Respiratory toxicity and immunotoxicity evaluations of microparticle and nanoparticle C60 fullerene aggregates in mice and rats following nose-only inhalation for 13 weeks.
C60 fullerene (C60), or buckminsterfullerene, is a spherical arrangement of 60 carbon atoms, having a diameter of approximately 1 nm, and is produced naturally as a by-product of combustion. Due to its small size, C60 has attracted much attention for use in a variety of applications; however, insufficient information is available regarding its toxicological effects. The effects on respiratory toxicity and immunotoxicity of C60 aggregates (50 nm [nano-C60] and 1 μm [micro-C60] diameter) were examined in B6C3F1/N mice and Wistar Han rats after nose-only inhalation for 13 weeks. Exposure concentrations were selected to allow for data evaluations using both mass-based and particle surface area-based exposure metrics. Nano-C60 exposure levels selected were 0.5 and 2 mg/m3 (0.033 and 0.112 m2/m3), while micro-C60 exposures were 2, 15 and 30 mg/m3 (0.011, 0.084 and 0.167 m2/m3). There were no systemic effects on innate, cell-mediated, or humoral immune function. Pulmonary inflammatory responses (histiocytic infiltration, macrophage pigmentation, chronic inflammation) were concentration-dependent and corresponded to increases in monocyte chemoattractant protein (MCP)-1 (rats) and macrophage inflammatory protein (MIP)-1α (mice) in bronchoalveolar lavage (BAL) fluid. Lung overload may have contributed to the pulmonary inflammatory responses observed following nano-C60 exposure at 2 mg/m3 and micro-C60 exposure at 30 mg/m3. Phenotype shifts in cells recovered from the BAL were also observed in all C60-exposed rats, regardless of the level of exposure. Overall, more severe pulmonary effects were observed for nano-C60 than for micro-C60 for mass-based exposure comparisons. However, for surface-area-based exposures, more severe pulmonary effects were observed for micro-C60 than for nano-C60, highlighting the importance of dosimetry when evaluating toxicity between nano- and microparticles.


Mutational screening of Indian families with hereditary congenital cataract.
To screen for pathogenic mutations in ten candidate genes in Indian families diagnosed with autosomal recessive and autosomal dominant cataracts. Families with two or more affected individuals with bilateral familial congenital/developmental cataract were ophthalmically evaluated, and blood samples were obtained. Genomic DNA extracted from the blood leukocytes was screened with PCR amplification of the exons and the flanking intronic regions of various genes selected for analysis. The amplified products were subjected to single strand conformation polymorphism (SSCP) analysis. The variants in SSCP analysis were subjected to bidirectional sequencing by automated methods. We identified four novel sequence changes that cosegregated with the disease phenotype in each family and were absent in at least 50 ethnically matched unrelated normal controls. These changes include a homozygous missense change of c.649G>A (Val196Met) in GJA8/connexin 50 (Cx50) in a family with autosomal recessive cataract, two heterozygous missense changes, c.658C>T (Pro199Ser) in GJA8/Cx50 and c.589C>T (Pro197Ser) in GJA3/connexin 46 (Cx46) in two separate families with autosomal dominant cataract, and a silent change ( c.84G>A/p.Val28Val, predicted to result in the creation of a new potential branch point) in GJA8 one family with an autosomal dominant inheritance of cataract. Of the four novel mutations identified, three mutations, Val196Met (GJA8), Pro199Ser (GJA8), and Pro197Ser (GJA3), are predicted to be in the second extracellular domain of the respective connexin proteins. Our report extends the mutation spectrum of connexin genes GJA8 and GJA3 and confirms that connexin genes are among the most frequently mutated genes in hereditary cataracts. Our results suggest that connexin gene (GJA8 and GJA3) mutations occur in approximately 10% (4/40 families) of families with congenital hereditary cataracts in a population from southern India.


Direct space time-characterization of the electric fields of ultrashort optical pulses.
We report the complete spatiotemporal characterization of ultrashort light pulses by use of a self-referencing device based on shearing interferometry in the space and frequency domains. The apparatus combines a spatially resolved spectral shearing interferometer with a spectrally resolved spatial shearing interferometer. The electric field as a function of one transverse spatial coordinate and time is obtained from a single experimental trace by means of a direct and fast algebraic phase reconstruction algorithm. The method has been tested in several common laboratory situations.


Pseudomonas flavescens sp. nov., isolated from walnut blight cankers.
Two pseudomonad strains that produce a yellow cellular pigment, in addition to a diffusible fluorescent pigment on Kings medium B, were isolated from cankers on walnut trees. Biochemical properties, such as a positive oxidase reaction, a negative arginine dihydrolase reaction, and the production of a fluorescent pigment, in addition to the results of an extensive nutritional characterization study and DNA-DNA hybridization experiments, indicated that these strains belong to a new Pseudomonas rRNA group I species. This conclusion was supported by the results of a determination of the sequence of the PCR-amplified 16S rRNA gene and a comparison with the 16S rRNA genes of other bacterial species. The genomic DNAs of the strains had a base composition of 63 mol% G+C. The name Pseudomonas flavescens sp. nov. is proposed. Strain B62 (= NCPPB 3063) is the type strain of the species.


In a subgroup of high-risk Asians, telmisartan was non-inferior to ramipril and better tolerated in the prevention of cardiovascular events.
Results of the recently published ONTARGET study (The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial) showed that telmisartan (80 mg/day) was non-inferior to ramipril (10 mg/day) in reducing cardiovascular events. Clinicians in Asia doubt tolerability of these doses for their patients. We therefore analyzed data from this study and a parallel study TRANSCEND (Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease). Our objectives were to compare Asians and non-Asians with respect to the following: 1) Effectiveness of telmisartan vs. ramipril in reducing cardiovascular events;2) Proportions who reached the full dose of telmisartan, ramipril or placebo; and3) Proportions of overall discontinuations, and discontinuations due to adverse effects. The ONTARGET study randomized 25,620 patients at risk of cardiovascular events to ramipril, telmisartan, or their combination. The primary composite endpoint was death caused by cardiovascular disease, acute MI, stroke, and hospitalization because of congestive heart failure. TRANSCEND randomized 5926 high-risk patients with a history of intolerance to ACE-inhibitors to telmisartan or placebo. The primary outcome was the same. In this substudy, we compared Asians and non-Asians as to how well they tolerated telmisartan (given in both studies) and ramipril (given in ONTARGET). 1) Telmisartan was non-inferior to ramipril in lowering the primary endpoint among Asians (RR = 0.92; 95% CI: 0.74, 1.13); 2) more Asians achieved the full dose of either drug; 3) less withdrew (overall); and 4) less withdrew for adverse effects. Furthermore, telmisartan was better tolerated than ramipril. This advantage was greater among Asians. Although Asians had lower BMI than non-Asians, Asians tolerated both drugs better. Regulatory agencies require reporting of safety and effectiveness data by ethnicity, but few comply with this requirement. This study shows that safety data in ethnic subgroups can help assess applicability of results to specific populations. ClinicalTrials.gov NCT00153101.


The systemic control of circadian gene expression.
The mammalian circadian timing system consists of a central pacemaker in the brain's suprachiasmatic nucleus (SCN) and subsidiary oscillators in nearly all body cells. The SCN clock, which is adjusted to geophysical time by the photoperiod, synchronizes peripheral clocks through a wide variety of systemic cues. The latter include signals depending on feeding cycles, glucocorticoid hormones, rhythmic blood-borne signals eliciting daily changes in actin dynamics and serum response factor (SRF) activity, and sensors of body temperature rhythms, such as heat shock transcription factors and the cold-inducible RNA-binding protein CIRP. To study these systemic signalling pathways, we designed and engineered a novel, highly photosensitive apparatus, dubbed RT-Biolumicorder. This device enables us to record circadian luciferase reporter gene expression in the liver and other organs of freely moving mice over months in real time. Owing to the multitude of systemic signalling pathway involved in the phase resetting of peripheral clocks the disruption of any particular one has only minor effects on the steady state phase of circadian gene expression in organs such as the liver. Nonetheless, the implication of specific pathways in the synchronization of clock gene expression can readily be assessed by monitoring the phase-shifting kinetics using the RT-Biolumicorder.


The impact of mesenchymal stem cell therapy in transplant rejection and tolerance.
Treatment with classical immunosuppressive drugs is associated with low specificity leading to toxicity, infections and malignancies. Cell therapy is emerging as an alternative for the pharmacological therapies and among them mesenchymal stem cells (MSCs) appear as a solid choice for the treatment of transplanted patients. The aim of the present review is to analyze the potency of MSCs cell therapy in solid organ transplantation. The increasing knowledge on the role of newly identified cell types like the pro-inflammatory Th17 cells, tolerogenic dendritic cells, regulatory macrophages and regulatory B cells among others in alloreactivity widened our understanding of the immune responses in transplantation patients. Recent studies suggest that MSCs interact with those populations as well as with classically studied Th1 cells to reduce alloreactivity and potentially promote graft acceptance. MSCs are arising as an immunomodulatory and potentially pro-tolerogenic tool in cell therapeutic intervention in solid organ transplantation and could substitute or minimize current immunosuppressive treatments.


The effect of fatty acids and starvation on the metabolism of gluconeogenic precursors by isolated sheep liver cells.
Isolated liver cells prepared from fed sheep synthesize glucose from propionate at twice the rate observed with cells from starved animals. Addition of palmitate or palmitate + carnitine to incubations of liver cells from starved animals inhibited the rate of glucose synthesis with lactate as a precursor, but had little effect when propionate and pyruvate were substrates. Liver cells from fed and starved sheep synthesized lactate and pyruvate when incubated with propionate. Fatty acids inhibited this formation of lactate and pyruvate from propionate. It is proposed that the different responses of gluconeogenic precursors to fatty acids can be explained by the effect of reducing equivalents on the transport of carbon atoms across the mitochondrial membrane.


