Extreme hypertriglyceridemia, pseudohyponatremia, and pseudoacidosis in a neonate with lipoprotein lipase deficiency due to segmental uniparental disomy.
Extreme hypertriglyceridemia is rare in the neonatal period. We report a neonate with lipoprotein lipase (LPL) deficiency who presented with diagnostic and management conundrum. A full-term 36-day-old female was noted to have "Pepto-Bismol like" blood when repeating a newborn screening. The initial plasma triglyceride level was 24,318 mg/dL. The laboratory tests revealed serum bicarbonate level of <5 mmol/L, sodium of 127 mmol/L, and severe anemia. There were no signs of acute distress. The point of care capillary blood testing, however, demonstrated normal serum pH (7.2), bicarbonate (25.4 mmol/L), and sodium (139 mmol/L). The patient had mild elevation of serum lactic acid and no ketonuria. A diagnosis of type I hyperlipoproteinemia was made. Oral feeding was stopped, and the infant received intravenous fluids for the next 7 days resulting in lowering of serum triglyceride levels to 1016 mg/dL. Oral feeding was initiated with an amino acid-rich formula to which medium chain triglycerides were slowly added, while maintaining the total fat content to <15% of total daily energy. Sequencing of the LPL gene revealed a homozygous c.644G>A, p.(Gly215Glu) mutation. Subsequent analysis of the parental samples revealed that only the father, but not the mother, was a heterozygous carrier of the same mutation. Analysis of 18 informative microsatellite markers on chromosome 8 revealed paternal segmental uniparental disomy with partial absence of the maternal chromosome 8p, confirmed by single-nucleotide polymorphism microarray. We conclude that besides pseudohyponatremia, extreme hypertriglyceridemia can rarely present as pseudoacidosis and uniparental disomy can be an underlying mechanism for autosomal recessive diseases such as LPL deficiency.


A >or=1 log rise in RQ-PCR transcript levels defines molecular relapse in core binding factor acute myeloid leukemia and predicts subsequent morphologic relapse.
Core binding factor acute myeloid leukemia (CBF AML), with t(8;21)(q22;q22), inv(16)(p13q22) or t(16;16)(p13;q22) and the associated fusion gene transcripts AML1/ETO or CBFbeta/MYH11, has a favourable clinical prognosis although significant numbers of patients still suffer relapse. We examined the prognostic utility of serial bone marrow minimal residual disease (MRD) monitoring by RQ-PCR in a cohort of patients with CBF AML with long term clinical follow-up. Twenty-nine patients were evaluated with a median follow of 34 months. Twelve relapses occurred at a median of 11 months (range 4 - 17) from diagnosis. RQ-PCR levels at diagnosis, post-induction chemotherapy and post-consolidation were not predictive of outcome. However, a >or=1 log(10) rise at any stage in transcript level relative to the level from a remission bone marrow sample correlated with inferior leukemia free survival (LFS) and imminent morphologic relapse (hazard ratio 8.6). Relapses occurred a median of 60 days (range 45 - 272) after a log(10) rise. A >or=1 log(10) rise in transcript levels strongly predicts subsequent morphologic relapse in CBF AML and therefore defines molecular relapse. Our data support a simple RQ-PCR model for prediction of impending relapse which has the potential for widespread clinical applicability. Prospective identification of high risk patients will enable clinical trials to assess the efficacy of treatment initiated at molecular relapse.


Structure of HAP1-PC7 bound to DNA: implications for DNA recognition and allosteric effects of DNA-binding on transcriptional activation.
HAP1 is a transcription factor in yeast whose DNA-binding domain has been implicated in directly affecting transcriptional activation. Two separate mutations in the DNA-binding domain, S63G (HAP1-PC7) and S63R (HAP1-18), retain wild-type binding affinity. However, HAP1-PC7 is transcriptionally silent while HAP1-18 shows highly elevated levels of transcription. We have determined the X-ray crystal structure of the DNA-binding domain of HAP1-PC7 bound to its DNA target, UAS(CYC7), and compared it to the previously solved HAP1-wt and HAP1-18 complexes to UAS(CYC7). Additionally, we have quantitatively compared the DNA-binding affinity and specificity of the HAP1-PC7, HAP1-18 and HAP1-wt DNA-binding domains. We show that, although the DNA-binding domains of these three proteins bind UAS(CYC7) with comparable affinity and specificity, the protein-DNA interactions are dramatically different between the three complexes. Conserved protein-DNA interactions are largely restricted to an internal DNA sequence that excludes one of the two conserved DNA half-sites of UAS(CYC7) suggesting a mode of recognition distinct from other HAP1 family members. Alternative protein-DNA interactions result in divergent DNA configurations between the three complexes. These results suggest that the differential transcriptional activities of the HAP1, HAP1-18 and HAP1-PC7 proteins are due, at least in part, to alternative protein-DNA contacts, and implies that HAP1-DNA interactions have direct allosteric effects on transcriptional activation.


Evidence-Based Medicine of Traumatic Thoracolumbar Burst Fractures: A Systematic Review of Operative Management across 20 Years.
Study Design Systematic literature review. Objective The management of traumatic thoracolumbar burst fractures (TLBF) remains challenging, and analyzing the levels of evidence (LOEs) for treatment practices can reform the decision-making process. However, no review has yet evaluated the operative management of traumatic thoracolumbar burst fractures with particular attention placed on LOE from an established methodology. The objective of the present study was to characterize the literature evidence for TLBF, specifically for operative management. Methods A comprehensive search of the English literature over the past 20 years was conducted using PubMed (MEDLINE). The inclusion criteria consisted of (1) traumatic burst fractures (2) in the thoracic or lumbar spine. Exclusion criteria included (1) osteoporotic burst fractures, (2) pathologic burst fractures, (3) cervical fractures, (4) biomechanical studies or those involving cadavers, and (5) computer-based studies. Studies were assigned an LOE and those meeting level 1 or 2 were included. Results From 1,138 abstracts, 272 studies met the criteria. Twenty-three studies (8.5%) met level 1 (n = 4, 1.5%) or 2 (n = 19, 7.0%) criteria. All 23 studies were reported. Conclusions The literature contains a high LOE to support the operative management of traumatic thoracolumbar burst fractures. For patients who are neurologically intact, a high LOE demonstrated similar functional outcomes, lower complication rates, and less costs with conservative management when compared with surgical management. There is a high LOE for short- or long-segment pedicle instrumentation without fusion and less invasive (percutaneous and paraspinal) approaches. Furthermore, the posterior approaches are associated with lower complications as opposed to the anterior or combined approaches.


Short- and long-term survival after cardiopulmonary resuscitation.
The objective was to evaluate the effect of patient characteristics and other factors on cardiopulmonary resuscitation (CPR) survival, hospital discharge survival and function, and long-term survival. All patients 18 years and older experiencing in-hospital CPR from December 1983 through November 1991 at Marshfield Medical Center (Marshfield Clinic and adjoining St Joseph's Hospital), Marshfield, Wis, were selected. We performed a retrospective medical record review and augmented these data with updated vital status information. Cardiopulmonary resuscitation survival, hospital discharge survival and function, and long-term survival. Of 948 admissions during which CPR was performed, 61.2% of patients survived the arrest and 32.2% survived to hospital discharge. Mechanism of arrest was the most important variable associated with hospital discharge. Patients with pulseless electrical activity had the worst chance of hospital discharge, followed by those with asystole and bradycardia. Follow-up information was available for 298 patients who survived to discharge. One year after hospital discharge, 24.5% of patients, regardless of age, had died. Survival was 18.5% at 7 years in those 70 years or older, compared with 45.4% in those aged 18 to 69 years. Heart rhythm at the time of arrest strongly influenced long-term survival. Bradyarrhythmias produced a nearly 2-fold increased mortality risk compared with normal sinus rhythm. Survival until hospital discharge after CPR at our institution during an 8-year period was higher than previously reported for other institutions. Long-term survival after discharge was equal to or higher than reported estimates from other institutions. Hospital admission practices and selection of patients receiving CPR may account for these findings.


An adaptive decision-making system supported on user preference predictions for human-robot interactive communication.
Adapting to dynamic environments is essential for artificial agents, especially those aiming to communicate with people interactively. In this context, a social robot that adapts its behaviour to different users and proactively suggests their favourite activities may produce a more successful interaction. In this work, we describe how the autonomous decision-making system embedded in our social robot Mini can produce a personalised interactive communication experience by considering the preferences of the user the robot interacts with. We compared the performance of Top Label as Class and Ranking by Pairwise Comparison, two promising algorithms in the area, to find the one that best predicts the user preferences. Although both algorithms provide robust results in preference prediction, we decided to integrate Ranking by Pairwise Comparison since it provides better estimations. The method proposed in this contribution allows the autonomous decision-making system of the robot to work on different modes, balancing activity exploration with the selection of the favourite entertaining activities. The operation of the preference learning system is shown in three real case studies where the decision-making system works differently depending on the user the robot is facing. Then, we conducted a human-robot interaction experiment to investigate whether the robot users perceive the personalised selection of activities more appropriate than selecting the activities at random. The results show how the study participants found the personalised activity selection more appropriate, improving their likeability towards the robot and how intelligent they perceive the system. query Please check the edit made in the article title.


A survey of inpatient practitioner knowledge of penicillin allergy at 2 community teaching hospitals.
The negative effect of the penicillin allergy label on antibiotic use and patient outcomes has brought to light the need for thorough penicillin allergy assessments and heightened practitioner education. To evaluate practitioner knowledge of penicillin allergy and the clinical approach to the patients with penicillin allergy. An electronic survey was distributed to attending physicians, residents, pharmacists, nurse practitioners, and physician assistants practicing adult inpatient medicine at 2 community-based teaching hospitals from February to April 2016. A total of 276 (39%) of 716 practitioners completed surveys were analyzed. Most respondents were attending physicians (45%) with more than 10 years of experience (53%). Approximately half of the respondents indicated that they were unfamiliar with the rate of cross-reactivity between penicillin and cephalosporin (46%), carbapenem (42%), and monobactam (48%) antibiotics. When evaluating the role of penicillin skin testing and temporary induction of drug tolerance in the case vignettes, only 41% and 19% of respondents appropriately considered these options as the leading antibiotic management plan, respectively. Despite acknowledging the need for allergy/immunology consultation in clinical scenarios, 86% of respondents indicated that they never consult an allergist or immunologist or do so only once per year. Overall, pharmacists had a better understanding of the natural history of penicillin allergy and antibiotic cross-reactivity (P < .05). There is an overall limited understanding of the management of patients with a history of penicillin allergy in the hospital setting, where collaborative efforts between allergy and nonallergy health care practitioners are sparse. The expansion of a multidisciplinary approach may optimize antimicrobial prescribing in this subset of patients.


