Vaccine-induced antigen archiving enhances local memory CD8+ T cell responses following an unrelated viral infection.
Viral and vaccine antigens persist or are archived in lymph node stromal cells (LNSC) such as lymphatic endothelial cells (LEC) and fibroblastic reticular cells (FRC). Here, we find that, during the time frame of antigen archiving, LEC apoptosis caused by a second, but unrelated, innate immune stimulus such as vaccina viral infection or CpG DNA administration boosted memory CD8+ T cells specific to the archived antigen. In contrast to "bystander" activation associated with unrelated infections, the memory CD8+ T cells specific to the vaccine archived antigen were significantly higher than memory CD8+ T cells of a different antigen specificity. Finally, the boosted memory CD8+ T cells resulted in increased protection against Listeria monocytogenes expressing the vaccine antigen, but only for the duration that the vaccine antigen was archived. These findings outline a novel mechanism by which LNSC archived antigens, in addition to bystander activation, can augment memory CD8+ T cell responses during repeated inflammatory insults.


Comparison of thread test of lacrimation to Schirmer test.
A modified Schirmer test using thread instead of filter paper has been previously reported. The present report compares the characteristics of thread and filter paper and establishes the normal range for the tear flow rate. The moisture absorption by a 5-mm wide strip of filter paper was 0.765 microL/mm and that by a thread was 0.054 microL/mm. The thread was 14 times more sensitive in detecting small amounts of fluid than was the filter paper. The thread test was used in 42 normal subjects. The normal range was 60% to 140% (+/- 3 SD), so a value of less than 60% was considered to indicate lacrimal hypofunction, and over 140%, hyperfunction.


Atypical Lymphoid Proliferations and Clonality in Helicobacter-associated Inflammatory Infiltrates in Children.
Helicobacter infection is considered the major predisposing factor for gastric mucosa-associated lymphoid tissue (MALT) lymphoma with initial infection likely occurring in childhood. Primary gastric MALT lymphoma most commonly occurs in patients older than 50 years which is attributed to the lengthy chronic infection time required before the development of MALT lymphoma. Our study analyzes the histologic features and presence of immunoglobulin heavy chain (IGH) clonality in Helicobacter-associated chronic gastritis (62 cases) and Helicobacter-negative chronic gastritis (17 cases) biopsies within the pediatric population, diagnosed between 1996 and 2018. Helicobacter-associated gastritis was more likely to show active inflammation (P=0.01), with no significant difference in number of germinal centers or the strength, linear property, or depth of the inflammatory infiltrate. In total, 47% (29/62) of the Helicobacter-associated cases had at least 1 lymphoepithelial lesion, equivocal or definitive (a modified Wotherspoon score of 3 to 5), compared with 24% (4/17) of the Helicobacter-negative cases (P=0.5). All cases with lymphoepithelial lesions were assessed for IGH clonality, showing the presence of monoclonality in 27% (8/30) of evaluable cases. None of our patients were diagnosed with gastric lymphoma within available follow-up data. Although 4% of our cases could be considered MALT lymphoma in an adult patient based on prominent lymphoepithelial lesions and IGH monoclonality, caution is advised when diagnosing lymphoma in the pediatric population given the good prognosis of Helicobacter-associated gastritis in this age group. It is unclear if these monoclonal lymphoid proliferations require close follow-up.


Hox-mediated endodermal identity patterns pharyngeal muscle formation in the chordate pharynx.
The chordate pharynx, possessing gill slits and the endostyle, is a complex of multiple tissues that are highly organized along the anterior-posterior (AP) axis. Although Hox genes show AP coordinated expression in the pharyngeal endoderm, tissue-specific roles of these factors for establishing the regional identities within this tissue have not been demonstrated. Here, we show that Hox1 is essential for the establishment of AP axial identity of the endostyle, a major structure of the pharyngeal endoderm, in the ascidian Ciona intestinalis We found that knockout of Hox1 causes posterior-to-anterior transformation of the endostyle identity, and that Hox1 represses Otx expression and anterior identity, and vice versa. Furthermore, alteration of the regional identity of the endostyle disrupts the formation of body wall muscles, suggesting that the endodermal axial identity is essential for coordinated pharyngeal development. Our results demonstrate an essential role of Hox genes in establishment of the AP regional identity in the pharyngeal endoderm and reveal crosstalk between endoderm and mesoderm during development of chordate pharynx.


Clinical and laboratory considerations in metabolic bone disease.
An overview of the common types of metabolic bone disease is described. When the disease is present in pure form, diagnosis is not difficult. When mixed disease is present, as may be the case, the pathophysiology involved must be clearly understood for accurate diagnosis and treatment.


Automatic annotation of medical records.
One of the research projects running at the medical informatics department of the Institute of Computer Science AS CR explores the problem of medical information representation and development of electronic health record (EHR). With respect to this effort an interesting problem arises: how to transfer knowledge from a medical record written in a free text form into a structured electronic format represented by the EHR. Currently, this task was solved by writing extraction rules (regular expressions) for every element of information that is to be extracted from the medical record. However, such approach is very time consuming and requires supervision of a skilled programmer whenever the target area of medicine is changed. In this article we explore the possibility to mechanize this process by automatically generating the extraction rules from a pre-annotated corpus of medical records. Since we are currently in the phase of data acquisition and preliminary tests we will not present any final results, rather we will sketch the technologies we intend to use and describe the tools that were developed so far as a part of this project.


Adolescents' physical activity trends over the years: a three-cohort study based on the Health Behaviour in School-aged Children (HBSC) Portuguese survey.
Many young people do not practise enough physical activity (PA) to benefit their health. The three-cohort study aimed to investigate the prevalence of PA and understand the trends between 2002 and 2010, using a representative sample of Portuguese adolescents. The participants were 8483 adolescents (4067 boys, 4416 girls) who participated in the Health Behaviour in School-aged Children Portuguese survey in 2002, 2006 and 2010. A questionnaire was used to collect data of PA. Analyses were run separately for boys and girls. Boys aged 15-17 reported practising 3.5±1.9 times a week in 2002, 3.9±1.9 times a week in 2006 and 3.8±1.9 times a week in 2010, with a significant increase from 2002 to 2006/2010 (p<0.05). PA practice during the past 7 days decreased from 4.2±2.1 to 3.9+1.9 between 2002 and 2006 (p<0.001) and also decreased from 4.4±2.1 to 3.8±1.9 between 2006 and 2010 (p<0.001). Among girls, PA practices during the past 7 days declined significantly from 3.5±1.9 to 2.7±1.7 between 2002 and 2006 (p<0.001), and from 3.3±1.9 to 2.9±1.7 between 2006 and 2010 (p<0.001). The study points to age as a factor related to diminished PA participation. The study also revealed that the prevalence of PA has decreased over the years for the same age groups.


Healthy and Patient Type 2 Innate Lymphoid Cells are Differently Affected by in vitro Culture Conditions.
Type 2 innate lymphoid cells (ILC2s) have emerged as key players in the development of type 2 driven diseases such as allergy and asthma. Due to their low number in the circulation, in vitro expansion is needed to unravel their mechanisms of action. The aim of this study is to assess the impact of different culture conditions and address whether the method of expansion may distinctly affect healthy donor or patient-derived ILC2s. Here, we described the impact of six different culture conditions on the proliferation, phenotype and function of human ILC2s freshly obtained from healthy donors (healthy ILC2s) and allergic patients (patient ILC2s). We showed that the cytokine cocktail or the PHA induced the highest proliferation of healthy ILC2s and patient ILC2s, respectively. We observed that the stromal cells OP9, used as ILC2 feeders, did not boost their proliferation, but impaired the activation marker expression and the function of patient ILC2s. Furthermore, we demonstrated that the culture conditions differently impacted the activation state of c-Kithigh and c-Kitlow ILC2s, in both healthy donors and allergic patients. Last, we also observed that ILC2s expanded only with IL-2 and IL-7 were the most prone to secrete IL-5 and IL-13 upon IL-33 stimulation. In contrast, in patients, the addition of OP9 cells during the expansion restrained their type 2 cytokine secretory functions. This report highlights that culture conditions distinctly impacted on the healthy or patient ILC2 behavior, with important consequences for their study in disease settings.


Fed up with fraud.
The national cost of health care reached 1.9 trillion dollars in 2004, or 6280 dollars for every man, woman, and child in the United States. And, although they are the exception rather than the norm, individuals intent on committing fraud and abuse are not far behind. According to the Centers for Medicare & Medicaid Services, the estimated annual loss to the government and health insurers from fraud continues to exceed 100 billion dollars. In a recent semiannual report to Congress, the Department of Health and Human Services (HHS) Office of Inspector General announced expected recoveries of 1.02 billion dollars for the first half of fiscal year 2006. At this rate, less than 5 percent of the losses from fraud and abuse are recovered annually.


Real-world efficacy and safety of dolutegravir plus lamivudine versus tenofovir plus lamivudine and efavirenz in ART-naïve HIV-1-infected adults.
Limited real-world data on dolutegravir (DTG) plus lamivudine (3TC) for HIV-1-infected individuals have been reported. This study aimed to evaluated the real-world efficacy and safety of DTG + 3TC in ART-naïve HIV-1-infected adults in China. This real-world prospective observational cohort study enrolled HIV-1-infected adults receiving ART initiation with DTG + 3TC (D3 group) or tenofovir plus lamivudine and efavirenz (TDF + 3TC + EFV, TLE group) with subgroups of low viral load (LVL, ≤500,000 copies/mL) and high viral load (HVL, >500,000 copies/mL) according to baseline HIV-1 RNA. Efficacy were assessed by proportion of virologic suppression, changes of CD4+ cell count and CD4/CD8 ratio, HIV-1 DNA decay, and safety by symptoms and changes of laboratory indicators at week 4, 12, 24, 36, and 48. Totally 45 participants in D3 group and 95 in TLE group were enrolled. The proportion of HIV RNA < 50 copies/mL were 48.7% (19/39), 84.6% (33/39), 100% (39/39), 100% (39/39) in D3-LVL subgroup at week 4, 12, 24, 48, compared with 1.3% (1/75), 14.7% (11/75), 86.7% (65/75), 96.0% (72/75) in TLE-LVL subgroup, with P < .05 at week 4, 12, and 36. The proportion were 0.0% (0/6), 66.7% (4/6), 83.3% (5/6), 100% (6/6) in D3-HVL subgroup compared with 0.0% (0/20), 5.0% (1/20), 85.0% (17/20), 100% (20/20) in TLE-HVL subgroup, with P < .05 at week 12. No virologic rebound was observed in D3 group. Mean change of CD4/CD8 ratio were higher in D3-LVL versus TLE-LVL subgroup at each scheduled visit (P < .05), while CD4+ cell counts increased significantly in D3-HVL versus TLE-HVL subgroup at week 4 and 12 (P < .05). Less complaint of dizziness, insomnia, dreaminess and amnesia, lower elevated level of triglyceride and higher elevated level of creatinine from baseline to week 48 were documented in D3 group (P < .05). Total HIV-1 DNA decayed along with HIV-1 RNA after DTG + 3TC initiation in both D3-LVL and D3-HVL subgroups. DTG + 3TC achieved virological suppression more rapidly and stably versus TDF + 3TC + EFV in ART-naïve HIV-1-infected adults, with better immunological response and less adverse drug effect, and reduced total HIV-1 DNA effectively. DTG + 3TC is a potent regimen for ART-naïve individuals with HIV-1 infection.