Trends in cancer imaging by indication, care setting, and hospital type during the COVID-19 pandemic and recovery at four hospitals in Massachusetts.
We aimed to investigate the effects of COVID-19 on computed tomography (CT) imaging of cancer. Cancer-related CTs performed at one academic hospital and three affiliated community hospitals in Massachusetts were retrospectively analyzed. Three periods of 2020 were considered as follows: pre-COVID-19 (1/5/20-3/14/20), COVID-19 peak (3/15/20-5/2/20), and post-COVID-19 peak (5/3/20-11/14/20). 15 March 2020 was the day a state of emergency was declared in MA; 3 May 2020 was the day our hospitals resumed to non-urgent imaging. The volumes were assessed by (1) Imaging indication: cancer screening, initial workup, active cancer, and surveillance; (2) Care setting: outpatient and inpatient, ED; (3) Hospital type: quaternary academic center (QAC), university-affiliated community hospital (UACH), and sole community hospitals (SCHs). During the COVID-19 peak, a significant drop in CT volumes was observed (-42.2%, p < 0.0001), with cancer screening, initial workup, active cancer, and cancer surveillance declining by 81.7%, 54.8%, 30.7%, and 44.7%, respectively (p < 0.0001). In the post-COVID-19 peak period, cancer screening and initial workup CTs did not recover (-11.7%, p = 0.037; -20.0%, p = 0.031), especially in the outpatient setting. CT volumes for active cancer recovered, but inconsistently across hospital types: the QAC experienced a 9.4% decline (p = 0.022) and the UACH a 41.5% increase (p < 0.001). Outpatient CTs recovered after the COVID-19 peak, but with a shift in utilization away from the QAC (-8.7%, p = 0.020) toward the UACH (+13.3%, p = 0.013). Inpatient and ED-based oncologic CTs increased post-peak (+20.0%, p = 0.004 and +33.2%, p = 0.009, respectively). Cancer imaging was severely impacted during the COVID-19 pandemic. CTs for cancer screening and initial workup did not recover to pre-COVID-19 levels well into 2020, a finding that suggests more patients with advanced cancers may present in the future. A redistribution of imaging utilization away from the QAC and outpatient settings, toward the community hospitals and inpatient setting/ED was observed.


Myoelectrical activity and intraluminal flow in human sigmoid colon.
Myoelectric spike bursts were recorded in the sigmoid colon by means of an intraluminal silastic tube equipped with 3 Ag-AgCl ring electrodes fixed 15 cm apart on the tube that was introduced by flexible sigmoidoscopy. In six subjects, the tube was also equipped with three catheters whose tip opened 1 cm aborad from each electrode, for pressure recordings. In six other subjects, the tube was equipped with both electrodes and a catheter opening at the tip of the probe for infusing fluids at a rate of 12 ml/min into the colonic lumen. The fluid was collected with another tube inserted in the rectum and the volume was measured at 1-min intervals. Colonic spiking activity was made of rhythmic stationary bursts (RSB) and of sporadic bursts that were either propagating (SPB) or not propagating (SNPB). All sporadic bursts were associated with intraluminal pressure waves whose amplitude was significantly higher than that associated with rhythmic bursts. In the infusion experiments, the volume of fluid collected did not change significantly whether rhythmic bursts were present or not (3.9 +/- 1.7 ml/min and 3.3 +/- 1.9 ml/min respectively) (mean +/- SD). However, the volume was significantly higher when sporadic nonpropagating bursts were present (9.4 +/- 4.1 ml/min), and even higher when the sporadic bursts were propagating (21.6 +/- 8.8 ml/min). These results indicate that the occurrence of sporadic bursts, particularly when propagating, is associated with intraluminal pressure waves that lead to significant propulsive movements; and rhythmic bursts do not seem to be involved in colonic propulsive activity.


Mastery in women's multiple roles and well-being: adult daughters providing care to impaired parents.
The current study focused on 296 adult daughter caregivers who were simultaneously providing care to an impaired parent, mothers to children living at home, wives, and employees. How mastery (perceived competence and control) in each of these 4 roles was related to well-being was examined. Women experienced higher levels of mastery in the employee role than in any other role. After controlling for household income and dispositional optimism, only employee mastery contributed unique variance to physical health, but mastery in each of the 4 roles contributed unique variance to either depression or life satisfaction. Results also suggest that women's satisfaction with life was related to an accumulation of mastery across roles. The study expands previous research by revealing that mastery in women's additional roles can supplement the benefits of mastery stemming from parent care.


RFLP analysis of chromosomal segregation in progeny from an interspecific hexaploid somatic hybrid between Solanum brevidens and Solanum tuberosum.
Segregation of restriction fragment length polymorphism (RFLP) loci was monitored to determine the degree of homeologous pairing and recombination in a hexaploid somatic hybrid, A206, the result of protoplast fusion between Solanum tuberosum (PI 203900, a tetraploid cultivated potato) and Solanum brevidens (PI 218228), a diploid, sexually incompatible, distant relative harboring several traits for disease resistance. Somatic hybrid A206 was crossed to Katahdin, a tetraploid potato cultivar, to generate a segregating population of pentaploid progeny. Although the clones of the tetraploid S. tuberosum lines PI 203900 and Katahdin were highly polymorphic, the diploid S. brevidens clone was homozygous at all but two of the tested RFLP loci. Thus, homeologous recombination could be detected only when S. tuberosum and S. brevidens chromosomes paired and the S. brevidens homologs then segregated into separate gametes. A bias toward homologous pairing was observed for all 12 chromosomes. At least four and perhaps six chromosomes participated in homologous pairing only; each of 24 progeny contained all S. brevidens-derived RFLP markers for chromosomes 4, 8, 9 and 10. The remaining six chromosomes paired with their homolog(s) about twice as often as expected if hexaploid pairings were completely random. Where detectable with RFLPs, homeologous recombination (both single and double) occurred at a frequency of 1.31 per chromosome. Cytological observations of meiosis I in the somatic hybrid indicated that homeologous pairing had occurred. Enhanced recombinational activity was observed for chromosome 2. A specific small deletion from chromosome 4 was detected in A206 and 11 other somatic hybrids out of 14 screened.(ABSTRACT TRUNCATED AT 250 WORDS)


EBCR: Empirical Bayes concordance ratio method to improve similarity measurement in memory-based collaborative filtering.
Recommender systems aim to provide users with a selection of items, based on predicting their preferences for items they have not yet rated, thus helping them filter out irrelevant ones from a large product catalogue. Collaborative filtering is a widely used mechanism to predict a particular user's interest in a given item, based on feedback from neighbour users with similar tastes. The way the user's neighbourhood is identified has a significant impact on prediction accuracy. Most methods estimate user proximity from ratings they assigned to co-rated items, regardless of their number. This paper introduces a similarity adjustment taking into account the number of co-ratings. The proposed method is based on a concordance ratio representing the probability that two users share the same taste for a new item. The probabilities are further adjusted by using the Empirical Bayes inference method before being used to weight similarities. The proposed approach improves existing similarity measures without increasing time complexity and the adjustment can be combined with all existing similarity measures. Experiments conducted on benchmark datasets confirmed that the proposed method systematically improved the recommender system's prediction accuracy performance for all considered similarity measures.


The canine betaine gamma-amino-n-butyric acid transporter gene: diverse mRNA isoforms are regulated by hypertonicity and are expressed in a tissue-specific manner.
The Na(+)- and Cl(-)-coupled betaine transporter, designated BGT1, a member of the neurotransmitter transporter gene family, is responsible for accumulation of betaine in hypertonic Madin-Darby canine kidney (MDCK) cells and presumably in the hypertonic renal medulla. The canine gene for the betaine gamma-amino-n-butyric acid transporter has been cloned and analyzed. The gene extends over 28 kb and consists of 18 exons. The 5' end of the gene has three alternative first exons (1A, 1B, and 1C+D). Analysis of BGT1 mRNA revealed that there is considerable divergence in the 5' untranslated sequence resulting from three different 5' end motifs (A, B, and C) followed by an alternative motif (D) as well as two internal acceptor sites for splicing. Eight kinds of BGT1 mRNA were classified into three types (A, B, and C) according to the 5' end sequence. Northern blot analysis using probes specific for the A, B, or C motif revealed that hypertonicity induces all three types in MDCK cells. Reverse transcription and polymerase chain reaction showed that each type was expressed in a tissue-specific manner. Primer extension and/or RNase protection assays as well as transfection assays into MDCK cells demonstrated that exons 1A, 1B, and 1C+D have independent transcription initiation sites under control of independent promoters. Diverse mRNA isoforms are regulated by hypertonicity and are expressed in a tissue-specific manner.


Family presence and environmental factors at the time of a patient's death in an ICU.
In an intensive care unit (ICU), privacy and proximity are reported to be important needs of dying patients and their family members. It is assumed that good communication between the ICU team and families about end-of-life decisions improves the possibilities of meeting families' needs, thus guaranteeing a dignified and peaceful death in accordance with end-of-life care guidelines. The aim of this study was to explore the circumstances under which patients die in Swedish ICUs by reporting on the presence of family and whether patients die in private or shared rooms. An additional aim was to investigate the frequency of end-of-life decisions and whether nurses and family members were informed about such decisions. A questionnaire based on the research questions was completed when a patient died in the 10 ICUs included in the study. Data were collected on 192 deaths. Forty per cent of the patients died without a next of kin at the bedside and 46% of deaths occurred in a shared room. This number decreased to 37% if a family member was present. Patients without a family member at their bedside received less analgesics and sedatives. There was a significant relationship between family presence, expected death and end-of-life decisions. The results indicate the necessity of improving the ICU environment to promote the need for proximity and privacy for dying patients and their families. The study also highlights the risk of underestimating the needs of patients without a next of kin at their bedside at the time of death.


Setting Expectations for ECMO: Improving Communication Between Clinical Teams and Decision Makers.
Transplant medicine is fraught with clinical-ethical issues. It is not uncommon to have ethicists on transplant teams to help navigate ethically complex cases and ethical questions. Clinical ethicists work in hospitals and/or other healthcare institutions identifying and addressing value-laden conflict and ethical uncertainties. As ethicists, we set out to describe our process and involvement in cases involving extracorporeal membrane oxygenation (ECMO). Our work centers on monitoring and optimizing communication among clinicians, families, and patients, with the goals of (1) aligning patient/family understanding of the nature and purpose of ECMO while encouraging realistic expectations for possible outcomes, and (2) proactively mitigating the moral distress of providers involved in complex ECMO cases. We close with recommendations for how to measure the impact of ethicists' involvement in ECMO cases.