Migration from packaging materials into foodstuffs--a need for more fundamental information.
During recent years considerable legislative attention has been focused on food packaging materials, especially plastics, and in a number of countries extensive legislation has been formulated. Such legislation often takes the form of a positive list of permitted substances accompanied either by compositional limits or migration limits in foods or stimulant liquids. In the UK this approach has not been followed owing to the general lack of fundamental information on which to base such a system. Instead, the UK has opted for a basic legislative framework supported by informal controls which rely to a large extent on close co-operation between Industry and Government. It is recognized, however, that in future years there is likely to be a move towards more extensive legislation on packaging materials in the UK, particularly as a result of the EEC's harmonization programme. It is imperative that any future legislation is placed on a sound scientific footing and affords adequate protection for the consumer. The Government of the UK is, therefore, currently sponsoring a number of studies aimed at providing this necessary basic information.


Cognitive status and future risk of frailty in older Mexican Americans.
Because cognitive impairment and frailty share common risk factors (eg, high proinflammatory cytokines), we examined whether poor cognition predicts subsequent risk of frailty in initially nonfrail Mexican Americans aged 67 years and older. Frailty was defined as meeting one or more of the following components: (a) unintentional weight loss of >10 pounds, (b) weakness, (c) self-reported exhaustion, and (d) slow walking speed. Sociodemographic factors, Mini-Mental State Examination, medical conditions (stroke, heart attack, diabetes, arthritis, cancer, and hypertension), and depressive symptoms were obtained. Main outcome measure was risk of becoming frail over 10 years. Out of 942 participants who were nonfrail at baseline (1995-1996), 57.8% were women and the mean age was 73.7 years (SD = 5.3). In general estimation equation models testing the relationship between Mini-Mental State Examination (<21 vs. ≥21) and the risk of becoming frail over a 10-year period, there was a significant association (odds ratio = 1.09, 95% confidence interval = 1.00-1.19; p = .0310)] between the cognition-by-time interaction and odds of becoming prefrail or frail over time. This association was independent of age, sex, marital status, education, time, and medical conditions, indicating that nonfrail participants with poor cognition had a 9% odds per year of becoming frail over time compared with those with good cognition. Low Mini-Mental State Examination score was independently associated with increased risk of frailty over a 10-year period in older Mexican Americans. Low Mini-Mental State Examination score may be an early marker for future risk of frailty.


Estrogen induction of VLDLy assembly in egg-laying hens.
The yolk of a 60-g chicken egg contains 6 g of triacylglycerols transported to the oocyte from the liver of the laying hen in apolipoprotein (apo) B-containing particles. With the onset of egg production, estrogen shifts hepatocytic lipoprotein production from generic VLDL to VLDLy (yolk targeted). These VLDLy are triacylglycerol-rich particles; they are reduced in size by one half, are resistant to lipoprotein lipase and are taken up intact by oocyte receptors. The VLDLy pathway for apoB provides sufficient energy for the caloric requirements of chick development. VLDLy size reduction occurs in spite of surplus liver triacylglycerols and is necessary for VLDL particles to pass through the granulosa basal lamina and reach the receptors located on the oocyte surface. New ultrastructural data show that some proximal tubule cells of bird kidney secrete generic VLDL, perhaps providing energy and other VLDL-associated nutrients to tissues bypassed by VLDLy. Birds are an apoB100-only species, providing a natural in vivo model with which to investigate mechanisms of apoB100 VLDL assembly. Preliminary studies of liver lipoprotein assembly intermediates isolated from the biosynthetic membranes (endoplasmic reticulum) of the laying hen are consistent with the presence of both putative first- and second-step precursor particles of VLDLy. These findings suggest that the two-step mechanism of apoB core lipidation is an ancient development in apoB biology, handed down to mammals from oviparous ancestors.


Study of microdosimetric energy deposition patterns in tissue-equivalent medium due to low-energy neutron fields using a graphite-walled proportional counter.
To improve radiation protection dosimetry for low-energy neutron fields encountered in nuclear power reactor environments, there is increasing interest in modeling neutron energy deposition in metrological instruments such as tissue-equivalent proportional counters (TEPCs). Along with these computational developments, there is also a need for experimental data with which to benchmark and test the results obtained from the modeling methods developed. The experimental work described in this paper is a study of the energy deposition in tissue-equivalent (TE) medium using an in-house built graphite-walled proportional counter (GPC) filled with TE gas. The GPC is a simple model of a standard TEPC because the response of the counter at these energies is almost entirely due to the neutron interactions in the sensitive volume of the counter. Energy deposition in tissue spheres of diameter 1, 2, 4 and 8 µm was measured in low-energy neutron fields below 500 keV. We have observed a continuously increasing trend in microdosimetric averages with an increase in neutron energy. The values of these averages decrease as we increase the simulated diameter at a given neutron energy. A similar trend for these microdosimetric averages has been observed for standard TEPCs and the Rossi-type, TE, spherical wall-less counter filled with propane-based TE gas in the same energy range. This implies that at the microdosimetric level, in the neutron energy range we employed in this study, the pattern of average energy deposited by starter and insider proton recoil events in the gas is similar to those generated cumulatively by crosser and stopper events originating from the counter wall plus starter and insider recoil events originating in the sensitive volume of a TEPC.


Selective and site-specific mobilization of dermal dendritic cells and Langerhans cells by Th1- and Th2-polarizing adjuvants.
Dendritic cells (DCs) initiate and polarize adaptive immune responses toward varying functional outcomes. By means of intravital two-photon microscopy, we report that dermal dendritic cells (DDCs) and Langerhans cells (LCs) are differentially mobilized during contact sensitization and by adjuvants such as unmethylated CpG oligonucleotide (CpG) and LPS that induce T helper type 1 (Th1) responses, or papain that induces T helper type 2 (Th2) responses. In ear pinna, contact sensitization, CpG, LPS, and papain all mobilized DDCs in three distinct phases: increased motility and dendritic probing, directed migration, and entry into lymphatic vessels. During the same treatments, the adjacent LCs in ear pinna remained immotile over a 48-hr period of observation. In contrast, footpads lacked DDCs and Th1-polarizing adjuvants selectively induced a delayed mobilization of LCs after 48 hr. Th1 polarization of CD4(+) T cells was independent of the immunization site, whereas ear immunization favored Th2 polarization, correlating with site-specific DC distribution and dynamics. Our results provide an initial description of peripheral DC dynamics in response to adjuvants and imply that LC mobilization enhances a Th1 response and is not sufficient to trigger a Th2 response, whereas mobilization of DDCs alone is sufficient to trigger T-cell proliferation and to polarize initial T-cell activation toward a Th2 response.


Identification of a FUS splicing mutation in a large family with amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease characterized by the degeneration of upper and lower motor neurons. Genetic studies have led, thus far, to the identification of 12 loci and 9 genes for familial ALS (FALS). Although the distribution and impact of superoxide dismutase 1 mutations has been extensively examined for over a decade, the recently identified FALS-associated FUS gene has been less studied. Therefore, we set out to screen our collection of FALS cases for FUS mutations. All 15 exons of FUS were amplified and sequenced in 154 unrelated FALS cases and 475 ethnically matched healthy individuals. One substitution located in the acceptor splice site of intron 14 was identified in all affected members of a large family, causing the skipping of the last 13 amino acids of the protein and the translation of 7 novel amino acids, resulting from the new translation of a part of the 3' untranslated region. Our study identified a new splicing mutation in the highly conserved C-terminal of the FUS protein. Thus far most FUS mutations are missenses, and our findings, combined with those of others, confirm the importance of the C-terminal portion of the protein, adding additional support for FUS mutations having a critical role in ALS.


Comorbidities of pediatric systemic lupus erythematosus: A 6-year nationwide population-based study.
Systemic lupus erythematous (SLE) is a systemic and complex disease that can involve multiple organs. To clarify the risk of developing associated comorbidities after a diagnosis of SLE in children, we used the National Health Insurance Research Database (NHIRD) in Taiwan to investigate diseases experienced in these patients. This is the first nationwide population-based study of the comorbidities of pediatric SLE patients. The study was based on data from the NHIRD in Taiwan. Children were enrolled who were below the age of 18 years and whose disease corresponded to the International Classification of Disease, Ninth Revision Clinical Modification (ICD-9-CM) diagnostic code of 710.0 (SLE). The comorbidities associated with SLE were defined by the ICD-9-CM codes of diseases that presented after the SLE diagnosis. We analyzed the common diseases in SLE patients and compared the frequency of these diseases between pediatric SLE patients and the non-SLE population. From January 1, 2003 to December 31, 2008, we enrolled 904 SLE patients (774 females, 130 males). Infection (86.36%) was the most common comorbidity in pediatric SLE. Other comorbidities were musculoskeletal diseases (16.7%), cardiovascular diseases (16.37%), ocular diseases (10.73%), and renal diseases (6.75%). Children with SLE had a higher risk of heart failure, hypertension, osteoporosis, cataracts, glaucoma, dyslipidemia, seizures, encephalopathy, and malignant changes, compared to non-SLE populations. The population-based cohort demonstrated several systemic and/or chronic diseases in pediatric SLE patients in Taiwan. Children with SLE were more susceptible to these diseases, including malignancy, compared to the non-SLE population.


Numb promotes cell proliferation and correlates with poor prognosis in hepatocellular carcinoma.
Numb is an evolutionary conserved protein that plays critical roles in cell fate determination, cell adhesion, cell migration and a number of signaling pathways, but evidence for a substantial involvement of Numb in HCC has remained unclear. The present study was aimed to investigate the clinical and prognostic significance of Numb and its role in hepatocellular carcinoma (HCC). The expression of Numb was detected in 107 cases of clinical paraffin-embedded hepatocellular carcinoma tissues,5 matched paris of fresh tissues and six hepatocellular cell lines by immunohistochemistry with clinicopathological analyses,RT-PCR or Western blot. Moreover, loss of function and gain of function assays were performed to evaluate the effect of Numb on cell proliferation in vitro. We found that Numb was obviously up-regulated in HCC tissues and cell lines (p<0.05). The Numb up-regulation correlated significantly with poor prognosis, and Numb status was identified as an independent prognostic factor. Over-expression of Numb increased proliferation in SMMC-7721 and BEL-7402 cells, while knock-down of Numb showed the opposite effect. Our study indicates that Numb up-regulation significantly correlates with cell proliferation and poor prognosis in hepatocellular carcinoma patients. It may be a useful biomarker for therapeutic strategy in hepatocellular carcinoma treatment.


