at room temperature because of its high resistivity and weak adsorption to NO2. After combination with g-C3N4 nanosheets, the g-C3N4/SnS2-based sensor exhibits an extremely high response (503%) and short recovery time (166 s) towards 1 ppm NO2 at room temperature. The improved sensing performance is primarily attributed to the increased adsorption sites and enhanced charge transfer induced by the 2D/2D heterojunctions with large interface contact area. This achievement of g-C3N4/SnS2 2D/2D heterostructures demonstrates a promising pathway for the design of sensitive gas-sensing material based on a 2D/2D heterojunction strategy.


An injectable and 3D printable pro-chondrogenic hyaluronic acid and collagen type II composite hydrogel for the repair of articular cartilage defects.
Current treatments for repairing articular cartilage defects are limited. However, pro-chondrogenic hydrogels formulated using articular cartilage matrix components (such as hyaluronic acid (HA) and collagen type II (Col II)), offer a potential solution if they could be injected into the defect via minimally invasive arthroscopic procedures, or used as bioinks to 3D print patient-specific customised regenerative scaffolds-potentially combined with cells. However, HA and Col II are difficult to incorporate into injectable/3D printable hydrogels due to poor physicochemical properties. This study aimed to overcome this by developing an articular cartilage matrix-inspired pro-chondrogenic hydrogel with improved physicochemical properties for both injectable and 3D printing (3DP) applications. To achieve this, HA was methacrylated to improve mechanical properties and mixed in a 1:1 ratio with Col I, a Col I/Col II blend or Col II. Col I possesses superior mechanical properties to Col II and so was hypothesised to enhance hydrogel mechanical properties. Rheological analysis showed that the pre-gels had viscoelastic and shear thinning properties. Subsequent physicochemical analysis of the crosslinked hydrogels showed that Col II inclusion resulted in a more swollen and softer polymer network, without affecting degradation time. While all hydrogels exhibited exemplary injectability, only the Col I-containing hydrogels had sufficient mechanical stability for 3DP applications. To facilitate 3DP of multi-layered scaffolds using methacrylated HA (MeHA)-Col I and MeHA-Col I/Col II, additional mechanical support in the form of a gelatin slurry support bath freeform reversible embedding of suspended hydrogels was utilised. Biological analysis revealed that Col II inclusion enhanced hydrogel-embedded MSC chondrogenesis, thus MeHA-Col II was selected as the optimal injectable hydrogel, and MeHA-Col I/Col II as the preferred bioink. In summary, this study demonstrates how tailoring biomaterial composition and physicochemical properties enables development of pro-chondrogenic hydrogels with potential for minimally invasive delivery to injured articular joints or 3DP of customised regenerative implants for cartilage repair.


A decision tree approach to screen drinking water contaminants for multiroute exposure potential in developing guideline values.
The consideration of inhalation and dermal routes of exposures in developing guideline values for drinking water contaminants is important. However, there is no guidance for determining the eligibility of a drinking water contaminant for its multiroute exposure potential. The objective of the present study was to develop a 4-step framework to screen chemicals for their dermal and inhalation exposure potential in the process of developing guideline values. The proposed framework emphasizes the importance of considering basic physicochemical properties prior to detailed assessment of dermal and inhalation routes of exposure to drinking water contaminants in setting guideline values.


Three new records of penicillium species isolated from insect specimens in Korea.
Three Penicillium species have been isolated from insect specimens in Korea; Penicillium sp., P. steckii, and P. polonicum. Penicillium sp. (KNU12-3-2) was isolated from Lixus imperessiventris, while P. polonicum (KNU12-1-8) and Penicillium steckii (KNU12-2-9) were isolated from Muljarus japonicas and Meloe proscarabaeus, respectively. The identification was based on the morphological characteristics of the fungi and in internal transcribed spacer analysis. This is the first report on the isolation of these three species of Penicillium from insects in Korea.


Narrowing the wingless-2 mutation to a 227 kb candidate region on chicken chromosome 12.
Wingless-2 (wg-2) is an autosomal recessive mutation in chicken that results in an embryonic lethal condition. Affected individuals exhibit a multisystem syndrome characterized by absent wings, truncated legs, and craniofacial, kidney, and feather malformations. Previously, work focused on phenotype description, establishing the autosomal recessive pattern of Mendelian inheritance and placing the mutation on an inbred genetic background to create the congenic line UCD Wingless-2.331. The research described in this paper employed the complementary tools of breeding, genetics, and genomics to map the chromosomal location of the mutation and successively narrow the size of the region for analysis of the causative element. Specifically, the wg-2 mutation was initially mapped to a 7 Mb region of chromosome 12 using an Illumina 3 K SNP array. Subsequent SNP genotyping and exon sequencing combined with analysis from improved genome assemblies narrowed the region of interest to a maximum size of 227 kb. Within this region, 3 validated and 3 predicted candidate genes are found, and these are described. The wg-2 mutation is a valuable resource to contribute to an improved understanding of the developmental pathways involved in chicken and avian limb development as well as serving as a model for human development, as the resulting syndrome shares features with human congenital disorders.


[Periprocedural myocardial damage: chronicle of a (cellular) death foretold].
Cardiac marker monitoring after percutaneous coronary intervention (PCI) is now widespread; thus, the recognition of just how frequently myocardial enzyme elevations result from even successful PCI has become increasingly important, despite some physician's interest in minimizing the significance of isolated asymptomatic creatine phosphokinase elevations without an angiographically apparent cause. The meaningfulness of elevated cardiac enzymes after revascularization procedures is one of the most controversial issues in interventional cardiology. The rate of periprocedural damage detection is highly dependent on the intensity of enzyme and ECG measurement. With the use of more sensitive and specific cardiac markers of myocardial necrosis, the traditional definition of "acute myocardial infarction" has been expanded to include even small and asymptomatic biomarker elevations. On the other hand, most debate has focused on the clinical relevance of an elevation in CK-MB levels to 1 to 3 times the upper limit of normal, and many cardiologists argue that the appropriate cut-off point after PCI is even higher. Doubts whether "small" cardiac marker elevations have per se any impact on survival after uncomplicated procedures, as well as the excess of fideism on the effectiveness of contemporary coronary stenting couple with the mistaken equation "excellent angiographic result = excellent clinical outcome". Pre and postprocedural ECG recording and serial cardiac marker measurement should be incorporated into clinical pathways, and routine CK-MB levels tracking is now mandatory even in asymptomatic subjects having successful PCI. A consensus about how to check myocardial damage after PCI (i.e. which and how serum markers should be measured and reported) is eagerly awaited. A broader agreement will contribute to a better understanding of pathophysiology and long-term prognostic implications of "minor" periprocedural myocardial damage, allowing to improve our strategies to prevent and treat it.


