Developmental differences in the relative weighing of informants' social attributes.
We examined whether similarity, familiarity, and reliability cues guide children's learning and whether these cues are weighed differently with age. Three- to 5-year-olds (n = 184) met 2 informant puppets, 1 of which was similar (Experiment 1) or familiar (Experiment 2) to the participants. Initially, children's preference for either informant was measured. Children selected similar and familiar informants--over dissimilar and unfamiliar ones--as information sources at above-chance levels. In Experiment 1 the similar informant later provided accurate or inaccurate information (counterbalanced). Children's initial preference for similar sources was modified by reliability cues. However, 5-year-olds continued to be influenced by similarity, being less likely to avoid inaccurate sources if similar than dissimilar. In Experiment 2 the familiar informant was later portrayed as interpersonally similar or dissimilar (counterbalanced). Only 5-year-olds were influenced by similarity, preferentially interacting with similar informants regardless of familiarity. These results suggest that similarity influences children's learning and that children's relative weighing of social cues varies with age--with younger children being especially focused on familiarity and older children being particularly attentive to similarity.


Human peripheral blood lymphocytes sensitised to PPD respond to in vitro stimulation with increased expression of CD69 and CD134 activation antigens and production of Th-1 type cytokines.
Individuals sensitised to Mycobacterium tuberculosis antigens by infection, vaccination or Mantoux test generate specific memory cells. The response to in vitro restimulation with PPD is observed as the lymphoid cell proliferation and production of Th-1 type cytokines. Cell-mediated immune response was measured by Mantoux test, lymphocyte blast transformation test, estimation of IFN-gamma production (Quantiferon, ELISPOT), and expression of CD69 and CD134 molecules on the T-helper lymphocytes (CD4+). All the methods used were compared for parity of the results. According to Mantoux test results, the patients could be distributed into two groups: responder and non-responder group. Induration in Mantoux test after a new contact with PPD in non-responders was smaller than 5 mm, they produced only small amounts of IFN-gamma, lymphocyte blast transformation was poor, and expression of CD69 and CD134 was low. In responders reaction was much more intensive in all tests measured. We conclude that the reactivity of memory cells to M. tuberculosis antigens can be effectively detected by Mantoux test. The same was true also for the in vitro tests presented but in addition the in vitro tests give more information about the mechanism involved in the immune response against M. tuberculosis.


Developmental dimorphism and expression of chemosensory-mediated behavior: habitat selection by a specialist marine herbivore.
Developmental dimorphisms provide an opportunity to compare sensory systems and behavior patterns between different forms of a single species. Alternative morphs differing in dispersal ability often show behavioral differences that mediate life-history trade-offs. We measured the behavioral responses of both long-lived, feeding larvae and short-lived, non-feeding larvae of the specialist marine herbivore Alderia modesta during habitat selection. Larvae immediately responded to waterborne cues from the adult host algae by increasing their turning rate, by changing their swimming speed in the water and by moving in rapid hops or spiraling along the bottom. These behavior patterns retained larvae in areas where the dissolved cue was initially perceived, and prolonged exposure to the cue increased the percentage of larvae that initiated metamorphosis. Despite their differences in life span and trophic mode, both larval morphs displayed similar behavior patterns when stimulated by the waterborne cue. Long-lived larvae had a stronger response, however, suggesting that settlement behavior may offset the costs of a prolonged larval life. This is the first study to examine the effects of dimorphic development on chemosensory-mediated behavior.


Ex-vivo analysis of human natural killer T cells demonstrates heterogeneity between tissues and within established CD4(+) and CD4(-) subsets.
Our understanding of human type 1 natural killer T (NKT) cells has been heavily dependent on studies of cells from peripheral blood. These have identified two functionally distinct subsets defined by expression of CD4, although it is widely believed that this underestimates the true number of subsets. Two recent studies supporting this view have provided more detail about diversity of the human NKT cells, but relied on analysis of NKT cells from human blood that had been expanded in vitro prior to analysis. In this study we extend those findings by assessing the heterogeneity of CD4(+) and CD4(-) human NKT cell subsets from peripheral blood, cord blood, thymus and spleen without prior expansion ex vivo, and identifying for the first time cytokines expressed by human NKT cells from spleen and thymus. Our comparative analysis reveals highly heterogeneous expression of surface antigens by CD4(+) and CD4(-) NKT cell subsets and identifies several antigens whose differential expression correlates with the cytokine response. Collectively, our findings reveal that the common classification of NKT cells into CD4(+) and CD4(-) subsets fails to reflect the diversity of this lineage, and that more studies are needed to establish the functional significance of the antigen expression patterns and tissue residency of human NKT cells.


Genetic manipulation of cell line derived reticulocytes enables dissection of host malaria invasion requirements.
Investigating the role that host erythrocyte proteins play in malaria infection is hampered by the genetic intractability of this anucleate cell. Here we report that reticulocytes derived through in vitro differentiation of an enucleation-competent immortalized erythroblast cell line (BEL-A) support both successful invasion and intracellular development of the malaria parasite Plasmodium falciparum. Using CRISPR-mediated gene knockout and subsequent complementation, we validate an essential role for the erythrocyte receptor basigin in P. falciparum invasion and demonstrate rescue of invasive susceptibility by receptor re-expression. Successful invasion of reticulocytes complemented with a truncated mutant excludes a functional role for the basigin cytoplasmic domain during invasion. Contrastingly, knockout of cyclophilin B, reported to participate in invasion and interact with basigin, did not impact invasive susceptibility of reticulocytes. These data establish the use of reticulocytes derived from immortalized erythroblasts as a powerful model system to explore hypotheses regarding host receptor requirements for P. falciparum invasion.


An e-learning reproductive health module to support improved student learning and interaction: a prospective interventional study at a medical school in Egypt.
The Public Health (PH) course at the medical college of Cairo University is based on traditional lectures. Large enrollment limits students' discussions and interactions with instructors. Evaluate students' learning outcomes as measured by improved knowledge acquisition and opinions of redesigning the Reproductive Health (RH) section of the PH course into e-learning and assessing e-course utilization. This prospective interventional study started with development of an e-learning course covering the RH section, with visual and interactive emphasis, to satisfy students' diverse learning styles. Two student groups participated in this study. The first group received traditional lecturing, while the second volunteered to enroll in the e-learning course, taking online course quizzes. Both groups answered knowledge and course evaluation questionnaires and were invited to group discussions. Additionally, the first group answered another questionnaire about reasons for non-participation. Students participating in the e-learning course showed significantly better results, than those receiving traditional tutoring. Students who originally shunned the e-course expressed eagerness to access the course before the end of the academic year. Overall, students using the redesigned e-course reported better learning experiences. An online course with interactivities and interaction, can overcome many educational drawbacks of large enrolment classes, enhance student's learning and complement pit-falls of large enrollment traditional tutoring.


Sca-1+ cardiac progenitor cells and heart-making: a critical synopsis.
The identification, in the adult, of cardiomyocyte turnover events and of cardiac progenitor cells (CPCs) has revolutionized the field of cardiovascular medicine. However, the low rate of CPCs differentiation events reported both in vitro and in vivo, even after injury, raised concerns on the biological significance of these subsets. In this Comprehensive Review, we discuss the current understanding of cardiac Lin(-)Sca-1(+) cells in light of what is also known for cellular compartments with similar phenotypes in other organs. The Lin(-)Sca-1(+) heart subset is heterogeneous and displays a mesenchymal profile, characterized by a limited ability to generate cardiomyocytes in vitro and in vivo, even after injury. There is no evidence for Sca-1 expression in embryonic cardiovascular progenitors. In other organs, Sca-1 expression is mainly observed on mesoderm-derived cells, although it is not restricted to stem/progenitor cell populations. It is urgent to determine, at a single cell level, to which extent cardiac Lin(-)Sca-1(+) cells overlap with the fibroblast compartment.


Use of free thin anterolateral thigh flaps combined with cervicoplasty for reconstruction of postburn anterior cervical contractures.
Free thin anterolateral thigh flaps combined with cervicoplasty were used in a series of seven patients undergoing reconstruction for previous burn injury from September of 2000 to May of 2001 at Chang Gung Memorial Hospital. This method uses a suprafascial dissection technique to provide a thin flap to improve cervical contour. Neck contractures had resulted from flame burns in six patients and from a chemical burn in one patient. The mean age was 32.7 years (range, 22 to 45 years). The size of excised scar ranged from 10 x 2 cm to 26 x 5 cm (mean, 19.7 x 3.3 cm). The size of flaps ranged from 11 x 5 cm to 26 x 8 cm (mean, 21.3 x 6.5 cm). Average operative time was 6 hours. Average hospital stay was 10 days. All flaps survived, with one flap sustaining partial marginal loss. The donor site was closed primarily in five cases and by using a split-thickness skin graft in two cases. At a mean follow-up time of 5 months, the functional improvement was measured as follows: a mean increase in extension of 30 degrees (preoperatively, 95 degrees; postoperatively, 125 degrees), a mean increase in rotation of 18 degrees (preoperatively, 59 degrees; postoperatively, 77 degrees), and a mean increase in lateral flexion of 12.5 degrees (preoperatively, 26.5 degrees; postoperatively, 39 degrees). The average cervicomandibular angle was improved by 25 degrees (preoperatively, 145 degrees; postoperatively, 120 degrees). This series demonstrates that the use of free thin anterolateral thigh flaps combined with cervicoplasty provides a one-stage reconstruction with a thin, pliable flap that achieves good cervical contour with low donor-site morbidity.


Investigating the effects of glyphosate on the bumblebee proteome and microbiota.
Glyphosate is one of the most widely used herbicides globally. It acts by inhibiting an enzyme in an aromatic amino acid synthesis pathway specific to plants and microbes, leading to the view that it poses no risk to other organisms. However, there is growing concern that glyphosate is associated with health effects in humans and an ever-increasing body of evidence that suggests potential deleterious effects on other animals including pollinating insects such as bees. Although pesticides have long been considered a factor in the decline of wild bee populations, most research on bees has focussed on demonstrating and understanding the effects of insecticides. To assess whether glyphosate poses a risk to bees, we characterised changes in survival, behaviour, sucrose solution consumption, the digestive tract proteome, and the microbiota in the bumblebee Bombus terrestris after chronic exposure to field relevant doses of technical grade glyphosate or the glyphosate-based formulation, RoundUp Optima+®. Regardless of source, there were changes in response to glyphosate exposure in important cellular and physiological processes in the digestive tract of B. terrestris, with proteins associated with oxidative stress regulation, metabolism, cellular adhesion, the extracellular matrix, and various signalling pathways altered. Interestingly, proteins associated with endocytosis, oxidative phosphorylation, the TCA cycle, and carbohydrate, lipid, and amino acid metabolism were differentially altered depending on whether the exposure source was glyphosate alone or RoundUp Optima+®. In addition, there were alterations to the digestive tract microbiota of bees depending on the glyphosate source No impacts on survival, behaviour, or food consumption were observed. Our research provides insights into the potential mode of action and consequences of glyphosate exposure at the molecular, cellular and organismal level in bumblebees and highlights issues with the current honeybee-centric risk assessment of pesticides and their formulations, where the impact of co-formulants on non-target organisms are generally overlooked.


