Validity of the Agency for Health Care Research and Quality Patient Safety Indicators and the Centers for Medicare and Medicaid Hospital-acquired Conditions: A Systematic Review and Meta-Analysis.
The Agency for Health Care Research and Quality Patient Safety Indicators (PSIs) and Centers for Medicare and Medicaid Services Hospital-acquired Conditions (HACs) are increasingly being used for pay-for-performance and public reporting despite concerns over their validity. Given the potential for these measures to misinform patients, misclassify hospitals, and misapply financial and reputational harm to hospitals, these need to be rigorously evaluated. We performed a systematic review and meta-analysis to assess PSI and HAC measure validity. We searched MEDLINE and the gray literature from January 1, 1990 through January 14, 2015 for studies that addressed the validity of the HAC measures and PSIs. Secondary outcomes included the effects of present on admission (POA) modifiers, and the most common reasons for discrepancies. We developed pooled results for measures evaluated by ≥3 studies. We propose a threshold of 80% for positive predictive value or sensitivity for pay-for-performance and public reporting suitability. Only 5 measures, Iatrogenic Pneumothorax (PSI 6/HAC 17), Central Line-associated Bloodstream Infections (PSI 7), Postoperative hemorrhage/hematoma (PSI 9), Postoperative deep vein thrombosis/pulmonary embolus (PSI 12), and Accidental Puncture/Laceration (PSI 15), had sufficient data for pooled meta-analysis. Only PSI 15 (Accidental Puncture and Laceration) met our proposed threshold for validity (positive predictive value only) but this result was weakened by considerable heterogeneity. Coding errors were the most common reasons for discrepancies between medical record review and administrative databases. POA modifiers may improve the validity of some measures. This systematic review finds that there is limited validity for the PSI and HAC measures when measured against the reference standard of a medical chart review. Their use, as they currently exist, for public reporting and pay-for-performance, should be publicly reevaluated in light of these findings.


Myocardial ischemia: ionic events in ischemia and anoxia.
The early stages of anoxemia and ischemia are associated with highly selective, reversible defects in sarcolemmal ionic exchange of potassium not necessarily the result of impaired sodium pump function. At a later stage structural defects in the membrane led to irreversible loss of intracellular potassium and creatine kinase. Similar stages can be demonstrated in the sarcolemmal selectivity for divalent cations. The degree of sarcolemmal injury from ischemia can be significantly influenced by the conditions of reperfusion. Reduced calcium content of blood reperfused for only 5 minutes can improve the mechanical recovery of ischemic rabbit ventricle. The influx of calcium during reperfusion impairs those processes required for restoration of sarcolemmal integrity.


Measurement precision bounds on aberrated single molecule emission patterns.
Single-Molecule Localization Microscopy (SMLM) has revolutionized the study of biological phenomena by providing exquisite nanoscale spatial resolution. However, optical aberrations induced by sample and system imperfections distort the single molecule emission patterns (i.e. PSFs), leading to reduced precision and resolution of SMLM, particularly in three-dimensional (3D) applications. While various methods, both analytical and instrumental, have been employed to mitigate these aberrations, a comprehensive analysis of how different types of commonly encountered aberrations affect single molecule experiments and their image formation remains missing. In this study, we addressed this gap by conducting a quantitative study of the theoretical precision limit for position and wavefront distortion measurements in the presence of aberrations. Leveraging Fisher information and Cramér-Rao lower bound (CRLB), we quantitively analyzed and compared the effects of different aberration types, including index mismatch aberrations, on localization precision in both biplane and astigmatism 3D modalities as well as 2D SMLM imaging. Furthermore, we studied the achievable wavefront estimation precision from aberrated single molecule emission patterns, a pivot step for successful adaptive optics in SMLM through thick specimens. This analysis lays a quantitative foundation for the development and application of SMLM in whole-cells, tissues and with large field of view, providing in-depth insights into the behavior of different aberration types in single molecule imaging and thus generating theoretical guidelines for developing highly efficient aberration correction strategies and enhancing the precision and reliability of 3D SMLM.


Pineal gland transplants into the cerebral hemisphere of newborn rats: a study of the blood brain barrier and innervation.
Pineal glands from neonatal (0-1 day) Long-Evans black-hooded rats were transplanted into the cerebral hemispheres of litter mates for periods of 1 to 5.5 months. Grafts exhibited differentiated pinealocytes that were intensely immunoreactive for serotonin. Transplant vasculature was permeable to endogenous IgG, comprised fenestrated endothelia with wide pericapillary spaces typical of in situ glands, and had a volume density intermediate to that of surrounding cortex and in situ pineals. Along the periphery, transplant capillaries tended to have continuous endothelia similar to those of host cortex. This peripheral zone was impermeable to endogenous IgG and appeared to increase in size in older grafts. The presence of noradrenergic-like fibers within the perivascular compartment suggested that transplants were innervated by peripheral sympathetic neurons from the superior cervical ganglia. In animals which had been superior cervical ganglionectomized, noradrenergic-like fibers were absent or degenerating. Neural regulation of transplant metabolic activity was suggested by the increased frequency of pinealocyte synaptic ribbons in denervated grafts. These findings are consistent with the hypothesis that factors from both graft and host influence vasculature physiology and differentiation in neural transplants. Furthermore, grafts appeared to receive appropriate neural input from the peripheral sympathetic system.


[Frequency-dependent sexual selection in a natural population of oak leaf-roller moth (Tortrix viridana L.)].
A mating system on the esterase locus Est-4 was studied in a natural population of oak leaf-roller moth Tortrix viridana L. Frequency-dependent sexual selection was revealed, which manifested itself in a "rare-type advantage". On the basis of obtained data, a new hypothesis for explanation of the "rare-type advantage" phenomenon is proposed. The hypothesis proceeds from the genetically determined choice of sexual partner, depending on the degree of phenotypic likeness.


Micrometer insights into Nepeta genus: Pollen micromorphology unveiled.
This study provides a comprehensive pollen micromorphology within the Nepeta genus, revealing intricate details about the pollen grains' structure and characteristics. The findings shed light on the evolutionary and taxonomical aspects of this plant genus, offering valuable insights for botanists and researchers studying Nepeta species. The pollen grains of 18 Nepeta species were studied using scanning electron microscopy (SEM) and light microscopy (LM) in Northern Pakistan. At the microscale, pollen quantitative measurements, qualitative traits, and diverse sculpturing patterns were reported and compared. Significant differences in pollen size, shape, ornamentation, and sculpturing patterns were discovered among the Nepeta species. Our data show that exine sculpturing is quite diverse, with most species exhibiting a reticulate perforate pollen pattern. Nepeta connata, Nepeta discolor, Nepeta elliptica, revealed a distinct bireticulate perforate exine stratification. Hexazonocolpate pollen is the most common. Furthermore, the surface membrane attributes of the colpus varied greatly, ranging from rough, scabrate, psilate, to sinuate patterns. Principal Component Analysis (PCA) was used to discover the key factors influencing pollen diversity. PCA results showed that polar and equatorial diameters, colpi size, and exine thickness were the most influential pollen features between Nepeta species. This study adds to our understanding of pollen morphology in the Nepeta genus, offering information on the vast range of characteristics found in this economically important group. The extensive characterization of pollen features provides useful insights for the categorization and differentiation of Nepeta species, adding to the Lamiaceae micromorphology.


The chitinase PfCHT1 from the human malaria parasite Plasmodium falciparum lacks proenzyme and chitin-binding domains and displays unique substrate preferences.
Within hours after the ingestion of a blood meal, the mosquito midgut epithelium synthesizes a chitinous sac, the peritrophic matrix. Plasmodium ookinetes traverse the peritrophic matrix while escaping the mosquito midgut. Chitinases (EC 18.104.22.168) are critical for parasite invasion of the midgut: the presence of the chitinase inhibitor, allosamidin, in an infectious blood meal prevents oocyst development. A chitinase gene, PgCHT1, recently has been identified in the avian malaria parasite P. gallinaceum. We used the sequence of PgCHT1 to identify a P. falciparum chitinase gene, PfCHT1, in the P. falciparum genome database. PfCHT1 differs from PgCHT1 in that the P. falciparum gene lacks proenzyme and chitin-binding domains. PfCHT1 was expressed as an active recombinant enzyme in Escherichia coli. PfCHT1 shares with PgCHT1 a substrate preference unique to Plasmodium chitinases: the enzymes cleave tri- and tetramers of GlcNAc from penta- and hexameric oligomers and are unable to cleave smaller native chitin oligosaccharides. The pH activity profile of PfCHT1 and its IC(50) (40 nM) to allosamidin are distinct from endochitinase activities secreted by P. gallinaceum ookinetes. Homology modeling predicts that PgCHT1 has a novel pocket in the catalytic active site that PfCHT1 lacks, which may explain the differential sensitivity of PfCHT1 and PgCHT1 to allosamidin. PfCHT1 may be the ortholog of a second, as yet unidentified, chitinase gene of P. gallinaceum. These results may allow us to develop novel strategies of blocking human malaria transmission based on interfering with P. falciparum chitinase.


Faulty inflation and deflation of urethral balloon catheters.
Attention is drawn to the faults encountered with urethral balloon catheters, with particular reference to difficulties with inflation and deflation of the balloon. Needle puncture has been found to be a simple method of removing catheters that cannot be deflated by the usual methods.


Invasion and persistence of the neuroadapted influenza virus A/WSN/33 in the mouse olfactory system.
Invasion and persistence of the neuroadapted influenza virus A/WSN/33 in the mouse olfactory system was studied. WSN/33 instilled intranasally infected neurons in the olfactory epithelium and was transported in axons to the olfactory bulbs in wild type mice that survived the infection. In adult mice lacking the recombination activating gene 1 (RAG-1-/-), infected neurons occurred in the olfactory bulbs for 22-65 days after which the mice developed a rapidly progressive lethal infection affecting neurons in olfactory projection pathways, i.e. primary olfactory cortex, raphe in upper brainstem and hypothalamus. Adult mice without genes for interferon (IFN)-alpha/beta receptor, IFN-gamma receptor, inducible nitric oxide synthase (iNOS), IgH, the transporter associated with antigen processing 1 (TAP1), and natural killer cell-depleted mice, all survived the infection. Viral RNA was found in the olfactory bulbs in more than 80 per cent of the surviving iNOS-/-, IFN-gamma receptor-/-, and TAP1-/- mice. Taken together, this study shows that influenza A virus can invade the brain through the olfactory pathways and that the cellular immune responses prevent establishment of persistent infections in the olfactory bulbs. Furthermore, innate responses in olfactory bulbs may for a period of time keep the infection under control.


