Development of a health-related lifestyle self-management intervention for patients with coronary heart disease.
Risk-factor modification after an acute coronary event is imperative, and intervention strategies are continuously being developed to assist patients with behavioral change and, consequently, decreasing the risk of further coronary episodes. This article describes the development of the health-related lifestyle self-management (HeLM) intervention, which is a brief structured intervention embedded within the transtheoretical model of behavioral change. The HeLM intervention was developed by undertaking three discrete yet interrelated studies and consisted of the following components: goal-setting, the HeLM booklet, feedback regarding personal risk, team-building and communication with the patient's family physician, three supportive telephone calls, trained interviewers, a refrigerator magnet, and a health diary for self-monitoring. The HeLM intervention has been successfully implemented in 50 patients with acute coronary syndrome after discharge from hospital and has been demonstrated to be feasible and practical and could easily be delivered by health care professionals.


Safety and Efficacy Profile of Corneas Harvested From Donors of Drowning Victims.
The aim of this study was to analyze the tissue quality and outcomes of corneal transplants from donor corneal tissues harvested from drowning victims. This retrospective study was conducted on corneal tissues harvested from drowning victims between March 2018 and September 2022. Details of the tissue quality and outcomes after keratoplasty were collected from the eye bank and outpatient records. Thirty-four donor corneas were collected from drowning victims during the study period. The mean age of the donors was 37.1 ± 20.3 years. The mean donor-to-preservation time was 4.9 ± 2.6 hours. The mean endothelial cell density was 3025 ± 271 cells/mm2. Twenty donor corneas (58.8%) were used at our institute, 2 were stored in glycerol for future use, and 12 were transported to other transplant centers. The overall utilization was 94.1% (32/34 corneas). Of the 20 corneas used at our institute, 17 were used for optical grafts and 3 for therapeutic indications. Of the 17 optical grafts, 10 were used for optical penetrating keratoplasty, 6 for endothelial keratoplasty, and 1 for anterior lamellar keratoplasty. The most common indication for keratoplasty was regrafting the previously failed grafts (25%). None of the transplanted eyes developed an infection in the immediate postoperative period. Eight eyes had clear grafts after 3 months. Of the 12 tissues transferred to other keratoplasty centers, 10 were used for optical grafts and 2 for therapeutic/tectonic grafts. Donor corneas retrieved from drowning victims may be considered safe for transplantation. The postoperative outcomes of the tissues obtained from these donors were satisfactory. Hence, these donor corneas can be optimally used in routine transplantation procedures.


Photophysical study of spiro-bifluorene bridged Pt(II), Os(II) and Ir(III) luminescent complexes and supramolecular arrays.
This paper describes expeditious stepwise synthesis of polynuclear complexes based on heteroleptic iridium(iii) and osmium(ii) fragments linked to a central Pt(ii) module via a spirobifluorene-bridge using a strategy based on the construction of preformed complexes. The luminescence features of the final multi-chromophoric array, i.e. a tetrad consisting of spirobifluorene-bridged Pt, Ir and Os complexes, have been studied by comparison with the features of reference complexes bearing two identical luminophores (Ir or Os) at the periphery. The (3)MPtLCT and (3)LC states of the Pt and spiro ligand undergo fast energy transfer into the (3)MIrLCT or the (3)MOsLCT state in the Pt-M2 (M = Ir or Os) arrays, whereas the (3)LC and the (3)MPtLCT states function as energy reservoirs for the metal excited states close in energy, resulting in a pronounced increase of the excited state lifetimes of these arrays. The tetrad efficiently works as an antenna system where the collected light energy is transferred to the Os unit acting as the final collector.


[Gerontologic nursing: reflexion on the work process].
This article had the objective to reflect about Gerontology Nursing subsided on the work process approach, according to Marx. It is a bibliographical study in which Gerontology Nursing concepts, theoretical arguments, objectives and work process are verified. The results point out that it has as purpose to promote health, prevent diseases, give specific care, recovery and rehabilitation of the elderly, maintaining their functional capacity; as object the older human being and the aging process in itself; as instrumental the specific knowledge about the object, the instruments and the conducts directed to the elder; as product the elder taking care of him/herself and, under that impossibility, being suitable cared by his/her family in an humanistic way, keeping his/her dignity until death. From the reflections done, we applied the learned concepts about the Gerontology Nursing work process, trying to awaken to the importance of including Gerontology subjects while forming Nursing professionals.


[Uterine collagens. General review].
Several collagen types (mainly types I, III, V and VI), elastin, fibronectin and some proteoglycans are active constituents of uterine myometer. They surround and associate smooth muscle cells. The type I collagen biosynthesis in the uterus is under the positive control of estrogens that in addition repress the collagenase secretion and in this way prevent collagen from degradation. The cervical softening and dilation are caused by a progressive degradation of collagen and by the synthesis of an additional proteoglycan that separates and disorganizes the collagen fibres. Prostaglandin E2 and relaxin participate in the activation of collagenases. After delivery, the drop in estrogens and progesterone permits collagenases to rapidly degrade uterine collagen in excess.


Multiplex polymerase chain reaction as an improved method for screening Histoplasma capsulatum mating types.
Histoplasmosis is a systemic mycosis infection caused by Histoplasma capsulatum, a heterothallic ascomycete. The sexual reproduction of this fungus is regulated by the mating type (MAT1) locus that contains MAT1-1 and MAT1-2 idiomorphs, which were identified by uniplex polymerase chain reaction (PCR). This study aimed to optimise single-step multiplex PCR for the accurate detection of the distinct mating types of H. capsulatum. Among the 26 isolates tested, 20 had MAT1-1 genotype, while six showed MAT1-2 genotype, in agreement with the uniplex PCR results. These results suggest that multiplex PCR is a fast and specific tool for screening H. capsulatum mating types.


IGFALS gene dosage effects on serum IGF-I and glucose metabolism, body composition, bone growth in length and width, and the pharmacokinetics of recombinant human IGF-I administration.
Acid labile subunit (ALS) deficiency, caused by IGFALS mutations, is a subtype of primary IGF-I deficiency (PIGFD) and has been associated with insulin resistance (IR) and osteopenia. Whether patients respond to recombinant human IGF-I (rhIGF-I) is unknown. This study determined the 14-hour pharmacokinetic response of free and total IGF-I and IGF binding protein 3 (IGFBP-3) to a single sc dose of rhIGF-I (120 μg/kg) in four ALS-deficient patients, compared with severe PIGFD, moderate PIGFD, and controls. Intravenous glucose tolerance tests, fasting blood levels, dual-energy X-ray absorptiometry, peripheral quantitative computed tomography, and metacarpal radiogrammetry were performed in the four patients and 12 heterozygous family members. IGF-I and IGFBP-3 increased above baseline (P < .05) for 2.5 hours, returning to baseline 7 hours after rhIGF-I injection. Mean (SD) IGF-I Z-score increased by 2.49 (0.90), whereas IGFBP-3 Z-score increased by 0.57 (0.10) only. IGF-I elimination rates in ALS deficiency were similar, but the IGF-I increment was lower than those for severe PIGFD. Significant gene dosage effects were found for all IGF-I peptides, height, forearm muscle size, and metacarpal width. Bone analysis showed that ALS deficiency creates a phenotype of slender bones with normal size-corrected density. Abnormal glucose handling and IR was found in three of four patients and 6 of 12 carriers. These gene dosage effects demonstrate that one functional IGFALS allele is insufficient to maintain normal ALS levels, endocrine IGF-I action, full growth potential, muscle size, and periosteal expansion. Similar gene dosage effects may exist for parameters of IR. Despite similar IGF-I elimination compared with severe PIGFD, ALS-deficient patients cannot mount a similar response. Alternative ways of rhIGF-I administration should be sought.


[Intravascular blood aspiration in large and giant parawedge aneurysm surgery].
The efficiency of a procedure of intravascular blood aspiration (IVBA) in patients with large and giant parawedge aneurysms of the internal carotid. The study was based on the analysis of clinical data and outcomes of surgical treatment in 20 patients with the aneurysms. The paper presents different procedures for IVBA, a complex of methods for preoperative examination of patients and intraoperative prediction of possible ischemic complications and defines indications for the IVBA procedure. Complete and partial aneurysm exclusion was achieved in 15 (75%) and 2 (10%) patients; the neck and walls of aneurysm were strengthened with surgical gauze in 2 (10%) patients. Incompetent clipping was observed in one case. There was recovery in 17 (85%), improvement in 2 (10%), 1 (5%) patients. No deaths occurred. The IVBA procedure for aneurysm is indicated for large and giant thin-walled non-thrombotic aneurysms of the parawedge carotid segment. It permit effective proximal monitoring of carotid blood flow and creates favourable conditions for preparing and excluding aneurysm, and, if necessary, forming a carotid lumen. Intraoperative monitoring of brain function is highly important and obligatory for early prediction and prevention of ischemic complications. Under intraoperative monitoring of brain function, fractional IVBA makes it effective even if collateral circulation is inadequate.


Modulation of Toll-like receptor activity by leukocyte Ig-like receptors and their effects during bacterial infection.
Toll-like receptors (TLRs) are a potent trigger for inflammatory immune responses. Without tight regulation their activation could lead to pathology, so it is imperative to extend our understanding of the regulatory mechanisms that govern TLR expression and function. One family of immunoregulatory proteins which can provide a balancing effect on TLR activity are the Leukocyte Ig-like receptors (LILRs), which act as innate immune receptors for self-proteins. Here we describe the LILR family, their inhibitory effect on TLR activity in cells of the monocytic lineage, their signalling pathway, and their antimicrobial effects during bacterial infection. Agents have already been identified which enhances or inhibits LILR activity raising the future possibility that modulation of LILR function could be used as a means to modulate TLR activity.


Modularity: genes, development and evolution.
Modularity has emerged as a central concept for evolutionary biology, providing the field with a theory of organismal structure and variation. This theory has reframed long standing questions and serves as a unified conceptual framework for genetics, developmental biology and multivariate evolution. Research programs in systems biology and quantitative genetics are bridging the gap between these fields. While this synthesis is ongoing, some major themes have emerged and empirical evidence for modularity has become abundant. In this review, we look at modularity from an historical perspective, highlighting its meaning at different levels of biological organization and the different methods that can be used to detect it. We then explore the relationship between quantitative genetic approaches to modularity and developmental genetic studies. We conclude by investigating the dynamic relationship between modularity and the adaptive landscape and how this potentially shapes evolution and can help bridge the gap between micro- and macroevolution.