Preventive Effects and Mechanisms of Garlic on Dyslipidemia and Gut Microbiome Dysbiosis.
Garlic (Allium sativum L.) contains prebiotic components, fructans, antibacterial compounds, and organosulfur compounds. The complex ingredients of garlic seem to impart a paradoxical result on the gut microbiome. In this study, we used a mouse model to clarify the effects of whole garlic on the gut microbiome. C57BL/6N male mice were fed with or without whole garlic in normal diet (ND) or in high-fat diet (HFD) for 12 weeks. Supplementation with whole garlic attenuated HFD-enhanced ratio of serum GPT/GOT (glutamic-pyruvic transaminase/glutamic-oxaloacetic transaminase), levels of T-Cho (total cholesterol) and LDLs (low-density lipoproteins), and index of homeostatic model assessment for insulin resistance (HOMA-IR), but had no significant effect in the levels of serum HDL-c (high density lipoprotein cholesterol), TG (total triacylglycerol), and glucose. Moreover, garlic supplementation meliorated the HFD-reduced ratio of villus height/crypt depth, cecum weight, and the concentration of cecal organic acids. Finally, gut microbiota characterization by high throughput 16S rRNA gene sequencing revealed that whole garlic supplementation increased the α-diversity of the gut microbiome, especially increasing the relative abundance of f_Lachnospiraceae and reducing the relative abundance of g_Prevotella. Taken together, our data demonstrated that whole garlic supplementation could meliorate the HFD-induced dyslipidemia and disturbance of gut microbiome.


Recurrent Spitz's nevi. A clinicopathologic investigation.
Spitz's nevi recur uncommonly following initial removal. A clinicopathologic investigation was performed on 16 such cases. The initial nevi in almost all cases extended to the margins of the sections. Otherwise, these lesions showed no unusual clinical or histologic features. The average recurrence time was 13 months, with a range from 2 months to 3 years. The recurrent lesions occasionally were mistaken clinically for keloids. Histologically, recurrent lesions were predominantly intradermal. Nests, fascicles, and individual spindle and/or epithelioid cells extended to the deep reticular dermis and occasionally into the subcutaneous fat. The surrounding stroma was densely fibrotic. Recurrent Spitz's nevi are different clinically and histologically from recurrent ordinary melanocytic nevi. They also often differ histologically and clinically from primary Spitz's nevi. Recurrent Spitz's nevi are similar histologically to the desmoplastic type of Spitz's nevus.


Classifying three imaginary states of the same upper extremity using time-domain features.
Brain-computer interface (BCI) allows collaboration between humans and machines. It translates the electrical activity of the brain to understandable commands to operate a machine or a device. In this study, we propose a method to improve the accuracy of a 3-class BCI using electroencephalographic (EEG) signals. This BCI discriminates rest against imaginary grasps and elbow movements of the same limb. This classification task is challenging because imaginary movements within the same limb have close spatial representations on the motor cortex area. The proposed method extracts time-domain features and classifies them using a support vector machine (SVM) with a radial basis kernel function (RBF). An average accuracy of 74.2% was obtained when using the proposed method on a dataset collected, prior to this study, from 12 healthy individuals. This accuracy was higher than that obtained when other widely used methods, such as common spatial patterns (CSP), filter bank CSP (FBCSP), and band power methods, were used on the same dataset. These results are encouraging and the proposed method could potentially be used in future applications including BCI-driven robotic devices, such as a portable exoskeleton for the arm, to assist individuals with impaired upper extremity functions in performing daily tasks.


A Case of Acute Type A Aortic Dissection after Coronary Artery Bypass Grafting.
The patient was a 69-year-old man who underwent emergency surgery for acute aortic dissection that developed 5 months after coronary artery bypass grafting. The left internal thoracic artery (LITA) graft anastomosed to the left descending artery was not affected by the aortic dissection, and during the ascending aortic replacement, the artery was not identified for clamping. Although fully sufficient cardioplegia was not achieved due to the patent LITA graft, the patient's postoperative cardiac function was good. The two anastomotic sites of the vein grafts to the ascending aorta were excised along with a remnant of the aortic wall in an island fashion and were reimplanted onto the artificial graft. Based on the site of intimal tear, we speculated that partial clamping during the previous surgery had caused the dissection.


Biological and phylogenetic characterization of pigeon paramyxovirus serotype 1 circulating in wild North American pigeons and doves.
As part of West Nile virus surveillance programs in Rhode Island and eastern Texas between 2000 and 2007, brain tissue was collected from 5,608 dead birds representing 21 avian orders found in public places or reported by homeowners. Fifteen Newcastle disease virus isolates were recovered only from birds of the order Columbiformes and were positively identified by the USDA-validated real-time reverse transcription-PCR assay targeting the matrix gene and more specifically as pigeon paramyxovirus serotype 1 (PPMV-1) by hemagglutinin inhibition with monoclonal antibodies. Based upon partial genomic sequencing and phylogenetic analysis, the newly isolated viruses represent a distinct sublineage within class II genotype VIb. All of the viruses (15/15) were classified as virulent based upon their fusion cleavage site motif ((112)RRKKRF(117)) and intracerebral pathogenicity indices of >0.7 (ranging from 0.98 to 1.35); however, these viruses escaped detection by the fusion gene-based real-time PCR test for virulence. Modifications introduced to the probe site of the fusion gene-based assay allowed rapid virulence detection within this distinct sublineage.


Homogenizing cellular tension by hepatocyte growth factor in expanding epithelial monolayer.
Hepatocyte growth factor (HGF) induces cell migration and scattering by mechanisms that are thought to tip a local balance of competing physical forces; cell-to-cell and cell-to-substrate forces. In this local process, HGF is known to attenuate local cadherin-dependent adhesion forces for cell-cell junction development and enhance local integrin-dependent contractile forces for pulling neighboring cells apart. Here we use an expanding island of confluent Madin-Darby canine kidney (MDCK) cells as a model system to quantify the collective cell migration. In the absence of HGF, cell trajectories are highly tortuous whereas in the presence of HGF, they become far less so, resembling free expansion of a gas. At the level of cell-to-cell junctions, HGF attenuates the linkage of stress fibers to cell-to-cell junctions with concomitant decrease in intercellular stress. At the level of cell-to-substrate junctions, HGF augments the linkage of stress fibers to cell-to-substrate junctions with no apparent effect on traction. Together, HGF induces both structural changes in the actin-bound junctional protein complex and physical forces spanning multicellular clusters, which further promotes the expansion of confluent cellular layer.


Total tubeless ultra-mini supine percutaneous nephrolithotomy: A feasibility study.
The ultra-mini percutaneous nephrolithotomy (PCNL) for treating low-volume renal nephrolithiasis is being used as an alternative modality to the conventional PCNL. However its use in the supine position has been scarcely reported. Patients who underwent ultra-mini PCNL in the supine position within the time frame of January 2017 to July 2017 were studied. All these patients had this as their first-line treatment. The patients had calculus limited to either a single calyx or just extending to the pelvis and the stone size was less than 2 cm in its maximal dimension. An 8.5 Fr operating nephroscope was used. The patients were positioned in the Galdakao modified Valdivia supine position. The stones were fragmented using Holmium-YAG laser. Various surgical outcomes including duration of the surgery, stone-free rate and any subsequent complications-if any-were analyzed. The study includes a series of 14 patients with 15 renal units (one patient treated with bilateral renal stone disease). The mean age of the patients was 39.07 years and body mass index was 25.5 kg/m2. Intrarenal stone location was as follows: lower calyx, n=8; middle calyx, n=3, upper calyx, n=1, and pelvis, n=3. Median operative time was 52.66 min (range: 40-70) and the stone-free rate was 93.3%. Only one patient had residual fragments and needed subsequent extracorporeal shock wave lithotripsy. Ultra-mini PCNL in supine position with a complete tubeless approach for renal stone disease is a safe method for treating low-volume disease. Studies with a larger cohort may be required to finally validate this technique.


Comparison of FIB-4 and transient elastography in evaluating liver fibrosis of chronic hepatitis C subjects in community.
The role of non-invasive methods to evaluate fibrosis severity of chronic hepatitis C (CHC) subjects in community needs to be explored. This study investigated FIB-4 and transient elastography (TE) in staging liver fibrosis of CHC subjects in community. A total of 905 subjects who were positive for anti-HCV antibody from five districts of Tainan City of Taiwan were invited to participate in surveillance activities for CHC. FIB-4 and TE were measured for each participant. A total of 502 subjects with detectable HCV RNA and valid TE were enrolled. The distribution of FIB-4 and TE values differed markedly. Both methods exhibited a strongest correlation in subjects with at age 50~60 years (r = 0.655, p <0.001). FIB-4 score increased proportionally with age (p <0.001), but TE did not (p = 0.142). The intraclass correlation efficient of both methods was 0.255 (p <0.001). Subjects with TE defined advanced fibrosis exhibited younger age, higher BMI, higher platelet count, lower FIB-4 score, higher incidence of fatty liver and splenomegaly, and higher controlled attenuation parameter value than those defined by FIB-4. By multivariate logistic regression analysis, higher ALT levels, higher incidence of fatty liver, and presence of splenomegaly were the independent factors associated with advanced fibrosis defined by TE rather than defined by FIB-4. FIB-4 and TE defined different distribution of fibrosis stages in same HCV population. FIB-4 was deeply influenced by age whereas TE was not. TE had the advantages over than FIB-4 in strong association with splenomegaly and in detecting the role of non-alcoholic fatty liver disease in advanced fibrosis.