Combination chemotherapy and radiation of human squamous cell carcinoma of the head and neck augments CTL-mediated lysis.
The combination of systemic multiagent chemotherapy (5-fluorouracil + cisplatin) and tumor irradiation is standard of care for head and neck squamous cell carcinoma (HNSCC). Furthermore, it has been shown that sublethal doses of radiation or chemotherapeutic drugs in diverse cancer types may alter the phenotype or biology of neoplastic cells, making them more susceptible to CTL-mediated cytotoxicity. However, little is known about the potential synergistic effect of drug plus radiation on CTL killing. Here, we examined whether the combination of two chemotherapeutics and ionizing radiation enhanced CTL-mediated destruction of HNSCC more so than either modality separately, as well as the basis for the enhanced tumor cell lysis. Several HNSCC cell lines with distinct biological features were treated with sublethal doses of cisplatin and 5-fluorouracil for 24 hours and with 10-Gy irradiation. Seventy-two hours postirradiation, tumor cells were exposed to an antigen-specific CD8+ CTL directed against carcinoembryonic antigen or MUC-1. In three of three tumor cell lines tested, enhanced CTL activity was observed when the two modalities (chemotherapy and radiation) were combined as compared with target cells exposed to either modality separately. CTL-mediated lysis was MHC restricted and antigen specific and occurred almost entirely via the perforin pathway. Moreover, the combination treatment regimen led to a 50% reduction in Bcl-2 expression whereas single modality treatment had little bearing on the expression of this antiapoptotic gene. Overall, these results reveal that (a) CTL killing can be enhanced by combining multiagent chemotherapy and radiation and (b) combination treatment enhanced or sensitized HNSCC to the perforin pathway, perhaps by down-regulating Bcl-2 expression. These studies thus form the rational basis for clinical trials of immunotherapy concomitant with the current standard of care of HNSCC.


The amphipathic helices of Arfrp1 and Arl14 are sufficient to determine subcellular localizations.
The subcellular localization of Arf family proteins is generally thought to be determined by their corresponding guanine nucleotide exchange factors. By promoting GTP binding, guanine nucleotide exchange factors induce conformational changes of Arf proteins exposing their N-terminal amphipathic helices, which then insert into the membranes to stabilize the membrane association process. Here, we found that the N-terminal amphipathic motifs of the Golgi-localized Arf family protein, Arfrp1, and the endosome- and plasma membrane-localized Arf family protein, Arl14, play critical roles in spatial determination. Exchanging the amphipathic helix motifs between these two Arf proteins causes the switch of their localizations. Moreover, the amphipathic helices of Arfrp1 and Arl14 are sufficient for cytosolic proteins to be localized into a specific cellular compartment. The spatial determination mediated by the Arfrp1 helix requires its binding partner Sys1. In addition, the residues that are required for the acetylation of the Arfrp1 helix and the myristoylation of the Arl14 helix are important for the specific subcellular localization. Interestingly, Arfrp1 and Arl14 are recruited to their specific cellular compartments independent of GTP binding. Our results demonstrate that the amphipathic motifs of Arfrp1 and Arl14 are sufficient for determining specific subcellular localizations in a GTP-independent manner, suggesting that the membrane association and activation of some Arf proteins are uncoupled.


Anti-cancer drugs: molecular mechanisms of action.
Genetic alterations are responsible for all cancers. These mutations produce, in turn, alterations in key proteins of certain signaling pathways. Amongst the best known and studied alterations related to malignant transformations are those which occur in Ras protein and p53. In most cases mutations in Ras and p53 lead to the appearance of practically most malignant transformations. Mutated Ras genes exist in approximately 20 to 30% of all human cancers. Ras proteins are switches that regulate diverse functions such as cell proliferation, differentiation and apoptosis. Normal p53 expression, also known as the "genome guardian", is a key molecule for suppressing cell proliferation. The great importance of these proteins rests on their intimacy with the events leading to cell proliferation or death. The comprehension of the extent of transformation on Ras and p53, and of the diverse biochemical pathways of intracellular signaling, activated by them, is of extreme importance for the understanding of malignant transformation, as well as its control, through the creation, for example, of new drugs which contribute to the elimination of these cells. To clarify the consequences originated by transformed Ras, p53 and their biochemical interlinks in the different intracellular pathways, besides the possible intervening points and pharmacological controls presently used in combating cancer, are the aims of this review.


Cardiovascular stimulant actions of bupropion in comparison to cocaine in the rat.
Stimulants are banned in competition by the World Anti-Doping Agency, except for a small number of therapeutic agents subject to monitoring, including bupropion. We have examined the potency of bupropion in comparison with two agents banned in competition, adrafinil and modafinil, and with cocaine and desipramine as blockers of the noradrenaline re-uptake transporter in peripheral tissues of the rat. For studies in vivo, the pressor response to noradrenaline in the anaesthetized rat was studied. Cocaine, desipramine and bupropion at doses of 0.1, 0.3 and 1mg/kg, respectively, significantly increased the pressor response to noradrenaline. Overall, cocaine and desipramine were approximately 2-5 times more potent than bupropion in vivo in the rat. Adrafinil and modafinil (both 3mg/kg) did not significantly affect the pressor response. Bupropion was chosen for further study. In 1Hz paced rat right ventricular strips, bupropion (30μM) significantly increased the potency of noradrenaline at increasing the force of contraction. In rat vas deferens, bupropion and cocaine produced concentration-dependent increases in the contractile response to nerve stimulation, and cocaine was 11 times more potent than bupropion. Since bupropion is used clinically in doses of up to 300mg, it is likely that bupropion has actions at the noradrenaline transporter, and thus cardiovascular stimulant actions, in clinical doses. This may explain findings of increased exercise performance with bupropion.


Mouse chromosome 17A3.3 contains 13 genes that encode functional tryptic-like serine proteases with distinct tissue and cell expression patterns.
Probing of the mouse EST data base at GenBank trade mark with known tryptase cDNAs resulted in the identification of undiscovered serine protease transcripts whose genes reside at a 1.5-Mb complex on mouse chromosome 17A3.3. Mouse tryptase-5 (mT5), tryptase-6 (mT6), and mast cell protease-11 (mMCP-11) are new members of this serine protease superfamily whose amino acid sequences are 36-54% identical to each other and to their other 10 family members. The 13 functional mouse proteases can be subdivided into two subgroups based on conserved features in their propeptides. Of the three new serine proteases, mT6 is most widely expressed in tissues. mT5 is preferentially expressed in smooth muscle, whereas mMCP-11 is preferentially expressed in the spleen and bone marrow. In contrast to mT5 and mT6, mMCP-11 is also expressed in mast cells. Although mT6 and mMCP-11 are constitutively secreted when expressed in mammalian and insect cells, mT5 remains membrane-associated. The fact that recombinant mT5, mT6, and mMCP-11 possess non-identical expression patterns and substrate specificities suggests that each protease has a unique function in vivo. Of the 13 functional mouse tryptase genes identified at the complex, 12 have orthologs that reside in the syntenic region of human chromosome 16p13.3. The establishment of these ortholog pairs helps clarify the evolutionary relationship of the serine protease locus in the two species. This information provides a useful framework for the functional analysis of each protease using gene targeting and other molecular approaches.


[Duchenne's muscular dystrophy in a girl with 45,X/46,XX chromosomal mosaicism].
The paper is concerned with a case history of a girl with a rare combination of 2 rare anomalies (only 4 cases in the world literature); monosomia by X chromosome and Duchenne's muscular dystrophy. Mosaicism 45,X/46,XX in a 5 year old girl with a mild picture of Duchenne's muscular dystrophy was confirmed by a study of the kariotype in lymphocytes of the peripheral blood and skin fibroblasts. The authors indicate to a necessity of a thorough cytogenetical study in girls, if there is a clinical picture of Duchennes muscular dystrophy.


Advances in the Genetics of Youth-Onset Type 2 Diabetes.
To provide an update on knowledge the role of genetics in youth-onset type 2 diabetes (T2D). The prevalence in youth of T2D, once thought to be exclusively a disease of adults, has increased by over 35% since 2001. Youth with T2D tend to have higher rates of complications, more aggressive disease, with more rapid loss of beta-cell function and a less favorable response to treatment than adults. Obesity is the most important risk factor for T2D, and the rise in childhood overweight and obesity appears responsible for the dramatic increase in T2D in youth. However, some obese children do not develop T2D, consistent with genetic differences in susceptibility to the disease in the setting of obesity and insulin resistance, currently far less well characterized in youth than in adults. Recent studies have begun to show associations of several established adult T2D genetic risk variants with youth-onset T2D and related glycemic quantitative traits, including the strongest known cross-population T2D genetic contributor TCF7L2. Maturity-onset diabetes of the young (MODY), a diabetes subtype distinct from type 1 diabetes (T1D) and T2D, is now known to result from a highly penetrant gene mutation in one of several genes. MODY has been shown to account for or contribute to at least 4.5% of clinically diagnosed T2D, even among those who are overweight or obese, impacting treatment decisions. The recently formed ProDiGY (Progress in Diabetes Genetics in Youth) Consortium is using genome-wide association studies and whole exome sequencing to understand the genetic architecture of T2D in youth, including how it differs from that of adults. The limited amount of research conducted to date on the genetics of youth-onset T2D, which tends to be a more aggressive disease than adult T2D, suggests some overlap with genes involved in adult T2D and a sizeable influence of highly penetrant monogenic diabetes variants. The ProDiGY Consortium is expected to provide a more comprehensive understanding of youth T2D genetics.