Use of bioresorbable vascular scaffold: a meta-analysis of patients with coronary artery disease.
Differences in outcomes between bioresorbable vascular scaffold (BVS) systems and drug-eluting metal stents (DES) have not been fully evaluated. We aimed to compare clinical and angiographic outcomes in randomised studies of patients with coronary artery disease (CAD), with a secondary analysis performed among registry studies. A meta-analysis comparing outcomes between BVS and DES in patients with CAD. Overall estimates of treatment effect were calculated with random-effects model and fixed-effects model. In 6 randomised trials (3818 patients), BVS increased the risk of subacute stent thrombosis (ST) over and above DES (OR 2.14; CI 1.01 to 4.53; p=0.05), with a trend towards an increase in the risk of myocardial infarction (MI) (125 events in those assigned to BVS and 50 to DES; OR 1.36; CI 0.97 to 1.91; p=0.07). The risk of in-device late lumen loss (LLL) was higher with BVS than DES (mean difference 0.08 mm; CI 0.03 to 0.13; p=0.004). There was no difference in the risk of death or target vessel revascularisation (TVR) between the two devices. In 6 registry studies (1845 patients), there was no difference in the risk of death, MI, TVR or subacute ST between the two stents. Final BVS dilation pressures were higher in registry than in randomised studies (18.7±4.6 vs 15.2±3.3 atm; p<0.001). Patients treated with BVS had an increased risk of subacute ST and slightly higher LLL compared with those with DES, but this might be related to inadequate implantation techniques, in particular device underexpansion.


Muscle glycogen stores and fatigue.
Studies performed at the beginning of the last century revealed the importance of carbohydrate as a fuel during exercise, and the importance of muscle glycogen on performance has subsequently been confirmed in numerous studies. However, the link between glycogen depletion and impaired muscle function during fatigue is not well understood and a direct cause-and-effect relationship between glycogen and muscle function remains to be established. The use of electron microscopy has revealed that glycogen is not homogeneously distributed in skeletal muscle fibres, but rather localized in distinct pools. Furthermore, each glycogen granule has its own metabolic machinery with glycolytic enzymes and regulating proteins. One pool of such glycogenolytic complexes is localized within the myofibrils in close contact with key proteins involved in the excitation-contraction coupling and Ca2+ release from the sarcoplasmic reticulum (SR). We and others have provided experimental evidence in favour of a direct role of decreased glycogen, localized within the myofibrils, for the reduction in SR Ca2+ release during fatigue. This is consistent with compartmentalized energy turnover and distinctly localized glycogen pools being of key importance for SR Ca2+ release and thereby affecting muscle contractility and fatigability.


Current Status of Handheld Otoscopy Training: A Systematic Review.
Otoscopy is a frequently performed procedure and competency in this skill is important across many specialties. We aim to systematically review current medical educational evidence for training of handheld otoscopy skills. Following the PRISMA guideline, studies reporting on training and/or assessment of handheld otoscopy were identified searching the following databases: PubMed, Embase, OVID, the Cochrane Library, PloS Medicine, Directory of Open Access Journal (DOAJ), and Web of Science. Two reviewers extracted data on study design, training intervention, educational outcomes, and results. Quality of educational evidence was assessed along with classification according to Kirkpatrick's model of educational outcomes. The searches yielded a total of 6064 studies with a final inclusion of 33 studies for the qualitative synthesis. Handheld otoscopy training could be divided into workshops, physical simulators, web-based training/e-learning, and smartphone-enabled otoscopy. Workshops were the most commonly described educational intervention and typically consisted of lectures, hands-on demonstrations, and training on peers. Almost all studies reported a favorable effect on either learner attitude, knowledge, or skills. The educational quality of the studies was reasonable but the educational outcomes were mostly evaluated on the lower Kirkpatrick levels with only a single study determining the effects of training on actual change in the learner behavior. Overall, it seems that any systematic approach to training of handheld otoscopy is beneficial in training regardless of learner level, but the heterogeneity of the studies makes comparisons between studies difficult and the relative effect sizes of the interventions could not be determined.


Role of endothelin in the control of peripheral vascular tone in human hypertension.
Endothelins are potent 21 amino acid vasoconstrictor isopeptides produced in different vascular tissues, including vascular endothelium. Endothelin-1 is the main endothelin generated by the endothelium and probably the most important in the cardiovascular system. Endothelin-1 acts through specific receptors termed ET(A), represented only on smooth muscle cells and having the function of growth promotion and mediating contractions, and ET(B), located both on smooth muscle cells, where they evoke contractions, and on endothelial cells, inducing relaxation by production of the endothelium-derived relaxing factor nitric oxide. In physiological conditions endothelin-1 administration causes vasodilation and vasoconstriction at low and high concentrations, respectively. However, administration of mixed ET(A)/(B) receptor antagonists causes slight or absent vasodilation, indicating that the direct vasoconstrictor effect of the peptide is probably masked by ET(B)-induced NO-dependent vasodilation. In essential hypertensive patients, the activity of exogenous endothelin-1 is either increased, similar or decreased as compared to normotensive subjects, depending on which vascular district or scheme of administration is considered. But although available evidence does not indicate increased endothelin-1 plasma levels in patients with essential hypertension, simultaneous antagonism of ET(A)/(B) receptors causes a greater degree of vasodilation in hypertensives than in normotensive subjects. Moreover administration of a selective ET(B) receptor antagonist causes vasoconstriction in normotensive subjects and vasodilation in essential hypertensive patients. Finally, the vasodilating effect of a mixed ET(A)/(B) receptor antagonist is inversely related to NO availability. Taken together these findings suggest that essential hypertension is characterized by increased endothelin-1 vasoconstrictor tone. This alteration seems to be dependent on decreased endothelial ET(B)-mediated NO production attributable to impaired NO availability. In such conditions endothelial ET(B)-induced vasodilation no longer compensates for the direct classical endothelin vasoconstrictor effect mediated by smooth muscle cell ET(A) and ET(B) receptors. Therefore endothelin-1 could potentially be involved in the pathogenesis of essential hypertension or of its complications, and blockade of this system is a fascinating new target for therapeutic intervention in this disease.


Successful ultrasound-guided drainage of an intra-abdominal collection in late pregnancy.
Pregnancy complicated by an intra-abdominal collection is uncommon and poses a challenge in the management. We present a case that illustrates successful treatment via ultrasound-guided drainage of a collection associated with a dermoid cyst in a 30 weeks pregnant patient presenting with fever and right-sided abdominal pain. Following treatment, the patient clinically improved rapidly. The drain was removed 3 days later and a repeat ultrasound scan showed no collection.


Associations Between Sexual Assault Severity and Psychological and Physical Health Outcomes: Similarities and Differences Among African American and Caucasian Survivors.
There are well-established associations between sexual assault victimization and deleterious psychological and physical health outcomes. The present study contributes to the emerging health disparities literature by examining similarities and differences in relationships between the severity of the sexual assault and health in a community sample of African American and Caucasian survivors. Although the overall pattern of relationships was expected to be comparable for all survivors, some associations were hypothesized to be stronger for African American survivors as compared with Caucasian survivors based on theories of chronic stress. Single, African American, and Caucasian women were recruited for a study of dating experiences through random digit dialing in one large metropolitan area. Participants who experienced a sexual assault since age 14 were included in this study (121 African American and 100 Caucasian women). Multigroup path analyses indicated that for both African American and Caucasian survivors, sexual assault severity was significantly positively associated with posttraumatic stress disorder (PTSD) symptoms, and depressive symptoms were significantly positively associated with physical health symptoms. Among African American survivors, sexual assault severity affected physical health symptoms indirectly through its impact on depressive symptoms, and assault severity indirectly affected drinking problems through its impact on PTSD symptoms; these relationships were not found for Caucasian survivors. These findings highlight the need for additional research that focuses on health disparities in sexual assault survivors' recovery process, so that treatment programs address culturally relevant issues.


Influence of orchiectomy on canine behaviour.
One hundred and twenty-two dog owners were interviewed to obtain information about the effects of orchiectomy on the behaviour, unwanted side effects, and testosterone-dependent disease processes in their dogs. Behavioural problems were the main reason for orchiectomy, unwanted sexual behaviour being the most common, together with roaming, aggression, and abnormal urination behaviour. Objectionable sexual behaviour, inter-male aggression, roaming, and abnormalurination were reduced after orchiectomy in approximately 60 per cent of the dogs. The side effects of orchiectomy included increased bodyweight, increased appetite and decreased activity in less than 50 per cent of the dogs, and there was a significant relationship between increased appetite and bodyweight. The clinical signs of testosterone-dependent disease in most of the dogs either decreased or disappeared after orchiectomy.


Convex growth arrest in the treatment of congenital spinal deformities, revisited.
The authors studied 32 patients to delineate the reliability of well-defined but frequently extended indications to define the ideal patient who will benefit from convex growth arrest. Mean age at the time of convex growth arrest was 29 (range 6-72) months, and average follow-up was 40 (24-120) months. Mean Cobb angle was 55 degrees (31-105 degrees) before surgery and 50 degrees (13-107 degrees) at final follow-up. Thirteen patients (41%) had a true epiphysiodesis effect, while 15 (47%) had fusion and 4 (12%) had progression. The age at surgery, magnitude, length and location of the curve, presence of intraspinal anomaly, and presence of sagittal plane or rib deformity were investigated in terms of the outcome, but none of these parameters was found to have an effect on the outcome. In conclusion, convex growth arrest is a safe and effective method in the management of the young patients with congenital spinal deformities. It can be performed for the balanced and cosmetically acceptable deformities of patients younger than 5 years of age regardless of the type, length, magnitude, and location of the curve, the existence of associated rib fusion, or the presence of sagittal plane abnormality.


Bacteremia and "Endotipsitis" following transjugular intrahepatic portosystemic shunting.
To identify all cases of bacteremia and suspected endotipsitis after Transjugular intrahepatic portosystemic shunting (TIPS) at our institution and to determine risk factors for their occurrence. We retrospectively reviewed records of all patients who underwent TIPS in our institution between 1996 and 2009. Data included: indications for TIPS, underlying liver disease, demographics, positive blood cultures after TIPS, microbiological characteristics, treatment and outcome. 49 men and 47 women were included with a mean age of 55.8 years (range 15-84). Indications for TIPS included variceal bleeding, refractory ascites, hydrothorax and hepatorenal syndrome. Positive blood cultures after TIPS were found in 39/96 (40%) patients at various time intervals following the procedure. Seven patients had persistent bacteremia fitting the definition of endotipsitis. Staphylococcus species grew in 66% of the positive cultures, Candida and enterococci species in 15% each of the isolates, and 3% cultures grew other species. Multi-variate regression analysis identified 4 variables: hypothyroidism, HCV, prophylactic use of antibiotics and the procedure duration as independent risk factors for positive blood cultures following TIPS (P < 0.0006, 0.005, 0.001, 0.0003, respectively). Prophylactic use of antibiotics before the procedure was associated with a decreased risk for bacteremia, preventing mainly early infections, occurring within 120 d of the procedure. Bacteremia is common following TIPS. Risk factors associated with bacteremia include failure to use prophylactic antibiotics, hypothyroidism, HCV and a long procedure. Our results strongly support the use of prophylaxis as a means to decrease early post TIPS infections.