Lower functional hippocampal connectivity in healthy adults is jointly associated with higher levels of leptin and insulin resistance.
Metabolic dysregulation is currently considered a major risk factor for hippocampal pathology. The aim of the present study was to characterize the influence of key metabolic drivers on functional connectivity of the hippocampus in healthy adults. Insulin resistance was directly quantified by measuring steady-state plasma glucose (SSPG) concentration during the insulin suppression test and fasting levels of insulin, glucose, leptin, and cortisol, and measurements of body mass index and waist circumference were obtained in a sample of healthy cognitively intact adults (n = 104). Resting-state neuroimaging data were also acquired for the quantification of hippocampal functional cohesiveness and integration with the major resting-state networks (RSNs). Data-driven analysis using unsupervised machine learning (k-means clustering) was then employed to identify clusters of individuals based on their metabolic and functional connectivity profiles. K-means clustering identified two clusters of increasing metabolic deviance evidenced by cluster differences in the plasma levels of leptin (40.36 (29.97) vs. 27.59 (25.58) μg/L) and the degree of insulin resistance (SSPG concentration: 161.63 (65.27) vs. 125.72 (66.81) mg/dL). Individuals in the cluster with higher metabolic deviance showed lower functional cohesiveness within each hippocampus and lower integration of posterior and anterior components of the left and right hippocampus with the major RSNs. The two clusters did not differ in general intellectual ability or episodic memory. We identified two clusters of individuals differentiated by abnormalities in insulin resistance, leptin levels, and hippocampal connectivity, with one of the clusters showing greater deviance. These findings support the link between metabolic dysregulation and hippocampal function even in nonclinical samples.


Comparison of the antibacterial effects of matrica & Persica™ and chlorhexidine gluconate mouthwashes in mechanically ventilated ICU patients: a double blind randomized clinical trial.
Accumulation of bacteria in the pharynx is one of the risk factors of pneumonia due to ventilation. One of the methods of prevention from accumulation of bacteria in the pharynx is the use of oral solutions. Chlorhexidine is considered as the gold standard, but it has various side effects. Present study was aimed to determine and compare anti-bacterial effects of the chlorhexidine gluconate 0.2%, herbal mouthwash of Matrica® (chamomile extracts) 10%, PersicaTM 10% and normal saline in intensive care unit patients. In this double blind randomized clinical trial, 80 patients who were admitted in ICU divided into four groups of 20 patients each one. Researchers applied PersicaTM to group one, chlorhexidine gluconate mouth wash 0.2% to group two and third group received Matrica, finally in the control group, normal saline were used. In order to culturing of Staphylococcus aureus and S. pneumoniae,salivary samples were obtained without any stimulation after six minimums oral rinsing. The data were processed in SPSS17 software and analyzed by appropriate statistical tests. Decreased rate of bacterial colonies after intervention in the whole four groups was significant (p < 0.001). The mouth wash of chlorhexidine (p < 0.001), PersicaTM (p: 0.008) and Matrica (p: 0.01) had a significant antibacterial effect on S. aureus and S. pneumoniae(p < 0.001). Herbal oral mouthwash of persica and matrica has the effect on S. pneumoniae and S. aureus of oropharynx area in mechanically ventilated patients. However, there is a need for further research to be considered as an alternative to chlorhexidine for prevention of VALP in ICU patients.


Performance of ordered-subset reconstruction algorithms under conditions of extreme attenuation and truncation in myocardial SPECT.
We studied the bias and variance characteristics of the ordered-subset expectation maximization (OSEM) and rescaled block-iterative EM (RBIEM) iterative reconstruction algorithms in myocardial SPECT under extreme, but realistic, conditions. We used the 2-dimensional mathematic cardiac torso phantom to simulate 2 patient anatomies: a large male with a raised diaphragm and a female with large breast size, approximating extreme cases of attenuation conditions found in the clinic. For each anatomy, realistic 201Tl projection data were simulated for a 180 degrees acquisition arc. Three cases of truncation for a 90 degrees-configured dual detector system were simulated: no truncation, moderate truncation, and extreme truncation. For each case, an ensemble of 250 noise simulations was generated, and each noisy dataset was reconstructed with the OSEM and RBIEM algorithms. The reconstructions modeled only the effects of nonuniform attenuation and used a range of subset configurations. Over the ensemble, we computed means and variances of activity in 8 regions of interest (ROIs) in the heart as a function of iteration. Under conditions of no truncation and moderate truncation, the results from OSEM and RBIEM were very close to those from maximum-likelihood EM (MLEM); in all cases, the difference in ROI means was <2.5%. For extreme truncation, the errors increased to as much as 11% with OSEM, but these were no greater than the errors for MLEM under the same conditions. The OSEM algorithm with 2 views per subset was found to result in much higher variance of ROI estimates for the same bias as compared with RBIEM or OSEM with 4 or more views per subset. The OSEM and RBIEM algorithms are at least as robust to highly attenuating patients and truncation as MLEM algorithm and can be adequate substitutes for MLEM, even in extreme cases. Clinical users should apply the smallest number of subsets that can be accommodated by allowable processing time to reduce image noise and variance in quantitative estimates.


Correlation Between the Social Network Structure and Well-Being of Health Care Workers in Intensive Care Units: Prospective Observational Study.
Effective communication strategies are becoming increasingly important in intensive care units (ICUs) where patients at high risk are treated. Distributed leadership promotes effective communication among health care professionals (HCPs). Moreover, beyond facilitating patient care, it may improve well-being among HCPs by fostering teamwork. However, the impact of distributed leadership on the communication structure and well-being of HCPs remains unclear. We performed a social network analysis (SNA) to assess the characteristics of each HCP in the network, identify the number of HCP connections, analyze 4 centralities that can measure an HCP's importance, and evaluate the impact of distributed leadership structure on the well-being and communication structure of the medical staff. Wearable sensors were used to obtain face-to-face interaction data from the ICU medical staff at Mie University Hospital, Japan. Participants wore a badge on the front of their clothing during working hours to measure the total frequency of face-to-face interactions. We collected data about the well-being of medical staff using the Center for Epidemiological Studies-Depression (CES-D) questionnaire and measured 4 centralities using SNA analysis. A CES-D questionnaire was administered during the study to measure the well-being of the HCPs. Overall, 247 ICU workers participated in this clinical study for 4 weeks yearly in February 2016, 2017, and 2018. The distributed leadership structure was established within the ICU in 2017 and 2018. We compared these results with those of the traditional leadership structure used in 2016. Most face-to-face interactions in the ICU were among nurses or between nurses and other professionals. In 2016, overall, 10 nurses could perform leadership tasks, which significantly increased to 24 in 2017 (P=.046) and 20 in 2018 (P=.046). Considering the increased number of nurses who could perform leadership duties and the collaboration created within the organization, SNA in 2018 showed that the betweenness (P=.001), degree (P<.001), and closeness (P<.001) centralities significantly increased compared with those in 2016. However, the eigenvector centrality significantly decreased in 2018 compared with that in 2016 (P=.01). The CES-D scores in 2018 also significantly decreased compared with those in 2016 (P=.01). The betweenness (r=0.269; P=.02), degree (r=0.262; P=.03), and eigenvector (r=0.261; P=.03) centralities and CES-D scores were positively correlated in 2016, whereas the closeness centrality and CES-D scores were negatively correlated (r=-0.318; P=.01). In 2018, the degree (r=-0.280; P=.01) and eigenvector (r=-0.284; P=.01) centralities were negatively correlated with CES-D scores. Face-to-face interactions of HCPs in the ICU were measured using wearable sensors, and nurses were found to be centrally located. However, the introduction of distributed leadership created collaboration and informal leadership in the organization, altering the social network structure of HCPs and increasing organizational well-being. University Hospital Medical Information Network (UMIN) UMIN000037046; https://center6.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000042211.


Current concepts review - fractures in the region of the elbow.
Elbow injuries continue to rise with increased athletic activity and life expectancy. Knowledge of anatomy and biomechanics of this sophisticated joint, various injury patterns, and the implication of injury to the static and dynamic stabilizers will result in improvement in specific diagnosis, and therapy. The surgical treatment of trauma to the adult elbow has evolved rapidly in recent years and many useful concepts and techniques have been established. This paper reviews the published scientific data and current opinion available to guide patient care.


Phosphocholine-containing, zwitterionic glycosphingolipids of adult Onchocerca volvulus as highly conserved antigenic structures of parasitic nematodes.
Human Onchocerca volvulus infection sera were found to recognize zwitterionic glycolipids of O. volvulus and to cross-react with those of other parasitic nematodes (Ascaris suum, Setaria digitata and Litomosoides sigmodontis). By the use of an epitope-specific monoclonal antibody, zwitterionic glycolipids of all these nematode species were observed to contain the antigenic determinant phosphocholine. A hyperimmune serum specific for arthro-series glycolipid structures reacted with the various neutral glycolipids of all these nematodes, which demonstrated that their oligosaccharide moieties belonged to the arthro-series of protostomial glycolipids. These results indicated that arthro-series glycosphingolipids carrying, in part, phosphocholine substituents, represent highly conserved, antigenic glycolipid markers of parasitic nematodes. Three glycolipid components of the O. volvulus zwitterionic fraction were structurally characterized by matrix-assisted laser-desorption/ionization time-of-flight MS, methylation analysis and exoglycosidase treatment. Their chemical structures were elucidated to be phosphocholine-6GlcNAc(beta1-3)Man(beta1-4)Glc(1-1)ceramide, GalNAc(beta1-4)[phosphocholine-6]GlcNAc(beta1-3)Man(beta1-4)Glc(1-1) ceramide and Gal(alpha1-3)GalNAc(beta1-4)[phosphocholine-6]GlcNAc(beta1-3)Man(beta 1-4)Glc(1-1)ceramide for the zwitterionic ceramide tri-, tetra- and penta-hexosides respectively. The ceramide composition was found to be dominated by 2-hydroxylated docosanoic (C(22h:0)), tricosanoic (C(23h:0)) and tetracosanoic (C(24h:0)) acids, and C(17) sphingosine (C(d17:1)) (where (h) is hydroxylated and (d) is dihydroxylated).