The pre-vaccination epidemiology of measles, mumps and rubella in Europe: implications for modelling studies.
Data on the pre-vaccination patterns of infection for measles, mumps and rubella are collated from a number of European countries in order to compare the epidemiology of the three viruses. Key epidemiological parameters, such as the age-specific force of infection and the basic reproduction number (R0) are estimated from case notification or serological data using standard techniques. A method is described to compare force of infection estimates derived from serological data. Analysis suggests that the pre-vaccination patterns of measles and mumps infection in the different countries were similar. In contrast, the epidemiology of rubella was highly variable between countries. This suggests that it may be acceptable to use parameter values estimated from other countries to model measles and mumps transmission, but that this approach to modelling rubella transmission requires more caution. Estimates of R0 depend on underlying mixing assumptions. Constraints were placed on R0 estimates by utilising knowledge of likely mixing patterns. The estimates for R0 were highest for measles, intermediate for mumps, and generally lowest for rubella. Analysis of within- and between-age-group transmission rates suggested that mumps transmission tends to be more concentrated within young children than the other two viruses. The implications for the design of immunization programmes are that mumps may be the easiest to control via infant immunization since it is predominantly transmitted between the very young and the variability in rubella epidemiology requires that careful consideration of the possible effects of vaccination options should be made using local data when planning rubella immunization programmes.


Congenital factor XIII deficiency in Pakistan: characterization of seven families and identification of four novel mutations.
Deficiency of coagulation factor XIII (FXIII) belongs to the rare bleeding disorders and its incidence is higher in populations with consanguineous marriages. The aims of this study were to characterize patients and relatives from seven families with suspected FXIII deficiency from Pakistan and to identify the underlying mutations. As a first indicator of FXIII deficiency, a 5M urea clot solubility test was used. Plasma FXIII A- and B-subunit antigen levels were determined by ELISA. FXIII activity was measured with an incorporation assay. Sequencing of all exons and intron/exon boundaries of F13A was performed, and a novel splice site defect was confirmed by RT-PCR analysis. Genetic analysis revealed six different mutations in the F13A gene. Two splice site mutations were detected, a novel c.1460+1G>A mutation in the first nucleotide of intron 11 and a previously reported c.2045G>A mutation in the last nucleotide of exon 14. Neither of them was expressed at protein level. A novel nonsense mutation in exon 4, c.567T>A, p.Cys188X, was identified, leading in homozygous form to severe FXIII deficiency. Two novel missense mutations were found in exons 8 and 9, c.1040C>A, p.Ala346Asp and c.1126T>C, p.Trp375Arg, and a previously reported missense mutation in exon 10, c.1241C>T, p.Ser413Leu. All patients homozygous for these missense mutations presented with severe FXIII deficiency. We have analysed a cohort of 27 individuals and reported four novel mutations leading to congenital FXIII deficiency.


Recovery from anorexia nervosa: the influence of women's sociocultural milieux.
Young women living in industrialised westernised societies have a higher prevalence of anorexia nervosa, partly due to a cultural emphasis on thinness as a beauty ideal. Sociocultural milieux might promote recovery from anorexia nervosa amongst young women. The current article is a commentary about the social influences on recovery from anorexia nervosa - based on social anthropology, narratives of people with lived experience, and clinical studies. Anorexia nervosa increases social withdrawal, and recovery leads to re-engagement with meaningful relationships. Recovery also empowers women as 'cultural critics' who challenge assumptions about the thinness beauty ideal and gender roles. The gradual process of full or partial recovery often occurs during emerging adulthood (aged 20-29). In this life stage, adolescent friendship groups are dissolving as women move from education to work, reducing the danger of weight-based teasing by peers, which is an environmental risk factor for disordered eating. Women recovering from anorexia nervosa may connect with those aspirations of peers and mentors that eschew a focus on weight and shape, but relate to the life-stage tasks of starting careers, beginning new friendships, selecting life partners and family formation - that is, a broader role in larger relationship networks.


[Treatment of localized prostate cancer: radical prostatectomy versus radiation therapy].
Between 1982 and 1990, 57 patients with prostate cancer (clinical stage T2-3) underwent pelvic lymphadenectomy at Fukui Medical School or Toyooka Public Hospital. The patients were subsequently treated either by radical prostatectomy (39 cases) or external radiation therapy (18 cases). The patients were between 56 and 85 years old (Mean 73). The outcome of the 47 patients without lymph node metastasis (prostatectomy 33, radiation 14) was examined. The 5-year disease-specific survival rate was 96% for the patients treated by prostatectomy and 93% for those treated by radiation. The 5-year progression-free survival rate for the prostatectomy group and radiation group was 94% and 41%, respectively (P = 0.004). The outcome of the 10 patients with lymph node metastasis (prostatectomy 6, radiation 4) was not satisfactory because of the high progression rate in the two groups (5-year progression-free survival, 22% in prostatectomy and 25% in radiation group). In the patients with no metastasized lymph nodes, we should choose radical prostatectomy, if our goal is to cure the patients.


Infants expect friends, but not rivals, to be happy for each other when they succeed.
A friend telling you good news earns them a smile while witnessing a rival win an award may make you wrinkle your nose. Emotions arise not just from people's own circumstances, but also from the experiences of friends and rivals. Across three moderated, online looking time studies, we asked if human infants hold expectations about others' vicarious emotions and if they expect those emotions to be guided by social relationships. Ten- and 11-month-old infants (N = 154) expected an observer to be happy rather than sad when the observer watched a friend successfully jump over a wall; infants looked longer at the sad response compared to the happy response. In contrast, infants did not expect the observer to be happy when the friend failed, nor when a different, rival jumper succeeded; infants' looking times to the two emotion responses in these conditions were not reliably different. These results suggest that infants are able to integrate knowledge across social contexts to guide expectations about vicarious emotional responses. Here infants connected an understanding of agents' goals and their outcomes with knowledge of social relationships to infer an emotion response. Biased concern for friends but not adversaries is not just a descriptive feature of human relationships, but an expectation about the social world present from early in development. Further, the successful integration of these information types welcomes the possibility that infants can jointly reason about goals, emotions, and social relationships under an intuitive theory of psychology. RESEARCH HIGHLIGHTS: 11-month-old infants use knowledge of relationships to make inferences about others' vicarious emotions. In Experiment 1 infants expected an observer to respond happily to a friend's success but not their failure. Experiments 2 and 3 varied the relationship between the observer and actor and found that infants' expectation of vicarious happiness is strongest for positive relationships and absent for negative relationships. The results may reflect an intuitive psychology in which infants expect friends to adopt concern for one another's goals and to thus experience one another's successes as rewarding.


Relationship Between Subglottal Pressure and Sound Pressure Level in Untrained Voices.
Subglottal pressure (P(s)) is strongly correlated with sound pressure level (SPL) and is easy to measure by means of commonly available equipment. The SPL/Ps ratio is strongly dependent on the efficiency of the phonatory apparatus and should be of great relevance to clinical practice. However, published normative data are still missing. The subjects produced sequences of the syllable [pæ], and P(s) was measured as the oral pressure during the [p] occlusion. The P(s) to SPL relationship was determined at four pitches produced by 16 female and 15 male healthy voices and analyzed by means of regression analysis. Average correlation between P(s) and SPL, average SPL produced with a P(s) of 10 cm H(2)O, and average SPL increase produced by a doubling of P(s) were calculated for the female and for the male subjects. The significance of sex and pitch conditions was analyzed by means of analysis of variance (ANOVA). Pitch was found to be an insignificant condition. The average correlation between P(s) and SPL was 0.83 and did not differ significantly between the female and male subjects. In female and male subjects, P(s) = 10 cm H(2)O produced 78.1 dB and 80.0 dB SPL at 0.3 m, and a doubling of P(s) generated 11.1 dB and 9.3 dB increase of SPL. Both these gender differences were statistically significant. The relationship between Ps and SPL can be reliably established from series of repetitions of the syllable [pæ] produced with a continuously changing degree of vocal loudness. Male subjects produce slightly higher SPL for a given pressure than female subjects but gain less for a doubling of P(s). As these relationships appear to be affected by phonation type, it seems possible that in the future, the method can be used for documenting degree of phonatory hypofunction and hyperfunction.


Serum ghrelin is inversely associated with risk of subsequent oesophageal squamous cell carcinoma.
Gastric atrophy, as determined by a low serum pepsinogen I:II ratio, may be associated with an increased risk of oesophageal squamous cell carcinoma (OSCC). Ghrelin, a hormone which, is also produced in the gastric fundic glands may be a marker of gastric atrophy, but its association with OSCC is not known. To examine the relationship between baseline serum ghrelin concentration and subsequent risk of OSCC, the authors conducted a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) study. 82 cases of OSCC were matched (1:1) by age and date of blood draw to controls from the ATBC study. Serum ghrelin was measured by radioimmunoassay. ORs and 95% CIs were calculated using conditional logistic regression with adjustment for potential confounders. For individuals in the lowest quartile of serum ghrelin, compared to those in the highest, the multivariate OR of subsequent OSCC was 6.83 (95% CI 1.46 to 31.84). These associations were dose dependent (p value for trend =0.005 for both), and independent of the effects of low pepsinogen I:II ratio and Helicobacter pylori infection. The significance of these associations remained even for individuals developing OSCC up to 10 years after baseline ghrelin measurement, although they become attenuated after 10 years. Lower baseline concentrations of serum ghrelin were associated with an increase in risk of OSCC. Further studies are needed to confirm this finding in other populations and to explore the role of ghrelin in the aetiology of OSCC.


The role of mitochondria in modifying calcium-sensitive cytoplasmic metabolic activities. Modification of pyruvate kinase activity.
1. The modification of pyruvate kinase activity in vitro was examined by altering the environmental [Mg(2+)]/[Ca(2+)] ratio with EDTA on the one hand and isolated rat liver mitochondria on the other. 2. Controlled additions of Ca(2+) and EDTA caused pyruvate kinase activity to be alternately and rapidly switched on and off. 3. By being able to accumulate Ca(2+) in preference to Mg(2+) rat liver mitochondria were able to alter the [Mg(2+)]/[Ca(2+)] ratio in the vicinity of pyruvate kinase and thereby modify the activity of this enzyme. 4. The possible role of mitochondria in modifying pyruvate kinase and other ion-sensitive cytoplasmic enzyme activities is discussed.


Doctor-patient relationship: from medical paternalism to enhanced autonomy.
For centuries, physicians have been allowed to interfere and overrule patient's preferences with the aim of securing patient benefit or preventing harm. With the radical rise in emphasis on individual control and freedom, medical paternalism no longer receives unquestioned acceptance by society as the dominant mode for decision-making in health care. But neither is a decision-making approach based on absolute patient autonomy a satisfactory one. A more ethical and effective approach is to enhance a patient's autonomy by advocating a medical beneficence that incorporates patients' values and perspectives. This can be achieved through a model for shared decision making, acknowledging that though the final choices reside ultimately in patients, only through physician beneficence can the patient be empowered to make meaningful decisions that serve them best. For such a model to function effectively, the restoration of trust in doctor-patient relationship and the adoption of patient-centred communication are both crucial.


