Association of polygenic risk scores with incident atherosclerotic cardiovascular disease events among individuals with coronary artery calcium score of zero: The multi-ethnic study of atherosclerosis.
Polygenic risk scores (PRS) are associated with atherosclerotic cardiovascular disease (ASCVD) events. We studied incident ASCVD among individuals with absent coronary artery calcium (CAC = 0), to investigate the association of PRS with incident ASCVD among such individuals. Data was used from Multi-Ethnic Study of Atherosclerosis (MESA), a prospective cohort study of participants free of clinical CVD at baseline. PRS were developed based on a literature-derived list of single-nucleotide polymorphisms (SNPs) weighted by effect size. The coronary heart disease (CHD) PRS contained 180 SNPs, and the stroke PRS had 32 SNPs. These SNPs were combined to compute an ASCVD PRS. The PRS were calculated among 3132 participants with CAC = 0. Multivariable-adjusted Cox proportional hazards models evaluated the association between each PRS (top 20% vs bottom 50%) and ASCVD. The study population included 3132 individuals with CAC = 0 [mean (SD) age 58 (9) years; 63% female, 33% White, 31% Black, 12% Chinese-American, 24% Hispanic]. Over a median follow-up of 16 years, there were 108 incident CHD events and 93 stroke events. ASCVD event rates were generally <7.5 per 1000-person years for all ASCVD events regardless of PRS risk stratum. The ASCVD PRS was significantly associated with incident ASCVD: (HR; 95% CI) (1.63; 1.11, 2.39). The CHD PRS was not associated with any ASCVD outcome, whereas the stroke PRS was significantly associated with ASCVD (1.84; 1.27, 2.68), CHD (1.79; 1.05, 3.06), and stroke (1.96; 1.19, 3.23). The stroke PRS results were significant among women and non-Whites. Among individuals with CAC = 0, the ASCVD PRS was associated with incident ASCVD events. This appears to be driven by genetic variants related to stroke but not CHD, and particularly among women and non-Whites. ASCVD event rates remained below the threshold recommended for consideration for initiation of statin therapy even in the high PRS groups.


Imaging of neuroendocrine tumours with gamma-emitting radiopharmaceuticals.
Nuclear medicine can image some tumors by means of receptor specific radiopharmaceuticals, and offers the possibility to characterize cancer through the detection of its receptor expression. This is the case of neuroendocrine tumours (NETs), that are visualized by different radiolabelled somatostatin analogues that bind 5 distinct somatostatin receptor types (named sstr1-5) that show different tissue distribution. The subtypes sstr2 and sstr5 are the most commonly expressed in NETs. Until now the most widely used radiolabelled somatostatin analogue for planar and single photon emission computed tomography (SPECT) has been [(111)In]pentetreotide, because of its commercial availability. Other analogues labelled with gamma emitting radionuclides are [(99m)Tc]EDDA/HYNIC-TOC, [(99m)Tc]P829, [(111)In]DOTA-lanreotide, [(111)In]DOTA-NOC-ATE, [(111)In]DOTA-BOC-ATE. However, these compounds have not been successful for the routine use. Moreover, NETs express various receptors that can be depicted by different radiopharmaceuticals, such as [(123)I]VIP and [(111)In]GLP-1. Besides this, some precursors of the catecholamines metabolism, as meta-iodo-benzyl-guanidine (MIBG), labelled with (123)I or (131)I, accumulates in neuroendocrine tissues, in particular those of sympathoadrenal lineage. MIBG scintigraphy is currently indicated for neuroblastoma, paraganglioma and phaeocromocitoma. An impressive technological progress has been achieved recently with PET and, in particular, with the development of hybrid instrumentations (PET/CT) combining nuclear imaging with radiological imaging providing both functional and morphologic information. Among positron emitting tracers, the [(18)F]FDG is the most diffuse in oncology, but other more effective tracers are available for NETs, such as the analogues labelled with 68Ga. The diagnostic sensitivity and accuracy of these technology is superior to that of gamma emitting radiopharmaceuticals, but the fact that they are not still registered limits their use in the clinical practice. This overview summarizes the state of art of NETs imaging, focusing the attention mainly on gamma-emitting tracers.


The myeloproliferative sarcoma virus causes transformation or erythroid progenitor cells in vitro.
The myeloproliferative sarcoma virus induces spleen focus formation in vivo and transforms fibroblasts in vitro. We showed in this study that in vitro infection of spleen or bone marrow cells from susceptible mice with the myeloproliferative sarcoma virus leads to the formation of erythroid bursts. Under optimal conditions erythroid bursts formed in the absence of added erythropoietin, but the addition of as little as 0.05 U of erythropoietin per ml to infected cultures resulted in a significant increase in numbers of erythroid bursts and the proportion of hemoglobinized cells. A comparison of the kinetics of burst formation and the size of the induced bursts with those induced with Friend virus suggested that either sarcoma virus such as the myeloproliferative sarcoma virus or the target cells for the two viruses were not the same. Density characterization and heat lability studies indicated that the increased erythroid proliferation in vitro was a virus-induced event, but the possibility that the induced erythroid burst formation is mediated via interaction with a nonerythroid target cell and subsequent release of a soluble factor cannot be ruled out.


Duchenne muscular dystrophy--a molecular service.
In 1987 a carrier detection and prenatal diagnostic service for Duchenne muscular dystrophy using molecular technology was instituted at the Department of Human Genetics, University of Cape Town, to serve affected families in southern Africa. DNA samples from 100 affected male subjects and 350 of their relatives from a total of 110 families have been banked. To date restriction fragment length polymorphism (RFLP) analysis and deletion screening has been performed on the DNA of 60 male patients and 116 female relatives at risk of being carriers of the faulty gene. The DNA probes used were pERT 87-1 (MspI polymorphism) pERT 87-15, pXJ1.1, pXJ2.3 (TaqI, polymorphism), pXJ1.2 (BclI polymorphism), P20 (MspI and EcoRV polymorphism) and the cDNA probes. DNA deletions have been detected in 30 of the 60 affected boys and the carrier risks of 49 women have been determined by RFLP analyses. In those families where the risks were uncertain because the affected males had died, prenatal exclusion testing was offered to potential carriers. Two pregnancies were terminated when male fetuses were shown to be affected, since they had the same deletion as that observed in the proband.


Pacific oyster (Crassostrea gigas) hemocyte are not affected by a mixture of pesticides in short-term in vitro assays.
Pesticides are frequently detected in estuaries among the pollutants found in estuarine and coastal areas and may have major ecological consequences. They could endanger organism growth, reproduction, or survival. In the context of high-mortality outbreaks affecting Pacific oysters, Crassostrea gigas, in France since 2008, it appears of importance to determine the putative effects of pesticides on oyster susceptibility to infectious agents. Massive mortality outbreaks reported in this species, mainly in spring and summer, may suggest an important role played by the seasonal use of pesticides and freshwater input in estuarine areas where oyster farms are frequently located. To understand the impact of some pesticides detected in French waters, their effects on Pacific oyster hemocytes were studied through short-term in vitro experiments. Bivalve immunity is mainly supported by hemocytes eliminating pathogens by phagocytosis and producing compounds including lysosomal enzymes and antimicrobial molecules. In this study, oyster hemocytes were incubated with a mixture of 14 pesticides and metaldehyde alone, a molecule used to eliminate land mollusks. Hemocyte parameters including dead/alive cells, nonspecific esterase activities, intracytoplasmic calcium, lysosome number and activity, and phagocytosis were monitored by flow cytometry. No significant effect of pesticides tested at different concentrations was reported on oyster hemocytes maintained in vitro for short-term periods in the present study. It could be assumed that these oyster cells were resistant to pesticide exposure in tested conditions and developing in vivo assays appears as necessary to better understand the effects of pollutants on immune system in mollusks.