High Surface Area Tunnels in Hexagonal WO₃.
High surface area in h-WO3 has been verified from the intracrystalline tunnels. This bottom-up approach differs from conventional templating-type methods. The 3.67 Å diameter tunnels are characterized by low-pressure CO2 adsorption isotherms with nonlocal density functional theory fitting, transmission electron microscopy, and thermal gravimetric analysis. These open and rigid tunnels absorb H(+) and Li(+), but not Na(+) in aqueous electrolytes without inducing a phase transformation, accessing both internal and external active sites. Moreover, these tunnel structures demonstrate high specific pseudocapacitance and good stability in an H2SO4 aqueous electrolyte. Thus, the high surface area created from 3.67 Å diameter tunnels in h-WO3 shows potential applications in electrochemical energy storage, selective ion transfer, and selective gas adsorption.


Hemangiopericytoma of supraglottis: A rare case report and review of literature.
In 1942, Stout and Murray first used the term hemangiopericytoma to describe a tumor which is distinguished histologically from other types of vascular neoplasm characterized by proliferation of pericytes. It is a rare neoplasm that was originally described as a vascular tumor derived from the pericytes. They account for 2%-3% of all soft tissue sarcomas in humans and they occur mainly in the musculoskeletal system. About 15%-30% of all hemangiopericytomas occur in the head and neck region. Hemangiopericytoma of supraglottis is very rare neoplasm with only nine cases reported in literature and ours is the tenth case overall and first case in pediatric age group. Herein, we are presenting an extremely rare case report of hemangiopericytoma of supraglottis in a 6-year-old male child who presented with stridor followed by which tracheostomy was done. Later, the patient was treated initially with radiotherapy followed by surgery, i.e., laryngectomy in view of residual disease postcurative radiotherapy. Hence, hemangiopericytoma is a very rare tumor overall and can present in pediatric age group and can be one most important differential diagnosis because many patients in this age group, stridor most commonly occurs due to the infectious causes such as influenza virus and diphtheria-induced croup, i.e., laryngotracheobronchitis.


[Inhibition of proliferation by retinoic acid on adult T cell leukemia cells].
We observed the effects of the retinoic acid (13-cis retinoic acid; 13-cis RA, and all-trans retinoic acid; ATRA) for the cell growth and the expression of CD 25 on peripheral blood mononuclear cells (PBMC) from 17 patients with adult T cell leukemia (ATL). Fourteen had acute type, 1 had chronic type, and 2 had smoldering type of ATL. We divided those patient into 3 groups (hyper-sensitive, sensitive and resistant group) by determined with reduction rate of [3H]-thymidine incorporation obtained before and after treatment with 13 -cis RA or ATRA respectively. Growth inhibition was not observed in normal PBMC by 13 -cis RA or ATRA. However, no down-regulation of CD 25 expression was observed on PBMC in all patients and normal individuals after treatment with 13-cis RA or ATRA. In the aspect of growth inhibition on PBMC in ATL patients, we tried to clarify the mechanism of the phenomenon. In agarose gel electrophoresis, extracted genomic DNA from retinoic acid treated PBMC in hyper-sensitive and sensitive ATL patients showed multimer DNA fragmentation pattern. On the other hand, genomic DNA from PBMC after treatment with retinoic acid in resistant ATL patients and normal individuals showed high molecular DNA pattern without fragmentation. Taken together, it is suggested that retinoic acid could induce growth inhibition of PBMC in some ATL patients resulting in DNA fragmentation, apoptosis. We deeply consider that retinoic acid may be an useful agent for ATL patients in clinical aspect.


Tumor necrosis factor (TNF)-α, soluble TNF receptors and endometrial cancer risk: the EPIC study.
Chronic inflammation has been hypothesized to play a role in endometrial cancer development. Tumor necrosis factor-α (TNF-α), one of the major pro-inflammatory cytokines, has also been implicated in endometrial physiology. We conducted a case-control study nested within the European prospective investigation into cancer and nutrition (EPIC) to examine the association of TNF-α and its two soluble receptors (sTNFR1 and sTNFR2) with endometrial cancer risk. Two-hundred-seventy cases and 518 matched controls were analyzed using conditional logistic regression. All statistical tests were two-sided. We observed an increased risk of endometrial cancer among women in the highest versus lowest quartile of TNF-α (odds ratio [OR]: 1.73, 95% CI: 1.09-2.73, P(trend) = 0.01), sTNFR1 (OR: 1.68, 95% CI: 0.99-2.86, P(trend) = 0.07) and sTNFR2 (OR: 1.53, 95%CI: 0.92-2.55, P(trend) = 0.03) after adjustment for body-mass-index, parity, age at menopause and previous postmenopausal hormone therapy use. Further adjustments for estrogens and C-peptide had minor effect on risk estimates. Our data show that elevated prediagnostic concentrations of TNF-α and its soluble receptors are related to a higher risk of endometrial cancer, particularly strong in women diagnosed within 2 years of blood donation. This is the first study of its kind and therefore deserves replication in further prospective studies.


[Congenital and acquired hemiplegia in children: epileptic crisis and eletrencephalografic signs].
The aim of the study is to compare the presence or absence of seizures and their relationship with the electroencephalographic findings in children with congenital and acquired hemiplegia. 35 children with congenital and acquired hemiplegia were studied by clinical and electroencephalographic features. We analyzed the frequency and seizures severity and their relationship between the background activity and epileptogenic discharges in the electroencephalogram (EEG). From the 35 children, 26 (74.6%) presented congenital hemiplegia and 9 (25.6%) acquired one. Seventeen (48.5%) had right hemiplegia and 18 (51.4%) left one. It was find 25 cases (71.4%) with seizures and 10 cases without seizures. All the patients with seizures presented abnormal EEG activity that was bilateral in 44% of the cases. The patient without seizures presented abnormal background activity in 90% of cases and only 10% were bilateral. Concerning epileptogenic activity, it was find 78% of patients with seizures and 68% of patients without seizures. There was statistical significance related to abnormal background activity and uncontrolled epileptic seizures. The bilateral disorganization of the background activity in the EEG is related with uncontrolled seizures. The background activity well organized in the opposite side of lesion has a good prognosis to control seizures. The epileptogenic focal activity isn't always related with the presence of seizures.


Synergism between etoposide and 17-AAG in leukemia cells: critical roles for Hsp90, FLT3, topoisomerase II, Chk1, and Rad51.
DNA-damaging agents, such as etoposide, while clinically useful in leukemia therapy, are limited by DNA repair pathways that are not well understood. 17-(Allylamino)-17-demethoxygeldanamycin (17-AAG), an inhibitor of the molecular chaperone heat shock protein 90 (Hsp90), inhibits growth and induces apoptosis in FLT3(+) leukemia cells. In this study, we evaluated the effects of etoposide and 17-AAG in leukemia cells and the roles of Hsp90, FMS-like tyrosine kinase 3 (FLT3), checkpoint kinase 1 (Chk1), Rad51, and topoisomerase II in this inhibition. The single and combined effects of 17-AAG and etoposide and the mechanism of these effects were evaluated. FLT3 and the DNA repair-related proteins, Chk1 and Rad51, were studied in small interfering RNA (siRNA)-induced cell growth inhibition experiments in human leukemia cells with wild-type or mutated FLT3. We found that etoposide and the Hsp90/FLT3 inhibitor 17-AAG, had synergistic inhibitory effects on FLT3(+) MLL-fusion gene leukemia cells. Cells with an internal tandem duplication (ITD) FLT3 (Molm13 and MV4;11) were more sensitive to etoposide/17-AAG than leukemias with wild-type FLT3 (HPB-Null and RS4;11). A critical role for FLT3 was shown in experiments with FLT3 ligand and siRNA targeted to FLT3. An important role for topoisomerase II and the DNA repair-related proteins, Chk1 and Rad51, in the synergistic effects was suggested from the results. The repair of potentially lethal DNA damage by etoposide in leukemia cells is dependent on intact and functioning FLT3 especially leukemias with ITD-FLT3. These data suggest a rational therapeutic strategy for FLT3(+) leukemias that combines etoposide or other DNA-damaging agents with Hsp90/FLT3 inhibitors such as 17-AAG.


Decoupling the Contributions of ZnO and Silica in the Characterization of Industrially-Mixed Filled Rubbers by Combining Small Angle Neutron and X-Ray Scattering.
Scattering techniques with neutrons and X-rays are powerful methods for the investigation of the hierarchical structure of reinforcing fillers in rubber matrices. However, when using only X-ray scattering, the independent determination of the filler response itself sometimes remains an issue because of a strong parasitic contribution of the ZnO catalyst and activator in the vulcanization process. Microscopic characterization of filler-rubber mixtures even with only catalytic amounts of ZnO is, therefore, inevitably complex. Here, we present a study of silica aggregates dispersed in an SBR rubber in the presence of the catalyst and show that accurate partial structure factors of both components can be determined separately from the combination of the two scattering probes, neutrons, and X-rays. A unique separation of the silica filler scattering function devoid of parasitic catalyst scattering becomes possible. From the combined analysis, the catalyst contribution is determined as well and results to be prominent in the correction scheme. The experimental nano-structure of the ZnO after the mixing process as the by-product of the scattering decomposition was found also to be affected by the presence or absence of silica in the rubber mixture, correlated with the shear forces in the mixing and milling processes during sample preparation. The presented method is well suited for studies of novel dual filler systems.


Initiation and execution of lipotoxic ER stress in pancreatic beta-cells.
Free fatty acids (FFA) cause apoptosis of pancreatic beta-cells and might contribute to beta-cell loss in type 2 diabetes via the induction of endoplasmic reticulum (ER) stress. We studied here the molecular mechanisms implicated in FFA-induced ER stress initiation and apoptosis in INS-1E cells, FACS-purified primary beta-cells and human islets exposed to oleate and/or palmitate. Treatment with saturated and/or unsaturated FFA led to differential ER stress signaling. Palmitate induced more apoptosis and markedly activated the IRE1, PERK and ATF6 pathways, owing to a sustained depletion of ER Ca(2+) stores, whereas the unsaturated FFA oleate led to milder PERK and IRE1 activation and comparable ATF6 signaling. Non-metabolizable methyl-FFA analogs induced neither ER stress nor beta-cell apoptosis. The FFA-induced ER stress response was not modified by high glucose concentrations, suggesting that ER stress in primary beta-cells is primarily lipotoxic, and not glucolipotoxic. Palmitate, but not oleate, activated JNK. JNK inhibitors reduced palmitate-mediated AP-1 activation and apoptosis. Blocking the transcription factor CHOP delayed palmitate-induced beta-cell apoptosis. In conclusion, saturated FFA induce ER stress via ER Ca(2+) depletion. The IRE1 and resulting JNK activation contribute to beta-cell apoptosis. PERK activation by palmitate also contributes to beta-cell apoptosis via CHOP.


