A critique of the historical-fire-regime concept in conservation.
Prescribed fire is widely accepted as a conservation tool because fire is essential to the maintenance of native biodiversity in many terrestrial communities. Approaches to this land-management technique vary greatly among continents, and sharing knowledge internationally can inform application of prescribed fire worldwide. In North America, decisions about how and when to apply prescribed fire are typically based on the historical-fire-regime concept (HFRC), which holds that replicating the pattern of fires ignited by lightning or preindustrial humans best promotes native species in fire-prone regions. The HFRC rests on 3 assumptions: it is possible to infer historical fire regimes accurately; fire-suppressed communities are ecologically degraded; and reinstating historical fire regimes is the best course of action despite the global shift toward novel abiotic and biotic conditions. We examined the underpinnings of these assumptions by conducting a literature review on the use of historical fire regimes to inform the application of prescribed fire. We found that the practice of inferring historical fire regimes for entire regions or ecosystems often entails substantial uncertainty and can yield equivocal results; ecological outcomes of fire suppression are complex and may not equate to degradation, depending on the ecosystem and context; and habitat fragmentation, invasive species, and other modern factors can interact with fire to produce novel and in some cases negative ecological outcomes. It is therefore unlikely that all 3 assumptions will be fully upheld for any landscape in which prescribed fire is being applied. Although the HFRC is a valuable starting point, it should not be viewed as the sole basis for developing prescribed fire programs. Rather, fire prescriptions should also account for other specific, measurable ecological parameters on a case-by-case basis. To best achieve conservation goals, researchers should seek to understand contemporary fire-biota interactions across trophic levels, functional groups, spatial and temporal scales, and management contexts.


Legal considerations. Current Florida law.
Legislation enacted in 1991 requires physicians licensed under Chapters 458 or 459, Florida Statutes, to earn continuing medical education in the area of HIV and AIDS and specifies what should be covered in the program. The law no longer requires that certain information be imparted to the patient prior to testing for the human immunodeficiency virus. Information is presented on who can consent to testing, when consent is not required, pre- and post-testing requirements, confidentiality of patient records and possible disclosure and testing as a condition of treatment or admission.


Safety and immunogenicity of a quadrivalent inactivated influenza vaccine compared to licensed trivalent inactivated influenza vaccines in adults.
To evaluate the safety and immunogenicity of a prototype quadrivalent inactivated influenza vaccine (QIV) containing two influenza B strains, one of each lineage, compared with licensed trivalent inactivated influenza vaccines (TIVs) containing either a Victoria B-lineage strain (2009-2010 TIV) or a Yamagata B-lineage strain (2008-2009 TIV). Healthy adults ≥18 years of age were eligible to participate in this phase II, open-label, randomized, controlled, multicenter study conducted in the US. Participants received a single dose of 2009-2010 TIV, 2008-2009 TIV, or QIV. Sera were collected before and 21 days after vaccine administration to test for hemagglutination inhibition (HAI) antibodies to each of the four influenza strains. Immunogenicity endpoints included geometric mean HAI antibody titers (GMTs) and rates of seroprotection (titer ≥1:40) and seroconversion (4-fold rise pre- to post-vaccination). Safety endpoints included frequency of solicited injection-site and systemic reactions occurring within 3 days of vaccination, and unsolicited non-serious adverse events (AEs) and serious AEs (SAEs) within 21 days of vaccination. One hundred and ninety participants were enrolled to each vaccine group. QIV induced GMTs to each A and B strain that were noninferior to those induced by the 2009-2010 and 2008-2009 TIVs (i.e., lower limit of the two-sided 95% confidence interval of the ratio of GMT(QIV)/GMT(TIV)>0.66 for each strain). Rates of seroprotection and seroconversion were similar in all groups. Incidence and severity of solicited injection-site and systemic reactions, AEs, and SAEs were similar among groups. QIV, containing two B strains (one from each B lineage), was as safe and immunogenic as licensed TIV. QIV has the potential to be a useful alternative to TIV and offer protection against both B lineages.


Fate of occupational asthma. A follow-up study of patients with occupational asthma due to Western Red Cedar (Thuja plicata).
Thirty-eight patients with red cedar asthma proved by inhalation provocation test were studied after they had left exposure for more than 6 months. Twenty-seven patients became asymptomatic, with normal lung function (group A). Three patients had persistent chronic bronchitis with a moderate degree of airway obstruction, probably as a result of cigarette smoking (group B1). Eight patients continued to have recurrent attacks of asthma that decreased in severity after cessation of exposure, and their symptoms were probably due to previous exposure (group B2). The effect of breathing helium on maximal expiratory flow at 50 per cent of the vital capacity was studied. All except one patient in group A were responders (change in maximal expiratory flow at 50 per cent of vital capacity greater than 30 per cent). Two patients in group B1 and 2 in group B2 were nonresponders, suggesting obstruction in the small airways. All patients with red cedar asthma demonstrated bronchial hyperreactivity to methacholine to the same extent as patients with nonoccupational asthma. This hyperreactivity persisted after they left exposure, irrespective of symptoms. It is not known at present whether bronchial hyperreactivity is the predisposing factor in occupational asthma or is the result of the disease.


X-ray microanalysis applied to the study of salivary glands.
X-ray microanalysis can be used to study the distribution of elements in salivary glands at the cellular and subcellular level in a variety of physiological and pathophysiological conditions. The acinar cells of the adult rat and mouse submandibular gland contain high concentrations of calcium due to the presence of calcium-rich secretory granules. The calcium concentration of the acinar cells can be increased under a variety of pathophysiological conditions, e.g., in animal models for cystic fibrosis, due to an increase in the number of secretory granules and changes in their calcium-binding properties. Cholinergic stimulation results in a decrease in the concentrations of Cl and K in all cell compartments in adult animals, but not in newborn rats. Also the secretory granules in the glands in adult animals lose Cl and K, indicating that ion (and water) transport mechanisms may be present in the membrane of the granules. During chemical fixation, the secretory granules in the adult glands swell and their morphology is different from that in freeze-substituted glands. The characteristics of the secretory granules in the acinar cells of newborn rats are different from those of adult animals.


Targeting to endothelial cells augments the protective effect of novel dual bioactive antioxidant/anti-inflammatory nanoparticles.
Oxidative stress and inflammation are intertwined contributors to numerous acute vascular pathologies. A novel dual bioactive nanoparticle with antioxidant/anti-inflammatory properties was developed based on the interactions of tocopherol phosphate and the manganese porphyrin SOD mimetic, MnTMPyP. The size and drug incorporation efficiency were shown to be dependent on the amount of MnTMPyP added as well as the choice of surfactant. MnTMPyP was shown to retain its SOD-like activity while in intact particles and to release in a slow and controlled manner. Conjugation of anti-PECAM antibody to the nanoparticles provided endothelial targeting and potentiated nanoparticle-mediated suppression of inflammatory activation of these cells manifested by expression of VCAM, E-selectin, and IL-8. This nanoparticle technology may find applicability with drug combinations relevant for other pathologies.


Monovalent type-1 oral poliovirus vaccine given at short intervals in Pakistan: a randomised controlled, four-arm, open-label, non-inferiority trial.
Supplementary immunisation activities with oral poliovirus vaccines (OPVs) are usually separated by 4 week intervals; however, shorter intervals have been used in security-compromised areas and for rapid outbreak responses. We assessed the immunogenicity of monovalent type-1 oral poliovirus vaccine (mOPV1) given at shorter than usual intervals in Karachi, Pakistan. This was a multicentre, randomised, controlled, four-arm, open-label, non-inferiority trial done at five primary health-care centres in low-income communities in and around Karachi, Pakistan. Eligible participants were healthy newborn babies with a birthweight of at least 2·5 kg, for whom informed consent was provided by their parent or guardian, and lived less than 30 km from the study clinic. After receiving a birth dose of trivalent OPV, we enrolled and randomly assigned newborn babies (1:1:1:1) to receive two doses of mOPV1 with an interval of 1 week (mOPV1-1 week), 2 weeks (mOPV1-2 weeks), or 4 weeks (mOPV1-4 weeks) between doses, or two doses of bivalent OPV (bOPV) with an interval of 4 weeks between doses (bOPV-4 weeks). We gave the first study dose of OPV at age 6 weeks. We did the randomisation with a centrally generated, computerised allocation sequence with blocks of 16; participants' families and study physicians could not feasibly be masked to the allocations. Trial participants were excluded from local supplementary immunisation activities during the study period. The primary outcome was non-inferiority (within a 20% margin) between groups in seroconversion to type-1 poliovirus. The primary and safety analyses were done in the per-protocol population of infants who received all three doses of vaccine. This trial is registered with ClinicalTrials.gov, number NCT01586572, and is closed to new participants. Between March 1, 2012, and May 31, 2013, we enrolled 1009 newborn babies, and randomly assigned 829 (82%) to treatment. 554 (67%) of the 829 babies were included in the per-protocol analysis. Proportions of seroconversion to type-1 poliovirus were 107/135 (79%, 95% CI 72·4-86·1) with mOPV1-1 week, 108/135 (80%, 73·2-86·8) with mOPV1-2 weeks, 129/148 (87%, 80·9-92·0) with mOPV1-4 weeks, and 107/136 (79%, 71·8-85·6) with bOPV-4 weeks. Non-inferiority was shown between groups and no significant differences were noted. Ten participants died during the trial. Seven of these deaths occurred during the lead-in period before randomisation (two from diarrhoea, five from unknown causes). Three infants died from sepsis after random assignment. No deaths were attributed to the procedures or vaccines. Additionally, we noted no events of vaccine-associated paralysis. We identified no significant differences in responses to mOPV1 given with shorter intervals between doses than with the standard 4 week intervals. The short-interval strategy could be particularly beneficial when temporary windows of opportunity for safe access can be granted in areas of conflict--eg, during cease-fire periods. In such situations, we recommend shortening the interval between OPV doses to 7 days. World Health Organization.


Architectural epigenetics: mitotic retention of mammalian transcriptional regulatory information.
Epigenetic regulatory information must be retained during mammalian cell division to sustain phenotype-specific and physiologically responsive gene expression in the progeny cells. Histone modifications, DNA methylation, and RNA-mediated silencing are well-defined epigenetic mechanisms that control the cellular phenotype by regulating gene expression. Recent results suggest that the mitotic retention of nuclease hypersensitivity, selective histone marks, as well as the lineage-specific transcription factor occupancy of promoter elements contribute to the epigenetic control of sustained cellular identity in progeny cells. We propose that these mitotic epigenetic signatures collectively constitute architectural epigenetics, a novel and essential mechanism that conveys regulatory information to sustain the control of phenotype and proliferation in progeny cells by bookmarking genes for activation or suppression.