Bordetella pertussis infection in mice: correlation of specific antibodies against two antigens, pertussis toxin, and filamentous hemagglutinin with mouse protectivity in an intracerebral or aerosol challenge system.
The correlation of titers of specific serum immunoglobulin G antibodies against two antigens, pertussis toxin (PT), and filamentous hemagglutinin (FHA), which are the main components of pertussis vaccine in Japan, with mouse protectivity was examined by both intracerebral and aerosol challenge systems with virulent Bordetella pertussis cells. Titer of the antibodies was calculated from the enzyme-linked immunosorbent assay (ELISA) unit given arbitrarily to reference antibodies. PT antibody titer which protected 50% of mice was indistinguishable in both active immunization followed by intracerebral challenge and passive immunization followed by aerosol challenge. The 50% effective dose was 23 ELISA U/ml in the former mice and 24 ELISA U/mouse in the latter. In the intracerebral challenge system, FHA did not elicit a protective response but was very helpful for PT as an immunizing antigen. When anti-FHA immunoglobulin G coexisted with anti-PT immunoglobulin G in mice, the 50% effective dose of PT antibody was 4.4 or 10 ELISA U/mouse in intracerebral or aerosol challenge systems, respectively. In this active immunization system, pertussis toxoid of 1 micrograms or 0.1 microgram/mouse produced PT antibody of ca. 20 or 5 ELISA U/ml, respectively. It was concluded that pertussis toxoid or its antibody was much more potent than Formalin-treated FHA or its antibody; Formalin-treated FHA or its antibody was helpful when it was administered with pertussis toxoid toxoid or its antibody, however.


Four consecutive reactions in one pot: cascade formation of an unprecedented triphosphatricyclo[3.2.1.02,7]oct-3-ene.
A hitherto unknown triphosphatricyclo[3.2.1.02,7]oct-3-ene was obtained in high yield by a total of four consecutive pericyclic reactions from di-2-pyrone and excess TMS-C[triple bond, length as m-dash]P. DFT calculations gave insight into the reaction mechanism. The chiral phosphorus cage readily forms coordination compounds with Au(i) and Cu(i).


Endorphin activity in childhood psychosis. Spinal fluid levels in 24 cases.
Twenty 2- to 13-year-old infantile autistic children (16 boys and four girls) and four 4- to 13-year-old children (two boys and two girls) with other kinds of childhood psychoses were compared with eight 6-month-old to 6-year-old normal children with regard to cerebrospinal fluid contents of endorphin fractions I and II. The psychosis groups showed higher mean cerebrospinal fluid endorphin fraction II levels, and 11 (55%) of the 20 autistic patients showed values higher than the highest in the group of normal children. There was a trend toward a correlation between high fraction II levels and self-destructiveness and decreased pain sensibility in the psychotic children. The results are regarded as preliminary but as warranting further research in this potentially fruitful field.


Induction of nitric oxide production by polyosides from the cell walls of Streptococcus mutans OMZ 175, a gram-positive bacterium, in the rat aorta.
The cardiovascular dysfunctions associated with septic shock induced by gram-negative or gram-positive bacteria (gram-positive or gram-negative septic shock) are comparable. In gram-negative septic shock, lipopolysaccharide (LPS) induces nitric oxide (NO) synthase, which contributes to the vascular hypotension and hyporeactivity to vasoconstrictors. The role of NO in gram-positive septic shock and the nature of the bacterial wall components responsible for the vascular effects of gram-positive bacteria are not well known. This study investigated the vascular effects of cell wall serotype polyosides, rhamnose glucose polymers (RGPs), from Streptococcus mutans, in comparison with lipoteichoic acid (LTA) from Staphylococcus aureus, on the induction of NO synthase activity in the rat aorta. We show that 10 microg of both RGPs and LTA per ml induced hyporeactivity to noradrenaline, L-arginine-induced relaxation, increases of 2.2- and 7.8-fold, respectively, of cyclic GMP production, and increases of 7- and 12-fold in nitrite release. All of these effects appeared after several hours of incubation and were inhibited by N(omega)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthase. Electron paramagnetic resonance spin trapping experiments demonstrated directly that RGPs and LTA induced NO overproduction (four- to eightfold, respectively) in rat aortic rings; this production was inhibited by L-NAME and prevented by dexamethasone. These results demonstrate directly the induction of NO production in vascular tissue by LTA and show that another, chemically different component of gram-positive bacteria can also have these properties. This result suggests that different components of the gram-positive bacterial wall could be implicated in the genesis of cardiovascular dysfunctions observed in gram-positive septic shock.


[Individual-typological distinctions of mental work capacity in aging].
Investigated age and personal features of mental serviceability. It is revealed that psychological stability of the person renders stronger influence on mental serviceability than age. It is shown that mental serviceability depends not only on properties of temperament, but also on character traits. In this connection paramount value has formation of the emotional--strong-willed character traits, and also such properties of character, as self-esteem, advantage, independence, confidence of the abilities, social maturity that will promote preservation of mental serviceability at ageing.


Social Desirability, defensiveness and self-report psychiatric inventory scores.
The effects of social desirability and defensiveness on scores on 2 self-report psychiatric inventories, the General Health Questionnaire (GHQ) and the Middlesex Hospital Questionnaire (MHQ) were investigated in a female subject group assessed for research purposes in an occupational setting. It was found that defensiveness did not affect the reporting of somatic symptoms, but it significantly affected the reporting of all psychological distress. The effect of social desirability was more specific, only the GHQ social dysfunction subscale showing a significant correlation, an effect attributable to the influence of the setting in which the data were obtained.


[Classification of thyroid gland disease on the basis of selenium concentration in serum].
The aim of this study was to estimate the concentration of total selenium in serum women with thyroid gland disease. Selenium was determined by atomic absorption spectrometry using the hydride generation method (HG-AAS). Research was determined in 94 patients with thyroid gland disease and in 28 healthy controls. Selenium concentration of serum was variously in patients than in control group and patients with different thyroid gland diseases. Concentration in control group was 0.06231 microg/ml, in goitre group--0.05612 microg/ml, in hyperthyroidism--0.07149 microg/ml and in hypothyroidism--0.09088 microg/ml.


Delivery strategies to target therapies to inflammatory tissue.
Inflammation plays a key role in many chronic disease processes as well as an acute role in injury and wound healing. Various cell types are recruited from the bloodstream to the inflamed site through adhesion molecules, cytokines, chemokines and others. This review examines many drug-targeting strategies that make use of these molecules or signaling pathways, and seeks to describe certain commonalities irrespective of the disease process or agent to be delivered. A survey of the literature, primarily within the last year, was performed. Search words included 'drug targeting' and 'inflammation' and of those, the scope was refined to include those studies that specifically sought to modify or ameliorate an aspect of the inflammatory process in the treatment of a disease. Inflammation plays a key role in many diseases, and many similar targets (such as adhesion molecules) are the focus of the treatment of those diseases.


Neonatal castration affects intrathymic kinetics of T-cell differentiation and the spleen T-cell level.
To test putative interdependence in the ontogenesis of the hypothalamic-pituitary-gonadal and thymic-lymphatic axes, thymocyte differentiation and maturation was examined in neonatally castrated (Cx) adult rats. In the hypercellular thymi of Cx rats, the proportion of the least mature CD4(-)CD8(-)TCRalphabeta(-) triple negative (TN) thymocytes was reduced, while the proportions of all downstream double positive (DP) subsets (TCRalphabeta(-), TCRalphabeta(low) and TCRalphabeta(high)) were increased when compared with neonatally sham-castrated (Sx) adult rats. This suggested an accelerated thymocyte transition from the TN to DP TCRalphabeta(low) developmental stage accompanied by an increased positive/ reduced negative thymocyte selection. The increased thymocyte surface density of Thy-1, which is implicated in thymocyte hyposensitivity to negative selection, in Cx rats further supports the previous assumption. The finding that the proportions of both single positive (SP) TCRalphabeta(high) thymocyte subsets were reduced, while their numbers were increased (CD4(+)CD8(-)) or unaltered (CD4(-)CD8(+)), coupled with results demonstrating an increased level of CD4(-)CD8(+) cells without changes in that of CD4(+)8(-) cells in the spleen indicate: (i) accelerated differentiation and maturation of the positively selected DP TCRalphabeta(high) thymocytes towards CD4(-)8(+) TCRalphabeta(high) cells followed by increased emigration of the mature cells and (ii) decelerated differentiation and maturation towards CD4(+)8(-)TCRalphabeta(high) cells in Cx rats. Furthermore, the unaltered proportion of intrathymically developing CD4(+)CD25(+)Foxp3(+) regulatory cells in Cx rats, in light of putative hyposensitivity of thymocytes to negative selection suggesting reduced elimination of autoreactive cells, may provide a firm basis for understanding the reasons behind increased susceptibility of Cx rats to autoimmune disease induction.


Estimating behavioral parameters in animal movement models using a state-augmented particle filter.
Data on fine-scale animal movement are being collected worldwide, with the number of species being tagged and the resolution of data rapidly increasing. In this study, a general methodology is proposed to understand the patterns in these high-resolution movement time series that relate to marine animal behavior. The approach is illustrated with dive data from a northern fur seal (Callorhinus ursinus) tagged on the Pribilof Islands, Alaska, USA. We apply a state-space model composed of a movement model and corresponding high-resolution vertical movement data. The central goal is to estimate parameters of this movement model, particularly their variation on appropriate time scales, thereby providing a direct link to behavior. A particle filter with state augmentation is used to jointly estimate the movement parameters and the state. A multiple iterated filter using overlapping data segments is implemented to match the parameter time scale with the behavioral inference. The time variation in the auto-covariance function facilitates identification of a movement model, allows separation of observation and process noise, and provides for validation of results. The analysis yields fitted parameters that show distinct time-evolving changes in fur seal behavior over time, matching well what is observed in the original data set.


Best Practice During Teleconsultations With Adolescents: A Scoping Review.
Teleconsultations are increasingly used to deliver health care, yet guidance on how to maximize health outcomes and ensure the quality and rights-based principles of adolescent health care during teleconsultations is lacking. This scoping review synthesized the literature on teleconsultations with adolescents, with the objective of informing a practical guidance for healthcare professionals. Eight databases were searched to identify articles published between 2010 and 2020 in English, French, or Spanish that provided evidence or guidance on synchronous teleconsultations with 10- to 19-year-olds. Web sites in six high-income countries and six low- to middle-income countries were also searched and a Google search was conducted. Data were analyzed using narrative synthesis. Of 59 total references, 51 were from high-income countries. References included primary research (n = 21), reviews (n = 13), clinical guidance (n = 9), case reports (n = 9), commentaries (n = 6), and a website (n = 1). Just under half (46%) were descriptive, qualitative, or expert opinion. The main focus was mental health and behavioral disorders. Good evidence on the complexities of conducting teleconsultations with adolescents is lacking. Questions remain regarding the scope and acuity of health issues for which teleconsultations are appropriate, their role in overcoming or contributing to inequalities, and the practicalities of conducting consultations.