MICRURGICAL STUDIES IN CELL PHYSIOLOGY : IV. COLORIMETRIC DETERMINATION OF THE NUCLEAR AND CYTOPLASMIC pH IN THE STARFISH EGG.
I. Cytoplasm. 1. The normal cytoplasmic pH, colorimetrically determined, of the starfish eggs in the unfertilized, fertilized, and first and second cleavage stages is 6.7 +/- 0.1. 2. Cytolysis lowers the pH to a value 5.5 +/- 0.1. 3. The cytolyzed material in time assumes the pH of its environing sea water. 4. The acid due to mechanical injury can also be detected in the environment of the egg. 5. Injury to the cytoplasm unaccompanied by visible disintegration causes an increase in acidity which is quickly neutralized. II. Germinal Vesicle. 6. The intranuclear pH, colorimetrically determined, of the immature Asterias egg is 7.5 +/- 0.1. 7. Injury to the nucleus does not change its pH. 8. The spherical nuclear remnant which persists after injury gradually assumes the pH of its environment. III. Plasmalemma. 9. A dye to which the cell is normally impermeable can penetrate through a tear in the surface from an environment more acid than normal. This may be due to a difference in the formation of the plasmalemma in a normal and an acid medium.


Combination of initial stimulation thyroglobulins and staging system by revised ATA guidelines can elaborately discriminate prognosis of patients with differentiated thyroid carcinoma after high-dose remnant ablation.
The aim of this study was to evaluate prognostic role of thyroglobulin (Tg) levels at the time of ablation (A-Tg) and stimulation Tg levels at 6-12 months after remnant ablation (S-Tg) combined with revised American Thyroid Association (ATA) guidelines risk stratification. Data of 359 patients (median follow-up duration: 66.3 months) with papillary thyroid carcinoma who had high-dose remnant ablation were analyzed. The cutoff value of A-Tg to predict the persistent/recurrent disease was calculated by receiver operating characteristic curve analysis. In each risk group by ATA guidelines, the association of A-Tg with persistent/recurrent disease was evaluated. The role of A-Tg and ATA risk stratification in each S-Tg group (group with S-Tg <2 ng/mL, 2-10 ng/mL, or >10 ng/mL) was also evaluated. Tg response was determined by the difference between A-Tg and S-Tg with consideration of the dose of radioactive iodine ablation. A-Tg above 5.22 ng/mL was associated with persistent/recurrent disease in all risk groups by ATA guidelines. A-Tg above the cutoff value and ATA risk assessment was related to persistent/recurrent disease in patients with S-Tg 2 to 10 ng/mL (P = 0.003) and S-Tg above 10 ng/mL (P = 0.019). However, no difference in the incidence of persistent/recurrent disease was found according to Tg response. The scoring system made up of A-Tg, S-Tg, and ATA staging showed elaborate discrimination of prognosis. Risk stratification using combined scoring with initial stimulated Tg levels, including A-Tg and S-Tg, and staging system by revised ATA guidelines can effectively predict persistent/recurrent disease in patients with papillary thyroid carcinoma.


Creating Good Employment Opportunities for the Rural Sector.
This paper examines the potential for sector-specific productivity growth, human capital, credit markets, and infrastructure to contribute to the development of stable, well-paid employment in rural areas of low-income countries. Particular emphasis is placed on the way that different sectors of the rural economy interact with each other and with local and regional product markets. A simple theoretical framework and descriptive analysis of panel data from India suggests that more emphasis should be placed on increasing the production of goods that incorporate local agricultural products as inputs.


Forest fire management to avoid unintended consequences: a case study of Portugal using system dynamics.
Forest fires are a serious management challenge in many regions, complicating the appropriate allocation to suppression and prevention efforts. Using a System Dynamics (SD) model, this paper explores how interactions between physical and political systems in forest fire management impact the effectiveness of different allocations. A core issue is that apparently sound management can have unintended consequences. An instinctive management response to periods of worsening fire severity is to increase fire suppression capacity, an approach with immediate appeal as it directly treats the symptom of devastating fires and appeases the public. However, the SD analysis indicates that a policy emphasizing suppression can degrade the long-run effectiveness of forest fire management. By crowding out efforts to preventative fuel removal, it exacerbates fuel loads and leads to greater fires, which further balloon suppression budgets. The business management literature refers to this problem as the firefighting trap, wherein focus on fixing problems diverts attention from preventing them, and thus leads to inferior outcomes. The paper illustrates these phenomena through a case study of Portugal, showing that a balanced approach to suppression and prevention efforts can mitigate the self-reinforcing consequences of this trap, and better manage long-term fire damages. These insights can help policymakers and fire managers better appreciate the interconnected systems in which their authorities reside and the dynamics that may undermine seemingly rational management decisions.


A Case of Undiagnosed Sleep Disorder with Hearing Difficulty and Dizziness.
The aim of this case report was to investigate the relationship between sleep disorders and audio vestibular symptoms. A case of undiagnosed sleep disorder, presenting as a temporary auditory processing difficulty, is presented. The disorder was initially treated as sudden deafness with dizziness. A 23-year-old male patient complained of acute hearing disturbance despite normal results on pure tone audiometry. The patient was initially administered a steroid injection in the hospital. After treatment, his hearing symptoms improved only slightly and he reported balance difficulty with rightward spontaneous nystagmus. Vestibular rehabilitation was performed. We also suspected that his hearing symptom was due to an auditory processing difficulty. Despite steroid treatment and vestibular rehabilitation, neither of his symptoms improved. We subsequently identified the presence of insomnia. He was prescribed zolpidem 5 mg, which slightly improved his symptoms, and referred to a sleep specialist for further examination. Polysomnography was performed, which identified restless leg syndrome and sleep disturbance with delayed sleep phase syndrome. After pharmacological treatment, his sleep disturbance, hearing difficulty, and balance disorder completely resolved. Sleep disorders may provoke reversible auditory processing difficulties. We should carefully evaluate patients for a potentially undiagnosed sleep disorder, even in patients chiefly complaining of intractable sensory dysfunction such as hearing or balance disturbance.


Rates, amounts, and determinants of ambulatory blood pressure monitoring claim reimbursements among Medicare beneficiaries.
Ambulatory blood pressure monitoring (ABPM) can be used to identify white coat hypertension and guide hypertensive treatment. We determined the percentage of ABPM claims submitted between 2007 and 2010 that were reimbursed. Among 1970 Medicare beneficiaries with submitted claims, ABPM was reimbursed for 93.8% of claims that had an International Classification of Diseases, Ninth Revision, diagnosis code of 796.2 ("elevated blood pressure reading without diagnosis of hypertension") versus 28.5% of claims without this code. Among claims without an International Classification of Diseases, Ninth Revision, diagnosis code of 796.2 listed, those for the component (eg, recording, scanning analysis, physician review, reporting) versus full ABPM procedures and performed by institutional versus non-institutional providers were each more than two times as likely to be successfully reimbursed. Of the claims reimbursed, the median payment was $52.01 (25th-75th percentiles, $32.95-$64.98). In conclusion, educating providers on the ABPM claims reimbursement process and evaluation of Medicare reimbursement may increase the appropriate use of ABPM and improve patient care.


Comparison of a manual and an automated method to estimate the number of uterine eggs in anisakid nematodes: to Coulter or not to Coulter. Is that the question?
Studies reporting numbers of eggs in vagina and utero in nematodes often give little information of the technique used for the estimations. This situation hampers comparison among studies, because, so far, differences in estimations provided by different techniques have not been assessed. This note examines whether a manual method based on visual counts in aliquots and an automated method using a Coulter counter yield equivalent estimations of egg numbers in vagina and utero of 3 anisakid nematode species (Anisakis simplex, Pseudoterranova decipiens, and Contracaecum osculatum). The number of eggs from 50 females per nematode species was estimated using both techniques. The automated and manual methods yielded similar egg counts (correlation coefficients >0.9 in the 3 species), but the methods were not always statistically equivalent. The automated method was more precise and seemed less dependent on egg density, whereas the manual method was less time-consuming (contrary to previous perceptions) and less expensive. Despite the higher precision of automated counts, the manual technique seemed to produce similar estimates; thus, it may be particularly useful in developing countries where nematode parasitism is prevalent in humans and domestic animals, but scientific resources are limited.


Ventricular septal defect and cardiomyopathy in mice lacking the transcription factor CHF1/Hey2.
Ventricular septal defects are common in human infants, but the genetic programs that control ventricular septation are poorly understood. Here we report that mice with a targeted disruption of the cardiovascular basic helix-loop-helix factor (CHF)1Hey2 gene show isolated ventricular septal defects. These defects result primarily in failure to thrive. Mice often succumbed within the first 3 wk after birth and showed pulmonary and liver congestion. The penetrance of this phenotype varied, depending on genetic background, suggesting the presence of modifier genes. Expression patterns of other cardiac-specific genes were not affected. Of the few animals on a mixed genetic background that survived to adulthood, most developed a cardiomyopathy but did not have ventricular septal defects. Our results indicate that CHF1 plays an important role in regulation of ventricular septation in mammalian heart development and is important for normal myocardial contractility. These mice provide a useful model for the study of the ontogeny and natural history of ventricular septal defects and cardiomyopathy.


Metabolic regulation of chromatin modifications and gene expression.
Dynamic regulation of gene expression in response to changing local conditions is critical for the survival of all organisms. In metazoans, coherent regulation of gene expression programs underlies the development of functionally distinct cell lineages. The cooperation between transcription factors and the chromatin landscape enables precise control of gene expression in response to cell-intrinsic and cell-extrinsic signals. Many of the chemical modifications that decorate DNA and histones are adducts derived from intermediates of cellular metabolic pathways. In addition, several of the enzymes that can remove these marks use metabolites as part of their enzymatic reaction. These observations have led to the hypothesis that fluctuations in metabolite levels influence the deposition and removal of chromatin modifications. In this review, we consider the emerging evidence that cellular metabolic activity contributes to gene expression and cell fate decisions through metabolite-dependent effects on chromatin organization.