High power density from Pt thin film electrodes based microbial fuel cell.
Microbial Fuel Cells (MFC) are robust devices capable of taping biological energy, converting sugars into potential sources of energy. Persistent efforts are directed towards increasing power output. However, they have not been researched to the extent of making them competitive with chemical fuel cells. The power generated in a dual-chamber MFC using neutral red (NR) as the electron mediator has been previously shown to be 152.4 mW/m2 at 412.5 mA/m2 of current density. In the present work we show that Pt thin film coated carbon paper as electrodes increase the performance of a microbial fuel cell compared to conventionally employed electrodes. The results obtained using E. coli based microbial fuel cell with methylene blue and neutral red as the electron mediator, potassium ferricyanide in the cathode compartment were systematically studied and the results obtained with Pt thin film coated over carbon paper as electrodes were compared with that of graphite electrodes. Platinum coated carbon electrodes were found to be better over the previously used for microbial fuel cells and at the same time are cheaper than the preferred pure platinum electrodes.


Peripheral vascular diseases resulting from chronic arsenical poisoning.
Drinking water contaminated by arsenic remains a major public health problem. Long-term arsenic exposure has been found to be associated with peripheral vascular diseases in a variety of studies. Reports of vascular effects of arsenic in drinking water, which span almost 100 years, have been published in Taiwan, Chile, Mexico, and China. This paper reviewed the association of peripheral vascular diseases resulting from arsenic exposure to drinking water from the clinical and pathological points of view. An endemic peripheral vascular disorder called "blackfoot disease" has been noticed in a limited area in Taiwan. This disease results in gangrene in the extremities. It has been associated with the ingestion of high concentrations of arsenic-tainted artesian well water. Epidemiological studies confirmed a dose-response relationship between long-term arsenic exposure and the occurrence of blackfoot disease. Whereas arsenic has induced various clinical manifestations of vascular effects in Chile, Mexico and China, they do not compare in magnitude or severity to the blackfoot disease found in Taiwan. The pathogenesis of vascular effects induced by arsenic is still controversial. The possible mechanisms include endothelial cell destruction, arsenic-associated atherogenesis, carotene and zinc deficiency, and/or some immunological mechanism. Microcirculatory assessments revealed that deficits of capillary blood flow and permeability exist in clinically normal skin of patients with chronic arsenical poisoning. The vascular effects of chronic arsenic poisoning may involve cardiovascular and cerebrovascular systems as well. In view of the increasing public health problems caused by arsenic exposure, vascular effects should be included in the future study of health effects of arsenic.


Surveys of Food Intake Just after the Nuclear Accident at the Fukushima Daiichi Nuclear Power Station.
As a result of the nuclear accident at the Fukushima Daiichi nuclear power station (FDNPS) after the Great East Japan Earthquake on March 11, 2011, volatile radionuclides including iodine-131 were released into the environment and contaminated open-field vegetables, raw milk, tap water, etc. It is important for the health care of residents to correctly comprehend the level of their exposure to radioactive substances released following the accident. However, an evaluation of the internal exposure doses of residents of Fukushima Prefecture as a result of the ingestion of foods, which is indicated in the report issued by United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR)1 is based on a number of assumptions. For instance, the estimation assumes that foods were ingested as usual, without regard to the places to which residents were evacuated after the accident, the places where food shipment restrictions were imposed, and so forth. The present report aims to improve the accuracy of estimation of the amount of food actually ingested at evacuation areas, in order to reduce as much as possible the level of uncertainty in conventional values estimated directly after the accident, which were in fact values based on conservative assumptions. More concretely, as basic source material to more accurately estimate internal exposure doses from food ingestion, various patterns of evacuation and dietary habits at the time of the accident of the residents of 13 municipalities in Fukushima Prefecture who were evacuated during the period from directly after the accident of March 11, 2011 until the end of March are clarified in this report. From survey results, most of the food that evacuees took immediately after the accident was confirmed to have been sourced from either stockpiles prepared before the accident, or relief supplies from outside of the affected areas. The restriction orders of food supplies such as contaminated vegetables and milk, and tap water intake were implemented within several days after the major release of radionuclides on March 15, 2011. In addition, collapse in supply chains, i.e., damage to distribution facilities, lack of transportation vehicles or electricity, and the closure of retail stores, contributed to a situation where food or supplies contaminated with iodine -131 were not consumed in large quantities in general, even before the food restriction order. Since people consumed tap water and water from other sources before the implementation of restriction orders in affected areas, we surveyed the status of water as a potential route of internal exposure.


Graves' animal models of Graves' hyperthyroidism.
Fifty years after the discovery of thyroid autoimmunity, several animal models of Graves' hyperthyroidism are now available. All are inducible types, and diseases are elicited by injecting living cells (professional or nonprofessional antigen-presenting cells) expressing the recombinant thyrotropin receptor (TSHR) or by DNA vaccination with TSHR cDNA in plasmid or adenovirus vectors. Thus most Graves' models are attributed to the cloning of the TSHR cDNA and involve in vivo expression of the TSHR. These breakthroughs have provided us important insights into our understanding of the pathogenesis of Graves' disease, and also indispensable means to exploring the possibility of development of novel therapeutic modalities. In particular, recent studies have begun to scrutinize the genetic factors contributing to the susceptibility to this ailment, and to delineate the roles for central and peripheral tolerance and also for fine balance between autoreactive effector T cells and regulatory T cells in the pathophysiology of anti-TSHR autoimmunity and Graves' hyperthyroidism. Moreover, preliminary, but novel, therapeutic approaches have also been started to treat experimental hyperthyroidism.


Transatrial-transpulmonary correction of tetralogy of Fallot: experience of a developing country.
Right ventricular dysfunction is a cause of morbidity and mortality after surgical correction of tetralogy of Fallot. The transatrial-transpulmonary approach allows preservation of right ventricular function. To report the immediate and long-term results of surgical treatment of tetralogy of Fallot using the transatrial-transpulmonary approach. This is a retrospective study including cases of tetralogy of Fallot operated on by the transatrial-transpulmonary approach between April 2009 and October 2010 in our institution. There were 19 patients including 10 girls and 9 boys with a mean age of 7.4 years (extremes: 3 and 19 years). All our patients benefited from closure of the ventricular septal defect by a right atrial approach and enlargement of the pulmonary pathway. In the immediate postoperative period, the pressure gradient between the pulmonary artery and the right ventricle was 18.77 mm Hg. We had 2 deaths (10.5%). Complications were dominated by conduction disorders (100%) such as right bundle branch block and pleuropulmonary complications (41.20%). After a mean follow-up of 11.43 ±0.81 years, no patient died and all were asymptomatic, without significant residual lesion. Complete cure of tetralogy of Fallot by the transatrial-transpulmonary route is associated with low morbidity and mortality in our experience. The long-term results are satisfactory.