Effect of CD38 on the multidrug resistance of human chronic myelogenous leukemia K562 cells to doxorubicin.
Drug resistance is a serious challenge in cancer chemotherapy. Alterations in the intracellular concentration and homeostasis of calcium (Ca2+) may contribute to the development of drug resistance. To investigate the mechanism of drug resistance in leukemia, the present study rendered human chronic myelogenous leukemia K562 cells resistant to the cytotoxic effect of doxorubicin by progressively adapting the sensitive parental K562 cells to doxorubicin. The resulting cells were termed K562/DOX. Subsequently, the expression of two multidrug resistance proteins, P-glycoprotein (P-gp) and multidrug resistance protein 1 (MRP1), was analyzed in K562/DOX cells. In addition to P-gp and MRP1, these cells also expressed cluster of differentiation (CD)38 and its active enzyme adenosine diphosphate (ADP)-ribosyl cyclase. The present study also demonstrated that K562/DOX cells responded to cyclic ADP-ribose-mediated increases in intracellular Ca2+. These data indicate that CD38 may participate in the development of drug resistance to doxorubicin in K562 cells.


Connexin37 reduces smooth muscle cell proliferation and intimal hyperplasia in a mouse model of carotid artery ligation.
Intimal hyperplasia (IH) is an abnormal response to vessel injury characterized by the dedifferentiation, migration, and proliferation of quiescent vascular smooth muscle cells (VSMC) to form a neointima layer. Vascular connexins (Cx) are involved in the pathophysiology of various vascular diseases, and Cx43, the main Cx expressed in VSMC, has been shown to promote VSMC proliferation and IH. The aim of this study was to investigate the participation of another Cx, namely Cx37, in the formation of the neointima layer. Wild-type (WT) and Cx37-deficient (Cx37-/-) C57BL/6J mice were subjected to carotid artery ligation (CAL), a model of vessel injury and IH. The neointima developed linearly in WT until 28 days post surgery. In contrast, the neointima layer was almost absent 14 days after surgery in Cx37-/- mice, and twice as more developed after 28 days compared to WT mice. This large neointima formation correlated with a two-fold increase in cell proliferation in the media and neointima regions between 14 and 28 days in Cx37-/- mice compared to WT mice. The CAL triggered Cx43 overexpression in the media and neointima layers of ligated carotids in WT mice, and selectively up-regulated Cx37 expression in the media layer, but not in the neointima layer. The de novo expression of Cx37 in human primary VSMC reduced cell proliferation and P-Akt levels, in association with lower Cx43 levels, whereas Cx43 overexpression increased P-Akt levels. The presence of Cx37 in the media layer of injured arteries restrains VSMC proliferation and limits the development of IH, presumably by interfering with the pro-proliferative effect of Cx43 and the Akt pathway.


Anaphylatoxin binding and degradation by rat peritoneal mast cells. Mechanisms of degranulation and control.
Incubation of radiolabeled human C3a with rat peritoneal mast cells resulted in high levels of uptake and extensive degradation of the ligand. Both cell-bound and free radiolabeled human C3a underwent extensive degradation by rat mast cells even at 0 degrees C. We examined several protease inhibitors for their ability to prevent degradation of radiolabeled human C3a by the rat mast cells. The inhibitors PMSF, chymostatin, and soybean trypsin inhibitor were most effective in preventing radiolabeled human C3a degradation. Degradation of the cell-bound ligand was totally inhibited only by PMSF. These compounds are effective inhibitors of a chymotrypsin-like enzyme (chymase) extracted from rat mast cells. Chemical cross-linking of radiolabeled human C3a to surface components on the rat mast cells, in the presence of PMSF, revealed one major and two minor bands. The mast cell component in both the major and minor bands proved to be chymase-associated based on a direct comparison with purified chymase isolated from rat mast cells. However, neither antichymase antibody nor chymase inhibitors influenced the degranulating activity of C3a on rat mast cells that occur independently of the C3a-chymase interactions. We conclude that there are neither specific C3a-binding sites on rat mast cells nor specific receptors whose occupancy leads to cellular activation. Although human C3ades Arg is inactive on guinea pig ileal and lung tissue, it binds to and induces degranulation of rat mast cells, as well as enhances vascular permeability in rat skin, at concentrations nearly identical to that of intact C3a. The fact that both C3a and C3ades Arg stimulated mast cell activation, at concentrations in excess of 10(-6) M, argues against specific binding sites for the anaphylatoxin on rat mast cells. It is proposed that the cationic C3a molecule activates rat mast cells in a secretory and nonlytic manner by a nonspecific mechanism similar to that of other polybasic compounds.


Household fuels, low birth weight, and neonatal death in India: the separate impacts of biomass, kerosene, and coal.
We examined the impact of maternal use of different household cooking fuels in India on low birth weight (LBW<2500g), and neonatal mortality (death within 28 days of birth). Using cross-sectional data from India's National Family Health Survey (NFHS-3), we separately analyzed the prevalence of these two outcomes in households utilizing three types of high-pollution fuels for cooking - biomass, coal, and kerosene - using low-pollution fuels (gas and biogas) as the comparison "control" group. Taking socioeconomic and child-specific factors into account, we employed logistic regression to examine the impact of fuel use on fetal and infant health. The results indicate that household use of high-pollution fuels is significantly associated with increased odds of LBW and neonatal death. Compared to households using cleaner fuels (in which the mean birth weight is 2901g), the primary use of coal, kerosene, and biomass fuels is associated with significant decreases in mean birth weight (of -110g for coal, -107g for kerosene, and -78g for biomass). Kerosene and biomass fuel use are also associated with increased risk of LBW (p<0.05). Results suggest that increased risk of neonatal death is strongly associated with household use of coal (OR 18.54; 95% CI: 6.31-54.45), and perhaps with kerosene (OR 2.30; 95% CI: 0.95-5.55). Biomass is associated with increased risk of neonatal death among infants born to women with no more than primary education (OR 7.56; 95% CI: 2.40-23.80). These results are consistent with a growing literature showing health impacts of household air pollution from these fuels.


Racial and gender differences in outcome after carotid endarterectomy.
Women and minorities were underrepresented in trials demonstrating carotid endarterectomy (CEA) is superior to medical treatment for significant carotid stenosis. These trials also revealed that the benefit of CEA is largely determined by the incidence of operative complications. Our series of 429 CEAs reflects a more diverse population (41% women, 24% blacks). We questioned if outcome was related to race, gender or other factors. Stroke occurred after 4.9 per cent of operations, cardiac events after 3 per cent, and death after 2 per cent. No factors correlated with cardiac events. Diabetes, smoking, neurologic symptoms, shunting, and patch closure did not correlate with complications. Chronic renal insufficiency (CRI), emergent operation, and operation by neurosurgeons correlated with stroke. Black females (BF) had significantly more strokes than did others (16% versus 3%). More BF had CRI, but their higher complication rate persisted when CRI patients were excluded. More BF were hypertensive (98% versus 74%), but hypertension did not correlate with complications. However, severe acute perioperative hypertension was common in BF experiencing complications and may be related to the differences observed. These findings highlight the need for better understanding of racial and gender outcome differences after CEA in order to improve risks and allow modification of selection criteria for high risk groups.


Climatic change in tasmania inferred from a 1089-year tree-ring chronology of huon pine.
A climatically sensitive huon pine tree-ring chronology from western Tasmania allows inferences about Austral summer temperature change since A.D. 900. Since 1965, huon pine growth has been unusually rapid for trees that are in many cases over 700 years old. This growth increase correlates well with recent anomalous warming in Tasmania on the basis of instrumental records and supports claims that a climatic change, perhaps influenced by greenhouse gases, is in progress. Although this temperature increase exceeds any that are inferred to have occurred during the past 1089 years at this location, it has not yet clearly emerged from the natural background variability of climate in this part of the Southern Hemisphere.


Association between unhygienic menstrual management practices and prevalence of lower reproductive tract infections: a hospital-based cross-sectional study in Odisha, India.
The extent to which reproductive tract infections (RTIs) are associated with poor menstrual hygiene management (MHM) practices has not been extensively studied. We aimed to determine whether poor menstrual hygiene practices were associated with three common infections of the lower reproductive tract; Bacterial vaginosis (BV), Candida, and Trichomonas vaginalis (TV). Non-pregnant women of reproductive age (18-45 years) and attending one of two hospitals in Odisha, India, between April 2015 and February 2016 were recruited for the study. A standardized questionnaire was used to collect information on: MHM practices, clinical symptoms for the three infections, and socio-economic and demographic information. Specimens from posterior vaginal fornix were collected using swabs for diagnosis of BV, Candida and TV infection. A total of 558 women were recruited for the study of whom 62.4% were diagnosed with at least one of the three tested infections and 52% presented with one or more RTI symptoms. BV was the most prevalent infection (41%), followed by Candida infection (34%) and TV infection (5.6%). After adjustment for potentially confounding factors, women diagnosed with Candida infection were more likely to use reusable absorbent material (aPRR = 1.54, 95%CI 1.2-2.0) and practice lower frequency of personal washing (aPRR = 1.34, 95%CI 1.07-1.7). Women with BV were more likely to practice personal washing less frequently (aPRR = 1.25, 95%CI 1.0-1.5), change absorbent material outside a toilet facility (aPRR = 1.21, 95%CI 1.0-1.48) whilst a higher frequency of absorbent material changing was protective (aPRR = 0.56, 95%CI 0.4-0.75). No studied factors were found to be associated with TV infection. In addition, among women reusing absorbent material, Candida but not BV or TV - infection was more frequent who dried their pads inside their houses and who stored the cloth hidden in the toilet compartment. The results of our study add to growing number of studies which demonstrate a strong and consistent association between poor menstrual hygiene practices and higher prevalence of lower RTIs.


Phase-gradient reconstruction from photon-limited stellar speckle images.
The phase-gradient process for reconstructing stellar speckle images is implemented in a photon-address mode for application to images containing small numbers of photons. Comparisons are made with an address-mode Knox-Thompson process which show that the phase-gradient approach has computational advantages and better SNR performance. Reconstructions from simulated data and real data for the binary source Beta Delphinius are presented.