Metamotivational state and dominance: Links with EMG gradients during isokinetic leg extension and a test of the misfit effect.
Although electromyographic (EMG) gradients have been observed in passive musculature during perceptual motor tasks, it is unclear whether this is related to metamotivational state or dominance. In addition, a misfit effect has been suggested whereby individuals report negative psychological responses when metamotivational state and dominance do not match. Research examining these phenomena within an exercise context is limited; therefore, this study used a reversal theory (Apter, 2001) framework to examine two hypotheses. The first hypothesis was that an EMG gradient would be observed when individuals performed isokinetic leg extensions in a telic metamotivational state, regardless of telic or paratelic metamotivational dominance. Second, it was hypothesizsed that telic-dominant individuals and paratelic-dominant individuals would perform better on this task when in the telic and paratelic state, respectively. Altogether, 14 telic-dominant and 12 paratelic-dominant individuals performed 100 self-paced isokinetic leg extensions at a rate of 90° · s(-1) in both telic and paratelic state manipulated conditions. Regardless of state, an EMG gradient was observed in telic-dominant individuals but not in paratelic-dominant individuals. Paratelic-dominant individuals performed better in the paratelic than the telic state condition, whereas in the telic state condition, telic-dominant individuals performed better than paratelic-dominant individuals. Findings add to the debate concerning the role of telic metamotivational state and dominance in the production of EMG gradients. Performance data support the misfit effect that outcomes are more positive when metamotivational state and dominance are congruent. Suggestions for research developments in this area are offered, as are tentative implications for applied practice.


Dietary soybeans worsen dextran sodium sulfate-induced colitis by disrupting intestinal ecology.
Food mediates susceptibility to inflammatory bowel diseases (IBDs) associated with the microbiome. Existing studies suggest that a high-sugar and high-fat diet promotes IBDs, but whether a plant-based diet is fully harmless to IBD improvement remains unknown. In this study, for the first time, we assessed the effect of soybean and its carbohydrates on dextran sodium sulfate (DSS)-induced colitis. In a DSS-induced colitis mouse model (BALB/C WT), the oral administration of soybeans worsened colitis, which was associated with higher disease activity index, histology score and expression of pro-inflammatory cytokines, and lower expression of anti-inflammatory cytokines. Here, 16S rRNA sequencing and elimination of gut bacteria by antibiotics showed that the exacerbating colitis caused by soybeans depends on the changes in the intestinal flora. Furthermore, the gavage of soybean carbohydrates such as sucrose and raffinose-family oligosaccharides altered the intestinal microbiota and worsened inflammation. When co-cultured with macrophages (RAW 264.7), the metabolites of the disordered intestinal flora, isolated Escherichia coli and purified LPS showed high macrophage toxicity to inhibit pathogen clearance. These results indicate that the intake of soybeans and soybean carbohydrates is not conducive to recovery from IBDs based on changes in gut microbiota and metabolites affecting the activities of macrophages.


Periapical Healing in Single-visit Endodontics under General Anesthesia in Special Needs Patients.
The aim of this study was to determine the prognostic factors of periapical healing of teeth after single-visit nonsurgical endodontic treatment under general anesthesia in special needs patients. This retrospective study collected 448 teeth from 241 patients (mean age = 27.4 years, standard deviation = 13.9 years). A total of 271 teeth (60.5%) with clinical and radiographic follow-up records longer than 12 months (mean [standard deviation] = 56.1 [27.9]) were included in the outcome analysis. Demographic, systemic, and dental information about the cases were compared between the healed and nonhealed groups using the Pearson chi-square test. Factors contributing to periapical healing were determined with multivariate logistic regression analysis. Complete periapical healing without clinical signs was observed in 221 teeth (81.5%), uncertain healing with decreased size of the periapical lesion was shown in 43 teeth (15.9%), and no reduction in lesion size was observed in 7 cases (2.6%). In the multivariate analysis, diet type, oral hygiene maintenance, pulp vitality, and root filling length were detected as contributing factors for complete resolution of periapical lesions (P < .05). Successful outcomes of single-visit endodontic treatment under general anesthesia were shown in special needs patients. The prognoses were influenced by the clinical circumstances of the patients and the preoperative conditions of their teeth.


The influence of Derrick T. Vail Sr, MD, and Edward M. Jackson, MD, on the creation of the American Board of Ophthalmology and the Specialist Board System in the United States.
The claim that Derrick T. Vail Sr, MD, was the innovator behind the formation of the American Board of Ophthalmology rests on an interpretation of a single paragraph in a speech he delivered in 1908. Using the technique of historical literary criticism, we identified fundamental flaws in this interpretation based on a misunderstanding of the context of the speech and his intent. Historical review of the period, including the writings and actions of others in leadership roles, supports our contention. Vail was an influential figure at the time but was only briefly involved in the activities that led to the formation of the American Board of Ophthalmology. On the other hand, Edward M. Jackson, MD, provided inspirational and persistent leadership during the 12 years needed to bring the board into existence. He should be considered the founder of the American Board of Ophthalmology.


Predictive biophysical modeling and understanding of the dynamics of mRNA translation and its evolution.
mRNA translation is the fundamental process of decoding the information encoded in mRNA molecules by the ribosome for the synthesis of proteins. The centrality of this process in various biomedical disciplines such as cell biology, evolution and biotechnology, encouraged the development of dozens of mathematical and computational models of translation in recent years. These models aimed at capturing various biophysical aspects of the process. The objective of this review is to survey these models, focusing on those based and/or validated on real large-scale genomic data. We consider aspects such as the complexity of the models, the biophysical aspects they regard and the predictions they may provide. Furthermore, we survey the central systems biology discoveries reported on their basis. This review demonstrates the fundamental advantages of employing computational biophysical translation models in general, and discusses the relative advantages of the different approaches and the challenges in the field.


[Effect of low temperature on electron transport in plant mitochondria respiratory chain].
The etiolated 2.5-day winter wheat sprouts were chilled at 3 degrees C during 24 to 144 hours. After 24 h cooling, shoot intact mitochondria showed a high degree of activation of the alternative oxidase, which was measured as sodium azide and benzohydroxamate sensitivity of the organelles respiration with succinate as a substrate. The role of the alternative oxidase in limiting the level of reactive oxygen species produced in the stressed plant tissues is discussed.


Identification of microRNA and bioinformatics target gene analysis in beef cattle intramuscular fat and subcutaneous fat.
MicroRNA (miRNA) is endogenous non-coding RNA that has been proposed to play an important role in the formation of body fat. However, the differential expression of miRNA and the role of these miRNAs in bovine intramuscular and subcutaneous fat tissue are still unknown. In this study, the profile of differentially expressed miRNA and the target gene analysis in intramuscular adipose and subcutaneous adipose of adult beef cattle were investigated by microarray and bioinformatics. The data identified 88 differentially expressed miRNAs in 213 miRNAs which were detected on the microarray, and 30 miRNAs among these 88 miRNAs were changed significantly between intramuscular and subcutaneous fat (fold change >1, P < 0.001). miR-143, miR-145, miR-26a, miR-2373-5p and miR-23b-3p were highly expressed in intramuscular fat, whilst miR-26a, miR-2373-5p, miR-2325c, miR-3613 and miR-2361 showed highest abundance in subcutaneous fat. Bioinformatics of KEGG pathway analysis and GO term enrichment suggested that these differentially expressed miRNAs involved in different pathways and target genes may regulate differently the fat deposition. Taken together, our study provides the first evidence for better understanding the differential expression and mechanisms of miRNA in bovine fat deposition, and provides thinking to improve the quality of beef by reducing subcutaneous fat and increasing intramuscular fat of beef cattle.


Determination of serum fPLI concentrations in cats with diabetes mellitus.
Diabetes mellitus (DM) is one of the most common feline endocrinopathies. Pancreatitis is a reported cause for poor control of DM in cats; however, its prevalence in diabetic cats is unknown. Measurement of serum feline pancreatic lipase immunoreactivity (fPLI) has been proposed as a sensitive and specific test for the detection of pancreatitis in cats. The aim of this study was to assess fPLI concentrations in diabetic cats and compare these with non-diabetic cats of similar age. Samples from 29 cats with DM and 23 non-diabetic cats were analysed. Serum fPLI concentrations were significantly higher in samples from diabetic cats (P<0.01). A weak association was found between serum fructosamine and fPLI concentrations (R(2)=0.355, P=0.015), but there was no association between fPLI concentrations and the degree of diabetic control. There were no significant differences in reported clinical signs between cats with or without DM regardless of serum fPLI concentration. This is the first study to demonstrate elevated serum fPLI concentrations in cats with DM, suggesting that pancreatitis could be a significant comorbidity in these cats.


Thermal transport in bismuth telluride quintuple layer: mode-resolved phonon properties and substrate effects.
The successful exfoliation of atomically-thin bismuth telluride (Bi2Te3) quintuple layer (QL) attracts tremendous research interest in this strongly anharmonic quasi-two-dimensional material. The thermal transport properties of this material are not well understood, especially the mode-wise properties and when it is coupled with a substrate. In this work, we have performed molecular dynamics simulations and normal mode analysis to study the mode-resolved thermal transport in freestanding and supported Bi2Te3 QL. The detailed mode-wise phonon properties are calculated and the accumulated thermal conductivities with respect to phonon mean free path (MFP) are constructed. It is shown that 60% of the thermal transport is contributed by phonons with MFP longer than 20 nm. Coupling with a-SiO2 substrate leads to about 60% reduction of thermal conductivity. Through varying the interfacial coupling strength and the atomic mass of substrate, we also find that phonon in Bi2Te3 QL is more strongly scattered by interfacial potential and its transport process is less affected by the dynamics of substrate. Our study provides an in-depth understanding of heat transport in Bi2Te3 QL and is helpful in further tailoring its thermal property through nanostructuring.