Phylogenetic transmission clusters among newly diagnosed antiretroviral drug-naïve patients with human immunodeficiency virus-1 in Korea: A study from 1999 to 2012.
Population-level phylogenetic patterns reflect both transmission dynamics and genetic changes, which accumulate because of selection or drift. In this study, we determined whether a longitudinally sampled dataset derived from human immunodeficiency virus (HIV)-1-infected individuals over a 14-year period (1999-2012) could shed light on the transmission processes involved in the initiation of the HIV-1 epidemic in Korea. In total, 927 sequences were acquired from 1999 to 2012; each sequence was acquired from an individual patient who had not received treatment. Sequences were used for drug resistance and phylogenetic analyses. Phylogenetic and other analyses were conducted using MEGA version 6.06 based on the GTR G+I parameter model and SAS. Of the 927 samples, 863 (93.1%) were classified as subtype B and 64 were classified as other subtypes. Phylogenetic analysis demonstrated that 104 of 927 patient samples (11.2%) were grouped into 37 clusters. Being part of a transmission cluster was significantly associated with subtype-B viruses, infection via sexual contact, and the infection of young males. Of all clusters, three (~8.1%) that comprised 10 individual samples (22.2% of 45 individuals) included at least one member with total transmitted drug resistance (TDR). In summary, HIV transmission cluster analyses can integrate laboratory data with behavioral data to enable the identification of key transmission patterns to develop tailored interventions aimed at interrupting transmission chains.


The potential for bridging of HIV transmission in the Russian Federation: sex risk behaviors and HIV prevalence among drug users (DUs) and their non-DU sex partners.
The HIV epidemic that began in Russia in the mid-1990s has been concentrated mostly among drug users (DUs). Recent evidence of increasing HIV cases among non-DUs attributed to sexual behavior raises potential concern about a more generalized epidemic. The purpose of this analysis is to examine the potential for HIV transmission from DUs to their non-DU sex partners. Analyses are conducted using data collected during 2005-2008 in St. Petersburg, Russia. A total of 631 DUs were recruited into the sample with an HIV prevalence of 45%. A majority (84%) of DUs reported being sexually active in the past 6 months, and the DU status of their sex partners was reported as follows: 54% DU, 40% non-DU, and 6% unknown DU status. In 41% of partnerships with an HIV-negative or unknown status partner not known to be DU (potential bridging partnerships), the last reported intercourse was unprotected. Female DUs with potential bridging partnerships were more likely than male DUs to be younger and report homelessness and to have multiple or new sex partners. Many non-DU sex partners of DUs enrolled in the study reported new sex partners in the past 6 months (66%), unprotected intercourse at last sex (60%), and multiple sex partners in the past 6 months (48%). HIV prevalence in this group was 15% (eight out of 53). The high prevalence of HIV among DUs, their sexual contact with non-DUs, and the high-risk sexual behaviors of this potential bridging population together indicate the real potential for an increasingly generalized epidemic. The degree to which there will be further transmission from non-DU sex partners of DUs who exhibit high levels of sex risk behaviors to other non-DU sex partners deserves further study.


Association study on long-living individuals from Southern Italy identifies rs10491334 in the CAMKIV gene that regulates survival proteins.
Long-living individuals (LLIs) are used to study exceptional longevity. A number of genetic variants have been found associated in LLIs to date, but further identification of variants would improve knowledge on the mechanisms regulating the rate of aging. Therefore, we performed a genome-wide association study on 410 LLIs and 553 young control individuals with a 317K single-nucleotide polymorphism (SNP) chip to identify novel traits associated with aging. Among the top (p < 1 × 10(-4)) SNPs initially identified, we found rs10491334 (CAMKIV) (odds ratio [OR] = 0.55; 95% confidence interval [CI] 0.42-0.73; p = 2.88 × 10(-5)), a variant previously reported associated with diastolic blood pressure, associated also in a replication set of 116 LLIs and 160 controls (OR = 0.54; 95% CI 0.32-0.90; p = 9 × 10(-3)). Furthermore, in vitro analysis established that calcium/calmodulin-dependent protein kinase IV (CAMKIV) activates the survival proteins AKT, SIRT1, and FOXO3A, and we found that homozygous carriers of rs10491334 have a significant reduction in CAMKIV expression. This, together with the observed reduction in minor-allele carriers among centenarians, points to a detrimental role for the SNP. In conclusion, prolongevity genes are activated by CAMKIV, the levels of which are influenced by rs10491334, a SNP associated with human longevity.


Sensitive Determination of Sertraline in Commercial Drugs and Its Stability Check in Simulated Gastric Juice.
A sensitive analytical method was developed for the determination of sertraline in commercial drug samples by using GC-MS. The selected-ion monitoring mode was used at the most sensitive m/z 274 to obtain a lower detection limit. LOD/LOQ values were obtained as 1.6/5.4 ng/mL for sertraline under the optimum conditions. The calibration plot was linear between 5.0 and 2000 ng/mL with the correlation coefficient of 0.9999. The validated method was successfully applied to three different brands of drug samples for both qualitative and quantitative measurement of sertraline. In this experiment, four replicate extractions were performed for each brand, and the results were compared to the values written on the labels of the drug brands. Spiking experiments were also performed to check the effect of the matrixes on the determination, and it was observed that there was no shift in the retention time of the analyte. In addition, simulated gastric juice experiments were performed to check the stability of sertraline in the stomach for 240 min, and it was observed that there was no change in the structure of the analyte.


Promotion of autoimmune diabetes by cereal diet in the presence or absence of microbes associated with gut immune activation, regulatory imbalance, and altered cathelicidin antimicrobial Peptide.
We are exposed to millions of microbial and dietary antigens via the gastrointestinal tract, which likely play a key role in type 1 diabetes (T1D). We differentiated the effects of these two major environmental factors on gut immunity and T1D. Diabetes-prone BioBreeding (BBdp) rats were housed in specific pathogen-free (SPF) or germ-free (GF) conditions and weaned onto diabetes-promoting cereal diets or a protective low-antigen hydrolyzed casein (HC) diet, and T1D incidence was monitored. Fecal microbiota 16S rRNA genes, immune cell distribution, and gene expression in the jejunum were analyzed. T1D was highest in cereal-SPF (65%) and cereal-GF rats (53%) but inhibited and delayed in HC-fed counterparts. Nearly all HC-GF rats remained diabetes-free, whereas HC-fed SPF rats were less protected (7 vs. 29%). Bacterial communities differed in SPF rats fed cereal compared with HC. Cereal-SPF rats displayed increased gut CD3(+) and CD8α(+) lymphocytes, ratio of Ifng to Il4 mRNA, and Lck expression, indicating T-cell activation. The ratio of CD3(+) T cells expressing the Treg marker Foxp3(+) was highest in HC-GF and lowest in cereal-SPF rats. Resident CD163(+) M2 macrophages were increased in HC-protected rats. The cathelicidin antimicrobial peptide (Camp) gene was upregulated in the jejunum of HC diet-protected rats, and CAMP(+) cells colocalized with CD163. A cereal diet was a stronger promoter of T1D than gut microbes in association with impaired gut immune homeostasis.


Higher flight activity in the offspring of migrants compared to residents in a migratory insect.
Migration has evolved among many animal taxa and migratory species are found across all major lineages. Insects are the most abundant and diverse terrestrial migrants, with trillions of animals migrating annually. Partial migration, where populations consist of resident and migratory individuals, is ubiquitous among many taxa. However, the underlying mechanisms are relatively poorly understood and may be driven by physiological, behavioural or genetic variation within populations. We investigated the differences in migratory tendency between migratory and resident phenotypes of the hoverfly, Episyrphus balteatus, using tethered flight mills. Further, to test whether migratory flight behaviour is heritable and to disentangle the effects of environment during development, we compared the flight behaviour of laboratory-reared offspring of migrating, overwintering and summer animals. Offspring of migrants initiated more flights than those of resident individuals. Interestingly, there were no differences among wild-caught phenotypes with regard to number of flights or total flight duration. Low activity in field-collected migrants might be explained by an energy-conserving state that migrants enter into when under laboratory conditions, or a lack of suitable environmental cues for triggering migration. Our results strongly suggest that flight behaviour is heritable and that genetic factors influence migratory tendency in E. balteatus These findings support the growing evidence that genetic factors play a role in partial migration and warrant careful further investigation.


Ventilator-associated pneumonia in neonatal and pediatric intensive care unit patients.
Ventilator-associated pneumonia (VAP) is the second most common hospital-acquired infection among pediatric intensive care unit (ICU) patients. Empiric therapy for VAP accounts for approximately 50% of antibiotic use in pediatric ICUs. VAP is associated with an excess of 3 days of mechanical ventilation among pediatric cardiothoracic surgery patients. The attributable mortality and excess length of ICU stay for patients with VAP have not been defined in matched case control studies. VAP is associated with an estimated $30,000 in attributable cost. Surveillance for VAP is complex and usually performed using clinical definitions established by the CDC. Invasive testing via bronchoalveolar lavage increases the sensitivity and specificity of the diagnosis. The pathogenesis in children is poorly understood, but several prospective cohort studies suggest that aspiration and immunodeficiency are risk factors. Educational interventions and efforts to improve adherence to hand hygiene for children have been associated with decreased VAP rates. Studies of antibiotic cycling in pediatric patients have not consistently shown this measure to prevent colonization with multidrug-resistant gram-negative rods. More consistent and precise approaches to the diagnosis of pediatric VAP are needed to better define the attributable morbidity and mortality, pathophysiology, and appropriate interventions to prevent this disease.


Calcium influx and male fertility in the context of the sperm proteome: an update.
Freshly ejaculated spermatozoa are incapable or poorly capable of fertilizing an oocyte. The fertilization aptness of spermatozoa depends on the appropriate and time-dependent acquisition of hyperactivation, chemotaxis, capacitation, and the acrosome reaction, where calcium (Ca(2+)) is extensively involved in almost every step. A literature review showed that several ion channel proteins are likely responsible for regulation of the Ca(2+) uptake in spermatozoa. Therefore, manipulation of the functions of channel proteins is closely related to Ca(2+) influx, ultimately affecting male fertility. Recently, it has been shown that, together with different physiological stimuli, protein-protein interaction also modifies the Ca(2+) influx mechanism in spermatozoa. Modern proteomic analyses have identified several sperm proteins, and, therefore, these findings might provide further insight into understanding the Ca(2+) influx, protein functions, and regulation of fertility. The objective of this review was to synthesize the published findings on the Ca(2+) influx mechanism in mammalian spermatozoa and its implications for the regulation of male fertility in the context of sperm proteins. Finally, Pathway Studio (9.0) was used to catalog the sperm proteins that regulate the Ca(2+) influx signaling by using the information available from the PubMed database following a MedScan Reader (5.0) search.