Functional characterization of naturally occurring mutant androgen receptors from subjects with complete androgen insensitivity.
Mutations in the androgen receptor (AR) are thought to cause complete androgen insensitivity (CAIS) in 46,XY human subjects who have a female phenotype despite normal adult male concentrations of plasma testosterone. Assays of AR binding in cultured skin fibroblasts from subjects with CAIS show either an apparent absence of AR (AR-) or normal levels of AR (AR+) binding. In several subjects with CAIS, AR-, no gross AR mutation was detected by Southern blot analyses of genomic DNA and normal sized 10 kilobase mRNA was present on Northern blots of poly(A+) RNA from cultured genital skin fibroblasts. We have used the polymerase chain reaction to amplify individual exons within the human AR gene of subjects with CAIS and have identified point mutations in three subjects. In one AR- subject (R774C), amino acid 774 was changed from arginine (CGC) to cysteine (TGC), in another AR- subject (R831Q), arginine (CGA) was changed to glutamine (CAA) at position 831, and in an AR+ subject (V866M) a methionine (ATG) was substituted for valine (GTG) at position 866. Transfection of wild type and mutant AR cDNA clones into COS cells results in detection of AR protein by immunoblotting. AR ligand binding activity is absent in cells transfected with AR mutants R774C and R831Q, but present with AR mutant V866M. Androgen binding in cells transfected with AR mutant V866M has a 6-fold lower apparent binding affinity than that of wild-type AR. Transcriptional activation of the MMTV-CAT reporter gene was androgen dependent and specific and nearly maximal at physiological concentrations (10(-10) M) of androgen when wild-type AR was transfected into cells, whereas neither AR mutants R774C nor R831Q were able to stimulate CAT activity even at 10(-8) M androgen. AR mutant V866M was able to stimulate CAT activity but the androgen dose dependency was shifted toward pharmacological concentrations of steroid that exceed in vivo levels. The molecular basis of CAIS in humans exhibits genetic heterogeneity. Our study shows that some cases of CAIS are explained by an inability to form a functional AR-steroid complex and hence, the AR is unable to activate transcription of genes essential for male sex differentiation during fetal development.


Noninvasive testing for carotid artery stenosis: I. Prospective analysis of three methods.
Oculoplethysmography-carotid phonoangiography and periorbital directional Doppler sonography are two techniques widely used in the noninvasive evaluation of possible carotid artery disease. Recent advances with sonographic Doppler devices now permit measurement of blood velocities in the extracranial carotid arteries by direct scanning with a color coded Doppler imaging system. A prospective study involving 216 patients being evaluated for possible carotid insufficiency was carried out to compare the results obtained with these three methods. With stenosis 65% or greater at angiography, the accuracy of the Doppler imaging system was 94%, that of oculoplethysmography-carotid phonoangiography was 84%, and that of periorbital directional Doppler sonography was 80%. These results demonstrate that direct Doppler examination of the carotid bifurcation is superior to either of the other two techniques for the detection of carotid artery stenosis.


A microscopy study of hyphal growth of Penicillium rubens on gypsum under dynamic humidity conditions.
To remediate indoor fungal growth, understanding the moisture relations of common indoor fungi is crucial. Indoor moisture conditions are commonly quantified by the relative humidity (RH). RH is a major determinant of the availability of water in porous indoor surfaces that fungi grow on. The influence of steady-state RH on growth is well understood. Typically, however, the indoor RH constantly changes so that fungi have to endure frequent periods of alternating low and high RH. Knowledge of how common indoor fungi survive and are affected by the low-RH periods is limited. In particular, the specific effects of a drop in RH on the growth of the mycelium remain unclear. In this work, video microscopy was used to monitor hyphal growth of Penicillium rubens on gypsum substrates under controlled dynamic humidity conditions. The effect of a single period of low RH (RH = 50-90%) interrupting favourable conditions (RH = 97%) was tested. It was found that hyphal tips ceased to extend when exposed to any tested decrease in RH. However, new hyphal growth always emerges, seemingly from the old mycelium, suggesting that this indoor fungus does not rely only on conidia to survive the humidity patterns considered. These findings are a fundamental step in unravelling the effect of RH on indoor fungal growth.


Rous sarcoma virus infection of synchronized cells establishes provirus integration during S-phase DNA synthesis prior to cellular division.
Synchronized chicken embryo fibroblasts, prepared by addition of serum to stationary cells arrested in Go, were exposed to the Prague strain of Rous sarcoma virus. At different times during the cell cycle, high molecular weight DNA was prepared from infected cells and examined for the presence of newly integrated viral DNA sequences. The results demonstrate that newly integrated viral sequences were first detected during S-phase DNA synthesis 9 hr after infection. The presence of colchicine prevented cellular division and delayed the appearance of progeny virus but it did not affect the appearance of viral specific DNA in the high molecular weight fraction of cellular DNA. Our results indicate that provirus integration, occurring during S-phase DNA synthesis, does not require cell division. Previous experiments have demonstrated that Rous sarcoma virus infection of chicken embryo fibroblasts requires cell division to initiate viral RNA synthesis and the production of progeny virus. The findings presented in this report support the hypothesis that division of the infected cells is required for an event that controls viral expression at the level of the integrated provirus.


Subacute care facilities: enormous cost savings raise health reform issues.
In summary, there is every reason to believe that subacute care providers will ultimately achieve their goal of reducing the cost of those subacute care services that are currently being furnished in the high-cost acute care setting. The degree to which this goal will be achieved, however, will depend upon the level of acceptance of subacute care within the public and private sectors of our health care system. Such acceptance will be greatly facilitated by thoughtful consideration of the economic impact of subacute care services on the health care system as a whole, and its ability to adapt to whatever changes are instituted as a result of the ongoing debate over health care reform. Further, anticipating and responding to concerns relating to the cost and quality of subacute care services will not only lend credibility to the subacute care movement, but will insure its place in the our soon-to-be-reformed health care system.


AHRA (American Healthcare Radiology Administrators) patient satisfaction survey.
Healthcare's focus has shifted from the institutional to the personal, requiring hospitals to carefully evaluate patient satisfaction. A carefully written survey can supply invaluable feedback from patients about their experiences in the department. The AHRA has developed and provides in this article a survey designed to measure the aspects of care that contribute most to patient satisfaction, such as length of wait, explanation of procedures and privacy, etc. When conducting the survey, use procedures that ensure a representative sample and adequate response rate. Computerized, on-site data collection is the most timely and accurate method when available. Results of the survey must receive action to correct problems and analyze perceptions of quality. CQI should be used to ensure continual improvement.


Treatment of oral cavity squamous cell carcinoma with adjuvant or definitive intensity-modulated radiation therapy.
The optimal management of oral cavity squamous cell carcinoma (OCSCC) typically involves surgical resection followed by adjuvant radiotherapy or chemoradiotherapy (CRT) in the setting of adverse pathologic features. Intensity-modulated radiation therapy (IMRT) is frequently used to treat oral cavity cancers, but published IMRT outcomes specific to this disease site are sparse. We report the Dana-Farber Cancer Institute experience with IMRT-based treatment for OCSCC. Retrospective study of all patients treated at Dana-Farber Cancer Institute for OCSCC with adjuvant or definitive IMRT between August 2004 and December 2009. The American Joint Committee on Cancer disease stage criteria distribution of this cohort included 5 patients (12%) with stage I; 10 patients (24%) with stage II (n = 10, 24%); 14 patients (33%) with stage III (n = 14, 33%); and 13 patients (31%) with stage IV. The primary endpoint was overall survival (OS); secondary endpoints were locoregional control (LRC) and acute and chronic toxicity. Forty-two patients with OCSCC were included, 30 of whom were initially treated with surgical resection. Twenty-three (77%) of 30 surgical patients treated with adjuvant IMRT also received concurrent chemotherapy, and 9 of 12 (75%) patients treated definitively without surgery were treated with CRT or induction chemotherapy and CRT. With a median follow-up of 2.1 years (interquartile range, 1.1-3.1 years) for all patients, the 2-year actuarial rates of OS and LRC following adjuvant IMRT were 85% and 91%, respectively, and the comparable results for definitive IMRT were 63% and 64% for OS and LRC, respectively. Only 1 patient developed symptomatic osteoradionecrosis, and among patients without evidence of disease, 35% experienced grade 2 to 3 late dysphagia, with only 1 patient who was continuously gastrostomy-dependent. In this single-institution series, postoperative IMRT was associated with promising LRC, OS, and lower late toxicity rates, and chemoradiotherapy was a successful treatment for patients with high-risk disease. In contrast, outcomes of radiation-based treatment for patients with inoperable locally advanced disease were markedly less successful.