The hypoxic tumour microenvironment.
Cancer progression often benefits from the selective conditions present in the tumour microenvironment, such as the presence of cancer-associated fibroblasts (CAFs), deregulated ECM deposition, expanded vascularisation and repression of the immune response. Generation of a hypoxic environment and activation of its main effector, hypoxia-inducible factor-1 (HIF-1), are common features of advanced cancers. In addition to the impact on tumour cell biology, the influence that hypoxia exerts on the surrounding cells represents a critical step in the tumorigenic process. Hypoxia indeed enables a number of events in the tumour microenvironment that lead to the expansion of aggressive clones from heterogeneous tumour cells and promote a lethal phenotype. In this article, we review the most relevant findings describing the influence of hypoxia and the contribution of HIF activation on the major components of the tumour microenvironment, and we summarise their role in cancer development and progression.


Short-term limb immobilization affects cognitive motor processes.
We examined the effects of a brief period of limb immobilization on the cognitive level of action control. A splint placed on the participants' left hand was used as a means of immobilization. We used a hand mental rotation task to investigate the immobilization-induced effects on motor imagery performance (Experiments 1 and 2) and a number mental rotation task to investigate whether immobilization-induced effects are also found when visual imagery is involved (Experiment 2). We also examined whether the effects of immobilization vary as a function of individuals' vividness of motor imagery (Experiment 2). The immobilized participants performed the mental rotation tasks before and immediately after the splint removal. The control group did not undergo the immobilization procedure. For hand stimuli, response time analysis showed a lack of task-repetition benefit following immobilization (Experiments 1 and 2) except when the visual imagery task was performed first (Experiment 2). Following immobilization, a flattening in the response time profile for left hand stimuli was observed as a function of stimuli rotation (Experiments 1 and 2), especially for participants with less vivid motor imagery (Experiment 2). We did not find an immobilization-induced effect on number stimuli. These findings revealed that the cognitive representation of hand movements is modified by immobilization and that sensorimotor deprivation specifically affects motor simulation of the immobilized hand. We discuss the possibility that immobilization affects the sensorimotor system due to the reduced processing of proprioceptive feedback, which lead some participants to switch from a motor to a visual imagery strategy.


Artifactual reduction of high-density lipoprotein cholesterol estimates after dextran sulfate--Mg2+ precipitation.
Estimates of serum or plasma high-density lipoprotein (HDL) concentrations are usually accomplished by measuring the residual cholesterol after polyanionic precipitation of the very low and low-density lipoproteins. A comparison was made of the HDL cholesterol values obtained using both heparin--MnCl2 and dextran sulfate--Mg2+ as precipitating agents. Enzymatic cholesterol determinations showed that the dextran sulfate--Mg2+ method led to gross underestimation of the serum HDL cholesterol concentration (approximately -25%), a difference that was even greater when ultracentrifugally isolated HDL concentrations were assayed rather than serum. Immunochemical determinations of the A-I and B apolipoproteins demonstrated that the discrepancy was attributable neither to incomplete precipitation of the lower density lipoproteins by heparin--MnCl2 nor to precipitation of HDL by dextran sulfate--Mg2+. Incubation of sera with reagents at 37 C, however, minimized or eliminated the differences in results. These findings indicate that temperature is a critical factor when enzymatic quantification of HDL cholesterol is performed after dextran sulfate--Mg2+ precipitation.


The diacylglycerol kinase inhibitor, R59022, potentiates cholecystokinin-induced enzyme secretion from rabbit pancreatic acini.
The putative inhibitor of diacylglycerol kinase activity, 6-(2-[(4-fluorophenyl)phenylmethylene]-1-piperidinyl)-ethyl-7-meth yl-5H- thiazolo[3,2-a]pyrimidin-5-one (R59022), markedly potentiated cholecystokinin-C-terminal-octapeptide(CCK-8-)stimulated enzyme secretion from isolated rabbit pancreatic acini. Maximal potentiation occurred when acini were stimulated in the presence of 5-10 microM R59022. Potentiation depended both on the concentration of R59022 and CCK-8. No potentiation was observed when acini were half-maximally stimulated, whereas the secretory response to maximal and supramaximal concentrations of secretagogue was increased by 50-60%. R59022 alone had no effect on basal enzyme secretion and the drug did not potentiate the secretory response to the Ca2+ ionophore A23187 or to the phorbol ester, 12-O-tetradecanoylphorbol 13-acetate. Moreover, no increase in basal secretion was observed when acini were incubated in the presence of both R59022 and forskolin. These observations strongly suggest that receptor-mediated activation of the inositol phospholipid pathway is required for R59022-induced potentiation. R59022 inhibited the CCK-8-stimulated incorporation of 32Pi into phosphatidic acid dose dependently, without affecting the CCK-8-stimulated hydrolysis of 32P-labelled phosphatidylinositol 4,5-bisphosphate. This is consistent with an inhibitory effect of R59022 on acinar cell diacylglycerol kinase activity. The potentiating effect of R59022 was mimicked by 12-O-tetradecanoylphorbol 13-acetate added simultaneously with CCK-8. Therefore, it is concluded that in the presence of 5-10 microM R59022 the receptor-mediated increase in acinar cell diacylglycerol content is enhanced leading to enhanced activation of protein kinase C and to potentiation of the secretory response. The fact that the secretory response to maximal and supramaximal concentrations of CCK-8 is potentiated by R59022 suggests that at these concentrations of secretagogue the diacylglycerol/protein kinase C branch of the signal-transduction route is rate-limiting.


Enhanced sludge dewaterability with sludge-derived biochar activating hydrogen peroxide: Synergism of Fe and Al elements in biochar.
Reuse of sludge-derived Fe-rich biochar as sludge conditioner is an attractive route for management of waste activated sludge at source. Homogeneous and heterogeneous Fenton reactions have been proved in sludge conditioning with Fe-rich biochar activating H2O2 to enhance sludge dewaterability. The FeAl2O4 phase in Fe-rich biochar was first identified during pyrolysis of sewage sludge after adding both Fe2O3 and Al2O3, since Fe and Al elements are two of major metal elements in Fe-rich sludge. Compared with the Fe-rich biochar that did not comprise FeAl2O4 phase, the capillary suction time (CST) and specific resistance to filterability (SRF) of the sludge conditioned with the Fe-rich biochar comprising FeAl2O4 phase could be efficiently decreased by 23% and 44%, respectively. The results indicated that FeAl2O4 phase in Fe-rich biochar could improve sludge dewaterability by enhancing heterogeneous Fenton reaction. Synergistic effect between Fe and Al in FeAl2O4 contributed to weak the O-O bond in H2O2 and reduce the activation energy of H2O2 decomposition for enhancing ·OH generation, which could be explained by density functional theory (DFT) calculations for the first time. Thus, the decomposition rate of H2O2 and the amount of ·OH generation were obviously promoted by FeAl2O4 phase in sludge-derived biochar during sludge conditioning, attributing to the destruction of sludge flocs, the release of bound water, and the improvement of sludge dewaterability.


Health spending projections for 2002-2012.
We forecast a slowdown in national health spending growth in 2002 and 2003, reflecting slower projected Medicare and private personal health spending growth. These factors outweigh higher projected Medicaid spending growth, caused by weak labor markets, and an expectation of continued high private health insurance premium inflation related to the underwriting cycle. Over the entire projection period, national health spending growth is still expected to outpace economic growth. The result is that the health share of gross domestic product is projected to increase from 14.1 percent in 2001 to 17.7 percent in 2012.


HIGH DIMENSIONAL COVARIANCE MATRIX ESTIMATION IN APPROXIMATE FACTOR MODELS.
The variance covariance matrix plays a central role in the inferential theories of high dimensional factor models in finance and economics. Popular regularization methods of directly exploiting sparsity are not directly applicable to many financial problems. Classical methods of estimating the covariance matrices are based on the strict factor models, assuming independent idiosyncratic components. This assumption, however, is restrictive in practical applications. By assuming sparse error covariance matrix, we allow the presence of the cross-sectional correlation even after taking out common factors, and it enables us to combine the merits of both methods. We estimate the sparse covariance using the adaptive thresholding technique as in Cai and Liu (2011), taking into account the fact that direct observations of the idiosyncratic components are unavailable. The impact of high dimensionality on the covariance matrix estimation based on the factor structure is then studied.


A Review of Structure Construction of Silk Fibroin Biomaterials from Single Structures to Multi-Level Structures.
The biological performance of artificial biomaterials is closely related to their structure characteristics. Cell adhesion, migration, proliferation, and differentiation are all strongly affected by the different scale structures of biomaterials. Silk fibroin (SF), extracted mainly from silkworms, has become a popular biomaterial due to its excellent biocompatibility, exceptional mechanical properties, tunable degradation, ease of processing, and sufficient supply. As a material with excellent processability, SF can be processed into various forms with different structures, including particulate, fiber, film, and three-dimensional (3D) porous scaffolds. This review discusses and summarizes the various constructions of SF-based materials, from single structures to multi-level structures, and their applications. In combination with single structures, new techniques for creating special multi-level structures of SF-based materials, such as micropatterning and 3D-printing, are also briefly addressed.