Quality of life in chronic illness: perceptions of parents and paediatricians.
To investigate the differences in perception of quality of life between parents of chronically ill children and paediatricians at diagnosis and follow up. Quality of life was assessed using the (HUI3). Longitudinal study (July 1999-January 2002) of 37 paediatricians and 181 parents of patients (children aged 1-17 years) with cystic fibrosis admitted for a pneumonia or patients with newly diagnosed acute lymphatic leukaemia, juvenile idiopathic arthritis, or asthma. Main outcome measure was percentage agreement on the attributes of the HUI3 between parents and paediatricians. Differences in perception of health and wellbeing between paediatricians and parents of children with a chronic disease were found, not only at diagnosis but also after a period of follow up. Differences were particularly clear in the subjective attributes emotion (range of agreement 28-68%) and pain/discomfort (range of agreement 11-33%). In all patient groups, at baseline and follow up, the paediatrician assessed the patient to have less pain/discomfort in comparison to the parents. Despite a prolonged patient- paediatrician relationship, differences at follow up did not decrease compared to baseline. At the onset of a chronic disease, but also after a period of follow up, quality of life of paediatric patients may be misunderstood by healthcare professionals, especially in the subjective attributes. Systematic assessment of quality of life may contribute to better understanding between physicians and parents.


Quantitation and localization of laminin A, B1, and B2 chain RNA transcripts in developing kidney.
To quantitate expression of laminin A, B1, and B2 chains during kidney development, we prepared riboprobes of similar size (318-365 nucleotides) and carried out scanning densitometry of Northern blots from newborn mouse and rat kidneys. Much higher expression of B1 than A or B2 mRNAs was observed with an A-to-B1-to-B2 ratio of approximately 1:8:4 in mice and approximately 1:12:1 in rats. In addition to the 9.5-kb laminin A chain transcript, we also observed specific hybridization of the A chain probe to approximately 6-kb band in both newborn mice and rats. To localize these mRNAs, newborn rat kidneys were sieved to obtain separate glomerular and tubule fractions. Northern blots from these samples showed that most of the B1, B2, and 9.5-kb laminin A chain mRNAs were in glomerular fractions, whereas tubules contained more of the 6-kb A chain band. Analyses of poly(A)+ mRNA from newborn and adult kidneys showed severalfold decreases in adult RNA encoding the three laminin chains and the alpha 1-chain type IV collagen. However, only a 20% decline from newborn levels was seen for heparan sulfate proteoglycan (HSPG) core protein message. These quantitative results provide additional evidence that different laminin isoforms are present in separate kidney basement membranes and that HSPG core protein synthesis remains at relatively high levels in adult kidneys.


Serotyping of Haemophilus influenzae a comparison of co-agglutination with countercurrent--immunoelectrophoresis and slide--agglutination.
30 out of 55 strains of H. influenzae could be assigned to one of the six serotypes A--F by slide agglutination, countercurrent-immunoelectrophoresis or co-agglutination. While slide-agglutination appeared less reliable due to non-specific agglutinations countercurrent-immunoelectrophoresis was of high specificity. No cross reactions were encountered in this test and results were unambiguously to evaluate. Co-agglutination is attractive because of its rapidity and simplicity without any need of special equipment. It was found to be of increased sensitivity in detecting type B capsular antigen when compared with countercurrent-immunoelectrophoresis, the problem of cross-reactions remains to be solved however. The use of co-agglutination for serotyping H. influenzae strains in combination with countercurrent-immunoelectrophoresis can be recommended.


Influence of inhomogeneous dental posts on stress distribution in tooth root and interfaces: Three-dimensional finite element analysis.
In post-and-core crown restorations, the use of flexible posts concentrates stresses at the dentin and the use of stiff posts concentrates stresses at the interfaces. A class of inhomogeneous materials (called functionally graded materials) has been proposed for posts to resolve the weaknesses of both flexible and rigid posts. The purpose of this in vitro study was to design an inhomogeneous post and investigate its influence on the stress distribution of post-and-core crown restorations. An extracted tooth was mounted, sectioned, and photographed to create a 3-dimensional model of the first premolar tooth. The post-and-core crown restoration was modeled with and without a ferrule. The surrounding tissues of the mandibular tooth, periodontal ligament, and cortical and trabecular bones were modeled. Fiber-reinforced composite (FRC), metallic, and inhomogeneous posts were investigated by finite element analysis and the stress distribution results compared. FRC posts resulted in the highest maximum tensile stress (MTS) at the remaining dentin (90.4 to 93.2 MPa), while inhomogeneous posts graded by index n=10 (FGM10) caused the lowest MTS, both with and without a ferrule (72.3 to 74.8 MPa). The use of FRC posts concentrated more MTS at the dentin and less MTS at the dentin-adhesive interface than metallic posts. Inhomogeneous posts (FGM10) resolved the weaknesses of both flexible and rigid posts by simultaneously reducing stresses at the dentin and interface. The ferrule effect resulted in fewer dentin and interface stresses.


How active are women who play bingo: a cross-sectional study from the Well!Bingo project.
The benefits of physical activity are well established, yet large numbers of people are not sufficiently active to gain health benefits. Certain population groups are less physically active than others, including older women from areas of high economic deprivation. The Well!Bingo project was established with the aim of engaging such women in the development of a health promotion intervention in a bingo club. This paper reports on the assessment of health status, physical activity and sedentary behaviour of women attending a bingo club in central Scotland, UK as part of the Well!Bingo project. Women attending the bingo club were invited to provide information on demographic characteristics, and self-reported physical activity and sedentary behaviour via a self-complete questionnaire as part of a cross-sectional study (n = 151). A sub-sample (n = 29) wore an accelerometer for an average of 5.7 ± 1.4 days. Differences between younger (under 60 years) and older adults (60 years and over) were assessed using a chi-square test for categorical data and the independent samples t-test was used to assess continuous data (p < 0.05). The mean age was 56.5 ± 17.7 years, with 57% living in areas of high deprivation (Scottish Index of Multiple Deprivation quintile one and two). Sixty-three percent of women (n = 87) reported they were meeting physical activity guidelines. However, objective accelerometer data showed that, on average, only 18.1 ± 17.3 min a day were spent in moderate to vigorous physical activity. Most accelerometer wear time was spent sedentary (9.6 ± 1.7 h). For both self-report and accelerometer data, older women were significantly less active and more sedentary than younger women. On average, older women spent 1.8 h more than younger women in sedentary activities per day, and took part in 21 min less moderate to vigorous physical activity (9.4 mins per day). The findings of this study suggest that bingo clubs are settings that attract women from areas of high deprivation and older women in bingo clubs in particular would benefit from interventions to target their physical activity and sedentary behaviour. Bingo clubs may therefore be potential intervention settings in which to influence these behaviours.


By the sound of it. An ERP investigation of human action sound processing in 7-month-old infants.
Recent evidence suggests that human adults perceive human action sounds as a distinct category from human vocalizations, environmental, and mechanical sounds, activating different neural networks (Engel et al., 2009; Lewis et al., 2011). Yet, little is known about the development of such specialization. Using event-related potentials (ERP), this study investigated neural correlates of 7-month-olds' processing of human action (HA) sounds in comparison to human vocalizations (HV), environmental (ENV), and mechanical (MEC) sounds. Relative to the other categories, HA sounds led to increased positive amplitudes between 470 and 570ms post-stimulus onset at left anterior temporal locations, while HV led to increased negative amplitudes at the more posterior temporal locations in both hemispheres. Collectively, human produced sounds (HA+HV) led to significantly different response profiles compared to non-living sound sources (ENV+MEC) at parietal and frontal locations in both hemispheres. Overall, by 7 months of age human action sounds are being differentially processed in the brain, consistent with a dichotomy for processing living versus non-living things. This provides novel evidence regarding the typical categorical processing of socially relevant sounds.


[Role of high mobility group box 1 in adriamycin-induced apoptosis in leukemia K562 cells].
High mobility group box l (HMGB1), a nuclear DNA-binding protein, stabilizes the structure and function of chromatin, regulates gene transcription. Recent studies found that HMGB1 is associated with the proliferation and metastasis of many tumors, including breast cancer, colon carcinoma, and melanoma, and is rich in various solid cancer tissues and immature cells. This study was to explore the role of HMGB1 in adriamycin (ADM)-induced apoptosis in leukemia K562 cells. K562 cells were transiently transfected with recombinant plasmid pcDNA3.1-HMGB1. The expression of HMGB1 in K562 cells were detected by Western blot and reverse transcription-polymerase chain reaction (RT-PCR). The 50% inhibition concentration (IC(50)) of ADM for K562 cells was determined by WST-8 assay. Cell apoptosis was assessed by flow cytometry. The protein level of Bcl-2 was detected by Western blot. The activities of Caspase-3 and Caspase-9 were assayed with Caspase Colorimetric Assay Kit. The mRNA and protein levels of HMGB1 in K562 cells transfected with pcDNA3.1-HMGB1 were increased by about 85% and 56% respectively as compared with those in K562 cells transfected with pcDNA3.1. Overexpression of HMGB1 in K562 cells by transient transfection significantly increased the resistance to ADM; the IC(50) of ADM was increased from (0.06+/-0.00) microg/mL to (3.46+/-0.06) microg/mL. When treated with 1 microg/mL ADM, the apoptosis rate was significantly lower in HMGB1-transfected K562 cells than in pcDNA3.1-transfected K562 cells [(12.00+/-1.26)% vs. (44.50+/-1.87)%, P<0.05]. Overexpression of HMGB1 in K562 cells significantly inhibited ADM-induced down-regulation of Bcl-2 protein. After treatment of ADM, the activities of Caspase-3 and Caspase-9 in HMGB1-transfected K562 cells were inhibited as compared with those in pcDNA3.1-transfected K562 cells (Caspase-3: 1.55+/-0.06 vs. 2.55+/-0.06 at 12 h, 1.86+/-0.10 vs. 2.85+/-0.06 at 24 h, P<0.05; Caspase-9: 1.40+/-0.08 vs. 2.03+/-0.05 at 12 h, 1.55+/-0.06 vs. 2.22+/-0.05 at 24 h, P<0.05). HMGB1 overexpression could inhibit ADM-induced apoptosis in leukemia K562 cells through regulating the protein level of Bcl-2 and the activities of Caspase-3 and Caspase-9.


