Female-attracting pheromone in newt cloacal glands.
It has been postulated that male newts emit pheromones that attract females of the same species. Female newts of the species Cynops pyrrhogaster were attracted to water in which sexually active conspecific males had been kept, but not to water in which abdominal gland-ablated males had been kept, indicating that the attracting pheromone was secreted by or through the abdominal gland of the cloaca. An attempt has been made to isolate and characterize the female-attracting pheromone in the abdominal glands of male newts. Female-attracting activity was monitored using a preference test. The active substance was isolated by two steps of purification using reverse-phase high-performance liquid chromatography. Direct sequencing of the final product revealed that it is a decapeptide with the amino acid sequence Ser-Ile-Pro-Ser-Lys-Asp-Ala-Leu-Leu-Lys. Its minimum effective concentration was estimated to be between 0.1 pM and 1.0 pM. The synthetic peptide showed a female-attracting activity similar to that of the native peptide. It seems to act through the olfactory organ of female newts, because the effect of the peptide was blocked by bilateral nostril plugging with cotton balls soaked in melted vaseline. An antiserum against sodefrin was generated in a rabbit. An immunoelectron microscopic study using this antiserum revealed that sodefrin exists predominantly within secretory granules in the epithelial cells of the abdominal glands. A radioimmunoassay for sodefrin was developed in which the antiserum was used along with sodefrin which was N-terminally extended with a tyrosine residue as a radioligand. The immunoassayable sodefrin content in C. pyrrhogaster males was diminished by castration and hypophysectomy. The sodefrin content was increased markedly in the castrated and hypophysectomized newts after treatment with both testosterone and prolactin. Testosterone but not prolactin increased the sodefrin content to a lesser extent. Aqueous extract of the abdominal glands of C. ensicauda showed no inhibition of binding in this assay. Moreover, C. ensicauda females were insensitive to sodefrin, although they were attracted to a water extract of abdominal glands from males of their own species. On the other hand, C. pyrrhogaster females responding to sodefrin were not attracted to the water extract of the abdominal glands from C. ensicauda males. Sequence analyses of sodefrin cDNA clones obtained from a C. ensicauda abdominal gland cDNA library revealed that the cDNA encoded a variant type of sodefrin peptide with substitutions of Leu3 and Gln8. The synthetic [Leu3, Gln8]-sodefrin attracted C. ensicauda females but not C. pyrrhogaster females. These results indicate that the female-attracting pheromone differs between these two species of genus Cynops.


Prevalence of chromosomal rearrangements involving non-ETS genes in prostate cancer.
Prostate cancer is characterized by structural rearrangements, most frequently including translocations between androgen-dependent genes and members of the ETS family of transcription factor like TMPRSS2:ERG. In a recent whole genome sequencing study we identified 140 gene fusions that were unrelated to ETS genes in 11 prostate cancers. The aim of the present study was to estimate the prevalence of non-ETS gene fusions. We randomly selected 27 of these rearrangements and analyzed them by fluorescence in situ hybridization (FISH) in a tissue microarray format containing 500 prostate cancers. Using break-apart FISH probes for one fusion partner each, we found rearrangements of 13 (48%) of the 27 analyzed genes in 300-400 analyzable cancers per gene. Recurrent breakage, often accompanied by partial deletion of the genes, was found for NCKAP5, SH3BGR and TTC3 in 3 (0.8%) tumors each, as well as for ARNTL2 and ENOX1 in 2 (0.5%) cancers each. One rearranged tumor sample was observed for each of VCL, ZNF578, IMMP2L, SLC16A12, PANK1, GPHN, LRP1 and ZHX2. Balanced rearrangements, indicating possible gene fusion, were found for ZNF578, SH3BGR, LPR12 and ZHX2 in individual cancers only. The results of the present study confirm that rearrangements involving non-ETS genes occur in prostate cancer, but demonstrate that they are highly individual and typically non-recurrent.


Urban rivers are hotspots of riverine greenhouse gas (N2O, CH4, CO2) emissions in the mixed-landscape chaohu lake basin.
Growing evidence shows that riverine networks surrounding urban landscapes may be hotspots of riverine greenhouse gas (GHG) emissions. This study strengthens the evidence by investigating the spatial variability of diffusive GHG (N2O, CH4, CO2) emissions from river reaches that drain from different types of landscapes (i.e., urban, agricultural, mixed, and forest landscapes), in the Chaohu Lake basin of eastern China. Our results showed that almost all the rivers were oversaturated with dissolved GHGs. Urban rivers were identified as emission hotspots, with mean fluxes of 470 μmol m-2d-1 for N2O, 7 mmol m-2d-1 for CH4, and 900 mmol m-2d-1 for CO2, corresponding to ~14, seven, and two times of those from the non-urban rivers in the Chaohu Lake basin, respectively. Factors related to the high N2O and CH4 emissions in urban rivers included large nutrient supply and hypoxic environments. The factors affecting CO2 were similar in all the rivers, which were temperature-dependent with suitable environments that allowed rapid decomposition of organic matter. Overall, this study highlights that better recognition of the influence that river networks have on global warming is required-particularly when it comes to urban rivers, as urban land cover and populations will continue to expand in the future. Management measures should incorporate regional hotspots to more efficiently mitigate GHG emissions.


Acute myeloid leukemia with normal cytogenetics.
Acute myeloid leukemia (AML) is proving to be a heterogeneous disease process that is driven by various genetic mutations and aberrant protein expression. As our population ages, the incidence of AML is likely to increase, with approximately a third of adult cases categorized with normal cytogenetics. Advances in technology are now allowing us to explore the genetic expression and protein transcription patterns of AML, providing more information that must find its place in the prognosis and the therapeutic algorithm of this disease. As we learn more, we hope to further categorize patients with normal karyotype AML into discrete risk categories that will help in treatment decision making and further elucidate the necessity for hematopoietic cell transplantation. However, at this time, many of the identified mutations and expression patterns are still experimental, requiring further analysis to determine their exact role in AML.


Comparative morphology and taxonomy of Sciacharis s. str., Chathamaenus Franz and Maorinus Franz (Coleoptera: Staphylinidae: Scydmaeninae).
Sciacharis s. str. is redefined based on the morphology of its type species, S. fulva Broun, and compared with sympatric genera Chathamaenus Franz (endemic to New Zealand) and Maorinus Franz (known from New Zealand and Australia). As a result, Chathamaenus is placed as a junior synonym of Sciacharis s. str., and Maorinus, originally described as a subgenus of Euconnus Thomson (under a preoccupied name Maoria Franz), subsequently elevated in rank, is here reduced to a subgenus of Sciacharis. Forty six new combinations resulted from this action are listed and Sciacharis (Maorinus) rakiuraensis nom. n. is proposed as a replacement name for Euconnus australis Franz, 1975, a junior primary homonym of Euconnus australis Franz, 1967.


Head impulse test reveals residual semicircular canal function after vestibular neurectomy.
Meniere disease patients sometimes report vertiginous Meniere attacks after vestibular neurectomy that spares hearing. To determine why, the authors compared postsurgical semicircular canal function in nine patients with preserved hearing with that of a control group with no preservation of hearing. The three-dimensional head impulse test revealed residual posterior canal function in all patients with vertigo attacks (eight). The control patients had no residual canal function. Thus, residual vestibular function on the ipsilesional side may cause vertiginous Meniere attacks.


The human milk microbiome changes over lactation and is shaped by maternal weight and mode of delivery.
Breast milk is recognized as the most important postpartum element in metabolic and immunologic programming of health of neonates. The factors influencing the milk microbiome and the potential impact of microbes on infant health have not yet been uncovered. Our objective was to identify pre- and postnatal factors that can potentially influence the bacterial communities inhabiting human milk. We characterized the milk microbial community at 3 different time points by pyrosequencing and quantitative polymerase chain reaction in mothers (n = 18) who varied in BMI, weight gain, and mode of delivery. We found that the human milk microbiome changes over lactation. Weisella, Leuconostoc, Staphylococcus, Streptococcus, and Lactococcus were predominant in colostrum samples, whereas in 1- and 6-mo milk samples the typical inhabitants of the oral cavity (eg, Veillonella, Leptotrichia, and Prevotella) increased significantly. Milk from obese mothers tended to contain a different and less diverse bacterial community compared with milk from normal-weight mothers. Milk samples from elective but not from nonelective mothers who underwent cesarean delivery contained a different bacterial community than did milk samples from individuals giving birth by vaginal delivery, suggesting that it is not the operation per se but rather the absence of physiological stress or hormonal signals that could influence the microbial transmission process to milk. Our results indicate that milk bacteria are not contaminants and suggest that the milk microbiome is influenced by several factors that significantly skew its composition. Because bacteria present in breast milk are among the very first microbes entering the human body, our data emphasize the necessity to understand the biological role that the milk microbiome could potentially play for human health.


Implementing receiver-driven handoffs to the emergency department to reduce miscommunication.
Miscommunications during care transfers are a leading cause of medical errors. Recent consensus-based recommendations to standardise information transfer from outpatient clinics to the emergency department (ED) have not been formally evaluated. We sought to determine whether a receiver-driven structured handoff intervention is associated with 1) increased inclusion of standardised elements; 2) reduced miscommunications and 3) increased perceived quality, safety and efficiency. We conducted a prospective intervention study in a paediatric ED and affiliated clinics in 2016-2018. We developed a bundled handoff intervention included a standard template, receiver training, awareness campaign and iterative feedback. We assessed a random sample of audio-recorded handoffs and associated medical records to measure rates of inclusion of standardised elements and rate of miscommunications. We surveyed key stakeholders pre-intervention and post-intervention to assess perceptions of quality, safety and efficiency of the handoff process. Across 162 handoffs, implementation of a receiver-driven intervention was associated with significantly increased inclusion of important elements, including illness severity (46% vs 77%), tasks completed (64% vs 83%), expectations (61% vs 76%), pending tests (0% vs 64%), contingency plans (0% vs 54%), detailed callback request (7% vs 81%) and synthesis (2% vs 73%). Miscommunications decreased from 48% to 26%, a relative reduction of 23% (95% CI -39% to -7%). Perceptions of quality (35% vs 59%), safety (43% vs 73%) and efficiency (17% vs 72%) improved significantly post-intervention. Implementation of a receiver-driven intervention to standardise clinic-to-ED handoffs was associated with improved communication quality. These findings suggest that expanded implementation of similar programmes may significantly improve the care of patients transferred to the paediatric ED.