Detection of CD40 on human thyroid follicular cells: analysis of expression and function.
Thyroid follicular cells (TFC) are a common target of autoimmune attack, but the role they play in inciting and maintaining this attack is unclear. TFC express cytokines, adhesion molecules, and class I and II major histocompatibility complex molecules, but without additional signals that costimulate T cells, they may down-regulate, rather than stimulate, T cell function. In this report, we have investigated whether TFC can express the CD40 molecule, which plays a crucial role in the reciprocal two-way communication between T and B cells. We have shown by immunohistochemistry and flow cytometry that CD40 is expressed by TFC in vivo and in vitro in both autoimmune and nonautoimmune glands. CD40 expression was up-regulated by interleukin-1alpha and interferon-gamma, but not by TSH. Although there was no significant effect of CD40 ligation on cAMP synthesis or [3H]thymidine incorporation, there was a significant increase in interleukin-6 release by TFC. Thus, although TFC do not express members of the B7 family of T cell costimulators, they do express CD40, indicating the possibility of mutually stimulatory T cell-TFC interaction. This has important implications, both for TFC synthesis of immunological mediators and for the biasing of T cell behavior toward a T helper 2-type phenotype.


Application of Caenorhabditis elegans for Research on Endoplasmic Reticulum Stress.
Caenorhabditis elegans is a versatile model organism that has been applied to research involving obesity, aging, and neurodegenerative diseases. C. elegans has many advantages over traditional animal models, including ease of handling, a short lifespan, a fully sequenced genome, ease of genetic manipulation, and a high similarity to human disease-related genes. With established C. elegans models of human disease, C. elegans provides a great platform for studying disease pathologies, including endoplasmic reticulum (ER) stress, which is characterized by the accumulation of unfolded and misfolded proteins involved in the pathologies of many diseases. ER stress can lead to activation of the unfolded and misfolded protein response, a mechanism that attenuates ER stress and recovers ER homeostasis. The current review gives an introduction to C. elegans and ER stress, along with the pathological role of ER stress in disease and the application of worm models in ER stress-related research.


DQ Herculis: Synchronous Photometry.
Synchronous signal averaging, applied to the photometry of the steller system DQ Herculis in order to study the 71.1-second pulsations discovered by Walker in 1956, yields a light curve which is a pure sinusoid, within the accuracy of measurement. The binary period is increasing, probably as a result of mass lost from the system.


Villous Tree Model with Active Contractions for Estimating Blood Flow Conditions in the Human Placenta.
In the human placenta, maternal and fetal bloods exchange substances through the surface of the villous trees: the fetal blood circulates in the villous trees, around which the maternal blood circulates. The blood flows directly influence fetal growth. Stem villi, the main supports of the villous tree, have contractile cells along the axes, whose contractions are expected to influence the blood circulations in the placenta. The displacement is neither measurable nor predictable while non-invasive measurements such as umbilical Doppler waveforms are helpful to predict the histological changes of the villous trees and vascularization in the placenta. The displacement caused by the contraction of the villous tree is necessary to predict the blood flows in the placenta. Hence, a computational villous tree model, which actively contracts, was developed in this study. The villous tree model was based on the previous reports: shear moduli of the human placenta; branching patterns in the stem villi. The displacement pattern in the placenta was estimated by the computational model when the shear elastic moduli were changed. The results show that the displacement caused by the contraction was influenced by the shear elastic moduli, but kept useful for the blood flows in the placenta. The characteristics agreed with the robustness of the blood flows in the placenta. The villous tree model, which actively contracts, was developed in this study. The combination of this computational model and non-invasive measurements will be useful to evaluate the condition of the placenta.


Evidence for the net addition of arene C-H bonds across a Ru(II)-hydroxide bond.
TpRu(PMe3)2(OH) (1) reacts with C6D6 to initiate H/D exchange between the hydroxide ligand and the deuterated benzene. In addition, complex 1 catalyzes H/D exchange between H2O and C6D6. Mechanistic and computational studies suggest that a likely reaction pathway for the H/D exchange involves loss of PMe3 to produce {TpRu(PMe3)(OH)}, followed by the net addition of a benzene C-H(D) bond across the Ru-OH bond to form the putative complex TpRu(PMe3)(OH2)(Ph).


[Surgical-technical problems of triple pelvic osteotomy. Early results of the polygonal method].
Since the first description of the triple pelvic osteotomies papers reporting on the improvement of the operative technique were continuously published. This is explained by the more problematic details of the operation. Authors worked out to the technique of the polygonal triple pelvic osteotomy, published by Kotz, Dávid and Uyka, a new exposure that makes more simple, quick and safe the performance of the operation. The essential feature is that the os ischii is reached after the osteotomy of the trochanter major from a lateral exposure and so the field of operation can be widely surveyed. At the same time transposition can also be performed. The experiences gained in 12 operations are reported, 8 of which were made according to their own method (follow-up: 8-22 months, in average 15 months). The patients were 14-33 years old and their complaints disappeared in every case. Authors suggest the operation for the correction of the dysplastic acetabulum in young adults and also in puberty after the fusion of the Y cartilage if no subluxation exists. Minor articular deformity and mild arthrosis are not considered as a contraindication.


[Management of the bleeding risk associated with antiplatelet agents].
Like all antithrombotic drugs, antiplatelet agents expose to a risk of bleeding complications. Clinical research has extensively focused on the efficacy of these drugs to reduce ischemic events. The bleeding risk associated with them was solely considered as an inevitable and acceptable complication. When two new potent P2Y12-receptor inhibitors, prasugrel and ticagrelor, were marketed, the risk of major bleeding increased. These new agents have modified the balance between the absolute risk reduction in ischemic events and the absolute risk increase in bleeding events. This paper is an update on the bleeding risk assessment associated with antiplatelet agents. It discusses the place of platelet function monitoring, and the optimal management of bleeding complications. It addresses the challenging issue of reversal of antiplatelet therapy, focusing especially on ticagrelor, which pharmacodynamics complicate bleeding management.


Biological imaging by soft x-ray diffraction microscopy.
We have used the method of x-ray diffraction microscopy to image the complex-valued exit wave of an intact and unstained yeast cell. The images of the freeze-dried cell, obtained by using 750-eV x-rays from different angular orientations, portray several of the cell's major internal components to 30-nm resolution. The good agreement among the independently recovered structures demonstrates the accuracy of the imaging technique. To obtain the best possible reconstructions, we have implemented procedures for handling noisy and incomplete diffraction data, and we propose a method for determining the reconstructed resolution. This work represents a previously uncharacterized application of x-ray diffraction microscopy to a specimen of this complexity and provides confidence in the feasibility of the ultimate goal of imaging biological specimens at 10-nm resolution in three dimensions.