Initial evaluation of the Older Adult Social-Evaluative Situations Questionnaire: a measure of social anxiety in older adults.
The assessment of social anxiety in late life has been examined in few studies (e.g. Gretarsdottir et al., 2004; Ciliberti et al., 2011). The present study describes the creation and initial psychometric evaluation of a new, content valid measure of social anxiety for older adults, the Older Adult Social-Evaluative Situations Questionnaire (OASES). Psychometric properties of the OASES were evaluated in a community dwelling sample of older adults (N = 137; 70.8% female). Convergent validity was established by examining the relation between the OASES and the Liebowitz Social Anxiety Scale (LSAS), Social Phobia and Anxiety Inventory (SPAI), and Beck Anxiety Inventory (BAI). Discriminant validity was established by examining the relation between the OASES and measures of depression (Geriatric Depression Scale, GDS), perceived health status (Short Form Health Survey, SF-12), and demographic variables. The validity analyses of the OASES were based on a smaller sample with n values ranging from 98 to 137 depending on missing data on each questionnaire. Internal consistency, measured by Cronbach's α, for the OASES total score was 0.96. All items on the OASES were endorsed by participants. Convergent validity was demonstrated by medium to large correlations with the SPAI, LSAS, and BAI. Support for discriminant validity was evidenced by small to medium correlations between the OASES and GDS, SF-12, and demographic variables. Evidence in support of convergent and discriminant validity of the OASES is discussed. Although the results from the present study suggest that this measure may assess anxiety in and avoidance of social situations salient to older adults, future studies are needed to further examine the psychometric properties of the OASES and replicate these results in both clinical and more diverse samples of older adults.


[Temporal code constants--a link between psychology and physiology in research of cognitive processes? Hypotheses and considerations of quantum structures in alpha activity of the brain].
Temporal code invariants as possible links between psychological and physiological characteristics of cognition: a tentative time quantum approach. Relationships between alpha activity and short-term memory performance are discussed referring to an approach suggested by Lebedev and Lutzky (1973). These authors suggest a secondary relationship in considering processing as well as storing of information as a result of the superposition of oscillatory processes which differ from one another an elementary period (relative refractoriness) specific to individuals. Some specifications of scan rate and STM span suggested by the authors seem to be untenable for empirical and logical reasons. Alternative explanations are proposed referring to the time quantum model (TQM) by Geissler (1985, 1987, 1990, 1991). Straight forward expansions of this model lead to the hypothesis of an "alpha band" consisting of 9 discrete frequencies. Predictions on scanning rhythms can be derived from this via the assumption that these represent segmentations caused by pairwise resonance. A modification of the Lebedev-Lutzky assumption on spans is proposed assuming an optimum code for stored information.


Inhibition of long myosin light-chain kinase activation alleviates intestinal damage after binge ethanol exposure and burn injury.
Laboratory evidence suggests that intestinal permeability is elevated following either binge ethanol exposure or burn injury alone, and this barrier dysfunction is further perturbed when these insults are combined. We and others have previously reported a rise in both systemic and local proinflammatory cytokine production in mice after the combined insult. Knowing that long myosin light-chain kinase (MLCK) is important for epithelial barrier maintenance and can be activated by proinflammatory cytokines, we examined whether inhibition of MLCK alleviated detrimental intestinal responses seen after ethanol exposure and burn injury. To accomplish this, mice were given vehicle or a single binge ethanol exposure followed by a sham or dorsal scald burn injury. Following injury, one group of mice received membrane permeant inhibitor of MLCK (PIK). At 6 and 24 h postinjury, bacterial translocation and intestinal levels of proinflammatory cytokines were measured, and changes in tight junction protein localization and total intestinal morphology were analyzed. Elevated morphological damage, ileal IL-1β and IL-6 levels, and bacterial translocation were seen in mice exposed to ethanol and burn injury relative to either insult alone. This increase was not seen in mice receiving PIK after injury. Ethanol-exposed and burn-injured mice had reduced zonula occludens protein-1 and occludin localization to the tight junction relative to sham-injured mice. However, the observed changes in junctional complexes were not seen in our PIK-treated mice following the combined insult. These data suggest that MLCK activity may promote morphological and inflammatory responses in the ileum following ethanol exposure and burn injury.


Abelisauridae (Dinosauria: Theropoda) from the Late Jurassic of Portugal and dentition-based phylogeny as a contribution for the identification of isolated theropod teeth.
Theropod dinosaurs form a highly diversified clade, and their teeth are some of the most common components of the Mesozoic dinosaur fossil record. This is the case in the Lourinhã Formation (Late Jurassic, Kimmeridgian-Tithonian) of Portugal, where theropod teeth are particularly abundant and diverse. Four isolated theropod teeth are here described and identified based on morphometric and anatomical data. They are included in a cladistic analysis performed on a data matrix of 141 dentition-based characters coded in 60 taxa, as well as a supermatrix combining our dataset with six recent datamatrices based on the whole theropod skeleton. The consensus tree resulting from the dentition-based data matrix reveals that theropod teeth provide reliable data for identification at approximately family level. Therefore, phylogenetic methods will help identifying theropod teeth with more confidence in the future. Although dental characters do not reliably indicate relationships among higher clades of theropods, they demonstrate interesting patterns of homoplasy suggesting dietary convergence in (1) alvarezsauroids, therizinosaurs and troodontids; (2) coelophysoids and spinosaurids; (3) compsognathids and dromaeosaurids; and (4) ceratosaurids, allosauroids and megalosaurids. Based on morphometric and cladistic analyses, the biggest tooth from Lourinhã is referred to a mesial crown of the megalosaurid Torvosaurus tanneri, due to the elliptical cross section of the crown base, the large size and elongation of the crown, medially positioned mesial and distal carinae, and the coarse denticles. The smallest tooth is identified as Richardoestesia, and as a close relative of R. gilmorei based on the weak constriction between crown and root, the "eight-shaped" outline of the base crown and, on the distal carina, the average of ten symmetrically rounded denticles per mm, as well as a subequal number of denticles basally and at mid-crown. Finally, the two medium-sized teeth belong to the same taxon and exhibit pronounced interdenticular sulci between distal denticles, hooked distal denticles for one of them, an irregular enamel texture, and a straight distal margin, a combination of features only observed in abelisaurids. They provide the first record of Abelisauridae in the Jurassic of Laurasia and one of the oldest records of this clade in the world, suggesting a possible radiation of Abelisauridae in Europe well before the Upper Cretaceous.


[Continuity of care of patient with diabetes and its affecting factors in Korea].
The objectives of this study were to estimate the continuity of care for all Koreans with diabetes and to identify factors affecting the continuity of care. We obtained National Health Insurance claims data for patients with diabetes who visited health-care providers during the year 2004. A total of 1,498,327 patients were included as study subjects. Most Frequent Provider Continuity (MFPC) and Modified, Modified Continuity Index (MMCI) were used as indexes of continuity of care. A multiple linear regression analysis was used to identify factors affecting continuity of care. The average continuity of care in the entire population of 1,498,327 patients was 0.89 +/- 0.17 as calculated by MFPC and 0.92 +/- 0.16 by MMCI. In a multiple linear regression analysis, both MFPC and MMCI were lower for females than males, disabled than non-disabled, Medicaid beneficiaries than health insurance beneficiaries, patients with low monthly insurance contributions, patients in rural residential areas, and patients whose most frequently visited provider is the hospital. The continuity of care for patients with diabetes is high in Korea. However, women, the disabled and people of low socio-economic status have relatively low continuity of care. Therefore, our first priority is to promote a diabetes management program for these patients.


Systemic low-grade inflammation in post-traumatic stress disorder: a systematic review.
Studies examining post-traumatic stress disorder (PTSD) have either emphasized a relationship between PTSD and a systemically pro-inflammatory state or identified a link between PTSD and chronic disease. The aim of this study was to evaluate the evidence for a relationship between individuals with PTSD and systemic low-grade inflammation that has been proposed to underlie chronic disease development in this population. The authors conducted a systematic review of the literature (January 2006 to April 2017) in accordance with the PRISMA statement in the following four databases: PubMed, MEDLINE, PsycINFO, and SPORTDiscus with Full Text. The search strategy was limited to articles published in peer-reviewed journals and to human studies. Nine studies measuring systemic inflammation and discussing its role in chronic disease development were selected for inclusion in this review. The association between markers of systemic inflammation and PTSD was evaluated by the measurement of a variety of systemic inflammatory markers including acute-phase proteins, complement proteins, pro- and anti-inflammatory cytokines, natural killer cells, and white blood cells. In general, systemic inflammatory biomarkers were elevated across the studies in the PTSD groups. There is evidence that PTSD is underpinned by the presence of a systemic low-grade inflammatory state. This inflammation may be the mechanism associated with increased risk for chronic disease in the PTSD population. From this, future research should focus on interventions that help to reduce inflammation, such as exercise.


Technetium myocardial perfusion scanning in prerenal transplant evaluation in the United kingdom.
Because death with a functioning graft remains one of the most important causes of long-term renal transplant failure, cardiac risk stratification and screening for coronary artery disease are essential components of pretransplant assessment. Pretransplant screening for occult coronary artery disease in a subset of these patients may improve outcome. The UK follows the European Best practice guideline 1.5.5 E. Although echocardiography, thallium myocardial perfusion scanning (MPS), dobutamine stress echocardiography, and coronary angiography have been suggested as means of cardiovascular assessment, the best means of assessment remains undetermined. Therefore, we investigated the role of 99m technetium sestamibi myocardial perfusion scanning as an assessment tool for identifying those patients with end-stage renal failure at high risk of cardiovascular death after renal transplantation. Retrospectively, we studied 126 patients that had a MPS as part of their pretransplant assessment. Overall unadjusted survival was 65% at 3 years. Twelve deaths resulted from cardiovascular causes. A reversible defect on MPS was associated with a fatal cardiac event and all-cause mortality. The unadjusted hazard ratio of cardiac event with reversible defect on MPS was 3.1 (95% confidence interval, 1.1 to 18.2) and hazard ratio of death with reversible defect on MPS was 1.92 (95% confidence interval, 1.1 to 4.4). Thus, MPS may be a useful tool in cardiac risk stratification and in selecting patients with a favorable outcome after renal transplantation. Our patients with a reversible defect in particular have increased cardiac mortality. This group may benefit from coronary angiography.


Non-neoplastic and neoplastic pleural endpoints following fiber exposure.
Exposure to asbestos fibers is associated with non-neoplastic pleural diseases including plaques, fibrosis, and benign effusions, as well as with diffuse malignant pleural mesothelioma. Translocation and retention of fibers are fundamental processes in understanding the interactions between the dose and dimensions of fibers retained at this anatomic site and the subsequent pathological reactions. The initial interaction of fibers with target cells in the pleura has been studied in cellular models in vitro and in experimental studies in vivo. The proposed biological mechanisms responsible for non-neoplastic and neoplastic pleural diseases and the physical and chemical properties of asbestos fibers relevant to these mechanisms are critically reviewed. Understanding mechanisms of asbestos fiber toxicity may help us anticipate the problems from future exposures both to asbestos and to novel fibrous materials such as nanotubes. Gaps in our understanding have been outlined as guides for future research.