Chromatin accessibility maps provide evidence of multilineage gene priming in hematopoietic stem cells.
Hematopoietic stem cells (HSCs) have the capacity to differentiate into vastly different types of mature blood cells. The epigenetic mechanisms regulating the multilineage ability, or multipotency, of HSCs are not well understood. To test the hypothesis that cis-regulatory elements that control fate decisions for all lineages are primed in HSCs, we used ATAC-seq to compare chromatin accessibility of HSCs with five unipotent cell types. We observed the highest similarity in accessibility profiles between megakaryocyte progenitors and HSCs, whereas B cells had the greatest number of regions with de novo gain in accessibility during differentiation. Despite these differences, we identified cis-regulatory elements from all lineages that displayed epigenetic priming in HSCs. These findings provide new insights into the regulation of stem cell multipotency, as well as a resource to identify functional drivers of lineage fate.


Neuropsychiatric disorders secondary to neurosyphilis in elderly people: one theme not to be ignored.
Neurosyphilis (NS) may present with neuropsychiatric disorders characterized by cognitive impairment, personality disorders, and confusion, among others. Very few studies have focused on neuropsychiatric disorders secondary to NS in elderly people. A retrospective chart review was performed to characterize the psychiatric findings, clinical signs and symptoms, laboratory findings, and brain magnetic resonance imaging results of ten elderly inpatients with NS. In these ten patients, the most common presenting symptoms included a wide variety of psychiatric manifestations. The serum rapid plasma regain (RPR) and Treponema pallidum particle agglutination assay (TPPA) of the ten patients were positive, with positive CSF TPPA and RPR rates of 100% and 60%, respectively. In addition, 90% of the patients demonstrated abnormal imaging, including cerebral atrophy, infarct ischemic stroke, and hydrocephalus. Our findings support the importance of serological tests for syphilis as a routine component of the evaluation of patients with clinically evident neurological or psychiatric symptoms. If the serology is positive, all of the patients should be examined with a lumbar puncture. Moreover, psychiatric illnesses secondary to NS in the elderly also deserve medical attention.


Comparison of properties of new sources of partially purified inulin to those of commercially pure chicory inulin.
Newly developed inulin powders were prepared from roots of Asparagus falcatus (AF) and Taraxacum javanicum (TJ) plants grown in Sri Lanka. Inulin content, analyzed by enzymatic spectrophotometric as well as high-performance liquid chromatographic methods, showed that AF and TJ inulin powders contain 65.5% and 45.4% (dry wt) inulin, respectively, compared with 72% dry wt in the commercially available chicory inulin. Treating the AF and TJ inulin powders using ion exchange techniques significantly (P < 0.05) reduced their contents of micro (Zn, Cu, Mn, Fe) and macro (Na, K, Ca, Mg) elements. Enzymatic hydrolysis of inulin into fructose and glucose by fructanase, and FT-IR analyses proved that the developed AF and TJ inulins have characteristic molecular composition similar to commercial inulin. TJ inulin contained significantly (P < 0.05) greater amounts of total phenolics (4.37 mg GAE/g), total flavonoids (2.79 mg QE/g), and antioxidant capacity (833.11 mM TE/g) than AF inulin, which contained 1.33 mg GAE/g of total phenolics, 0.43 mg QE/g of total flavonoids, and 406.26 mM TE/g antioxidant capacity. The current study suggests that the newly developed inulin from AF and TJ roots could be used as an alternative commercial source of inulin for the food industry.


Localized juvenile spongiotic gingival hyperplasia featuring unusual p16INK4A labeling and negative human papillomavirus status by polymerase chain reaction.
Localized juvenile spongiotic gingival hyperplasia (LJSGH) is a distinct type of gingival hyperplastic lesion with specific clinicopathologic features. Evaluation of the morphological characteristics of LJSGH indicates the potential role of human papillomavirus (HPV) infection as an underlying etiopathogenetic mechanism. All cases of LJSGH from 2008 to present were retrieved. Clinical and demographic data were collected. HPV status was investigated by p16INK4A immunohistochemistry and HPV-Polymerase chain reaction (PCR). Twenty-one cases of LJSGH were identified, 14 (66.7%) affecting males and seven (33.3%) females (M:F = 2:1, age range: 8-36, mean: 13 years). All lesions were well-demarcated, exophytic, erythematous, and hemorrhagic with granular or slightly papillary surface. Preponderance for the maxillary gingiva (19, 90.5%) was observed. Two (9.5%) patients presented with recurrence 20 and 21 months after excision (mean follow-up: 18.7 months). Histopathologically, all LJSGH lesions featured epithelial hyperplasia with intense neutrophilic exocytosis and spongiosis. All cases demonstrated positivity for p16INK4A with the majority of specimens (47.6%) intensely decorated in >50% of the overlying epithelium with focal immunostaining observed in 47.6% and diffuse in 52.4%. Thirteen cases (61.9%) were negative for HPV DNA by PCR, while two (9.5%) were suspicious for the presence of low levels of HPV DNA but definitive genotyping was not possible. One case (4.8%) displayed positivity for HPV-31. The remaining five cases failed the PCR reaction. Human papillomavirus does not participate in the pathogenesis of LJSGH. P16INK4A expression in the absence of detectable HPV DNA can likely be attributed to the intense inflammation associated with LJSGH.


Biochemical and pharmacological activities of SR 27417, a highly potent, long-acting platelet-activating factor receptor antagonist.
SR 27417 [N-(2-dimethylamino ethyl)-N-(3-pyridinyl methyl)[4- (2,4,6-triisopropylphenyl) thiazol-2-yl]amine] is the first member of a newly developed platelet-activating factor (PAF) antagonist series. It is a highly potent, competitive and selective antagonist of the binding of [3H]PAF to its receptor in rabbit platelets. It exhibits an equilibrium inhibition constant for PAF binding of 57 pM, a value that is at least 5-fold lower than that of unlabeled PAF itself. SR 27417 potently inhibited PAF-induced aggregation of rabbit and human platelets in vitro (IC50 = 0.10 and 0.50 nM, respectively) but had no effect on the action of other platelet-aggregating agents. In comparison with the triazolothienodiazepine WEB-2086, SR 27417 was 470 and 70 times more potent against PAF-induced aggregation of rabbit and human platelets, respectively. SR 27417 displayed marked in vitro inhibition of PAF-induced oxidative burst in guinea pig macrophages (IC50 = 32 nM). In an in vivo model, it protected mice from 100 micrograms/kg PAF-induced death when given i.v. (ED50 = 7.5 micrograms/kg) 5 min before PAF challenge or p.o. (ED50 = 45 micrograms/kg) 3 hr before PAF administration. SR 27417 inhibited PAF-induced death in mice with an impressive p.o. or i.v. duration of action of 30 to 48 hr. In anesthetized guinea pigs, SR 27417 inhibited i.v. and p.o. 100 ng/kg PAF-induced bronchoconstriction (ED50 = 14 and 140 micrograms/kg, respectively), hemoconcentration (ED50 = 20 and 270 micrograms/kg, respectively), thrombocytopenia (ED50 = 30 and 240 micrograms/kg, respectively) and leukopenia (ED50 = 0.1 and 1.5 mg/kg, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)


[Incidental versus clinical renal adenocarcinoma: comparative study (1970-1994)].
A revision has been made of 286 renal adenocarcinoma treated in the Urology service at the Hospital marqués de Valdecilla, Santander, during the period from January 1970 through December 1994, dividing the study in two groups based on diagnosis being incidental or clinically suspected, and comparing the following parameters: 5-year intervals incidence, age, gender, intrarenal location, tumoral diameter, histology, nuclear grade, tumour stage and survival. The objective was to analyze the possible differences between renal cell neoplasias diagnosed based on clinical behaviour and those diagnosed incidentally over a 25 year period. Of the 286 renal adenocarcinomas, 217 (77.5%) were symptomatic at diagnosis, 63 (22.5% were found accidentally, while presentation in 6 cases is unknown. The percentage of incidental diagnosis increases gradually from 0% during the 1970-75 period to 44.2% from 1990 to 1994. No significant differences were found between incidental and clinical cases with regard to gender, age at presentation, affected side or intrarenal location of the tumours. The tumoral diameter of incidental cases was 6.74 +/- 3.31 cm, and 8.53 +/- 3.66 in the clinical ones, the difference being significant (p < 0.001). Nuclear grade is lower in incidental cases than in clinical ones, with a significant difference (p < 0.01). Asymptomatic tumours occur with higher proportion at low Robson stages, 60.3% stage I vs. 30.5% of symptomatic cases (p < 0.001). A comparison of survival shows the existence of significant differences (p < 0.001) between incidentalomas and clinical adenocarcinomas, the significance in this differences fading when both groups are compared based on the stage. Relative to suspected cases, incidental tumours present less size, lower nuclear grade, lower stage and better survival, all these differences being highly significant. No significant differences are seen in survival between incidentalomas and symptomatic ones when compared by stage at tumour presentation.


The effects of interactivity on information processing and attitude change: implications for mental health stigma.
Interactive media such as the Web have become a popular and important vehicle for communicating health information. However, little attention has been given to theorizing and empirically testing the effects of interactive media and the theoretical construct of interactivity. In this paper, we clearly identify and define the nature of interactivity examined. We then develop and test a theoretical model of website interactivity on information processing, involvement with communication, and attitude change in the context of stigma of mental illness. The results of an experiment revealed that interactivity of the website had positive main and moderating effects on dependent variables, while involvement with communication played a significant role in explaining the effects of interactivity. Implications for future research and for health communication campaigns for mental illness stigma are discussed.