A relationship between Autism-Spectrum Quotient and face viewing behavior in 98 participants.
Faces are one of the most important stimuli that we encounter, but humans vary dramatically in their behavior when viewing a face: some individuals preferentially fixate the eyes, others fixate the mouth, and still others show an intermediate pattern. The determinants of these large individual differences are unknown. However, individuals with Autism Spectrum Disorder (ASD) spend less time fixating the eyes of a viewed face than controls, suggesting the hypothesis that autistic traits in healthy adults might explain individual differences in face viewing behavior. Autistic traits were measured in 98 healthy adults recruited from an academic setting using the Autism-Spectrum Quotient, a validated 50-statement questionnaire. Fixations were measured using a video-based eye tracker while participants viewed two different types of audiovisual movies: short videos of talker speaking single syllables and longer videos of talkers speaking sentences in a social context. For both types of movies, there was a positive correlation between Autism-Spectrum Quotient score and percent of time fixating the lower half of the face that explained from 4% to 10% of the variance in individual face viewing behavior. This effect suggests that in healthy adults, autistic traits are one of many factors that contribute to individual differences in face viewing behavior.


Enzyme activity and bacteriophage infection. I. Breakdown of adenosinetriphosphate.
Experiments have been performed on the apyrase activity of E. coli, strain B. Although the dependence on pH and substrate is similar to that of rat tissue, the bacterial extracts are inhibited by Ca(++) and stimulated by Mg(++). In bacterial extracts the rate of phosphate release decreases in the course of the reaction, possibly owing to product inhibition. With multiple bacteriophage infection, the apyrase activity of the intact cells increased several fold, and the activity of extracts increased about 30 per cent. It is suggested that the changes could be attributed to an increase in the amount of enzyme although other alternatives cannot be precluded at present.


Calcium-sensing receptor (CASR) is involved in porcine in vitro fertilisation and early embryo development.
It has been demonstrated that extracellular calcium is necessary in fertilisation and embryo development but the mechanism is still not well understood. The present study mainly focussed on the extracellular calcium effector called the calcium-sensing receptor (CASR) and examined its expression in porcine gametes and embryos and its function during fertilisation and early embryo development. By using reverse transcription polymerase chain reaction, CASR was found to be expressed in porcine oocytes, spermatozoa and embryos at different developmental stages. Functionally, medium supplementation with a CASR agonist or an antagonist during in vitro fertilisation (IVF) and in vitro culture (IVC) was tested. During fertilisation, the presence of a CASR agonist increased sperm penetration rate and decreased polyspermy rate leading to an increased normal fertilisation rate. During embryo development, for the IVF embryos, agonist treatment during IVC significantly increased cleavage rate and blastocyst formation rate compared with the control group. Furthermore, parthenogenetically activated embryos showed similar results with lower cleavage and blastocyst formation rates in the antagonist group than in the other groups. It was concluded that CASR, as the effector of extracellular calcium, modulates porcine fertilisation and early embryo development.


[Reactive hyperplasia and pseudo-lymphomas with hypergammaglobulinemia. I. Benign lymphadenopathies].
The association of adenopathies, having sometimes a tumoral aspect, and a polyclonal hypergammaglobulinemia in the blood can be observed in various illnesses. In all these diseases the increase in the volume of the lymph nodes is partly due to the hyperplasia of the lymphoid B regions. Lymph node biopsy allows a precise diagnosis to be made, providing a thorough analytical study of the histopathological lesions is performed. In this first part, the histopathological lesions of benign lymphadenitis, having a pseudo-tumoral aspect from a clinical view, are described. The following are thus successively studied: sarcoidosis; acquired toxoplasmosis; the various aspects which can be attributed to infectious mononucleosis; vaccinal reactions; the Destombes-Rosai-Dorfman syndrome or massive lymphadenopathy by sinusal histiocytosis with hemophagocytosis; angiofollicular lymphoid hyperplasia or pseudo-tumour of Castleman; angio-follicular and plasmocytic polyadenopathy; the adenopathies of collagenosis and those due to protein deposits. For each disease, the morphological data are discussed and compared to clinical state and biological modifications.


Digital pathology systems enabling quality patient care.
Pathology laboratories are undergoing digital transformations, adopting innovative technologies to enhance patient care. Digital pathology systems impact clinical, education, and research use cases where pathologists use digital technologies to perform tasks in lieu of using glass slides and a microscope. Pathology professional societies have established clinical validation guidelines, and the US Food and Drug Administration have also authorized digital pathology systems for primary diagnosis, including image analysis and machine learning systems. Whole slide images, or digital slides, can be viewed and navigated similar to glass slides on a microscope. These modern tools not only enable pathologists to practice their routine clinical activities, but can potentially enable digital computational discovery. Assimilation of whole slide images in pathology clinical workflow can further empower machine learning systems to support computer assisted diagnostics. The potential enrichment these systems can provide is unprecedented in the field of pathology. With appropriate integration, these clinical decision support systems will allow pathologists to increase the delivery of quality patient care. This review describes the digital pathology transformation process, applicable clinical use cases, incorporation of image analysis and machine learning systems in the clinical workflow, as well as future technologies that may further disrupt pathology modalities to deliver quality patient care.


Evidence that precursor cells of monocytes and B-lymphocytes are closely related.
Various data in the literature suggest that progenitor cells of monocytes and B cells are closely related. In this study we have investigated this notion by using two-dimensional gel electrophoresis patterns of total cellular phosphoproteins to assess the similarity and thus the close relationships between erythroid, granulocyte, monocyte, and B-lymphocyte cell lines that typify immature cells of these lineages. In previous studies, six proteins had been identified whose constitutive phosphorylation correlated with the capacity of HL60 variant cell lines to differentiate towards either neutrophils (four proteins) or monocytes (two proteins). The presence or absence of five of these phosphoproteins in autoradiographs obtained for the pre-B-cell lines Nalm6 and SMSB showed that the pre-B-cell lines most closely resembled lines able to differentiate towards monocytes (HL6015-12, HL60M2, U937, and ML-1) as opposed to lines restricted to neutrophil (HL60Ast3) or erythroid differentiation (K562). The K562 phosphoprotein pattern resembled that obtained for HL60Ast3. Progressive changes in the constitutive phosphorylation of the five proteins were observed suggesting that cells that have acquired the potential for either neutrophil, monocyte, or B-cell differentiation have initially diversified in a linear progressive manner. This observation supports a model for hemopoiesis that suggests that, during progenitor cell development, differentiation potentials are expressed individually in the above order. Two additional phosphoprotein spots were found to be restricted to the pre-B-cell lines. These phosphoproteins, together with those that change their intensity in autoradiographs of erythroid, myeloid, and B-cell lines, suggest that protein phosphorylation plays an important role during cell diversification.


Phlorizin-like effect of Fraxinus excelsior in normal and diabetic rats.
The purpose of this study was to determine the underlying mechanism of the hypoglycaemic activity of the aqueous extract perfusion of Fraxinus excelsior L. (FE) in normal and streptozotocin-induced diabetic rats. The aqueous extract was administered intravenously and the blood glucose changes were determined within four hours after starting the treatment. Plasma insulin concentrations and glycosuria were determined. The aqueous extract at a dose of 10 mg/kg/h produced a significant decrease in blood glucose levels in normal rats (P < 0.001) and even more in diabetic rats (P < 0.001). This hypoglycaemic effect might be due to an extra-pancreatic action of the aqueous extract of FE, since the basal plasma insulin concentrations were unchanged after FE treatment. A potent increase of glycosuria was observed both in normal and diabetic rats (P < 0.001). We conclude that aqueous extract perfusion of FE caused a potent inhibition of renal glucose reabsorption. This renal effect might be at least one mechanism explaining the observed hypoglycaemic activity of this plant in normal and diabetic rats.