Haloadaptation: insights from comparative modeling studies between halotolerant and non-halotolerant dehalogenases.
Halophiles are extremophilic microorganisms that grow optimally at high salt concentrations by producing a myriad of equally halotolerant enzymes. Structural haloadaptation of these enzymes adept to thriving under high-salt environments, though are not fully understood. Herein, the study attempts an in silico investigation to identify and comprehend the evolutionary structural adaptation of a halotolerant dehalogenase, DehHX (GenBank accession number: KR297065) of the halotolerant Pseudomonas halophila, over its non-halotolerant counterpart, DehMX1 (GenBank accession number KY129692) produced by Pseudomonas aeruginosa. GC content of the halotolerant DehHX DNA sequence was distinctively higher (58.9%) than the non-halotolerant dehalogenases (55% average GC). Its acidic residues, Asp and Glu were 8.27% and 12.06%, respectively, compared to an average 5.5% Asp and 7% Glu, in the latter; but lower contents of basic and hydrophobic residues in the DehHX. The secondary structure of DehHX interestingly revealed a lower incidence of α-helix forming regions (29%) and a higher percentage of coils (57%), compared to 49% and 29% in the non-halotolerant homologues, respectively. Simulation models showed the DehHX is stable under a highly saline environment (25% w/v) by adopting a highly negative-charged surface with a concomitant weakly interacting hydrophobic core. The study thus, established that a halotolerant dehalogenase undergoes notable evolutionary structural changes related to GC content over its non-halotolerant counterpart, in order to adapt and thrive under highly saline environments.Communicated by Ramaswamy H. Sarma.


Factors influencing litter size and puppy losses in the Entlebucher Mountain dog.
A good reproductive performance is a central element of animal breeding. The breeders of Entlebucher Mountain dogs observed a decrease of the mean litter size and an increase of the number of unsuccessful matings in the past years. The aim of the present study was to identify factors with an influence on fertility in this breed. In total, 915 litters from 202 sires and 348 dams from 1986 to 2013 entered the analyses. The total puppy losses (7.4%) reduced the mean litter size at birth of 5.49 ± 2.13 to a mean litter size at registration of 5.08 ± 2.05. There was no deviation from the expected equal sex distribution for puppies at birth and at registration, as well as for puppy losses consisting of stillborn puppies and puppies which died or had to be euthanized before registration. The mean annual litter inbreeding coefficient increased from 0.37 in 1986 to 0.40 in 2013 and was correlated with the year of birth of the litter (Kendall's tau b = 0.46). The age of the dam and parental inbreeding were identified as significant predictors with a negative effect on litter size at birth. For the litter size at registration the age and inbreeding of the dam had a significant negative effect and a 1% increase of dam inbreeding is expected to decrease the litter size at birth and registration by 0.1 and 0.09 puppies, respectively. The occurrence of total puppy losses decreased during the years and was more frequent in larger litters. In addition, in litters of older parents the occurrence of puppy losses was more frequent than in litters from younger parents. The final generalized linear mixed-effects models for litter size at birth, litter size at registration and for total puppy losses explained 36%, 33% and 22% of the total variance, respectively. The impact of inbreeding and parental age on fertility of the Entlebucher Mountain dog was small and the influence of the dam was much bigger than the one of the sire. Other factors must be responsible for the variability of litter sizes not explained by the models. Without changes of breeding circumstances, a further increase of inbreeding must be expected. Therefore, a close monitoring and minimizing of inbreeding must be followed up by the breeding community.


Involvement of glutathione, sulfhydryl compounds, nitric oxide, vasoactive intestinal peptide, and heat-shock protein-70 in the gastroprotective mechanism of Croton cajucara Benth. (Euphorbiaceae) essential oil.
This study aimed to evaluate the gastroprotective mechanism of action of the essential oil of Croton cajucara Benth. (Euphorbiaceae) stem bark in ethanol-induced gastric ulcers and its in vitro anti-Helicobacter pylori activity. The involvement of heat-shock protein-70, vasoactive intestinal peptide, glutathione, nitric oxide, and nonprotein sulfhydryl compounds in the gastroprotective effect was determined in male Wistar rats. The minimum inhibitory concentration against H. pylori was determined in vitro. The results were analyzed by analysis of variance followed by the Dunnett test, and a P value less than 0.05 was considered to represent a statistically significant difference. C. cajucara decreased ethanol-induced ulcer area in 100% of ulcers and decreased the histologic lesions. In the C. cajucara group, the area marked by heat-shock protein-70 was significantly higher than the area in the control group; this finding was not seen for vasoactive intestinal peptide. C. cajucara could not maintain glutathione levels close to those in the sham group. The gastric ulcer area of rats treated with the sulfhydryl compound blocker was decreased, but the ulcer area of rats treated with nitric oxide synthase inhibitor showed no alteration. The minimum inhibitory concentration obtained for C. cajucara was 125 μg/mL. These findings suggest that sulfhydryl compounds and heat-shock protein-70, but not nitric oxide, glutathione, or vasoactive intestinal peptide, are involved in the C. cajucara gastroprotective effect against ethanol-induced gastric ulcers.


Changes in bacterial diversity and composition in the faeces and colon of weaned piglets after feeding fermented soybean meal.
The microbiota composition of faeces and colonic contents were analysed to investigate the mechaninsm by which fermented soybean meal improves intestinal microbial communities, growth and immunity in weaning piglets. Microbiota were investigated using16S rRNA gene sequencing and systematical bio-information Operational Taxonomic Units; α-diversity analyses indicated that fermented soybean meal increased bacterial species diversity. The levels of Actinobacteria and Proteobacteia in faeces, and Firmicutes and Tenericutes in the colon, increased significantly in piglets fed fermented soybean meal (P<0.05). The relative abundance of Clostridium sensu stricto1, Lachnospira and Bacteoides had positive correlations with diarrhoea in the piglets. Lactobacillus, Blautia and Clostridium sensu stricto1 levels were correlated with increases in the average daily feed intake of piglets. Lactobacillus and Lachnospira also had positive relationships with IgM levels, and lymphocytes levels were increased relative to Clostridium sensu stricto1. Lymphocyte numbers also increased with higher levels of Blautia and decreased with Clostridium sensu stricto1. Increased levels of Blautia were also correlated with significant increases in white blood cells. The significant differences in faecal and colonic bacteria were correlated with enhanced immunity and overall improved health in the weaning piglets.


In Situ Observation of Nanoparticle Exsolution from Perovskite Oxides: From Atomic Scale Mechanistic Insight to Nanostructure Tailoring.
Understanding and controlling the formation of nanoparticles at the surface of functional oxide supports is critical for tuning activity and stability for catalytic and energy conversion applications. Here, we use a latest generation environmental transmission electron microscope to follow the exsolution of individual nanoparticles at the surface of perovskite oxides, with ultrahigh spatial and temporal resolution. Qualitative and quantitative analysis of the data reveals the atomic scale processes that underpin the formation of the socketed, strain-inducing interface that confers exsolved particles their exceptional stability and reactivity. This insight also enabled us to discover that the shape of exsolved particles can be controlled by changing the atmosphere in which exsolution is carried out, and additionally, this could also produce intriguing heterostructures consisting of metal-metal oxide coupled nanoparticles. Our results not only provide insight into the in situ formation of nanoparticles but also demonstrate the tailoring of nanostructures and nanointerfaces.


Plasma Exchange Downregulates Activated Monocytes and Restores Regulatory T Cells in Kawasaki Disease.
In Kawasaki disease (KD), the effect of plasma exchange (PE) on immune cells has not been fully elucidated. Therefore, we examined the changes in the number of CD14+ CD16+ activated monocytes, regulatory T (Treg ), and T-helper type 17 (Th17) cells in KD patients treated with PE. The percentage of total monocytes and subclasses of lymphocytes, including CD4+ and CD8+ T cells, and CD19+ B cells, showed no significant difference before and after PE. However, the percentage of CD14+ CD16+ monocytes in total leukocytes decreased significantly after PE (1.1% ± 1.5% vs. 2.1% ± 2.3%, P < 0.05). Furthermore, while the percentage of Th17 cells in CD4+ T cells did not change, the percentage of Treg cells in CD4+ T cells increased significantly after PE (11.1% ± 5.1% vs. 8.0% ± 4.4%, P < 0.05). Therefore, PE downregulates activated monocytes and upregulates Treg cells toward normal levels and thus attenuates inflammation in KD.


Undetectable serum thyroglobulin levels in patients with medullary thyroid carcinoma after total thyroidectomy without radioiodine ablation.
Recently, we reported that the thyroglobulin (Tg) doubling time (DT) was the most potent prognostic factor in patients with papillary thyroid carcinoma (PTC) who underwent total thyroidectomy. Interestingly 16.2% of the study patients had a decrease in Tg levels over time, giving negative values in Tg-DT. These patients had an excellent outcome. However, most of the patients did not receive ablation with radioactive iodine. Therefore, whether the Tg in these patients was derived from persistent disease or residual thyroid tissue could not be concluded. To resolve this question, we measured serum Tg levels in patients with medullary thyroid carcinoma (MTC) who underwent total thyroidectomy using similar surgical techniques for the treatment of PTC. Twenty-seven consecutive patients with MTC who underwent total thyroidectomy were selected. Of them, five patients with antibodies to Tg were excluded from the study. In the remaining 22 patients, serum Tg levels were measured before and after surgery. None of the patients received radioactive iodine ablation. They were prescribed levothyroxine as a replacement for the lost thyroid function. Serum Tg levels were detectable preoperatively, while postoperative serum Tg levels were lower than the detectable level, 0.5 ng/mL, in all 22 patients. The results indicate that most of the patients with detectable Tg levels and negative Tg-DT values after total thyroidectomy for PTC in our previous study had persistent disease, and that their serum Tg was not from residual thyroid tissue, suggesting that up to 50% of patients with persistent PTC have a decrease in serum Tg levels in response to thyroid-stimulating hormone-suppressive therapy.