Masitinib antagonizes ATP-binding cassette subfamily C member 10-mediated paclitaxel resistance: a preclinical study.
Paclitaxel displays clinical activity against a wide variety of solid tumors. However, resistance to paclitaxel significantly attenuates the response to chemotherapy. The ABC transporter subfamily C member 10 (ABCC10), also known as multidrug resistance protein 7 (MRP7) efflux transporter, is a major mediator of paclitaxel resistance. In this study, we show that masitinib, a small molecule stem-cell growth factor receptor (c-Kit) tyrosine kinase inhibitor, at nontoxic concentrations, significantly attenuates paclitaxel resistance in HEK293 cells transfected with ABCC10. Our in vitro studies indicated that masitinib (2.5 μmol/L) enhanced the intracellular accumulation and decreased the efflux of paclitaxel by inhibiting the ABCC10 transport activity without altering the expression level of ABCC10 protein. Furthermore, masitinib, in combination with paclitaxel, significantly inhibited the growth of ABCC10-expressing tumors in nude athymic mice in vivo. Masitinib administration also resulted in a significant increase in the levels of paclitaxel in the plasma, tumors, and lungs compared with paclitaxel alone. In conclusion, the combination of paclitaxel and masitinib could serve as a novel and useful therapeutic strategy to reverse paclitaxel resistance mediated by ABCC10.


Behavioral convergence and adaptive radiation: effects of habitat use on territorial behavior in Anolis lizards.
Most studies of adaptive radiations focus on morphological aspects of differentiation, yet behavior is also an important component of evolutionary diversification, often mediating the relationship between animal ecology and morphology. In species within radiations that are convergent in ecology and morphology, we then also expect convergence in behavior. Here, we examined 13 Anolis lizard species to determine whether territorial strategies have evolved convergently with morphology and habitat use. We evaluated two aspects of territoriality: behavioral defense of space via territorial displays, and territory overlap within and between sexes. Controlling for the phylogenetic relationships of the taxa in our study, we found that species similar in perch height and diameter convergently evolved patterns of territory overlap, whereas species similar in habitat visibility (the proportion of space that can be seen from a perch) convergently evolved display behavior. We also found that species with greater display time have more extensive male-male territory overlap. This study provides strong evidence for the role of habitat in the evolution of territoriality and suggests that the social structure of a species ultimately evolves in concert with habitat use and morphology.


Impaired non-homologous end joining in human primary alveolar type II cells in emphysema.
Emphysema is characterized by alveolar wall destruction induced mainly by cigarette smoke. Oxidative damage of DNA may contribute to the pathophysiology of this disease. We studied the impairment of the non-homologous end joining (NHEJ) repair pathway and DNA damage in alveolar type II (ATII) cells and emphysema development. We isolated primary ATII cells from control smokers, nonsmokers, and patients with emphysema to determine DNA damage and repair. We found higher reactive oxygen species generation and DNA damage in ATII cells obtained from individuals with this disease in comparison with controls. We also observed low phosphorylation of H2AX, which activates DSBs repair signaling, in emphysema. Our results indicate the impairement of NHEJ, as detected by low XLF expression. We also analyzed the role of DJ-1, which has a cytoprotective activity. We detected DJ-1 and XLF interaction in ATII cells in emphysema, which suggests the impairment of their function. Moreover, we found that DJ-1 KO mice are more susceptible to DNA damage induced by cigarette smoke. Our results suggest that oxidative DNA damage and ineffective the DSBs repair via the impaired NHEJ may contribute to ATII cell death in emphysema.


Heat-Related Illness in Emergency and Critical Care: Recommendations for Recognition and Management with Medico-Legal Considerations.
Hyperthermia is an internal body temperature increase above 40.5 °C; normally internal body temperature is kept constant through natural homeostatic mechanisms. Heat-related illnesses occur due to exposure to high environmental temperatures in conditions in which an organism is unable to maintain adequate homeostasis. This can happen, for example, when the organism is unable to dissipate heat adequately. Heat dissipation occurs through evaporation, conduction, convection, and radiation. Heat disease exhibits a continuum of signs and symptoms ranging from minor to major clinical pictures. Minor clinical pictures include cramps, syncope, edema, tetany, and exhaustion. Major clinical pictures include heatstroke and life-threatening heat stroke and typically are expressed in the presence of an extremely high body temperature. There are also some categories of people at greater risk of developing these diseases, due to exposure in particular geographic areas (e.g., hot humid environments), to unchangeable predisposing conditions (e.g., advanced age, young age (i.e., children), diabetes, skin disease with reduced sweating), to modifiable risk factors (e.g., alcoholism, excessive exercise, infections), to partially modifiable risk factors (obesity), to certain types of professional activity (e.g., athletes, military personnel, and outdoor laborers) or to the effects of drug treatment (e.g., beta-blockers, anticholinergics, diuretics). Heat-related illness is largely preventable.


Gross, histologic, cytochemical, and immunocytochemical study of medullary thyroid carcinoma in sixteen dogs.
The gross, histomorphologic, cytochemical, and immunocytochemical findings in 16 dogs with medullary thyroid carcinoma were evaluated. Grossly, the neoplasms were encapsulated, firm, lobulated, and grey-white to tan. The typical histologic pattern was groups or sheets of round to polygonal cells with fibrovascular stroma, which was thickened and hyalinized in places. Variants of clear cell (two dogs), giant cell (one dog), and oxyphil cell (one dog) types were also seen. In all 16 dogs, Grimelius-stained sections of the neoplasms revealed intracytoplasmic silver granules; ten tumors contained amyloid and four contained mucin. Immunohistochemically, the neoplasms reacted to AE1/AE3 (n = 13), S-100 protein (n = 5), neuron specific enolase (n = 14), synaptophysin (n = 11), calcitonin (n = 16), somatostatin (n = 4), gastrin (n = 7), and serotonin (n = 6). Only one neoplasm was positive for vimentin. None of the neoplasms reacted to antibodies for neurofilaments, thyroglobulin, insulin, glucagon, or adrenocorticotrophic hormone. Eleven neoplasms contained multiple (two to four) peptides, in various combinations. It was concluded that in dogs, gross and histologic features can be used to distinguish medullary thyroid carcinoma from other thyroid malignancies. Cytochemical and immunocytochemical studies with neuron specific enolase, synaptophysin, and calcitonin can be used to establish the diagnosis of medullary thyroid carcinoma in dogs.


A mouse model of adult-onset anaemia due to erythropoietin deficiency.
Erythropoietin regulates erythropoiesis in a hypoxia-inducible manner. Here we generate inherited super-anaemic mice (ISAM) as a mouse model of adult-onset anaemia caused by erythropoietin deficiency. ISAM express erythropoietin in the liver but lack erythropoietin production in the kidney. Around weaning age, when the major erythropoietin-producing organ switches from the liver to the kidney, ISAM develop anaemia due to erythropoietin deficiency, which is curable by administration of recombinant erythropoietin. In ISAM severe chronic anaemia enhances transgenic green fluorescent protein and Cre expression driven by the complete erythropoietin-gene regulatory regions, which facilitates efficient labelling of renal erythropoietin-producing cells. We show that the majority of cortical and outer medullary fibroblasts have the innate potential to produce erythropoietin, and also reveal a new set of erythropoietin target genes. ISAM are a useful tool for the evaluation of erythropoiesis-stimulating agents and to trace the dynamics of erythropoietin-producing cells.


Material-Dependent Evolution of Mechanical Folding Instabilities in Two-Dimensional Atomic Membranes.
Inducing and controlling three-dimensional deformations in monolayer two-dimensional materials is important for applications from stretchable electronics to origami nanoelectromechanical systems. For these applications, it is critical to understand how the properties of different materials influence the morphologies of two-dimensional atomic membranes under mechanical loading. Here, we systematically investigate the evolution of mechanical folding instabilities in uniaxially compressed monolayer graphene and MoS2 on a soft polydimethylsiloxane substrate. We examine the morphology of the compressed membranes using atomic force microscopy for compression from 0 to 33%. We find the membranes display roughly evenly spaced folds and observe two distinct stress release mechanisms under increasing compression. At low compression, the membranes delaminate to generate new folds. At higher compression, the membranes slip over the surface to enlarge existing folds. We observe a material-dependent transition between these two behaviors at a critical fold spacing of 1000 ± 250 nm for graphene and 550 ± 20 nm for MoS2. We establish a simple shear-lag model which attributes the transition to a competition between static friction and adhesion and gives the maximum interfacial static friction on polydimethylsiloxane of 3.8 ± 0.8 MPa for graphene and 7.7 ± 2.5 MPa for MoS2. Furthermore, in graphene, we observe an additional transition from standing folds to fallen folds at 8.5 ± 2.3 nm fold height. These results provide a framework to control the nanoscale fold structure of monolayer atomic membranes, which is a critical step in deterministically designing stretchable or foldable nanosystems based on two-dimensional materials.


CXCR6 upregulation contributes to a proinflammatory tumor microenvironment that drives metastasis and poor patient outcomes in hepatocellular carcinoma.
CXC chemokines and their cognate receptors have been implicated widely in cancer pathogenesis. In this study, we report a critical causal relationship between CXCR6 expression and tumorigenesis in the setting of human hepatocellular carcinoma (HCC). Among the CXC chemokine receptors, only CXCR6 was detected in all the hepatoma cell lines studied. Moreover, in HCC tissue, CXCR6 expression was significantly higher than in noncancerous liver tissues. Reduction of CXCR6 or its ligand CXCL16 in cancer cells reduced cell invasion in vitro and tumor growth, angiogenesis, and metastases in vivo. Importantly, loss of CXCR6 led to reduced Gr-1+ neutrophil infiltration and decreased neoangiogenesis in hepatoma xenografts via inhibition of proinflammatory cytokine production. Clinically, high expression of CXCR6 was an independent predictor of increased recurrence and poor survival in HCCs. Human HCC samples expressing high levels of CXCR6 also contained an increased number of CD66b+ neutrophils and microvessels, and the combination of CXCR6 and neutrophils was a superior predictor of recurrence and survival than either marker used alone. Together, our findings suggest that elevated expression of CXCR6 promotes HCC invasiveness and a protumor inflammatory environment and is associated with poor patient outcome. These results support the concept that inhibition of the CXCR6-CXCL16 pathway may improve prognosis after HCC treatment.