Modeling and Simulation of a Machining Process Chain for the Precision Manufacture of Polar Microstructure.
This paper presents a functional microstructured surface, named Polar Microstructure. Polar microstructure is a three dimensional (3D) structured surface possessing a pattern of distribution of latitude and longitude micro-topographies with geometrical characteristics, which is similar to that in the Earth's north or south pole. The spacing of its small surface features can achieve form accuracy at the micrometer level. Polar microstructure has great potential for applications in precision measurement of angle displacement based on the characteristics of its surface features. This paper presents the development of a machining process chain system that integrates single point diamond turning (SPDT) and diamond broaching together to fabricate polar microstructure. A framework of a machining process chain system is presented which is composed of input module, design module, simulation module, output module, and metrology module. After that, modeling of the machining process chain composed of SPDT and diamond broaching is built up. The model takes into consideration the initial surface topography of the workpiece. Simulations have been conducted to obtain the optimal machining parameters in each machining process. A series of experiments was conducted for the ultra-precision machining of various types of polar microstructures. The machining results show that the machining process chain system is technically feasible and effective in the precision manufacturing of polar microstructure. The experimental results agree well with the simulated results.


Cutaneous pancreatic metastasis: a case report and review of literature.
Pancreatic cancer is one of the most lethal human cancers and continues to be a major unsolved health problem as we enter the 21st century. This is the case despite advances in imaging technology and surgical management. Indeed, 80-90% of pancreatic cancers are diagnosed either at the locally advanced stage or metastatic stage. Cutaneous metastases originating from pancreatic cancer are relatively rare. The most common site of cutaneous metastasis is the umbilicus, and it is known as the Sister Joseph's nodule. Very few patients have been reported with cutaneous lesions disclosing pancreatic carcinoma at sites other than the umbilical area. To our knowledge, there were no previous reports on cutaneous pancreatic metastasis in Egypt. This is a report of a patient with cutaneous pancreatic metastases at the neck, followed by a review of reported non-umbilical cutaneous metastases from pancreatic carcinoma in the literature.


What is the most appropriate comparator group to use in assessing the performance of primary total hip prostheses within the community?
There are variations in the performance of individual prostheses used in hip replacements. Some of which have unexpectedly higher revision rates - outliers. The Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) has established a standardised multi-stage approach for identifying these devices. This is done by comparing the revision rates of individual prostheses to all other prostheses in class, with the exception of large head metal-on-metal (LHMoM) prostheses. However, improvements in device design and performance over time have required a need to reconsider the comparator group. This study aimed to identify a more specific comparator to better reflect contemporary surgical practice. The time to first revision was estimated on the data of 413,417 primary total conventional hip replacements undertaken for osteoarthritis (OA) from 01 January 2003 to 31 December 2019. Survivorship analyses with stepwise exclusions were undertaken. The first exclusion was LHMoM, followed by other non-modern bearing surfaces (defined as all the bearing couples except metal or ceramic heads on cross-linked polyethylene and mixed ceramic-on-ceramic), and then devices with modular neck-stem design or used for specific purposes (incl. constrained, dual-mobility, and head size <28 mm). Lastly, all remaining prostheses previously identified as having a higher than anticipated rate of revision (HTARR) were also excluded. These exclusions progressively reduced the cumulative percent revision (CPR) rate. The final comparator, which only includes satisfactory-performed prostheses of contemporary design and use, has a 10-year CPR of 4.30% (95% CI, 4.2-4.41) which is lower than 4.93% (95% CI, 4.84-5.02) for the current comparator used by the AOANJRR (all prostheses excluding LHMOM). Over the study period, 13 additional components were identified utilising the modified comparator. The calculation of the comparator revision rate should be re-evaluated to include only modern prosthesis constructs to ensure that poorly performing prostheses are identified early.


Releasing Antiaromaticity in Metal-Bridgehead Naphthalene.
As a fundamental chemical property, aromaticity guides the synthesis of novel structures and materials. Replacing the carbon moieties of aromatic hydrocarbons with transition metal fragments is a promising strategy to synthesize intriguing organometallic counterparts with a similar aromaticity to their organic parents. However, since antiaromaticity will endow compound instability, it is a great challenge to obtain an antiaromatic organometallic counterpart based on such transition metal replacement in aromatic hydrocarbons. Here, we report an efficient aromaticity transformation on aromatic naphthalene through the bridgehead replacement of an osmium fragment, leading to the unprecedented synthesis of metal-bridgehead naphthalene featuring a highly twisted structure as confirmed by X-ray crystallography characterization. Such a twisted conformation works together with its phosphonium substituents to release the antiaromaticity in the planar conformation of the metal-bridgehead naphthalene. Our findings prove the bridgehead involvement of transition metals in unexpected aromaticity modifications and open an avenue for novel metal-bridgehead complexes.


RiboTag translatomic profiling of Drosophila oenocytes under aging and induced oxidative stress.
Aging is accompanied with loss of tissue homeostasis and accumulation of cellular damages. As one of the important metabolic centers, liver shows age-related dysregulation of lipid metabolism, impaired detoxification pathway, increased inflammation and oxidative stress response. However, the mechanisms for these age-related changes still remain unclear. In the fruit fly, Drosophila melanogaster, liver-like functions are controlled by two distinct tissues, fat body and oenocytes. Compared to fat body, little is known about how oenocytes age and what are their roles in aging regulation. To characterize age- and stress-regulated gene expression in oenocytes, we performed cell-type-specific ribosome profiling (RiboTag) to examine the impacts of aging and oxidative stress on oenocyte translatome in Drosophila. We show that aging and oxidant paraquat significantly increased the levels of reactive oxygen species (ROS) in adult oenocytes of Drosophila, and aged oenocytes exhibited reduced sensitivity to paraquat treatment. Through RiboTag sequencing, we identified 3324 and 949 differentially expressed genes in oenocytes under aging and paraquat treatment, respectively. Aging and paraquat exhibit both shared and distinct regulations on oenocyte translatome. Among all age-regulated genes, oxidative phosphorylation, ribosome, proteasome, fatty acid metabolism, and cytochrome P450 pathways were down-regulated, whereas DNA replication and immune response pathways were up-regulated. In addition, most of the peroxisomal genes were down-regulated in aged oenocytes, including genes involved in peroxisomal biogenesis factors and fatty acid beta-oxidation. Many age-related mRNA translational changes in oenocytes are similar to aged mammalian liver, such as up-regulation of innate immune response and Ras/MAPK signaling pathway and down-regulation of peroxisome and fatty acid metabolism. Furthermore, oenocytes highly expressed genes involving in liver-like processes (e.g., ketogenesis). Our oenocyte-specific translatome analysis identified many genes and pathways that are shared between Drosophila oenocytes and mammalian liver, highlighting the molecular and functional similarities between the two tissues. Many of these genes were altered in both oenocytes and liver during aging. Thus, our translatome analysis provide important genomic resource for future dissection of oenocyte function and its role in lipid metabolism, stress response and aging regulation.


[Prediction of pharmacological effect of octreotide in acromegaly by means of 111In-pentetreotide scintigraphy and calculation of a pituitary uptake index].
The aim of our prospective study was to optimize the determination of the pituitary somatostatin receptor status by means of 111-In-pentetreotide scintigraphy and to compare it intraindividually with the pharmacological effect of octreotide in active acromegaly. In n = 22 patients with growth hormone (GH) secreting pituitary adenoma, 111-In-pentetreotide scintigraphy was performed, and the specific radionuclide accumulation in the pituitary area (evaluation visually as well as semiquantitatively by means of ROI technique and calculation of various uptake indices) was correlated with the acute drop of GH after administration of 100 micrograms octreotide s. c. (octreotide acute test). The uptake index we propose (cts/pixel-ratio circular pituitary ROI: irregular cerebrum ROI after background correction in the sagittal SPECT slice with maximum pituitary uptake 24 h p.i.) correlates best with the pharmacological effect (acute decrease of GH levels) of octreotide; its upper normal limit amounts of 3.5. As often the normal pituitary gland can be visualized scintigraphically, the purely visual differentiation between a normal and a pathological receptor status sometimes is equivocal. A pituitary uptake index, calculated by means of a standardized ROI technique, facilitates this discrimination and so contributes to select possible responders for a treatment with octreotide.


LPS-Induced Systemic Inflammation Does Not Alter Atherosclerotic Plaque Area or Inflammation in APOE3*LEIDEN Mice in the Early Phase Up to 15 Days.
Observational studies show a peak incidence in cardiovascular events during and early after clinical conditions associated with substantial systemic inflammation, such as pneumonia. The acuteness of this increased risk suggests rapid plaque destabilization and associated intraplaque inflammation. We evaluated whether lipopolysaccharides (LPS)-evoked acute systemic inflammation would induce such detrimental vascular changes in murine aortas with manifest atherosclerotic lesions. ApoE3*Leiden mice were fed a high cholesterol diet for 20 weeks to establish atherosclerosis. Thereafter, mice received a single intraperitoneal injection with LPS to induce systemic inflammation, or saline for control. Mice were sacrificed 2 or 15 days post-LPS injection (n = 17) or post-saline injection (n = 13). Serum amyloid A, a sensitive marker of systemic inflammation, increased 250-fold in LPS-treated mice. Aortic root plaques were assessed for total plaque area, plaque severity, and inflammatory cell content. No significant differences in total surface area of atherosclerotic plaque were found between control and LPS groups sacrificed after 2 days (resp. 0.409 ± 0.228 × 10 μm vs. 0.285 ± 0.169 × 10 μm) (P = 0.31), and 15 days (resp. 0.950 ± 0.938 × 10 μm vs. 0.612 ± 0.413 × 10 μm) (P = 0.80). Furthermore, plaque type and number of lesions were unaltered and intraplaque density of macrophages and lymphocytes were comparable in both the groups. Intraperitoneal LPS injection in ApoE3*Leiden mice triggers a profound systemic inflammatory response, but does not increase atherosclerotic plaque area or inflammatory cell density. This model of LPS-induced inflammation in atherosclerosis-prone mice argues against intraplaque alterations as an explanation for acute inflammation-induced cardiovascular event risk.