The effect of managed care on quality: a review of recent evidence.
This article reviews recent evidence about the relationship between managed care and quality. With one exception, the studies reviewed represent observation periods that extend through 1990 or a more recent year. The review has led to the conclusion that managed care has not decreased the overall effectiveness of care. However, evidence suggests that managed care may adversely affect the health of some vulnerable subpopulations. Evidence also suggests that enrollees in managed care plans are less satisfied with their care and have more problems accessing specialized services. In addition, younger, wealthier, and healthier persons were more satisfied with their health plans than older, poorer, and sicker persons, even after adjusting for the type of health plan.The findings of the studies reviewed do not provide definitive results about the effect of managed care on quality. Indeed, relatively few studies include data from the 1990s, and little is known about the newer types of health maintenance organizations that invest heavily in information systems and rely on financial incentives to alter practice patterns. Furthermore, managed care is not a uniform method that is applied identically by all health plans, and research studying the different dimensions of managed care also is needed.


PHYLOGEOGRAPHY OF SPOTTED OWL (STRIX OCCIDENTALIS) POPULATIONS BASED ON MITOCHONDRIAL DNA SEQUENCES: GENE FLOW, GENETIC STRUCTURE, AND A NOVEL BIOGEOGRAPHIC PATTERN.
Mitochondrial DNA control region sequences of spotted owls (Strix occidentalis) allowed us to investigate gene flow, genetic structure, and biogeographic relationships among these forest-dwelling birds of western North America Estimates of gene flow based on genetic partitioning and the phylogeography of haplotypes indicate substantial dispersal within three long-recognized subspecies. However, patterns of individual phyletic relationships indicate a historical absence of gene flow among the subspecies, which are essentially monophyletic. The pattern of haplotype coalescence enabled us to identify the approximate timing and direction of a recent episode of gene flow from the Sierra Nevada to the northern coastal ranges. The three subspecies comprise phylogenetic species, and the northern spotted owl (S. o. caurina) is sister to a clade of California (S. o. occidentalis) plus Mexican spotted owls (S o lucida); this represents a novel biogeographic pattern within birds. The California spotted owl had substantially lower nucleotide diversity than the other two subspecies; this result is inconsistent with present patterns of population density A causal explanation requires postulating a severe bottleneck or a selective sweep, either of which was confined to only one geographic region.


'No daddy', 'A kind of daddy': words used by donor conceived children and (aspiring) parents to refer to the sperm donor.
Research has shown that the recipients of donor sperm can experience difficulties finding appropriate language to refer to the donor. Based on two qualitative analysis techniques, namely word count and empirical discourse analysis, we studied the words used to refer to the donor in heterosexual and lesbian (aspiring) parents and in donor conceived children. Findings show that the words used in these households are highly diverse and have at least four different interlinked functions: (1) to position the donor in relation to the nuclear family; (2) to safeguard the role of the social parent; (3) to clarify family structure; and (4) to present a positive picture of the donor. Both parents and children consciously reflect on what words to use to refer to the donor. Although parents try to keep words like 'father' and 'daddy' out of the family narrative, children use these words. These findings show that it is important for healthcare personnel and policy makers to reflect on the careful use of terminology when they address questions around sperm donation because the terminology invokes specific meanings that have an effect on how the recipients and their children perceive the role of the donor.


Potential urban distribution of Phlebotomus mascittii Grassi and Phlebotomus neglectus Tonn. (Diptera: Psychodidae) in 2021-50 in Budapest, Hungary.
In the Carpathian Basin, the most northern populations of Phlebotomus (sandfly) species, including the two studied species (Phlebotomus mascittii and Phlebotomus neglectus), are reported from central Hungary. The most important limiting factor of the distribution of Phlebotomus species in the region is the annual minimum temperature which may be positively affected by the urban heat island and the climate change in the future. The main objective of the study is to prove and predict the overwintering possibility of Phlebotomus species in urban environment. Based on the latest reports of occurrence of sandfly species, climate envelope model was built for the period 1961-90 and 2025-50 to project the potential urban distribution of the species. The climatic data were obtained from RegCM regional climate model and MODIS satellite images. The recent occurrence of the species in central Hungary indicates that Phlebotomus species can overwinter in non-heated shelters in built environment. Jointly heat island and the increase of minimum temperature in winter due to climate change seem to be able to provide suitable environment for the studied species in urban areas to a great extent.


Cholera, rotavirus and ETEC diarrhoea: some clinico-epidemiological features.
This paper analyses a few selected features from the history and clinical examination of 1258 patients with acute diarrhoea and a single laboratory diagnosis of either cholera, rotavirus, or enterotoxigenic (ETEC) Escherichia coli infection. Age distribution and seasonality in Bangladesh were also studied. The duration of illness before admission was not significantly different in the 3 groups. Cholera occurred especially in the spring and early winter. Most cholera patients were between 3 and 10 years of age. Over 37% of the patients developed severe dehydration. In about 90% of cholera cases, the stools were alkaline (pH greater than 7). ETEC infections were seen mostly in April-May and September-October. Infants were frequently affected but from age 25 onwards the age distribution closely followed that of cholera. Severe dehydration occurred in 8.3% of patients and was more frequent than in rotavirus cases. Stool pH was as frequently acidic as basic. Rotavirus cases were concentrated during the winter in patients under 2 years of age. They had marked vomiting, yet severe dehydration was almost absent. Cough was present in half of them. The stools were usually acidic. In spite of considerable overlap of signs and symptoms between the 3 aetiological groups, a presumptive diagnosis of cholera could be made in patients past infancy and early childhood who showed very severe dehydration. However, age-specific prevalence was strikingly different and seasonal variations considerable.


Human megakaryocytopoiesis--normal and abnormal.
Regulation of megakaryocyte and platelet production remains poorly understood. In culture system two separate activities are needed for maximum production of megakaryocyte progenitors: promotor of clonal expansion and promoter of maturation, other growth factors and cells also contribute to regulation of megakaryocytopoiesis. Increased proliferation of megakaryocytes is observed in myeloproliferative disorders and idiopathic thrombocytopenic purpura, and decreased proliferation is found in aplastic anaemia and hypomegakaryocytic thrombocytopenia. Dysmegakaryocytopoiesis is present in myelodysplastic syndromes and acute leukaemia, and a proliferation of immature megakaryocytes in acute megakaryoblastic leukaemia. Increased understanding of human megakaryocytopoiesis is beginning to help in rational clinical management.


Fabrication of long period fiber gratings of subnanometric bandwidth.
This Letter reports on the fabrication of long period fiber gratings having subnanometric bandwidths in the 1500 nm spectral region. Large gratings have been photo inscribed in a high NA fiber; the grating pitch and the order of the HE cladding mode are optimized to produce gratings with a large number of periods and prevent the coupling to TE, TM, or EH modes. Resonances with a FWHM of 0.83 and 0.68 nm have been achieved for gratings 15 and 20 cm long, respectively; the free spectral range between the transmission notches is 125 nm. The polarization effects and the sensitivity of the gratings to temperature and to strain variations are presented as well.


Hidden Realities of Infant Feeding: Systematic Review of Qualitative Findings from Parents.
A growing, global conversation, regarding realities and challenges that parents experience today is ever-present. To understand recent parent's attitudes, beliefs, and perceptions regarding infant feeding, we sought to systematically identify and synthesize original qualitative research findings. Following the Enhancing Transparency in Reporting the Synthesis of Qualitative Research (ENTREQ) framework, electronic databases were searched with a priori terms applied to title/abstract fields and limited to studies published in English from 2015 to 2019, inclusive. Study quality assessment was conducted using the Critical Appraisal Skills Programme (CASP) checklist, and thematic analyses performed. Of 73 studies meeting inclusion criteria, four major themes emerged. (1) Breastfeeding is best for an infant; (2) Distinct attitudes, beliefs, and perceptions of mothers that breastfeed, and those that could not or chose not to breastfeed, are evident; (3) Infant feeding behaviors are influenced by the socio-cultural environment of the family, and (4) Parent's expectations of education and support addressing personal infant feeding choices from health care providers are not always met. This systematic review, guided by constructs within behavioral models and theories, provides updated findings to help inform the development of nutrition education curricula and public policy programs. Results can be applied within scale-up nutrition and behavioral education interventions that support parents during infant feeding.


Exploring the bidirectional interactions between human cytomegalovirus and hepatitis C virus replication after liver transplantation.
Recurrence of Hepatitis C (HCV) post-liver transplantation (LT) is universal and its course is more aggressive than in immunocompetent individuals. Human cytomegalovirus (CMV) infection is a common post-LT infection and has immunomodulatory effects that could adversely affect the outcome of HCV. To date, the effect of HCV replication on the dynamics of CMV have not been investigated. From 2000 to 2004, a cohort of 69 HCV-infected liver transplant recipients and 188 HCV-negative liver transplant recipients (NON-HCV cohort) were monitored for CMV infection twice weekly by CMV polymerase chain reaction (PCR) with preemptive therapy initiated after 2 consecutive positive results. None of the patients received CMV prophylaxis. A subset of 18 HCV-infected patients had their HCV viral load monitored regularly post-LT by quantitative PCR. CMV DNAemia (>200 genomes/mL blood) did not influence the level of HCV replication within 150 days posttransplantation or the stage of liver fibrosis in liver biopsies at 1 yr post-LT. There were no differences in the incidence of CMV DNAemia or replication dynamics in the HCV cohort compared to the NON-HCV cohort. In conclusion, short term CMV viremia does not enhance the replication of HCV after LT, while HCV replication does not alter the replication dynamics of CMV.