ERBB4 is over-expressed in human colon cancer and enhances cellular transformation.
The ERBB4 receptor tyrosine kinase promotes colonocyte survival. Herein, we tested whether ERBB4's antiapoptotic signaling promotes transformation and colorectal tumorigenesis. ERBB4 alterations in a The Cancer Genome Atlas colorectal cancer (CRC) data set stratified survival, and in a combined Moffitt Cancer Center and Vanderbilt Medical Center CRC expression data set, ERBB4 message levels were increased at all tumor stages. Similarly, western blot and immunohistochemistry on additional CRC tissue banks showed elevated ERBB4 protein in tumors. ERBB4 was highly expressed in aggressive, dedifferentiated CRC cell lines, and its knockdown in LIM2405 cells reduced anchorage-independent colony formation. In nude mouse xenograft studies, ERBB4 alone was insufficient to induce tumor establishment of non-transformed mouse colonocytes, but its over-expression in cells harboring Apc(min) and v-Ha-Ras caused a doubling of tumor size. ERBB4-expressing xenografts displayed increased activation of survival pathways, including epidermal growth factor receptor and Akt phosphorylation and COX-2 expression, and decreased apoptotic signals. Finally, ERBB4 deletion from mouse intestinal epithelium impaired stem cell replication and in vitro enteroid establishment. In summary, we report that ERBB4 is over-expressed in human CRC, and in experimental systems enhances the survival and growth of cells driven by Ras and/or WNT signaling. Chronic ERBB4 over-expression in the context of, for example, inflammation may contribute to colorectal carcinogenesis. Tumors with high receptor levels are likely to have enhanced cell survival signaling through epidermal growth factor receptor, PI3K and COX-2. These results suggest ERBB4 as a novel therapeutic target in a subset of CRC.


Energy level and sleep quality following bone marrow transplantation.
While problems with sleep and energy level (ie fatigue) are commonly reported during recovery from bone marrow transplantation (BMT), little in-depth information regarding these two problem areas in BMT patients is available. Using both questionnaire and telephone interview methods, information regarding current sleep and energy level problems was obtained from 172 adult BMT survivors drawn from five different BMT treatment centers. Respondents were a mean of 43.5 months post-BMT at the time of the initial assessment. Similar questionnaire data was obtained from 137 respondents (80%) at a follow-up assessment 18 months after the initial assessment. Results suggested that half to two-thirds of disease-free BMT recipients experience problems with regard to current energy level or sleep quality. While for the majority of patients these problems were rated as mild, 15-20% of BMT recipients showed moderate to severe problems in these areas with corresponding decrements in quality of life. Furthermore, both cross-sectional and longitudinal analyses suggested that problems in these areas did not simply abate with time. Only low to moderate correlations were obtained between indices of sleep and energy problems and measures of anxious and depressed mood. Finally, the presence of current sleep problems was associated with older age at BMT, receipt of TBI during pre-BMT conditioning, and female gender. Further research needs to address the specific etiology of chronic problems with sleep and energy level in BMT recipients as well as evaluate biobehavioral strategies for managing these problems.


Summary of adverse drug events for hydroxychloroquine, azithromycin, and chloroquine during the COVID-19 pandemic.
Given the increased use of hydroxychloroquine (HCQ), chloroquine (CQ), and azithromycin (AZM) during the early months of the coronavirus disease 2019 (COVID-19) pandemic, there is a need to evaluate the associated safety concerns. The objective of this study was to summarize the adverse drug events (ADEs) associated with HCQ, CQ, and AZM use during the national COVID-19 emergency and compare the results with known adverse reactions listed in the drugs' package inserts. A cross-sectional study design was used. The publicly available Food and Drug Administration Adverse Event Reporting System quarterly data extract files from January 1, 2020 to June 30, 2020 were downloaded. A disproportionality analysis was conducted using the proportional reporting ratio to identify possible ADE signals. A Poisson regression was used to assess if the number of ADE reports for the 3 drugs increased over time. There was a statistically significant increasing trend in the reported ADEs for both HCQ (P < 0.001) and AZM (P < 0.001). Before the declaration of the national emergency, there were 592 reported drug-ADE pairs for the 3 drugs compared with 2492 drug-ADE pairs reported after March 13, 2020. These 2492 drug-ADE pairs represented 848 ADEs across the 3 drugs, of which 114 (13.4%) were identified as potential signals including 55 (48.2%) that were not listed in the prescribing information. Our results showed that the reported ADEs for HCQ and AZM have increased during the COVID-19 pandemic. Differences were observed in both the type of and frequency of the highest reported ADEs for the 3 selected drugs before and after the national emergency declaration. Although causation cannot be determined from ADE reports, further investigation of some reports may be warranted. Our results highlight the need for pharmacovigilance and education of health care professionals on the safety of these drugs when being used for COVID-19 prophylaxis or treatment.


Assignment of a locus (GLC3A) for primary congenital glaucoma (Buphthalmos) to 2p21 and evidence for genetic heterogeneity.
Primary congenital glaucoma (GLC3) is an inherited eye disorder that accounts for 0.01-0.04% of total blindness. Although a large number of chromosomal abnormalities have already been reported in patients with congenital glaucoma, the precise location and pathogenesis of this condition remain elusive. By using a group of 17 GLC3 families and a combination of both candidate regional and general positional mapping strategies, we have mapped a locus for GLC3 to the short arm of chromosome 2. Eleven families showed no recombination with 3 tightly linked markers of D2S177 (Z = 9.40), D2S1346 (Z = 8.83), and D2S1348 (Z = 8.90) with a combined haplotype lod score of 11.50. Haplotype and multipoint linkage analyses of 14 DNA markers from 2p indicated that the disease gene is located in the 2p21 region and is flanked by DNA markers D2S1788/D2S1325 (theta = 0.03; Z = 5.42) and D2S1356 (theta = 0.05; Z = 4.69). Inspection of haplotype and heterogeneity analysis confirmed that 6 families are not linked to the 2p21 region, thus providing the first proof of genetic heterogeneity for this phenotype. We therefore designated the locus on 2p21 GLC3A and positioned it in the overall linkage map of Tel-D2S405-D2S367-(D2S1788/D2S1325)-[(GLC3A++ +, D2S177)/(D2S1346/D2S1348)]-D2S1356-D2S119- D2S1761-D2S1248-D2S1352-D2S406- D2S441-Cen. Of the seven genes mapping to the 2p21 region, CAD, CALM2, and LHCGR are centromeric to D2S119 and can be excluded as a candidate for GLC3A, but mutations in PRKR, TIK, SOS1, or SPTBN1 may still be accountable for this phenotype. As human 2p21 shows homology with mouse chromosomes 11 and 17, the homolog of GLC3A is expected to reside on one of these two chromosomes.


Brucella endocarditis of pseudoaneurysm of an aortic composite graft.
The occurrence of Brucella endocarditis following Bentall operation is a rare and life threatening condition, particularly when it is complicated by development of a pseudoaneurysm. Here we present a 40-year-old veterinarian with bicuspid aortic valve, who developed type A aortic root dissection and required Bentall operation. His past medical history was positive for an episode of treated brucellosis. Four months after the operation, he developed signs, symptoms and serological findings of brucellosis for the second time and was treated with antibiotics. Then after he was well untill about 14 days prior to his recent admission, when he again developed hip pain, fever, shortness of breath, profound fatigue and weakness. His transthoracic echocardiography was suggestive of endocarditis. A transesophageal echocardiogram revealed detachment of valve-conduit from the annulus and the mitral-aortic intervalvular fibrosa and the presence of a large aortic pseudoaneurysm with multiple vegetations attached to its Dacron walls. A huge pseudoaneurysm was detected at surgery and the whole valve-conduit was replaced with a 25 mm homograft. Blood and vegetation cultures turned to be positive for Brucella melitensis. Early echocardiographic diagnosis and prompt surgical intervention were helpful for survival of our patient who had aortic pseudoaneurysm complicated by Brucella endocarditis.