[Endoscopic negative pressure treatment : From management of complications to pre-emptive active reflux drainage in abdominothoracic esophageal resection-A new safety concept for esophageal surgery].
Early postoperative reflux (PR) can compromise anastomotic healing after Ivor Lewis esophagectomy (ILE) and poses a risk for aspiration. Anastomotic insufficiency is the most threatening surgical complication. We present the protective method of pre-emptive active reflux drainage (PARD) with simultaneous enteral feeding. We report our experience with this new safety concept in esophageal surgery in a cohort of 43 patients. For PARD we use a double lumen open porous film drainage (dOFD). To create the dOFD, the gastric tube of a Trelumina probe (Freka®Trelumina, Fresenius) is coated with a double-layered open-pore drainage film (Suprasorb®CNP drainage film, Lohmann & Rauscher) over a length of 25 cm. The dOFD is endoscopically inserted into the tubular stomach intraoperatively after completion of the anastomosis. Continuous negative pressure is applied with an electronic pump (-125 mm Hg). The PR is continuously aspirated completely and the stomach and anastomotic region are decompressed. At the same time, nutrition is delivered via an integrated intestinal tube. Depending on the results of the endoscopic control after 5 days, PARD is either continued or terminated. During the observation period (2017-2023), PARD was used in all patients (n = 43) with ILE. The healing rate under PARD was 100% and healing was observed in all anastomoses. No additional endoscopic procedures or surgical revisions of the anastomoses were required. The median duration of PARD was 8 days (range 4-21). We observed problems in the healing of the anastomosis in 20 of 43 patients (47%) for whom we defined endoscopic criteria for at-risk anastomosis. Our results suggest that PARD has a strong protective effect on anastomotic healing and may reduce the risk of anastomotic insufficiency. The integrated feeding tube of the dOFD allows early postoperative enteral feeding while simultaneously applying negative pressure. PARD appears to prevent the negative consequences of impaired anastomotic healing.


Viewing Trends and Users' Perceptions of the Effect of Sleep-Aiding Music on YouTube: Quantification and Thematic Content Analysis.
Sleep plays an essential role in the psychological and physiological functioning of humans. A report from the Centers for Disease Control and Prevention (CDC) found that sleep duration was significantly reduced among US adults in 2012 compared to 1985. Studies have described a significant association between listening to soothing music and an improvement in sleep quality and sleep duration. YouTube is a platform where users can access sleep-aiding music videos. No literature exists pertaining to the use of sleep-aiding music on YouTube. This study aimed to examine the patterns of viewing sleep-aiding music videos on YouTube. We also performed a content analysis of the comments left on sleep-aiding music video posts, to describe the perception of users regarding the effects of these music videos on their sleep quality. We searched for sleep-aiding music videos published on YouTube between January 1, 2012, and December 31, 2017. We sorted videos by view number (highest to lowest) and used a targeted sampling approach to select eligible videos for qualitative content analysis. To perform the content analysis, we imported comments into a mixed-method analytical software. We summarized variables including total views, likes, dislikes, play duration, and age of published music videos. All descriptive statistics were completed with SAS statistical software. We found a total of 238 sleep-aiding music videos on YouTube that met the inclusion criteria. The total view count was 1,467,747,018 and the total playtime was 84,252 minutes. The median play length was 186 minutes (IQR 122 to 480 minutes) and the like to dislike ratio was approximately 9 to 1. In total, 135 (56.7%) videos had over 1 million views, and 124 (52.1%) of the published sleep-aiding music videos had stayed active for 1 to 2 years. Overall, 4023 comments were extracted from 20 selected sleep-aiding music videos. Five overarching themes emerged in the reviewed comments, including viewers experiencing a sleep problem, perspective on the positive impact of the sleep-aiding music videos, no effect of the sleep-aiding music videos, time to initiation of sleep or sleep duration, and location of viewers. The overall κ statistic for the codes was 0.87 (range 0.85-0.96). This is the first study to examine the patterns of viewing sleep-aiding music videos on YouTube. We observed a substantial increase in the number of people using sleep-aiding music videos, with a wide variation in viewer location. This study supports the hypothesis that listening to soothing music has a positive impact on sleep habits.


Protein subunit vaccines of parainfluenza type 3 virus: immunogenic effect in lambs and mice.
Protein subunit vaccines were prepared from a mixture of the haemagglutinin (HN) and fusion (F) glycoproteins of parainfluenza type 3 virus (PI-3). The glycoproteins were isolated in three different forms and characterized by their sedimentation coefficients: 30S protein micelles (a complex of several HN and F glycoproteins devoid of detergent and lipid), 18S protein-TX complexes (a complex of several glycoproteins containing the detergent Triton X-100), and 4S protein-TX complexes (probably monomers of the glycoproteins complexed to Triton X-100). These preparations were tested as vaccines in mice and lambs. The immune response in the mice was assayed both in the serum and in extracts from the lungs using an ELISA technique. Both of the multimeric complexes were highly immunogenic. The 30S protein micelles induced a high antibody response after two injections with either 10 or 1 microgram protein. The serum IgG titres reached levels of about 90 micrograms/ml and 40 micrograms/ml respectively. Similar titres were reached with the 18S protein-TX complexes. After two injections of either the 30S or the 18S complexes IgA antibody responses were detected in the lung extracts. The 4S protein-TX complexes were poor immunogens and induced low antibody responses in mice. The lambs were vaccinated with the 30S protein micelles, and the immune response was evaluated serologically and in challenge experiments. The 30S protein micelles in an oil adjuvant induced detectable serum antibody titres as well as protective immunity against the pneumonia caused by the PI-3 virus.


[Surgical and long-term problems in biliary atresia].
The outcome of biliary atresia (BA) has improved after developments in hepatic portojejunostomy since the 1950s. The key to successful hepatic portojejunostomy is an optimal dissection line of the hepatic hilar remnant and anastomotic technique without microductule injury on the dissected surface. Most recent articles have reported that remnant hilar tissue should be dissected and the liver capsule preserved. The long-term problems in BA patients, such as cholangitis, became apparent after increased long-term native-liver survival. When hepatic function is preserved and the cause of cholangitis is localized, both surgical intervention and liver transplantation are viable options. The most appropriate treatment option is chosen based on efficacy, invasiveness, and ability to restore hepatic function. Digestive varices and hypersplenism due to portal hypertension are often controllable via symptomatic treatment. Long-term survivors of BA need to be closely monitored for secondary pulmonary perfusion abnormality; the condition necessitates liver transplantation and affects the outcome of the procedure. Some female survivors of BA conceive, which increases the risk of cholangitis and gastrointestinal bleeding during and after pregnancy. Such patients therefore must be monitored closely. Understanding the etiology and pathophysiology of BA is necessary for a good clinical course with native-liver survival.


Genetic diversity of transcriptional activator-like effector genes in Chinese isolates of Xanthomonas oryzae pv. oryzicola.
Xanthomonas oryzae pv. oryzicola causes bacterial leaf streak (BLS), a devastating disease of rice in Asia countries. X. oryzae pv. oryzicola utilizes repertoires of transcriptional activator-like effectors (TALEs) to manipulate host resistance or susceptibility; thus, TALEs can determine the outcome of BLS. In this report, we studied genetic diversity in putative tale genes of 65 X. oryzae pv. oryzicola strains that originated from nine provinces of southern China. Genomic DNAs from the 65 strains were digested with BamHI and hybridized with an internal fragment of avrXa3, a tale gene originating from the related pathogen, X. oryzae pv. oryzae, which causes bacterial leaf blight (BLB). Southern blot analysis indicated that the strains contained a variable number (9 to 22) of avrXa3-hybridizing fragments (e.g., putative tale genes). Based on the number and size of hybridizing bands, strains were classified into 14 genotypes (designated 1 to 14), and genotypes 3 and 10 represented 29.23 and 24.64% of the total, respectively. A high molecular weight BamHI fragment (HMWB; ≈6.0 kb) was present in 12 of the 14 genotypes, and sequence analysis of the HMWB revealed the presence of a C-terminally truncated tale, an insertion element related to IS1403, and genes encoding phosphoglycerate mutase and endonuclease V. Primers were developed from the 6.0-kb HMWB fragment and showed potential in genotyping X. oryzae pv. oryzicola strains by polymerase chain reaction. Virulence of X. oryzae pv. oryzicola strains was assessed on 23 rice cultivars containing different resistance genes for BLB. The X. oryzae pv. oryzicola strains could be grouped into 14 pathotypes (I to XIV), and the grouping of strains was almost identical to the categories determined by genotypic analysis. In general, strains containing higher numbers of putative tale genes were more virulent on rice than strains containing fewer tales. The results also indicate that there are no gene-for-gene relationships between the tested rice lines and X. oryzae pv. oryzicola strains. To our knowledge, this is the first description of genetic diversity of X. oryzae pv. oryzicola strains based on tale gene analysis.


CT coronary imaging-a fast evolving world.
Computed tomography (CT) has become an important modality in the evaluation of coronary artery disease (CAD). The tremendous technological advances in CT in the last two decades has made it possible to obtain high quality images of coronary arteries with high spatial and temporal resolutions. Multiple trials have confirmed the accuracy of CT compared to invasive catheter angiography. CT is also able to evaluate beyond the lumen in characterizing and quantifying atherosclerotic plaques, including evaluation of high risk features. Although CTA has low specificity in identification of lesion-specific ischemia, functional techniques are now possible such as CT myocardial perfusion and CT-fractional flow reserve (FFR) which evaluate the hemodynamic significance of stenosis and help with revascularization strategies. Multi-energy CT provides additional information beyond what is possible with a conventional CT and is useful in variety of clinical applications, including myocardial perfusion imaging, lesion characterization and low contrast studies. Large trials have confirmed the ability of CT to predict major adverse cardiovascular events and recent trials have even demonstrated improved clinical outcomes by using CT for the evaluation of CAD. CT is also useful in structural heart disease and 3 D printing is now increasingly used for surgical/interventional planning. Machine learning is evolving rapidly and is likely to impact diagnosis and management.