[The effect of platelet transfusion on traumatic intracranial hemorrhage among patients treated with aspirin].
Head trauma represents a serious medical and socio-economical problem owing to its related morbidity and mortality. One of its serious complications is traumatic intracranial hemorrhage (TICH). There is evidence that TICH has a tendency to expand, especially during the first hours following injury. Aspirin has a central role in preventing thromboembolic complications in atherosclerotic conditions. This effect is mediated through the inhibition of platelet activity. There is a theoretical concern that treatment prior to the head injury with aspirin may expand the size of TICH. The purpose of the current study was to evaluate the effect of platelet transfusion on the extent of TICH expansion among patients treated with aspirin. This retrospective study includes patients admitted to the Tel-Aviv Medical Center and the Tel-Hashomer Medical Center between 1/12/2004 and 31/10/2008. Patients were included if they underwent closed head injury, were treated regularly with aspirin prior to the injury, and had radiological evidence of an intraparenchymal hemorrhage or contusion (IPHC) or an acute subdural hematoma (ASDH]. The interval between the injury and the first computed tomography [CT] scan was not longer than 12 hours, and the interval between the first CT scan and the control CT scan was not longer than 24 hours. The effect of platelet transfusion administered between these two CT scans on the radiological and clinical outcomes was evaluated by a comparison between a group of patients treated with platelet transfusion (group A) and a group of patients who weren't treated with it (group B). A total of 44 patients were included in the study: 14 patients had IPHC, 40 had ASDH and 10 had both IPHC and ASDH. In the IPHC group the frequency of hemorrhagic expansion and the extent of expansion were greater in group A than in group B. Possibly, an earlier first CT, longer duration between both CT scans and a larger hemorrhage volume on CT1 in group A may explain these differences. In the ASDH group the frequency of hemorrhagic expansion was lower in group A than in group B, but without statistical significance. There was no significant difference in the extent of hemorrhagic expansion between the two treatment groups. From this study it appears that platelet transfusion within 36 hours post injury for patients with TICH who were treated with aspirin prior to the head injury does not reduce the rate or extent of hemorrhagic expansion. However, owing to the limitations of the present study, this conclusion should be considered with caution. We recommend evaluating this issue in a prospective, randomized, multi-center study.


mTORC1 signaling: what we still don't know.
The mammalian target of rapamycin (mTOR) is a protein kinase that plays key roles in cellular regulation. It forms complexes with additional proteins. The best-understood one is mTOR complex 1 (mTORC1). The regulation and cellular functions of mTORC1 have been the subjects of intense study; despite this, many questions remain to be answered. They include questions about the actual mechanisms by which mTORC1 signaling is stimulated by hormones and growth factors, which involves the small GTPase Rheb, and by amino acids, which involves other GTPase proteins. The control of Rheb and the mechanism by which it activates mTORC1 remain incompletely understood. Although it has been known for many years that rapamycin interferes with some functions of mTORC1, it is not known how it does this, or why only some functions of mTORC1 are affected. mTORC1 regulates diverse cellular functions. Several mTORC1 substrates are now known, although in several cases their physiological roles are poorly or incompletely understood. In the case of several processes, although it is clear that they are regulated by mTORC1, it is not known how mTORC1 does this. Lastly, mTORC1 is implicated in ageing, but again it is unclear what mechanisms account for this. Given the importance of mTORC1 signaling both for cellular functions and in human disease, it is a high priority to gain further insights into the control of mTORC1 signaling and the mechanisms by which it controls cellular functions and animal physiology.


Restoring brain function after stroke - bridging the gap between animals and humans.
Stroke is the leading cause of complex adult disability in the world. Recovery from stroke is often incomplete, which leaves many people dependent on others for their care. The improvement of long-term outcomes should, therefore, be a clinical and research priority. As a result of advances in our understanding of the biological mechanisms involved in recovery and repair after stroke, therapeutic opportunities to promote recovery through manipulation of poststroke plasticity have never been greater. This work has almost exclusively been carried out in preclinical animal models of stroke with little translation into human studies. The challenge ahead is to develop a mechanistic understanding of recovery from stroke in humans. Advances in neuroimaging techniques now enable us to reconcile behavioural accounts of recovery with molecular and cellular changes. Consequently, clinical trials can be designed in a stratified manner that takes into account when an intervention should be delivered and who is most likely to benefit. This approach is expected to lead to a substantial change in how restorative therapeutic strategies are delivered in patients after stroke.


PET/CT imaging: what radiologists need to know.
Positron emission tomography (PET)/computed tomography (CT) imaging is frequently requested in Oncology. Radiologists and nuclear medicine physicians are often asked to perform a panel of imaging examinations as part of the initial staging or follow-up of cancer patients. Medical imaging must therefore integrate polyvalent skills enabling imaging specialists to understand and interpret all types of images. In this context, PET imaging combined with non-enhanced CT, and diagnostic quality contrast-enhanced CT scan and optimisation of CT settings, is part of this multidisciplinary approach requiring the specific skills of a radiologist and a nuclear medicine physician. This approach must therefore be conducted in both directions: radiologists and nuclear medicine physicians should both know how to correlate PET and CT images, while preserving the specificities of each discipline. Radiologists need to be aware of several aspects of PET imaging: PET technology, the examination procedure and injection of iodinated contrast agent for high quality diagnostic CT, ideally followed by double interpretation of CT images, PET images and fused images. Radiologists should be familiar with PET imaging, as this procedure may be associated with several pitfalls and artefacts that need interpretation by a trained specialist. The authors analyse the examination technique of PET combined with non-enhanced and/or contrast-enhanced CT and the proposals for optimal interpretation of normal or pathological PET/CT fusion images.


Synthesis and characterization of a trisheteroleptic Ru(II) -based molecular switch.
The synthesis of a trisheteroleptic ruthenium complex [Ru(tb)(dppz)(tmbiH2 )][PF6 ]2 (tb=4,4'-di-tert-butyl-2,2'-bipyridine, dppz=dipyrido[3,2-a:2',3'-c]phenazin, tmbiH2 =5,6,5',6'-tetramethyl-2,2'-bibenzimidazole) is described. In addition, the structural characterisation by means of 1D, 2D (1) H NMR spectroscopy, and mass spectrometry, along with determination of the solid-state structure of the important precursor Ru(tb)(dppz)Cl2 , supports the proposed octahedral coordination geometry. The capability of tmbiH2 to form hydrogen bonds is corroborated by the solid-state structure. The photochemical characteristics of this complex can be described as a combination of the "light switch" effects, which are either attributed to the dppz or to the tmbiH2 ligand. To illustrate the molecule's double switchable features, steady-state absorption and emission measurements were performed, which include the determination of the quantum yield and the pKa values of the acidic protons of the tmbiH2 ligand. Notably, the emission lifetimes are sensitive to the solvents used. This phenomenon is due to a proton-coupled deactivation of the excited metal-to-ligand charge transfer (MLCT) state of the complex.


Autophagy up and down by outsmarting the incredible ULK.
Macroautophagy/autophagy initiation is finely regulated by post-translational modifications of key proteins, to comply with the fast kinetics of the cellular response to several stress stimuli. Phosphorylation and ubiquitination play a central role in controlling autophagy by influencing the activity, recruitment and turnover of autophagic components. Recently, we found that, upon autophagy progression, ULK1 kinase is specifically ubiquitinated by the E3 ligase NEDD4L and then degraded via the proteasome. However, during prolonged autophagy, while the ULK1 protein undergoes this inhibition, ULK1 mRNA is actively transcribed, translated and then inhibited again by MTOR-dependent inhibitory phosphorylation. This regulation is essential to promptly restore the ULK1 protein to its original levels to keep autophagy under a safe and physiological threshold.


Consent to organ donation: a review.
Successful transplant medicine hinges on consent to deceased organ donation. Yet rates of consent remain suboptimal. To increase the availability of transplantable organs, several policy strategies along with a rich body of evidence aimed at identifying best practices for obtaining consent have accumulated. This review describes past and current policies and practices, presents evidence illustrating the impact of these policies and practices on consent, and summarizes future directions and recommendations for the field. Key findings include evidence that although past policies such as required request have been unsuccessful, the recent policy, first-person authorization, shows promise. Additionally, practices such as decoupling and detailed discussions of brain death are unwarranted. On the other hand, the Organ Donation Breakthrough Collaboration was successful. We also underscore the impact of alternative procedures such as donation after cardiac death. Last, effective communication that is delivered by trained, caring requesters at the appropriate time, in a supportive environment, and allows sufficient time for families to make an informed decision, optimizes the request process. Organ procurement organizations' adoption of such request practices, implementation of evidence-based policies regarding donation after cardiac death, and further investigations of the medical basis for dual brain death examinations are recommended.


The Power of Music: Enhancing Muscle Strength in Older People.
Sarcopenia is a major problem occurring in the aging population. Based on previous research, music appears to have a positive influence on many aspects of life, including physical performance. This led to the question of whether listening to self-selected favorite music could improve peripheral muscle strength in older people. In this crossover study, community-dwelling people aged 65 and older were included. All participants performed handgrip strength measurements in three different circumstances: while listening to their favorite music, their most disliked music, and no music at all. As the primary outcome measurement, the within-person differences in maximum handgrip strength between the three music conditions were analyzed. A total of 153 participants (aged 73.0 ± 6 years) were included. Listening to favorite music resulted in an increase in maximum handgrip strength of +0.87 kgf (0.54-1.21, p < 0.001) compared to no music, and of +0.97 kgf (0.56-1.37, p < 0.001) compared to least favorite music. Thus, listening to favorite music has a positive effect on handgrip strength in older people. Apart from its implications for scientific grip strength measurements, this effect may be used as a fun and innocent stimulant in rehabilitation and workout classes with seniors, which could be further tested in a range of older people.


Structure-Based Discovery of a Novel Class of Small-Molecule Pure Antagonists of Integrin αVβ3.
Inhibitors of integrin αVβ3 have therapeutic promise for a variety of diseases. Most αVβ3-targeting small molecules patterned after the RGD motif are partial agonists because they induce a high-affinity, ligand-binding conformation and prime the receptor to bind the ligand without an activating stimulus, in part via a charge-charge interaction between their aspartic acid carboxyl group and the metal ion in the metal-ion-dependent adhesion site (MIDAS). Building upon our previous studies on the related integrin αIIbβ3, we searched for pure αVβ3 antagonists that lack this typical aspartic acid carboxyl group and instead engage through direct binding to one of the coordinating residues of the MIDAS metal ion, specifically β3 E220. By in silico screening of two large chemical libraries for compounds interacting with β3 E220, we indeed discovered a novel molecule that does not contain an acidic carboxyl group and does not induce the high-affinity, ligand-binding state of the receptor. Functional and structural characterization of a chemically optimized version of this compound led to the discovery of a novel small-molecule pure αVβ3 antagonist that (i) does not prime the receptor to bind the ligand and does not induce hybrid domain swing-out or receptor extension as judged by antibody binding and negative-stain electron microscopy, (ii) binds at the RGD-binding site as predicted by metadynamics rescoring of induced-fit docking poses and confirmed by a cryo-electron microscopy structure of the compound-bound integrin, and (iii) coordinates the MIDAS metal ion via a quinoline moiety instead of an acidic carboxyl group.