Sex pheromone systems in goldfish: comparisons to vomeronasal systems in tetrapods.
Most amphibians, reptiles and mammals possess a well defined dual olfactory system comprised of separate neural pathways that regulate different olfactory functions. One pathway originates in the nasal cavity and gives rise to what is commonly referred to as the main olfactory system. The other pathway originates in the vomeronasal organ (VNO) and gives rise to the accessory olfactory system. Functionally, the main olfactory system is thought to subserve, olfactory-mediated tasks such as feeding and grooming, while the accessory olfactory system is believed to be primarily involved in mediating behavioral and physiological responses to sex pheromones. Traditionally, it has been difficult to address whether teleosts possess any components of the vomeronasal system, since they generally do not meet the criteria used to identify vomeronasal systems in other vertebrates. Previous conclusions that the nasal epithelia of fish is olfactory and not vomeronasal in nature are based on observations that teleosts lack a separate VNO-like chemosensory structure and an anatomically distinct accessory olfactory bulb. However, because sex pheromones have been identified in the goldfish, it is now possible to compare the neural substrates that regulate pheromone-induced responses in teleosts to those that mediate similar responses in other vertebrates. The olfactory system in goldfish is particularly well suited for such comparisons, because it comprises anatomical and functional subdivisions that resemble those associated with the main and accessory olfactory systems in tetrapods. The olfactory pathways that mediate endocrine and behavioral responses to sex pheromones in goldfish are described and then compared to the main and accessory olfactory systems of tetrapods. In making these comparisons, a number of similarities become apparent. First, the olfactory pathways that regulate responses to sex pheromones in goldfish are different from those that serve a more general olfactory function. Second, these functional differences appear to be subserved by separate and anatomically distinct olfactory tract projections to the brain. Third, the lateral olfactory tracts and their central projections in goldfish appear to serve a function analogous to that of the main olfactory system, while the medial olfactory tracts and their central projections comprise a pathway remarkably similar to the vomeronasal-accessory olfactory system. These findings suggest that teleosts may possess functional correlates of tetrapod vomeronasal systems, but in a form that has yet to be recognized. If so, medial olfactory tract projections in goldfish may be evolutionarily conserved and expressed in tetrapods as the vomeronasal system, or the medial olfactory tract projections may be new pathways that have evolved to serve the same function.


Activation of isolated NADH:ubiquinone reductase I (complex I) from Escherichia coli by detergent and phospholipids. Recovery of ubiquinone reductase activity and changes in EPR signals of iron-sulfur clusters.
NADH:ubiquinone oxidoreductase (NDH-1 or complex I) from Escherichia coli was purified using a combination of anion exchange chromatography and centrifugation in sucrose density gradient. The dependence of enzyme activity on detergent and phospholipids was studied. Artificial hexaammineruthenium reductase activity was not affected by dodecyl maltoside (DDM) and asolectin. Ubiquinone reductase activity had a bell-shape dependence on DDM concentration; 7-10-fold activation could be achieved. Treatment with asolectin subsequently yields additional 2-fold activation with a corresponding increase in the apparent V(max) and without significant changes in apparent K(m). Comparative EPR studies of complex I reduced with NADH, "as prepared" and "activated by asolectin" showed an increase in the signals derived mainly from two [4Fe-4S] clusters in the activated enzyme. One of these signals could be simulated with an axial spectrum with g values of g(xyz)= 1.895, 1.904, 2.05, which corresponds to the parameters reported for the N2 cluster. This data indicates conformational rearrangements of catalytic importance in complex I upon binding of phospholipids.


Ingestion of yeast forms of Sporothrix schenckii by mouse peritoneal macrophages.
The ingestion by thioglycolate-elicited mouse peritoneal macrophages of yeast forms of two strains of Sporothrix schenckii was studied. Yeast forms opsonized with concanavalin A (ConA) were extensively phagocytized, and the phagocytic indexes depended on the concentration of ConA and apparently on the number of lectin receptors at the yeast surface as well. Neuraminidase treatment of S. schenckii increased the ingestion of unopsonized yeasts 7.7-fold. The addition of monosaccharides and derivatives partially inhibited phagocytosis. Mannose, rhamnose, and galactose, which are major constituents of S. schenckii surface antigens, reduced the phagocytic indexes by 40 to 50%. Glucosamine, N-acetylglucosamine, and N-acetylneuraminic acid were equally effective as inhibitors of phagocytosis. A mixture of five neutral sugars and glucosamine inhibited phagocytosis by 73%. The inhibitory effect of simple sugars could be amplified by using neuraminidase-treated yeast cells. Pentoses and glucose were inactive or slightly inhibitory. A purified rhamnomannan inhibited phagocytosis of the homologous strain, whereas partially purified peptidopolysaccharides were toxic to peritoneal macrophages. A partially purified galactomannan from S. schenckii was inhibitory (62% inhibition), and a peptidopolysaccharide fraction in which the O-linked carbohydrate chains had been removed neither was toxic to macrophages nor inhibited phagocytosis. Pretreatment of macrophages with simple sugars under conditions inhibiting ingestion or binding of S. schenckii did not affect phagocytosis of latex particles or sensitized sheep erythrocytes. The presence of receptors at the peritoneal macrophages which bind S. schenckii cell surface components is suggested.


Cryptococcus neoformans releases proteins during intracellular residence that affect the outcome of the fungal-macrophage interaction.
Cryptococcus neoformans is a facultative intracellular pathogen that can replicate and disseminate in mammalian macrophages. In this study, we analyzed fungal proteins identified in murine macrophage-like cells after infection with C. neoformans. To accomplish this, we developed a protocol to identify proteins released from cryptococcal cells inside macrophage-like cells; we identified 127 proteins of fungal origin in infected macrophage-like cells. Among the proteins identified was urease, a known virulence factor, and others such as transaldolase and phospholipase D, which have catalytic activities that could contribute to virulence. This method provides a straightforward methodology to study host-pathogen interactions. We chose to study further Yeast Oligomycin Resistance (Yor1), a relatively uncharacterized protein belonging to the large family of ATP binding cassette transporter (ABC transporters). These transporters belong to a large and ancient protein family found in all extant phyla. While ABC transporters have an enormous diversity of functions across varied species, in pathogenic fungi they are better studied as drug efflux pumps. Analysis of C. neoformans yor1Δ strains revealed defects in nonlytic exocytosis, capsule size, and dimensions of extracellular vesicles, when compared to wild-type strains. We detected no difference in growth rates and cell body size. Our results indicate that C. neoformans releases a large suite of proteins during macrophage infection, some of which can modulate fungal virulence and are likely to affect the fungal-macrophage interaction.


Nonnutritive sucking during tube feedings: effects on preterm neonates in an intensive care unit.
Preterm neonates (mean 32 weeks' gestation, 1,300 gm birth weight) were provided a pacifier for nonnutritive sucking during tube feedings in the intensive care nursery. Their clinical course, subsequent bottle feeding behavior, and performance on the Brazelton Neonatal Behavior Assessment scale were compared with those of control group infants. The infants provided with pacifiers averaged 27 fewer tube feedings, started bottle feeding three days earlier, averaged a greater weight gain per day, and were discharged eight days earlier for an average hospital cost savings of approximately $3,500. Formula intake was similar for the two groups, although nurses appeared to provide more feeding stimulation for the control infants. On the Brazelton scale, the infants provided with pacifiers showed weak reflexes more frequently. Increased restfulness and diminished activity level in these infants may have contributed to the appearance of weak reflexes. The consistency between these findings and those of previous investigators suggests that the provision of a pacifier for nonnutritive sucking during tube feedings may be a cost-effective form of intervention.


Including additional controls from public databases improves the power of a genome-wide association study.
Though genome-wide association studies (GWAS) have identified numerous susceptibility loci for common diseases, their use is limited due to the expense of genotyping large cohorts of individuals. One potential solution is to use 'additional controls', or genotype data from control individuals deposited in public repositories. While this approach has been used by several groups, the genetically heterogeneous nature of the population of the United States makes this approach potentially problematic. We empirically investigated the utility of this approach in a US-based GWAS. In a small GWAS of pancreatic cancer in New York, we observed clear population structure differences relative to controls from the database of Genotypes and Phenotypes (dbGaP). When we conduct the GWAS using these additional controls, we find large inflation of the test statistic that is properly corrected by using eigenvectors from principal components analysis as covariates. To deal with errors introduced due to different sources, we propose simultaneously genotyping a small number of controls along with cases and then comparing this group to the additional controls. We show that removing SNPs that show differences between these control groups reduces false-positive findings. Thus, through an empirical approach, this report provides practical guidance for using additional controls from publicly available datasets.


Factors Impacting Clinicians' Adoption of a Clinical Photo Documentation App and its Implications for Clinical Workflows and Quality of Care: Qualitative Case Study.
Mobile health (mHealth) tools have shown promise in clinical photo and wound documentation for their potential to improve workflows, expand access to care, and improve the quality of patient care. However, some barriers to adoption persist. This study aims to understand the social, organizational, and technical factors affecting clinicians' adoption of a clinical photo documentation mHealth app and its implications for clinical workflows and quality of care. A qualitative case study of a clinical photo and wound documentation app called imitoCam was conducted. The data were collected through 20 in-depth interviews with mHealth providers, clinicians, and medical informatics experts from 8 clinics and hospitals in Switzerland and Germany. According to the study participants, the use of mHealth in clinical photo and wound documentation provides numerous benefits such as time-saving and efficacy, better patient safety and quality of care, enhanced data security and validation, and better accessibility. The clinical workflow may also improve when the app is a good fit, resulting in better collaboration and transparency, streamlined daily work, clinician empowerment, and improved quality of care. The findings included important factors that may contribute to or hinder adoption. Factors may be related to the material nature of the tool, such as the perceived usefulness, ease of use, interoperability, cost, or security of the app, or social aspects such as personal experience, attitudes, awareness, or culture. Organizational and policy barriers include the available clinical practice infrastructure, workload and resources, the complexity of decision making, training, and ambiguity or lack of regulations. User engagement in the development and implementation process is a vital contributor to the successful adoption of mHealth apps. The promising potential of mHealth in clinical photo and wound documentation is clear and may enhance clinical workflow and quality of care; however, the factors affecting adoption go beyond the technical features of the tool itself to embrace significant social and organizational elements. Technology providers, clinicians, and decision makers should work together to carefully address any barriers to improve adoption and harness the potential of these tools.


Serum biomarkers associated with aging and neurodegeneration in common marmosets (Callithrix jacchus).
The common marmoset (Callithrix jacchus), a small South American monkey, is an important nonhuman primate model in the study of aging and age-related neurodegenerative disease, including Alzheimer's disease, Parkinson's disease, and related dementias. Thorough characterization of the wild type marmoset brain agingmodel, including biomarkers of aging and neural degeneration, will further the marmoset's utility in translational research. We measured serum concentration of four key biomarkers of neural degeneration [total tau (T-tau), glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and ubiquitin C-terminal hydrolase-L1 (UCH-L1)] via single molecule array from 24 marmosets (female n = 13, male n = 11) ranging in age from 1.3 to 18.7 years. Aged marmosets (>7 years) had significantly higher GFAP, NfL, UCH-L1, and T-tau than adult marmosets. Sex differences were not detected for any of these biomarker concentrations. These data provide an important initial range of reference values for GFAP, NfL, T-tau, and UCH-L1 to evaluate aging and neural health in marmosets, as well as evaluation of therapeutics in clinical models of disease.