Development of molecular simulation methods to accurately represent protein-surface interactions: Method assessment for the calculation of electrostatic effects.
The simulation of the interactions of proteins with charged surfaces in a condensed-phase aqueous solution containing electrolytes using empirical force field based methods is predominantly governed by nonbonded interactions between the atoms of the protein, surface, and the solvent. Electrostatic effects represent the strongest type of these interactions and the type that is most difficult to accurately represent because of their long-range influence. While many different methods have been developed to represent electrostatic interactions, the particle mesh Ewald summation (PME) method is generally considered to be the most accurate one for calculating these effects. However, the PME method was designed for systems with three-dimensional (3D) periodicity, and not for interfacial systems such as the case of protein adsorption to a charged surface. Interfacial systems such as these have only two-dimensional periodicity, which may not be appropriate for treatment with PME due to the possibility that the presence of multiple charged image surfaces parallel to the primary simulation cell's surface, may introduce nonphysical effects on the behavior of the charged molecules in the system. In an effort to address this issue, the authors have conducted a set of nanosecond-scale molecular dynamics simulations to calculate the equilibrium distribution of Na(+) and Cl(-) ions near a charged surface using PME and a range of radial cutoff methods for treating electrostatic interactions, where the cutoffs prevent interaction with the periodic images of the system. The resulting ion concentration profiles were compared to one another and to a continuum analytical solution of the theoretical ion distribution obtained from the Poisson-Boltzmann equation. Their results show that the PME method does not introduce the suspected nonphysical effects in the ion distributions due to the 3D periodic images of the system, thus indicating that it is appropriate for use for this type of molecular simulation. Although their interest is motivated by protein-surface interactions, the conclusions are applicable for the treatment of electrostatics in other aqueous systems with two-dimensional periodicity.


Frailty and Associated Environmental Factors Only Have Small Effects on Age of Onset in Huntington's Disease.
Over one third of age of onset variation in Huntington's disease is unexplained by CAG repeat length. In Alzheimer's disease, frailty partly modulates the relationship between neuropathology and dementia. We investigated whether a multi-domain frailty index, reflecting non-genetic factors in Huntington's disease, similarly modulates the relationship between CAG repeat length and age of onset. We created a frailty index assessing comorbidities, substance abuse, polypharmacy, and education. We applied multiple linear regression models to 2,741 subjects with manifest Huntington's disease from the Enroll-HD cohort study, including 729 subjects with late-onset (post-60 years) disease, using frailty index or constituent item scores and CAG repeat length as independent variables. We used actual and "residual" ages of onset (difference between actual and CAG-based predicted onset) as dependent variables, the latter offsetting the increased time available to accumulate comorbidities in older subjects. Higher frailty index scores were associated with significantly lower residual ages of onset in the late-onset subgroup (p = 0.03), though the effect was small (R2 = 0.27 with frailty as a predictor vs. 0.26 without). Number of comorbidities was also associated with significantly lower residual ages of onset in the late-onset subgroup (p = 0.04). Drug abuse and smoking were associated with significantly earlier ages of onset in the whole cohort (p < 0.01, p = 0.02) and late-onset subgroup (p < 0.01, p = 0.03). The impact of non-genetic factors on age of onset, assessed using a frailty index or separately, in Huntington's disease is limited.


The role of ultrasound in molecular imaging.
Ultrasound has received less attention than other imaging modalities for molecular imaging, but has a number of potential advantages. It is cheap, widely available and portable. Using Doppler methods, flow information can be obtained easily and non-invasively. It is arguably the most physiological modality, able to image structure and function with less sedation than other modalities. This means that function is minimally disturbed, and multiple repeat studies or the effect of interventions can easily be assessed. High frame rates of over 200 frames a second are achievable on current commercial systems, allowing for convenient cardiac studies in small animals. It can be used to guide interventional or invasive studies, such as needle placement. Ultrasound is also unique in being both an imaging and therapeutic tool and its value in gene therapy has received much recent interest. Ultrasound biomicroscopy has been used for in utero imaging and can guide injection of virus and cells. Ultrahigh frequency ultrasound can be used to determine cell mechanical properties. The development of microbubble contrast agents has opened many new opportunities, including new functional imaging methods, the ability to image capillary flow and the possibility of molecular targeting using labelled microbubbles.


Alzheimer disease and neuroplasticity.
Alzheimer's disease (AD) is considered the most harmful form of dementia in the elderly population. At present, there are no effective treatments and this is likely due to the incomplete understanding of the pathophysiology. Recent data indicate that synaptic dysfunction could be a central element of AD pathophysiology. It was found that a synaptic breakdown is an early event that heralds neuronal degeneration. Transcranial magnetic stimulation (TMS) has been recently introduced as a novel approach to identify the early signatures of synaptic dysfunction characterizing AD pathophysiology. In this chapter, we review the new neurophysiologic signatures of AD that have been emphasized by TMS studies. We show how TMS measurement of neuroplasticity identified long-term potentiation (LTP)-like cortical plasticity as a key element of AD synaptic dysfunction. These measurements are useful to increase the accuracy of differential diagnosis, predict disease progression, and anticipate response to therapy. Moreover, enhancing neuroplasticity holds as a promising therapeutic approach to improve cognition in AD. In recent years, studies showed treatments with multiple sessions of rTMS can influence cognition in people with neurodegenerative diseases. In the second part of this chapter, we also consider novel therapeutic approaches based on the clinical use of rTMS.


Contained Morcellation: Review of Current Methods and Future Directions.
Power morcellation of surgical specimen during laparoscopic surgery is a practical technology that provides the opportunity to perform several minimally invasive procedures. However, this technology brought forward additional risks and complications associated with dissemination of both benign and malignant tissues inside the abdominal cavity. Based on startling cases, Food and Drug Administration (FDA) announced a discouraging statement on the use of power morcellators that decreased the number of minimally invasive approaches in the following period. As a response to these concerns and negative impacts of the FDA statement, researchers developed several new approaches resulting in contained or in-bag morcellation methods. In this review, we aimed to discuss these current methods and provide an insight for future developments.


Self-aligning universal beam coupler.
We propose a device that can take an arbitrary monochromatic input beam and, automatically and without any calculations, couple it into a single-mode guide or beam. Simple feedback loops from detectors to modulator elements allow the device to adapt to any specific input beam form. Potential applications include automatic compensation for misalignment and defocusing of an input beam, coupling of complex modes or multiple beams from fibers or free space to single-mode guides, and retaining coupling to a moving source. Straightforward extensions allow multiple different overlapping orthogonal input beams to be separated simultaneously to different single-mode guides with no splitting loss in principle. The approach is suitable for implementation in integrated optics platforms that offer elements such as phase shifters, Mach-Zehnder interferometers, grating couplers, and integrated monitoring detectors, and the basic approach is applicable in principle to other types of waves, such as microwaves or acoustics.


Venous embolus to a transplanted kidney. Diagnosis and treatment.
We are reporting the first case, to our knowledge, of a venous embolus to a transplanted kidney. The embolus occurred five days after transplantation of a cadaver kidney in a 31-year-old woman who was receiving estrogen-progesterone therapy for menorrhagia. Five hours after acute onset of left flank pain and anuria, the embolus was identified at the anastomosis of the donor renal vein to the external iliac vein. The embolus was manipulated distally in the external iliac vein and excluded by proximal division of the vein. Recovery was eventually complete, despite two major postoperative complications, acute tubular necrosis and a perirenal hematoma secondary to heparin sodium therapy. Radionuclide scanning was critically important in establishing the diagnosis and in assessing the potential for the kidney to recover from acute tubular necrosis. On the basis of this experience, we believe that prompt surgical intervention is indicated for acute venous occlusion.


Inhibition of carboxypeptidase A by ketones and alcohols that are isosteric with peptide substrates.
The Ki's of three peptide ketone and three peptide alcohol inhibitors of carboxypeptidase A are compared with Ki's of their respective isosteric peptide substrates, N alpha-benzoyl-L-phenylalanine, N alpha-benzoylglycyl-L-phenylalanine, and N alpha-carbobenzoxyglycylglycyl-L-phenylalanine. For the isosteric ketone analogues of these substrates, the respective Ki's are as follows: (2RS)-2-benzyl-4-(3-methoxyphenyl)-4-oxobutanoic acid, 180 +/- 40 microM; (2RS)-5-benzamido-2-benzyl-4-oxopentanoic acid (V), 48 +/- 7 microM; (2RS)-2-benzyl-5-(carbobenzoxyglycinamido)-4-oxopentanoic acid (IX), 9 +/- 0.1 microM. For the alcohols derived by reduction of each of these ketones, Ki's are as follows: (2RS,4RS)-2-benzyl-4-(3-methoxyphenyl)-4-hydroxybutanoic acid, 190 +/- 10 microM; (2RS,4RS)-5-benzamido-2-benzyl-4-hydroxybutanoic acid (IV), 160 +/- 62 microM; (2RS,4RS)-2-benzyl-5-(carbobenzoxyglycinamido)-4-hy droxypentanoic acid (XI), 600 +/- 100 microM. Ki values for the competitive peptide ketone inhibitors decrease with increasing peptide chain length. This is consistent with the possibility of increased binding interaction between inhibitor and enzyme by simple occupation of additional binding subsites by adding more amino acid residues to the inhibitor. In contrast, the Ki values of the alcohols (competitive or mixed inhibition) increased or remain essentially unchanged with increasing chain length. Increasing the chain length of ketone inhibitor V to give IX decreases Ki by one-fifth. The Ki of ketone IX is also less than 1/30th the Ki of its isosteric peptide and almost 1/70th that of its isosteric alcohol, XI.(ABSTRACT TRUNCATED AT 250 WORDS)


Dietary supplementation of ark clams protects gut health and modifies gut microbiota in d-galactose-induced aging rats.
Ark clams, a seafood abundant in various nutrients, are widely consumed worldwide. This study aimed to investigate the protective benefits of two common ark clams in Korea, Scapharca subcrenata (SS) and Tegillarca granosa (TG), on gut health in d-galactose (d-gal)-induced aging rats. Thirty-two Wistar rats (11 weeks old) were randomly allocated into four groups: a CON group (normal diet + saline intraperitoneal (i.p.) injection), a CD group (normal diet + d-gal i.p. injection), an SS group (normal diet with 5% SS supplementation + d-gal i.p. injection), and a TG group (normal diet with 5% TG supplementation + d-gal i.p. injection). After 12 weeks of treatment, histopathological results showed that gut barrier damage was alleviated in rats of the SS and TG groups, as evidenced by increases in mucus layer thickness and goblet cell numbers. Meanwhile, the two groups supplemented with ark clams showed an evident reduction in oxidative stress biomarkers (malondialdehyde and protein carbonyl content levels in the colon) and an increase in the immune-related factor (immunoglobulin A level in the plasma) in rats. The 16S ribosomal RNA analysis revealed that SS and TG ark clams significantly increased the proliferations of Bacteroidetes at the phylum level and Parabacteroides at the genus level. Additionally, the levels of the three main short-chain fatty acids in the cecal contents were also significantly increased in the SS and TG groups. Our results indicated a potent preventive effect of SS and TG ark clams on d-gal-induced gut injury, suggesting that ark clams may be a promising dietary component for intervening in aging. © 2023 Society of Chemical Industry.