The memory gene dunce+ encodes a remarkable set of RNAs with internal heterogeneity.
We have previously isolated the region of the Drosophila melanogaster X chromosome which contains the dunce+ gene and mapped the dunce2 mutation by recombination to a 10- to 12-kilobase (kb) interval (R. L. Davis and N. Davidson, Mol. Cell. Biol. 4:358-367, 1984). Here, we examine the expression of the dunce+ chromosomal region and identify the dunce+ gene within that region. A region of ca. 25 kb which contains the 10- to 12-kb interval to which dunce2 was mapped codes for polyadenylated RNAs of 9.6, 7.4, 7.2, 7.0, 5.4, and 4.5 kb in adult flies. These transcripts are encoded by the same DNA strand and share sequences of some exons, indicating that the transcripts arise from the same gene. Some genome probes internal to the ca. 25-kb coding region show transcript-specific hybridization, demonstrating alternate usage of exonic sequence information in the formation of the mature transcripts. The basis for this internal heterogeneity in RNAs is most likely alternative splicing. Two dunce mutants examined show aberrant RNA expression from this coding region, confirming that this region is the dunce gene. The developmental expression of these transcripts has been examined. The 5.4-kb RNA is present at all developmental stages. The 9.6-, 7.4-, 7.2-, and 7.0-kb RNAs are not expressed at detectable levels in embryos, but are detected in late embryogenesis and in later developmental stages. The 4.5-kb species is found in early embryos and adults, but not in intermediate stages. We discuss the remarkable transcript heterogeneity and expression pattern with respect to the important function this gene performs in neurobiological and other physiological processes.


[Spatial structure of the cro-repressor in a solution. I. Identification of interaction in a hydrophobic cluster using the nuclear Overhauser effect].
The structure of a bacteriophage lambda cro repressor hydrophobic globule was studied by the technique of 1H NMR spectroscopy at 500 MHz. The analysis of NOE difference spectra and building of the molecular models for the most probable fragments of the secondary structure allowed us to assign many signals in the protein spectrum and to identify the intramolecular interactions which stabilized the hydrophobic globule and the tertiary structure of the molecule. The results suggest that the structure of the cro repressor hydrophobic globule in solution coincides with the crystal one, although there are some differences in the mutual arrangement of the alpha 1 helix and the three-fold beta-sheet. Resonance assignment has made it possible to study conformational changes and specific interactions of the cro repressor by using suitable reporter groups.


Topological magnon insulator with a Kekulé bond modulation.
We examine the combined effects of a Kekulé coupling texture (KC) and a Dzyaloshinskii-Moriya interaction (DMI) in a two-dimensional ferromagnetic honeycomb lattice. By analyzing the gap closing conditions and the inversions of the bulk bands, we identify the parameter range in which the system behaves as a trivial or a nontrivial topological magnon insulator. We find four topological phases in terms of the KC parameter and the DMI strength. We present the bulk-edge correspondence for the magnons in a honeycomb lattice with an armchair or a zigzag boundary. Furthermore, we find Tamm-like edge states due to the intrinsic on-site interactions along the boundary sites. Our results may have significant implications to magnon transport properties in the 2D magnets at low temperatures.


A nomogram to predict nosocomial infection in patients on venoarterial extracorporeal membrane oxygenation after cardiac surgery.
After cardiac surgery, patients on venoarterial extracorporeal membrane oxygenation (VA-ECMO) have a higher risk of nosocomial infection in the intensive care unit (ICU). We aimed to establish an intuitive nomogram to predict the probability of nosocomial infection in patients on VA-ECMO after cardiac surgery. We included patients on VA-ECMO after cardiac surgery between January 2011 and December 2020 at a single center. We developed a nomogram based on independent predictors identified using univariate and multivariate logistic regression analyses. We selected the optimal model and assessed its performance through internal validation and decision-curve analyses. Overall, 503 patients were included; 363 and 140 patients were randomly divided into development and validation sets, respectively. Independent predictors derived from the development set to predict nosocomial infection included older age, white blood cell (WBC) count abnormality, ECMO environment in the ICU, and mechanical ventilation (MV) duration, which were entered into the model to create the nomogram. The model showed good discrimination, with areas under the curve (95% confidence interval) of 0.743 (0.692-0.794) in the development set and 0.732 (0.643-0.820) in the validation set. The optimal cutoff probability of the model was 0.457 in the development set (sensitivity, 0.683; specificity, 0.719). The model showed qualified calibration in both the development and validation sets (Hosmer-Lemeshow test, p > .05). The threshold probabilities ranged from 0.20 to 0.70. For adult patients receiving VA-ECMO treatment after cardiac surgery, a nomogram-monitoring tool could be used in clinical practice to identify patients with high-risk nosocomial infections and provide an early warning.


Crosstalk Between Autophagy and Hypoxia-Inducible Factor-1α in Antifungal Immunity.
Modern medicine is challenged by several potentially severe fungal pathogens such as Aspergillus fumigatus, Candida albicans, or Histoplasma capsulatum. Though not all fungal pathogens have evolved as primary pathogens, opportunistic pathogens can still cause fatal infections in immuno-compromised patients. After infection with these fungi, the ingestion and clearance by innate immune cells is an important part of the host immune response. Innate immune cells utilize two different autophagic pathways, the canonical pathway and the non-canonical pathway, also called microtubule-associated protein 1A/1B-light chain 3 (LC3) -associated pathway (LAP), to clear fungal pathogens from the intracellular environment. The outcome of autophagy-related host immune responses depends on the pathogen and cell type. Therefore, the understanding of underlying molecular mechanisms of autophagy is crucial for the development and improvement of antifungal therapies. One of those molecular mechanisms is the interaction of the transcription-factor hypoxia-inducible factor 1α (HIF-1α) with the autophagic immune response. During this review, we will focus on a comprehensive overview of the role of autophagy and HIF-1α on the outcome of fungal infections.


Natural enemies recovered from Spodoptera frugiperda J.E. Smith (Lepidoptera: Noctuidae) larvae infesting the cartridge, ear and stem of corn plants under conventional and organic farming systems in Brazil.
The corn cropping system can influence the natural enemy identity and the number of Spodoptera frugiperda J.E. Smith, 1797 (Lepidoptera: Noctuidae) individuals infesting the cartridge, ear and stem of this plant. The objectives were to identify the S. frugiperda natural enemies and differences in the number of individuals infesting the cartridge, ear and stem of corn plants under conventional and organic cropping systems, in Brazil after an initial collection of adult males through semiochemical traps. We also evaluated key morphometrical parameters of the larva and factors contributing with the viability of S. frugiperda. A total of 16 and 136 adult males was trapped, and 1,124 and 1,112 larvae was recovered from conventional and organic systems with 4.7 and 6.7% of them parasitized by dipteran and hymenopteran, respectively. Most of the parasitoids recovered had occurrence in both cropping systems, except Cremastinae and Ophion flavidus Brullé, 1846 (Hymenoptera: Ichneumonidae), which were recorded only in organic and Campoletis sp. (Hymenoptera: Ichneumonidae) only in conventional corns. The number of parasitoids recovered was similar in corn plant samples between both cropping systems. A total of 152 and 31 larvae was recovered from corn ears under conventional and organic systems, respectively. Doru luteipes (Scudder, 1876) (Dermaptera: Forficulidae) was recovered from all samples under conventional system. The larva length was overall similar between cropping systems. Parasitism by dipteran and hymenopteran, infection by microorganisms, larva mortality by undetermined causes, and differences in viability of S. frugiperda stages were factors contributing with the supression of this pest. The new associations and parasitoids reported represent possibilities of expanding the biological control strategies to manage S. frugiperda in corn crops.


Preliminary Evidences of Safety and Efficacy of Flavonoids- and Omega 3-Based Compound for Muscular Dystrophies Treatment: A Randomized Double-Blind Placebo Controlled Pilot Clinical Trial.
Background: Nutritional compounds can exert both anti-inflammatory and anti-oxidant effects. Since these events exacerbate the pathophysiology of muscular dystrophies, we investigated nutraceutical supplementation as an adjuvant therapy in dystrophic patients, to low costs and easy route of administration. Moreover, this treatment could represent an alternative therapeutic strategy for dystrophic patients who do not respond to corticosteroid treatment. Objective: A 24 weeks randomized double-blind placebo-controlled clinical study was aimed at evaluating the safety and efficacy of daily oral administration of flavonoids- and omega3-based natural supplement (FLAVOMEGA) in patients affected by muscular dystrophy with recognized muscle inflammation. Design: We screened 60 patients diagnosed for Duchenne (DMD), Facioscapulohumeral (FSHD), and Limb Girdle Muscular Dystrophy (LGMD). Using a computer-generated random allocation sequence, we stratified patients in a 2:1:1 ratio (DMD:FSHD:LGMD) to one of two treatment groups: continuous FLAVOMEGA, continuous placebo. Of 29 patients included, only 24 completed the study: 15 were given FLAVOMEGA, 14 placebo. Results: FLAVOMEGA was well tolerated with no reported adverse events. Significant treatment differences in the change from baseline in 6 min walk distance (6MWD; secondary efficacy endpoint) (P = 0.033) and in isokinetic knee extension (P = 0.039) (primary efficacy endpoint) were observed in LGMD and FSHD subjects. Serum CK levels (secondary efficacy endpoint) decreased in all FLAVOMEGA treated groups with significant difference in DMD subjects (P = 0.039). Conclusions: Although the small number of patients and the wide range of disease severity among patients reduced statistical significance, we obtained an optimal profile of safety and tolerability for the compound, showing valuable data of efficacy in primary and secondary endpoints. Trial registration number: NCT03317171 Retrospectively registered 25/10/2017.


Clinical features of celiac disease: a prospective birth cohort.
To investigate clinical features of celiac disease (CD) and their association with risk factors for CD in a genetic risk birth cohort. Children from 6 clinical centers in 4 countries positive for HLA-DR3-DQ2 or DR4-DQ8 were annually screened for tissue transglutaminase antibodies (tTGA) and assessed for symptoms by questionnaires. Associations of symptoms with anthropometrics, known risk factors for CD, tTGA levels, and mucosal lesions in those biopsied were examined. Of 6706 screened children, 914 developed persistent positive tTGA, 406 underwent biopsies, and 340 had CD. Compared with age-matched tTGA-negative children, those with persistent tTGA were more likely to have symptoms at 2 (34% vs 19%, P < .001) and 3 years of age (28% vs 19%, P = .009) but not at 4 years (27% vs 21%, NS). Z-scores for height, weight, and BMI did not differ between groups. In children with persistent tTGA, having ≥ 1 symptom was associated with family history of CD (odds ratio = 2.59, 95% confidence interval, 1.21-5.57) but not with age, gender, or HLA-DR3-DQ2 homozygosity. At seroconversion, tTGA levels were higher in symptomatic than asymptomatic children (P < .001), in those from CD families (P < .001), and in US participants (P < .001) but not associated with age, gender, or HLA genotype. tTGA levels correlated with severity of mucosal lesions both in symptomatic (r = 0.53, P < .001) and asymptomatic children (r = 0.22, P = .01). A majority of children detected with persistent tTGA in screenings are asymptomatic and have normal growth by age 4 years. tTGA levels correlate more strongly with severity of mucosal lesions in symptomatic as compared with asymptomatic children.