Triptolide inhibits the differentiation of Th17 cells and suppresses collagen-induced arthritis.
Triptolide, a diterpenoid isolated from the Chinese herb Tripterygium wilfordii Hook F, has been demonstrated to be effective in the treatment of a variety of autoimmune diseases. T helper type 17 (Th17) cells represent a novel subset of CD4(+) T cells involved in the immunopathogenesis of autoimmune diseases. Currently, the effects of triptolide on the differentiation of Th17 cells remain unclear. Here, we found that triptolide significantly inhibited the generation of Th17 cells from murine splenocytes and purified CD4(+) T cells in a dose-dependent manner. The suppressive effects of triptolide were persistent even after it had been removed from cell cultures. Importantly, triptolide inhibited the transcription of interleukin-17 (IL-17) mRNA and IL-6-induced phosphorylation of STAT3, a key signalling molecule involved in the development of Th17 cells. Moreover, these suppressive effects of triptolide on Th17 differentiation were not due to cytotoxicity of triptolide because the numbers of viable cells had no significant difference between triptolide-treated and non-triptolide-treated cells. In vivo studies demonstrated that the treatment of collagen-induced arthritis (CIA) mice with triptolide reduced arthritis scores and swollen degree of joints. At the same time, the levels of collagen type II (CII)-specific IL-17 production and the percentages of CII-specific IL-17(+)CD4(+) T cells in the cells from draining lymph nodes and spleens were significantly reduced in CIA mice treated with triptolide. These results suggested that triptolide displayed an immunosuppressive effect on CIA by down-regulating CII-specific Th17 cells. Taken together, our results may provide a new light on the potential mechanism of the immunosuppressive and anti-inflammatory effects of triptolid.


Clinical and Histopathologic Characteristics of Recurrent Sarcoidosis in Posttransplant Lungs: 25 Years of Experience.
Lung transplantation is the definitive therapy for end-stage pulmonary sarcoidosis. While recurrent sarcoidosis in allografts has been described in several case reports, the incidence and clinicopathologic characteristics remain unclear. In this study, we characterize the clinical and histopathologic features of recurrent sarcoidosis diagnosed in posttransplant lung surveillance transbronchial biopsies (TBBx). We identified 35 patients who underwent lung transplant for pulmonary sarcoidosis during the study period. Among them, 18 patients (51%) experienced recurrent sarcoidosis posttransplant. These included 7 females and 11 males with mean age at recurrence of 51.6 years. The average time interval from transplant to recurrence was 252 days (22 to 984 d). All TBBx contained >4 pieces of alveolated lung tissue with no evidence of International Society for Heart and Lung Transplantation (ISHLT) grade A2, A3, or A4 acute cellular rejection; chronic rejection; or antibody-mediated rejection. There were 33 surveillance TBBx that contained granulomatous inflammation with a mean of 3.6 well-formed granulomas per TBBx (range: 1 to >20). Multinucleated giant cells were identified in 11 TBBx (33.3%), with 1 case containing asteroid bodies. While most of the granulomas were "naked granulomas," 5 cases (15.2%) showed prominent lymphoid cuffing. Two cases showed evidence of fibrosis. One of the granulomas had focal necrosis; however, no infectious organisms were identified by special stains and clinical correlation suggested this case represented recurrent sarcoidosis. Biopsies of recurrent sarcoidosis usually show multiple well-formed granulomas with giant cells in more than half of the cases, while lymphoid cuffing, fibrosis, asteroid bodies, and necrotizing granulomas are uncommon findings. Pathologists should be aware of these features, as recurrence of sarcoidosis following lung transplant occurs in more than half of patients.


RANK Signaling in the Differentiation and Regeneration of Thymic Epithelial Cells.
Thymic epithelial cells (TECs) provide essential clues for the proliferation, survival, migration, and differentiation of thymocytes. Recent advances in mouse and human have revealed that TECs constitute a highly heterogeneous cell population with distinct functional properties. Importantly, TECs are sensitive to thymic damages engendered by myeloablative conditioning regimen used for bone marrow transplantation. These detrimental effects on TECs delay de novo T-cell production, which can increase the risk of morbidity and mortality in many patients. Alike that TECs guide the development of thymocytes, reciprocally thymocytes control the differentiation and organization of TECs. These bidirectional interactions are referred to as thymic crosstalk. The tumor necrosis factor receptor superfamily (TNFRSF) member, receptor activator of nuclear factor kappa-B (RANK) and its cognate ligand RANKL have emerged as key players of the crosstalk between TECs and thymocytes. RANKL, mainly provided by positively selected CD4+ thymocytes and a subset of group 3 innate lymphoid cells, controls mTEC proliferation/differentiation and TEC regeneration. In this review, I discuss recent advances that have unraveled the high heterogeneity of TECs and the implication of the RANK-RANKL signaling axis in TEC differentiation and regeneration. Targeting this cell-signaling pathway opens novel therapeutic perspectives to recover TEC function and T-cell production.


Sovereignty and international politics in the negotiation of the avian influenza Material Transfer Agreement.
Indonesia's action in 2007 to withhold samples of avian influenza viruses was a declaration of sovereignty over biological resources. This assertion of sovereign rights resulted in conflicting international views which can be broadly characterised as a demonstration of the diverse perspectives between the developed and developing countries about the fair and equitable use of biological resources and the acknowledgment of sovereignty within that context. The relevant international agreements were drafted with the use of acceptable diplomatic language that hides the varied political views of the participants. The use of neutral language results in different interpretations of the final text; this is particularly relevant to the application of the Convention on Biological Diversity and the International Health Regulations to the sharing of virus samples. Within this political context the intended interpretation of the text becomes difficult to determine. This article illustrates the political conflicts in the context of the sharing of virus samples and benefits and determines that the likely resolution will be through political compromise.


Sensing platform for neuron specific enolase based on molecularly imprinted polymerized ionic liquids in between gold nanoarrays.
A molecularly imprinted electrochemical sensor for neuron specific enolase (NSE) was developed by electrochemical polymerizing ionic liquid, which was functionalized with pyrrole moiety, in between gold nanoarrays. A well-defined 3D structured gold nanoarray was fabricated on a glassy carbon electrode (GCE) surface by using template-assisted electrochemical deposition technique. 1-(3-mercaptopropyl)-3-vinyl-imidazolium tetrafluoroborate was self-assembled onto the surface of gold nanoarrays to produce active sites for anchoring the molecularly imprinted film. Subsequently, an electrochemical polymerization procedure was carried out in an aqueous solution containing 1,3-di(3-N-pyrrolpropyl)imidazolium bromine ionic liquid and neuron specific enolase (NSE). After removing NSE templates, a molecularly imprinted sensor was successfully fabricated. The sensor showed high selectivity and sensitivity towards NSE, produced a linear response in the concentration range from 0.01 to 1.0ngmL-1 and had a detection limit of 2.6pgmL-1 with an incubation time of 15min. The developed sensor was demonstrated successful in determining NSE in clinical serum samples.


The Multi-center Evaluation of the Accuracy of the Contrast MEdium INduced Pd/Pa RaTiO in Predicting FFR (MEMENTO-FFR) Study.
Adenosine administration is needed for the achievement of maximal hyperaemia fractional flow reserve (FFR) assessment. The objective was to test the accuracy of Pd/Pa ratio registered during submaximal hyperaemia induced by non-ionic contrast medium (contrast FFR [cFFR]) in predicting FFR and comparing it to the performance of resting Pd/Pa in a collaborative registry of 926 patients enrolled in 10 hospitals from four European countries (Italy, Spain, France and Portugal). Resting Pd/Pa, cFFR and FFR were measured in 1,026 coronary stenoses functionally evaluated using commercially available pressure wires. cFFR was obtained after intracoronary injection of contrast medium, while FFR was measured after administration of adenosine. Resting Pd/Pa and cFFR were significantly higher than FFR (0.93±0.05 vs. 0.87±0.08 vs. 0.84±0.08, p<0.001). A strong correlation and a close agreement at Bland-Altman analysis between cFFR and FFR were observed (r=0.90, p<0.001 and 95% CI of disagreement: from -0.042 to 0.11). ROC curve analysis showed an excellent accuracy (89%) of the cFFR cut-off of ≤0.85 in predicting an FFR value ≤0.80 (AUC 0.95 [95% CI: 0.94-0.96]), significantly better than that observed using resting Pd/Pa (AUC: 0.90, 95% CI: 0.88-0.91; p<0.001). A cFFR/FFR hybrid approach showed a significantly lower number of lesions requiring adenosine than a resting Pd/Pa/FFR hybrid approach (22% vs. 44%, p<0.0001). cFFR is accurate in predicting the functional significance of coronary stenosis. This could allow limiting the use of adenosine to obtain FFR to a minority of stenoses with considerable savings of time and costs.


Phaeochromocytoma combined with subclinical Cushing's syndrome and pituitary microadenoma.
Phaeochromocytoma (PHEO) occasionally associates with pathological lesions of the adrenal cortex. The coexistence of PHEO and pre-clinical Cushing's syndrome (PCS) of the same adrenal gland has rarely been reported. We report a case of PHEO and PCS originating from the same adrenal gland and discuss the peculiar diagnostic aspects of this entity. A 64 yr old man was hospitalized to evaluate the right adrenal mass which was discovered incidentally by ultrasonography. He had a history of type 2 diabetes mellitus and hyperlipidemia. Blood pressure measurements were all normal during his hospital stay. Laboratory examination showed: urinary catecholamines were markedly increased. HbA1C of 14.3 %, midnight cortisol of 11(microg/dL), cortisol was not suppressed after the overnight 1 mg oral dexamethasone suppression test (DST): 3.42(microg/dL), 24 hr free cortisol in the urine : 213 microg/day (10-100), cortisol levels were suppressed more than 50% with 8 mg of dexamethasone. CT scan of the adrenal glands showed a 6 cm well encapsulated right adrenal mass together with a clearly normal left adrenal gland. MRI investigation of the sella turcica revealed a pituitary microadenoma on the right side of the adenohypophysis He was treated with alpha and subsequent beta blockers after the diagnosis of PHEO and PCS was made. Right adrenalectomy was performed. The pathology showed typical PHEO with adrenocortical hyperplasia. VMA, metanefrin and free cortisol levels were normalized one month after surgery. The present report is a rare case of PHEO combined with PCS in the same adrenal gland.