Respiratory diseases and their effects on respiratory function and exercise capacity.
Given that aerobic metabolism is the predominant energy pathway for most sports, the respiratory system can be a rate-limiting factor in the exercise capacity of fit and healthy horses. Consequently, respiratory diseases, even in mild forms, are potentially deleterious to any athletic performance. The functional impairment associated with a respiratory condition depends on the degree of severity of the disease and the equestrian discipline involved. Respiratory abnormalities generally result in an increase in respiratory impedance and work of breathing and a reduced level of ventilation that can be detected objectively by deterioration in breathing mechanics and arterial blood gas tensions and/or lactataemia. The overall prevalence of airway diseases is comparatively high in equine athletes and may affect the upper airways, lower airways or both. Diseases of the airways have been associated with a wide variety of anatomical and/or inflammatory conditions. In some instances, the diagnosis is challenging because conditions can be subclinical in horses at rest and become clinically relevant only during exercise. In such cases, an exercise test may be warranted in the evaluation of the patient. The design of the exercise test is critical to inducing the clinical signs of the problem and establishing an accurate diagnosis. Additional diagnostic techniques, such as airway sampling, can be valuable in the diagnosis of subclinical lower airway problems that have the capacity to impair performance. As all these techniques become more widely used in practice, they should inevitably enhance veterinarians' diagnostic capabilities and improve their assessment of treatment effectiveness and the long-term management of equine athletes.


Contact mechanics of reverse total shoulder arthroplasty during abduction: the effect of neck-shaft angle, humeral cup depth, and glenosphere diameter.
Implant design parameters can be changed during reverse shoulder arthroplasty (RSA) to improve range of motion and stability; however, little is known regarding their impact on articular contact mechanics. The purpose of this finite element study was to investigate RSA contact mechanics during abduction for different neck-shaft angles, glenosphere sizes, and polyethylene cup depths. Finite element RSA models with varying neck-shaft angles (155°, 145°, 135°), sizes (38 mm, 42 mm), and cup depths (deep, normal, shallow) were loaded with 400 N at physiological abduction angles. The contact area and maximum contact stress were computed. The contact patch and the location of maximum contact stress were typically located inferomedially in the polyethylene cup. On average for all abduction angles investigated, reducing the neck-shaft angle reduced the contact area by 29% for 155° to 145° and by 59% for 155° to 135° and increased maximum contact stress by 71% for 155° to 145° and by 286% for 155° to 135°. Increasing the glenosphere size increased the contact area by 12% but only decreased maximum contact stress by 2%. Decreasing the cup depth reduced the contact area by 40% and increased maximum contact stress by 81%, whereas increasing the depth produced the opposite effect (+52% and -36%, respectively). The location of the contact patch and maximum contact stress in this study matches the area of damage seen frequently on clinical retrievals. This finding suggests that damage to the inferior cup due to notching may be potentiated by contact stresses. Increasing the glenosphere diameter improved the joint contact area and did not affect maximum contact stress. However, although reducing the neck-shaft angle and cup depth can improve range of motion, our study shows that this also has some negative effects on RSA contact mechanics, particularly when combined.


In vivo and in vitro studies of Bacillus subtilis ferrochelatase mutants suggest substrate channeling in the heme biosynthesis pathway.
Ferrochelatase (EC 220.127.116.11) catalyzes the last reaction in the heme biosynthetic pathway. The enzyme was studied in the bacterium Bacillus subtilis, for which the ferrochelatase three-dimensional structure is known. Two conserved amino acid residues, S54 and Q63, were changed to alanine by site-directed mutagenesis in order to detect any function they might have. The effects of these changes were studied in vivo and in vitro. S54 and Q63 are both located at helix alpha3. The functional group of S54 points out from the enzyme, while Q63 is located in the interior of the structure. None of these residues interact with any other amino acid residues in the ferrochelatase and their function is not understood from the three-dimensional structure. The exchange S54A, but not Q63A, reduced the growth rate of B. subtilis and resulted in the accumulation of coproporphyrin III in the growth medium. This was in contrast to the in vitro activity measurements with the purified enzymes. The ferrochelatase with the exchange S54A was as active as wild-type ferrochelatase, whereas the exchange Q63A caused a 16-fold reduction in V(max). The function of Q63 remains unclear, but it is suggested that S54 is involved in substrate reception or delivery of the enzymatic product.


Implicit gender bias among US resident physicians.
The purpose of this study was to characterize implicit gender bias among residents in US Emergency Medicine and OB/GYN residencies. We conducted a survey of all allopathic Emergency Medicine and OB/GYN residency programs including questions about leadership as well as an implicit association test (IAT) for unconscious gender bias. We used descriptive statistics to analyze the Likert-type survey responses and used standard IAT analysis methods. We conducted univariate and multivariate analyses to identify factors that were associated with implicit bias. We conducted a subgroup analysis of study sites involved in a multi-site intervention study to determine if responses were different in this group. Overall, 74% of the programs had at least one respondent. Out of 14,234 eligible, 1634 respondents completed the survey (11.5%). Of the five sites enrolled in the intervention study, 244 of 359 eligible residents completed the survey (68%). Male residents had a mean IAT score of 0.31 (SD 0.23) and females 0.14 (SD 0.24), both favoring males in leadership roles and the difference was statistically significant (p < 0.01). IAT scores did not differ by postgraduate year (PGY). Multivariable analysis of IAT score and participant demographics confirmed a significant association between female gender and lower IAT score. Explicit bias favoring males in leadership roles was associated with increased implicit bias favoring males in leadership roles (r = 0.1 p < 0.001). We found that gender bias is present among US residents favoring men in leadership positions, this bias differs between male and female residents, and is associated with discipline. Implicit bias did not differ across training years, and is associated with explicit bias.


Takotsubo syndrome and estrogen receptor genes: partners in crime?
We aimed to analyze genetic polymorphism of estrogen receptor (ESR) 1 and ESR2 in a series of postmenopausal women with Takotsubo syndrome (TS). In total, 81 consecutive white women were prospectively enrolled: 22 with TS (TS group; mean age 71.2 ± 9.8 years), 22 with acute myocardial infarction (MI group; mean age 73.2 ± 8 years), and 37 asymptomatic healthy controls (CTRL group; mean age 69 ± 4.2 years). Genotyping of ESR1 -397C>T (rs2234693) and -351A>G (rs9340799) and ESR2 -1839G>T (rs 1271572) and 1082G>A (rs1256049) genetic variants was performed. We estimated the odds ratio (OR) between the genotype of each examined locus with the occurrence of TS or MI. The risk of experiencing TS was higher for those study participants carrying the T allele at the rs2234693 locus of the ESR1 gene [OR: 2.0, 95% confidence interval (CI): 0.973-4.11, P = 0.04, TS vs. MI + CTRL; OR: 2.79, 95% CI: 1.17-6.64, P = 0.016, TS vs. MI alone]. Women carrying a T allele at the rs1271572 locus of the ESR2 gene demonstrated an even higher risk (OR: 3.23, 95% CI: 1.55-6.73, P = 0.0019, TS vs. MI + CTRL; OR: 9.13, 95% CI: 2.78-29.9, P = 0.0001, TS vs. MI alone). The study reports preliminary findings suggesting a possible link between ESR polymorphisms and the occurrence of TS. Larger studies are needed to confirm our results.


Anticoagulation in patients with cancer: an overview of reviews.
Relative benefits and harms of anticoagulants are required for judgments regarding appropriate anticoagulation in patients with cancer. To review the benefits and harms of anticoagulants for prophylactic, therapeutic, and survival improvement indications in patients with cancer. Overview of 6 systematic reviews of anticoagulation in cancer following the Cochrane Collaboration and Grading of Recommendations Assessment, Development and Evaluation methodology. Central venous catheters thromboprophylaxis with heparin or warfarin does not significantly reduce the incidence of symptomatic deep vein thrombosis (DVT) (relative risk [RR] 0.43, 95% CI 0.18-1.06 and RR 0.62, 95% CI 0.30-1.27 respectively). For perioperative thromboprophylaxis, low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH) have similar effects on mortality (RR 0.89, 95% CI 0.61-1.28) and morbidity outcomes. For the initial treatment of venous thromboembolism (VTE), LMWH compared with UFH reduces mortality at 3 months (RR 0.71, 95% CI 0.52-0.98). For the long-term treatment of VTE, LMWH compared with vitamin K antagonists reduces VTE recurrence (hazard ratio [HR] 0.47, 95% CI 0.32-0.71) but not mortality (HR 0.96, 95% CI 0.81-1.14). As interventions to improve survival, warfarin suggests a survival benefit at 6 months in the subgroup of small cell lung cancer (SCLC) (RR 0.69, 95% CI 0.50-0.96) while heparin suggests a survival benefit in patients with cancer in general (HR 0.77, 95% CI 0.65-0.91) and in those with limited SCLC in particular (HR 0.56, 95% CI 0.38-0.83). In patients with cancer, current evidence does not support routine use of thromboprophylaxis for central venous catheters or a specific anticoagulant for perioperative thromboprophylaxis. Anticoagulants may improve survival, but more data will be useful in deciding which subgroups benefit most.


The Embodied God: Core Intuitions About Person Physicality Coexist and Interfere With Acquired Christian Beliefs About God, the Holy Spirit, and Jesus.
Why are disembodied extraordinary beings like gods and spirits prevalent in past and present theologies? Under the intuitive Cartesian dualism hypothesis, this is because it is natural to conceptualize of minds as separate from bodies; under the counterintuitiveness hypothesis, this is because beliefs in minds without bodies are unnatural-such beliefs violate core knowledge intuitions about person physicality and consequently have a social transmission advantage. We report on a critical test of these contrasting hypotheses. Prior research found that among adult Christian religious adherents, intuitions about person psychology coexist and interfere with theological conceptualizations of God (e.g., infallibility). Here, we use a sentence verification paradigm where participants are asked to evaluate as true or false statements on which core knowledge intuitions about person physicality and psychology and Christian theology about God are inconsistent (true on one and false on the other) versus consistent (both true or both false). We find, as predicted by the counterintuitiveness hypothesis but not the Cartesian dualism hypothesis, that Christian religious adherents show worse performance (lower accuracy and slower response time) on statements where Christian theological doctrines about God's physicality (e.g., incorporeality, omnipresence) conflict with intuitions about person physicality. We find these effects for other extraordinary beings in Christianity-the Holy Spirit and Jesus-but not for an ordinary being (priest). We conclude that it is unintuitive to conceptualize extraordinary beings as disembodied, and that this, rather than inherent Cartesian dualism, may explain the prevalence of beliefs in such beings.