Preferential synthesis of the G1m(1) allotype of IgG1 in the central nervous system of multiple sclerosis patients.
Quantitations of the G1m(1) and G1m(3) allotypic determinants of human immunoglobulin G were performed by radioimmunoassay on cerebrospinal fluid and serum samples from patients with multiple sclerosis and from patients with other neurological disorders. In multiple sclerosis patients that were heterozygous for these determinants, G1m(1) concentration in the cerebrospinal fluid was greatly increased-reflected by an increased ratio of G1m(1)-in comparison with that of patients with other neurological disorders. These results suggest that in the heterozygous multiple sclerosis patients, most of the plasma cells in the central nervous system that secrete oligoclonal immunoglobulin G preferentially synthesize G1m(1) IgG1 molecules.


Integrative analysis of the transcriptome profiles observed in type 1, type 2 and gestational diabetes mellitus reveals the role of inflammation.
Type 1 diabetes (T1D) is an autoimmune disease, while type 2 (T2D) and gestational diabetes (GDM) are considered metabolic disturbances. In a previous study evaluating the transcript profiling of peripheral mononuclear blood cells obtained from T1D, T2D and GDM patients we showed that the gene profile of T1D patients was closer to GDM than to T2D. To understand the influence of demographical, clinical, laboratory, pathogenetic and treatment features on the diabetes transcript profiling, we performed an analysis integrating these features with the gene expression profiles of the annotated genes included in databases containing information regarding GWAS and immune cell expression signatures. Samples from 56 (19 T1D, 20 T2D, and 17 GDM) patients were hybridized to whole genome one-color Agilent 4x44k microarrays. Non-informative genes were filtered by partitioning, and differentially expressed genes were obtained by rank product analysis. Functional analyses were carried out using the DAVID database, and module maps were constructed using the Genomica tool. The functional analyses were able to discriminate between T1D and GDM patients based on genes involved in inflammation. Module maps of differentially expressed genes revealed that modulated genes: i) exhibited transcription profiles typical of macrophage and dendritic cells; ii) had been previously associated with diabetic complications by association and by meta-analysis studies, and iii) were influenced by disease duration, obesity, number of gestations, glucose serum levels and the use of medications, such as metformin. This is the first module map study to show the influence of epidemiological, clinical, laboratory, immunopathogenic and treatment features on the transcription profiles of T1D, T2D and GDM patients.


Plasma membrane-cytoskeleton-endoplasmic reticulum complexes in neurons and astrocytes.
The possibility that certain integral plasma membrane (PM) proteins involved in Ca(2+) homeostasis form junctional units with adjacent endoplasmic reticulum (ER) in neurons and glia was explored using immunoprecipitation and immunocytochemistry. Rat brain membranes were solubilized with the mild, non-ionic detergent, IGEPAL CA-630. Na(+)/Ca(2+) exchanger type 1 (NCX1), a key PM Ca(2+) transporter, was immunoprecipitated from the detergent-soluble fraction. Several abundant PM proteins co-immunoprecipitated with NCX1, including the alpha2 and alpha3 isoforms of the Na(+) pump catalytic (alpha) subunit, and the alpha2 subunit of the dihydropyridine receptor. The adaptor protein, ankyrin 2 (Ank 2), and the cytoskeletal proteins, alpha-fodrin and beta-spectrin, also selectively co-immunoprecipitated with NCX1, as did the ER proteins, Ca(2+) pump type 2 (SERCA 2), and inositol-trisphosphate receptor type 1 (IP(3)R-1). In contrast, a number of other abundant PMs, adaptors, and cytoskeletal proteins did not co-immunoprecipitate with NCX1, including the Na(+) pump alpha1 isoform, PM Ca(2+) pump type 1 (PMCA1), beta-fodrin, and Ank 3. In reciprocal experiments, immunoprecipitation with antibodies to the Na(+) pump alpha2 and alpha3 isoforms, but not alpha1, co-immunoprecipitated NCX1; the antibodies to alpha1 did, however, co-immunoprecipitate PMCA1. Antibodies to Ank 2, alpha-fodrin, beta-spectrin and IP(3)R-1 all co-immunoprecipitated NCX1. Immunocytochemistry revealed partial co-localization of beta-spectrin with NCX1, Na(+) pump alpha3, and IP(3)R-1 in neurons and of alpha-fodrin with NCX1 and SERCA2 in astrocytes. The data support the idea that in neurons and glia PM microdomains containing NCX1 and Na(+) pumps with alpha2 or alpha3 subunits form Ca(2+) signaling complexes with underlying ER containing SERCA2 and IP(3)R-1. These PM and ER components appear to be linked through the cytoskeletal spectrin network, to which they are probably tethered by Ank 2.


Trimethylamine and trimethylamine N-oxide are supplementary energy sources for a marine heterotrophic bacterium: implications for marine carbon and nitrogen cycling.
Bacteria of the marine Roseobacter clade are characterised by their ability to utilise a wide range of organic and inorganic compounds to support growth. Trimethylamine (TMA) and trimethylamine N-oxide (TMAO) are methylated amines (MA) and form part of the dissolved organic nitrogen pool, the second largest source of nitrogen after N2 gas, in the oceans. We investigated if the marine heterotrophic bacterium, Ruegeria pomeroyi DSS-3, could utilise TMA and TMAO as a supplementary energy source and whether this trait had any beneficial effect on growth. In R. pomeroyi, catabolism of TMA and TMAO resulted in the production of intracellular ATP which in turn helped to enhance growth rate and growth yield as well as enhancing cell survival during prolonged energy starvation. Furthermore, the simultaneous use of two different exogenous energy sources led to a greater enhancement of chemoorganoheterotrophic growth. The use of TMA and TMAO primarily as an energy source resulted in the remineralisation of nitrogen in the form of ammonium, which could cross feed into another bacterium. This study provides greater insight into the microbial metabolism of MAs in the marine environment and how it may affect both nutrient flow within marine surface waters and the flux of these climatically important compounds into the atmosphere.


A comparison of the association between large haplotype blocks under selection and the presence/absence of inversions.
Inversions may contribute to ecological adaptation and phenotypic diversity, and with the advent of "second" and "third" generation sequencing technologies, the ability to detect inversion polymorphisms has been enhanced dramatically. A key molecular consequence of an inversion is the suppression of recombination allowing independent accumulation of genetic changes between alleles over time. This may lead to the development of divergent haplotype blocks maintained by balancing selection. Thus, divergent haplotype blocks are often considered as indicating the presence of an inversion. In this paper, we first review the features of a 7.7 Mb inversion causing the Rose-comb phenotype in chicken, as a model for how inversions evolve and directly affect phenotypes. Second, we compare the genetic basis for alternative mating strategies in ruff and timing of reproduction in Atlantic herring, both associated with divergent haplotype blocks. Alternative male mating strategies in ruff are associated with a 4.5 Mb inversion that occurred about 4 million years ago. In fact, the ruff inversion shares some striking features with the Rose-comb inversion such as disruption of a gene at one of the inversion breakpoints and generation of a new allele by recombination between the inverted and noninverted alleles. In contrast, inversions do not appear to be a major reason for the fairly large haplotype blocks (range 10-200 kb) associated with ecological adaptation in the herring. Thus, it is important to note that divergent haplotypes may also be maintained by natural selection in the absence of structural variation.


Interaction of recombinant IL-1 and recombinant tumor necrosis factor in the induction of mouse acute phase proteins.
Recombinant mouse and human IL-1 (alpha and beta forms), as well as rTNF-alpha when administered in vivo, induced the production of the mouse acute phase reactants: serum amyloid P-component (SAP), C3, and fibrinogen. The SAP response to all three rIL-1 proteins reached a maximum at a dose of 10(4) U/mouse, which corresponds to 1 to 10 micrograms of protein. The maximum in vivo response consisted of a 10-fold increase in SAP levels, a 2-fold increase in C3 levels, and a 3-fold increase in fibrinogen concentration. By contrast, rTNF-alpha induced a much smaller acute phase (AP) protein response (4-fold increase in SAP) when administered in vivo. Administration of a combination if rIL-1 and rTNF resulted in an AP response that was additive for SAP, synergistic for fibrinogen, but resulted in only the same amount of C3 induced by IL-1 alone. Both recombinant monokines induced new SAP synthesis by isolated hepatocytes in vitro with an optimal response occurring with either 1 U of rIL-1/ml per 2 x 10(5) hepatocytes or 10(-3) U/ml of rTNF. The hepatocyte response to IL-1 was of the same magnitude as the response of intact mice; however, the response to TNF was approximately 10(4) times more efficient in vitro. A mixture of the monokines induced an in vitro SAP response that was additive when suboptimal doses of rIL-1 were combined with optimal amounts of rTNF-alpha. Overall, the findings indicate that both monokines directly trigger hepatocyte synthesis of SAP and that their combined effect probably accounts for a substantial portion of the synthesis of these AP proteins in mice.


Commodity risk assessment of Nerium oleander plants from Turkey.
The European Commission requested the EFSA Panel on Plant Health to prepare and deliver risk assessments for commodities listed in Commission Implementing Regulation EU/2018/2019 as 'High risk plants, plant products and other objects'. This Scientific Opinion covers plant health risks posed by bare rooted and potted plants of Nerium oleander that are imported from Turkey, taking into account the available scientific information, including the technical information provided by the Turkish NPPO. The relevance of any pest for this opinion was based on evidence following defined criteria. One species, the EU non-regulated pest Phenacoccus solenopsis, fulfilled all relevant criteria and was selected for further evaluation. For this pest, the risk mitigation measures proposed in the technical dossier from Turkey were evaluated taking into account the possible limiting factors. For this pest, an expert judgement is given on the likelihood of pest freedom taking into consideration the risk mitigation measures acting on the pest, including uncertainties associated with the assessment. The Expert Knowledge Elicitation indicated, with 95% certainty, that between 9,719 and 10,000 plants per 10,000 would be free of P. solenopsis.