The best endpoint for acute GVHD treatment trials.
The optimal primary endpoint for acute graft-versus-host disease (GVHD) therapeutic trials has not been established. In a retrospective analysis, we examined the response of 864 patients who received prednisone 60 mg/m(2)/d for 14 days, followed by an 8-week taper, as initial therapy for acute GVHD from 1990-2007 at the University of Minnesota. Patients received grafts of human leukocyte antigen-matched sibling bone marrow (BM) or peripheral blood (PB; n = 315), partially matched sibling BM or PB (n = 24), unrelated donor BM or PB (n = 313), single (n = 89) or double (n = 123) umbilical cord blood. Day 28 responses were similar to day 56 responses and better than day 14 responses in predicting transplantation-related mortality (TRM). In multiple regression analysis, patients with no response at day 28 were 2.78 times (95% CI, 2.17-3.56 times; P < .001) more likely to experience TRM before 2 years than patients with a response. Other factors associated with significantly worse 2-year TRM include older age, high-risk disease, severe GVHD, and partially matched related BM/PB. No other differences in response by donor source were observed. These data suggest that day 28 is the best early endpoint for acute GVHD therapeutic trials in predicting 2-year TRM.


Design, synthesis and bioevaluation of novel prenylated chalcones derivatives as potential antitumor agents.
A series of novel prenylated chalcone derivatives with broad spectrum anticancer potential were designed and synthesized. Some of the synthesized target compounds showed potent anti-proliferative activities toward LNCaP (prostate cancer cell line), K562 (human leukemia cells), A549 (human lung carcinoma cell line) and HeLa (cervical cancer cell line) cell lines. Among of the active compounds, (E)-1-(4-(2-(diethylamino)ethoxy)-2-hydroxy-6-methoxy-3-(3-methylbut-2-en-1-yl)phenyl)-3-(pyridin-3-yl)prop-2-en-1-one (C36) was directly interacted with protein kinase B (PKB), also known as AKT, significantly inhibited the pPI3K, pAKT(Ser473) protein levels to repress the growth of cancer cells by inducing apoptosis, arresting cell cycle. Our studies provide support for prenylated chalcone derivatives potential applications in cancer treatment as a potential AKT inhibitor.


Applicability of the Kubelka-Munk theory for the evaluation of reflectance spectra demonstrated for haemoglobin-free perfused heart tissue.
Reflectance spectrometry is a useful tool for studying in vivo kinetic changes in the oxygen saturation of haemoglobin and myoglobin as well as the redox state of cytochromes. A method is given which allows the quantification of tissue reflectance spectra using multicomponent analysis. This method utilizes the Kubelka-Munk theory for modelling the measured tissue spectra. To test this approach, reflectance spectra of a haemoglobin-free perfused guinea pig heart were measured by a fast scanning spectrophotometer (100 spectra/s, spectral resolution 1.0 nm) and evaluated using the component absorbance spectra measured separately. A relative mean spectral residual error of 0.15% was achieved by least-squares fitting. Using statistical error propagation, oxygenation of myoglobin is obtained within a relative precision of 1%, and the redox state of cytochromes aa3 and c are determined simultaneously within a margin of 3%; the results for the redox-state of cytochrome b, however, are less precise. Special component error functions are presented to provide a reliability measure for the concentration prediction using this multicomponent assay. The consistency of the theory and the component absorptivity data is tested by regressing the actual concentrations obtained for each of the redox pair components during the various states of tissue oxygenation. A method is described for the recognition and reduction of systematic errors.


21st century challenge of ovarian cancer in the elderly. A personal perspective.
The incidence of ovarian cancer is highest in women over 70 years old, and the disease is the leading cause of death from gynecologic malignancies in the United States and Europe. Nevertheless, improving the quality of medical care for elderly women with ovarian cancer continues to be a challenge. This paper presents the major issues related to the surgical management of presumed early-stage ovarian cancer, surgery and chemotherapy for advanced-stage ovarian cancer in the elderly, and a proposed 21st century algorithm for dealing with these major issues in ovarian cancer in the elderly.


Laparoscopic adrenalectomy: indications, technique, complications and follow-up.
Developments in laparoscopic surgery have rendered it an efficient tool for many complex surgical procedures. In the last few years, laparoscopic adrenalectomy has become a more viable option for removal of adrenal pathology, with many surgeons preferring it to the conventional open technique. To describe the indications, technique, complications and follow-up of patients undergoing laparoscopic adrenalectomy in our department. The hospital files of 30 patients who underwent the procedure were reviewed. There were 19 females and 11 males with a mean age of 45 years. Indications for surgery differed and included hypersecreting adenoma, pheochromocytoma, suspected malignancy, and incidentaloma. Of the 31 laparoscopic adrenalectomies performed, 11 were right, 18 were left, and 1 was bilateral. The conversion rate to an open procedure was 3%. The mean duration of procedure was 120 minutes. Only one patient required blood transfusion. Complications occurred in 20% of patients, all reversible. There was no mortality. Mean hospitalization duration was 3.4 days and median follow-up 17 months. There were no late complications. All patients operated on for benign diseases are alive. Laparoscopic adrenalectomy appears to be a useful tool for the treatment of a range of adrenal pathologies.


Effects of childhood trauma on working memory in affective and non-affective psychotic disorders.
Childhood trauma is a significant risk factor for the development of psychotic disorders, and may influence executive brain functions. We thus set out to investigate the long-term effects of childhood trauma exposure on brain function of adult chronic patients diagnosed with schizophrenia, schizoaffective disorder and (psychotic) bipolar-I disorder while performing a standard 2/0-back working memory task. Participants were 50 cases diagnosed with schizophrenia/schizoaffective disorder (SCZ), 42 cases with bipolar-I disorder (BD), and 47 healthy controls (HC). Among this sample, 56 clinical cases (SCZ = 32; BD = 24) and 17 HC reported significant levels of childhood trauma, while 36 clinical cases (SCZ = 18; BD = 18) and 30 HC did not. Effects of childhood trauma on working memory-related brain activation were examined in combined samples of clinical cases (independently of diagnosis) relative to HCs, as well as within each diagnostic category. Case-control analyses revealed increased activation of the left inferior parietal lobule as a main effect of trauma exposure. In addition, trauma exposure interacted with a diagnosis of SCZ or BD to reveal trauma-related increased activation in the cuneus in clinical cases and decreased activation in this region in controls. Disorder-specific functional alterations were also evident in the SCZ sample, but not BD. Childhood trauma exposure elicits aberrant function of parietal regions involved in working memory performance regardless of clinical status, as well as task-relevant visual regions that participates to attentional processes. Childhood trauma may therefore contribute to alterations in attention in SCZ and BD while performing an n-back working memory task.


Parasite local adaptation in a geographic mosaic.
A central prediction of the geographic mosaic theory of coevolution is that coevolving interspecific interactions will show varying degrees of local maladaptation. According to the theory, much of this local maladaptation is driven by selection mosaics and spatially intermingled coevolutionary hot and cold spots, rather than a simple balance between gene flow and selection. Here I develop a genetic model of host-parasite coevolution that is sufficiently general to incorporate selection mosaics, coevolutionary hot and cold spots, and a diverse array of genetic systems of infection/resistance. Results from this model show that the selection mosaics experienced by the interacting species are an important determinant of the sign and magnitude of local maladaptation. In some cases, this effect may be stronger than a previously described effect of relative rates of parasite and host gene flow. These results provide the first theoretical evidence that selection mosaics and coevolutionary hot and cold spots per se determine the magnitude and sign of local maladaptation. At the same time, however, these results demonstrate that coevolution in a geographic mosaic can lead to virtually any pattern of local adaptation or local maladaptation. Consequently, empirical studies that describe only patterns of local adaptation or maladaptation do not provide evidence either for or against the theory.


Relationship between splenomegaly and hematologic findings in patients with hepatosplenic schistosomiasis.
Schistosomiasis is a tropical disease. Patients who develop hepatosplenic schistosomiasis have clinical findings including periportal fibrosis, portal hypertension, cytopenia, splenomegaly and gastrointestinal hemorrhage. The aim of this study was to analyze the hemostatic and hematologic findings of patients with schistosomiasis and correlate these to the size of the spleen. Fifty-five adults with hepatosplenic schistosomiasis and 30 healthy subjects were selected through a history of contact with contaminated water, physical examination and ultrasound characteristics such as periportal fibrosis and splenomegaly in the Gastroenterology Service of the Universidade Federal de Pernambuco. Blood samples were collected to determine liver function, blood counts, prothrombin (international normalized ratio), partial thromboplastin time and fibrinogen and D-Dimer levels using the Pentra 120 hematological analyzer (HORIBA/ABX), Density Plus (test photo-optical Trinity Biotech, Ireland) and COBAS analyzer 6000 (Roche). Furthermore, the longitudinal size of the spleen was measured by ultrasound (Acuson X analyzer 150, Siemens). The Student t-test, the Fisher test and Pearson's correlation were used to analyze the results with statistical significance being set for a p-value < 0.05. The mean age was higher for the Study Group than for the Control Group (54 ± 13.9 vs. 38 ± 12.7 years). The average longitudinal diameter of the spleen was 16.9 cm (Range: 12.3-26.3 cm). Anemia is a common finding in patients with schistosomiasis (36.3%). The mean platelet and leukocyte counts of patients were lower than for the Control Group (p-value < 0.001). Moreover, the international normalized ratio (1.42 vs. 1.04), partial thromboplastin time (37.9 vs. 30.5 seconds) and D-Dimer concentration (393 vs. 86.5 ng/mL) were higher for the Study Group compared to the Control Group. This study suggests that hematological and hemostatic abnormalities are associated with splenomegaly, hypersplenism and portal hypertension.


Studying the binding interactions of allosteric agonists and antagonists of the CXCR4 receptor.
Several examples of allosteric modulators of GPCRs have been reported recently in the literature, but understanding their molecular mechanism presents a new challenge for medicinal chemistry. For the specific case of the cellular receptor CXCR4, it is known that pepducins (lipidated fragments of intracellular GPCR loops) such as ATI-2341 modulate CXCR4 activity agonistically via an allosteric mechanism. Moreover, there are also examples of small organic molecules such as AMD11070 and GSK812397 which may also act as allosteric antagonists. However, incomplete knowledge of the ligand-binding sites has hampered a detailed molecular understanding of how these inhibitors work. Here, we attempt to answer this question by analysing the binding interactions between the CXCR4 receptor and the above-mentioned allosteric modulators. We propose two different allosteric binding sites, one located in the intracellular loops 1, 2 and 3 (ICL1, ICL2 and ICL3) which binds the pepducin agonist ATI-2341, and the other at a subsite of the main extracellular orthosteric binding pocket between extracellular loops 1 and 2 and the N-terminus, which binds the antagonists AMD11070 and GSK812397. Allosteric interactions between the CXCR4 and ATI-2341 were predicted by combining different modeling approaches. First, a rotational blind docking search was applied and the best poses were subsequently refined using flexible docking methods and molecular dynamic simulations. For the AMD11070 and GSK812397 antagonists, the entire CXCR4 protein surface was explored by blind docking in order to define the binding region. A second docking analysis by subsites was then performed to refine the allosteric interactions. Finally, we identified the binding residues that appear to be essential for CXCR4 allosteric modulators.