The mammalian peroxin Pex5pL, the longer isoform of the mobile peroxisome targeting signal (PTS) type 1 transporter, translocates the Pex7p.PTS2 protein complex into peroxisomes via its initial docking site, Pex14p.
In mammals, two isoforms of the peroxisome targeting signal (PTS) type 1 receptor Pex5p, i.e. Pex5pS and Pex5pL with an internal 37-amino acid insertion, have previously been identified. Expression of either type of Pex5p complements the impaired PTS1 import in Chinese hamster ovary pex5 mutants, but only Pex5pL can rescue the PTS2 import defect noted in a subgroup of pex5 mutants such as ZP105. In this work, we found that Pex5pL directly interacts with the PTS2 receptor Pex7p, carrying its cargo PTS2 protein in the cytosol. Pex5pL, but not Pex5pS, mediated the binding of PTS2 protein to Pex14p by translocating Pex7p, demonstrating that Pex5pL plays a pivotal role in peroxisomal PTS2 import. Pex5p was localized mostly in the cytosol in wild-type CHO-K1 and Pex14p-deficient mutant cells, whereas it accumulated in the peroxisomal remnants in cell mutants defective in Pex13p or the RING family peroxins such as Pex2p and Pex12p. Furthermore, overexpression of Pex14p, but not Pex10p, Pex12p, or Pex13p, caused accumulation of Pex5p in peroxisomal membranes, with concomitant interference with PTS1 and PTS2 import. Therefore, Pex5p carrying the cargoes most likely docks with the initial site (Pex14p) in a putative import machinery, subsequently translocating to other components such as Pex13p, Pex2p, Pex10p, and Pex12p.


[The academic background of the physician and the communication of a patient's death to family members].
Communicating the death of a patient always brings about a certain degree of insecurity in the physician. To evaluate this issue, 121 family members of patients who died at our hospital as well as the professional who conveyed the information were interviewed. We verified that 12.1% of the families disapproved of how they were told about the death, and that 26.4% did not receive any attention at all from the medical staff. Physicians find that the most difficult situations arise when they have to notify the death of young patients (43.3%), death from an acute disease (56.6%), and when the family does not understand the situation (17%). Only 18.9% of the professionals considered their academic background adequate on this subject. Communication between the medical staff and the family members should take place after the death. The more difficult cases require a good relationship between the parties. Training of the professionals on the subject should be improved since it directly affects how family and relatives are dealt with.


Reproducibility of peak oxygen uptake and other cardiopulmonary exercise testing parameters in patients with heart failure (from the Heart Failure and A Controlled Trial Investigating Outcomes of exercise traiNing).
Peak oxygen uptake (pVo2) is an important parameter in assessing the functional capacity and prognosis of patients with heart failure. In heart failure trials, change in pVo2 was often used to assess the effectiveness of an intervention. However, the within-subject variability of pVo2 on serial testing may limit its usefulness. This study was designed to evaluate the within-subject variability of pVo2 over 2 baseline cardiopulmonary exercise tests. As a substudy of the HF-ACTION trial, 398 subjects (73% men, 27% women; mean age 59 years) with heart failure and left ventricular ejection fraction < or =35% underwent 2 baseline cardiopulmonary exercise tests within 14 days. Mean pVo2 was unchanged from test 1 to test 2 (15.16 +/- 4.97 vs 15.18 +/- 4.97 ml/kg/min; p = 0.78). However, mean within-subject absolute change was 1.3 ml/kg/min (10th, 90th percentiles 0.1, 3.0), with 46% of subjects increasing and 48% decreasing on the second test. Other parameters, including the ventilation-to-carbon-dioxide production slope and Vo2 at ventilatory threshold, also showed significant within-subject variation with minimal mean differences between tests. In conclusion, pVo2 showed substantial within-subject variability in patients with heart failure and should be taken into account in clinical applications. However, on repeated baseline cardiopulmonary exercise tests, there appears to be no familiarization effect for Vo2 in patients with HF. Therefore, in multicenter trials, there is no need to perform >1 baseline cardiopulmonary exercise test.


Identification of epigenetic modulators in human breast cancer by integrated analysis of DNA methylation and RNA-Seq data.
Human tumors undergo massive changes in DNA methylation. Recent studies showed that site-specific methylation of CpG sites is determined by the DNA sequence context surrounding the CpG site, which alludes to a possible mechanism for site-specific aberrant DNA methylation in cancer through DNA-binding proteins. In this paper, DNA methylation data and RNA-Seq data of breast tumors and normal tissues in the database of The Cancer Genome Atlas (TCGA) were integrated with information of DNA motifs in seven databases to find DNA-binding proteins and their binding motifs that were involved in aberrant DNA methylation in breast cancer. A total of 42,850 differentially methylated regions (DMRs) that include 77,298 CpG sites were detected in breast cancer. One hundred eight DNA motifs were found to be enriched in DMRs, and 109 genes encoding proteins binding to these motifs were determined. Based on these motifs and genes, 63 methylation modulator genes were identified to regulate differentially methylated CpG sites in breast cancer. A network of these 63 modulator genes and 645 transcription factors was constructed, and 20 network modules were determined. A number of pathways and gene sets related to breast cancer were found to be enriched in these network modules. The 63 methylation modulator genes identified may play an important role in aberrant methylation of CpG sites in breast cancer. They may help to understand site-specific dysregulation of DNA methylation and provide epigenetic markers for breast cancer.


[Effect of carbon dioxide laser on Mycobacterium tuberculosis and microflora].
The effect of CO2 laser on M. tuberculosis (MT) and nonspecific micro-organisms has been studied. Radiation of MT in suspension causes a decrease in the number of colonies. Laser action on MT and microflora after their growing in a solid nutrient media produces a bactericidal action in the exposed zone with the area of growth inhibition being in a direct proportion to the laser power and the time of its action.


Implication of glycogen synthase kinase 3 in diabetes-associated islet inflammation.
Islet inflammation is associated with defective β cell function and mass in type 2 diabetes (T2D). Glycogen synthase kinase 3 (GSK3) has been identified as an important regulator of inflammation in different diseased conditions. However, the role of GSK3 in islet inflammation in the context of diabetes remains unexplored. In this study, we investigated the direct implication of GSK3 in islet inflammation in vitro and tested the impact of GSK3 inhibition in vivo, on the reduction of islet inflammation, and the improvement of glucose metabolism in the Goto-Kakizaki (GK) rat, a spontaneous model of T2D. GK rats were chronically treated with infra-therapeutic doses of lithium, a widely used inhibitor of GSK3. We analyzed parameters of glucose homeostasis as well as islet inflammation and fibrosis in the endocrine pancreas. Ex vivo, we tested the impact of GSK3 inhibition on the autonomous inflammatory response of non-diabetic rat and human islets, exposed to a mix of pro-inflammatory cytokines to mimic an inflammatory environment. Treatment of young GK rats with lithium prevented the development of overt diabetes. Lithium treatment resulted in reduced expression of pro-inflammatory cytokines in the islets. It decreased islet fibrosis and partially restored the glucose-induced insulin secretion in GK rats. Studies in non-diabetic human and rat islets exposed to inflammatory environment revealed the direct implication of GSK3 in the islet autonomous inflammatory response. We show for the first time, the implication of GSK3 in islet inflammation and suggest this enzyme as a viable target to treat diabetes-associated inflammation.


Multilayered slab waveguide design using a hybrid field vector.
A model is introduced that facilitates an easy scheme to design planar multilayered waveguides. The basis of this model is a field related vector that follows simply shaped trajectories as a function of the depth coordinate in the waveguide. Its diagram provides qualitative insight into the effects upon guided modes of a change in the number of layers, in their phase thicknesses and in the state of polarization. In addition, the method offers the possibility of studying the corresponding effects upon field components inside the waveguide.