Stimulation by antidiuretic hormone of electrolyte tubular reabsorption in rat kidney.
The effects of 1-desamino-8-D-arginine vasopressin (dDAVP) on renal excretion and tubular transport of water and electrolytes were investigated in homozygous DI Brattleboro rats. To ascertain these effects on the loop of Henle, circulating glucagon, parathyroid hormone, and thyrocalcitonin were reduced before the experiments, as these hormones are believed to stimulate the same cells of the thick ascending limb as ADH. dDAVP did not alter either glomerular or proximal tubular functions. In the loop, it consistently raised reabsorption of Mg, Ca, K, and, to a lesser extent, Na and Cl, but phosphate transport was not affected. dDAVP lowered the urinary excretion rates for Mg, Ca, K, Cl, and total solutes. For Mg, this reduction was independent of the drop in the urinary flow rate following dDAVP administration but was significantly correlated to this drop in the case of Ca, K, Cl, and total solutes. Na and P excretions were not altered by dDAVP. It is concluded that, in vivo, administration of ADH 1) stimulates reabsorption of Na, Cl, Mg, Ca, and K by the thick ascending limb, 2) consistently enhances Mg reabsorption by the whole kidney by enhancing reabsorption in the loop of Henle, and 3) at maximal antidiuresis, raises Ca, K, Cl, and total solute reabsorption, probably because of the drop in tubular flow rates in the distal parts of the nephron consequent to the hormone administration.


[Olfactory ensheathing cells promote the survival of newborn rat spiral ganglion cells in vitro].
The objective of this study is to explore whether olfactory ensheathing cells (OECs) can promote the survival of newborn rat spiral ganglion cells (SGCs) and the underlying possible mechanisms. Co-culture of OECs from adult rats with SGCs from newborn rat cochlea was established and single culture of SGCs acted as control. OECs were obtained and purified based on their special rate of attachment which was different from the other harvested cell types during culture. OECs and SGCs were immunocytochemically characterized and confirmed by expression of low-affinity nerve growth factor receptor p75 or positive label of neuron-specific betaIII-tubulin. To investigate the mechanisms of the role of OECs in survival of SGCs, brain derived neurotrophic factor (BDNF) and anti-BDNF antibody (IgY) were added into the media of the co-cultures respectively, and the surviving SGCs were examined after treatment. Single layer of OECs (92% pure) was seen seven days after plating. Surviving SGCs, which extended their primary neurites, were found on the surface of the layer in the co-cultures. When OECs and SGCs were co-cultured, the number of surviving SGCs was significantly greater than that in the single culture (P<0.01). Nine days after culture, there was even no change in the number of surviving SGCs in the co-culture while the number reduced to almost zero in the single culture. In comparison with co-culture without treatment, addition of BDNF (500 pg/mL) into the media had no obvious promoting effect on the survival of SGCs. The number of surviving SGCs reduced significantly when anti-BDNF antibody was applied into the media of co-cultures (P<0.01). These results suggest that OECs can promote the survival of SGCs when they are co-cultured in vitro. BDNF released from OECs, as one of the survival factors, plays an important role in the survival of SGCs.


Improved random-starting method for the EM algorithm for finite mixtures of regressions.
Two methods for generating random starting values for the expectation maximization (EM) algorithm are compared in terms of yielding maximum likelihood parameter estimates in finite mixtures of regressions. One of these methods is ubiquitous in applications of finite mixture regression, whereas the other method is an alternative that appears not to have been used so far. The two methods are compared in two simulation studies and on an illustrative data set. The results show that the alternative method yields solutions with likelihood values at least as high as, and often higher than, those returned by the standard method. Moreover, analyses of the illustrative data set show that the results obtained by the two methods may differ considerably with regard to some of the substantive conclusions. The results reported in this article indicate that in applications of finite mixture regression, consideration should be given to the type of mechanism chosen to generate random starting values for the EM algorithm. In order to facilitate the use of the proposed alternative method, an R function implementing the approach is provided in the Appendix of the article.


A Monte Carlo study of the quality dependence of diamond thermoluminescent dosimeters in radiotherapy beams.
Monte Carlo simulations with the EGS4 code system have been performed to determine the quality dependence of diamond TLDs in photon beams ranging from 25 kV to 25 MV x-rays and also in megavoltage electron beams. It has been shown that diamond TLDs in the form of discs of thickness 0.3 mm and diameter 5.64 mm show no significant dependence on the incident energy in clinical electron beams when irradiated close to dmax, but require an energy correction factor of 1.050 +/- 0.008 compared with diamond TLDs irradiated in 60Co gamma-rays. The correction factor increases with depth of irradiation and this effect is greater for thicker detectors. The Monte Carlo predicted sensitivity in x-ray beams is constant within 2.5% over the energy range 250 kV to 25 MV. However the sensitivity decreases by about 60% for 25 kV x-rays compared with 60Co gamma-rays.


Current status and strategies for viral hepatitis control in Korea.
Viral hepatitis is one of major global health challenges with increasing disease burden worldwide. Hepatitis B virus and hepatitis C virus infections are major causes of chronic liver diseases. They can lead to cirrhosis, hepatocellular carcinoma, and death in significant portion of affected people. Transmission of hepatitis B virus can be blocked by vaccination. Progression of hepatitis B virus-related liver diseases can be prevented by long-term viral suppression with effective drugs. Although vaccine for hepatitis C virus is currently unavailable, hepatitis C virus infection can be eradicated by oral direct antiviral agents. To eliminate viral hepatitis, World Health Organization (WHO) has urged countries to develop national goals and targets through reducing 90% of new infections and providing universal access to key treatment services up to 80%. This can lead to 65% reduction of viral hepatitis-related mortality. Here, we discuss some key features of viral hepatitis, strategies to control viral hepatitis suggested by WHO, and current status and strategies for viral hepatitis control in South Korea. To achieve the goal of viral hepatitis elimination by 2030 in South Korea, an independent 'viral hepatitis sector' in Centers for Disease Control & Prevention (CDC) needs to be established to organize and execute comprehensive strategy for the management of viral hepatitis in South Korea.


Methods for quantifying Staphylococcus aureus in indoor air.
Staphylococcus aureus has been detected in indoor air and linked to human infection. Quantifying S. aureus by efficient sampling methods followed by appropriate sample storage treatments is essential to characterize the exposure risk of humans. This laboratory study evaluated the effects of sampler type (all-glass impinger (AGI-30), BioSampler, and Andersen one-stage sampler (Andersen 1-STG)), collection fluid (deionized water (DW), phosphate-buffered saline (PBS), and Tween mixture (TM)), and sampling time (3-60 min) on cell recovery. Effects of storage settings on bacterial concentration were also assessed over 48 h. Results showed BioSampler performed better than Andersen 1-STG and AGI-30 (P < 0.05) and TM was superior to PBS and DW (P < 0.05). An increase in sampling time negatively affected the recoveries of cells in PBS of BioSampler and AGI-30 (P < 0.05), whereas cell recoveries in TM were increased at sampling of 6-15 min compared with 3 min. Concentrations of cells collected in PBS were decreased with storage time at 4 and 23 °C (P < 0.05), while cells stored in TM showed stable concentrations at 4 °C (P > 0.05) and increased cell counts at 23 °C (P < 0.05). Overall, sampling by BioSampler with TM followed by sample transportation and storage at 4 °C is recommended.


Optic Neuritis and Cranial Neuropathies Diagnosis Rates before Coronavirus Disease 2019, in the Initial Pandemic Phase, and Post-Vaccine Introduction.
To compare rates of diagnosis of neuro-ophthalmic conditions across the Coronavirus Disease 2019 (COVID-19) pandemic with pre-pandemic levels. Multicenter, retrospective, observational study. Patients seen for eye care between March 11, 2019, and December 31, 2021. A multicenter electronic health record database, Sight Outcomes Research Collaborative (SOURCE), was queried for new diagnoses of neuro-ophthalmic conditions (cranial nerve [CN] III, IV, VI, and VII palsy; diplopia; and optic neuritis) and new diagnoses of other ophthalmic conditions from January 1, 2016, to December 31, 2021. Data were divided into 3 periods (pre-COVID, pre-COVID vaccine, and after introduction of COVID vaccine), with a 3-year look-back period. Logistic regressions were used to compare diagnosis rates across periods. Two-sample z-test was used to compare the log odds ratio (OR) of the diagnosis in each period with emergent ocular conditions: retinal detachment (RD) and acute angle-closure glaucoma (AACG). Diagnosis rate of neuro-ophthalmic conditions in each study period. A total of 323 261 unique patients (median age 59 years [interquartile range, 43-70], 58% female, 68% White) across 5 academic centers were included, with 180 009 patients seen in the pre-COVID period, 149 835 patients seen in the pre-COVID vaccine period, and 164 778 patients seen in the COVID vaccine period. Diagnosis rates of CN VII palsy, diplopia, glaucoma, and cataract decreased from the pre-COVID period to the pre-vaccine period. However, the optic neuritis diagnoses increased, in contrast to a decrease in RD diagnoses (P = 0.021). By comparing the diagnosis rates before and after widespread vaccination, all eye conditions evaluated were diagnosed at higher rates in the COVID vaccination period compared with pre-COVID and pre-vaccine periods. The log OR of neuro-ophthalmic diagnosis rates across every period comparison were largely similar to emergency conditions (RD and AACG, P > 0.05). However, the log OR of cataract and glaucoma diagnoses were different to RD or AACG (P < 0.05) in each period comparison. Neuro-ophthalmic diagnoses had a similar reduction in diagnosis rates as emergent eye conditions in the first part of the pandemic, except optic neuritis. After widespread COVID-19 vaccination, all ophthalmic diagnosis rates increased compared with pre-pandemic rates, and the increase in neuro-ophthalmic diagnosis rates did not exceed the increase in RD and AACG diagnosis rates. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.


Ready-to-eat cereals and the burden of obesity in the context of their nutritional contribution: are all ready-to-eat cereals equally healthy? A systematic review.
A significant increase in the prevalence of obesity has occurred worldwide and the importance of considering the role of diet in the prevention and treatment of obesity is widely acknowledged. A growing body of evidence encourages the consumption of ready-to-eat cereals (RTEC) as part of a healthful diet. Research has shown an inverse association between the consumption of RTEC and the rate of obesity. However, other findings claim that this association was only attributed to the consumption of whole-grain cereals and not the refined-grain ones. Although meta-analyses of clinical trials support the use of a low-glycaemic index diet on weight loss, findings from other studies on the effect of the dietary glycaemic index on body weight have not been consistent. Thus, further research into the role of glycaemic index in the prevention and management of obesity and chronic disease is needed. Moreover, significant differences have been observed in composition among the marketed RTEC. In light of the revealing protective role of whole-grain, fibre-rich, low-energy-dense and low-glycaemic index/glycaemic load foods against obesity, public health professionals could drive their efforts towards the promotion of even more healthier RTEC when issuing advice on weight management. It seems, however, that despite any differences in their composition, the frequent consumption of RTEC due to their nutritional contribution is recommended in moderation and under the current recommendations in the context of a healthy balanced diet.