Properties of cardiac conduction in a cell-based computational model.
The conduction of electrical signals through cardiac tissue is essential for maintaining the function of the heart, and conduction abnormalities are known to potentially lead to life-threatening arrhythmias. The properties of cardiac conduction have therefore been the topic of intense study for decades, but a number of questions related to the mechanisms of conduction still remain unresolved. In this paper, we demonstrate how the so-called EMI model may be used to study some of these open questions. In the EMI model, the extracellular space, the cell membrane, the intracellular space and the cell connections are all represented as separate parts of the computational domain, and the model therefore allows for study of local properties that are hard to represent in the classical homogenized bidomain or monodomain models commonly used to study cardiac conduction. We conclude that a non-uniform sodium channel distribution increases the conduction velocity and decreases the time delays over gap junctions of reduced coupling in the EMI model simulations. We also present a theoretical optimal cell length with respect to conduction velocity and consider the possibility of ephaptic coupling (i.e. cell-to-cell coupling through the extracellular potential) acting as an alternative or supporting mechanism to gap junction coupling. We conclude that for a non-uniform distribution of sodium channels and a sufficiently small intercellular distance, ephaptic coupling can influence the dynamics of the sodium channels and potentially provide cell-to-cell coupling when the gap junction connection is absent.


Biplanar cardiac blood-pool tomography.
Dynamic transverse axial wall tomograms of the left ventricle (LV) are reconstructed by a new technique from anterior and LAO views acquired with a conventional scintillation camera imaging the distribution of in-vivo Tc-99m-labeled red blood cells. By confining reconstruction to the singular contiguous uniform concentration of activity in the LV, the requisite angular samplings for a given level of accuracy are substantially reduced in this restricted form of emission computed tomography (ECT). Static phantom studies using a series of volumes having various cross-sectional dimensions demonstrate tomographic edge reconstruction with less than or equal to 12% rms radial error. The dynamic cardiac ECT is demonstrated in a series of representative patient studies by reconstruction of wall tomograms in the end-diastolic and end-systolic phases of the 28-frame cardiac cycle. In contrast to the conventional dual multiframe projection views, the motion tomograms derived from the reconstructions clearly show the complete three-dimensional perspective of wall displacement.


Elevated CO2 reduces the resistance and tolerance of tomato plants to Helicoverpa armigera by suppressing the JA signaling pathway.
Both resistance and tolerance, which are two strategies that plants use to limit biotic stress, are affected by the abiotic environment including atmospheric CO(2) levels. We tested the hypothesis that elevated CO(2) would reduce resistance (i.e., the ability to prevent damage) but enhance tolerance (i.e., the ability to regrow and compensate for damage after the damage has occurred) of tomato plants to the cotton bollworm, Helicoverpa armigera. The results showed that elevated CO(2) reduced resistance by decreasing the jasmonic acid (JA) level and activities of lipoxygenase, proteinase inhibitors, and polyphenol oxidase in wild-type (WT) plants infested with H. armigera. Consequently, the activities of total protease, trypsin-like enzymes, and weak and active alkaline trypsin-like enzymes increased in the midgut of H. armigera when fed on WT plants grown under elevated CO(2). Unexpectedly, the tolerance of the WT to H. armigera (in terms of photosynthetic rate, activity of sucrose phosphate synthases, flower number, and plant biomass and height) was also reduced by elevated CO(2). Under ambient CO(2), the expression of resistance and tolerance to H. armigera was much greater in wild type than in spr2 (a JA-deficient genotype) plants, but elevated CO(2) reduced these differences of the resistance and tolerance between WT and spr2 plants. The results suggest that the JA signaling pathway contributes to both plant resistance and tolerance to herbivorous insects and that by suppressing the JA signaling pathway, elevated CO(2) will simultaneously reduce the resistance and tolerance of tomato plants.


The bed nucleus-amygdala continuum in human and monkey.
The cytoarchitecture and distributions of seven neuropeptides were examined in the the bed nucleus of the stria terminalis (BST), substantia innominata (SI), and central and medial nuclei of the amygdala of human and monkey to determine whether neurons of these regions form an anatomical continuum in primate brain. The BST and centromedial amygdala have common cyto- and chemo-architectonic characteristics, and these regions are components of a distinct neuronal complex. This neuronal continuum extends dorsally, with the stria terminalis, from the BST and merges with the amygdala; it extends ventrally from the BST through the SI to the centromedial amygdala. The cytoarchitectonics of the BST-amygdala complex are heterogeneous and compartmental. The BST is parcellated broadly into anterior, lateral, medial, ventral, supracapsular, and sublenticular divisions. The central and medial nuclei of the amygdala are also parcellated into several subdivisions. Neurons of central and medial nuclei of the amygdala are similar to neurons in the lateral and medial divisions of the BST, respectively. Neurons in the SI form cellular bridges between the BST and amygdala. The BST, SI, and amygdala share several neuropeptide transmitters, and patterns of peptide immunoreactivity parallel cytological findings. Specific chemoarchitectonic zones were delineated by perikaryal, peridendritic/perisomatic, axonal, and terminal immunoreactivities. The results of this investigation demonstrate that there is a neuronal continuity between the BST and amygdala and that the BST-amygdala complex is prominent and discretely compartmental in forebrains of human and monkey.


Electrophysiology Measurements of Metal Transport by MntH2 from Enterococcus faecalis.
Transition metals are essential trace elements and their high-affinity uptake is required for many organisms. Metal transporters are often characterised using metal-sensitive fluorescent dyes, limiting the metals and experimental conditions that can be studied. Here, we have tested whether metal transport by Enterococcus faecalis MntH2 can be measured with an electrophysiology method that is based on the solid-supported membrane technology. E. faecalis MntH2 belongs to the Natural Resistance-Associated Macrophage Protein (Nramp) family of proton-coupled transporters, which transport divalent transition metals and do not transport the earth metals. Electrophysiology confirms transport of Mn(II), Co(II), Zn(II) and Cd(II) by MntH2. However, no uptake responses for Cu(II), Fe(II) and Ni(II) were observed, while the presence of these metals abolishes the uptake signals for Mn(II). Fluorescence assays confirm that Ni(II) is transported. The data are discussed with respect to properties and structures of Nramp-type family members and the ability of electrophysiology to measure charge transport and not directly substrate transport.


Anti-epileptic drugs and bone loss: Phenytoin reduces pro-collagen I and alters the electrophoretic mobility of osteonectin in cultured bone cells.
Phenytoin is an antiepileptic drug used in the management of partial and tonic-clonic seizures. In previous studies we have shown that valproate, another antiepileptic drug, reduced the amount of two key bone proteins, pro-collagen I and osteonectin (SPARC, BM-40), in both skin fibroblasts and cultured osteoblast-like cells. Here we show that phenytoin also reduces pro-collagen I production in osteoblast-like cells, but does not appear to cause a decrease in osteonectin message or protein production. Instead, a 24h exposure to a clinically relevant concentration of phenytoin resulted in a dose-dependent change in electrophoretic mobility of osteonectin, which was suggestive of a change in post-translational modification status. The perturbation of these important bone proteins could be one of the mechanisms to explain the bone loss that has been reported following long-term treatment with phenytoin.


[The personal experience of aging. Multidimensionality and multidirectionality in relation to successful aging and well-being].
The positive and negative aspects that aging persons distinguish in different dimensions of the experience of their own aging process were studied. To examine the role of the aging experience in individual functioning, its relation with indicators of successful aging and well-being was focused on. The Dutch Aging Survey, using a representative sample of the present and future generations of elderly (40-85 years; N = 975), provided data on the experience of aging (positive and negative aspects, own aging as physical and social decline as well as continued growth), successful aging (health problems, loneliness and hope), and well-being (life satisfaction and positive and negative affect). Physical and social decline are the most prominent negative aspects and social gains and psychological growth are the most prominent positive aspects of one's own aging experience. The relation between aging experience and indicators of successful aging shows that individuals interpret their life situation in terms of their own aging process. Both negative and positive aspects of the aging experience are related to well-being, in particular for the group in transition to old age (55-69 years).


Face affect recognition deficits in personality-disordered offenders: association with psychopathy.
There is a limited literature examining face affect recognition in offenders. In line with the Integrated Emotion Systems (IES) model, existing studies suggest a psychopathy-related deficit in sad/fear recognition. However, many of these studies have small samples, and few include a healthy control group in order to examine the contribution of criminality. We compared the performance of male criminals with dissocial (antisocial) personality disorder (PD group) and healthy male IQ-matched controls, on a morphed face affect-processing task and examined the relationship between psychopathy (assessed using the Psychopathy Checklist: Screening Version, PCL: SV), score and performance on this task in the PD sample. The PD group had a specific deficit in the recognition of sad facial affect that was present even at 100% expression intensity. This deficit could not be attributed to impulsive responding as the PD group generally had longer mean reaction times than healthy controls. Within the PD group, those with high scores on the PCL: SV were less accurate than low scorers at classifying sad facial affect. There was also a significant negative correlation between total psychopathy score and sad affect recognition accuracy. There were no specific relationships between affect recognition and the subcomponents of psychopathy. The findings suggest that criminality/antisocial personality may be associated with a deficit in the recognition of aversive cues in others, and that this deficit is more severe in psychopathic offenders. The findings lend further support to the IES model.


Deoxycytidine kinase is overexpressed in poor outcome breast cancer and determines responsiveness to nucleoside analogs.
Only a minority of breast cancer patients responds to chemotherapy and we lack predictive biomarkers that help to select a patient-tailored therapy that takes into consideration the molecular heterogeneity of the cancer type. Responsiveness to the clinically important nucleoside analogs gemcitabine and decitabine may be critically determined by Deoxycytidine kinase (DCK) expression as this enzyme is required to convert the inactive prodrugs into their pharmacologically active forms. Here, we examined whether DCK is differentially expressed in breast cancer and evaluated whether DCK expression levels control responsiveness to these nucleoside analogs in vitro by experimentally modulating DCK expression levels. We examined DCK expression in gene expression data sets of breast tumors including the series of 295 consecutive patients that have been classified into low or high risk for recurrence using the MammaPrint 70 gene profile. We found that DCK is expressed at higher levels in patients having poor clinical outcome as judged by the MammaPrint assay. As such, patients that have a poor prognosis may thus be susceptible to treatment with nucleoside analogs. In support of this, we found a causal relationship between DCK levels and sensitivity to these nucleoside analogs in breast cancer cell lines. The data indicate that breast cancers that are at high risk of recurrence express higher levels of DCK, which we find to be strongly correlated to a favorable response to nucleoside analogs. The data suggest that DCK expression in breast cancer could be exploited to select patients that are likely to respond to treatment with nucleoside analogs.