Molecular epidemiology of an outbreak of multidrug-resistant Enterobacter aerogenes infections and in vivo emergence of imipenem resistance.
Molecular typing was used to investigate an outbreak of infection caused by multidrug-resistant Enterobacter aerogenes (MREA) susceptible only to gentamicin and imipenem in an intensive care unit (ICU). Over a 9-month period, ciprofloxacin-resistant E. aerogenes isolates were isolated from 34 patients, or 4.1% of ICU admissions, compared with a baseline rate of 0.1% in the previous period (P < 0.001). Infection developed in 15 (44%) patients. In vivo emergence of imipenem resistance (MIC, 32 micrograms/ml) of organisms causing deep-seated infection was observed in two (13%) of these patients following prolonged therapy with imipenem and gentamicin. Arbitrarily primed PCR (AP-PCR) analysis with ERIC1R and ERIC2 primers and pulsed-field gel electrophoresis (PFGE) analysis of XbaI macrorestriction patterns concordantly showed that outbreak-associated MREA isolates were clonally related and distinct from epidemiologically unrelated strains. AP-PCR and PFGE showed discrimination indices of 0.88 and 0.98, respectively. Space-time clustering of cases within units suggests that the epidemic-related MREA isolates were transmitted on the hands of the health care personnel. A case-control study and repeated environmental culture surveys failed to identify a common source or procedure associated with transmission. In spite of the early implementation of isolation measures, the incidence of MREA colonization remained stable until all colonized patients were discharged. This study confirms the usefulness of AP-PCR and PFGE analyses for the epidemiological study of E. aerogenes and underscores the difficulty of controlling the spread of multiresistant clones of this organism in the ICU setting. The emergence of imipenem resistance represents a threat because virtually no therapeutic option is available for such strains.


[History of blood transfusion].
The idea of transfusing blood of an animal to another or from an animal to a man or from one to another man, is very ancient. When the doctrine of blood circulation was diffused, in the first third of the XVII century, this idea was give fresh impetus. On began also to inject some substance into the blood, wich will permit to introduce medicaments intravenously. It is worthy to be remembered that in the same year when the Harveyan monography De motu cordis et sanguinis in animalibus was published (1628), the Paduan professor Giovanni Colle suggested a procedure for blood transfusions. Later (1645) the Tuscan physician Francesco Folli showed another procedure, in the presence of the great duke of Toscana, Ferdinando II de Medici. On his side, the surgeon Giovanni Guglielmo Riva realized blood transfusions from animals to men in 1668. Transfusions were already carried out by Richard Lower in London and by Jean-Baptiste Denis in Paris. During the XVIII century, blood transfusions were not effectuated because of some failure occurred in the formed century and of the proscription by civil and religious authorities. Nevertheless these were renewed during the first third of the XIX century in England as well as in the continental Europe. In Mexico the first blood transfusion was effectuated in 1845 by the physician Matias D. Beistegui. At the time persisted the problem of blood coagulation, which could be resolved during the XX century in North America (Crile, 1906) as well as in Latin America (Luis Agote, 1914). Moreover the blood groups were described in 1900 by the Austrian physician Karl Landsteiner, who identified later the Rh factor. It seems completely justified the inscription shining on the façade of the National Archive in Washington: "The past is only prologue".


Fruit and vegetable consumption and cognitive decline in aging women.
We prospectively examined fruit and vegetable intake in relation to cognitive function and decline among aging women. Participants were followed from in 1976 with biennial questionnaires, and food frequency questionnaires were administered in 1984, 1986, and every 4 years thereafter. From 1995 to 2001, we administered, by telephone, six cognitive tests measuring general cognition, verbal memory, category fluency, and working memory. We repeated assessments two years later for 13,388 women (>90% follow-up). We averaged dietary intakes from 1984 through the first cognitive assessment, and used linear regression to obtain multivariable-adjusted mean differences in performance and decline in performance across intake levels. Fruits were not associated with cognition or cognitive decline. However, total vegetable intake was significantly associated with less decline. Specifically, on a global score combining all tests, women in the highest quintile of cruciferous vegetables declined slower (by 0.04 unit; 95% confidence interval, 0.003, 0.07; p trend = 0.1) compared with the lowest quintile. Women consuming the most green leafy vegetables also experienced slower decline than women consuming the least amount (by 0.05 unit; 95% confidence interval, 0.02, 0.09; p trend < 0.001). These mean differences were equivalent to those observed for women about 1 to 2 years apart in age.


Triple drug chemotherapy for advanced ovarian carcinoma: comparative study of two regimens.
Two consecutive studies were undertaken in patients with advanced adenocarcinoma of the ovary to compare melphalan, adriamycin and 5-fluorouracil (MAF) with cyclophosphamide, adriamycin and 5-fluorouracil (CAF). Twenty-one patients received MAF and 19 received CAF. The objective response rate was 35% for MAF and 62% for CAF patients, and complete remission occurred in 23% of MAF, and in 56% of CAF, patients. These differences were not statistically significant. In both groups, complete remission had a statistically significant and favourable influence on survival. Toxic effects were predominantly haemopoietic and gastrointestinal, MAF having a significantly greater thrombocytopenic potential than CAF, but over-all tolerance was good on both protocols. MAF and CAF are comparable and effective combinations for the treatment of advanced ovarian cancer, but do not demonstrate superiority to single alkylating agent therapy or to other combinations. This emphasizes the continuing need for well designed randomized trials comparing single alkylating agents with combinations of known active agents.


[Adrenal hyperandrogenia and lipid metabolism].
The aim of our study was to evaluate the influence of adrenal androgen-DHEAS on lipid metabolism. Observational cross-sectional study was carried out in 57 women aged up to 30 years. Clinical, ultrasound, hormonal investigations were performed. Markers of lipid metabolism-total cholesterol (TC), triglycerides (TG), high density lipoproteides (HDL), low density lipoproteides (LDL), very low density lipoproteides (VLDL) and atherogenic index (IAT) were detected. According to our results DHEAS decreases the production of TC, TG, LDL, VLDL and blocks atherogenic effect of the testosterone. It may be concluded that adrenal androgen-DHEAS has antiatherogenic effect. It has a long-lasting action on the lipid exchange and induces decrease of the level of atherogenic lipids.


Is recent Afghanistan survey data suitable for fertility analysis? A regional investigation based on fertility inhibiting determinants.
Afghanistan has been a country blighted by war over the past five decades and limited research is available on its demography. This study seeks to assess the suitability of recent survey data for Afghanistan (the 2010 Afghanistan Mortality Survey (AMS)and the 2015 Afghanistan Demographic and Health Survey (ADHS)) for estimating levels and trends in fertility. As several fertility measures rely on the quality of age data, we first apply demographic tools for the identification of age misreporting, finding evidence that it is severe. We then explore the consistency of fertility reporting across the two surveys, finding that the 2015 ADHS reports higher fertility among older women than the 2010 AMS although the seasonal pattern of fertility is consistent across the two surveys. We then estimate total fertility rates in 2008-2010 and 2012-2015 and measures of Bongaarts's key proximate determinants of fertility for Afghanistan and its provinces for urban and rural areas separately. The results show that fertility is similar in urban and rural Afghanistan. Although most of the provincial data on the proximate determinants is reasonably consistent with the fertility rates, there are anomalies in some provinces which indicate the possible under-reporting of births. Overall, we conclude that the fertility data in the two surveys can be used with care to give an indication of broad regional fertility patterns and trends in the country.


Racial and ethnic minority college students' stigma associated with seeking psychological help: Examining psychocultural correlates.
Many college students underuse professional psychological help for mental health difficulties. The stigma associated with seeking such help appears to be one of the reasons for this underuse. Levels of psychological distress and past use of counseling/psychotherapy have been found to be important correlates of stigma associated with seeking psychological help (Obasi & Leong, 2009; Vogel, Wade, & Haake, 2006). For racial and ethnic minorities, the hindering effects of self-stigma and perceived stigmatization by others on treatment seeking may further be compounded by their relationships with their own ethnic groups, with other ethnic groups, and with the dominant society. This study used structural equation modeling (SEM) to test a model that explored the effects of psychological distress and psychocultural variables (i.e., ethnic identity, other-group orientation, perceived discrimination) on perceived stigmatization by others and self-stigma for seeking psychological help, controlling for past use of counseling/psychotherapy. The sample consisted of 260 African American, 166 Asian American, and 183 Latino American students. SEM multigroup analyses indicated measurement invariance, but partial structural invariance, across racial/ethnic groups. Across all 3 groups, higher levels of psychological distress and perceived racial/ethnic discrimination, respectively, predicted higher levels of perceived stigmatization by others for seeking psychological help, which, in turn, predicted greater self-stigma for seeking psychological help. Higher levels of other-group orientation predicted lower levels of self-stigma of seeking psychological help across groups. Higher levels of ethnic identity predicted lower levels of self-stigma of seeking psychological help only for African Americans. Implications for research and practice are discussed.


Genome-Resolved Metagenomic Analyses Reveal the Presence of a Putative Bacterial Endosymbiont in an Avian Nasal Mite (Rhinonyssidae; Mesostigmata).
Rhinonyssidae (Mesostigmata) is a family of nasal mites only found in birds. All species are hematophagous endoparasites, which may damage the nasal cavities of birds, and also could be potential reservoirs or vectors of other infections. However, the role of members of Rhinonyssidae as disease vectors in wild bird populations remains uninvestigated, with studies of the microbiomes of Rhinonyssidae being almost non-existent. In the nasal mite (Tinaminyssus melloi) from rock doves (Columba livia), a previous study found evidence of a highly abundant putatively endosymbiotic bacteria from Class Alphaproteobacteria. Here, we expanded the sample size of this species (two different hosts- ten nasal mites from two independent samples per host), incorporated contamination controls, and increased sequencing depth in shotgun sequencing and genome-resolved metagenomic analyses. Our goal was to increase the information regarding this mite species and its putative endosymbiont. We obtained a metagenome assembled genome (MAG) that was estimated to be 98.1% complete and containing only 0.9% possible contamination. Moreover, the MAG has characteristics typical of endosymbionts (namely, small genome size an AT bias). Overall, our results support the presence of a potential endosymbiont, which is the first described for avian nasal mites to date, and improve the overall understanding of the microbiota inhabiting these mites.