[Priapism secondary to a bilateral abscess of the corpora cavernosa].
Presentation of an exceptional case of priapism in an 82-year-old male, secondary to primary bilateral abscess corpus cavernosum. Diagnosis was reached through aspiration puncture and pus drainage, which also allowed the resolution of the condition. After a literature review, no similar case was found. This was a painful, long-lasting erection that resulted from corpus cavernosum repletion with purulent material instead of blood.


Comparison of 18F-T807 and 18F-THK5117 PET in a Mouse Model of Tau Pathology.
Positron-emission-tomography (PET) imaging of tau pathology has facilitated development of anti-tau therapies. While members of the arylquinoline and pyridoindole families have been the most frequently used tau radioligands so far, analyses of their comparative performance in vivo are scantly documented. Here, we conducted a head-to-head PET comparison of the arylquinoline 18FT807 and the pyridoindole 18FTHK5117 PET in a mouse model of tau pathology. PET recordings were obtained in groups of (N = 5-7) P301S and wild-type (WT) mice at 6 and 9 months of age. Volume-of-interest based analysis (standard-uptake-value ratio, SUVR) was used to calculate effect sizes (Cohen's d) for each tracer and age. Statistical parametric mapping (SPM) was used to assess regional similarity (dice coefficient) of tracer binding alterations for the two tracers. Immunohistochemistry staining of neurofibrillary tangles was performed for validation ex vivo. Significantly elevated 18F-T807 binding in the brainstem of P301S mice was already evident at 6 months (+14%, p < 0.01, d = 1.64), and increased further at 9 months (+23%, p < 0.001, d = 2.70). 18F-THK5117 indicated weaker increases and effect sizes at 6 months (+5%, p < 0.05, d = 1.07) and 9 months (+10%, p < 0.001, d = 1.49). Regional similarity of binding of the two tracers was high (71%) at 9 months. 18F-T807 was more sensitive than 18F-THK5117 to tau pathology in this model, although both tracers present certain obstacles, which need to be considered in the design of longitudinal preclinical tau imaging studies.


Molecular detection of measles virus from children during a sporadic outbreak in two semi-urban areas in Nigeria.
According to the World Health Organization (WHO), African region accounts for 36% of deaths caused by measles worldwide. Nigeria has, over the years, recorded the highest average annual measles incidence per 100,000 populations in Africa. Measles epidemics have consistently been reported in northern Nigeria, but not in the South; reports of reduced protective haemagglutination inhibition antibody titers among children in Ibadan, southern Nigeria was made. Investigation of the viral agent responsible for the disease outbreak among children presenting with rash in two semi urban areas in southern Nigeria was carried out to confirm the etiology of the disease. Twenty six throat swabs (TS), and nineteen urine samples were collected from twenty six children residing in Onireke and Sabo areas of Ibadan following the report of an outbreak of rashes among children. Active case finding with the support of community leaders was used to locate the affected children. Multiplex reverse transcriptase polymerase chain reaction (MRT-PCR), was used to identify the agent. 21 of the 26 children screened tested positive for measles virus, but none was positive for Rubella virus. There was significant association between measles infection, and households with higher number of persons. Mass measles vaccination that targets overcrowded, rural and inaccessible areas is needed to increase herd immunity. Public health enlightenment on the benefits of vaccination is encouraged.


Isolation, Purification, and Application of Protoplasts and Transient Expression Systems in Plants.
Protoplasts, derived from plant cells, exhibit remarkable totipotency and hold significant value across a wide spectrum of biological and biotechnological applications. These versatile applications encompass protein subcellular localization and interaction analysis, gene expression regulation, functional characterization, gene editing techniques, and single-cell sequencing. Protoplasts' usability stems from their inherent accessibility and their ability to efficiently incorporate exogenous genes. In this review, we provide a comprehensive overview, including details on isolation procedures and influencing factors, purification and viability assessment methodologies, and the utilization of the protoplast transient expression system. The aim is to provide a comprehensive overview of current applications and offer valuable insights into protoplast isolation and the establishment of transient expression systems in a diverse range of plant species, thereby serving as a valuable resource for the plant science community.


[Lung cancer in the young adult and results of surgical treatment].
Sixty patients with primary lung cancer and under 40 years of age were operated from Jan. 1960 to June 1983. It comprised 3.7% of 1,635 lung cancers in all during the same period. The average age was 34.4 (17-39) years old. 35 were male and 25 female with a sex ratio of 1.4:1 which was lower than that reported for all lung cancers. Of the 60 patients, 31 (51.7%) presented with cough, 27 (45%) with bloody sputum, 23 (43.3%) chest pain and 13 (21.7%) feverishness. The average delay before the first medical examination was 6.4 months. It was over 1 year in 8 patients. The misdiagnosis rate was 76.7%. According to the TNM classification, the lesions were: stage I in 16.7%, stage II in 23.3% and stage III in 60%. By pathology, 45% were adenocarcinoma, 25% squamous cell carcinoma, 23.3% undifferentiated carcinoma and 6.7% squamous-adenocarcinoma. The resection rate was 83.3% (50 patients). The 1, 3, 5, 7 and 10 year survival rates were 83.3%, 42.5%, 32.3%, 18.5% and 21.1% which show that the survival rate of lung cancer in the young adults was similar to that of all ages. Most of the patients treated only by exploration died within 1.5 years. The authors believe that early diagnosis, early resection supplemented by radiotherapy, chemotherapy and immunotherapy might improve the survival rate of lung cancer in the young adults.


Stimulus-response uncoupling in the neutrophil. Adenosine A2-receptor occupancy inhibits the sustained, but not the early, events of stimulus transduction in human neutrophils by a mechanism independent of actin-filament formation.
Generation of superoxide anion (O2-) in response to occupancy of neutrophil chemoattractant receptors requires both early events ('triggering') and sustained signals ('activation'). We have previously demonstrated that occupancy of adenosine A2 receptors inhibits O2- generation by neutrophils. In parallel, adenosine-receptor occupancy promotes association of bound N-formylmethionyl-leucyl-phenylalanine (fMLP) receptors with the cytoskeleton, a process associated with termination of neutrophil activation (stimulus-response uncoupling). We undertook this study to determine whether inhibition of neutrophil function by adenosine-receptor occupancy requires intact actin filaments and to examine the effect of adenosine-receptor occupancy on the stimulated generation of intracellular signals involved in neutrophil triggering and activation. Occupancy of adenosine A2 receptors by 5'-N-ethylcarboxamidoadenosine (NECA, 1 microM) significantly increased (130 +/- 1% of control, P less than 0.001, n = 3) association of [3H]fMLP with cytoskeletal preparations. Cytochalasin B (5 micrograms/ml), an agent which disrupts actin filaments, completely blocked association of [3H]fMLP with cytoskeletal preparations, as previously reported. However, NECA markedly increased association of [3H]fMLP with the cytoskeleton even in the presence of cytochalasin B (P less than 0.0002). Moreover, NECA did not significantly affect either the early (30s) or the late (5 min) formation of actin filaments after stimulation by chemoattractant (fMLP, 0.1-100 nM). Cytochalasin B markedly inhibited actin-filament formation by stimulated neutrophils, and NECA did not reverse the effect of cytochalasin B on actin-filament formation. Adenosine-receptor occupancy did not affect the rapid peak in diacylglycerol generation (less than or equal to 15 s) from either [3H]arachidonate- or [14C]glycerol-labelled phospholipid pools. However, as would be predicted if occupancy of the adenosine receptor was a signal for early termination of cell activation, NECA (1 microM) markedly diminished the slow sustained generation of diacylglycerol. These results suggest that adenosine-A2-receptor occupancy does not affect triggering of the neutrophil, but that occupancy of adenosine receptors is an early signal for the termination of neutrophil activation, i.e. the 'premature' finish of signal transduction. Moreover, these data indicate that at least two pathways are available for increasing the association of ligated chemoattractant receptors with the cytoskeleton of neutrophils: F-actin-dependent and -independent.


Self-control in rhesus macaques (Macaca mulatta): controlling for differential stimulus exposure.
Previous research on self-control using macaques (Macaca fascicularis) showed these animals have a strong bias for a delayed, larger reinforcer (Self-control) over an immediate, smaller reinforcer (Impulsive). Typical studies of self-control have used a discrete trials methodology with a secondary discriminative stimulus during the delay periods. This results in a greater exposure to the stimulus representing the self-controlled option and may account for some of the early exclusive preference for self-control observed. The present experiment examined self-control bias in three rhesus macaques (Macaca mulatta) while controlling for differential durations of stimulus exposure. Subjects were presented stimuli via a computer monitor and made choices by touching the stimulus at which point both stimuli were removed for the delay periods. All three subjects displayed a nearly exclusive bias for the delayed, larger reinforcer self-control). These results are consistent with previous studies, despite the variations in methodology and species.


Force encoding in muscle spindles during stretch of passive muscle.
Muscle spindle proprioceptive receptors play a primary role in encoding the effects of external mechanical perturbations to the body. During externally-imposed stretches of passive, i.e. electrically-quiescent, muscles, the instantaneous firing rates (IFRs) of muscle spindles are associated with characteristics of stretch such as length and velocity. However, even in passive muscle, there are history-dependent transients of muscle spindle firing that are not uniquely related to muscle length and velocity, nor reproduced by current muscle spindle models. These include acceleration-dependent initial bursts, increased dynamic response to stretch velocity if a muscle has been isometric, and rate relaxation, i.e., a decrease in tonic IFR when a muscle is held at a constant length after being stretched. We collected muscle spindle spike trains across a variety of muscle stretch kinematic conditions, including systematic changes in peak length, velocity, and acceleration. We demonstrate that muscle spindle primary afferents in passive muscle fire in direct relationship to muscle force-related variables, rather than length-related variables. Linear combinations of whole muscle-tendon force and the first time derivative of force (dF/dt) predict the entire time course of transient IFRs in muscle spindle Ia afferents during stretch (i.e., lengthening) of passive muscle, including the initial burst, the dynamic response to lengthening, and rate relaxation following lengthening. Similar to acceleration scaling found previously in postural responses to perturbations, initial burst amplitude scaled equally well to initial stretch acceleration or dF/dt, though later transients were only described by dF/dt. The transient increase in dF/dt at the onset of lengthening reflects muscle short-range stiffness due to cross-bridge dynamics. Our work demonstrates a critical role of muscle cross-bridge dynamics in history-dependent muscle spindle IFRs in passive muscle lengthening conditions relevant to the detection and sensorimotor response to mechanical perturbations to the body, and to previously-described history-dependence in perception of limb position.