Design of Morphology-Controllable ZnO Nanorods/Nanopariticles Composite for Enhanced Performance of Dye-Sensitized Solar Cells.
A facile one-pot approach was developed for the synthesis of ZnO nanorods (NRs)/nanoparticles (NPs) architectures with controllable morphologies. The concrete state of existence of NPs and NRs could rationally be controlled through reaction temperature manipulation, i.e., reactions occured at 120, 140, 160, and 180 °C without stirring resulted in orderly aligned NRs, disordered but connected NRs/NPs, and relatively dispersed NRs/NPs with different sizes and lengths, respectively. The as-obained ZnO nanostructures were then applied to construct photoanodes of dye-sensitized solar cells, and the thicknesses of the resultant films were controlled for performance optimization. Under an optimized condition (i.e., with a film thickness of 14.7 µm), the device fabricated with the material synthesized at 160 °C exhibited the highest conversion efficiency of 4.30% with an elevated current density of 14.50 mA·cm-2 and an open circuit voltage of 0.567 V. The enhanced performance could be attributed to the coordination effects of the significantly enhanced dye absorption capability arising from the introduced NPs and the intrinsic fast electron transport property of NRs as confirmed by electrochemical impedance spectroscopy (EIS) and ultraviolet-visible (UV-vis) absorption.


Surfactin Ameliorated the Internalization and Inhibitory Performances of Bleomycin Family Compounds in Tumor Cells.
The cationic glycopeptide bleomycin (BLM) is a broad-spectrum chemotherapy drug clinically applied to treat various malignant tumors. The poor cell membrane permeability of BLM, which is prone to high dose usage and may consequently induce dose-dependent lung toxicity, is a sticking point to limit clinical applications of BLM. As a commercial biosurfactant, the anionic lipopeptide surfactin (SF) is well known for its potent ability to disturb membranes and widely applied in cosmetic area as a permeabilization synergist. In this work, our in vitro investigations showed that SF could ameliorate the cell internalization of BLM, and the combined usage of SF notably improved the antitumor activity of BLM or its analogues while having no obvious effects on normal cells. Subsequent in vivo assessments on the subcutaneous treatment of A375 melanoma in mice demonstrated that SF could also enhance the therapeutic effects of BLM family compounds in subeffective doses, with no obvious toxicities on lungs and skin. Also, our preliminary results suggested the formation of complex micelles at the nanoscale by the self-assembly of BLM and SF, which may contribute to the ameliorated internalization and the antitumor effect of BLM. Therefore, SF could be applied as a potential synergist for BLM to reduce its treatment dose while maintaining the therapeutic effect on treatment of skin carcinoma, which provides us an alternative way to minimize the side effects of clinical BLM and facilitate the development of new BLM-type drugs.


Biochemical principles underlying the stable maintenance of LTP by the CaMKII/NMDAR complex.
Memory involves the storage of information at synapses by an LTP-like process. This information storage is synapse specific and can endure for years despite the turnover of all synaptic proteins. There must, therefore, be special principles that underlie the stability of LTP. Recent experimental results suggest that LTP is maintained by the complex of CaMKII with the NMDAR. Here we consider the specifics of the CaMKII/NMDAR molecular switch, with the goal of understanding the biochemical principles that underlie stable information storage by synapses. Consideration of a variety of experimental results suggests that multiple principles are involved. One switch requirement is to prevent spontaneous transitions from the off to the on state. The highly cooperative nature of CaMKII autophosphorylation by Ca(2+) (Hill coefficient of 8) and the fact that formation of the CaMKII/NMDAR complex requires release of CaMKII from actin are mechanisms that stabilize the off state. The stability of the on state depends critically on intersubunit autophosphorylation, a process that restores any loss of pT286 due to phosphatase activity. Intersubunit autophosphorylation is also important in explaining why on state stability is not compromised by protein turnover. Recent evidence suggests that turnover occurs by subunit exchange. Thus, stability could be achieved if a newly inserted unphosphorylated subunit was autophosphorylated by a neighboring subunit. Based on other recent work, we posit a novel mechanism that enhances the stability of the on state by protection of pT286 from phosphatases. We posit that the binding of the NMNDAR to CaMKII forces pT286 into the catalytic site of a neighboring subunit, thereby protecting pT286 from phosphatases. A final principle concerns the role of structural changes. The binding of CaMKII to the NMDAR may act as a tag to organize the binding of further proteins that produce the synapse enlargement that underlies late LTP. We argue that these structural changes not only enhance transmission, but also enhance the stability of the CaMKII/NMDAR complex. Together, these principles provide a mechanistic framework for understanding how individual synapses produce stable information storage. This article is part of a Special Issue entitled SI: Brain and Memory.


Oxygen tension and the selective tropism of K-virus for mouse pulmonary endothelium.
This study focused on the unique nature of K-virus pneumonitis in suckling mice. This process, rather than being a conventional pneumonitis, is characterized by viral replication and cytopathic effects restricted exclusively to pulmonary endothelium. The selective viral attack on this air-blood interface suggests that K-virus is an endotheliotrope that requires a richly oxygenated intracellular milieu for replication. This possibility has been explored by studies of the course of K-virus infection in suckling mice under conditions of normal (21 per cent), increased (40 per cent), and decreased (10 per cent) 02 content of inspired air. The absence of critical modulating influences of these varied environmental conditions rules out a significant role of tissue 02 concentrations as determinants of the selective tropism of K-virus.


Modifications of receptor concentrations for adrenaline, steroid hormones, prostaglandin F2alpha and gonadotropins in hypophysis and ovary of dairy cows with ovarian cysts.
Receptor concentrations for adrenaline, steroid hormones, PGF2alpha, LH and FSH were measured in the hypophysis and ovary of dairy cows with ovarian cysts and the results were compared with those of healthy animals. Significant modifications were found in all receptor concentrations, either between follicular and luteal structures or between the hypophyseal and ovarian receptorial status. The correlations between catecholaminergic and steroidal systems have already been demonstrated, particularly those existing between beta-adrenoceptors and steroid hormone receptors. Particular attention has been given to the possibility that a derangement in neurogenic inputs may be at the basis of some ovarian pathologies. The results of the present study suggest that the modifications of the ovarian and hypophyseal receptorial status of healthy and affected cows could play an important role in the pathogenesis of ovarian cysts.


Right intracavitary cardiac tumors. Surgical management.
The surgical treatment of 6 patients affected by right cardiac tumors is reported. Three of them showed a right atrial myxoma, 1 metastases from an occult embryonal carcinoma and 1 a leiomyosarcoma of the pulmonary artery. While clinical diagnosis was not reliable, the echocardiographic examination was able to assess the site of the tumor, supplying useful information for the anatomy and surgery in 5 cases out of 6; in one case, the diagnosis was reached intraoperatively. All the patients survived the surgical treatment: while those with atrial myxoma recovered completely, the others with malignant tumors died from metastases 5 to 10 months postoperatively. The importance of early diagnosis is stressed together with the role of surgery, which permits the recovery of cases with benign tumors and a longer survival of cases with malignant tumors.


Studies on prolyl endopeptidase from shakashimeji (Lyophyllum cinerascens): purification and enzymatic properties.
High prolyl endopeptidase (post-proline cleaving enzyme) [EC 188.8.131.52] activity was detected in fruit bodies of shakashimeji (Lyophyllum cinerascens), tsukuritake (mushroom: Agaricus bisporus), hirohachichitake (Lactarius hygrophoroides), and yaburebenitake (Russula lepida) which belong to the genus Basidiomycetes. Cell-free extract of shakashimeji showed high activities of proline iminopeptidase and arylamidase as well as prolyl endopeptidase. The prolyl endopeptidase was purified from the extract of shakashimeji by sequential chromatographies on DEAE-Toyopearl, DEAE-Sephadex and hydroxyapatite, and high-performance liquid chromatography with a DEAE-5PW column. The purified enzyme was homogeneous as judged by disc gel electrophoresis. The enzyme was most active at pH 6.8 as checked with Z-Gly-Pro-beta-naphthylamide as a substrate and was stable in the range of pH 5.8-7.4. The isoelectric point of the enzyme was 5.2 and the molecular weight was estimated to be 76,000 by gel filtration on Sephadex G-150 and by sodium dodecyl sulfate (SDS) gel electrophoresis, suggesting that the enzyme was a monomer. The enzyme was completely inhibited by diisopropyl fluorophosphate (DFP), Z-Gly-Pro-CH2Cl, and Z-Pro-prolinal, while it was not inhibited by p-chloromercuribenzoate (PCMB), phenylmethylsulfonyl fluoride (PMSF), or metal chelators. It was estimated that at least five subsites were concerned with the enzyme-substrate binding. Among them, the S1, S2, and S1' sites showed high stereospecificity, as in mammalian, microbial, and plant enzymes. The enzyme hydrolyzed TRH at the carboxyl side of the proline residue. The mushroom enzyme, that was sensitive to DFP, Z-Pro-prolinal, and Z-Gly-Pro-CH2Cl, but not to PCMB, were quite similar in characteristics to the Flavobacterium enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)


Cubatic phase for tetrapods.
We investigate the phase behavior of tetrapods, hard nonconvex bodies formed by four rods connected under tetrahedral angles. We predict that, depending on the relative lengths of the rods these particles can form a uniaxial nematic phase, and more surprisingly they can exhibit a cubatic phase, a special case of the biaxial nematic phase. These predictions may be experimentally testable, as experimental realizations of tetrapods have recently become available.


Functio Laesa: Cancer Inflammation and Therapeutic Resistance.
Tumor, calor, rubor, and dolor describe four cardinal signs of inflammation. The fifth-functio laesa, or loss of function-was promulgated by Rudolf Virchow, who, in the 19th century, also noted an intricate link between inflammation and cancer. However, the role of cancer inflammation in driving loss of therapeutic efficacy has only recently been fully appreciated, as a result of molecular and immunohistochemical approaches applied in clinical medicine and the availability of novel agents for modulating inflammation. This review focuses on clinical evidence from solid malignancies that have shaped our view of how the immune system regulates cancer development, progression, and response to treatment. Understanding the multifaceted relationship between inflammation and patient outcomes has the potential to advance prognostic tools and uncover therapeutic opportunities for improving clinical outcomes.