Reducing Variability in the Infant Sepsis Evaluation (REVISE): A National Quality Initiative.
Substantial variability exists in the care of febrile, well-appearing infants. We aimed to assess the impact of a national quality initiative on appropriate hospitalization and length of stay (LOS) in this population. The initiative, entitled Reducing Variability in the Infant Sepsis Evaluation (REVISE), was designed to standardize care for well-appearing infants ages 7 to 60 days evaluated for fever without an obvious source. Twelve months of baseline and 12 months of implementation data were collected from emergency departments and inpatient units. Ill-appearing infants and those with comorbid conditions were excluded. Participating sites received change tools, run charts, a mobile application, live webinars, coaching, and a LISTSERV. Analyses were performed via statistical process control charts and interrupted time series regression. The 2 outcome measures were the percentage of hospitalized infants who were evaluated and hospitalized appropriately and the percentage of hospitalized infants who were discharged with an appropriate LOS. In total, 124 hospitals from 38 states provided data on 20 570 infants. The median site improvement in percentages of infants who were evaluated and hospitalized appropriately and in those with appropriate LOS was 5.3% (interquartile range = -2.5% to 13.7%) and 15.5% (interquartile range = 2.9 to 31.3), respectively. Special cause variation toward the target was identified for both measures. There was no change in delayed treatment or missed bacterial infections (slope difference 0.1; 95% confidence interval, -8.3 to 9.1). Reducing Variability in the Infant Sepsis Evaluation noted improvement in key aspects of febrile infant management. Similar projects may be used to improve care in other clinical conditions.


Effects of hypercapnia and hyperoxia on metabolism during exercise.
It has been postulated that the respiratory acidosis associated with hyperoxia (HO) may mediate some of the metabolic effects that are traditionally attributed to the elevation in PaO2. Five subjects performed 30 min of steady-state exercise (65% VO2max) on eight occasions while inspiring either 21 or 60% O2 in combination with 0, 2, 4, or 6% CO2. Statistical significance was accepted if P less than 0.05. The four HO tests were associated with increased VO2 and lower R and blood lactate. However, when compared to the four normoxic tests, all of the hypercapnic (HC) conditions (independent of the inspired O2 percent) had statistically lower blood lactate. Hypercapnia was associated with lower R values and increased blood H+. Regression analysis demonstrated relationships between H+ and R, as well as between H+ and blood lactate. These findings are independent of whether 21 or 60% O2 was inspired, and support the hypothesis that acidosis, not PO2, mediates the effects related to HO.


Late coronary stent dislodgement following coronary artery stenting.
Recently, coronary artery stenting has been successful when used as an intervention for percutaneous coronary artery disease. However, the procedure may frequently produce complications. Although rare, stent dislodgement is one such complication, which may result in serious problems including coronary artery dissection, myocardial infarction, peripheral embolisation and death. Stent dislodgement is known to be an early complication of the coronary artery stenting procedure. In this case report, we present a 53-year-old male with late coronary stent dislodgement. To the best of our knowledge, no such case has been addressed in the literature to date.


Congenital Heart Surgery Nomenclature and Database Project: anomalies of the coronary arteries.
The extant nomenclature for coronary artery anomalies is reviewed for the purpose of establishing a unified reporting system. The subject was debated and reviewed by members of the STS-Congenital Heart Surgery Database Committee and representatives from the European Association for Cardiothoracic Surgery. All efforts were made to include all relevant nomenclature categories using synonyms where appropriate. The seven major categories of coronary artery anomalies are: anomalous pulmonary artery origins of the coronaries, anomalous aortic origins of the coronaries, congenital atresia of the left main coronary artery, coronary artery fistulas, coronary artery bridging, coronary aneurysms, and coronary stenosis. A comprehensive database set is presented which is based on a hierarchical scheme. Data are entered at various levels of complexity and detail, which can be determined by the clinician. These data can lay the foundation for comprehensive risk stratification analyses. A minimum database set is also presented, which will allow for data sharing and would lend itself to basic interpretation of trends. Outcome tables relating diagnoses, procedures, and various risk factors are presented.


Pseudoangiomatous stromal hyperplasia with giant cells in the female breast. No association with neurofibromatosis?
A simultaneous finding of pseudoangiomatous stromal hyperplasia (PASH) and stromal multinucleated giant cells (MGC) in mammary tissue was previously observed in patients with type-1 neurofibromatosis, indicating that it can represent a morphologic marker for this syndrome. Here, we present PASH with MGC occurring in the left breast of a 39-years-old woman who does not have neurofibromatosis. This case, along with two additional ones reported previously, indicates that PASH with MGC in the female breast may not be associated with neurofibromatosis.


DNA barcode library for European Gelechiidae (Lepidoptera) suggests greatly underestimated species diversity.
For the first time, a nearly complete barcode library for European Gelechiidae is provided. DNA barcode sequences (COI gene - cytochrome c oxidase 1) from 751 out of 865 nominal species, belonging to 105 genera, were successfully recovered. A total of 741 species represented by specimens with sequences ≥ 500bp and an additional ten species represented by specimens with shorter sequences were used to produce 53 NJ trees. Intraspecific barcode divergence averaged only 0.54% whereas distance to the Nearest-Neighbour species averaged 5.58%. Of these, 710 species possessed unique DNA barcodes, but 31 species could not be reliably discriminated because of barcode sharing or partial barcode overlap. Species discrimination based on the Barcode Index System (BIN) was successful for 668 out of 723 species which clustered from minimum one to maximum 22 unique BINs. Fifty-five species shared a BIN with up to four species and identification from DNA barcode data is uncertain. Finally, 65 clusters with a unique BIN remained unidentified to species level. These putative taxa, as well as 114 nominal species with more than one BIN, suggest the presence of considerable cryptic diversity, cases which should be examined in future revisionary studies.


Stress during pregnancy alters the offspring hypothalamic, pituitary, adrenal, and testicular response to isolation on the day of weaning.
Subjecting pregnant female rats to situations that activate the hypothalamic-pituitary-adrenal (HPA) axis can have long-term effects on the development of the offspring. Restraint under bright lights is a common method of stressing pregnant females that results in consistent behavioral changes in the offspring. We investigated the effects of gestationally administered restraint, bright lights, and heat on the HPA axis response of 21-day-old offspring following exposure to isolation in a novel environment or under resting conditions. Corticotropin-releasing factor titers in the hypothalamus were unaffected following isolation. Nonetheless, adrenocorticotropin hormone (ACTH) was found to be lower in the gestationally stressed offspring prior to or following the isolation period. Corticosterone was attenuated in gestationally stressed offspring following the postnatal stressor and there was also a tendency for the gestationally stressed females to have lower concentrations of aldosterone. Plasmatic testosterone levels were higher in the gestationally stressed males following the period of isolation. The present data suggest that the HPA axis of the offspring is differentially affected by the gestational stress procedure, that is, it is attenuated at the level of the pituitary and adrenal, but not at the level of the hypothalamus. These data have implications for behavioral differences observed in gestationally stressed animals.


Rules versus prototype matching: strategies of perception of emotional facial expressions in the autism spectrum.
When perceiving emotional facial expressions, people with autistic spectrum disorders (ASD) appear to focus on individual facial features rather than configurations. This paper tests whether individuals with ASD use these features in a rule-based strategy of emotional perception, rather than a typical, template-based strategy by considering outcome implications of these strategies. Rule-based strategies are more tolerant of extreme stimuli than are template-based ones. Tolerance for exaggerated emotional facial expressions in individuals with ASD compared to IQ and education matched controls was tested in a forced-choice paradigm. For five of six emotions, those with ASD were more likely to accept the most exaggerated images as most realistic. People with ASD appear to rely more heavily on a rule-based strategy than a template-based strategy in perceiving emotional facial expressions.


Characterization of gallotannins from Astronium species by flow injection analysis- electrospray ionization-ion trap-tandem mass spectrometry and matrix-assisted laser desorption/ionization time-of- flight mass spectrometry.
The species Astronium urundeuva (Allemao) Engl. and Astronium graveolens Jacq., which are used in Brazilian folk medicine to treat allergies, inflammation, diarrhea and ulcers, were investigated for their composition. The aim of this study was to define a rapid and reliable analytical approach, based on the flow-injection analysis-electrospray ionization-ion trap-tandem mass spectrometry (FIA-ESI-IT-MS-MS) and matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-ToF-MS), to investigate the full range of hydrolyzable tannins present in the extracts of these Astronium species. The MALDI-ToF-MS analysis allowed us to ascertain the presence of hydrolysable tannins in both Astronium species as a series of gallotannins with degrees of polymerization of 7 to 13 galloyl units. Moreover, the analysis by FIA-ESI-IT-MS-MS, as well as confirming this result and chemically defining gallotannins as galloylglucose compounds, highlighted the presence of further classes of hydrolysable tannins, such as hexahydrodiphenoyl esters of glucose and some gallic acid derivatives, providing information about their structure by a careful study of their fragmentation patterns. Finally, the evaluation of the number of positional isomers of gallotannins occurring in both Astronium species was obtained by high-performance liquid chromatography-electrospray ionization-ion trap mass spectrometry (HPLC/ESI-IT-MS). This is the first mass spectrometric evidence relating to the existence of gallotannins in Astronium genus.