Accuracy of revised Bethesda guidelines, microsatellite instability, and immunohistochemistry for the identification of patients with hereditary nonpolyposis colorectal cancer.
The selection of individuals for hereditary nonpolyposis colorectal cancer (HNPCC) genetic testing is challenging. Recently, the National Cancer Institute outlined a new set of recommendations, the revised Bethesda guidelines, for the identification of individuals with HNPCC who should be tested for microsatellite instability. To establish the most effective and efficient strategy for the detection of MSH2/MLH1 gene carriers. A prospective, multicenter, nationwide study (the EPICOLON study) in 20 hospitals in the general community in Spain of 1222 patients with newly diagnosed colorectal cancer between November 1, 2000, and October 31, 2001. Microsatellite instability testing and MSH2/MLH1 immunostaining in all patients regardless of age, personal or family history, and tumor characteristics. Patients whose tumors exhibited microsatellite instability and/or lack of protein expression underwent MSH2/MLH1 germline testing. Effectiveness and efficiency of both microsatellite instability testing and immunostaining, either directly or previous selection of patients according to the revised Bethesda guidelines, were evaluated with respect to the presence of MSH2/MLH1 germline mutations. Two hundred eighty-seven patients (23.5%) fulfilled the revised Bethesda guidelines. Ninety-one patients (7.4%) had a mismatch repair deficiency, with tumors exhibiting either microsatellite instability (n = 83) or loss of protein expression (n = 81). Germline testing identified 11 mutations (0.9%) in either MSH2 (7 cases) or MLH1 (4 cases) genes. Strategies based on either microsatellite instability testing or immunostaining previous selection of patients according to the revised Bethesda guidelines were the most effective (sensitivity, 81.8% and 81.8%; specificity, 98.0% and 98.2%; positive predictive value, 27.3% and 29.0%, respectively) to identify MSH2/MLH1 gene carriers. Logistic regression analysis confirmed the revised Bethesda guidelines as the most discriminating set of clinical parameters (odds ratio, 33.3; 95% confidence interval, 4.3-250; P = .001). The revised Bethesda guidelines constitute a useful approach to identify patients at risk for HNPCC. In patients fulfilling these criteria, both microsatellite instability testing and immunostaining are equivalent and highly effective strategies to further select those patients who should be tested for MSH2/MLH1 germline mutations.


Effects of a phytogenic feed additive on growth performance and ileal nutrient digestibility in broiler chickens.
A study was undertaken to examine the effects of a phytogenic feed additive (PFA) containing essential oils of thyme and star anise as lead active components on the growth performance and apparent ileal nutrient digestibility in broiler chickens. In total, 528 one-day-old Cobb male broilers were randomly divided into 4 dietary treatment groups with 6 replicate pens per treatment group (22 birds each). The dietary treatments were a control starter and grower basal diet without PFA or 150, 750, or 1,500 mg/kg of PFA. Body weight, weight gain, and feed intake were not significantly influenced by the feed additive, but the feed conversion ratio during the grower (22-42 d) and overall (1-42 d) periods improved linearly (P < 0.05) by the administration of PFA compared with that of the control diet. The average weights of the liver, heart, kidneys, and spleen were not significantly affected by the PFA. The results of the apparent ileal digestibility of crude ash, CP, crude fat, calcium, and phosphorus showed a linear increase (P < 0.05) related to the increase of PFA dose in the diet. Therefore, the means of digestibility of these nutrients were significantly higher in birds fed the PFA for all categories of age compared with the digestibility of these nutrients in the controls. In conclusion, the mode of action of the tested PFA can be explained by an improvement in the nutrient digestibility in the small intestine. The underlying physiological mechanisms, however, need to be characterized further.


Enhanced Fermentable Sugar Production from Enteromorpha Polysaccharides by the Crude Enzymes of Vibrio sp. H11.
In recent years, large-scale outbreaks of the green alga Enteromorpha prolifera in China's offshore waters have posed a serious threat. This study aimed to improve Enteromorpha polysaccharide (EP) enzymatic sugar production using the hydrolase system of Vibrio sp. H11, an EP-utilizing microbial strain. Strain H11 was found to contain 711 carbohydrate-related genes, and 259 genes belong to glycoside hydrolases that have the potential to hydrolyze EP. To maximize the capability of strain H11 to hydrolyze EP, both the culture medium and the composition were optimized. Response surface methodology analysis showed that maximal enzymatic production from strain H11 was 8.43 U/mL after 26-h incubation. When 50 g/L of EP were treated with crude H11 enzyme, the concentration of fermentation sugars increased by 36.12%. Under these conditions, the hydrolysates were capable of generating 3,217 mL/L of biogas and 6.74 g/L of biosolvents, with increases of 28.17 and 7.29%, respectively, compared to controls. The combined application of the H11 enzymatic system and anaerobic fermentation has the potential to improve the comprehensive application of EP.


First Whole Genome Sequence of Anaplasma platys, an Obligate Intracellular Rickettsial Pathogen of Dogs.
We have assembled the first genome draft of Anaplasma platys, an obligate intracellular rickettsia, and the only known bacterial pathogen infecting canine platelets. A. platys is a not-yet-cultivated bacterium that causes infectious cyclic canine thrombocytopenia, a potentially fatal disease in dogs. Despite its global distribution and veterinary relevance, no genome sequence has been published so far for this pathogen. Here, we used a strategy based on metagenome assembly to generate a draft of the A. platys genome using the blood of an infected dog. The assembled draft is similar to other Anaplasma genomes in size, gene content, and synteny. Notable differences are the apparent absence of rbfA, a gene encoding a 30S ribosome-binding factor acting as a cold-shock protein, as well as two genes involved in biotin metabolism. We also observed differences associated with expanded gene families, including those encoding outer membrane proteins, a type IV secretion system, ankyrin repeat-containing proteins, and proteins with predicted intrinsically disordered regions. Several of these families have members highly divergent in sequence, likely to be associated with survival and interactions within the host and the vector. The sequence of the A. platys genome can benefit future studies regarding invasion, survival, and pathogenesis of Anaplasma species, while paving the way for the better design of treatment and prevention strategies against these neglected intracellular pathogens.


The antidepressant-like action of metabotropic glutamate 7 receptor agonist N,N'-bis(diphenylmethyl)-1,2-ethanediamine (AMN082) is serotonin-dependent.
Behavioral studies show that modulation of the glutamatergic system might be an efficient way to achieve antidepressant activity. Among the group III metabotropic glutamate (mGlu) receptors, the mGlu7 receptor subtype seems to be the most promising target for potential antidepressants. It has been shown that a selective, allosteric mGlu7 receptor agonist, N,N'-bis (diphenylmethyl)-1,2-ethanediamine (AMN082), induced antidepressant-like action in behavioral tests in mice, although the mechanisms responsible for this action remained unknown. Here, we decided to investigate the possible role of the serotonergic system in the antidepressant-like activity of AMN082 in both the forced swim test (FST) in rats and the tail suspension test (TST) in mice. We found that AMN082 (1-10 mg/kg i.p.) induced a dose-dependent reduction in the immobility of rats and an increase in their swimming behavior, whereas there were not any changes in climbing behavior in the FST in rats. In the TST in mice we found that AMN082 (3 mg/kg i.p.) did not induce an antidepressant-like effect after depletion of serotonin (5-HT) with para-chlorophenylalanine. Moreover, we revealed that citalopram, but not reboxetine, when combined with AMN082 (all compounds used at low subeffective doses), induced a significant antidepressant-like effect in the TST. We also discovered that the 5-HT1A receptor antagonist N-{2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl}-N-(2-pyridynyl) cyclohexane-carboxamide (WAY100635) (0.1 mg/kg s.c.), but not the 5-HT2A/2C receptor antagonist ritanserin (0.5 mg/kg i.p.), blocked the antidepressant-like action of AMN082. Altogether, the results of our studies show that the antidepressant-like action of the mGlu7 receptor-positive modulator AMN082 depends on the activation of the serotonergic system.


Mortality among employees of an Ontario asbestos-cement factory.
Mortality among 535 asbestos-exposed and 205 nonexposed employees of an asbestos-cement factory was investigated. In the period beyond 20 yr from first exposure, the exposed workers had standardized mortality ratios of 175 for all causes of death, 370 for all malignancies, 480 for lung cancer, 240 for gastrointestinal cancers, and 17 deaths from mesothelioma; the factory control subjects had mortality rates similar to the general population. The cell-type distribution of the lung cancers was similar to that occurring in middle-aged smokers. Cumulative fiber exposures were calculated for the production workers, and mortality rates for the asbestos-associated malignancies were found to have significant trends with exposure. Exposure-related lung cancer risks were noted, with a large margin of uncertainty, to be similar to those observed in an American study of manmade mineral fiber workers.