SIPL1-facilitated PTEN ubiquitination contributes to its association with PTEN.
PTEN is post-translationally modified by ubiquitin via association with multiple E3 ubiquitin ligases, including NEDD4-1, XIAP, and WWP2. Despite the rapid progress made in researching the impact of ubiquitination on PTEN function, our understanding remains fragmented. Building on the previously observed interaction between SIPL1 and PTEN, we report here that SIPL1 promotes PTEN polyubiquitination via lysine 48 (K48)-independent polyubiquitin chains. Substitution of the K48 residue of ubiquitin with arginine (R) enhanced SIPL1-mediated PTEN polyubiquitination. In contrast, the K63R substitution significantly reduced it. The ubiquitin-like (UBL) domain is required for SIPL1-induced PTEN polyubiquitination. This post-translational modification promoted the association of SIPL1 with PTEN. Elevated amounts of the SIPL1/PTEN complex were precipitated in 293T cells co-transfected with PTEN, SIPL1, and ubiquitin compared to cells co-transfected with SIPL1 and PTEN only. Additionally, formation of the SIPL1/PTEN complex was inhibited when either lysine-less (K0) ubiquitin or K63R ubiquitin was co-transfected together with SIPL1+PTEN. The PTEN component in the SIPL1/PTEN complex contained polyubiquitin chains. The ubiquitination reaction may play a structural role, stabilizing the SIPL1/PTEN complex, as a ubiquitin binding-defective SIPL1 mutant (TFLV) is proficient in PTEN association. Collectively, we demonstrate that SIPL1 binds PTEN and enhances PTEN polyubiquitination which in turn promotes the interaction between SIPL1 and PTEN.


Comparison of field olfactometers in a controlled chamber using hydrogen sulfide as the test odorant.
A standard method for measuring and quantifying odour in the ambient air utilizes a portable odour detecting and measuring device known as a field olfactometer (US Public Health Service Project Grant A-58-541). The field olfactometer dynamically dilutes the ambient air with carbon-filtered air in distinct ratios known as "Dilutions-to-Threshold" dilution factors (D/Ts), i.e. 2, 4, 7, 15, etc. Thirteen US states and several cities in North America currently utilize field olfactometry as a key component of determining compliance to odour regulations and ordinances. A controlled environmental chamber was utilized, with hydrogen sulfide as the known test odorant. A hydrogen sulfide environment was created in this controlled chamber using an Advanced Calibration Designs, Inc. Cal2000 Hydrogen Sulfide Generator. The hydrogen sulfide concentration inside the chamber was monitored using an Arizona Instruments, Inc. Jerome Model 631 H2S Analyzer. When the environmental chamber reached a desired test concentration, test operators entered the chamber. The dilution-to-threshold odour concentration was measured using a Nasal Ranger Field Olfactometer (St Croix Sensory, Inc.) and a Barnebey Sutcliffe Corp. Scentometer. The actual hydrogen sulfide concentration was also measured at the location in the room where the operators were standing while using the two types of field olfactometers. This paper presents a correlation between dilution-to-threshold values (D/T) and hydrogen sulfide ambient concentration. For example, a D/T of 7 corresponds to ambient H2S concentrations of 5.7-15.6 microg/m3 (4-11 ppbv). During this study, no significant difference was found between results obtained using the Scentometer or the Nasal Ranger (r = 0.82). Also, no significant difference was found between results of multiple Nasal Ranger users (p = 0.309). The field olfactometers yielded hydrogen sulfide thresholds of 0.7-3.0 microg/m3 (0.5-2.0 ppbv). Laboratory olfactometry yielded comparable thresholds of 0.64-1.3 microg/m3 (0.45-0.9 ppbv). These thresholds are consistent with published values.


Exploring Selective Inhibition of the First Bromodomain of the Human Bromodomain and Extra-terminal Domain (BET) Proteins.
A midthroughput screening follow-up program targeting the first bromodomain of the human BRD4 protein, BRD4(BD1), identified an acetylated-mimic xanthine derivative inhibitor. This compound binds with an affinity in the low micromolar range yet exerts suitable unexpected selectivity in vitro against the other members of the bromodomain and extra-terminal domain (BET) family. A structure-based program pinpointed a role of the ZA loop, paving the way for the development of potent and selective BET-BRDi probes.


Molecular docking and network pharmacological analysis of Scutellaria baicalensis against renal cell carcinoma.
This paper employs network pharmacology and molecular docking to analyze the active components, targets, and molecular mechanisms of Scutellaria baicalensis in treating renal cell carcinoma (RCC). The potential active target genes and components of Scutellaria baicalensis are obtained by searching the TCMSP database, and RCC targets are obtained using OMIM, Genecards, and Drugbank databases. The interaction of target proteins is analyzed thanks to STRING, and the component target disease network diagram is constructed through Cytoscape 3.8.2 software. Besides, KEGG, and GO enrichment analysis is performed using the Bioconductor bioinformatics R software package. AutoDock Vina 1.1.2, PyMol 2.5 and Maestro 12.9 software are used for molecular docking. According to the results, Scutellaria baicalensis, which has 36 active ingredients, 500 drug targets, and 85 drug-disease common targets in the treatment of RCC, relies mainly on active ingredients, including wogonin, baicalein, acacetin, oroxylin A, moslosooflavone, salvigenin, and neobaicalein. In addition, the core components within Scutellaria baicalensis that contribute to the treatment of renal cancer are TP53, CCND1, STAT3, CASP3, JUN, VEGFA, AKT1, and EGFR; while the main molecular mechanisms that helps relieve RCC include PI3K-Akt, Ras, MAPK, p53, VEGF, and JAK-STAT signaling pathway. Molecular docking suggested that wogonin had a good binding affinity with core proteins CASP3, CCND1, JUN, STAT3, TP53, and VEGFA. This study confirms that Scutellaria baicalensis can treat RCC in a multi-component, multi-target, and multi-way manner.


Predictors of Walking App Users With Comparison of Current Users, Previous Users, and Informed Nonusers in a Sample of Dutch Adults: Questionnaire Study.
The last decade has seen a substantial increase in the use of mobile health apps and research into the effects of those apps on health and health behaviors. In parallel, research has aimed at identifying population subgroups that are more likely to use those health apps. Current evidence is limited by two issues. First, research has focused on broad health apps, and little is known about app usage for a specific health behavior. Second, research has focused on comparing current users and current nonusers, without considering subgroups of nonusers. We aimed to provide profile distributions of current users, previous users, and informed nonusers, and to identify predictor variables relevant for profile classification. Data were available from 1683 people who participated in a Dutch walking event in Amsterdam that was held in September 2017. They provided information on demographics, self-reported walking behavior, and walking app usage, as well as items from User Acceptance of Information Technology, in an online survey. Data were analyzed using discriminant function analysis and multinomial logistic regression analysis. Most participants were current walking app users (899/1683, 53.4%), while fewer participants were informed nonusers (663/1683, 39.4%) and very few were previous walking app users (121/1683, 7.2%). Current walking app users were more likely to report walking at least 5 days per week and for at least 30 minutes per bout (odds ratio [OR] 1.44, 95% CI 1.11-1.85; P=.005) and more likely to be overweight (OR 1.72, 95% CI 1.24-2.37; P=.001) or obese (OR 1.49, 95% CI 1.08-2.08; P=.005) as compared with informed nonusers. Further, current walking app users perceived their walking apps to be less boring, easy to use and retrieve information, and more helpful to achieve their goals. Effect sizes ranged from 0.10 (95% CI 0.08-0.30) to 1.58 (95% CI 1.47-1.70). The distributions for walking app usage appeared different from the distributions for more general health app usage. Further, the inclusion of two specific subgroups of nonusers (previous users and informed nonusers) provides important information for health practitioners and app developers to stimulate continued walking app usage, including making information in those apps easy to understand and making it easy to obtain information from the apps, as well as preventing apps from becoming boring and difficult to use for goal attainment.


The identification of pseudomonads and related bacteria in a clinical laboratory.
Non-fermenting, catalase-positive Gram-negative bacilli that grow on nutrient agar are often isolated in clinical laboratories. We have applied biochemical techniques appropriate to a typical clinical microbiology laboratory, and for the most part described in Cowan and Steel's Manual for the identification of medical bacteria (Cowan, 1974), to 428 clinical isolates and have evolved a scheme for their identification. Organisms were subdivided into groups on the basis of three tests, namely the glucose oxidation-fermentation test and tests for oxidase activity and motility. A choice was then made among other tests to produce indentification tables, containing only the most useful tests, for the various groups. The most complicated table has only 16 tests. This simple system identified 96.5% of the 428 organisms, as well as many subsequent isolates of the more common organisms.


[Serum antibodies in celiac disease].
Accurate diagnosis of celiac disease is important because patients are advised to adhere to a strict gluten-free diet for life. This management is critical to avoid disease complications such as malignancies. In this review the new terminology for the disease clinical features (active, silent, latent and potential celiac disease) and the disease association with other conditions are commented. The value and efficacy of the assessment of serum antigliadin antibodies and of antireticulin, antiendomysial and tissue transglutaminase autoantibodies in the diagnosis and follow-up of the celiac disease are particularly evaluated.