[Relation of the physical-sport activity practice and alcohol consumption of citizens older than 14 years old].
The aim of the current research is to ascertain any possible relationship that could exist between the alcohol consumption of the population and several sociodemographic variables, in addition to the influence of physical exercise/sports on the creation of healthy lifestyle habits. The sample comprised 1102 subjects from Almeria Spain, over 14 years of age, to whom we administered the "physical exercise/sporting habits and life styles" questionnaire, selecting the sections on physical exercise/sporting habits in leisure, fitness and state of health perception and alcohol consumption habits, related to attitudes, behavioural and sociodemographic variables. We used an innovative tool for data analysis in the sphere of physical exercise, known as the Bayesian networks, emphasizing a positive relationship between alcohol consumption and physical exercise/sporting activities, it being the active people, with an interest in physical exercise/sports, who have a good perception of their health and physical fitness who are the ones who make habitual and occasional use of this substance. The profile of the individual who does not drink alcohol is female, over 44 years of age, with no studies, housewives who have a poor perception of their health, and who do not do any physical exercise or plays sports, whereas the populations with health risks, are men between 15 and 44 years of age who have secondary school studies or a degree and who work in the public or private sector.


Porphyrin Immobilized Nanographene Oxide for Enhanced and Targeted Photothermal Therapy of Brain Cancer.
Brain cancer is a fatal disease that is difficult to treat because of poor targeting and low permeability of chemotherapeutic drugs through the blood brain barrier. In a comparison to current treatments, such as surgery followed by chemotherapy and/or radiotherapy, photothermal therapy is a remarkable noninvasive therapy developed in recent years. In this work, porphyrin immobilized nanographene oxide (PNG) was synthesized and bioconjugated with a peptide to achieve enhanced and targeted photothermal therapy for brain cancer. PNG was dispersed into the agar based artificial tissue model and demonstrated a photo-to-thermal conversion efficiency of 19.93% at a PNG concentration of only 0.5 wt %, with a heating rate of 0.6 °C/s at the beginning of irradiation. In comparison, 0.5 wt % graphene oxide (GO) indicated a photo-to-thermal conversion efficiency of 12.20% and a heating rate of 0.3 °C/s. To actively target brain tumor cells without harming healthy cells and tissues surrounding the laser path, a tripeptide l-arginyl-glycyl-l-aspartic (RGD) was further grafted to PNG. The photothermal therapy effects of PNG-RGD completely eliminated the tumor in vivo, indicating its excellent therapeutic effect for the treatment of brain cancer.


MRI in the presurgical evaluation of patients with frontal lobe epilepsy and children with temporal lobe epilepsy: pathologic correlation and prognostic importance.
We performed magnetic resonance imaging (MRI) using a high-field strength magnet (1.5 T) in two series of 53 patients with intractable partial epilepsy of frontal lobe or temporal lobe origin who subsequently received ablative surgery for their seizure disorder. In the first series of patients the pathologic correlation and prognostic importance of an MRI-identified lesion in the frontal lobe were assessed. Twenty-five percent of the patients with negative MRI studies and 67% of patients with neuroimaging abnormalities restricted to the frontal lobe, were seizure-free at a minimum duration of follow-up of 1 year. None of the patients with a multilobar MRI-detected abnormality was seizure-free postoperatively. In the second study the sensitivity and specificity of MRI-based hippocampal volumetry was determined in pediatric patients with partial epilepsy of temporal lobe origin unrelated to foreign-tissue pathology. Hippocampal formation atrophy in the epileptic temporal lobe was identified in 63% of patients. The sensitivity and specificity of hippocampal volumetry was 100% in patients with mesial temporal sclerosis. The presence of an MRI-detected epileptogenic lesion in the frontal lobe and hippocampal formation atrophy in the temporal lobe may correlate with the underlying pathology and affect the identification of potential candidates for epilepsy surgery.


Effect of weak magnetic fields on growth of cells in tissue culture.
Normal Chinese hamster V79 cells were grown in vitro for more than one year in a magnetic field of 10(-7) tesla to test recently hypothesized effects of weak magnetic fields on biological systems. No significant difference was observed between growth rate in such fields and that in the ambient geomagnetic field.


Selective 226Ra2+ ionophores provided by self-assembly of guanosine and isoguanosine derivatives.
The self-assembled guanosine (G 1)-based hexadecamers and isoguanosine (isoG 2)-based decamers are excellent 226Ra2+ selective ionophores even in the presence of excess alkali (Na+, K+, Rb+, and Cs+) and alkaline earth (Mg2+, Ca2+, Sr2+, and Ba2+) cations over the pH range 3-11. G 1 requires additional picrate anions to provide a neutral assembly, whereas the isoG 2 assembly extracts 226Ra2+ cations without any such additives. Both G 1-picrate and isoG 2 assemblies show 226Ra2+ extraction even at a 0.35 x 10(6) fold excess of Na+, K+, Rb+, Cs+, Mg2+, or Ca2+ (10(-2) M) to 226Ra2+ (2.9 x 10(-8) M) and at a 100-fold salt to ionophore excess. In the case of the G 1-picrate assembly, more competition was observed from Sr2+ and Ba2+, as extraction of 226Ra2+ ceased at an M2+/226Ra2+ ratio of 10(6) and 10(4), respectively. With the isoG 2 assembly, 226Ra2+ extraction also occurred at a Sr2+/226Ra2+ ratio of 10(6) but ceased at a 10(6) excess of Ba2+. The results clearly demonstrate the power of molecular self-assembly for the construction of highly selective ionophores.


Synonym-Based Word Frequency Analysis to Support the Development and Presentation of a Public Health Quality Improvement Taxonomy.
Researchers and analysts have not completely examined word frequency analysis as an approach to creating a public health quality improvement taxonomy. To develop a taxonomy of public health quality improvement concepts for an online exchange of quality improvement work. We analyzed documents, conducted an expert review, and employed a user-centered design along with a faceted search approach to make online entries searchable for users. To provide the most targeted facets to users, we used word frequency to analyze 334 published public health quality improvement documents to find the most common clusters of word meanings. We then reviewed the highest-weighted concepts and categorized their relationships to quality improvement details in our taxonomy. Next, we mapped meanings to items in our taxonomy and presented them in order of their weighted percentages in the data. Using these methods, we developed and sorted concepts in the faceted search presentation so that online exchange users could access relevant search criteria. We reviewed 50 of the top synonym clusters and identified 12 categories for our taxonomy data. The final categories were as follows: Summary; Planning and Execution Details; Health Impact; Training and Preparation; Information About the Community; Information About the Health Department; Results; Quality Improvement (QI) Staff; Information; Accreditation Details; Collaborations; and Contact Information of the Submitter. Feedback about the elements in the taxonomy and presentation of elements in our search environment from users has been positive. When relevant data are available, the word frequency analysis method may be useful in other taxonomy development efforts for public health.


The effects of suppressing the biological stress systems on social threat-assessment following acute stress.
Stress is associated with increased sensitivity to threat. Previous investigations examining how stress affects threat processing have largely focused on biomarker responses associated with either the sympathetic-nervous-system (SNS) or the hypothalamus-pituitary-adrenal (HPA) axis. We pharmacologically suppressed activations of SNS, HPA, or both, prior to stress and investigated how each stress system modulates social threat assessment. One hundred sixty-one healthy men and women were randomized in a between-subject design, to one of four pharmacological or placebo conditions: dexamethasone-placebo, placebo-propranolol, dexamethasone-propranolol, or placebo-placebo. Participants provided threat assessments for angry and neutral human faces on a baseline day, and immediately after stress induction on a testing day. With both systems responding normally to stress (placebo-placebo), threat assessment was higher for neutral faces compared with angry. Compared with placebo, SNS suppression resulted in increased threat assessment for angry faces. HPA suppression resulted in decreased threat assessment for neutral and angry faces. When both systems were suppressed, there was an increase in threat assessment for angry faces, and no difference from placebo for neutral. Our findings demonstrated that when intact, the biological stress systems adaptively support organisms during stress by focusing attention towards specific stimuli that are relevant to the threat. Dysregulations of the stress systems result in important system specific consequences on threat evaluation, such that suppression of either stress system alone resulted in reduced threat assessment for contextually relevant threatening stimuli, whereas when both systems were suppressed, individuals appear indiscriminately attentive to all potential threats in the environment, resulting in increased threat processing of both contextually relevant and irrelevant stimuli. Given that stress-related psychopathologies have been associated with dysregulations of the stress systems and biased responses to social threat, a systematic understanding of the mechanisms that underlie how stress systems modulate social threat assessment is needed, and can provide important insights into the cognitive processes that are involved in the development and maintenance of stress-related psychopathologies.


Sensitivity of US Preventive Services Task Force and PLCOm2012 lung cancer screening eligibility criteria in individuals with lung cancer in South Dakota self-reporting as Indigenous and non-Indigenous.
Lung cancer is the leading cause of cancer deaths. Screening individuals who are at elevated risk using low-dose computed tomography reduces lung cancer mortality by ≥20%. Individuals who have community-based factors that contribute to an increased risk of developing lung cancer have high lung cancer rates and are diagnosed at younger ages. In this study of lung cancer in South Dakota, the authors compared the sensitivity of screening eligibility criteria for self-reported Indigenous race and evaluated the need for screening at younger ages. US Preventive Services Task Force (USPSTF) 2013 and 2021 (USPSTF2013 and USPSTF2021) criteria and two versions of the PLCOm2012 risk-prediction model (based on the 2012 Prostate, Lung, Colorectal, and Ovarian [PLCO] Cancer Screening Trial), one with a predictor for race and one without, were applied at USPSTF-equivalent thresholds of ≥1.7% in 6 years and ≥1.0% in 6 years to 1565 individuals who were sequentially diagnosed with lung cancer (of whom 12.7% self-reported as Indigenous) at the Monument Health Cancer Care Institute in South Dakota (2010-2019). Eligibility sensitivities of USPSTF criteria did not differ significantly between individuals who self-reported their race as Indigenous and those who did not (p > .05). Sensitivities of both PLCOm2012 models were significantly higher than comparable USPSTF criteria. The sensitivity of USPSTF2021 criteria was 66.1% and, for comparable PLCOm2012 models with and without race, sensitivity was 90.7% and 89.6%, respectively (both p < .001); 1.4% of individuals were younger than 50 years, and proportions did not differ by Indigenous classification (p = .518). Disparities in screening eligibility were not observed for individuals who self-reported their race as Indigenous. USPSTF criteria had lower sensitivities for lung cancer eligibility. Both PLCOm2012 models had high sensitivities, with higher sensitivity for the model that included race. The PLCOm2012noRace model selected effectively in this population, and screening individuals younger than 50 years did not appear to be justified. Lung cancer is the leading cause of cancer deaths. Studies show that using low-dose computed tomography scans to screen people who smoke or who used to smoke and are at elevated risk for lung cancer reduces lung cancer deaths. This study of 1565 individuals with lung cancer in South Dakota compared screening eligibility using US Preventive Services Task Force (USPSTF) criteria and a lung cancer risk-prediction model (PLCOm2012; from the 2012 Prostate, Lung, Colorectal, and Ovarian [PLCO] Cancer Screening Trial). The model had higher sensitivity and picked more people with lung cancer to screen compared with USPSTF criteria. Eligibility sensitivities were similar for individuals who self-reported as Indigenous versus those who did not between USPSTF criteria and the model.