Dialysis and transplantation in Sudan.
In this report we present the current status of the renal replacement therapy in Sudan. Sudan is a large country with 30 million inhabitants. Peritoneal Dialysis was started in 1968, while hemodialysis was started in 1973. At present, there are only 16 hemodialysis machines serving 56 patients in two centers in Sudan. There are also 15 peritoneal dialysis beds for 70 intermittent peritoneal dialysis patients in three centers. Continuous ambulatory peritoneal dialysis is not being practiced in Sudan. The first renal transplant was in 1974, and till now more than 30 transplants have been performed in two transplant centers. All the transplants have been from living donors. The scholars of Islam in Sudan oppose to donation from cadavers. There are 200 renal transplant patients being followed up in Sudan and the majority had their renal transplants abroad. We conclude that there is a tremendous shortage of renal services in Sudan. There are more efforts being made to improve these services.


Diagnosis and treatment of tinea pedis. A review and update.
Fungal foot infections are becoming an increasingly common public health problem as the population ages. New studies have shown that some of the traditional therapeutic antifungal agents have multiple actions that enable them to be more efficacious than previously thought, and more efficacious than other agents without multiple actions. In this review article, the pedal infections commonly referred to as tinea pedis, or athlete's foot, are described. The etiologic agents involved in the pathogenesis, the methodologies for proper diagnosis, and the therapeutic agents commercially available for treatment are reviewed.


Inhibition of protein synthesis by a toxic lectin from Viscum album L. (mistletoe).
1. The haemagglutinating and toxic lectin from Viscum album L. (mistletoe) inhibits protein synthesis in a lysate of rabbit reticulocytes, with an ID50 (concentration giving 50% inhibition) of 2.6 microgram/ml. This effect is enhanced (ID50 0.21 microgram/ml) if the lectin is reduced with 2-mercaptoethanol. 2. The lectin inhibits protein synthesis also in BL8L cells in culture. Inhibition occurs after a lag time of 3 h. The ID50 is 7 ng/ml, and increases after reduction of the lectin. 3. This and the gross lesions observed in rats poisoned with V. album lectin indicate this is a toxin very similar to ricin.


Implementation of a Value-Driven Outcomes Program to Identify High Variability in Clinical Costs and Outcomes and Association With Reduced Cost and Improved Quality.
Transformation of US health care from volume to value requires meaningful quantification of costs and outcomes at the level of individual patients. To measure the association of a value-driven outcomes tool that allocates costs of care and quality measures to individual patient encounters with cost reduction and health outcome optimization. Uncontrolled, pre-post, longitudinal, observational study measuring quality and outcomes relative to cost from 2012 to 2016 at University of Utah Health Care. Clinical improvement projects included total hip and knee joint replacement, hospitalist laboratory utilization, and management of sepsis. Physicians were given access to a tool with information about outcomes, costs (not charges), and variation and partnered with process improvement experts. Total and component inpatient and outpatient direct costs across departments; cost variability for Medicare severity diagnosis related groups measured as coefficient of variation (CV); and care costs and composite quality indexes. From July 1, 2014, to June 30, 2015, there were 1.7 million total patient visits, including 34 000 inpatient discharges. Professional costs accounted for 24.3% of total costs for inpatient episodes ($114.4 million of $470.4 million) and 41.9% of total costs for outpatient visits ($231.7 million of $553.1 million). For Medicare severity diagnosis related groups with the highest total direct costs, cost variability was highest for postoperative infection (CV = 1.71) and sepsis (CV = 1.37) and among the lowest for organ transplantation (CV ≤ 0.43). For total joint replacement, a composite quality index was 54% at baseline (n = 233 encounters) and 80% 1 year into the implementation (n = 188 encounters) (absolute change, 26%; 95% CI, 18%-35%; P < .001). Compared with the baseline year, mean direct costs were 7% lower in the implementation year (95% CI, 3%-11%; P < .001) and 11% lower in the postimplementation year (95% CI, 7%-14%; P < .001). The hospitalist laboratory testing mean cost per day was $138 (median [IQR], $113 [$79-160]; n = 2034 encounters) at baseline and $123 (median [IQR], $99 [$66-147]; n = 4276 encounters) in the evaluation period (mean difference, -$15; 95% CI, -$19 to -$11; P < .001), with no significant change in mean length of stay. For a pilot sepsis intervention, the mean time to anti-infective administration following fulfillment of systemic inflammatory response syndrome criteria in patients with infection was 7.8 hours (median [IQR], 3.4 [0.8-7.8] hours; n = 29 encounters) at baseline and 3.6 hours (median [IQR], 2.2 [1.0-4.5] hours; n = 76 encounters) in the evaluation period (mean difference, -4.1 hours; 95% CI, -9.9 to -1.0 hours; P = .02). Implementation of a multifaceted value-driven outcomes tool to identify high variability in costs and outcomes in a large single health care system was associated with reduced costs and improved quality for 3 selected clinical projects. There may be benefit for individual physicians to understand actual care costs (not charges) and outcomes achieved for individual patients with defined clinical conditions.


Contractile effects of TxA2 and endoperoxide analogues on cultured rat glomerular mesangial cells.
Vasoconstrictor metabolites of arachidonic acid (AA) affect renal hemodynamics in various disease models. Since mesangial contraction could be involved in the glomerular response to vasoconstrictors, we studied the effects of thromboxane A2 (TxA2), synthesized by sheep platelet microsomes, and of two stable prostaglandin (PG) endoperoxide analogues (END), U-44069 and U-46619, on the morphology of cultured rat mesangial cells. Computer-assisted image analysis microscopy was employed to measure cross-sectional area (CSA) of individual cells during 40-min incubations with the agonists. Both END induced a dose-dependent increase of contracting cells (U-44069, 1 pM, 14.2%; 1 nM, 25.0%; 1 microM, 34.4%; maximum CSA decrease, 16.6 +/- 2.9%; U-46619, 1 pM, 11.4%; 1 nM, 25.6%; 1 microM, 37.2%; maximum CSA decrease, 23.6 +/- 2.2%). TxA2 contracted 30.1% of the cells, with a maximum CSA decrease of 20.5 +/- 2.4%. The TxA2-receptor antagonists EP 092 (EP) and SQ 27,427 (SQ) significantly (P less than 0.05) reduced the number of cells contracting in response to U-44069 (+EP 7.3%, +SQ 10.8%) or U-46619 (+EP 14.2%, +SQ 11.1%), and eliminated TxA2-induced contraction. END also stimulated mesangial immunoreactive prostaglandin E2 (PGE2) synthesis (U-44069, 1 nM, from 2.17 +/- 0.62 to 4.36 +/- 1.0; U-46619, 1 nM, from 2.09 +/- 0.64 to 5.05 +/- 1.04, ng X mg protein-1 X 15 min-1 +/- SE). These results suggest that mesangial contraction, with resulting reduction of filtration surface area, may contribute to the effects of TxA2 and endoperoxides on glomerular hemodynamics.


Pulmonary endothelium: a dynamic interface.
Appreciation of the cell biology of endothelial cells has contributed greatly to understanding of endothelium as a tissue. Endothelium can no longer be considered simply as an inert barrier with fixed permeabilities, nor as an unreactive expanse of non-thrombogenic surface. Pulmonary endothelium is now recognized to be a tissue composed of metabolically active, functionally responsive cells, that interact with circulating substrates and formed elements in ways that regulate the composition of systemic arterial blood, affect target organ functions, and contribute to thrombosis, hemostasis and immune reactions. Much impetus for the new appreciation of endothelial cell structures and functions has been derived from the ability to isolate and culture pulmonary endothelial cells. Improvements in culture conditions and the growing awareness that biochemical, ultrastructural, as well as physical (fluid mechanical), considerations must be taken into account should pave the way for greater understanding of the role of the endothelium in health and disease.


[Application of xenogeneic bioprostheses in reconstruction of the arteries of infrainguinal localization].
The application of 37 xenogenous bioprostheses was carried out in reconstruction of the arteries of infrainguinal localization in 37 patients (34 men and 3 women). Patients older than 60 years made up 67.2%. Most of the patients had occlusion of the femoral artery and lesions of the tibial arteries: one artery in 26 (70.2%), two arteries in 3 (8.1%) patients. The femoro-proximal-popliteal shunt was performed in 15 (40.5%) patients, in 22 (59.5%) patients long shunts were implanted (in 9--femoro-proximal-popliteal shunting, in 13--femoral-tibial). During the shunting operations a reconstruction of the inflow pathways was carried on (aorto-femoral shunting, endarterectomy from the iliac-femoral segment). The results of the reconstructive operations on the lower extremities with the application of xenoprostheses were estimated as good in 28 (75.6%) patients, in 6 (16.2%) patients--as satisfactory, in 3 (8.2%)--as bad. There were no lethal outcomes.


Differences in risk behaviors and partnership patterns between younger and older men who have sex with men in New York City.
Men who have sex with men (MSM) account for a higher proportion of HIV diagnoses than any other risk group in the United States. Given that in NYC MSM younger than 30 years represent a growing proportion of new diagnoses among MSM, we examined differences between MSM by age. We analyzed NYC surveillance and partner services (PS) data for MSM newly diagnosed with HIV from January 2007 to December 2008. We compared demographics, HIV-related risk behaviors, and sexual partner characteristics between younger MSM (<30 years old) (YMSM) and MSM ≥30 years old. Three hundred and thirty-six MSM were interviewed for PS (180 YMSM and 156 older MSM). MSM were mostly black or Hispanic (91%). YMSM were more likely than older MSM to report gay sexual identity (70% vs. 58%, P < 0.01), and a recent sexually transmitted infection (29% vs. 15%, P < 0.01). More YMSM named ≥1 male partner for HIV notification (66% vs. 36%, P < 0.01). YMSM were more likely than older MSM to name partners who were 5 or more years older (42% vs. 25%, P < 0.01). More YMSM tested for HIV at least once in the past 2 years than older MSM (66% vs. 40%, P < 0.01). Our study has identified important differences in HIV risk behaviors and sexual partnerships between YMSM and older MSM newly diagnosed with HIV. YMSM were more willing to provide the names of male sex partners for the purposes of partner notification than were older MSM, suggesting that PS may be particularly effective at identifying new cases of HIV.