Origins of altruism diversity II: Runaway coevolution of altruistic strategies via "reciprocal niche construction".
Understanding the evolution of altruism requires knowledge of both its constraints and its drivers. Here we show that, paradoxically, ecological constraints on altruism may ultimately be its strongest driver. We construct a two-trait, coevolutionary adaptive dynamics model of social evolution in a genetically structured population with local resource competition. The intensity of local resource competition, which influences the direction and strength of social selection and which is typically treated as a static parameter, is here allowed to be an evolvable trait. Evolution of survival/fecundity altruism, which requires weak local competition, increases local competition as it evolves, creating negative environmental feedback that ultimately inhibits its further evolutionary advance. Alternatively, evolution of resource-based altruism, which requires strong local competition, weakens local competition as it evolves, also ultimately causing its own evolution to stall. When evolving independently, these altruistic strategies are intrinsically self-limiting. However, the coexistence of these two altruism types transforms the negative ecoevolutionary feedback generated by each strategy on itself into positive feedback on the other, allowing the presence of one trait to drive the evolution of the other. We call this feedback conversion "reciprocal niche construction." In the absence of constraints, this process leads to runaway coevolution of altruism types. We discuss applications to the origins and evolution of eusociality, division of labor, the inordinate ecological success of eusocial species, and the interaction between technology and demography in human evolution. Our theory suggests that the evolution of extreme sociality may often be an autocatalytic process.


Circular RNA 0060745, a Novel circRNA, Promotes Colorectal Cancer Cell Proliferation and Metastasis Through miR-4736 Sponging.
Recent studies have shown that noncoding RNAs (ncRNAs) play essential roles in the development of a number of cancers. Circular RNAs (circRNAs) have been shown to contribute to the progression of colorectal cancer (CRC). In this study, the expression levels of circular RNA 0060745 (circ_0060745), and microRNA 4736 (miR-4736) were measured using qRT-PCR. Kaplan-Meier survival analysis and receiver operating characteristic (ROC) analysis were used to evaluate the diagnostic value of circ_0060745. Transwell assay and cell counting kit-8 (CCK8) assay were used to determine the metastatic and proliferative capacity of CRC cells. The expression of chromosome segregation one like (CSE1L) was measured using Western blotting and immunohistochemistry (IHC). In addition, RNA pull-down assay and luciferase assay were performed to verify the targeted binding between miR-473,6 and circ_0060745, and between as miR-4736 and CSE1L. We showed that circ_0060745 was upregulated in CRC, and was associated with unfavorable clinicopathological characteristics. We also showed that circ_0060745 acted as an oncogene and promoted CRC cell proliferation and metastasis. Circ_0060745 was primarily located in the cytoplasm. Furthermore, miR-4736 was downregulated in CRC, was a downstream target of circ_0060745, and mediated proliferation and metastasis. We showed that circ_0060745 sequestered miR-4736, which resulted in CRC cell proliferation and metastasis. Finally, we showed that CSE1L, a downstream target of miR-4736, was upregulated in CRC and mediated suppression of proliferation and metastasis in CRC. The results of this study showed that circ_0060745 promoted CRC cell proliferation and metastasis via modulation of miR-4736/CSE1L signaling. The Circ_0060745/miR-4736/CSE1L axis might be a novel target for the treatment of CRC.


Rate of cognitive decline in premotor Parkinson's disease: a prospective study (NEDICES).
Previous research has documented cognitive impairment in the early stages of Parkinson's disease (PD). It is not known when this decline starts or if decline progresses at an accelerated rate during the premotor period of the disorder. In this population-based prospective study of older people (≥65 years) from the Neurological Disorders in Central Spain (NEDICES) cohort, we compared the rates of cognitive decline in 3 groups: (1) non-PD elderly controls; (2) prevalent PD patients (those diagnosed with the disease at baseline, 1994-95); and (3) premotor PD subjects (those diagnosed with the disease at follow up, 1997-98, but not at baseline). A 37-item version of the Mini-Mental State Examination (37-MMSE) was administered in the 2 visits of the study. From 2487 participants (age, 72.8 ± 6.0 years), including 2429 controls, we recruited 21 premotor PD cases, and 37 prevalent PD cases. At baseline, the mean 37-MMSE score was 28.5 ± 4.7 in prevalent cases, 28.1 ± 4.6 in premotor cases, and 29.9 ± 5.0 in controls (P = .046). During the 3-year follow-up period, there was a significant score decline of 2.4 ± 4.6 points in prevalent cases versus 0.2 ± 4.1 points in premotor cases and 0.3 ± 4.0 points in controls (Kruskal-Wallis test, P = .03). In the NEDICES cohort, cognitive test scores of prevalent PD cases declined at a rate above and beyond that observed in premotor PD cases and in controls. The rate of cognitive decline in premotor PD and controls was similar. Our data suggest that a decline in global cognitive function does not occur in premotor PD.


COVID-19 Infection and Mortality in State Veterans Homes: A Multilevel Approach.
Some state veterans homes (SVHs) received media attention in the wake of the COVID-19 pandemic because of allegations of poor infection control and excess mortality. However, little research has investigated how these facilities differ from community nursing homes (CNHs) and what the geographical trends of these infection and mortality differences are. We aimed to test (1) whether infection was overall lower in SVHs than CNHs, (2) whether mortality was overall lower in SVHs than CNHs, as well as the geographic distribution of nursing home infection and mortality across the United States. Retrospective nationwide cohort study. Skilled nursing facilities in the United States from May 2020 to July 2022 during the COVID-19 pandemic. Using multilevel negative binomial regression, we modeled COVID-19 infection and mortality rates in skilled nursing homes, testing for overall SVH differences from May 2020 to July 2022, placing random effects on counties to calculate adjusted county-level infection and mortality rates. SVHs experienced 18% fewer cases but 25% more deaths overall compared with CNHs. Counties with the highest levels of facility infection were situated mainly in Midwestern, Atlantic, and Southern states, with the majority of counties with low infection levels in Central and Western states. Counties with the highest levels of facility mortality emerged in Rust Belt and Midwestern states down to Southern states as well as westward to Central and Western states to a lesser degree. SVHs experienced lower infection levels but higher mortality levels than CNHs, and fewer extremely high infection and mortality rates in counties containing SVHs despite higher mortality risk in SVHs, suggesting unobserved facility-level differences such as gender and age distributions and future research opportunities using more granular geographical aggregations to better understand facility-level SVH risk within the broader neighborhood context.


Engineered chitosan for improved 3D tissue growth through Paxillin-FAK-ERK activation.
Scaffold engineering has attracted significant attention for three-dimensional (3D) growth, proliferation and differentiation of stem cells in vitro. Currently available scaffolds suffer from issues such as poor ability for cell adhesion, migration and proliferation. This paper addresses these issues with 3D porous chitosan scaffold, fabricated and functionalized with cysteine-terminated Arg-Gly-Asp (Cys-RGD) tri-peptide on their walls. The study reveals that the compressive moduli of the scaffold is independent to RGD functionalization but shows dependence on the applied freezing temperature (TM) during the fabrication process. The low freezing TM (-80°C) produces scaffold with high compressive moduli (14.64 ± 1.38 kPa) and high TM (-30°C) produces scaffold with low compressive moduli (5.6 ± 0.38 kPa). The Cys-RGD functionalized scaffolds lead to significant improvements in adhesion (150%) and proliferation (300%) of human mesenchymal stem cell (hMSC). The RGD-integrin coupling activates the focal adhesion signaling (Paxillin-FAK-ERK) pathways, as confirmed by the expression of p-Paxillin, p-FAK and p-ERK protein, and results in the observed improvement of cell adhesion and proliferation. The proliferation of hMSC on RGD functionalized surface was evaluated with scanning electron microscopy imaging and distribution though pore was confirmed by histochemistry of transversely sectioned scaffold. The hMSC adhesion and proliferation in scaffold with high compressive moduli showed a constant enhancement (with a slope value 9.97) of compressive strength throughout the experimental period of 28 days. The improved cell adhesion and proliferation with RGD functionalized chitosan scaffold, together with their mechanical stability, will enable new interesting avenues for 3D cell growth and differentiation in numerous applications including regenerative tissue implants.


Mobile community-based active case-finding for tuberculosis among older populations in rural Cambodia.
OBJECTIVE: To systematically screen older rural populations in Cambodia for tuberculosis (TB) and develop an effective active case-finding (ACF) model for this TB high-risk group.DESIGN: A retrospective study using routinely collected programmatic data on community-based ACF among people aged ≥55 years using TB symptoms and systematic chest radiography (CXR) screening, followed by Xpert® MTB/RIF testing for participants with positive screening results and TB culture for certain Xpert-negative specimens.RESULTS: Of 22 101 participants included in the analysis, 7469 (33.8%) were screening-positive and 5960 (27.0%) underwent Xpert testing. Pulmonary TB was identified in 482 (2.2%) individuals: 288 (1.3%) were bacteriologically confirmed (253 using Xpert, 35 using culture) and 194 (0.9%) were clinically diagnosed. Eighty-seven people needed to be screened in order to diagnose one Xpert-positive case. Among the Xpert-positive cases, only 31.6% (80/253) reported cough ≥2 weeks, and 39.9% (101/253) were asymptomatic but had a CXR suggestive of active TB. Treatment uptake was 97.3% (469/482), and treatment success was 88.0% (424/482).CONCLUSIONS: Community-based ACF was effective in detecting and successfully treating older TB patients, most of whom might otherwise have remained undiagnosed. Mobile CXR appears to be crucial in identifying a high number of asymptomatic, bacteriologically confirmed cases.


Edge of Scotoma Sensitivity as a Microperimetry Clinical Trial End Point in USH2A Retinopathy.
Microperimetry is commonly used to assess retinal function. We perform cross-sectional and longitudinal analysis on microperimetry parameters in USH2A retinopathy and explore end points suitable for future clinical trials. Microperimetry was performed using two grids, Grid 1 (18° diameter) and Grid 2 (6° diameter). In Grid 1, four parameters (number of nonscotomatous loci, mean sensitivity [MS], responding point sensitivity [RPS], and edge of scotoma sensitivity [ESS]) were analyzed. In Grid 2, number of nonscotomatous loci and MS were examined. Interocular symmetry was also examined. Longitudinal analysis was conducted in a subset of eyes. Microperimetry could be performed in 16 of 21 patients. In Grid 1 (n = 15; average age, 35.6 years), average number of nonscotomatous loci, MS, RPS, and ESS were 46.6 loci, 10.0 dB, 14.7 and 9.6 dB, respectively. In Grid 2 (n = 13; average age, 37.4 years), 12 eyes had measurable sensitivity across the entire grid. Average MS was 23.8 dB. Interocular analysis revealed large 95% confidence intervals for all parameters. Longitudinally, Grid 1 (n = 12, average follow-up 2.6 years) ESS showed the fastest rate of decline (-1.84 dB/y) compared with MS (-0.34 dB/y) and RPS (-0.90 dB/y). Our data suggest that ESS may be more useful than MS and RPS in test grids that cover a large extent of the macula. We caution the use of contralateral eye as an internal control. ESS may decrease the duration or sample size of treatment trials in USH2A retinopathy.