Not All Bad Comes to Harm: Enhanced Recovery after Surgery for Rectosigmoid Endometriosis.
To assess the impact of implementing an enhanced recovery after surgery (ERAS) protocol on the length of hospitalization in women undergoing laparoscopy for rectosigmoid deep infiltrating endometriosis (DIE). A retrospective cohort study. An academic referral center for endometriosis and minimally invasive gynecologic surgery. Women aged between 18 and 50 years scheduled for laparoscopic excision (shaving, full-thickness anterior wall resection, segmental resection) of rectosigmoid endometriosis between February 2017 and February 2023. We divided patients into 2 groups (non-ERAS and ERAS) based on the timing of surgery (before or after March 5, 2020). Starting from this day, restrictions were issued to limit the spread of the coronavirus disease 2019 pandemic, inducing our group to implement an ERAS protocol for patients hospitalized after surgery for posterior DIE. We included 579 patients in the analysis, 316 (54.6%) in the non-ERAS group and 263 (45.4%) in the ERAS group. In the ERAS group, we observed a shorter length of hospital stay (5.8 ± 3.1 days vs 4.8 ± 2.9 days; p <.001) and lower complications rates (33, 12.5% vs 60, 19.0%; p = .04), despite a decreased frequency of conservative surgical approaches (shaving procedures 121 vs 196; p <.001). Repeated surgery or hospital readmissions owing to postdischarge complications were infrequent, with no significant differences between the 2 groups. The multiple linear regression analysis strengthened our results given the higher prevalence of bowel resection surgeries (both full-thickness anterior wall or segmental), showing that patients managed with a multimodal protocol had an overall reduction of hospital stay by 1.5 days. The implementation of an ERAS program in patients undergoing laparoscopic surgery for DIE is associated with a significant reduction in hospital stay, without an increase in perioperative or postoperative complication rates.


Phylogeographical patterns in the American Pacific Northwest: lessons from the arionid slug Prophysaon coeruleum.
Some of the earliest studies of phylogenetic concordance involve native plants from the Pacific Northwest where many taxa showed clear genetic breaks between southern and northern populations. To test whether similar breaks also occur in invertebrate species with low dispersal capacities, genetic data from two mitochondrial genes are assembled for individuals of the arionid slug Prophysaon coeruleum throughout the species' range. Bayesian inference revealed three major clades and a total of eight subclades. It is argued that the demographic and genealogical past of P. coeruleum has resulted in a deep and shallow phylogeographical structure. The deep structure is at least 2.6-5.9 million years old and therefore clearly predates the Pleistocene period. Superimposed on this structure is a shallow structure that is most likely less than 2 million years old and probably the result of Pleistocene perturbations. Molecular analyses revealed that the three known colour traits in P. coeruleum do not represent monophyletic groups and that they do not match the patterns of genetic structure found. It is argued that the colour traits are perhaps a response to different levels of UV-radiation. The study adds to the increasing evidence that the phylogeographical structure of some taxa is more complex than previously thought. Moreover, it shows that genealogical concordance should not be deduced from phylogeographical patterns alone but should be based on an understanding of timing and causes of historical processes that lead to those patterns.


An IgE inhibition assay for the detection of allergen specific IgE.
A method for the detection of specific IgE in human serum is described, using a modified radioimmune assay termed the Inhibition Assay Technique (IAT) The technique is based on the ability of specific IgE to bind with allergen. The difference in total IgE before incubation with the allergen and after incubation with the allergen gives a relative concentration of specific IgE to that particular allergenic substance. The assay has been shown to correlate with both the intradermal skin test as well as the standard RAST now used to determine specific IgE.


[Isolated mediastinal fibromatosis (clinical study and a brief review of the literature)].
Fibrosing processes of connective tissue of unknown etiology affect different anatomical sites either in an isolated or a combined way, masking frequently as tumorous diseases. Clinical manifestations are nonspecific, determined by the site and spread of a process and appear in the form of the syndrome of compression of the adjacent organs. Organ site of a process determines complications and prognosis of disease. Fibromatosis can be diagnosed only in histological investigation. A physician should made aware of a history of traumas surgical interventions, intoxication, fever, increased ESR, dilatation of the aortic arch shadow during x-ray examination, GI tract bleeding, and outline the most effective therapeutic tactics for a patient with mediastinal fibromatosis.


Parathyroid function study in patients submitted to laryngeal surgery for squamous cell carcinoma.
Aim of this study was to investigate any eventual quantitative variations in the serological concentration of parathormone in a homogenous sample of patients suffering from laryngeal squamous cell carcinoma who underwent only surgery. A total of 12 patients (2 female, 10 male), aged between 58 and 76 years, were treated between June 2002 and June 2003. The patients were all affected by T2-T3 laryngeal squamous cell carcinoma. Serum intact parathyroid hormone and calcaemia were measured pre- and post-operatively. Of these patients, 2 underwent total laryngectomy (including thyroid isthmectomy), 5 patients received partial supraglottic laryngectomy, while the remaining 5 were submitted to supracricoid laryngectomy. Results showed a progressive regression of parathyroid hormone level, in only one case and was not, however, below normal limits. Contrary to data reported in the literature, this study indicated that the incidence of hypoparathyroidism following laryngeal surgery, even in radical surgical approaches, proved to be closer to zero.


Effect of different concentrations of soybean lecithin and virgin coconut oil in Tris-based extender on the quality of chilled and frozen-thawed bull semen.
The objective of this study was to evaluate the effects of different concentrations of soybean lecithin (SL) and virgin coconut oil (VCO) in Tris-based extender on chilled and frozen-thawed bull semen quality parameters. A total of 24 ejaculates were collected from four bulls via an electroejaculator. Semen samples were diluted with 2% VCO in Tris-based extender which consists of various concentrations of SL (1, 1.25, 1.5, and 1.75%). A 20% egg yolk in Tris used as a positive control (C+). The diluted semen samples were divided into two fractions; one for chilling which were stored at 4°C for 24, 72, and 144 h before evaluated for semen quality parameters. The second fraction used for freezing was chilled for 3 h at 4°C, packed into 0.25 mL straws and then cryopreserved in liquid nitrogen. The samples were then evaluated after 7 and 14 days. Chilled and frozen semen samples were thawed at 37°C and assessed for general motility using computer-assisted semen analysis, viability, acrosome integrity and morphology (eosin-nigrosin stain), membrane integrity, and lipid peroxidation using thiobarbituric acid reaction test. The results showed that all the quality parameters assessed were significantly (p<0.05) improved at 1.5% SL concentration in chilled semen. Treatment groups of 1, 1.25, 1.5, and 1.75% SL were higher in quality parameters than the control group (C+) in chilled semen. However, all the quality parameters in frozen-thawed semen were significantly higher in the C+ than the treated groups. In conclusion, supplementation of 1.5% SL in 2% VCO Tris-based extender enhanced the chilled bull semen. However, there was no marked improvement in the frozen-thawed quality parameters after treatment.