Captive coyotes compared to their counterparts in the wild: does environmental enrichment help?
This article attempts to determine the effects of environment (captive or wild) and a simple form of environmental enrichment on the behavior and physiology of a nonhuman animal. Specifically, analyses first compared behavioral budgets and stereotypic behavior of captive coyotes (Canis latrans) in kennels and pens to their counterparts in the wild. Second, experiments examined the effect of a simple form of environmental enrichment for captive coyotes (food-filled bones) on behavioral budgets, stereotypies, and corticosteroid levels. Overall, behavioral budgets of captive coyotes in both kennels and pens were similar to those observed in the wild, but coyotes in captivity exhibited significantly more stereotypic behavior. Intermittently providing a bone generally lowered resting and increased foraging behaviors but did not significantly reduce stereotypic behavior or alter corticosteroid levels. Thus, coyote behavior in captivity can be similar to that exhibited in the wild; in addition, although enrichment can affect proportions of elicited behaviors, abnormal behaviors and corticosteroid levels may require more than a simple form of environmental enrichment for their reduction.


Rabies in urban foxes (Vulpes vulpes) in Britain: the use of a spatial stochastic simulation model to examine the pattern of spread and evaluate the efficacy of different control régimes.
The threat of rabies being reintroduced into Britain is probably greater now than at any time over the last 60 years. This threat is reviewed with particular regard to the problems that would be posed should rabies be introduced to the high-density fox populations found in many cities in southern England. Computer models can provide a valuable means of understanding the pattern of rabies spread in fox populations and the likely problems of control, so the construction of previous rabies models was reviewed. None were found to be suitable for analysing the particular problems posed by high-density, spatially heterogeneous, urban fox populations. Therefore, a new spatial stochastic simulation model was produced, based on demographic and other data collected during a long-term study on the urban fox population in Bristol, and fox density data collected from a number of cities in southern England. The simulation model was used to analyse the effects of spatial heterogeneity in the fox population on the pattern of rabies spread. Simulations were then used to evaluate the effects of: (i) varying levels of fox control; (ii) changing the size of the control zone; (iii) the onset of the rabies epizooty at different times of the year: and (iv) delay before the commencement of control on the chances of containing the disease. These simulations were run for four cities (Bournemouth and Poole, Bristol, Leicester and the West Midlands conurbation) with different mean fox population densities. It was found that the variance in the monthly velocity of the rabies front was greater for heterogeneous fox populations. In cities with high fox densities, low or moderate levels of control were unsuccessful in containing the disease, but these urban areas had the highest rates of success with the highest levels of control. A three-month delay in the commencement of a rabies control campaign on average reduced the chance of successfully controlling the disease by 10-20%, although this was higher in lower-density fox populations. Rabies outbreaks in the dispersal period were on average 10% less likely to be contained. Increasing the size of the control zone increased the chances of successfully containing the disease, although this effect was density dependent, so the effect was less in low-density fox populations. These results are discussed in relation to the current rabies contingency plans for British urban areas.


[Long-term results of radical lumbar ganglionectomy. Our experience].
We present our experience of 15 patients operated on by lumbar sympathectomies between 1987-1993, to confirm the effective and permanent efficacy of sympathectomy in peripheral vascular disease of the lower limbs. The patients, 9 men and 6 women (age 58-86) presented with rest pain (12), and minimal toe lesions (3). After an eco color-Doppler and angiography of the lower limbs, a radical operative sympathectomy (L2-L5) was performed in all patients. Associated diseases were: ischemic cardiopathy (61.7%), renal failure (25%), diabetic disease (61.7%), carotid stenosis (25%), abdominal aortic aneurysm (12%). In four patients, was performed during the same surgical time, 2 abdominal aortic aneurysm repairs, and 2 aorto-bifemoral bypasses. No patients died, operative morbidity was 12.5% (2 cases). The clinical and instrumental follow-up performed on 6 patients (38.3%) after 3 years, demonstrated in all cases the regression of the rest pain (12 patients) and the healing of the toe lesions (3 diabetic patients). Our results confirm the efficacy of sympathectomy especially when performed in young patients. The small number of diabetic patients in our study made statistical evaluation difficult, but it is generally considered that the results are worse in diabetic patients, because the microvascular lesions in these patients reduce peripheral vasodilatation.


Multifaceted empathy of healthy volunteers after single doses of MDMA: A pooled sample of placebo-controlled studies.
Previous placebo-controlled experimental studies have shown that a single dose of MDMA can increase emotional empathy in the multifaceted empathy test (MET) without affecting cognitive empathy. Although sufficiently powered to detect main effects of MDMA, these studies were generally underpowered to also validly assess contributions of additional parameters, such as sex, drug use history, trait empathy and MDMA or oxytocin plasma concentrations. The present study examined the robustness of the MDMA effect on empathy and investigated the moderating role of these additional parameters. Participants ( n = 118) from six placebo-controlled within-subject studies and two laboratories were included in the present pooled analysis. Empathy (MET), MDMA and oxytocin plasma concentrations were assessed after oral administration of MDMA (single dose, 75 or 125 mg). Trait empathy was assessed using the interpersonal reactivity index. We confirmed that MDMA increased emotional empathy at both doses without affecting cognitive empathy. This MDMA-related increase in empathy was most pronounced during presentation of positive emotions as compared with negative emotions. MDMA-induced empathy enhancement was positively related to MDMA blood concentrations measured before the test, but independent of sex, drug use history and trait empathy. Oxytocin concentrations increased after MDMA administration but were not associated with behavioral effects. The MDMA effects on emotional empathy were stable across laboratories and doses. Sex did not play a moderating role in this effect, and oxytocin levels, trait empathy and drug use history were also unrelated. Acute drug exposure was of significant relevance in the MDMA-induced emotional empathy elevation.


[Age-related characteristics of the regional distribution of total water in the human brain].
With aging there occurred a clear increase of the content of total water in several structures of the brain, most pronounced in the hypothalamus. The content of total water in the grey and white matter showed a reduction in the fronto-caudal direction both in the younger and older age groups though in the old this regularity was less pronounced. In the young the content of total water was higher in the structures of the anterior hypothalamus as compared with the posterior.


A pre-training and self-training approach for biomedical named entity recognition.
Named entity recognition (NER) is a key component of many scientific literature mining tasks, such as information retrieval, information extraction, and question answering; however, many modern approaches require large amounts of labeled training data in order to be effective. This severely limits the effectiveness of NER models in applications where expert annotations are difficult and expensive to obtain. In this work, we explore the effectiveness of transfer learning and semi-supervised self-training to improve the performance of NER models in biomedical settings with very limited labeled data (250-2000 labeled samples). We first pre-train a BiLSTM-CRF and a BERT model on a very large general biomedical NER corpus such as MedMentions or Semantic Medline, and then we fine-tune the model on a more specific target NER task that has very limited training data; finally, we apply semi-supervised self-training using unlabeled data to further boost model performance. We show that in NER tasks that focus on common biomedical entity types such as those in the Unified Medical Language System (UMLS), combining transfer learning with self-training enables a NER model such as a BiLSTM-CRF or BERT to obtain similar performance with the same model trained on 3x-8x the amount of labeled data. We further show that our approach can also boost performance in a low-resource application where entities types are more rare and not specifically covered in UMLS.


Transactivation functions facilitate the disruption of chromatin structure by estrogen receptor derivatives in vivo.
The activation of gene transcription by nuclear receptors is invariably associated with alterations in chromatin structure at hormone-responsive elements of target genes. To identify the molecular functions underlying receptor-mediated chromatin structure alterations we have evaluated the effects of DNA binding and transactivation of estrogen receptor derivatives on the promoter chromatin structure of estrogen-responsive reporter minichromosomes in Saccharomyces cerevisiae. We report here that the DNase I-hypersensitive chromatin structure at the promoter region is not simply a consequence of estrogen receptor binding to estrogen-responsive elements but is greatly enhanced by transactivation functions. These chromatin structure alterations are dependent on the presence of more than one estrogen-responsive element as well as downstream promoter sequences and appear to be correlated with transcriptional competence of the promoter. Our results imply that a disruption of chromatin structure at promoters is associated with the establishment of active transcription complexes. Since RNA polymerase cannot initiate transcription on nucleosomal DNA in vitro (Lorch, Y., Lapointe, J.W., and Kornberg, R.D. (1987) Cell 49, 203-210) this local disruption of chromatin structure may represent a nucleosome-free window, allowing initiation to occur in vivo.


Essential role of a kinesin-like protein in Arabidopsis trichome morphogenesis.
Little is known about how cell shape is controlled. We are using the morphogenesis of trichomes (plant hairs) on the plant Arabidopsis thaliana as a model to study how cell shape is controlled. Wild-type Arabidopsis trichomes are large, single epidermal cells with a stalk and three or four branches, whereas in zwichel (zwi) mutants the trichomes have a shortened stalk and only two branches. To further understand the role of the ZWI gene in trichome morphogenesis we have cloned the wild-type ZWICHEL (ZWI) gene by T-DNA tagging, and report here that it encodes a member of the kinesin superfamily of microtubule motor proteins. Kinesin proteins transport diverse cellular materials in a directional manner along microtubules. Kinesin-like proteins are characterized by a highly conserved "head" region that comprises the motor domain, and a nonconserved "tail" region that is thought to participate in recognition and binding of the appropriate cargo.


Genetic and functional complementation of the HSV1 UL27 gene and gB glycoprotein by simian alpha-herpesvirus homologs.
Utilizing co-transfection of DNA from glycoprotein gB- strain of HSV1 and cloned fragments of several simian alpha-herpesviruses containing the UL26, UL27 (gB glycoprotein), and UL28 gene homologs, replication-competent recombinant viruses were produced. Genetic analysis of one HSV1/SA8 recombinant (HSV1/SgB) demonstrated the presence of SA8 DNA comprising the entire UL27 (gB) gene and parts of the UL28 and UL26 ORFs in an otherwise HSV1 genome. The recombinant was shown to express the SA8 gB and p40 proteins (UL27 & UL26.5 gene products, respectively); all other proteins were indistinguishable from those of HSV1. The recombinant behaved like SA8 in gB-specific virus neutralization and cell surface antibody binding assays, while plaque morphology and replication kinetics were very similar to HSV1. Despite its overwhelming HSV1 genetic constitution, the recombinant displayed a pathogenic phenotype in mice very different from the parental HSV1. While HSV1 produced corneal disease in ocularly infected mice and readily spread to the nervous system. HSV1/SgB was markedly impaired in both respects. These results demonstrate the functional equivalency of the cercopithecine monkey virus gB glycoproteins and genes (including transcriptional regulatory elements) in HSV1, the functional nature of HSV1/SA8 chimeric UL28 and UL26 genes/proteins, and that UL28, gB and/or p40 proteins may effect the pathogenicity of HSV1.