A comparison of calls subjected to a malpractice claim versus 'normal calls' within the Swedish healthcare direct: a case-control study.
The purpose of this study is to compare communication patterns in calls subjected to a malpractice claim with matched controls. In many countries, telephone advice nursing is patients' first contact with healthcare. Telenurses' assessment of callers' symptoms and needs are based on verbal communication only, and problems with over-triage and under-triage have been reported. A total sample of all reported medical errors (n=33) during the period 2003-2010 within Swedish Healthcare Direct was retrieved. Corresponding calls were thereafter identified and collected as sound files from the manager in charge at the respective call centres. For technical reasons, calls from four of the cases were not possible to retrieve. For the present study, matched control calls (n=26) based on the patient's age, gender and main symptom presented by the caller were collected. Male patients were in majority (n=16), and the most common reasons for calling were abdominal pain (n=10) and chest pain (n=5). There were statistically significant differences between the communication in the cases and controls: telenurses used fewer open-ended medical questions (p<0.001) in the cases compared to the control calls; callers provided telenurses with more medical information in the control calls compared to the cases (p=0.001); and telenurses used more facilitation and patient activation activities in the control calls (p=0.034), such as back-channel response (p=0.001), compared to the cases. The present study shows that telenurses in malpractice claimed calls used more closed-ended questioning compared to those in control calls, who used more open-ended questioning and back-channel response, which provided them with richer medical descriptions and more information from the caller. Hence, these communicative techniques are important in addition to solid medical and nursing competence and sound decision aid systems.


Digital behavioural signatures reveal trans-diagnostic clusters of Schizophrenia and Alzheimer's disease patients.
The current neuropsychiatric nosological categories underlie pragmatic treatment choice, regulation and clinical research but does not encompass biological rationale. However, subgroups of patients suffering from schizophrenia or Alzheimer's disease have more in common than the neuropsychiatric nature of their condition, such as the expression of social dysfunction. The PRISM project presents here initial quantitative biological insights allowing the first steps toward a novel trans-diagnostic classification of psychiatric and neurological symptomatology intended to reinvigorate drug discovery in this area. In this study, we applied spectral clustering on digital behavioural endpoints derived from passive smartphone monitoring data in a subgroup of Schizophrenia and Alzheimer's disease patients, as well as age matched healthy controls, as part of the PRISM clinical study. This analysis provided an objective social functioning characterization with three differential clusters that transcended initial diagnostic classification and was shown to be linked to quantitative neurobiological parameters assessed. This emerging quantitative framework will both offer new ways to classify individuals in biologically homogenous clusters irrespective of their initial diagnosis, and also offer insights into the pathophysiological mechanisms underlying these clusters.


Inferring and analysis of social networks using RFID check-in data in China.
Social networks play an important role in our daily lives. However, social ties are rather elusive to quantify, especially for large groups of subjects over prolonged periods of time. In this work, we first propose a methodology for extracting social ties from long spatio-temporal data streams, where the subjects are 17,795 undergraduates from a university of China and the data streams are the 9,147,106 time-stamped RFID check-in records left behind by them during one academic year. By several metrics mentioned below, we then analyze the structure of the social network. Our results center around three main observations. First, we characterize the global structure of the network, and we confirm the small-world phenomenon on a global scale. Second, we find that the network shows clear community structure. And we observe that younger students at lower levels tend to form large communities, while students at higher levels mostly form smaller communities. Third, we characterize the assortativity patterns by studying the basic demographic and network properties of users. We observe clear degree assortativity on a global scale. Furthermore, we find a strong effect of grade and school on tie formation preference, but we do not find any strong region homophily. Our research may help us to elucidate the structural characteristics and the preference of the formation of social ties in college students' social network.


[Effect of jingui shenqi pill on morphology of injured spinal cell apoptosis in rats caused by brachytherapy].
To study the effect of Jingui Shenqi Pill (JSP) on morphology of spinal cell apoptosis in rats injured by 192Ir irradiation. One hundred and twenty rats were randomly divided into four groups: the model group, the JSP group, the prednisone group and the normal group. Corresponding pharmaceutics were given to rats once a day for 14 days respectively. Then except rats in the normal group, the others received 192Ir interstitial irradiation with the dosage of 22 Gy using back-fixing technology. The injured segments of spinal cord were taken out for HE staining, TUNEL examination and observation with electron microscope 8 hrs, 24 hrs and 4 weeks after irradiation. HE staining examination showed no obvious histological change in rats 8 and 24 hrs after irradiation, but pathological changes, as tissue rarefaction and hemorrhage did found in white matter of spinal cord shown by TUNEL 4 weeks later. Electron microscopic examination and TUNEL staining showed that as compared with the model group, the apoptotic index in the JSP and predinisone treated groups was significantly lower (P < 0.01) 8 hrs after radiation, but it showed insignificant difference between groups at the time points of 24 hrs and 4 weeks after radiation (P > 0.05). JSP could act against apoptosis of gliocyte in spinal cord of rats in early stage after brachytherapy, indicating that JSP possessing a prednisone-like action.


Ensemble perspective for understanding temporal credit assignment.
Recurrent neural networks are widely used for modeling spatiotemporal sequences in both nature language processing and neural population dynamics. However, understanding the temporal credit assignment is hard. Here, we propose that each individual connection in the recurrent computation is modeled by a spike and slab distribution, rather than a precise weight value. We then derive the mean-field algorithm to train the network at the ensemble level. The method is then applied to classify handwritten digits when pixels are read in sequence, and to the multisensory integration task that is a fundamental cognitive function of animals. Our model reveals important connections that determine the overall performance of the network. The model also shows how spatiotemporal information is processed through the hyperparameters of the distribution, and moreover reveals distinct types of emergent neural selectivity. To provide a mechanistic analysis of the ensemble learning, we first derive an analytic solution of the learning at the infinitely large network limit. We then carry out a low-dimensional projection of both neural and synaptic dynamics, analyze symmetry breaking in the parameter space, and finally demonstrate the role of stochastic plasticity in the recurrent computation. Therefore, our study sheds light on mechanisms of how weight uncertainty impacts the temporal credit assignment in recurrent neural networks from the ensemble perspective.


Supramolecular Modulation of Structural Polymorphism in Pathogenic α-Synuclein Fibrils Using Copper(II) Coordination.
Structural variation of α-synuclein (αSyn) fibrils has been linked to the diverse etiologies of synucleinopathies. However, little is known about what specific mechanism provides αSyn fibrils with pathologic features. Herein, we demonstrate Cu(II)-based supramolecular approach for unraveling the formation process of pathogenic αSyn fibrils and its application in a neurotoxic mechanism study. The conformation of αSyn monomer was strained by macrochelation with Cu(II), thereby disrupting the fibril elongation while promoting its nucleation. This non-canonical process formed shortened, β-sheet enriched αSyn fibrils (<0.2 μm) that were rapidly transmitted and accumulated to neuronal cells, causing neuronal cell death, in sharp contrast to typical αSyn fibrils (ca. 1 μm). Our approach provided the supramolecular basis for the formation of pathogenic fibrils through physiological factors, such as brain Cu(II).


Combined radiofrequency ablation and hot saline injection in rabbit liver.
To determine whether combining hot saline injection (HSI) and radiofrequency ablation (RFA) can increase the extent of thermally mediated coagulation in in vivo rabbit liver tissue. In 66 rabbits, RF energy and/or hot saline-induced coagulations were produced using a 17-gauge cooled electrode or 21-gauge needle under ultrasound guidance. Rabbits were allocated into 1 of 5 groups: group A, RFA alone (n = 15); group B, HSI (1 mL hot saline infused, n = 10); group C, combined therapy for HSI followed by RFA (n = 21); group D, combined therapy for RFA immediately followed by HSI (n = 10); and group E, 1 mL room temperature saline infusion before RFA (n = 10). RF energy (30 W) was applied for 3 minutes. The changes in tissue impedance, current, power output, and temperature of the electrode tip were automatically measured. Before RFA, precontrast computed tomography was performed, and after RFA, pre- and postcontrast spiral computed tomographic scans were acquired. The maximum diameters of the thermal lesions on the gross specimens and complications of each group were compared. All procedures were technically successful. There were 9 of 61 procedure-related complications (14.8%) including 6 localized hematomas and 3 thermal injuries to the diaphragm and the stomach. In rabbits in groups C and E, a marked decrease of tissue impedance (43.4 omega, 44.1 omega) and an increase of current (709 mA, 722 mA) occurred with instillation of saline infusion compared with RFA only. Combined therapy for HSI followed by RFA produced a greater short-axis mean diameter of coagulation (14.6 +/- 4.3 mm) than that in rabbits of other groups, for RFA only (10.4 +/- 2.4 mm), HSI only (8.7 +/- 3.3 mm), and combined therapy for RFA immediately followed by HIS (12.0 +/- 1.4 mm; P < 0.05). Combined therapy for HSI followed by RFA can increase the volume of RFA-induced coagulation in the liver with a single application, and therefore may improve the results of RFA for the treatment of larger tumors.


Initial experience of single-incision laparoscopic hepaticojejunostomy using conventional instruments for correctable biliary atresia.
Single-incision laparoscopic surgery aims to minimize surgical trauma. Yet there has been no report on its application to the treatment of correctable biliary atresia (BA). We present here our initial mini-series of successful single-incision laparoscopic hepaticojejunostomy (SILH) for correctable BA. We reviewed 4 correctable BA patients (Type I/II, 3/1) who underwent SILH between May and July 2011. Ultrasonography, upper gastrointestinal contrast studies, and blood tests were performed during the follow-up period. The age at operation, operative time, postoperative hospital stay, resumption of full diet, postoperative complications, and perioperative laboratory tests were evaluated. The median age at operation was 21 days. The median operative time was 2 hours. Blood loss was minimal. The median follow-up duration was 4.5 months. Jaundice gradually declined after 3-5 days in Type I and 6 days in Type II BA patient. There was no mortality or surgical complication so far. In experienced hands, SILH for treatment of correctable BA is safe and effective.


Basal metabolic rate of endotherms can be modeled using heat-transfer principles and physiological concepts: reply to "can the basal metabolic rate of endotherms be explained by biophysical modeling?".
Our recent article (Roberts et al. 2010 ) proposes a mechanistic model for the relation between basal metabolic rate (BMR) and body mass (M) in mammals. The model is based on heat-transfer principles in the form of an equation for distributed heat generation within the body. The model can also be written in the form of the allometric equation BMR = aM(b), in which a is the coefficient of the mass term and b is the allometric exponent. The model generates two interesting results: it predicts that b takes the value 2/3, indicating that BMR is proportional to surface area in endotherms. It also provides an explanation of the physiological components that make up a, that is, respiratory heat loss, core-skin thermal conductance, and core-skin thermal gradient. Some of the ideas in our article have been questioned (Seymour and White 2011 ), and this is our response to those questions. We specifically address the following points: whether a heat-transfer model can explain the level of BMR in mammals, whether our test of the model is inadequate because it uses the same literature data that generated the values of the physiological variables, and whether geometry and empirical values combine to make a "coincidence" that makes the model only appear to conform to real processes.