Spatially Resolved Genetic Analysis of Tissue Sections Enabled by Microscale Flow Confinement Retrieval and Isotachophoretic Purification.
We have developed a method for spatially resolved genetic analysis of formalin-fixed paraffin-embedded (FFPE) cell block and tissue sections. This method involves local sampling using hydrodynamic flow confinement of a lysis buffer, followed by electrokinetic purification of nucleic acids from the sampled lysate. We characterized the method by locally sampling an array of points with a circa 200 μm diameter footprint, enabling the detection of single KRAS and BRAF point mutations in small populations of RKO and MCF-7 FFPE cell blocks. To illustrate the utility of this approach for genetic analysis, we demonstrate spatially resolved genotyping of FFPE sections of human breast invasive ductal carcinoma.


The 'functional muscle-cartilage unit': a reasonable approach to describe a putative relationship between muscle force and longitudinal growth at the forearm in children and adolescents?
Several reports give evidence that the perichondral ossificiation of bone tubes (modeling) strongly depends on muscular forces in children and adolescents. The present analyses intend to investigate the hypothesis that muscular forces also partly determine enchondral ossification and, therefore, longitudinal growth of bone tubes. Analyses were based on a single cross-sectional investigation with peripheral quantitative computed tomography in 296 individuals (age 5-19 years) participating in the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study. Forearm length (FL) was correlated with body height in gender-related subgroups of prepubertal and pubertal individuals (rs between 0.76 and 0.86). Cross-sectional muscle area (MA) increased faster than FL and faster than cross-sectional bone area (BA) close to the distal growth plate in puberty. Close to the growth plate, longitudinal growth was faster than perichondral ossification in females. The ratio MA/BA (surrogate of pressure on the distal growth plate) was correlated with FL in prepubertal boys (r = -0.249, p = 0.043) and pubertal individuals (r = 0.153, p = 0.051). Results support the hypothesis that longitudinal growth precedes modeling at the distal forearm. Confounding variables such as puberty may modify the relationship between muscle forces and longitudinal growth at the forearm in boys.


[Characterization of cookies made with deseeded grape pomace].
Characterization of cookies made with deseeded grape pomace. The objective of this study was to evaluate deseeded grape pomace as a potential ingredient to elaborate some food products. Cookies were made with flour containing four levels of deseeded grape pomace (0, 5, 7.5 and 10%). Moisture, protein, ashes, fat, tannins and dietary fiber contents were determined in both the deseeded of grape pomace and the cookies. Besides, color, sensorial acceptability and biological evaluations of Net Protein Ratio (NPR), Apparent Digestibility (AD) and True Digestibility (TD) of Protein were determined to the cookies. Substantial amounts of dietary fiber and ashes were found in both the deseeded grape pomace and the cookies. Total dietary fiber increased while adding more deseeded grape pomace. Cookies were well accepted as observed in the sensory evaluation, showing no significative differences among the four levels of deseeded grape pomace addition. The addition of deseeded grape pomace imparted a darker color to the cookies. The dark color was greater in the samples containing more fiber which was indicated by the lower L color value. Regarding nutritional analysis, the higher the deseeded grape pomace addition, the lower the NPR, AD, and TD values. The NPR was affected in greater degree, although these differences were not significant. It is possible to use deseeded grape pomace as an ingredient to make high fiber cookies with acceptable sensorial attributes.


Extraction of biomolecules using phosphonium-based ionic liquids + K(3)PO(4) aqueous biphasic systems.
Aqueous biphasic systems (ABS) provide an alternative and efficient approach for the extraction, recovery and purification of biomolecules through their partitioning between two liquid aqueous phases. In this work, the ability of hydrophilic phosphonium-based ionic liquids (ILs) to form ABS with aqueous K(3)PO(4) solutions was evaluated for the first time. Ternary phase diagrams, and respective tie-lines and tie-lines length, formed by distinct phosphonium-based ILs, water, and K(3)PO(4) at 298 K, were measured and are reported. The studied phosphonium-based ILs have shown to be more effective in promoting ABS compared to the imidazolium-based counterparts with similar anions. Moreover, the extractive capability of such systems was assessed for distinct biomolecules (including amino acids, food colourants and alkaloids). Densities and viscosities of both aqueous phases, at the mass fraction compositions used for the biomolecules extraction, were also determined. The evaluated IL-based ABS have been shown to be prospective extraction media, particularly for hydrophobic biomolecules, with several advantages over conventional polymer-inorganic salt ABS.


Expression and characterization of the naturally occurring mutation L394R in human gamma-glutamyl carboxylase.
Patients with mutation L394R in gamma-glutamyl carboxylase have a severe bleeding disorder because of decreased biological activities of all vitamin K-dependent coagulation proteins. Vitamin K administration partially corrects this deficiency. To characterize L394R, we purified recombinant mutant L394R and wild-type carboxylase expressed in baculovirus-infected insect cells. By kinetic studies, we analyzed the catalytic activity of mutant L394R and its binding to factor IX's propeptide and vitamin KH(2). Mutant L394R differs from its wild-type counterpart as follows: 1) 110-fold higher K(i) for Boc-mEEV, an active site-specific, competitive inhibitor of FLEEL; 2) 30-fold lower V(max)/K(m) toward the substrate FLEEL in the presence of the propeptide; 3) severely reduced activity toward FLEEL carboxylation in the absence of the propeptide; 4) 7-fold decreased affinity for the propeptide; 5) 9-fold higher K(m) for FIXproGla, a substrate containing the propeptide and the Gla domain of human factor IX; and 6) 5-fold higher K(m) for vitamin KH(2). The primary defect in mutant L394R appears to be in its glutamate-binding site. To a lesser degree, the propeptide and KH(2) binding properties are altered in the L394R mutant. Compared with its wild-type counterpart, the L394R mutant shows an augmented activation of FLEEL carboxylation by the propeptide.


Extreme resistance as a host counter-counter defense against viral suppression of RNA silencing.
RNA silencing mediated by small RNAs (sRNAs) is a conserved regulatory process with key antiviral and antimicrobial roles in eukaryotes. A widespread counter-defensive strategy of viruses against RNA silencing is to deploy viral suppressors of RNA silencing (VSRs), epitomized by the P19 protein of tombusviruses, which sequesters sRNAs and compromises their downstream action. Here, we provide evidence that specific Nicotiana species are able to sense and, in turn, antagonize the effects of P19 by activating a highly potent immune response that protects tissues against Tomato bushy stunt virus infection. This immunity is salicylate- and ethylene-dependent, and occurs without microscopic cell death, providing an example of "extreme resistance" (ER). We show that the capacity of P19 to bind sRNA, which is mandatory for its VSR function, is also necessary to induce ER, and that effects downstream of P19-sRNA complex formation are the likely determinants of the induced resistance. Accordingly, VSRs unrelated to P19 that also bind sRNA compromise the onset of P19-elicited defense, but do not alter a resistance phenotype conferred by a viral protein without VSR activity. These results show that plants have evolved specific responses against the damages incurred by VSRs to the cellular silencing machinery, a likely necessary step in the never-ending molecular arms race opposing pathogens to their hosts.


HIV-1 RNA genome dimerizes on the plasma membrane in the presence of Gag protein.
Retroviruses package a dimeric genome comprising two copies of the viral RNA. Each RNA contains all of the genetic information for viral replication. Packaging a dimeric genome allows the recovery of genetic information from damaged RNA genomes during DNA synthesis and promotes frequent recombination to increase diversity in the viral population. Therefore, the strategy of packaging dimeric RNA affects viral replication and viral evolution. Although its biological importance is appreciated, very little is known about the genome dimerization process. HIV-1 RNA genomes dimerize before packaging into virions, and RNA interacts with the viral structural protein Gag in the cytoplasm. Thus, it is often hypothesized that RNAs dimerize in the cytoplasm and the RNA-Gag complex is transported to the plasma membrane for virus assembly. In this report, we tagged HIV-1 RNAs with fluorescent proteins, via interactions of RNA-binding proteins and motifs in the RNA genomes, and studied their behavior at the plasma membrane by using total internal reflection fluorescence microscopy. We showed that HIV-1 RNAs dimerize not in the cytoplasm but on the plasma membrane. Dynamic interactions occur among HIV-1 RNAs, and stabilization of the RNA dimer requires Gag protein. Dimerization often occurs at an early stage of the virus assembly process. Furthermore, the dimerization process is probably mediated by the interactions of two RNA-Gag complexes, rather than two RNAs. These findings advance the current understanding of HIV-1 assembly and reveal important insights into viral replication mechanisms.


Comorbidity is an independent prognostic factor in patients with advanced-stage diffuse large B-cell lymphoma treated with R-CHOP: a population-based cohort study.
An observational population-based cohort study was performed to investigate the role of comorbidity on outcome and treatment-related toxicity in patients with newly diagnosed advanced-stage diffuse large B-cell lymphoma (DLBCL) treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). Data for the clinical characteristics of 154 patients (median age 69 years), including Charlson Comorbidity Index (CCI), treatment, toxicity and outcome were evaluated. Forty-five percent of the patients had an International Prognistic index ≥3 and 16% had a CCI ≥2. The planned R-CHOP schedule was completed by 84% and 75% reached complete remission (CR). In those with CCI ≥2, 67% completed treatment with 46% CR. In patients with a CCI <2, overall survival (OS) after 1, 2 and 5 years was 84%, 79% and 65% respectively and it was 64%, 48% and 48% for those with CCI ≥2. Grade III/IV toxicity was documented in 53%, most frequently febrile neutropenia (27%) and infections (23%). In multivariate analysis CCI ≥2 and IPI ≥3 were independent risk indicators for OS and grade III/IV toxicity. In conclusion, comorbidity is an independent risk indicator for worse OS in patients with advanced DLBCL treated with R-CHOP by interference with intensive treatment schedules and more grade III/IV toxicity. Future studies are warranted to determine the optimal treatment approach in patients with significant comorbidities.