One-pot chemoenzymatic preparation of coenzyme A analogues.
A rapid and stoichiometric method for the synthesis of analogues of coenzyme A is described. The method links the enzymes pantothenate kinase, phosphopantotheine adenylyltransferase, and dephosphocoenzyme A kinase in vitro to generate a variety of CoA analogues from chemically synthesized pantothenic acid derivatives. The Escherichia coli CoA biosynthetic enzymes were overexpressed as hexa-histidine-tagged proteins, providing an abundant source of pure active catalysts for the reaction. The synthesis of five novel CoA derivatives is reported and the method is shown to be robust and tolerant of a number of different pantothenic acid structures, which indicates that the procedure should be widely applicable.


Thermodynamics of microbial consortia: Enthalpies and Gibbs energies of microorganism live matter and macromolecules of E. coli, G. oxydans, P. fluorescens, S. thermophilus and P. chrysogenum.
Every microorganism represents a biothermodynamic system, characterized by an empirical formula and thermodynamic properties of biosynthesis. Gibbs energy of biosynthesis influences the multiplication rate of a microorganism. In case of a mixed culture (microbial consortia) biosynthesis processes of microbial species are competitive. This is why Gibbs energy of biosynthesis determines the growth in a mixed culture. This paper gives a mechanistic model that explains growth of microorganisms in mixed culture and ability to grow in microbial consortia. Detailed biosynthesis reactions were formulated for the first time for five microorganism species, which include metallic elements. Moreover, thermodynamic properties of live matter and biosynthesis were calculated for the first time for five microorganism species and macromolecules.


Serotonin transporter allelic variation in mothers predicts maternal sensitivity, behavior and attitudes toward 6-month-old infants.
Maternal behavior in the new mother is a multidimensional set of responses to infant cues that are influenced by the mother's early life experiences. In this study, we wanted to test if mothers' early life experiences and mothers' genotype have interactive effects on maternal behaviors and attitudes, something which has not been previously explored. In a sample of 204 mothers, we assessed maternal genotype at the serotonin transporter-linked polymorphic region (5-HTTLPR) and an adjacent upstream polymorphism (rs25531), together giving rise to three alleles: short (S), L(G) and L(A). Controlling for maternal age and parity, we showed that this genotype can predict differences in maternal sensitivity at 6 months postpartum: mothers with an S (or the functionally similar L(G)) allele were more sensitive than mothers who lacked the allele during a 30-min recorded mother-infant interaction (F (4,140) = 3.43; P = 0.01). Furthermore, we found highly significant gene-environment interactions in association with maternal behavior, such that mothers with no S or L(G) alleles oriented away more frequently from their babies if they also reported more negative early care quality (F (5,138) = 3.28; P = 0.008). Finally, we found significant gene-environment associations with maternal attitudes; mothers with the S allele and with greater early care quality scored higher on ratings of their perceived attachment to their baby (F (5,125) = 3.27; P = 0.008). The regression results show significant interactions between the reported quality of care mothers received from their own parents and genotype on both their frequency of orienting away from the infant during the interaction (F(5, 138) = 3.28; P = 0.008, Fig. 1a) and their perceived attachment feelings to the infant (F(5, 125) = 3.27; P = 0.008, Fig. 1b); however the direction of the effects for these two outcome measures were different from one another. With increasing care quality, mothers with the L(A)L(A) genotype (no S or L(G) allele) oriented away less frequently, while S or L(G) allele carriers showed no significant change. In contrast, with increasing early care quality. L(A)L(A) (no S or L(G) allele) mothers scored lower on perceived attachment to their infants, whereas S or L(G) allele carrying mothers scored higher. [corrected].


Fine-Needle Aspiration Cytology of Noninvasive Follicular Variant of Papillary Thyroid Carcinoma Is Cytomorphologically Distinct From the Invasive Counterpart.
To review a series of noninvasive encapsulated follicular variant of papillary thyroid carcinomas (FVPTCs) in an attempt to further define the role of cytopathology in the diagnosis of noninvasive follicular thyroid neoplasm with papillary-like nuclear features and invasive FVPTC. Surgical pathology cases diagnosed as FVPTC with correlating thyroid fine-needle aspiration (FNA) were identified and divided into two FVPTC groups: noninvasive and invasive. Cytologic diagnoses were compared between them. We identified 23 cases that met the criteria for noninvasive FVPTC and 27 cases that were typical infiltrative FVPTC (n = 16) or encapsulated FVPTC with either capsular and/or lymphovascular invasion (n = 11). Of the noninvasive FVPTC cases, there were four benign lesions, 14 follicular lesions of undetermined significance (FLUS), four follicular neoplasms (FNs), one suspicious case, and no papillary thyroid carcinomas (PTCs). In the invasive FVPTC group, there were no benign cases, four FLUS, three FNs, 12 suspicious cases, and eight PTCs. There is a distinction in the cytologic diagnosis between noninvasive and invasive FVPTC. The invasive subtype was diagnosed by FNA as suspicious for PTC or PTC in nearly 75% of cases, while only one (4%) case for the noninvasive subtype was diagnosed as suspicious for PTC (P < .05).


Design of a built-in baffle for a Ritchey-Chretien optical system.
A baffle effectively prevents direct rays of stray light from entering an optical system. Existing design methods can result in very long outer baffle lengths, increasing the weight and volume of the optical system, or large secondary mirror baffle sizes, increasing the central obscuration and resulting in the reduction of the illumination beam on the image. To overcome these challenges, a design method for a built-in baffle is presented. The designed built-in baffle for a typical Ritchey-Chretien optical system is compared with a conventionally designed baffle. The results show that when the length of outer baffle is shortened from 3456 to 2349.9 mm, the modulation transfer function (MTF) increases from 0.361 to 0.421 in case 1, and when the length is shortened from 3456 to 1924.2 mm, the MTF increases from 0.361 to 0.408 in case 2. Meanwhile, the stray light suppression capability is close to that of the traditional method.


Administration of PLK-1 small interfering RNA with atelocollagen prevents the growth of liver metastases of lung cancer.
Liver metastasis is one of the most important prognostic factors in lung cancer patients. However, current therapies are not sufficient. RNA interference provides us a powerful and promising approach for treating human diseases including cancers. Herein, we investigated the in vitro effects of PLK-1 small interfering RNA (siRNA) on human lung cancer cell lines and the in vivo usage of PLK-1 siRNA with atelocollagen as a drug delivery system in a murine liver metastasis model of lung cancer. PLK-1 was overexpressed in cell lines and in cancerous tissues from lung cancer patients. PLK-1 siRNA treatment inhibited growth and induced apoptosis in a concentration-dependent manner. To verify in vivo efficacy, we confirmed that atelocollagen was a useful drug delivery system in our model of implanted luciferase-labeled A549LUC cells by detecting reduced bioluminescence after an i.v. injection of luciferase GL3 siRNA/atelocollagen. PLK-1 siRNA/atelocollagen was also successfully transfected into cells and inhibited the progression of metastases. This study shows the efficacy of i.v. administration of PLK-1 siRNA/atelocollagen for liver metastases of lung cancer. We believe siRNA therapy will be a powerful and promising strategy against advanced lung cancer.


Elevated nuclear Foxo1 suppresses excitability of skeletal muscle fibers.
Forkhead box O 1 (Foxo1) controls the expression of proteins that carry out processes leading to skeletal muscle atrophy, making Foxo1 of therapeutic interest in conditions of muscle wasting. The transcription of Foxo1-regulated proteins is dependent on the translocation of Foxo1 to the nucleus, which can be repressed by insulin-like growth factor-1 (IGF-1) treatment. The role of Foxo1 in muscle atrophy has been explored at length, but whether Foxo1 nuclear activity affects skeletal muscle excitation-contraction (EC) coupling has not yet been examined. Here, we use cultured adult mouse skeletal muscle fibers to investigate the effects of Foxo1 overexpression on EC coupling. Fibers expressing Foxo1-green fluorescent protein (GFP) exhibit an inability to contract, impaired propagation of action potentials, and ablation of calcium transients in response to electrical stimulation compared with fibers expressing GFP alone. Evaluation of the transverse (T)-tubule system morphology, the membranous system involved in the radial propagation of the action potential, revealed an intact T-tubule network in fibers overexpressing Foxo1-GFP. Interestingly, long-term IGF-1 treatment of Foxo1-GFP fibers, which maintains Foxo1-GFP outside the nucleus, prevented the loss of normal calcium transients, indicating that Foxo1 translocation and the atrogenes it regulates affect the expression of proteins involved in the generation and/or propagation of action potentials. A reduction in the sodium channel Nav1.4 expression in fibers overexpressing Foxo1-GFP was also observed in the absence of IGF-1. We conclude that increased nuclear activity of Foxo1 prevents the normal muscle responses to electrical stimulation and that this indicates a novel capability of Foxo1 to disable the functional activity of skeletal muscle.


Hemodynamic Instability Secondary to Vasopressin Withdrawal in Septic Shock.
Vasopressors such as norepinephrine are first line for support of mean arterial pressure (MAP) in the management of septic shock. Their use, however, is commonly associated with many adverse events. These detriments frequently trigger the use of alternative, noncatecholamine therapies, including vasopressin. Vasopressin deficiency is a known physiologic consequence of septic shock, and while guidelines recommend vasopressin in addition to norepinephrine, no consensus exists on the duration of deficiency or ideal time of cessation. Studies have suggested that vasopressin discontinuation prior to other vasopressors may lead to hypotension; however, data are limited. This study evaluates the optimal sequence for the discontinuation of vasopressin therapy in septic shock. This was a 1-year retrospective study of 152 patients admitted to the medical intensive care unit (ICU) with septic shock who received concurrent norepinephrine and vasopressin for vasoactive support. Patients were excluded if death occurred on vasopressors, within 24 hours after discontinuation of vasopressors, or within 48 hours of ICU admission. The primary outcome of hemodynamic instability included incidence of hypotension after vasopressor discontinuation (2 consecutive MAPs < 60 mm Hg), fluid bolus administration, greater than 0.05 μg/kg/min increase in norepinephrine requirements, or addition of an alternative vasopressor. Secondary outcomes included time to hypotension, total vasopressor duration, arrhythmias, mortality, and length of stay. Ninety-one patients met exclusion criteria, resulting in 61 patients for evaluation. Vasopressin was the first vasoactive therapy to be discontinued in 19 patients and last in 42 patients. Baseline characteristics and the use of potentially confounding treatments known to effect MAP were similar between groups. Discontinuation of vasopressin first was associated with a significant increase in hemodynamic instability (74% vs 16.7%, P < .01), with a shorter time to hemodynamic instability (5 vs 15 hours, P < .01). Secondary outcomes were similar. Vasopressin discontinuation prior to cessation of norepinephrine infusion was associated with an increased risk of hemodynamic instability.