Electrocution due to contact of industrial equipment with power lines.
Electrocution due to contact of construction equipment with power lines is not uncommon as a source of industrial injury. We report seven such cases. Two patients sustained cardiac arrest and were successfully resuscitated at the scene. Four patients lost consciousness and in two cases, amnesia for the event was encountered. No long-term cardiac or neurologic effects were noted. Surgery including amputation was sometimes required. In all cases, the patient was on the ground touching the machinery or touching cables connected to the machinery at the time of injury. The importance of exercising due care in industrial safety measures is stressed. Prompt CPR was life saving in two cases.


Reduced sensitivity to affiliation and psychopathic traits.
Psychopathy is characterized by affective and interpersonal deficits, deviant lifestyle, and antisocial behaviors. Much research has been dedicated to understanding the impairments in reinforcement learning, fear conditioning, and sensitivity to threat, distress, or fear in others, which are thought to underpin psychopathic traits. Fewer studies have examined deficits in affiliative processes, which could provide insight into mechanisms giving rise to the impairments in social bonding, closeness with others, and cooperation that also characterize individuals high on psychopathy. The current study examined whether reduced sensitivity to affiliation was related to psychopathic traits among 407 adults from the community (female, 59%). Sensitivity to affiliation was modeled as a latent construct capturing item-level variance shared across 4 measures that assessed sensitivity to emotional and physical cues of affiliation, including stimuli presented as videos or images, and via self-report ratings about sensitivity to positive affiliative and affective cues. Results indicated that lower sensitivity to affiliation was related to higher total psychopathy scores. In particular, in models parsing the overlap of psychopathy factor and facet scores, lower sensitivity to affiliation was uniquely related to higher Factor 1 and affective facet scores, as well as higher scores on a measure of callous-unemotional traits. Our findings provide support for the existence of important socioaffiliative and motivational deficits that may underpin the affective features of psychopathy and speak to the potential to target such mechanisms in interventions and treatments to reduce psychopathic traits. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Evaluation of the Anti-Inflammatory, Antioxidant and Immunomodulatory Effects of the Organic Extract of the Red Sea Marine Sponge Xestospongia testudinaria against Carrageenan Induced Rat Paw Inflammation.
Marine sponges are found to be a rich source of bioactive compounds which show a wide range of biological activities including antiviral, antibacterial, and anti-inflammatory activities. This study aimed to investigate the possible anti-inflammatory, antioxidant and immunomodulator effects of the methanolic extract of the Red Sea marine sponge Xestospongia testudinaria. The chemical composition of the Xestospongia testudinaria methanolic extract was determined using Gas chromatography-mass spectroscopy (GC-MS) analysis. DPPH (2, 2-diphenyl-1-picryl-hydrazyl) was measured to assess the antioxidant activity of the sponge extract. Carrageenan-induced rat hind paw edema was adopted in this study. Six groups of rats were used: group1: Control, group 2: Carrageenan, group 3: indomethacin (10 mg/kg), group 4-6: Xestospongia testudinaria methanolic extract (25, 50, and 100 mg/kg). Evaluation of the anti-inflammatory activity was performed by both calculating the percentage increase in paw weight and hisopathologically. Assessment of the antioxidant and immunomodulatory activity was performed. GC-MS analysis revealed that there were 41 different compounds present in the methanolic extract. Sponge extract exhibited antioxidant activity against DPPH free radicals. Xestospongia testudinaria methanolic extract (100 mg/kg) significantly decreased % increase in paw weight measured at 1, 2, 3 and 4 h after carrageenan injection. Histopathologically, the extract caused a marked decrease in the capillary congestion and inflammatory cells infiltrate. The extract decreased paw malondialdehyde (MDA) and nitric oxide (NO) and increased the reduced glutathione (GSH), glutathione peroxidase (GPx), and catalase (CAT) activity. It also decreased the inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-1 β(IL-1β) and IL-6. The results of this study demonstrated the anti-inflammatory, antioxidant, and immunomodulatory effects of the methanolic extract of the Red Sea sponge Xestospongia testudinaria (100 mg/kg).


Local and global dynamics of multi-resolved polymer chains: Effects of the interactions atoms-beads on the dynamic of the chains.
We present a thorough analysis of the dynamic behaviour of hybrid atomistic/coarse-grained (CG) models of polymer melts. While structural properties are well preserved in a dual-resolved model, we show how the dynamic of the chains can be influenced by the simultaneous presence of atoms and beads. We show that although the polymer chains are long enough to exhibit reptation, the corresponding CG model is unable to capture the expected subdiffusive regimes and seems to still follow the Rouse dynamics. The introduction of atoms in the chain restores the correct dynamic regime, and the dynamics of hybrid systems becomes comparable to that of the atomistic dynamics as the atoms/beads ratio is increased.


Trends in late HIV diagnosis among men who have sex with men in Jiangsu province, China: Results from four consecutive community-based surveys, 2011-2014.
To examine trends in HIV testing, late HIV diagnosis and associated factors among men who have sex with men (MSM) in Jiangsu province, China. Four consecutive community-based cross-sectional surveys were conducted among MSM from 2011 to 2014 in eight cities in the province. Participants were recruited from MSM venues and via the internet. HIV bio-behavioral surveys were conducted to collect demographic and behavioral data and measure HIV infection. HIV-infected participants with CD4 counts less than 350 cells/uL were defined as having a late HIV diagnosis. Chi-square trend tests were used to compare temporal changes over the years and multivariable logistic regression analyses were used to identify factors associated with late diagnosis. A total of 2,441, 2,677, 2,591 and 2,610 participants were enrolled in 2011, 2012, 2013 and 2014, respectively. Testing for HIV in the last 12 months decreased over the time period, from 59.9% to 52.5% (p<0.001). Late HIV diagnosis remained high and steady, ranging from 33.3% to 44.2% over the years with no significant change over time (p = 0.418). MSM who were older than 24 years (aOR = 1.748, p = 0.020 for 25-39 years old; aOR = 3.148, p<0.001 for 40 years old or older), were recruited via internet (aOR = 1.596, p = 0.024), and did not have an HIV test in the past 12 months (aOR = 3.385, p<0.001) were more likely to be late diagnosed. Our study showed a plateau in HIV testing among MSM in China, in parallel to high levels of late diagnosis. Emerging and innovative strategies such as HIV self-testing and reaching more MSM by internet, both highly acceptable to MSM in China, may reduce late diagnosis.


Kinetics of hydrolysis of diltiazem hydrochloride in aqueous solutions.
The kinetics of hydrolysis of diltiazem hydrochloride in aqueous solutions at 313, 323, 333 and 353 K over the pH-range 0.4-9.7 has been investigated. The decomposition was followed by the HPLC method. The pH-rate profile was accounted for by the specific acid- and base-catalysed reactions and also by assuming spontaneous or water-catalysed decomposition of both dissociated and undissociated molecules of diltiazem. Various buffer substances were found to exhibit general acid and base catalysis of the degradation. Thermodynamic parameters of the reaction: energy and enthalpy of activation and the frequency factor for the specific rate constants were determined.


The effect of prolonged and exclusive breast-feeding on dental caries in early school-age children. New evidence from a large randomized trial.
To study the effects of prolonged and exclusive breast-feeding on dental caries, we followed up children participating in the Promotion of Breastfeeding Intervention Trial (PROBIT), a cluster-randomized trial of a breast-feeding promotion intervention based on the WHO/UNICEF Baby-Friendly Hospital Initiative. A total of 17,046 healthy, mother-infant breast-feeding pairs were enrolled from 31 Belarussian maternity hospitals and affiliated polyclinics, of whom 13,889 (81.5%) were followed up at 6.5 years. At follow-up, polyclinic pediatricians transcribed the reports of a standard dental examination performed by public health dentists at age 6 years and recorded in the children's polyclinic charts. Analysis was based on intention to treat, with a statistical model that accounts for clustering within hospitals/clinics to permit inferences at the individual level. The experimental intervention led to a large increase in exclusive breast-feeding at 3 months (43.3 vs. 6.4%, p < 0.001) and a significantly higher prevalence of any breast-feeding at all ages up to and including 12 months. No significant intervention effects were observed on dental caries. Our results, based on the largest randomized trial ever conducted in the area of human lactation, provide no evidence of beneficial or harmful effects of prolonged and exclusive breast-feeding on dental caries at early school age.


Near-field acoustical holography and acoustic power analysis of a simulated, highly heated supersonic jet.
Although near-field acoustical holography (NAH) and acoustic intensity analysis have previously been used to investigate the apparent jet noise sources produced by military aircraft, explicit connections to supersonic jet characteristics cannot be made due to a lack of information about the exhaust plume. To begin to bridge this gap and better understand the source information yielded by NAH, the current study instead applies NAH to a virtual measurement of the near-field pressures of a highly heated laboratory-scale supersonic jet generated by large-eddy simulation (LES). The holographic reconstructions of the pressure, particle velocity, and acoustic intensity are found to match the LES-generated acoustic field well and are used to calculate the acoustic power of the jet. The jet's calculated overall acoustic power is compared to the free-stream mechanical power, resulting in an acoustic efficiency of 1.5%. Ray-tracing of the acoustic intensity to the jet centerline generates an axial distribution of the acoustic power origin, showing that almost all the power originates from the supersonic portion of the flow and with the distribution peak upstream of the potential core tip. Holographic reconstruction of the pressures along the nozzle lipline captures the general spectral shape of the LES-generated pressures, though it underestimates the amplitude.