HER-2 protein concentrations in breast cancer cells increase before immunohistochemical and fluorescence in situ hybridization analysis turn positive.
The level of HER-2/neu in breast cancer cells is normally measured by immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH). It determines whether patients should be treated with trastuzumab (Herceptin). In this study, HER-2 protein in breast cancer tissue was measured using a quantitative method. Tissue samples of malignant and adjacent benign breast tissue were collected from 118 consecutive women admitted for surgical treatment of breast cancer. The HER-2 protein concentration was determined by 2 HER-2 assays: ELISA and the Bayer ADVIA Centaur assay. Paraffin-embedded tissue sections of the corresponding tumors were analyzed by IHC and FISH. Increased HER-2 concentrations in cancer tissue were found compared to autologous reference tissue (p<0.0001, Wilcoxon test) and normal breast tissue (p<0.0001, Mann-Whitney test). Good concordance rates were observed between the methods: 95.8% for IHC and FISH; 86.4% for IHC and ELISA; and 87.3% for FISH and ELISA. The HER-2 positivity rate was determined to 26.3% by ELISA, 12.7% by IHC and 16.9% by FISH. No correlation was found with tumor grade, axillary node status or serum HER-2 levels. Detection of HER-2 overexpression by measuring HER-2 in tissue extracts by ELISA seems to be more sensitive than IHC and FISH. This suggests that some patients deprived of Herceptin treatment may benefit from this treatment and may also explain the conversion phenomenon from HER-2-negative to HER-2-positive observed in relapse and metastatic disease.


Orthodontic treatment for a patient with multiple sclerosis.
Multiple sclerosis (MS) is a chronic, autoimmune inflammatory disorder of the central nervous system (CNS) that affects myelinated axons, destroying the myelin and damaging axons to varying degrees. The course of MS is highly varied and unpredictable. Metals used during orthodontic treatment can negatively affect imaging techniques used to diagnose and monitor the progression of MS, while medications used to treat MS can negatively affect orthodontic tooth movement. The present case report highlights some of the challenges encountered during orthodontic treatment of a patient with MS and how to overcome them. The patient was a 20-year-old woman with complaints of diastema and spacing in the upper arch. Although closing the spaces was challenging due to some of the MS medications, she was treated successfully, without complications, within 20 months using closing loops.


Reproducibility of surface EMG during dynamic shoulder forward flexions: a study of clinically healthy subjects.
There is a shortage of studies concerning the reproducibility of surface electromyography (EMG) during dynamic contractions. The movement per se introduces factors that could have the potential to affect the characteristics of the electromyogram. The aim of this study was to investigate the during-the-day reproducibility (using intra-class coefficient, ICC) of the peak torque (PT) and the EMG variables (without removing electrodes) of dynamic shoulder forward flexions. Eleven healthy women performed three sets of 10 dynamic maximum right-shoulder flexions at 1 h intervals using an isokinetic dynamometer. The PT of each flexion was determined. EMG signals were recorded from four muscles (trapezius, deltoid, infraspinatus and biceps brachii) using surface electrodes, and the mean frequency of the power spectrum (MNF [Hz]) and the signal amplitude (RMS [microV]), were computed. The ability to relax between maximum flexions was calculated as a ratio between the RMS during the passive extension phase and the RMS during the active flexion phase of each contraction cycle. This ratio is the signal amplitude ratio (SAR). The present study showed good reproducibility for PT, MNF and RMS, while the reproducibility of SAR was generally acceptable (fair) according to the criteria used.


Risk factors for recurrence of primary spontaneous pneumothorax after thoracoscopic surgery.
Primary spontaneous pneumothorax recurs at a certain rate after thoracoscopic surgery, and risk factors for that recurrence are in question. The medical records of 248 patients with primary spontaneous pneumothorax who were followed for more than 2 years after thoracoscopic surgery were reviewed and retrospectively analyzed. Univariate and multivariate binary logistic regression analysis were used to identify possible risk factors. Twelve patients experienced the recurrence of primary spontaneous pneumothorax. Patients who experienced the recurrence of primary spontaneous pneumothorax were younger than patients who experienced no recurrence. A larger proportion of the patients who experienced recurrence did not undergo pleurodesis. The variables age, height, weight, body mass index, duration of air leakage, and pleurodesis (performed or not) with a p value less than 0.2 in univariate analysis were entered in multivariate analysis. A younger age and not undergoing pleurodesis were associated with a higher risk of postoperative ipsilateral recurrence of primary spontaneous pneumothorax. Not undergoing pleurodesis and a younger age are possible risk factors for recurrence of primary spontaneous pneumothorax after thoracoscopic surgery. Thoracic surgeons should pay more attention to pleurodesis, especially in younger patients.


R2oDNA designer: computational design of biologically neutral synthetic DNA sequences.
R2oDNA Designer is a web application that stochastically generates orthogonal sets of synthetic DNA sequences designed to be biologically neutral. Biologically neutral sequences may be used for directing efficient DNA assembly by overlap-directed methods, as a negative control for functional DNA, as barcodes, or potentially as spacer regions to insulate biological parts from local context. The software creates optimized sequences using a Monte Carlo simulated annealing approach followed by the elimination of sequences homologous to host genomes and commonly used biological parts. An orthogonal set is finally determined by using a network elimination algorithm. Design constraints can be defined using either a web-based graphical user interface (GUI) or uploading a file containing a set of text commands.


Natural history of human immunodeficiency virus type 1 infection in children: a five-year prospective study in Rwanda. Mother-to-Child HIV-1 Transmission Study Group.
To compare morbidity and mortality of human immunodeficiency virus type 1 (HIV-1)-infected and HIV-1-uninfected children and to identify predictors of acquired immunodeficiency syndrome (AIDS) and death among HIV-1-infected children in the context of a developing country. Prospective cohort study. Maternal and child health clinic of the Centre Hospitalier de Kigali, Rwanda. Two hundred eighteen children born to HIV-1-seropositive mothers and 218 born to seronegative mothers of the same age and parity were enrolled at birth. Deaths, clinical AIDS, nonspecific HIV-related manifestations, and use of health care services. Fifty-four infected and 347 uninfected children were followed up for a median of 27 and 51 months, respectively. With the exception of chronic cough, the risk of occurrence of nonspecific HIV-related conditions was 3 to 13 times higher in infected than in uninfected children. The recurrence rate and severity of these findings were increased systematically in infected infants. Estimated cumulative risk of developing AIDS was 28% and 35% at 2 and 5 years of age, respectively. Estimated risk of death among infected children at 2 and 5 years of age was 45% and 62%, respectively, a rate 21 times higher than in uninfected children. Median survival time after estimated infection was 12.4 months. Early infection, early onset of HIV-related conditions, failure to thrive, and generalized lymphadenopathy were associated with subsequent risk of death and/or AIDS, whereas lymphoid interstitial pneumonitis was predictive of a milder disease. In Africa, HIV-1-infected children develop disease manifestations early in life. Specific clinical findings are predictive of HIV-1 disease, AIDS stage, and death. Bimodal expression of HIV-1 pediatric disease is encountered in Africa, as in industrialized countries, but prognosis is poorer. human immunodeficiency virus infection, children, vertical transmission, natural history, Africa.


Farnesol-induced cell death and stimulation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity in tobacco cv bright yellow-2 cells.
Growth inhibition of tobacco (Nicotiana tabacum L. cv Bright Yellow-2) cells by mevinolin, a specific inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR) could be partially overcome by the addition of farnesol. However, farnesol alone inhibited cell division and growth as measured by determination of fresh weight increase. When 7-d-old tobacco cv Bright Yellow-2 cells were diluted 40-fold into fresh culture, the cells exhibited a dose-dependent sensitivity to farnesol, with 25 microM sufficient to cause 100% cell death, as measured by different staining techniques, cytometry, and monitoring of fragmentation of genomic DNA. Cells were less sensitive to the effects of farnesol when diluted only 4-fold. Farnesol was absorbed by the cells, as examined by [1-(3)H]farnesol uptake, with a greater relative enrichment by the more diluted cells. Both mevinolin and farnesol treatments stimulated apparent HMGR activity. The stimulation by farnesol was also reflected in corresponding changes in the steady-state levels of HMGR mRNA and enzyme protein with respect to HMGR gene expression and enzyme protein accumulation.


Epstein-Barr virus nuclear protein 2 (EBNA2) binds to a component of the human SNF-SWI complex, hSNF5/Ini1.
Epstein-Barr nuclear antigen 2 (EBNA2), one of the six viral nuclear proteins expressed in latently infected B lymphocytes, is essential to the immortalization of B cells by Epstein-Barr virus (EBV). EBNA2 promotes transcriptional transactivation of viral and cellular genes by acting as an adapter molecule that binds to cellular sequence-specific DNA-binding proteins, JK recombination signal-binding protein (RBP-JK), and PU.1 and engages multiple members of the RNA polymerase II transcription complex. In the present study, we show that EBNA2 also interacts with hSNF5/Ini1, the human homolog of the yeast transcription factor SNF5. Gel filtration fractionation of partially purified EBV-positive lymphocyte nuclear extracts shows that a fraction of EBNA2 coelutes with both hSNF5/Ini1 and BRG1, a human homolog of SWI/SNF2, in the high-molecular-mass region (1.5 to 2.0 MDa) of a Superose 6 chromatogram. An affinity-purified rabbit antibody directed against hSNF5/Ini1 coimmunoprecipitates EBNA2 from this high-molecular-mass nuclear protein fraction, demonstrating that EBNA2 and hSNF5/Ini1 interact in vivo. This interaction is restricted to a subpopulation of phosphorylated viral EBNA2. Deletion mutation analysis of EBNA2 shows that the proline-rich aminoterminal end and a domain within the divergent region of EBNA2 mediate EBNA2-hSNF5/Ini1 interaction. Since the SNF-SWI complex participates in gene regulation through the alteration of nucleosome configuration and may be a component of the RNA polymerase II holoenzyme, the EBNA2-hSNF5/Ini1 interaction supports the hypothesis that EBNA2 facilitates transcriptional transactivation by acting as a transcription adapter molecule. We postulate that EBNA2 engages the hSNF-SWI complex to generate an open chromatin conformation at the EBNA2-responsive target genes, thereby potentiating the function of the RBP-JK-EBNA2-polymerase II transcription complex.