Massive osteolysis. A review of seven cases.
Seven cases of massive osteolysis are presented. The aetiology of this disease is as yet unknown; neither age nor sex seems to be a factor in its incidence, nor are standard bone grafts or radiotherapy successful methods of treatment. However, in this series, operation produced a satisfactory outcome for five patients at a mean follow-up of 17 years; in three of these patients a custom-built prosthesis was inserted, and in one a conventional bone graft was combined with intramedullary nailing.


Angiogenesis and airway reactivity in asthmatic Brown Norway rats.
Expanded and aberrant bronchial vascularity, a prominent feature of the chronic asthmatic airway, might explain persistent airway wall edema and sustained leukocyte recruitment. Since it is well established that there are causal relationships between exposure to house dust mite (HDM) and the development of asthma, determining the effects of HDM in rats, mammals with a bronchial vasculature similar to humans, provides an opportunity to study the effects of bronchial angiogenesis on airway function directly. We studied rats exposed bi-weekly to HDM (Der p 1; 50 μg/challenge by intranasal aspiration, 1, 2, 3 weeks) and measured the time course of appearance of increased blood vessels within the airway wall. Results demonstrated that within 3 weeks of HDM exposure, the number of vessels counted within airway walls of bronchial airways (0.5-3 mm perimeter) increased significantly. These vascular changes were accompanied by increased airway responsiveness to methacholine. A shorter exposure regimen (2 weeks of bi-weekly exposure) was insufficient to cause a significant increase in functional vessels or reactivity. Yet, 19F/1H MR imaging at 3T following αvβ3-targeted perfluorocarbon nanoparticle infusion revealed a significant increase in 19F signal in rat airways after 2 weeks of bi-weekly HDM, suggesting earlier activation of the process of neovascularization. Although many antigen-induced mouse models exist, mice lack a bronchial vasculature and consequently lack the requisite human parallels to study bronchial edema. Overall, our results provide an important new model to study the impact of bronchial angiogenesis on chronic inflammation and airways hyperreactivity.


Compliance in an anti-hypertension trial: a latent process model for binary longitudinal data.
We propose an alternative to the method of generalized estimating equations (GEE) for inference about binary longitudinal data. Unlike GEE, the method is practicable when the data consist of long time series on each subject and the set of observation times is not necessarily common to all subjects. Instead of modelling the intra-series correlations explicitly, we assume that a subject's propensity to respond is governed by an underlying, but unobserved, stationary continuous process. Given a realization of this process, we assume that the binary responses are conditionally independent, with the probability that a subject responds positively at any given time t depending on the value of the underlying process at that time and also on any covariates specific to the subject at that time. We develop an algorithm for estimating the parameters in this model, and investigate its effectiveness using simulation methods. We also apply the methodology to data collected in a trial investigating the effect of self-measurement of blood pressure on compliance in taking medication during a course of anti-hypertension treatment.


Multiple dosing of simvastatin inhibits airway mucus production of epithelial cells: implications in the treatment of chronic obstructive airway pathologies.
Chronic obstructive pulmonary disease (COPD) is characterised by mucus hyper-production. This pathology, together with other inflammatory contributions, leads to airway obstruction and breathing complications. Newer therapeutic approaches are of increased interest, including the use of HMG-CoA reductase inhibitors. Retrospective studies have shown that statins are effective in reducing patient mortality and blood cytokines levels. These findings suggest statins may also provide a new therapeutic approach in COPD treatment. The aim of the present work was to study the transport of simvastatin (SV) across Calu-3 epithelial cells and to investigate its pharmacological action with respect to reduction in mucus production. Calu-3 cells were grown under liquid covered culture (LCC) conditions for transport studies in order to demonstrate the ability of SV to transport across the monolayer. For mucus detection, cells were grown under air interface culture (AIC) conditions. Samples collected for microscope analysis were stained with alcian blue; images of the stained cell surface were acquired and the mucus was quantified as the RGBB ratio. SV was transported through the cell monolayer and 'retained' inside the Calu-3 cells. Colour analysis of stained Calu-3 monolayers microscope-images showed that chronic administration of SV for 14 days caused a significant inhibition in mucus production. These findings suggest that local delivery of SV directly to the lungs may provide a promising treatment and potential disease management approach of COPD, with significant effects on mucus reduction.


Suppression of voluntary ethanol intake in mice under constant light and constant darkness.
Seasonal variations in photoperiod are associated with alterations in human mood and behavior. Similarly, manipulation of the environmental lighting regimen can exert pronounced effects on affective behavior in experimental animals. These observations may be due, in part, to light-induced alterations in circadian rhythms, but it seems likely that other, non-circadian factors also contribute. Several studies have shown that voluntary alcohol (ethanol) consumption can be affected by lighting conditions in rodents, suggesting that photoperiodic variation may account for seasonal and geographic patterns of human alcohol consumption. Nevertheless, the existing animal data are somewhat inconsistent, and little work in this area has been performed in mice. In the present study, we monitored circadian activity rhythms and voluntary ethanol consumption under standard 12:12 light-dark (LD) cycles, and in constant light (LL) and constant darkness (DD). Experiment 1 employed male C3H/He inbred mice, while Experiment 2 employed males and females from a genetically heterogeneous line (WSC). Relative to LD conditions, ethanol intake and ethanol preference were reduced under both LL and DD in both experiments. Because similar effects were seen in both LL and DD, neither circadian disruption nor a classical photoperiodic mechanism are likely to account fully for these findings. Instead, we suggest that the absence of circadian entrainment may function as a mild stressor, resulting in reduced ethanol consumption.


[Gunshot injuries of the spleen].
The gunshots injuries of the spleen are relative uncommon by comparison with others abdominal trauma The rate is 1 to 3% of all injuries to the abdomen. This review presents the most widespread classifications of spleen trauma, current diagnostic - physical examination, sonography, CT, DPL, laparoscopy. The surgical treatment is discussed in the following trends - nonoperative and operative approach depending on patient's condition. The nonoperative treatment is applied to hemodynamically stable patients with established superficial lesions and ceased hemorrhage. In the other cases the operative approach is indicated. The splenectomy is the method of choice and in defined situations spleen tissue autotransplantation is applicable. Other procedures are outlined: spleen preserving resections, splenorrhaphy, mesh repair, ligation of sanguinating vessels, omentoplastic, hemostatic glue or mesh, argon plasma electrocoagulation, Most reported complications following spleen trauma are hemorrhage, infections, thrombocytosis, partial necrosis of stomach, pancreatitis, postsplenectomy sepsis. The mortality varies between 5 and 65%.


The effect of 3 commonly used surgical approaches for total hip arthroplasty on mid- to long-term patient-reported outcome measures.
The most effective surgical approach for total hip arthroplasty (THA) remains controversial. Comparisons of surgical approach based on patient-reported outcome measures (PROMs) have been limited to short- to mid-term outcomes or the comparison of only 2 approaches. The aim of this study was to compare PROMs for the 3 main approaches for THA with up to 10 years follow-up. A total of 906 patients who underwent primary THA at a single hospital between 2009 and 2020 through an anterior (312), lateral (211) or posterior (383) approach were evaluated using the Oxford Hip Score (OHS), EuroQoL-5-Dimension (EQ-5D-5L) and visual analogue scale/verbal rating scale for pain (VAS/VRS). PROMs were prospectively collected before surgery and routinely at 6 weeks, 6 months and 1, 2, 5 and 10 years after surgery. There was no significant difference in demographics or comorbidities between the 3 groups. All 3 approaches resulted in a significant improvement in overall PROMs after THA, and plateaued after 6 months postoperatively, with no difference between the approaches (OHS, p < 0.01;EQ-5D-5L Index, p < 0.01;VAS/VRS, p < 0.01). The EQ-5D-5L mobility dimension showed that the lateral approach resulted in 20% more patients reporting problems with mobility than the posterior and anterior approaches at the 6-week, 6-month, 2-year and 10-year follow-up. This study shows that all 3 common THA approaches substantially and similarly improve the OHS, EQ-5D-5L Index and VRS between 6 months and 10 years postoperatively. However, patient-reported mobility was poorer after a lateral approach and continued to be so at long-term follow-up.


Thermal behavior of a human glioma cell line and its response to combinations of hyperthermia and lonidamine.
The effect of hyperthermia and lonidamine, alone and in combination, on the clonogenic activity of a human glioma cell line was investigated. The time-temperature relationship of asynchronous, exponentially growing cells was defined in the range of 40-45 degrees C. All survival curves were exponential and an Arrhenius plot for heat killing was linear over the temperature range tested, with an activation energy of 192 Kcal/mol. The survival curve of lonidamine-treated cells was also exponential after an initial shoulder. The analysis of the interaction between lonidamine and hyperthermia, performed by the isobolar method, demonstrated an additivity of response so that the effectiveness of the combined treatment was the result of two independent effects. Lonidamine inhibits the neoplastic growth mainly through an ATP depletion, but the thermal killing was not mediated by the drug-induced changes in the energy status of the cell. The effectiveness of the combined treatment was strongly influenced by the schedule of administration. In fact, the sequence lonidamine-->hyperthermia made the cells less sensitive to heat so that the pre-established end-point, i.e. 30% survival, was never achieved whichever combination was used. This "drug-induced heat resistance" was not associated with the induction of heat shock proteins, but rather with modification of cell cycle. On the contrary, showing a purely additive effect, the sequence hyperthermia-->lonidamine allowed achievement of the pre-established cell killing (70%), with exposure times (1-2 hr) and with a temperature (42 degrees C) generally accepted as clinically achievable. Therefore, also considering its low systemic toxicity, lonidamine may be useful in reducing the side effects of hyperthermia.


Abbreviated laparotomy or damage control laparotomy: Why, when and how to do it?
The goal of abbreviated laparotomy is to treat severely injured patients whose condition requires an immediate surgical operation but for whom a prolonged procedure would worsen physiological impairment and metabolic failure. Indeed, in severely injured patients, blood loss and tissue injuries enhance the onset of the "bloody vicious circle", triggered by the triad of acidosis-hypothermia-coagulopathy. Abbreviated laparotomy is a surgical strategy that forgoes the completeness of operation in favor of a physiological approach, the overriding preference going to rapidity and limiting the procedure to control the injuries. Management is based on sequential association of the shortest possible preoperative resuscitation with surgery limited to essential steps to control injury (stop the bleeding and contamination), without definitive repair. The latter will be ensured during a scheduled re-operation after a period of resuscitation aiming to correct physiological abnormalities induced by the trauma and its treatment. This strategy necessitates a pre-defined plan and involvement of the entire medical and nursing staff to reduce time loss to a strict minimum.