Integrated Analysis of circRNA-miRNA-mRNA Regulatory Networks in the Intestine of Sebastes schlegelii Following Edwardsiella tarda Challenge.
Sebastes schlegelii, an important aquaculture species, has been widely cultured in East Asian countries. With the increase in the cultivation scale, various diseases have become major threats to the industry. Evidence has shown that non-coding RNAs (ncRNAs) have remarkable functions in the interactions between pathogens and their hosts. However, little is known about the mechanisms of circular RNAs (circRNAs) and coding RNAs in the process of preventing pathogen infection in the intestine in teleosts. In this study, we aimed to uncover the global landscape of mRNAs, circRNAs, and microRNAs (miRNAs) in response to Edwardsiella tarda infection at different time points (0, 2, 6, 12, and 24 h) and to construct regulatory networks for exploring the immune regulatory mechanism in the intestine of S. schlegelii. In total, 1,794 mRNAs, 87 circRNAs, and 79 miRNAs were differentially expressed. The differentially expressed RNAs were quantitatively validated using qRT-PCR. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that most of the differentially expressed mRNA genes and the target genes of ncRNAs were related to immune signaling pathways, such as the NF-κB signal pathway, pathogen recognition receptors related to signaling pathways (Toll-like receptors and Nod-like receptors), and the chemokine signaling pathway. Based on these differentially expressed genes, 624 circRNA-miRNA pairs and 2,694 miRNA-mRNA pairs were predicted using the miRanda software. Integrated analyses generated 25 circRNA-miRNA-mRNA interaction networks. In a novel_circ_0004195/novel-530/IκB interaction network, novel_530 was upregulated, while its two targets, novel_circ_0004195 and IκB, were downregulated after E. tarda infection. In addition, two circRNA-miRNA-mRNA networks related to apoptosis (novel_circ_0003210/novel_152/apoptosis-stimulating of p53 protein 1) and interleukin (novel_circ_0001907/novel_127/interleukin-1 receptor type 2) were also identified in our study. We thus speculated that the downstream NF-κB signaling pathway, p53 signaling pathway, and apoptosis pathway might play vital roles in the immune response in the intestine of S. schlegelii. This study revealed a landscape of RNAs in the intestine of S. schlegelii during E. tarda infection and provided clues for further study on the immune mechanisms and signaling networks based on the circRNA-miRNA-mRNA axis in S. schlegelii.


Combined stress of ocean acidification and warming influence survival and drives differential gene expression patterns in the Antarctic pteropod, Limacina helicina antarctica.
The ecologically important thecosome pteropods in the Limacina spp. complex have recently been the focus of studies examining the impacts global change factors - e.g., ocean acidification (OA) and ocean warming (OW) - on their performance and physiology. This focus is driven by conservation concerns where the health of pteropod populations is threatened by the high susceptibility of their shells to dissolution in low aragonite saturation states associated with OA and how coupling of these stressors may push pteropods past the limits of physiological plasticity. In this manipulation experiment, we describe changes in the transcriptome of the Antarctic pteropod, Limacina helicina antarctica, to these combined stressors. The conditions used in the laboratory treatments met or exceeded those projected for the Southern Ocean by the year 2100. We made two general observations regarding the outcome of the data: (1) Temperature was more influential than pH in terms of changing patterns of gene expression, and (2) these Antarctic pteropods appeared to have a significant degree of transcriptomic plasticity to respond to acute abiotic stress in the laboratory. In general, differential gene expression was observed amongst the treatments; here, for example, transcripts associated with maintaining protein structure and cell proliferation were up-regulated. To disentangle the effects of OA and OW, we used a weighted gene co-expression network analysis to explore patterns of change in the transcriptome. This approach identified gene networks associated with OW that were enriched for transcripts proposed to be involved in increasing membrane fluidity at warmer temperatures. Together these data provide evidence that L.h.antarctica has a limited capacity to acclimate to the combined conditions of OA and OW used in this study. This reduced scope of acclimation argues for continued study of how adaptation to polar aquatic environments may limit the plasticity of present-day populations in responding to future environmental change.


Blastocystis hominis infection in a post-cardiotomy patient on extracorporeal membrane oxygenation support: A case report and literature review.
Opportunistic pathogens can cause severe damage leading to irreversible complications in immune-compromised patients. Here we describe a patient who sustained Blastocystis hominis infection resulting in severe sepsis while on extracorporeal membrane oxygenation (ECMO) support, and the course of treatment taken to treat him. Our case, a 34-year-old Filipino man, was hospitalized for valvular disease and received valve replacements. ECMO and an intra-aortic balloon pump (IABP) were implemented when the patient developed progressive heart failure after cardiac surgery. Unfortunately, the patient suffered from sepsis with persistent fever and diarrhea, and subsequent examinations indicated the patient was infected by B. hominis. After adequate administration of the antibiotic metronidazole, the patient's symptoms subsided and he was discharged. Blastocystis hominis is a unicellular protozoa commonly found in the intestinal tract, and the prevalence of B. hominis is 1.5-10% in developed countries and 30-50% in developing countries. The patient needed the support of ECMO and IABP, was immunocompromised to a certain extent; B. hominis can be a harmful opportunistic pathogen for them and lead to severe irreversible complications such as death. This is the first published article showing that the opportunistic pathogen, B. hominis, can cause severe infection in patients on ECMO support, a result that should be kept in mind when patients come from a place with a high prevalence of B. hominis. The prophylactic medication should be administered routinely when patients live in the region and extracorporeal life-support is used.


Overview of the molecular carcinogenesis of mouse lung tumor models of human lung cancer.
Lung cancer is the leading cause of cancer death worldwide, and the need to develop better diagnostic techniques and therapies is urgent. Mouse models have been utilized for studying carcinogenesis of human lung cancers, and many of the major genetic alterations detected in human lung cancers have also been identified in mouse lung tumors. The importance of mouse models for understanding human lung carcinogenic processes and in developing early diagnostic techniques, preventive measures and therapies cannot be overstated. In this report, the major known molecular alterations in lung tumorigenesis of mice are reviewed and compared to those in humans.


Mechanisms of disease reversal in focal and segmental glomerulosclerosis.
It is well known that progression of chronic kidney disease can be ameliorated or stabilized by different interventions, but more studies indicate that it can even be reversed. Most data suggest that current therapy, especially renin-angiotensin system inhibition alone, is not sufficient to initiate and maintain long-term regression of glomerular structural injury. In this article, we review the potential reversal of glomerulosclerosis and evidence from both human and animal studies. We discuss mechanisms that involve matrix remodeling, capillary reorganization, and podocyte reconstitution. In the future, a multipronged strategy including novel anti-inflammatory and antifibrotic molecules should be considered to potentiate regression of glomerulosclerosis.


Auxological and endocrinological evaluation of children with hydrocephalus and/or meningomyelocele.
Short stature and precocious puberty are frequently found in children with hydrocephalus and/or meningomyelocele (MMC). However, aetiology and pathophysiology have not been well characterized. In this study, 108 patients aged between 3 and 17.8 years were evaluated. Growth was documented on the basis of arm span measurements. Short arm span was found in 47 (43.5%) children with hydrocephalus and/or MMC. Mean arm span was -2.0 standard deviation score (SDS) (-6.4 to +0.8) in 43 girls and -14 SDS (-5.6 to +1.3) in 65 boys. When growth deficiency (more than -2.0 SDS) was diagnosed by arm span measurement (24 F, 23 M) or when early sexual maturation was found (6 F, 9 M), endocrine evaluation followed. Levels of serum insulin-like growth factor and insulin-like growth factor binding protein-3 were low in 22 of 62 (33.8%) patients. In 9 of 62 (14.5%) patients, insulin-like growth factor-1 and insulin-like growth factor binding protein-3 levels were found to be increased. Growth hormone (GH) deficiency was diagnosed by means of two different stimulation tests (clonidine and arginine) in 7 of 62 (11.3%) patients. In another 3 of 62 (4.8%) children, 12 h night time GH sampling showed low maximum peak levels and decreased area under the curve values, suggesting neurosecretory GH dysfunction. Precocious puberty or early onset of puberty associated with elevated luteinising hormone and follicle stimulating hormone concentrations after stimulation with luteinising hormone releasing hormone was found in 13 of 108 (12.0%) patients (age 7-9 years). Free thyroxine was abnormally low in 2 of 62 (3.2%) patients. Cortisol was within the normal range in all 62 (100%) tested patients. Short arm span in children with hydrocephalus and/or MMC is frequently accompanied by GH deficiency or neurosecretory GH dysfunction. Early onset of puberty is another frequent finding. Both hormonal disorders may be the consequence of damage to the hypothalamus or the pituitary gland caused by increased intracerebral pressure or increased mass of cerebrospinal fluid.


The Designation Degree of Tool Wear after Machining of the Surface Layer of Duplex Stainless Steel.
This paper presents problems related to the machining of the surface layer. It is important that steel structures are used in material engineering and machine construction. Austenitic, ferritic, martensitic and two-phase corrosion resistant steel was widely used in the petrochemical and shipbuilding industries. Duplex stainless steel was used in sea water and acid installations. The shafts of centrifugal pumps can be made of stainless steel and are used in acid or seawater pumps. The surface layer of corrosion resistant steel shafts must have a low surface roughness. Machine elements made of stainless steel, and in particular of the duplex type, are difficult-to-cut materials. This article aims to study the effect of parameters on tool life and tool wear. The influence of technological parameters such as depth of cut, cutting speed, feed on maximum value tool wear is presented. The treatment of the surface layer was performed using carbide inserts. The highest wear and the lowest roughness were used as selection criteria. This problem is a significant issue due to the ability of the machine parts for the required reliable operation of devices and machines. To determine the degree of tool wear to increase of the surface layer quality after shaping DSS.


Smooth muscle-endothelial cell communication activates Reelin signaling and regulates lymphatic vessel formation.
Active lymph transport relies on smooth muscle cell (SMC) contractions around collecting lymphatic vessels, yet regulation of lymphatic vessel wall assembly and lymphatic pumping are poorly understood. Here, we identify Reelin, an extracellular matrix glycoprotein previously implicated in central nervous system development, as an important regulator of lymphatic vascular development. Reelin-deficient mice showed abnormal collecting lymphatic vessels, characterized by a reduced number of SMCs, abnormal expression of lymphatic capillary marker lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), and impaired function. Furthermore, we show that SMC recruitment to lymphatic vessels stimulated release and proteolytic processing of endothelium-derived Reelin. Lymphatic endothelial cells in turn responded to Reelin by up-regulating monocyte chemotactic protein 1 (MCP1) expression, which suggests an autocrine mechanism for Reelin-mediated control of endothelial factor expression upstream of SMC recruitment. These results uncover a mechanism by which Reelin signaling is activated by communication between the two cell types of the collecting lymphatic vessels--smooth muscle and endothelial cells--and highlight a hitherto unrecognized and important function for SMCs in lymphatic vessel morphogenesis and function.