Activation of the hypothalamic-pituitary-adrenal axis in IL-1 beta-converting enzyme-deficient mice.
Interleukin-1beta (IL-1beta) plays a key role in immune, behavioral and neuroendocrine responses to inflammation or infection. IL-1beta could also be involved in the response of the hypothalamic-pituitary-adrenal (HPA) axis during stress. Mature IL-1beta derives from a 31-kD precursor (pro-IL-1beta) that is processed by IL-1beta-converting enzyme (ICE). Mice in which the ICE gene has been nullated by homologous recombination were used to investigate the role of IL-1beta in the HPA axis response. Plasma levels of corticosterone and adrenocorticotropic hormone (ACTH) in response to an intraperitoneal injection of 5 microg lipopolysaccharide (LPS) were similar in ICE-deficient mice and wild-type (WT) controls. In contrast, plasma ACTH response to restraint or to 200 ng of rat recombinant IL-1beta (rrIL-1beta) was higher in ICE-deficient mice as compared to WT animals. This hyperreactivity of the HPA axis in ICE knockout mice appears not to be related to the production of plasma IL-1beta or IL-6, which was similar to that of WT mice after rrIL-1beta injection. After lipopolysaccharide, ICE-deficient mice exhibited a smaller increase in plasma-immunoreactive IL-1beta and IL-6 as compared to WT controls. After restraint stress neither increase in plasma IL-1beta nor IL-6 was observed. The mechanisms responsible for the increased reactivity of the HPA axis in ICE-deficient mice may result from a higher sensitivity of the HPA axis to inflammatory cytokines or to cleavage products of pro-IL-1beta processed by non-ICE proteases.


Dual energy CT of the chest: how about the dose?
New generation Dual Source computed tomography (CT) scanners offer different x-ray spectra for Dual Energy imaging. Yet, an objective, manufacturer independent verification of the dose required for the different spectral combinations is lacking. The aim of this study was to assess dose and image noise of 2 different Dual Energy CT settings with reference to a standard chest scan and to compare image noise and contrast to noise ratios (CNR). Also, exact effective dose length products (E/DLP) conversion factors were to be established based on the objectively measured dose. An anthropomorphic Alderson phantom was assembled with thermoluminescent detectors (TLD) and its chest was scanned on a Dual Source CT (Siemens Somatom Definition) in dual energy mode at 140 and 80 kVp with 14 x 1.2 mm collimation. The same was performed on another Dual Source CT (Siemens Somatom Definition Flash) at 140 kVp with 0.8 mm tin filter (Sn) and 100 kVp at 128 x 0.6 mm collimation. Reference scans were obtained at 120 kVp with 64 x 0.6 mm collimation at equivalent CT dose index of 5.4 mGy*cm. Syringes filled with water and 17.5 mg iodine/mL were scanned with the same settings. Dose was calculated from the TLD measurements and the dose length products of the scanner. Image noise was measured in the phantom scans and CNR and spectral contrast were determined in the iodine and water samples. E/DLP conversion factors were calculated as ratio between the measured dose form the TLDs and the dose length product given in the patient protocol. The effective dose measured with TLDs was 2.61, 2.69, and 2.70 mSv, respectively, for the 140/80 kVp, the 140 Sn/100 kVp, and the standard 120 kVp scans. Image noise measured in the average images of the phantom scans was 11.0, 10.7, and 9.9 HU (P > 0.05). The CNR of iodine with optimized image blending was 33.4 at 140/80 kVp, 30.7 at 140Sn/100 kVp and 14.6 at 120 kVp. E/DLP conversion factors were 0.0161 mSv/mGy*cm for the 140/80 kVp protocol, 0.0181 mSv/mGy*cm for the Sn140/100 kVp mode and 0.0180 mSv/mGy*cm for the 120 kVp examination. Dual Energy CT is feasible without additional dose. There is no significant difference in image noise, while CNR can be doubled with optimized dual energy CT reconstructions. A restriction in collimation is required for dose-neutrality at 140/80 kVp, whereas this is not necessary at 140 Sn/100 kVp. Thus, CT can be performed routinely in Dual Energy mode without additional dose or compromises in image quality.


A Bimetallic Polymerization Network for Effective Increase in Labile Iron Pool and Robust Activation of cGAS/STING Induces Ferroptosis-Based Tumor Immunotherapy.
Due to the inherent low immunogenicity and immunosuppressive tumor microenvironment (TME) of malignant cancers, the clinical efficacy and application of tumor immunotherapy have been limited. Herein, a bimetallic drug-gene co-loading network (Cu/ZIF-8@U-104@siNFS1-HA) is developed that increased the intracellular labile iron pool (LIP) and enhanced the weakly acidic TME by co-suppressing the dual enzymatic activities of carbonic anhydrase IX (CA IX) and cysteine desulfurylase (NFS1), inducing a safe and efficient initial tumor immunogenic ferroptosis. During this process, Cu2+ is responsively released to deplete glutathione (GSH) and reduce the enzyme activity of glutathione peroxidase 4 (GPX4), achieving the co-inhibition of the three enzymes and further inducing lipid peroxidation (LPO). Additionally, the reactive oxygen species (ROS) storm in target cells promoted the generation of large numbers of double-stranded DNA breaks. The presence of Zn2+ substantially increased the expression of cGAS/STING, which cooperated with ferroptosis to strengthen the immunogenic cell death (ICD) response and remodel the immunosuppressive TME. In brief, Cu/ZIF-8@U-104@siNFS1-HA linked ferroptosis with immunotherapy through multiple pathways, including the increase in LIP, regulation of pH, depletion of GSH/GPX4, and activation of STING, effectively inhibiting cancer growth and metastasis.


Evolution of Hepatitis C Virus Treatment During the Era of Sofosbuvir-Based Therapies: A Real-World Experience in France.
Treatment of hepatitis C virus (HCV) has been dramatically improved with the introduction of direct-acting antiviral agents (DAAs). Universal access to pangenotypic DAAs was provided in France from 2017, expanding the type of patients treated. Real-world studies are important to confirm effectiveness and safety in clinical practice, particularly in vulnerable populations. To assess real-world effectiveness and safety of sofosbuvir-based therapy in adults with chronic HCV infection before and after universal access to DAAs in France. This multicenter, non-interventional, prospective study assessed the effectiveness, safety, patient-reported outcomes and adherence with sofosbuvir-based regimens from October 2015 to July 2016 (Period 1: sofosbuvir-based therapy excluding sofosbuvir/velpatasvir) and from October 2017 to July 2018 (Period 2: pangenotypic sofosbuvir/velpatasvir-based therapy). Baseline data were documented for 1029 patients. Overall, 797 (77%) had sustained virologic response data available ≥ 9 weeks after treatment completion. Per protocol response was high (97%) irrespective of age, alcohol consumption, recreational drug use, or HIV/HCV coinfection. Adverse events occurred in approximately 25% of patients with the majority experiencing Grade 1 or 2 events. Sofosbuvir-based regimens improved health-related quality of life from baseline to end of treatment in patients with data at all timepoints. Overall, 99% of patients reported total or almost total adherence to therapy. Sofosbuvir-based therapy, including pangenotypic sofosbuvir/velpatasvir, is effective for the treatment of HCV in real-world clinical practice. This is an important step towards HCV elimination.


A meta-analysis of preference-performance relationships in phytophagous insects.
The extent to which behavioural choices reflect fine-tuned evolutionary adaptation remains an open debate. For herbivorous insects, the preference-performance hypothesis (PPH) states that female insects will evolve to oviposit on hosts on which their offspring fare best. In this study, we use meta-analysis to assess the balance of evidence for and against the PPH, and to evaluate the role of individual factors proposed to influence host selection by female insects. We do so in an explicitly bitrophic context (herbivores versus plants). Overall, our analyses offer clear support for the PPH: Offspring survive better on preferred plant types, and females lay more eggs on plant types conducive to offspring performance. We also found evidence for an effect of diet breadth on host choice: female preference for 'good quality plants' was stronger in oligophagous insects than in polyphagous insects. Nonetheless, despite the large numbers of preference-performance studies conducted to date, sample sizes in our meta-analysis are low due to the inconsistent format used by authors to present their results. To improve the situation, we invite authors to contribute to the data base emerging from this work, with the aim of reaching a strengthened synthesis of the subject field.


[Importance of biotin metabolism].
Biotin is a water soluble enzyme cofactor that belongs to the vitamin B complex. In humans, biotin is involved in important metabolic pathways such as gluconeogenesis, fatty acid synthesis, and amino acid catabolism by acting a as prosthetic group for pyruvate carboxylase, propionyl-CoA carboxylase, beta-methylcrotinyl-CoA carboxylase, and acetyl-CoA carboxylase. Carboxylases are synthesized as apo-carboxylases without biotin and the active form is produced by their covalent binding of biotin to the epsilon-amino group of a lysine residue of the apocarboxylases. This reaction is catalyzed by the holo-carboxylase synthetase. The last step in the degradation of carboxylases, the cleavage of the biotinyl moiety from the epsilon-amino group lysine residues, is catalyzed by biotinidase and results in the release of free biotin, which can be recycled. Biotin regulates the catabolic enzyme propionyl-CoA carboxylase at the posttranscriptional level whereas the holo-carboxylase synthetase is regulated at the transcriptional level. Aside from its role in the regulation of gene expression of carboxylases, biotin has been implicated in the induction of the receptor for the asialoglycoprotein, glycolytic enzymes and of egg yolk biotin binding proteins. Biotin deficiency in humans is extremely rare and is generally associated with prolonged parenteral nutrition, the consumption of large quantities of avidin, usually in the form of raw eggs, severe malnutrition and, inherited metabolic disorders. In humans, there are autosomal recessive disorders of biotin metabolism that result from the disruption of the activity of biotinidase or holo-carboxylase synthetase.


Hypothesis: set-points and long-term control of arterial pressure. A theoretical argument for a long-term arterial pressure control system in the brain rather than the kidney.
1. It has been hypothesised that the 'set-point' for the long-term control of mean arterial (MAP) resides within the kidney. In this model, the set-point of the 'chronic renal function curve' establishes the steady state relationship between renal perfusion pressure and urinary excretion of sodium and water, which, in turn, affects blood volume and cardiac output. The 'renal-MAP set-point' theory predicts that the kidney controls MAP to maintain its own excretory function and that long-term regulation of blood volume and cardiac output are paramount to the regulation of arterial pressure. 2. An alternative hypothesis is proposed in which the 'set-point' for the long-term control of MAP resides within the central nervous system (CNS) rather than the kidney. In contrast with the 'renal-MAP set-point' model, the 'CNS-MAP set-point' model dictates that the brain controls MAP to maintain cerebral blood flow and CNS function. 3. The 'CNS-MAP set-point hypothesis' predicts that long-term regulation of MAP is paramount to the regulation of blood volume and cardiac output. It is proposed that the 'CNS-MAP set-point' system operates independently of the arterial baroreceptor reflex, which is a short-term controller of MAP. 4. The precise mechanisms by which the CNS 'senses' MAP are complex and remain to be discovered. The MAP 'sensor' likely involves integration of hormone levels linked to body fluid homeostasis and osmoreceptor and baroreceptor inputs. It is also proposed that an as yet undiscovered 'central baroreceptor' exists within the brain itself. 5. The 'CNS-MAP set-point hypothesis' predicts that many forms of experimental and essential hypertension are due to a primary shift in the CNS-MAP set-point.