Adherence to Oral Antihyperglycemic Agents Among Older Adults With Mental Disorders and Its Effect on Health Care Costs, Quebec, Canada, 2005-2008.
Nonadherence to oral antihyperglycemic agents (OHAs) leads to an increase in use of health care resources and overall expenditures due to type 2 diabetes and its complications. People with type 2 diabetes are almost twice as likely to have anxiety and depression as the general population. Our aim was to examine health care costs associated with adherence to OHAs and the effect of depression and anxiety disorders on these in older adults with type 2 diabetes. We used data from a representative sample (N = 2,811) of community-dwelling adults in Quebec aged 65 years or older who participated in the Étude sur la Santé des Aînés survey. The final sample consisted of 301 participants who were diagnosed with type 2 diabetes and who were taking OHAs. Total health care costs were calculated as the sum of the costs of hospitalizations and outpatient clinic services. Adherence to OHAs was measured using the medication possession ratio. Depression and anxiety disorders were assessed using criteria from the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition. We also analyzed data by the Charlson Comorbidity Index, age, sex, education, and marital status, using generalized linear models. Nonadherence among people without depression or anxiety was associated with higher total health care costs ($4,477; 95% confidence interval [CI], $3,754-$5,201; P < .001), as was nonadherence among people with depression or anxiety ($11,124; 95% CI, $9,685-$12,562; P < .001). Improving adherence to OHAs among people with type 2 diabetes, particularly those with underlying mental disorders such as depression or anxiety, can decrease health care costs.


Bone mineral content of the femoral neck and shaft: relation between cortical and trabecular bone.
Bone mineral content (BMC) of the femoral neck and shaft was determined with dual photon absorptiometry, using 153Gd. Comparison of BMC with the amount of hydroxyapatite (HA) of in vitro specimen showed correlation coefficients of 0.992 and 0.996 for the femoral neck and shaft respectively. In the femoral neck the amount of cortical bone in a bone section varies from 16% ash weight in the proximal part to 71% in the distal part. Corresponding to the site of BMC measurements, the cortical bone constitutes 57% in the femoral neck and 95% in the femoral shaft. The precision error of measurements of BMC in vivo, expressed as the coefficient of variation for repeated determinations, was 1.4% for the femoral neck and 1.3% for the femoral shaft. In the femoral neck it is possible to distinguish between structures consisting mainly of cortical bone and structures containing mostly trabecular bone. While the cortical bone value decreases only slowly with age in normal women, corresponding to BMC of the femoral shaft, the trabecular bone value decreases rapidly even compared with BMC of the femoral neck. Despite the significant correlation between the values for cortical and trabecular bone a distinction seems essential from a clinical point of view.


Identifying Risk Factors for Osteonecrosis After Talar Fracture.
To identify patient, injury, and treatment factors associated with the development of avascular necrosis (AVN) after talar fractures, with particular interest in modifiable factors. Retrospective chart review. 21 US trauma centers and 1 UK trauma center. Patients with talar neck and/or body fractures from 2008 through 2018 were retrospectively reviewed. Only patients who were at least 18 years of age with fractures of the talar neck or body and minimum 12 months follow-up or earlier diagnosis of AVN were included. Further exclusion criteria included non-operatively treated fractures, pathologic fractures, pantalar dislocations, and fractures treated with primary arthrodesis or primary amputation. The primary outcome measure was development of AVN. Infection, nonunion, and arthritis were secondary outcomes. In total, 798 patients (409 men; 389 women; age 18-81 years, average 38.6 years) with 798 (532 right; 264 left) fractures were included and were classified as Hawkins I (51), IIA (71), IIB (113), III (158), IV (40), neck plus body (177), and body (188). In total, 336 of 798 developed AVN (42%), more commonly after any neck fracture (47.0%) versus isolated body fracture (26.1%, P < 0.001). More severe Hawkins classification, combined neck and body fractures, body mass index, tobacco smoking, right-sided fractures, open fracture, dual anteromedial and anterolateral surgical approaches, and associated medial malleolus fracture were associated with AVN ( P < 0.05). After multivariate regression, fracture type, tobacco smoking, open fractures, dual approaches, age, and body mass index remained significant ( P < 0.05). Excluding late cases (>7 days), time to joint reduction for Hawkins type IIB-IV neck injuries was no different for those who developed AVN or not. AVN rates for reduction of dislocations within 6 hours of injury versus >6 hours were 48.8% and 57.5%, respectively. Complications included 60 (7.5%) infections and 70 (8.8%) nonunions. Forty-two percent of all talar fracture patients developed AVN, with talar neck fractures, more displaced fractures, and open injuries having higher rates. Injury-related factors are most prognostic of AVN risk. Surgical technique to emphasize anatomic reduction, without iatrogenic damage to remaining blood supply appears to be prudent. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.


Can Thermodynamic Behavior of Alice's Particle Affect Bob's Particle?
We propose an experiment to investigate the possibility of long-distance thermodynamic relationships between two entangled particles. We consider a pair of spin-[Formula: see text] particles prepared in an entangled singlet state in which one particle is sent to Alice and the other to her distant mate Bob, who are spatially separated. Our proposed experiment consists of three different setups: First, both particles are coupled to two heat baths with various temperatures. In the second setup, only Alice's particle is coupled to a heat bath and finally, in the last setup, only Bob's particle is coupled to a heat bath. We study the evolution of an open quantum system using the first law of thermodynamics based on the concepts of ergotropy, adiabatic work, and operational heat, in a quantum fashion. We analyze and compare ergotropy and heat transfer in three setups. Our results show that the heat transfer for each entangled particle is not independent of the thermalization process that occurs for the other one. We prove that the existence of quantum correlations affects the thermodynamic behavior of distant particles in an entangled state.


Processing of herpes simplex virus proteins and evidence that translation of thymidine kinase mRNA is initiated at three separate AUG codons.
The role which post-translational modification plays in the genesis of herpes simplex virus-induced polypeptides was investigated. Two-dimensional gel electrophoresis was used to identify those polypeptides (i) synthesized in vitro, (ii) labeled in vivo during a pulse, and (iii) labeled after a chase. Excluding glycoproteins, we detected 36 precursor or short-lived polypeptides, 8 polypeptides which were generated by post-translational modification, 46 polypeptides which were apparently not modified after synthesis, and 19 polypeptides which were either transient intermediates or not modified. Comparison of polypeptides synthesized in vitro and during an in vivo pulse showed that translation in vitro resembles quite closely translation in vivo and that amounts of protein synthesized in vivo are determined largely by the levels of mRNA. This analysis provided the basis for an investigation of the suggestion (C.M. Preston and D.J. McGeoch, J. Virol. 38:593-605, 1981) that the two polypeptides of apparent molecular weights of 43,000 (VI 43) and 39,000 (VI 39) encoded by the herpes simplex virus type 1 thymidine kinase gene are translated from a single mRNA by two in-phase initiation codons. Hybrid arrest was used to identify in vitro translation products encoded by the thymidine kinase gene. Two-dimensional gel electrophoresis showed that VI 39 was more acidic than VI 43, consistent with the predicted amino acid composition of a polypeptide whose synthesis was initiated at the second AUG codon, located 135 bases downstream from the first. Furthermore, two-dimensional gels revealed a third polypeptide whose synthesis was arrested by the same fragment. Its pI and apparent molecular weight (38,000) were compatible with initiation of translation at a third AUG codon an additional 42 bases downstream. Our findings provide strong evidence that downstream initiation codons within the thymidine kinase mRNA are used.


How we approach sharing child-caregiver PRO disagreement.
Researchers use patient-reported outcomes (PRO) to capture the patient experience, and in pediatrics, parent report of symptom and function often accompanies the child's assessment. Children with cancer and their family caregivers frequently evaluate symptom burden and functional status differently. Child-caregiver PRO disagreement often worries pediatric oncology clinicians, who do not know how to best approach sharing it with families. Openly discussing differences in symptom and functional status reporting is a crucial element of supporting families and can improve family harmony throughout the child's illness journey. This paper offers strategies and language for communicating with families about PRO disagreement.


Carbapenem-Resistant Enterobacterales Infection After Massive Blast Injury: Use of Cefiderocol Based Combination Therapy.
A military soldier sustained a blast injury in Afghanistan, resulting in amputations and hemipelvectomy. He developed New Delhi metallo-beta-lactamase-producing E. coli bacteremia, soft-tissue infection, and sacral osteomyelitis. These organisms are being increasingly discovered in different communities around the world. He was successfully treated with tigecycline and cefiderocol. Cefiderocol is a novel siderophore-based cephalosporine developed to treat serious infections, including those caused by carbapenem-resistant Enterobacterales.


Identification and characterization of endoplasmic reticulum-associated degradation proteins differentially affected by endoplasmic reticulum stress.
The disposal of misfolded proteins from the lumen of the endoplasmic reticulum (ER) is one of the quality control mechanisms present in the protein secretory pathway. Through ER-associated degradation, misfolded substrates are targeted to the cytosol where they are degraded by the proteasome. We have identified four maize (Zea mays) Der1-like genes (Zm Derlins) that encode homologs of Der1p, a yeast (Saccharomyces cerevisiae) protein implicated in ER-associated degradation. Zm Derlins are capable of functionally complementing a yeast Der1 deletion mutant. Such complementation indicates that the Der1p function is conserved among species. Zm Derlin genes are expressed at low levels throughout the plant, but appear prevalent in tissues with high activity of secretory protein accumulation, including developing endosperm cells. Expression of three of the four Zm Derlin genes increases during ER stress, with Zm Derlin1-1 showing the strongest induction. Subcellular fractionation experiments localized Zm Derlin proteins to the membrane fraction of microsomes. In maize endosperm, Zm Derlin proteins were found primarily associated with ER-derived protein bodies regardless of the presence of an ER stress response.


High-performance energy-storage architectures from carbon nanotubes and nanocrystal building blocks.
High-performance energy-storage architectures are fabricated by forming conformal coatings of active nanocrystal building blocks on preformed carbon nanotube conductive scaffolds for lithium ion electrodes. This unique structure offers effective pathways for charge transport, high active-material loading, structure robustness, and flexibility. This general approach enables the fabrication of a new family of high-performance architectures for energy storage and many other applications.