Functionalization of Cellulose Nanocrystals with POEGMA Copolymers via Copper-Catalyzed Azide-Alkyne Cycloaddition for Potential Drug-Delivery Applications.
Elongated colloidal nanoparticles (NPs) have significant potential for drug delivery and imaging applications in cancer therapy, but progress depends on developing a deeper understanding of how their physicochemical properties affect their interactions with cells and with tumors. Cellulose nanocrystals (CNCs) are biocompatible, rodlike colloids that are broadly surface-functionalizable, making them interesting as modular drug carriers. In this report, we describe the attachment of a statistical copolymer containing oligoethylene glycol methacrylate (OEGMA; Mn ≈ 500 Da) and small amounts of aminopropylmethacrylamide (APMA) to CNCs. Here, the copolymer is designed to serve as a "stealth" corona to minimize protein adsorption, and the amino groups provide functionality for the attachment of diagnostic or therapeutic moieties. The corona polymer with a terminal azide group was synthesized by atom transfer radical polymerization using tert-butyloxycarbonyl (tBoc)-protected APMA as the comonomer. A key step in this synthesis was the grafting of acetylene groups to the CNC surface via a reaction with NaOH plus propargyl bromide in aqueous dimethyl sulfoxide. The copolymer was attached to the CNCs using copper-catalyzed azide-alkyne cycloaddition (CuAAC) "click" chemistry. By determining the mean number of amino groups per copolymer and amino group content of the CNC sample, we were able to infer that there were on average ca. 300 polymer molecules per CNC. Preliminary evaluation in a human ovarian cancer cell line (HEYA8) and a human breast cancer cell line (MDA-MB-436) demonstrated that these CNCs are nontoxic. We also assessed the cellular uptake of these CNC NPs in the same two cell lines using flow cytometry and distinguished between NPs being internalized by the cell or surface-bound using a trypan blue quenching experiment. These results provide support for applications of polymer-coated CNCs in medicine and are encouraging for further studies in vitro and in vivo to evaluate their potential as drug-delivery vehicles.


Smallest near-infrared fluorescent protein evolved from cyanobacteriochrome as versatile tag for spectral multiplexing.
From a single domain of cyanobacteriochrome (CBCR) we developed a near-infrared (NIR) fluorescent protein (FP), termed miRFP670nano, with excitation at 645 nm and emission at 670 nm. This is the first CBCR-derived NIR FP evolved to efficiently bind endogenous biliverdin chromophore and brightly fluoresce in mammalian cells. miRFP670nano is a monomer with molecular weight of 17 kDa that is 2-fold smaller than bacterial phytochrome (BphP)-based NIR FPs and 1.6-fold smaller than GFP-like FPs. Crystal structure of the CBCR-based NIR FP with biliverdin reveals a molecular basis of its spectral and biochemical properties. Unlike BphP-derived NIR FPs, miRFP670nano is highly stable to denaturation and degradation and can be used as an internal protein tag. miRFP670nano is an effective FRET donor for red-shifted NIR FPs, enabling engineering NIR FRET biosensors spectrally compatible with GFP-like FPs and blue-green optogenetic tools. miRFP670nano unlocks a new source of diverse CBCR templates for NIR FPs.


The Health and Working Conditions of Women Employed in Child Care.
Over one million women are employed in child care and are among the lowest wage workers in the US. The health and working conditions of 674 child care workers (118 administrators and 556 staff) from 74 centers is described using baseline data from a larger intervention trial. Participants were 39.9 (±13.0) years old; 55.4% African American, 37.1% Caucasian, and 5.3% of Hispanic ethnicity. Seventy-six percent reported having an Associate's degree or less; 42% were classified as at or below poverty (<$20,000); and exhibited many health risks such as excess weight, insufficient activity, poor diet, and inadequate sleep. We investigated potential differences by income and job category. Lower income participants were significantly more likely to be current smokers (19.9% vs. 11.7%), drink more sweetened beverages (1.9 vs. 1.5), and report higher depressive symptoms (15.5 vs. 12.6). Administrators worked more hours weekly compared to staff (46.4 vs. 40.6), are less active (100 vs. 126 min/week), more sedentary (501 vs. 477 min/day), and reported higher job demands (13.3 vs. 12.5). Given the numerous health issues and challenging work conditions, we hope our results serve as a call to action for addressing low wages and the work environment as a means of influencing the health and well-being of child care workers.


Glasgow Coma Scale for outcome prediction after cardiac surgery: is it applicable?
The Glasgow Coma Scale (GCS) is used commonly for assessing patients' neurologic condition and outcome in intensive care units (ICUs); however, its reliability in cardiac surgical patients has been questioned. It has been claimed that active sedation is the cause of its unsuitability for these patients. This study aimed to compare the accuracy of GCS in cardiac surgical patients with and without active sedation to find out if the inapplicability of GCS in surgical patients is related to active sedation. This was an observational cohort study. The study was conducted in a cardiac surgical intensive care unit between January 1, 2007 and December 31, 2009. All consecutive adult cardiac surgical patients were included in this study. All types of cardiac surgical procedures performed during the study period were included without any exceptions. The study population was divided into 2 groups: sedated and non-sedated. GCS was calculated daily for the first 7 postoperative days. The authors developed a new 4-point neurologic descriptor (ND): (1) neurologically free, (2) ICU psychosis, (3) actively sedated, and (4) documented focal neurologic deficits. The accuracy of both scales (GCS and ND) at predicting ICU mortality was compared by replacing the GCS in the Sequential Organ Failure Assessment (SOFA) score with the new ND, producing a modified SOFA. GCS was not an accurate outcome predictor in non-sedated or sedated patients. The ND was superior to GCS. Correspondingly, the modified SOFA showed a significantly higher accuracy of ICU-mortality prediction than the original SOFA. Regardless of active sedation, GCS is not accurate at outcome prediction for cardiac surgical patients. The suggested ND is a simple and more accurate risk stratification variable in cardiac surgical ICUs.


HIV viral load as an independent risk factor for tuberculosis in South Africa: collaborative analysis of cohort studies.
Chronic immune activation due to ongoing HIV replication may lead to impaired immune responses against opportunistic infections such as tuberculosis (TB). We studied the role of HIV replication as a risk factor for incident TB after starting antiretroviral therapy (ART). We included all HIV-positive adult patients (≥16 years) in care between 2000 and 2014 at three ART programmes in South Africa. Patients with previous TB were excluded. Missing CD4 cell counts and HIV-RNA viral loads at ART start (baseline) and during follow-up were imputed. We used parametric survival models to assess TB incidence (pulmonary and extrapulmonary) by CD4 cell and HIV-RNA levels, and estimated the rate ratios for TB by including age, sex, baseline viral loads, CD4 cell counts, and WHO clinical stage in the model. We also used Poisson general additive regression models with time-updated CD4 and HIV-RNA values, adjusting for age and sex. We included 44,260 patients with a median follow-up time of 2.7 years (interquartile range [IQR] 1.0-5.0); 3,819 incident TB cases were recorded (8.6%). At baseline, the median age was 34 years (IQR 28-41); 30,675 patients (69.3%) were female. The median CD4 cell count was 156 cells/µL (IQR 79-229) and the median HIV-RNA viral load 58,000 copies/mL (IQR 6,000-240,000). Overall TB incidence was 26.2/1,000 person-years (95% confidence interval [CI] 25.3-27.0). Compared to the lowest viral load category (0-999 copies/mL), the adjusted rate ratio for TB was 1.41 (95% CI 1.15-1.75, p < 0.001) in the highest group (>10,000 copies/mL). Time-updated analyses for CD4/HIV-RNA confirmed the association of viral load with the risk for TB. Our results indicate that ongoing HIV replication is an important risk factor for TB, regardless of CD4 cell counts, and underline the importance of early ART start and retention on ART.


Efficient analysis of mammalian polysomes in cells and tissues using Ribo Mega-SEC.
We describe Ribo Mega-SEC, a powerful approach for the separation and biochemical analysis of mammalian polysomes and ribosomal subunits using Size Exclusion Chromatography and uHPLC. Using extracts from either cells, or tissues, polysomes can be separated within 15 min from sample injection to fraction collection. Ribo Mega-SEC shows translating ribosomes exist predominantly in polysome complexes in human cell lines and mouse liver tissue. Changes in polysomes are easily quantified between treatments, such as the cellular response to amino acid starvation. Ribo Mega-SEC is shown to provide an efficient, convenient and highly reproducible method for studying functional translation complexes. We show that Ribo Mega-SEC is readily combined with high-throughput MS-based proteomics to characterize proteins associated with polysomes and ribosomal subunits. It also facilitates isolation of complexes for electron microscopy and structural studies.


Role of P-selectin in thromboembolic events in patients with cancer.
The objective of the present study was to evaluate the role of P-selectin in patients with cancer with suspected thromboembolic events (TEEs). Patients with cancer have a four times greater risk of developing TEEs. P-selectin is a glycoprotein that has the function of facilitating the interaction (adhesion) of leukocytes with the endothelium, or with platelets. There is a well-defined relationship between P-selectin and thrombosis; however, it is likely that the cut-off value of P-selectin for patients with cancer should be considered differently from that of the general population. In the present report, a prospective cross-sectional study was performed with patients of the Cancer Hospital of Barretos who were suspected of having TEEs. Among the 178 study participants, 167 (93.82%) were suspected of having deep vein thrombosis, while 59 of them (35.33%) were confirmed as such; and 11 (6.18%) were suspected of having pulmonary thromboembolism, while 3 of them were confirmed as such (27.69%). The mean results obtained were: P-selectin, 25.37 ng/ml; and D-dimer, 2,181.22 ng/ml. The P-selectin levels averaged 33.60 ng/ml with the confirmed TEE group compared with 20.40 ng/ml with the unconfirmed TEE group, with a standard deviation of 23.35 compared with 6.92 (P<0.001); and the level of D-dimer was 4,615.38 ng/ml compared with 977.52 ng/ml, with a standard deviation of 6,460.54 compared with 2,145.50 (P<0.001). Multiple logistic regression adjusted for distant metastases and the Eastern Cooperative Oncology Group (ECOG) score (2,3 and 4) were constructed. The cut-off value of P-selectin for patients with cancer was identified to be different from that reported in the literature for the general population, and the models using D-dimer and P-selectin therefore have been demonstrated to be a potentially useful tool to be used in a panel of tests to predict TEEs, either independently or in a prediction score.


Booze and beach bans: turning the tide through community action in New Zealand.
Many beach and holiday resorts experience major problems with alcohol-related public disorder. Following an escalation in alcohol-related incidents in the New Zealand beach community of Piha, a community-driven response to address issues of community well-being and safety was initiated by concerned residents. A case study evaluation reported on the development of a community coalition involving community and statutory stakeholders and the successful implementation of local community action strategies. These included a beach alcohol ban, extensive local publicity and a community policing presence over successive summers. An examination of the case study suggests that inter-sectoral collaboration, and multiple level strategies through policy, promotion and enforcement activities are key factors in enabling communities to successfully reduce alcohol-related harm.