Communicating printed headings to the ear.
Two experiments compared three methods of translating printed headings into an auditory format. In both experiments, college students listened to a text with instructions to stop the recording whenever they heard a heading and type the hierarchical level and exact wording of the heading. Listeners were poor at identifying headings and their levels if the headings were not distinguished from the rest of the text. However, listeners were very good at identifying headings if any method of signalling was used to distinguish headings and communicate their hierarchical level. The methods included: (1) tones preceding headings, (2) changes of speaker to indicate headings or (3) verbal labels preceding headings. Although all three signalling methods improved identification of a heading's hierarchical level, the labelling method was the most effective means of communicating hierarchical level. Thus, the study identifies a simple method of effectively communicating headings in spoken text. Practitioner Summary: The study attempted to identify effective ways of communicating heading information in spoken text. College students listened to texts in order to detect headings and record their wording and hierarchical level. Performance was excellent when headings were preceded by verbal phrases that signalled the upcoming headings and their levels.


Genetic basis of coaggregation receptor polysaccharide biosynthesis in Streptococcus sanguinis and related species.
Interbacterial adhesion between streptococci and actinomyces promotes early dental plaque biofilm development. Recognition of coaggregation receptor polysaccharides (RPS) on strains of Streptococcus sanguinis, Streptococcus gordonii and Streptococcus oralis by Actinomyces spp. type 2 fimbriae is the principal mechanism of these interactions. Previous studies of genetic loci for synthesis of RPS (rps) and RPS precursors (rml, galE1 and galE2) in S. gordonii 38 and S. oralis 34 revealed differences between these strains. To determine whether these differences are strain-specific or species-specific, we identified and compared loci for polysaccharide biosynthesis in additional strains of these species and in several strains of the previously unstudied species, S. sanguinis. Genes for synthesis of RPS precursors distinguished the rps loci of different streptococci. Hence, rml genes for synthesis of TDP-L-Rha were in rps loci of S. oralis strains but at other loci in S. gordonii and S. sanguinis. Genes for two distinct galactose epimerases were also distributed differently. Hence, galE1 for epimerization of UDP-Glc and UDP-Gal was in galactose operons of S. gordonii and S. sanguinis strains but surprisingly, this gene was not present in S. oralis. Moreover, galE2 for epimerization of both UDP-Glc and UDP-Gal and UDP-GlcNAc and UDP-GalNAc was at a different locus in each species, including rps operons of S. sanguinis. The findings provide insight into cell surface properties that distinguish different RPS-producing streptococci and open an approach for identifying these bacteria based on the arrangement of genes for synthesis of polysaccharide precursors.


A Single Biosensor for Evaluating the Levels of Copper Ion and L-Cysteine in a Live Rat Brain with Alzheimer's Disease.
Copper ion (Cu(2+)) and L-cysteine (CySH) are closely correlated with physiological and pathological events of Alzheimer's Disease (AD), however the detailed mechanism is still unclear, mainly owing to a lack of accurate analytical methods in live brains. Herein, we report a single biosensor for electrochemical ratiometric detection of Cu(2+) and CySH in live rat brains with AD. N,N-di-(2-picoly)ethylenediamine (DPEA) is first synthesized for specific recognition of Cu(2+) to form a DPEA-Cu(2+) complex. This complex shows high selectivity for CySH owing to the release of Cu(2+) from the complex through CySH binding to Cu(2+) center. In parallel, 5'-MB-GGCGCGATTTTTTTTTTTTT-SH-3' (HS-DNA-MB, MB=Methylene Blue) is designed as an inner-reference for providing a built-in correction to improve the accuracy. As a result, combined with the amplified effect of Au nanoleaves, our single ratiometric biosensor can be successfully applied in real-time detection of Cu(2+) and CySH in the live rat brains with AD. To our knowledge, this is the first report on the accurate concentrations of Cu(2+) and CySH in live rat brains with AD.


Enhancement of Birefringence in Reduced Graphene Oxide Doped Liquid Crystal.
We investigated the effect of reduced graphene oxide (rGO) doping on the birefringence of 5CB liquid crystal (LC). The characteristics of the synthesized rGO and LC-rGO composite with different rGO concentrations were analyzed by atomic force microscopy, X-ray photoelectron spectroscopy, white light polarized microscopy, voltage-dependent transmission measurement, and differential scanning calorimetry. We found that doping LC with an appropriate concentration of rGO enhances the birefringence of the LC. This is mainly due to the improved anisotropy of polarizability, which stems from the high shape anisotropy of rGO. However, the aggregation of rGO reduces the birefringence by decreasing the anisotropy of polarizability as well as the order parameter. Our study shows the promising potential of LC-rGO for developing various electro-optic devices that offer improved electro-optic effects.


Metabolic syndrome and short-term heart rate variability in adults with intellectual disabilities.
Metabolic syndrome (MetS) increases the risk of cardiovascular events. Heart rate variability (HRV) represents autonomic functioning, and reduced HRV significantly increases cardiovascular mortality. The aims of the present paper are to assess the prevalence of MetS in adults with intellectual disabilities (ID), the difference in short-term HRV between the healthy and ID population, and the association of short-term HRV with MetS. In this study, we analyzed 129 ID subjects who participated in routine health check-ups in October 2010. We measured their metabolic components and evaluated the relationships of MetS with short-term HRV indices. The study found that MetS and obesity are common in persons with ID. ID subjects have significantly lower HRV than healthy adults, and persons with ID persons with MetS have significantly lower HRV than ID subjects without MetS. The individual components of MetS are differentially associated with HRV in ID men and women. Metabolic syndrome adversely affects autonomic cardiac control, and reduced autonomic cardiac control could contribute to an increased risk of subsequent cardiovascular events in individuals who exhibit metabolic syndrome. Sex differences in vagal activity and sympathovagal balance may partly explain the greater increase in cardiovascular risk associated with MetS in ID women compared with ID men.