[Norwegian newspapers' presentation of Salmonella].
Compared to other microbes, Salmonella gets rather frequent coverage in Norwegian newspapers. This article reports a qualitative content analysis of three Norwegian newspapers' coverage of Salmonella in the period January 1996 to July 1998. We focus on aspects of the "risk image" given to Salmonella, with special emphasis on the type of solutions or measures that are associated with the Salmonella problem. The analysis shows that when a newspaper defines Salmonella as a potential risk in Norway, the responsibility and relevant solutions are placed mainly at the political and to some extent at the central administrative level. When Salmonella is defined as a current risk, there seems to be a shift to central and individual levels. With individual solutions the responsibility for Salmonella illness is placed at the consumers and their personal and food hygiene, and a relevant measure seems to be to educate the consumers to cope with the Salmonella risk themselves. In Norway, Salmonella is a minor health problem compared to other countries. With the ongoing harmonisation between Norwegian and EU regulations, the Salmonella situation may change, and the relevant solutions may then imply a transfer of the responsibility for health to the individual. This raises the question of whether solutions based on individuals bearing responsibility for their personal health are desirable when it comes to such aspects as food, microbes and related risks.


Upper airway collapsibility in habitual snorers and sleep apneics: evaluation with drug-induced sleep endoscopy.
Increased upper airway collapsibility has been suspected of being involved in the pathogenesis of sleep-related diseases. It is assumed that patients with severe obstructive sleep apnea syndrome (OSAS) show a stronger collapse of the upper airway compared with habitual snorers. It was the objective of this study to analyze the patterns of upper airway collapse in habitual snorers and patients with OSAS and to correlate these results with data from polysomnography. Endoscopy was carried out during drug-induced sleep (with propofol) and collapsibility was analyzed at two major levels (palatal and tongue base). A total of 207 habitual snorers and 117 patients with OSAS underwent endoscopy after overnight polysomnography in our sleep laboratory. In 95% of cases we were able to induce snoring during drug-induced sleep. The collapsibility in the area of the base of the tongue correlated with higher values of the respiratory disturbance index (RDI) as recorded by standard polysomnography. Patients with OSAS showed significantly stronger collapsibility compared with snorers. The difference was more evident at the tongue-base level. We found no significant correlation between the applied CPAP pressure and collapsibility in patients with OSAS. These results show that collapsibility at the tongue-base level is a factor relevant in sleep-related breathing disorders.


Electron delocalisation in conjugated sulfur heterocycles probed by resonant Auger spectroscopy.
We propose a novel approach for an indirect probing of conjugation and hyperconjugation in core-excited molecules using resonant Auger spectroscopy. Our work demonstrates that the changes in the electronic structure of thiophene (C4H4S) and thiazole (C3H3NS), occurring in the process of resonant sulfur K-shell excitation and Auger decay, affect the stabilisation energy resulting from π-conjugation and hyperconjugation. The variations in the stabilisation energy manifest themselves in the resonant S KL2,3L2,3 Auger spectra of thiophene and thiazole. The comparison of the results obtained for the conjugated molecules and for thiolane (C4H8S), the saturated analogue of thiophene, has been performed. The experimental observations are interpreted using high-level quantum-mechanical calculations and the natural bond orbital analysis.


Cerebral schistosomiasis: MR and CT appearance.
After returning from Africa, a 54-year-old man began to have episodes of headache and nausea, then a cerebral convulsion. Clinical and laboratory findings and response to chemotherapy indicated the diagnosis of cerebral schistosomiasis. Three lesions were seen on CT and MR studies: two appeared to be subacute intracerebral hematomas, one in the right parietal lobe and one in the frontal lobe; the third lesion, in the cortex of the left occipital lobe, appeared to be a cyst. These lesions could represent small granulomatous tissue reactions with secondary hemorrhages.


Beta-1-adrenoceptor agonists with low adenylate cyclase activation--theoretical and clinical implications.
Several partial beta-agonists such as TA-064, prenalterol, ICI 89,963 and ICI 119,033 possess pronounced positive inotropic effects but induce only limited activation of myocardial adenylate cyclase; this results in low cyclic AMP levels. Partial agonists, as compared to isoproterenol, need high receptor occupancy for maximal physiological response, and demonstrate inadequate coupling between receptor and adenylate cyclase. However, the biochemical mechanisms which generate the final biological effects originating from cyclic AMP are tissue-specific, and for that reason, can maintain a pronounced positive inotropic action. Clinical data with TA-064 and prenalterol have established positive inotropic effects without significant changes in heart rate. Partial beta-agonists with diminished cyclic AMP may be less arrhythmogenic than full beta-agonists. The clinical importance of partial beta-1-agonists remains to be established, particularly with relevance to long-term exposure and inherent beta blockade.


Strategies for Attention to Diversity: Perceptions of Secondary School Teaching Staff.
(1) Background: Attention to diversity constitutes an aspect that influences system quality and offers a perspective of the capacity of educational centres to respond to educational needs. The present study carried out an examination of the perceptions held by secondary school teachers and the level of importance conferred by them to the variables that should be integrated into plans and will influence the degree of compliance. (2) Methods: Quantitative descriptive research was performed using a survey to collect data from teachers at schools that had a Quality Management System available. (3) Results: Interaction with families is necessary to agree upon the centre's objectives to address diversity and to define an optimisation strategy for resources in virtue of their availability within the centre. It is key to establish an appropriate teacher-student ratio to encourage compliance. (4) Conclusions: Teachers are the great pillars of quality education. Their perceptions are the route through which deficient aspects and the dimensions that must be improved when formulating these strategies can be recognised with attention to diversity.


Incomitant strabismus associated with instability of rectus pulleys.
Connective tissue pulleys serve as functional mechanical origins of the extraocular muscles (EOMs) and are normally stable relative to the orbit during gaze shifts. This study evaluated pulley stability in incomitant strabismus. Contiguous 2- or 3-mm thick magnetic resonance images (MRIs) perpendicular to the orbital axis spanned the anteroposterior extents of 12 orbits of six patients with incomitant strabismus. Imaging was performed in central gaze, supraduction, infraduction, abduction, and adduction. Rectus EOM paths were defined by their area centroids and plotted in a normalized, oculocentric coordinate system. Paths of EOMs ran toward the pulleys. Sharp EOM path inflections in secondary gaze indicated pulley locations in three dimensions. MRI revealed substantial inferior shift of the lateral rectus (LR) pulley of up to 1 mm during vertical gaze shifts in patients with axial high myopia and a posterior shift from abduction to adduction in simulated Brown syndrome. There was substantial LR pulley shift opposite the direction of vertical gaze in a subject with X-pattern exotropia who had undergone repeated LR surgery. The medial rectus (MR) pulley shifted inferiorly with gaze elevation in Marfan syndrome. Pulley instability was associated with significantly increased globe translation during gaze shifts. Pulley instability, resulting in EOM sideslip during ductions, occurs in some cases of incomitant strabismus. Resultant patterns of strabismus may depend on static pulley positions, pulley instability, and coexisting globe translation that alters pulley locations relative to the globe. Translational instability of pulleys and the globe could produce abnormalities in actions of otherwise normal EOMs, and connective tissue disorders causing these instabilities should be considered as potential causes of strabismus.


Does intestinal anastomosis in resection of colon cancer have a significant impact onto early postoperative outcome and long-term survival?
To investigate the influence of anastomosis on the early postoperative and long-term oncological outcomes of patients with primary colon carcinoma (CA). All consecutive patients with the histologically diagnosed primary colon CA (design, prospective multicenter observational study) were registered with regard to patient-, diagnostic-, tumor (Tu) finding-, and treatment-related aspects using a computer-based registry with 60 items to characterize early postoperative and long-term oncological outcome. Basic data: From 2010 to 2016, data from a total of 14,466 patients were documented (mean age, 72.8 [range, 22-96] years; sex ratio, m:f=7,696:6,770). - 717/14,466 patients (4.96 %) were included in a matched-pair analysis. The majority of these patients underwent elective surgery (n=12,620 patients; 87.2 %) regardless of whether a bowel anastomosis or an ostomy was created. In emergency surgery, a bowel anastomosis was possible in a large proportion (n=1,332 patients [72.1 %]). In contrast, in 514 patients (27.9 %) who underwent emergency surgery, an ostomy was created. Interestingly, ostomy had to be created even less frequently in patients who had undergone planned surgery (n=366 [2.5 %]). - Early postoperative outcome: Cases of postoperative mortality were mainly due to general complications. Especially among the patients treated in an emergency situation without intestinal anastomosis, a high proportion died of their pre-existing condition (17.0 %). Patients who underwent ostomy creation or emergency surgery had a worse risk profile (incl. arterial hypertension, diabetes mellitus, and secondary cardiac or renal diseases) which led to the decision to operate without anastomosis. Furthermore, data show no matter which technique had been used, patients that had undergone surgical intervention without anastomosis were more likely to develop complications. - Long-term oncosurgical outcome: The most important factors influencing long-term survival were age, resection status, and tumor stage (according to TNM and UICC). The more advanced the tumor growth, the lower the long-term survival. Patients categorized with the same tumor stage, age, and risk factors had a better chance of survival, if they underwent elective surgical intervention and with intestinal anastomosis. Interestingly, the multivariable analysis showed that older patients and such with distant metastasis benefit from a discontinuity resection. The association of intraoperative and postoperative complications with increased postoperative mortality, as well as preexisting risk factors and perioperative complications is in line with findings of current studies. Furthermore, current studies also agree that older patients and such with reduced general condition benefit from discontinuity resection.


Algae metabolites: from in vitro growth inhibitory effects to promising anticancer activity.
Covering: 1957 to 2017 Algae constitute a heterogeneous group of eukaryotic photosynthetic organisms, mainly found in the marine environment. Algae produce numerous metabolites that help them cope with the harsh conditions of the marine environment. Because of their structural diversity and uniqueness, these molecules have recently gained a lot of interest for the identification of medicinally useful agents, including those with potential anticancer activities. In the current review, which is not a catalogue-based one, we first highlight the major biological events that lead to various types of cancer, including metastatic ones, to chemoresistance, thus to any types of current anticancer treatment relating to the use of chemotherapeutics. We then review algal metabolites for which scientific literature reports anticancer activity. Lastly, we focus on algal metabolites with promising anticancer activity based on their ability to target biological characteristics of cancer cells responsible for poor treatment outcomes. Thus, we highlight compounds that have, among others, one or more of the following characteristics: selectivity in reducing the proliferation of cancer cells over normal ones, potential for killing cancer cells through non-apoptotic signaling pathways, ability to circumvent MDR-related efflux pumps, and activity in vivo in relevant pre-clinical models.