Hemodynamic defense response to thyrotropin-releasing hormone injected into medial preoptic nucleus in rats.
The role of thyrotropin-releasing hormone (TRH) and glutamate in central cardiovascular control was studied by microinjections (50 nl) of these agents into the medial or median preoptic nuclei of conscious rats (n = 49) with continuous recording of mean arterial pressure, heart rate, blood flow, and vascular resistance in hindquarter, renal, and mesenteric blood vessels. In addition, the effect of TRH on renal sympathetic nerve activity was studied in anesthetized rats. TRH (2.4-240 pmol) elicited the typical hemodynamic pattern of the "defense response" consisting of increased blood pressure, tachycardia, hindquarter vasodilation, and constriction of renal and mesenteric blood vessels. Maximum changes in cardiovascular variables after the 24-pmol dose were +12 +/- 2 mmHg (mean arterial pressure), +73 +/- 15 beats/min (heart rate), -21 +/- 6% (hindquarter resistance), +15 +/- 6% (renal resistance), and +31 +/- 6% (mesenteric resistance), P less than 0.05 compared with saline. In anesthetized rats, TRH at the 2.4-pmol dose increased renal sympathetic nerve activity (greater than 200%, n = 5, P less than 0.05 compared with control) with no effect on blood pressure or renal flow. Glutamate (10 or 100 nmol) produced a similar pattern of hemodynamic changes as TRH. Peak effects after the 100-nmol dose of glutamate were +16 +/- 2 mmHg (mean arterial pressure), +57 +/- 11 beats/min (heart rate), -31 +/- 3% (hindquarter resistance), +29 +/- 9% (renal resistance), and +87 +/- 22% (mesenteric resistance), P less than 0.05 compared with saline. The glutamate N-methyl-D-aspartate (NMDA) receptor blocker MK-801 (300 micrograms/kg iv) attenuated the pressor-tachycardic responses to TRH and the pressor-mesenteric constrictor responses to glutamate.(ABSTRACT TRUNCATED AT 250 WORDS)


Patch-clamp studies of isolated mouse olfactory receptor neurons.
Olfactory receptor neurons isolated from embryonic, neonatal, and adult mice were studied using the patch-clamp technique. Several distinct types of ion channels were characterized in patches of membrane from the neuronal soma and the dendritic knob of receptor neurons, including a 130-pS Ca++-activated K+ channel with voltage-dependent kinetics, an 80-pS Ca++-activated K+ channel with voltage-insensitive kinetics, a 25-pS K+ channel with properties similar to inward rectifiers, and a 40-pS K+ channel that was activated and then inactivated by rapid depolarization. Evidence of large-conductance (greater than 200 pS) Cl- channels, which were Ca++ insensitive and increasingly active at depolarizing membrane potentials, and voltage-activated Ca++ channels (16 pS) was also obtained. From K+ channel activity recorded from cell-attached patches, the intracellular [Ca++] was inferred to be below 0.1 microM, and the membrane potential was inferred to be approximately -50 mV. The receptor neurons had high input resistances, and action potentials could be elicited by picoampere amounts of depolarizing current. The receptor neurons responded to applied odorant molecules and to forskolin with increases in membrane conductance. These results provide a description of the membrane properties of olfactory receptor neurons and a basis for understanding their electrical activity and response to odorants.


High-dose therapy and autologous peripheral-blood stem-cell transplantation as salvage treatment for HIV-associated lymphoma in patients receiving highly active antiretroviral therapy.
High-dose therapy (HDT) and peripheral-blood stem-cell transplantation (PBSCT) in HIV-associated lymphoma (HIV-Ly) has been recently reported in selected patients. We describe the results of a multi-institutional program of HDT and PBSCT as salvage therapy in HIV-Ly responsive to highly active antiretroviral therapy (HAART) in unselected patients. Patients with resistant or relapsed HIV-Ly after first-line chemotherapy (CT) underwent PBSC collection after a course of second-line CT or cyclophosphamide and granulocyte colony-stimulating factor. Patients with chemotherapy-sensitive disease received carmustine, etoposide, cytarabine, and melphalan (BEAM regimen) and PBSC reinfusion. Effective HAART was maintained during the entire program. Sixteen consecutive patients entered the program. Adequate collection of PBSC was obtained in 80% of patients (median CD34+ cells 6.8 x 106/kg). Three patients had early progression. Ten patients (62%) received PBSCT with prompt engraftment in all patients (neutrophils and platelet engraftment after a median of 10 days [range, 8 to 10 days] and 13 days [range, 8 to 18 days], respectively). No patients died as a result of opportunistic or other infections or treatment-related complications. Eight of nine assessable patients achieved complete remission (one patient after radiotherapy for residual disease) and one patient achieved partial remission. Two patients experienced relapse and died at +10 and +14 months. Six patients are alive and disease free at a median of 8 months after transplantation. Our data confirm that HDT plus PBSCT is feasible and active as salvage therapy in HIV-Ly on a multi-institutional basis and in unselected HAART-responding patients. HIV infection should no longer preclude the opportunity of HDT in patients with lymphoma.


Characterizing the HIV/AIDS Epidemic in the United States and China.
The HIV/AIDS data from the national surveillance systems of China and the United States from 1985 to 2014 were compared to characterize the HIV/AIDS epidemic in both countries. The current estimated national HIV prevalence rate in China and the United States are 0.0598% and 0.348%, respectively. In the United States, the annual number of new HIV infections has remained relatively stable (~50,000 each year) and has shown a downward trend in recent years. The Chinese national HIV prevalence is still low, and new HIV infections have been contained at a low level (50,000-100,000 each year). However, the epidemic has showed an increasing trend since 2012. By risk group, in both countries, men who have sex with men (MSM), heterosexual sex, and injection drug use (IDU) are the most common modes of transmission of new HIV infections. However, in the United States, MSM is the dominant transmission route, accounting for >60% of new infections; whereas in China, heterosexual sex has now become the dominant route, also accounting for >60% of new infections. A rapid increase in the proportion of HIV cases that were attributed to MSM and an obvious decrease in the proportion of HIV cases attributed to IDU in China in recent years imply that the China's epidemic is still evolving, to some extent, copying what was experienced in the United States. By age group, the proportions of HIV cases that were attributed to the age group 25-59 were comparable between the two countries. However, the United States had a higher proportion of cases that were attributed to age groups 15-19 and 20-24 than China, indicating that youth account for more infections in the United States. One other fact worth noting: in China there is a significant increase in the number of HIV new infections in individuals over 50 years of age, which results in much higher proportion of cases that were attributed to age groups 60-64 and over 65 in China than those in the United States. By race/ethnicity, in the United States, Blacks/African Americans continue to experience the most severe HIV burden, followed by Hispanics/Latinos. In China, no official data on race/ethnicity disparities are currently available. Thus, region, risk group, age are important factors in the HIV epidemics in both countries.


Soldier-relevant loads impact lower limb biomechanics during anticipated and unanticipated single-leg cutting movements.
This study quantified how body borne load impacts hip and knee biomechanics during anticipated and unanticipated single-leg cutting maneuvers. Fifteen male military personnel performed a series of single-leg cutting maneuvers with three different load configurations (light, ~6 kg, medium, ~20 kg, and heavy, ~40 kg). Subject-based means of the specific lower limb biomechanical variables were submitted to repeated measures ANOVA to test the main and interaction effects of body borne load and movement type. With body borne load, stance time (P<0.001) increased, while larger hip (P=0.027) and knee flexion (P=0.004), and hip adduction (P<0.001) moments, and decreased hip (P=0.002) and knee flexion (P<0.001), and hip adduction (P=0.003) postures were evident. Further, the hip (P<0.001) and ankle (P=0.024) increased energy absorption, while the knee (P=0.020) increased energy generation with body borne load. During the unanticipated maneuvers, the hip (P=0.009) and knee (P=0.032) increased energy generation, and peak hip flexion moment (P=0.002) increased relative to the anticipated movements. With the body borne load, participants adopted biomechanical patterns that decreased their locomotive ability including larger moments and reduced flexion postures of the lower limb. During the single-leg cut, participants used greater energy absorption from the large, proximal muscles of the hip and greater energy generation from the knee with the addition of load. Participant's performance when carrying a range of loads was not compromised by anticipation, as they did not exhibit the hip and knee kinetic and kinematic adaptations previously demonstrated when reacting to an unplanned stimulus.