Retrograde concealed conduction in the atrioventricular node: differential manifestations related to level of intranodal penetration.
Although concealed conduction in the atrioventricular node (AVN) has been the focus of numerous experimental and clinical studies, little is known about the differential effects on AVN functional behavior of prior concealed retrograde impulse penetration alone vs prior anterograde or dual AVN activation. This study was undertaken specifically to investigate this aspect of human AVN physiology in patients without intact ventriculoatrial conduction to provide a model with which to analyze concealed retrograde AVN conduction. In 13 such patients AVN behavior during a subsequent anterograde input was characterized for each of three different manners of prior AVN activation: anterograde alone (method I), simultaneous anterograde and retrograde excitation (method II), or equivalently timed retrograde concealed AVN penetration alone (method III). In all patients evidence for retrograde AVN concealment was documented by longer anterograde conduction in the AVN during method III than that observed when the retrograde impulse was omitted (method IV). Furthermore, in these patients lacking intact ventriculoatrial conduction, anterograde conduction in the AVN was facilitated and refractoriness was decreased during dual excitation vs anterograde activation alone (method II vs method I). However, when each of methods I and II were compared with concealed retrograde AVN penetration alone (method III), two patterns of AVN responses were observed: In 11 of 13 patients (group A) conduction in the AVN was "worse" and refractoriness was greater both in methods I and II compared with method III; in the remaining two patients (group B) the opposite relationships were observed. The results suggest that among patients with no ventriculoatrial AVN conduction there exist at least two subpopulations whose AVN functional characteristics differ markedly when the effects of anterograde and dual excitation are compared with equivalently timed concealed retrograde activation alone. These findings may be related to differences in level of retrograde AVN concealment in groups A and B, which can be unmasked by the outlined pacing techniques.


Characterization of human and mouse rod cGMP phosphodiesterase delta subunit (PDE6D) and chromosomal localization of the human gene.
The mammalian multisubunit photoreceptor cGMP phosphodiesterase PDE alpha beta gamma 2 (PDE6 family) is a peripherally membrane-associated enzyme. A novel subunit, termed PDE delta (HGMW-approved symbol, PDE6D; MW 17 kDa), is able to detach PDE partially from bovine rod outer segment membranes under physiological conditions. Cloning of human and mouse PDE delta cDNAs revealed that PDE delta is a nearly perfectly conserved polypeptide of 150 amino acids that shows partial sequence homology to photoreceptor RG4 of unknown function. Multiple-species Southern blot analysis demonstrates that the PDE delta gene has been well conserved during evolution and is detectable at high stringency in invertebrates. The human and mouse genes are contained in less than 8 kb of genomic DNA and consist of four exons and three introns (0.7-4 kb in human, 0.7-2.2 kb in mouse). The PDE delta gene structure is identical to that of the C27H5.1 gene identified in the eyeless nematode Caenorhabditis elegans. The human PDE delta gene (locus designation PDE6D) was localized to the long arm of chromosome 2 (2q35-q36) by fluorescence in situ hybridization. By synteny, the mouse PDE delta gene is predicted to reside on chromosome 1.


Pathogenesis of ANCA-associated vasculitis: an emerging role for immunometabolism.
ANCA-associated vasculitis (AAV) is a severe systemic autoimmune disease. A key feature of AAV is the presence of Anti-Neutrophil Cytoplasmic Antibodies (ANCA) directed against myeloperoxidase (MPO) or proteinase-3 (PR3). ANCA are key to the pathogenesis of AAV, where they activate innate immune cells to drive inflammation. Pre-activation or 'priming' of immune cells appears to be important for complete cellular activation in AAV. The burgeoning field of immunometabolism has illuminated the governance of immune cell function by distinct metabolic pathways. There is ample evidence that the priming events synonymous with AAV alter immune cell metabolism. In this review we discuss the pathogenesis of AAV and its intersection with recent insights into immune cell metabolism.


Acute effects of beetroot juice and caffeine co-ingestion during a team-sport-specific intermittent exercise test in semi-professional soccer players: a randomized, double-blind, placebo-controlled study.
Beetroot juice (BJ) and caffeine (CAF) are considered as ergogenic aids among athletes to enhance performance, however, the ergogenic effects of BJ and CAF co-ingestion are unclear during team-sport-specific performance. This study aimed to investigate the acute effects of BJ and CAF co-ingestion on team-sport-specific performance, compared with placebo (PL), BJ, and CAF alone. Sixteen semi-professional male soccer players (age: 19.8 ± 2.2 years, body mass: 69.2 ± 6.1 kg, height: 177.3 ± 6.0 cm) completed four experimental trials using a randomized, double-blind study design: BJ + CAF, CAF + PL, BJ + PL, and PL + PL. Countermovement jump with arm swing (CMJAS) performance and cognitive function by Stroop Word-Color test were evaluated before and after the Yo-Yo Intermittent Recovery Test level 1 (YYIR1). Also, rate of perceived exertion (RPE), heart rate, and gastrointestinal (GI) discomfort were measured during each session. No significant differences were shown between test conditions for total distance covered in YYIR1 (BJ + CAF: 1858 ± 455 m, CAF + PL: 1798 ± 422 m, BJ + PL: 1845 ± 408 m, PL + PL 1740 ± 362 m; p = 0.55). Moreover, CMJAS performance, cognitive function, and RPE during the YYIR1 were not significantly different among conditions (p > 0.05). However, the average heart rate during the YYIR1 was higher in CAF + PL compared to PL + PL (by 6 ± 9 beats/min; p < 0.05), and GI distress was greater in BJ + CAF compared to PL + PL (by 2.4 ± 3.6 a.u.; p < 0.05). These results suggest, neither acute co-ingestion of BJ + CAF nor BJ or CAF supplementation alone significantly affected team-sport-specific performance compared to the PL treatment.


Saffron carotenoids change the superoxide dismutase activity in breast cancer: In vitro, in vivo and in silico studies.
Superoxide dismutase (SOD) is an important member of the antioxidant defense system and is proposed as a therapeutic agent against the ROS-mediated diseases, and a therapeutic target for cancer treatment. Saffron carotenoids, crocin (Cro) and crocetin (Crt), are antioxidants with anticancer activity. In the present study, we investigated the effects of Cro/Crt on the SOD activity in both in vivo and in vitro models of breast cancer. Both Cro and Crt showed strong radical scavenging activity and SOD inhibition in the MCF-7 breast cancer cell line. The UVVis, circular dichroism and fluorometry studies proposed the binding of both Cro and Crt with SOD; the ΔG° of binding at 310 °K was -8.6 and -4.4 kcal/mol, respectively. The docking analysis predicted the Cro/Crt binding near the active site channel, but in different sites. According to the obtained data, Cro inhibits SOD activity by scavenging superoxide radical (O2), while Crt inhibits SOD by affecting the copper-binding site. In contrast to the in vitro data, both Cro and Crt effectively increased SOD activity in breast tumors of BALB/c mice, after one month of treatment. The mechanism that is important to compensate for the SOD decreased activity in cancer.