Dose-response relationship between serum 2,3,7,8-tetrachlorodibenzo-p-dioxin and diabetes mellitus: a meta-analysis.
We systematically evaluated studies published through May 2014 in which investigators assessed the dose-response relationship between serum levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the occurrence of diabetes mellitus (DM), and we investigated the extent and sources of interstudy heterogeneity. The dose-response relationship between serum TCDD and DM across studies was examined using 2 dependent variables: an exposure level-specific proportion of persons with DM and a corresponding natural log-transformed ratio measure of the association between TCDD and DM. Regression slopes for each dependent variable were obtained for each study and included in a random-effects meta-analysis. Sensitivity analyses were used to assess the influence of inclusion and exclusion decisions, and sources of heterogeneity were explored using meta-regression models and a series of subanalyses. None of the summary estimates in the main models or in the sensitivity analyses indicated a statistically significant association. We found a pronounced dichotomy: a positive dose-response in cross-sectional studies of populations with low-level TCDD exposures (serum concentrations <10 pg/g lipid) and heterogeneous, but on balance null, results for prospective studies of persons with high prediagnosis TCDD body burdens. Considering the discrepancy of results for low current versus high past TCDD levels, the available data do not indicate that increasing TCDD exposure is associated with an increased risk of DM.


Review: the dynamics of the nuclear lamins during the cell cycle-- relationship between structure and function.
The nuclear lamins are members of the intermediate filament (IF) family of proteins. The lamins have an essential role in maintaining nuclear integrity, as do the other IF family members in the cytoplasm. Also like cytoplasmic IFs, the organization of lamins is dynamic. The lamins are found not only at the nuclear periphery but also in the interior of the nucleus, as distinct nucleoplasmic foci and possibly as a network throughout the nucleus. Nuclear processes such as DNA replication may be organized around these structures. In this review, we discuss changes in the structure and organization of the nuclear lamins during the cell cycle and during cell differentiation. These changes are correlated with changes in nuclear structure and function. For example, the interactions of lamins with chromatin and nuclear envelope components occur very early during nuclear assembly following mitosis. During S-phase, the lamins colocalize with markers of DNA replication, and proper lamin organization must be maintained for replication to proceed. When cells differentiate, the expression pattern of lamin isotypes changes. In addition, changes in lamin organization and expression patterns accompany the nuclear alterations observed in transformed cells. These lamin structures may modulate nuclear function in each of these processes.


Social-Pragmatic Skills and Length of Bilingualism Predict Inhibitory Control in Children.
There is conflicting evidence regarding effects of bilingualism on inhibition, and the mechanisms that might underlie the effects remain unclear. A prominent account views additional demands on structural language use in bilinguals as being at the root of bilingual effects on inhibition. In this study, we tested the novel hypothesis that social-pragmatic skills (alone or together with structural language skills) are associated with inhibition in bilingual children. Parents of 114 typically developing 8- to 11-year-old Spanish-English bilingual children completed the Children's Communication Checklist-Second Edition to index social pragmatics and the Behavior Rating Inventory of Executive Function to index executive functioning skills. The Inhibit clinical scale score reflected children's inhibition. Children's language ability was indexed by the Clinical Evaluation of Language Fundamentals-Fourth Edition in English and Spanish. Length of bilingualism was operationalized continuously as the length of time children had been exposed to both languages in their lifetime. Moderation analyses tested the effects of structural language, social-pragmatic skills, and length of bilingual experience, and their interactions on inhibition. While structural language skills were not associated with inhibition, they moderated the relation between social-pragmatic skills and inhibition, such that children with better social-pragmatic skills demonstrated better inhibition, and this effect was stronger for children with better structural language skills. Furthermore, longer length of bilingual experience was associated with better inhibition, and this effect was not moderated by any other predictor. These results confirm a graded relationship between bilingualism and inhibition, and indicate that this association is not qualified by structural language or social-pragmatic skills. https://doi.org/10.23641/asha.21183916.


Physical fitness and depressive symptoms during army basic combat training.
Mental health-related problems are a significant cause of attrition during basic combat training (BCT). Evidence in civilian populations suggests that physical fitness is associated with psychological benefits in civilians, but little is known about the association between physical fitness and psychological adjustment during BCT. This study prospectively examined the association between physical fitness and depressive symptoms in 300 BCT soldiers from May to July 2012 at Fort Jackson, Columbia, SC. Soldiers completed a baseline Army Physical Fitness Test (APFT) and survey within 1 wk of arriving at BCT and an end-of-cycle survey after 8 wk of BCT. Soldiers were assigned to the "high" fitness category if they had a passing score on the standard APFT of greater than or equal to 180 out of 300 points. Soldiers scoring less than 180 points on the APFT were assigned to the "low" fitness category. Depressive symptoms were measured using the 20-item Center for Epidemiologic Studies Depression scale. In multivariate analyses, adjusting for baseline demographics, self-reported sleep before BCT, BCT confidence, Army identification, and depressive symptoms, the odds of reporting depressive symptoms were 60% lower for soldiers in the high fitness category (odds ratio, 0.40; 95% confidence interval, 0.19-0.84) compared with soldiers in the low fitness category. Analogous to other positive outcomes of soldier fitness, improvement of soldier physical fitness before BCT might improve soldiers' psychological health outcomes.


Changes in plasma membrane Ca-ATPase and stromal interacting molecule 1 expression levels for Ca(2+) signaling in dystrophic mdx mouse muscle.
The majority of the skeletal muscle plasma membrane is internalized as part of the tubular (t-) system, forming a standing junction with the sarcoplasmic reticulum (SR) membrane throughout the muscle fiber. This arrangement facilitates not only a rapid and large release of Ca(2+) from the SR for contraction upon excitation of the fiber, but has also direct implications for other interdependent cellular regulators of Ca(2+). The t-system plasma membrane Ca-ATPase (PMCA) and store-operated Ca(2+) entry (SOCE) can also be activated upon release of SR Ca(2+). In muscle, the SR Ca(2+) sensor responsible for rapidly activated SOCE appears to be the stromal interacting molecule 1L (STIM1L) isoform of STIM1 protein, which directly interacts with the Orai1 Ca(2+) channel in the t-system. The common isoform of STIM1 is STIM1S, and it has been shown that STIM1 together with Orai1 in a complex with the partner protein of STIM (POST) reduces the activity of the PMCA. We have previously shown that Orai1 and STIM1 are upregulated in dystrophic mdx mouse muscle, and here we show that STIM1L and PMCA are also upregulated in mdx muscle. Moreover, we show that the ratios of STIM1L to STIM1S in wild-type (WT) and mdx muscle are not different. We also show a greater store-dependent Ca(2+) influx in mdx compared with WT muscle for similar levels of SR Ca(2+) release while normal activation and deactivation properties were maintained. Interestingly, the fiber-averaged ability of WT and mdx muscle to extrude Ca(2+) via PMCA was found to be the same despite differences in PMCA densities. This suggests that there is a close relationship among PMCA, STIM1L, STIM1S, Orai1, and also POST expression in mdx muscle to maintain the same Ca(2+) extrusion properties as in the WT muscle.


Maternal feeding controls fetal biological clock.
It is widely accepted that circadian physiological rhythms of the fetus are affected by oscillators in the maternal brain that are coupled to the environmental light-dark (LD) cycle. To study the link between fetal and maternal biological clocks, we investigated the effects of cycles of maternal food availability on the rhythms of Per1 gene expression in the fetal suprachiasmatic nucleus (SCN) and liver using a transgenic rat model whose tissues express luciferase in vitro. Although the maternal SCN remained phase-locked to the LD cycle, maternal restricted feeding phase-advanced the fetal SCN and liver by 5 and 7 hours respectively within the 22-day pregnancy. Our results demonstrate that maternal feeding entrains the fetal SCN and liver independently of both the maternal SCN and the LD cycle. This indicates that maternal-feeding signals can be more influential for the fetal SCN and particular organ oscillators than hormonal signals controlled by the maternal SCN, suggesting the importance of a regular maternal feeding schedule for appropriate fetal molecular clockwork during pregnancy.


[Changes in the dimensions of motor neurons and their components with different forms of nerve center activation].
Experiments in frogs have shown that a prolonged orthodromic rhythmical activation of motoneurons induce changes in their size and staining. Under these conditions the size of all components of motoneurons (cytoplasm, nucleus, nucleolus) is changed. The cytoplasm size changes are more pronounced than those of the nucleus. Under prolongation of the low frequency stimulation (1 per sec.) of the dorsal roots the changes are of phasic character: an initial enlargement (10 minute-long stimulation) and a subsequent decrease of all the above spinal cord motoneuron components (25 minute stimulation). After the 10 minute high frequency stimulation (50 impulses per second) of nerve centers there occur a sharp decrease of the size of the cytoplasm and the nucleus.


Doctor, what are my options? A prospective cohort study of an individualized care plan for patients with gastrointestinal cancer.
For cancer patients, information about their disease and its treatment is often delivered within a short time period, potentially leading to patient misunderstanding, which can impede optimal patient care. In this 3-part clinical study, we investigated the utility of an individualized care plan for patients with gastrointestinal (gi) cancer starting a new treatment. In part 1, a comprehensive literature search identified items for potential inclusion in the care plan. Those items were formatted into a questionnaire. The questionnaire was then administered to patients as a structured interview. In part 2, health care professionals involved in the care of patients with gi cancer evaluated the resulting care plan for content and relevancy. In part 3, a 20-week prospective cohort study (10 weeks using standard of care, 10 weeks using individualized care plans) was conducted. Outcomes were assessed at baseline and at 2-4 weeks after administration of the care plan. In part 1, a 73-item questionnaire was developed and completed by 20 patients in semi-structured interviews. In part 2, long and short versions of the care plan were created. Most health care professionals preferred the long version. Based on their comments, a final version of the care plan was created. The part 3 study enrolled 104 patients. Overall satisfaction scores were significantly higher in the intervention group at baseline (p = 0.010) and follow-up (p = 0.005). Compared with control patients, the intervention cohort also reported significantly higher overall quality of life (p = 0.044) and fewer symptoms of anxiety (p = 0.048) at follow-up. Provision of an individualized care plan resulted in improvements in outcome measures at both baseline and follow-up. Future studies are needed to confirm these findings.