Preradiation Chemotherapy for Adult High-risk Medulloblastoma: A Trial of the ECOG-ACRIN Cancer Research Group (E4397).
To assess the long-term outcomes and objective response (OR) to preradiation chemotherapy and radiation in adult high-risk medulloblastoma. In this prospective phase II trial, adults with high-risk medulloblastoma were treated with 3 cycles of preradiation cisplatin, etoposide, cyclophosphamide, and vincristine followed by craniospinal radiation (CSI). OR, progression-free survival (PFS), overall survival (OS), and toxicities were assessed. Eleven patients were enrolled over a 6-year period. Six (55%) had subarachnoid metastases. Two (18%) had an OR to preradiation chemotherapy. Two (18%) progressed while on chemotherapy. Completion of CSI was not compromised. The OR rate after chemotherapy and radiation was 45% (5/11). Nonevaluable patients at both time-points weakened the response data conclusions. Median PFS was 43.8 months. Five-year PFS was 27%. Five-year OS was 55%. Nonmetastatic (M0) and metastatic (M+) patients had similar outcomes. The OR to this preradiation chemotherapy regimen is lower than anticipated from the adult and pediatric literature raising a question about comparative efficacy of chemotherapy in different age groups. The OS achieved is similar to retrospective adult series, but worse than pediatric outcomes. Although this regimen can be administered without compromising delivery of CSI, our results do not provide support for the use of this neoadjuvant chemotherapy for adult medulloblastoma.


Do "any willing provider" and "freedom of choice" laws affect HMO market share?
This study examines the effects of "any willing provider" (AWP) and "freedom of choice" (FOC) laws on the market share of health maintenance organizations (HMOs) in metropolitan statistical areas over the period 1989-95. We use pooled cross-section time-series regression techniques with year and state fixed effects. HMO market share is hypothesized to be a function of state laws, market characteristics, and state preference for managed care regulation. AWP and FOC laws are characterized by three alternative measures of regulatory intensity. The results suggest that FOC laws have a greater impact on market share than do AWP laws. More comprehensive regulation has a bigger impact than less encompassing laws, and laws limiting selective contracting with physicians are more effective in reducing HMO market share than are laws covering hospitals or pharmacies.


The Effect of Variability of Practice at Execution Redundancy Level in Skilled and Novice Basketball Players.
We investigated the effect of practice variability through execution redundancy in skilled and novice basketball players on free throw skills. Twelve skilled basketball players and 12 novices (mean age = 25.4 years, SD = 4.3) were divided into four groups (skilled constant, skilled variable, novice constant, and novice variable). After a pretest, participants practiced free throw action. The variable groups threw the ball over an obstacle of varying heights on each trial in random order, whereas the obstacle's height was fixed for the constant groups. After 7 and 14 consecutive days of practice, participants performed two posttests with constant and variable distances from the basket. The results showed that practicing different solutions of a task did not affect the performance of skilled players but had an immediate negative effect on the performance of novice players. Learning a complex task is the result of learning task-related parameters, and practice variability can create a mismatch between task difficulty and new learner skill levels.


Bordetella bronchiseptica responses to physiological reactive nitrogen and oxygen stresses.
Bordetella bronchiseptica can establish prolonged airway infection consistent with a highly developed ability to evade mammalian host immune responses. Upon initial interaction with the host upper respiratory tract mucosa, B. bronchiseptica are subjected to antimicrobial reactive nitrogen species (RNS) and reactive oxygen species (ROS), effector molecules of the innate immune system. However, the responses of B. bronchiseptica to redox species at physiologically relevant concentrations (nM-microM) have not been investigated. Using predicted physiological concentrations of nitric oxide (NO), superoxide and hydrogen peroxide (H2O2) on low numbers of CFU of B. bronchiseptica, all redox active species displayed dose-dependent antimicrobial activity. Susceptibility to individual redox active species was significantly increased upon introduction of a second species at subantimicrobial concentrations. An increased bacteriostatic activity of NO was observed relative to H2O2. The understanding of Bordetella responses to physiologically relevant levels of exogenous RNS and ROS will aid in defining the role of endogenous production of these molecules in host innate immunity against Bordetella and other respiratory pathogens.


Effects of a systematically offered social and preventive medicine consultation on training and health attitudes of young people not in employment, education or training (NEETs): An interventional study in France.
NEETs (young people not in employment, education or training) are at higher risk for poorer mental and physical health. In France, the Missions locales (MLs) are the only social structures dedicated to this population. We sought to determine whether the systematic offer of a social and preventive medicine consultation at a ML might increase NEET participants' access to training in the 12 months following the intervention. This intervention research was a parallel randomised controlled interventional study conducted at five MLs in mainland France in 2011-2012. It included 976 NEETs aged 18 to 25 years who attended one of the five MLs. At inclusion, participants were randomly assigned (1:1:1) to three groups: those in the first group were invited to see a social worker (not studied in this paper), those in the second group were invited to see a doctor and a social worker (intervention group), and the third was a control group. The primary outcome was participation in at least one training session during the year following study inclusion. Among the 976 participants, 504 were randomly assigned to the intervention group and 472 to the control group; 704 (72.1%) were included in the analyses. A significantly higher proportion of the participants in the intervention group participated in a training session in the 12 months following the intervention than of those in the control group (63.3% vs 55.6%; p = 0.04). This difference was significantly greater for women, those less than 21 years of age, those unstably housed and those with a lower level of education. Social and preventive medicine consultations that are fully integrated into the social services for NEETs have an impact on their access to training and contribute to changing some of their health-related behaviours. This may improve their access to the labour market.


Treatment of Iron-Loaded Veterinary Sarcoma by Artemisia annua.
Artemisinin, a constituent of Artemisia annua L., is a well-known antimalarial drug. Artemisinin-type drugs also inhibit cancer growth in vitro and in vivo. Herbal extracts of A. annua inhibit the growth of cancer cell lines. Here, we report on the use of capsules containing powder of Herba Artemisiae annuae to treat pet sarcoma. The surgical tumor removal as standard treatment was supplemented by adjuvant therapy with A. annua. One cat and one dog with fibrosarcoma survived 40 and 37 months, respectively, without tumor relapse. Two other dogs suffering from fibrosarcoma and hemangioendothelial sarcoma also showed complete remission and are still alive after 39 and 26 months, respectively. A. annua was well tolerated without noticeable side effects. These four cases indicate that A. annua may be a promising herbal drug for cancer therapy.


Evaluation of a young child's behavior: effects of attractiveness and sex.
Facial drawings of 2- or 4-yr.-old boys or girls differing in attractiveness were attached to an episode which depicted a mild misbehavior. Neither the attribution of responsibility for the behavior nor the choice of an indulgent vs punitive response was associated with the child's attractiveness, sex, or age. These findings suggest that the halo effects of attractiveness discriminations may not be fully operative at these ages.


Composition of TWIST1 dimers regulates fibroblast activation and tissue fibrosis.
TWIST1 is a member of the class B of basic helix-loop-helix transcription factors that regulates cell lineage determination and differentiation and has been implicated in epithelial-to-mesenchymal transition. Here, we aimed to investigate the role of TWIST1 for the activation of resident fibroblasts in systemic sclerosis (SSc). The expression of Twist1 in fibroblasts was modulated by forced overexpression or siRNA-mediated knockdown. Interaction of Twist1, E12 and inhibitor Of differentiation (Id) was analysed by co-immunoprecipitation. The role of Twist1 in vivo was evaluated using inducible, conditional knockout mice with either ubiquitous or fibroblast-specific depletion of Twist1. Mice were either challenged with bleomycin or overexpressing a constitutively active transforming growth factor (TGF)β receptor I. The expression of TWIST1 was increased in fibroblasts in fibrotic human and murine skin in a TGFβ/SMAD3-dependent manner. TWIST1 in turn enhanced TGFβ-induced fibroblast activation in a p38-dependent manner. The stimulatory effects of TWIST1 on resident fibroblasts were mediated by TWIST1 homodimers. TGFβ promotes the formation of TWIST1 homodimers by upregulation of TWIST1 and by induction of inhibitor of DNA-binding proteins, which have high affinity for E12/E47 and compete against TWIST1 for E12/E47 binding. Mice with selective depletion of Twist1 in fibroblasts are protected from experimental skin fibrosis in different murine models to a comparable degree as mice with ubiquitous depletion of Twist1. Our data identify TWIST1 as a central pro-fibrotic factor in SSc, which facilitates fibroblast activation by amplifying TGFβ signalling. Targeting of TWIST1 may thus be a novel approach to normalise aberrant TGFβ signalling in SSc.