Uncovering the eruptive patterns of the 2019 double paroxysm eruption crisis of Stromboli volcano.
In 2019, Stromboli volcano experienced one of the most violent eruptive crises in the last hundred years. Two paroxysmal explosions interrupted the 'normal' mild explosive activity during the tourist season. Here we integrate visual and field observations, textural and chemical data of eruptive products, and numerical simulations to analyze the eruptive patterns leading to the paroxysmal explosions. Heralded by 24 days of intensified normal activity and 45 min of lava outpouring, on 3 July a paroxysm ejected ~6 × 107 kg of bombs, lapilli and ash up to 6 km high, damaging the monitoring network and falling towards SW on the inhabited areas. Intensified activity continued until the less energetic, 28 August paroxysm, which dispersed tephra mainly towards NE. We argue that all paroxysms at Stromboli share a common pre-eruptive weeks-to months-long unrest phase, marking the perturbation of the magmatic system. Our analysis points to an urgent implementation of volcanic monitoring at Stromboli to detect such long-term precursors.


Mothers' perceptions of children's refusal to undergo dental treatment: an exploratory qualitative study.
Very little is known about mothers' beliefs concerning children's refusal of dental treatment. This qualitative study aimed to explore mothers' perceptions of their children's refusal to submit to dental treatment. Semistructured interviews were conducted with 14 mothers of 4-12-yr-old children resistant to dental treatment who were attending two pediatric dentists. Thematic content analysis was used to interpret the data. From this, three categories were developed and labeled origins of child behavior, caregiver attitudes, and the culture of resistance. The origins of the children's behavior were related to the childs' temperament, behavior disorders, lack of affection, level of development, and refusal to submit to health procedures or other situations. Caregiver's attitudes included discipline, protection, incoherence, partnership in dental treatment, and mother-child feeling. The culture of resistance referred to the parents' or guardians' refusal of dental treatment and the mothers' recognition of this. In conclusion, the wide variety of mothers' accounts reinforced the idea that every child is unique, and it is not possible to standardize child behavior models in a dental setting.


Time of follicular transformation to the rapid growth phase in relation to the ovulatory cycle of laying hens.
To demonstrate time of transformation of ovarian follicles from the resting stage to the rapid growth phase, Sudan black in ethanol was intravenously injected into laying hens, and 4 hr later Sudan red in water was injected into the same hens; the hens were killed 4 hr after the last injection for observation of the follicles. Injections were made at various times during an ovulatory cycle. In an additional experiment, hourly yolk deposition in the dark period (1900 to 0500 hr) was compared with that in the light period. Follicular transformation occurred at a high frequency within the period of 8 to 14 hr after ovulation. This period corresponded to the time between 1700 and 2400 hr. Hourly yolk deposition in the dark period was higher than that in the light period.


Cell-specific abnormalities of glutamate transporters in schizophrenia: sick astrocytes and compensating relay neurons?
Excitatory amino-acid transporters (EAATs) bind and transport glutamate, limiting spillover from synapses due to their dense perisynaptic expression primarily on astroglia. Converging evidence suggests that abnormalities in the astroglial glutamate transporter localization and function may underlie a disease mechanism with pathological glutamate spillover as well as alterations in the kinetics of perisynaptic glutamate buffering and uptake contributing to dysfunction of thalamo-cortical circuits in schizophrenia. We explored this hypothesis by performing cell- and region-level studies of EAAT1 and EAAT2 expression in the mediodorsal nucleus of the thalamus in an elderly cohort of subjects with schizophrenia. We found decreased protein expression for the typically astroglial-localized glutamate transporters in the mediodorsal and ventral tier nuclei. We next used laser-capture microdissection and quantitative polymerase chain reaction to assess cell-level expression of the transporters and their splice variants. In the mediodorsal nucleus, we found lower expression of transporter transcripts in a population of cells enriched for astrocytes, and higher expression of transporter transcripts in a population of cells enriched for relay neurons. We confirmed expression of transporter protein in neurons in schizophrenia using dual-label immunofluorescence. Finally, the pattern of transporter mRNA and protein expression in rodents treated for 9 months with antipsychotic medication suggests that our findings are not due to the effects of antipsychotic treatment. We found a compensatory increase in transporter expression in neurons that might be secondary to a loss of transporter expression in astrocytes. These changes suggest a profound abnormality in astrocyte functions that support, nourish and maintain neuronal fidelity and synaptic activity.


Surgical Management of Brain Metastasis: Challenges and Nuances.
Brain metastasis is the most common type of intracranial tumor. The contemporary management of brain metastasis is a challenging issue and traditionally has carried a poor prognosis as these lesions typically occur in the setting of advanced cancer. However, improvement in systemic therapy, advances in radiation techniques and multimodal therapy tailored to the individual patient, has given hope to this patient population. Surgical resection has a well-established role in the management of brain metastasis. Here we discuss the evolving role of surgery in the treatment of this diverse patient population.


Isothermal microcalorimetry accurately detects bacteria, tumorous microtissues, and parasitic worms in a label-free well-plate assay.
Isothermal microcalorimetry is a label-free assay that allows monitoring of enzymatic and metabolic activities. The technique has strengths, but most instruments have a low throughput, which has limited their use for bioassays. Here, an isothermal microcalorimeter, equipped with a vessel holder similar to a 48-well plate, was used. The increased throughput of this microcalorimeter makes it valuable for biomedical and pharmaceutical applications. Our results show that the sensitivity of the instrument allows the detection of 3 × 10(4) bacteria per vial. Growth of P. mirabilis in Luria Broth medium was detected between 2 and 9 h with decreasing inoculum. The culture released 2.1J with a maximum thermal power of 76 μW. The growth rate calculated using calorimetric and spectrophotometric data were 0.60 and 0.57 h(-1) , respectively. Additional insight on protease activities of P. mirabilis matching the last peak in heat production could be gathered as well. Growth of tumor microtissues releasing a maximum thermal power of 2.1 μW was also monitored and corresponds to a diameter increase of the microtissues from ca. 100 to 428 μm. This opens new research avenues in cancer research, diagnostics, and development of new antitumor drugs. For parasitic worms, the technique allows assessment of parasite survival using motor and metabolic activities even with a single worm.


Weight gain with antidepressants and lithium.
Undesired weight gain is a common complaint of patients receiving pharmacological treatment for major affective disorders. It has been found to jeopardize patient compliance and may pose additional health hazards. A review of the literature on weight gain associated with tricyclic antidepressants, monoamine oxidase inhibitors, and lithium was carried out with the aim of deriving practical management strategies. Tricyclic antidepressants were found to stimulate appetite, carbohydrate craving, and a dose-dependent continuous weight gain of 0.57 to 1.37 kg per month of treatment. Proposed mechanisms include noradrenergic or antihistaminic inhibition of satiety and decreased metabolic rate. Novel serotonergic and dopaminergic antidepressants were found to be anorectic. Monoamine oxidase inhibitors may stimulate appetite and potentiate insulin-induced hypoglycemia. Lithium maintenance therapy stimulates weight gains of over 10 kg in 20% of patients. Documented mechanisms include insulin-like actions on carbohydrate and fat metabolism, polydipsia, and sodium retention. Recommendations regarding choice of antidepressant drug as well as dietary and behavioral strategies to prevent excessive weight gain are presented. Potential adjunctive drug approaches to severe weight gain are reviewed.