Patterns and Impact of Arterial CO2 Management in Patients With Acute Respiratory Distress Syndrome: Insights From the LUNG SAFE Study.
Considerable variability exists regarding CO2 management in early ARDS, with the impact of arterial CO2 tension on management and outcomes poorly understood. To determine the prevalence and impact of hypocapnia and hypercapnia on the management and outcomes of patients with early ARDS enrolled in the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) study, an international multicenter observational study. Our primary objective was to examine the prevalence of day 1 and sustained (day 1 and 2) hypocapnia (Paco2 < 35 mm Hg), normocapnia (Paco2 35-45 mm Hg), and hypercapnia (Paco2 > 45 mm Hg) in patients with ARDS. Secondary objectives included elucidating the effect of CO2 tension on ventilatory management and examining the relationship with ARDS outcome. Of 2,813 patients analyzed, 551 (19.6%; 95%CI, 18.1-21.1) were hypocapnic, 1,018 (36.2%; 95% CI, 34.4-38.0) were normocapnic, and 1,214 (43.2%; 95% CI, 41.3-45.0) were hypercapnic, on day 1. Sustained hypocapnia was seen in 252 (9.3%; 95% CI, 8.2-10.4), sustained normocapnia in 544 (19.3%; 95% CI, 17.9-20.8), and sustained hypercapnia in 654 (24.1%; 95% CI, 22.5-25.7) patients. Hypocapnia was more frequent and severe in patients receiving noninvasive ventilation but also was observed in patients on controlled mechanical ventilation. Sustained hypocapnia was more frequent in middle-income countries, whereas sustained hypercapnia was more frequent in Europe. ARDS severity profile was highest in sustained hypercapnia, and these patients received more protective ventilation. No independent association was seen between arterial CO2 and outcome. In propensity-matched analyses, the hospital mortality rate was 36% in both sustained normocapnic and hypercapnic patients (P = 1.0). ICU mortality was higher in patients with mild to moderate ARDS receiving sustained hypocapnia (38.1%) compared with normocapnia (27.1%). No evidence was found for benefit or harm with hypercapnia. Of concern, ICU mortality was higher with sustained hypocapnia in mild to moderate ARDS.


Brain Death and Organ Transplantation in Nepal: Navigating Cultural, Legal, and Ethical Landscapes.
Organ transplantation after brain death is challenging in Nepal due to cultural beliefs, legal frameworks, and ethical considerations. The Human Body Organ Transplantation (Regulation and Prohibition) Act (HBOTA) has not met with substantial success after its amendment. This review critically appraises the current state of brain death and organ transplantation in Nepal. It explores challenges, evaluates progress, and provides recommendations. Literature review of databases was conducted to find articles on brain death, organ donation, and transplantation in Nepal. Analysis of cultural, legal, ethical, and practical factors influencing implementation. Key challenges include limited awareness, religious beliefs, infrastructure gaps, and family consent barriers. HBOTA amendments in 2016 enabled brain death donations, however, donation rates remain low. Strategies are needed to improve public education, resources, personnel training, and collaboration. Cultural sensitivity and stakeholder engagement are crucial. A multifaceted approach addressing cultural, legal, ethical and practical dimensions is essential to improve organ donation rates in Nepal. Despite progress, substantial challenges persist requiring evidence-based strategies focused on awareness, capacity building, policy improvements, and culturally appropriate community engagement.


Inadvertent hypothermia prevention: the anaesthetic nurses' role.
Up to 90% of patients experience hypothermia perioperatively. Inadvertent hypothermia can have a profound physiological effect on the body, varying from mild vasoconstriction and feeling cold to cardiac arrest and death. Anaesthesia, general or regional, increases the risk as the normal protective reflexes such as shivering are absent, particularly when muscle relaxants are used. The very young and the elderly are particularly vulnerable. Preoperative assessment is essential. The greatest reduction in temperature occurs in the first hour of surgery, as a result of patient exposure, skin disinfection with cold fluids, inhalation of cold volatile gases and the administration of cold intravenous fluids, as well as exposure to cool theatre temperatures. If the theatre temperature drops below 21 degrees C, all patients will develop hypothermia. Patients lose heat through radiation, convention and conduction, with conduction having the greatest effect. Forced air warmers such as the Bair Hugger are the most effective means of preventing and treating heat loss. They should be used routinely although their contribution to infection also needs to be considered. Nurses should be aware of the risks of hypothermia so that modes of prevention can be employed to minimize the risks of inadvertent hypothermia.


Desired attributes and skills of program managers in translation of evidence-based interventions.
Successful chronic disease project management, especially of multiyear initiatives using evidence-based interventions (EBIs), is of great importance to funders, health care decision makers, and researchers, particularly in light of limited funding. However, a gap in knowledge may exist regarding which attributes and skills are most desirable in a program manager to help him or her ensure successful implementation of EBIs. Although some literature examines the dynamics contributing to the success of community coalitions, public health leadership, and community health education, there is minimal literature exploring the significance of a program manager's role in the conceptualization, implementation, and sustainability of initiatives to improve patient and community health. The authors present their experiences as participants in a large-scale asthma initiative implemented in priority communities, as well as results of a survey distributed among all personnel of the program sites. The survey aimed to assess the key skills and attributes, in addition to contextual factors, that contribute to the strength of a program manager overseeing EBIs in asthma initiatives. The results suggest that certain attributes and skills are desirable in recruiting and hiring of a program manager, especially when augmented by ongoing skill-building training, and can help ensure program and research success.


Accidents at work and costs analysis: a field study in a large Italian company.
Accidents at work are still a heavy burden in social and economic terms, and action to improve health and safety standards at work offers great potential gains not only to employers, but also to individuals and society as a whole. However, companies often are not interested to measure the costs of accidents even if cost information may facilitate preventive occupational health and safety management initiatives. The field study, carried out in a large Italian company, illustrates technical and organisational aspects associated with the implementation of an accident costs analysis tool. The results indicate that the implementation (and the use) of the tool requires a considerable commitment by the company, that accident costs analysis should serve to reinforce the importance of health and safety prevention and that the economic dimension of accidents is substantial. The study also suggests practical ways to facilitate the implementation and the moral acceptance of the accounting technology.


[Survey on the attitude of families which have taken care of patients until their death at home].
The results of our survey using a questionnaire were as follows: (1) patients' families had a positive attitude toward the patients' death at home, (2) a good communication was established between the nurses from our institution and the patients or their families, (3) the nurses were considered reliable and friendly, (4) for several days or immediately before the patients' death, which was the most severe period for the patients and their families, the patients and their families needed more support from the nurses.


NASBOD 2013: design, definitions, and metrics.
Iran has witnessed a substantial demographic and health transition, especially during the past 2 decades, which necessitates updated evidence-based policies at national and indeed at subnational scale. The National and Subnational Burden of Diseases, Injuries, and Risk Factors (NASBOD) Study aims to provide the required evidence based on updated data sources available in Iran and novel methods partly adopted from Global Burden of Disease 2010. This paper aims at explaining the motives behind the study, the design, the definitions, the metrics, and the challenges due to limitations in data availability. All available published and unpublished data sources will be used for estimating the burden of 291 diseases and 67 risk factors from 1990 to 2013 at national and subnational scale. Published data will be extracted through systematic review. Existing population-based data sources include: registries (death and cancer), Demographic and Health Surveys, National Health Surveys, and other population-based surveys such as Non_Communicable Diseases Surveillance Surveys. Covariates will be extracted from censuses and household expenditure surveys. Hospital records and outpatient data will be actively collected as two distinct projects. Due to lack of data points by year and province, statistical methods will be used to impute the lacking data points based on determined covariates. Two main models will be used for data imputation: Bayesian Autoregressive Multi-level models and Spatio-Temporal regression models. The results from all available models will be used in an Ensemble Model to obtain the final estimates. Five metrics will be used for estimating the burden: prevalence, death, Years of Life Lost due to premature death (YLL), Years of Life Lost due to Disability (YLD), and Disability-Adjusted Life Years Lost (DALY). Burden attributable to risk factors will be estimated through comparative risk assessment based on Population Attributable Fraction (PAF). Uncertainty Intervals (UIs) will be calculated and reported for all aforementioned metrics. We will estimate trends in terms of prevalence, deaths, YLLs, YLDs, and DALYs for Diseases, Injuries, and Risk Factors province from 1990 to 2013. Results of the present study will have implications for policy making as they address health gaps in Iranian population and their inequality between provinces.


Infectious complications of noncombat trauma patients provided care at a military trauma center.
Infectious complications are reported frequently in combat trauma patients treated at military hospitals. Infections in 4566 noncombat related trauma patients treated at a military trauma center were retrospectively reviewed from 1/2003 to 5/2007 using registry data. Burns, penetrating, and blunt trauma accounted for 17%, 19%, and 64%, respectively; the median age was 38 and 22% were female. Pulmonary infections were present in 4.2% of patients, 2.4% had cellulitis and wound infections, 2.2% urinary infections, and 0.7% sepsis. On univariate analysis, infected patients were more likely to be admitted to the ICU, have longer ICU and hospital lengths of stay (LOS), and to die (p < 0.05). Multivariate analysis revealed associations between infection and hospital LOS, preexisting medical conditions, and lower Glasgow Coma Scale in nonburned patients. In burned patients, infection was associated with total body surface area burned and preexisting conditions (p < 0.01). Enhanced infection control in targeted trauma populations may improve outcomes.


Active nuclear import and export pathways regulate E2F-5 subcellular localization.
Epidermal keratinocyte differentiation is accompanied by differential regulation of E2F genes, including up-regulation of E2F-5 and its concomitant association with the retinoblastoma family protein p130. This complex appears to play a role in irreversible withdrawal from the cell cycle in differentiating keratinocytes. We now report that keratinocyte differentiation is also accompanied by changes in E2F-5 subcellular localization, from the cytoplasm to the nucleus. To define the molecular determinants of E2F-5 nuclear import, we tested its ability to enter the nucleus in import assays in vitro using digitonin-permeabilized cells. We found that E2F-5 enters the nucleus through mediated transport processes that involve formation of nuclear pore complexes. It has been proposed that E2F-4 and E2F-5, which lack defined nuclear localization signal (NLS) consensus sequences, enter the nucleus in association with NLS-containing DP-2 or pRB family proteins. However, we show that nuclear import of E2F-5 only requires the first N-terminal 56 amino acid residues and is not dependent on interaction with DP or pRB family proteins. Because E2F-5 is predominantly cytoplasmic in undifferentiated keratinocytes and in other intact cells, we also examined whether this protein is subjected to active nuclear export. Indeed, E2F-5 is exported from the nucleus through leptomycin B-sensitive, CRM1-mediated transport, through a region corresponding to amino acid residues 130-154. This region excludes the DNA- and the p130-binding domains. Thus, the subcellular distribution of E2F-5 is tightly regulated in intact cells, through multiple functional domains that direct nucleocytoplasmic shuttling of this protein.