AlGaN/GaN asymmetric graded-index separate confinement heterostructures designed for electron-beam pumped UV lasers.
We present a study of undoped AlGaN/GaN separate confinement heterostructures designed to operate as electron beam pumped ultraviolet lasers. We discuss the effect of spontaneous and piezoelectric polarization on carrier diffusion, comparing the results of cathodoluminescence with electronic simulations of the band structure and Monte Carlo calculations of the electron trajectories. Carrier collection is significantly improved using an asymmetric graded-index separate confinement heterostructure (GRINSCH). The graded layers avoid potential barriers induced by polarization differences in the heterostructure and serve as strain transition buffers which reduce the mosaicity of the active region and the linewidth of spontaneous emission.


Laparoscopic resection of a pelvic schwannoma.
Schwannomas are rare retroperitoneal and pelvic tumors that often present as an enlarging mass. Preoperative imaging by computerized tomography and magnetic resonance imaging can be suggestive of the diagnosis. Traditionally, these benign tumors have been treated at laparotomy. Presented herein is a case of a pelvic retroperitoneal schwannoma that was successfully resected using laparoscopic surgical techniques. The prognosis for these tumors is favorable, but long-term follow-up is necessary.


Extreme air pollution events from bushfires and dust storms and their association with mortality in Sydney, Australia 1994-2007.
Extreme air pollution events due to bushfire smoke and dust storms are expected to increase as a consequence of climate change, yet little has been published about their population health impacts. We examined the association between air pollution events and mortality in Sydney from 1997 to 2004. Events were defined as days for which the 24h city-wide concentration of PM(10) exceeded the 99th percentile. All events were researched and categorised as being caused by either smoke or dust. We used a time-stratified case-crossover design with conditional logistic regression modelling adjusted for influenza epidemics, same day and lagged temperature and humidity. Reported odds ratios (OR) and 95% confidence intervals are for mortality on event days compared with non-event days. The contribution of elevated average temperatures to mortality during smoke events was explored. There were 52 event days, 48 attributable to bushfire smoke, six to dust and two affected by both. Smoke events were associated with a 5% increase in non-accidental mortality at a lag of 1 day OR (95% confidence interval (CI)) 1.05 (95%CI: 1.00-1.10). When same day temperature was removed from the model, additional same day associations were observed with non-accidental mortality OR 1.05 (95%CI: 1.00-1.09), and with cardiovascular mortality OR (95%CI) 1.10 (95%CI: 1.00-1.20). Dust events were associated with a 15% increase in non-accidental mortality at a lag of 3 days, OR (95%CI) 1.16 (95%CI: 1.03-1.30). The magnitude and temporal patterns of association with mortality were different for smoke and dust events. Public health advisories during bushfire smoke pollution episodes should include advice about hot weather in addition to air pollution.


Vitamin K-dependent protein S is similar to rat androgen-binding protein.
Vitamin K-dependent protein S belongs to the family of clotting factors (e.g. Factors IX and X, and protein C). Unlike the other clotting factors, the C-terminal half (residues 250-634) of protein S is not a serine proteinase. In fact, the function of residues 250-634 of protein S is unknown. By using computer programs designed to detect evolutionary relationships between proteins, we find that this part of protein S is similar to rat androgen-binding protein, a protein produced and secreted by testicular Sertoli cells. The homology between protein S and androgen-binding protein suggests new approaches for elucidating their functions.


[The permeability of the blood-cerebrospinal fluid barrier in the first 24 hours after cranio-cerebral injury].
The permeability of the blood-liquor barrier (BLB) for blood proteins was studied in 30 patients within 24 hours after craniocerebral injuries of various severity and 21 patients whose condition was critical within 24 hours after different neurosurgical interventions. BLB permeability was assessed from the ratio of albumin/IgG in the cerebrospinal fluid and blood. A direct though not always statistically significant relationship between BLB permeability and the severity of injury was revealed. The authors suppose that this methodological approach, combined with other methods of investigation, may be useful in assessing the course of brain edema. Local IgG synthesis in the central nervous system was detected in half of the injured patients and in half of those in the critical condition. Local immune humoral reaction of the central nervous system appears to be largely related to the trauma severity and not influencing the outcome. This phenomenon is to be verified by specific immunologic methods.


Isolation of human dermis derived mesenchymal stem cells using explants culture method: expansion and phenotypical characterization.
Recent studies have reported that stem cells can be isolated from a wide range of tissues including bone marrow, fatty tissue, adipose tissue and placenta. Moreover, several studies also suggest that skin dermis could serve as a source of stem cells, but are of unclear phenotype. Therefore, we isolated and investigated to determine the potential of stem cell within human skin dermis. We isolated cells from human dermis, termed here as human dermis-derived mesenchymal stem cells (hDMSCs) which is able to be isolated by using explants culture method. Our method has an advantage over the enzymatic method as it is easier, less expensive and less cell damage. hDMSCs were maintained in basal culture media and proliferation potential was measured. hDMSCs were highly proliferative and successfully expanded with no additional growth factor. In addition, hDMSCs revealed normal karyotype and expressed high levels of CD90, CD73 and CD105 while did not express the surface markers for CD34, CD45 and HLA-DR. Also, we confirmed that hDMSCs possess the capacity to differentiate into multiple lineage including adipocyte, osteocyte, chondrocyte and precursor of hepatocyte lineage. Considering these results, we suggest that hDMSCs might be a valuable source of stem cells and could potentially be a useful source of clinical application.


Momentum amplituhedron meets kinematic associahedron.
In this paper we study a relation between two positive geometries: the momen- tum amplituhedron, relevant for tree-level scattering amplitudes in N = 4 super Yang-Mills theory, and the kinematic associahedron, encoding tree-level amplitudes in bi-adjoint scalar φ 3 theory. We study the implications of restricting the latter to four spacetime dimensions and give a direct link between its canonical form and the canonical form for the momentum amplituhedron. After removing the little group scaling dependence of the gauge theory, we find that we can compare the resulting reduced forms with the pull-back of the associahedron form. In particular, the associahedron form is the sum over all helicity sectors of the reduced momentum amplituhedron forms. This relation highlights the common sin- gularity structure of the respective amplitudes; in particular, the factorization channels, corresponding to vanishing planar Mandelstam variables, are the same. Additionally, we also find a relation between these canonical forms directly on the kinematic space of the scalar theory when reduced to four spacetime dimensions by Gram determinant constraints. As a by-product of our work we provide a detailed analysis of the kinematic spaces relevant for the four-dimensional gauge and scalar theories, and provide direct links between them.


DeepDive: Declarative Knowledge Base Construction.
The dark data extraction or knowledge base construction (KBC) problem is to populate a SQL database with information from unstructured data sources including emails, webpages, and pdf reports. KBC is a long-standing problem in industry and research that encompasses problems of data extraction, cleaning, and integration. We describe DeepDive, a system that combines database and machine learning ideas to help develop KBC systems. The key idea in DeepDive is that statistical inference and machine learning are key tools to attack classical data problems in extraction, cleaning, and integration in a unified and more effective manner. DeepDive programs are declarative in that one cannot write probabilistic inference algorithms; instead, one interacts by defining features or rules about the domain. A key reason for this design choice is to enable domain experts to build their own KBC systems. We present the applications, abstractions, and techniques of DeepDive employed to accelerate construction of KBC systems.


Aggregation and neurotoxicity of recombinant α-synuclein aggregates initiated by dimerization.
Aggregation of the α-Synuclein (α-Syn) protein, amyloid fibril formation and progressive neurodegeneration are the neuropathological hallmarks of Parkinson's Disease (PD). However, a detailed mechanism of α-Syn aggregation/fibrillogenesis and the exact nature of toxic oligomeric species produced during amyloid formation process are still unknown. In this study, the rates of α-Syn aggregation were compared for the recombinant wild-type (WT) α-Syn and a structurally relevant chimeric homologous protein containing an inducible Fv dimerizing domain (α-SynFv), capable to form dimers in the presence of a divalent ligand (AP20187). In the presence of AP20187, we report a rapid random coil into β-sheet conformational transformation of α-SynFv within 24 h, whereas WT α-Syn showed 24 h delay to achieve β-sheet structure after 48 h. Fluorescence ANS and ThT binding experiments demonstrate an accelerated oligomer/amyloid formation of dimerized α-SynFv, compared to the slower oligomerization and amyloidogenesis of WT α-Syn or α-SynFv without dimerizer AP20187. Both α-SynFv and α-Syn pre-fibrillar aggregates internalized cells and induced neurotoxicity when injected into the hippocampus of wild-type mice. These recombinant toxic aggregates further converted into non-toxic amyloids which were successfully amplified by protein misfolding cyclic amplification method, providing the first evidence for the in vitro propagation of synthetic α-Syn aggregates. Together, we show that dimerization is important for α-Syn conformational transition and aggregation. In addition, α-Syn dimerization can accelerate the formation of neurotoxic aggregates and amyloid fibrils which can be amplified in vitro. A detailed characterization of the mechanism of α-Syn aggregation/amyloidogenesis and toxicity is crucial to comprehend Parkinson's disease pathology at the molecular level.


Chronic DOCA treatment increases Ca absorption: role of hypercalciuria and vitamin D.
To examine the effects of mineralocorticoidism on calcium (Ca) absorption and to define the mechanism, rats received a high-salt diet and injections of vehicle or deoxycorticosterone acetate (DOCA). Net (44.2 vs. 31.4 mg/day) and percent Ca absorption (28.1 vs. 20.1%) was increased after 5 days of DOCA. This was associated with increased duodenal 45Ca uptake. Thus despite the hypercalciuria, Ca balance was similar. Although the hypercalciuria persisted chronically, the gut effects were sustained, which maintained normal ionized Ca, bone Ca, and Ca balance. Urinary cyclic adenosine monophosphate was elevated by DOCA. Compared with appropriate controls, neither DOCA alone nor polydipsia (elicited by dextrose) produced similar magnitudes of hypercalciuria as DOCA plus high-salt diet. These maneuvers also failed to increase Ca absorption. Neutralization of the metabolic alkalosis neither attenuated the DOCA-induced hypercalciuria nor abolished the Ca hyperabsorption. In vitamin D-deprived rats, the hypercalciuria but not the intestinal effects of DOCA were reproduced. Serum 1,25-dihydroxyvitamin D3 levels were increased during chronic DOCA treatment (224 vs. 139 pg/ml). These data best fit the hypothesis that increased Ca absorption is secondary to the calciuric effects of DOCA and high-salt diet and is mediated via the increased parathyroid hormone and 1,25-dihydroxyvitamin D3 activities.