Post-exercise respirometry underestimates maximum metabolic rate in juvenile salmon.
Experimental biologists now routinely quantify maximum metabolic rate (MMR) in fishes using respirometry, often with the goal of calculating aerobic scope and answering important ecological and evolutionary questions. Methods used for estimating MMR vary considerably, with the two most common methods being (i) the 'chase method', where fish are manually chased to exhaustion and immediately sealed into a respirometer for post-exercise measurement of oxygen consumption rate (Ṁ O2), and (ii) the 'swim tunnel method', whereby Ṁ O2 is measured while the fish swims at high speed in a swim tunnel respirometer. In this study, we compared estimates for MMR made using a 3-min exhaustive chase (followed by measurement of Ṁ O2 in a static respirometer) versus those made via maximal swimming in a swim tunnel respirometer. We made a total of 134 estimates of MMR using the two methods with juveniles of two salmonids (Atlantic salmon Salmo salar and Chinook salmon Oncorhynchus tshawytscha) across a 6°C temperature range. We found that the chase method underestimated 'true' MMR (based on the swim tunnel method) by ca. 20% in these species. The gap in MMR estimates between the two methods was not significantly affected by temperature (range of ca. 15-21°C) nor was it affected by body mass (overall range of 53.5-236 g). Our data support some previous studies that have suggested the use of a swim tunnel respirometer generates markedly higher estimates of MMR than does the chase method, at least for species in which a swim tunnel respirometer is viable (e.g. 'athletic' ram ventilating fishes). We recommend that the chase method could be used as a 'proxy' (i.e. with a correction factor) for MMR in future studies if supported by a species-specific calibration with a relevant range of temperatures, body sizes or other covariates of interest.


Structural plasticity in human heterochromatin protein 1β.
As essential components of the molecular machine assembling heterochromatin in eukaryotes, HP1 (Heterochromatin Protein 1) proteins are key regulators of genome function. While several high-resolution structures of the two globular regions of HP1, chromo and chromoshadow domains, in their free form or in complex with recognition-motif peptides are available, less is known about the conformational behavior of the full-length protein. Here, we used NMR spectroscopy in combination with small angle X-ray scattering and dynamic light scattering to characterize the dynamic and structural properties of full-length human HP1β (hHP1β) in solution. We show that the hinge region is highly flexible and enables a largely unrestricted spatial search by the two globular domains for their binding partners. In addition, the binding pockets within the chromo and chromoshadow domains experience internal dynamics that can be useful for the versatile recognition of different binding partners. In particular, we provide evidence for the presence of a distinct structural propensity in free hHP1β that prepares a binding-competent interface for the formation of the intermolecular β-sheet with methylated histone H3. The structural plasticity of hHP1β supports its ability to bind and connect a wide variety of binding partners in epigenetic processes.


Fatty acid composition and gene expression profiles are altered in aryl hydrocarbon receptor-1 mutant Caenorhabditis elegans.
The aryl hydrocarbon receptor (AHR) is a eukaryotic transcription factor that plays an essential role in neuronal, immune, vascular, hepatic and hematopoietic development. In mammals, AHR induces metabolism-associated genes in response to xenobiotics. AHR is evolutionarily conserved, and the C. elegans AHR ortholog likely shares many physiologic functions with the mammalian version. While the role of AHR in development is known, the molecular basis of AHR action is less well understood. To understand the physiologic role of AHR in C. elegans, a combination of fatty acid profiling, transcriptomics, and phenotyping approaches was used. Fatty acid profiles from L4 larval stage whole animals indicated that C17isoA, C18:1n9t, C20:3n6 and C20:4n6 were significantly increased in an ahr-1 mutant compared to wild-type. Consistent with these changes, we observed a significant 5.8 fold increase in fat-7, and 1.7-1.9 fold increases in elo-5, nhr-49, and mdt-15 gene expression during the L4 stage. The ahr-1(ju145) mutant displayed deficits in growth and development including a reduced number of eggs laid, a higher proportion of dead embryos, delay in time to reach L4 stage, and movement deficits including a fewer number of body bends and a longer defecation cycle. To understand global effects of AHR-1 on transcription, microarray analysis was performed on L1 stage animals. Expression changes (324 under- and 238 over-expressed) were found in genes associated with metabolism, growth, and development. These results indicate a role for C. elegans AHR in regulating fatty acid composition and in contributing to some aspects of development. Since the transcriptional control of AHR targets may be evolutionarily conserved, these results provide a deeper understanding of the molecular actions of AHR in a model invertebrate system that may be informative for higher organisms.


Liver histopathology and biochemical biomarkers in Gobius niger and Zosterisessor ophiocephalus from polluted and non-polluted Tunisian lagoons (Southern Mediterranean Sea).
The aim of this study was to appraise the response of a multi-marker approach in fish species, Gobius niger and Zosterisessor ophiocephalus, in a polluted lagoon (Bizerte lagoon: MB and ML sites) and in a reference site (Ghar-El-Melh lagoon entrance) by the analysis of physiological indexes, liver histopathology and some biochemical biomarkers. The results showed liver hypertrophy in fish collected from Bizerte lagoon as well as many non-specific lesions, unlike the reference site. All Bizerte lagoon sites had the same prevalence of histopathological lesions, but the mean intensity (MI) of parasites seemed to be more sensible as an indicator of pollution levels. Indeed, parasite MI was more important in MB site that has a higher pollution level. Also, biochemical biomarkers showed an induction in Bizerte lagoon sites with some differences within sites and species. The impact of the continuous release of pollution on the biomarker's response is discussed.


Engineering fibrin-based tissue constructs from myofibroblasts and application of constraints and strain to induce cell and collagen reorganization.
Collagen content and organization in developing collagenous tissues can be influenced by local tissue strains and tissue constraint. Tissue engineers aim to use these principles to create tissues with predefined collagen architectures. A full understanding of the exact underlying processes of collagen remodeling to control the final tissue architecture, however, is lacking. In particular, little is known about the (re)orientation of collagen fibers in response to changes in tissue mechanical loading conditions. We developed an in vitro model system, consisting of biaxially-constrained myofibroblast-seeded fibrin constructs, to further elucidate collagen (re)orientation in response to i) reverting biaxial to uniaxial static loading conditions and ii) cyclic uniaxial loading of the biaxially-constrained constructs before and after a change in loading direction, with use of the Flexcell FX4000T loading device. Time-lapse confocal imaging is used to visualize collagen (re)orientation in a nondestructive manner. Cell and collagen organization in the constructs can be visualized in real-time, and an internal reference system allows us to relocate cells and collagen structures for time-lapse analysis. Various aspects of the model system can be adjusted, like cell source or use of healthy and diseased cells. Additives can be used to further elucidate mechanisms underlying collagen remodeling, by for example adding MMPs or blocking integrins. Shape and size of the construct can be easily adapted to specific needs, resulting in a highly tunable model system to study cell and collagen (re)organization.


Brain sources of EEG gamma frequency during volitionally meditation-induced, altered states of consciousness, and experience of the self.
Multichannel EEG of an advanced meditator was recorded during four different, repeated meditations. Locations of intracerebral source gravity centers as well as Low Resolution Electromagnetic Tomography (LORETA) functional images of the EEG 'gamma' (35-44 Hz) frequency band activity differed significantly between meditations. Thus, during volitionally self-initiated, altered states of consciousness that were associated with different subjective meditation states, different brain neuronal populations were active. The brain areas predominantly involved during the self-induced meditation states aiming at visualization (right posterior) and verbalization (left central) agreed with known brain functional neuroanatomy. The brain areas involved in the self-induced, meditational dissolution and reconstitution of the experience of the self (right fronto-temporal) are discussed in the context of neural substrates implicated in normal self-representation and reality testing, as well as in depersonalization disorders and detachment from self after brain lesions.


Smart IM-MS and NMR study of natural diastereomers: the study case of the essential oil from Senecio transiens.
Unambiguous identification of the components of a natural mixture remains a challenging and meticulous issue. Usually, different analytical techniques and laborious separation protocols are employed; nevertheless, in some cases, delicate and equivocal problems are hardly addressed by traditional methods. In this context, an original methodology for the analysis of natural samples consisting of recent mass spectrometry methods based on ion mobility (MS-IM) is proposed. As an example, a polar fraction obtained by the essential oil prepared from Senecio transiens, an endemic plant harvested on the Corsica Island, was selected for this study to show how IM-MS-based methods easily provide very useful insights suggesting the presence of two diastereomers. To unambiguously confirm this hypothesis and verify reliability of the IM-MS results, the purified compounds were further analysed by means of nuclear magnetic resonance (NMR) methodologies, allowing the structural elucidation and the identification of two new natural compounds, diastereomers of 4-acetoxy-5,9-dimethyl-3-(2-methylpropenyl)-2-oxabicyclo[4.4.0] dec-9-ene, reported here for the first time.


Treatment outcomes on neovascularization after CRAO treated with hyperbaric oxygen.
Central retinal artery occlusion (CRAO) is a condition that causes sudden vision loss due to obstruction of the retinal artery, typically from a thrombotic or embolic source. It is often associated with atherosclerotic risk factors, including cardiovascular disease, diabetes, hyperlipidemia, and a history of cerebrovascular disease. CRAO often leads to a poor visual outcome as well as neovascularization of the iris, retina, and optic disc, which can exacerbate vision loss and cause pain. While there are several treatment modalities for CRAO, few have been proven to be effective in decreasing the effects of neovascularization. The use of hyperbaric oxygen (HBO2) therapy is often used in the treatment of CRAO due to its ease of use and relatively benign side effect profile. This study aims to assess the degree of improvement in visual acuity (VA) and neovascularization following HBO2. Our data ultimately shows that 20% of patients developed neovascularization after HBO2 compared to 29.8% of those who did not undergo HBO2 (p<.05). Our findings suggest that HBO2 has a statistically significant protective effect against neovascularization and may improve long-term visual acuity.