Safety assessment of botanicals and botanical preparations used as ingredients in food supplements: testing an European Food Safety Authority-tiered approach.
This article describes results obtained by testing the European Food Safety Authority-tiered guidance approach for safety assessment of botanicals and botanical preparations intended for use in food supplements. Main conclusions emerging are as follows. (i) Botanical ingredients must be identified by their scientific (binomial) name, in most cases down to the subspecies level or lower. (ii) Adequate characterization and description of the botanical parts and preparation methodology used is needed. Safety of a botanical ingredient cannot be assumed only relying on the long-term safe use of other preparations of the same botanical. (iii) Because of possible adulterations, misclassifications, replacements or falsifications, and restorations, establishment of adequate quality control is necessary. (iv) The strength of the evidence underlying concerns over a botanical ingredient should be included in the safety assessment. (v) The matrix effect should be taken into account in the safety assessment on a case-by-case basis. (vi) Adequate data and methods for appropriate exposure assessment are often missing. (vii) Safety regulations concerning toxic contaminants have to be complied with. The application of the guidance approach can result in the conclusion that safety can be presumed, that the botanical ingredient is of safety concern, or that further data are needed to assess safety.


Analytical derivatives of the individual state energies in ensemble density functional theory. II. Implementation on graphical processing units (GPUs).
Conical intersections control excited state reactivity, and thus, elucidating and predicting their geometric and energetic characteristics are crucial for understanding photochemistry. Locating these intersections requires accurate and efficient electronic structure methods. Unfortunately, the most accurate methods (e.g., multireference perturbation theories such as XMS-CASPT2) are computationally challenging for large molecules. The state-interaction state-averaged restricted ensemble referenced Kohn-Sham (SI-SA-REKS) method is a computationally efficient alternative. The application of SI-SA-REKS to photochemistry was previously hampered by a lack of analytical nuclear gradients and nonadiabatic coupling matrix elements. We have recently derived analytical energy derivatives for the SI-SA-REKS method and implemented the method effectively on graphical processing units. We demonstrate that our implementation gives the correct conical intersection topography and energetics for several examples. Furthermore, our implementation of SI-SA-REKS is computationally efficient, with observed sub-quadratic scaling as a function of molecular size. This demonstrates the promise of SI-SA-REKS for excited state dynamics of large molecular systems.


Activation of microglia by histamine and substance P.
Activated microglia perform many of the immune effector functions typically associated with macrophages. However, the regulators involved in microglial activation are not well defined. Because microglia play a pivotal role in immune surveillance of the CNS, we studied the effect of the neuromediators histamine and substance P on microglia. The induction of microglial activation by histamine and substance P was examined using primary cultured microglia. Fluorescent images were acquired with a confocal microscope. The levels of TNF-α and IL-6 were measured with a commercial ELISA kit. Intracellular reactive oxygen species (ROS) levels were determined by dichlorodihydrofluorescein oxidation. The mitochondrial membrane potential was assessed with the MitoProbe™ JC-1 assay kit. We found that the neuromediators histamine and substance P were able to stimulate microglial activation and the subsequent production of ROS and proinflammatory factors TNF-α and IL-6. These effects were partially abolished by antagonists of the histamine receptors H1 and H4 and of the substance P receptors NK-1, NK-2 and NK-3. Histamine induced mitochondrial membrane depolarization in microglia. These results indicate that the neuromediators histamine and SP can trigger microglial activation and release of pro-inflammatory factors from microglia, thus contributing to the development of microglia-mediated inflammation in the brain.


Simulated unobtrusive falls detection with multiple persons.
One serious issue related to falls among the elderly living at home or in a residential care facility is the "long lie" scenario, which involves being unable to get up from the floor after a fall for 60 min or more. This research uses a simulated environment to investigate the potential effectiveness of using wireless ambient sensors (dual-technology (microwave/infrared) motion detectors and pressure mats) to track the movement of multiple persons and to unobtrusively detect falls when they occur, therefore reducing the rate of occurrence of "long lie" scenarios. A path-finding algorithm (A*) is used to simulate the movement of one or more persons through the residential area. For analysis, the sensor network is represented as an undirected graph, where nodes in the graph represent sensors, and edges between nodes in the graph imply that these sensors share an overlapping physical region in their area of sensitivity. A second undirected graph is used to represent the physical adjacency of the sensors (even where they do not overlap in their monitored regions). These graphical representations enable the tracking of multiple subjects/groups within the environment, by analyzing the sensor activation and adjacency profiles, hence allowing individuals/groups to be isolated when multiple persons are present, and subsequently monitoring falls events. A falls algorithm, based on a heuristic decision tree classifier model, was tested on 15 scenarios, each including one or more persons; three scenarios of activity of daily living, and 12 different types of falls (four types of fall, each with three postfall scenarios). The sensitivity, specificity, and accuracy of the falls algorithm are 100.00%, 77.14%, and 89.33%, respectively.


[Use of unconventional lipid substrates in parental nutrition].
In addition to the classic soybean oil fat emulsion, developed more than 40 years ago and still widely used, emulsions with other lipid substrates are available today for parenteral nutrition; these substrates implement the benefits offered by soybean oil when mixed with it in given proportions. Soybean oil triglycerides are rich in linoleic acid, a long chain omega-6 polyunsaturated fatty acid, which is essential and is an indispensable component of parenteral nutrition. However, very high doses of omega-6 polyunsaturated fatty acids should be avoided, particularly in some critical illnesses. Medium chain triglycerides, long well known to nutritionists and dietitians for their easy intestinal absorption, have become available in parenteral nutrition emulsions in a mixture with soybean oil. Medium chain triglycerides are completely and readily used for energy production and do not interfere significantly in the production of inflammatory mediators, in the composition of cell membranes and in body organ and system functions. Omega-3 polyunsaturated fatty acids, essential fatty acids derived from fish oil, permeate cell structure and affect cell activity with different mechanisms, playing also an important role in the modulation of inflammatory processes. Omega-3 emulsions in parenteral nutrition are currently added as a supplement to other fat emulsions. Knowledge of these "non-conventional" fat emulsions is being continuously improved by investigative work and clinical experience.


Mesenchymal stromal cells from human perinatal tissues: From biology to cell therapy.
Cell-based regenerative medicine is of growing interest in biomedical research. The role of stem cells in this context is under intense scrutiny and may help to define principles of organ regeneration and develop innovative therapeutics for organ failure. Utilizing stem and progenitor cells for organ replacement has been conducted for many years when performing hematopoietic stem cell transplantation. Since the first successful transplantation of umbilical cord blood to treat hematological malignancies, non-hematopoietic stem and progenitor cell populations have recently been identified within umbilical cord blood and other perinatal and fetal tissues. A cell population entitled mesenchymal stromal cells (MSCs) emerged as one of the most intensely studied as it subsumes a variety of capacities: MSCs can differentiate into various subtypes of the mesodermal lineage, they secrete a large array of trophic factors suitable of recruiting endogenous repair processes and they are immunomodulatory.Focusing on perinatal tissues to isolate MSCs, we will discuss some of the challenges associated with these cell types concentrating on concepts of isolation and expansion, the comparison with cells derived from other tissue sources, regarding phenotype and differentiation capacity and finally their therapeutic potential.


First Preliminary Report on Isolation and Characterization of Novel Acinetobacter spp. in Casing Soil Used for Cultivation of Button Mushroom, Agaricus bisporus (Lange) Imbach.
Despite evaluation of large number of agroindustrial wastes for their use as casing material for Agaricus bisporus (Lange) Imbach cultivation, scant attention has been given to the importance of biological properties of casing materials. In the present study, an attempt was made to characterize the bacterial flora in casing layer, namely, Farm Yard Manure (FYM) and Spent Mushroom Substrate/spent compost (SMS/SC) (FYM+SC, 3 : 1) and FYM and Vermi Compost (VC) (FYM+VC, 3 : 1), employing partial 16S rDNA sequencing. Available data showed a significant variety of organisms that included Acinetobacter and Pseudomonas of the γ-proteobacteria, that were the most frequently encountered genera. This is the first preliminary report on the microbial diversity of casing soils and demonstrates the presence of Acinetobacter spp. that has not been previously described in casing material.


Echocardiography as an outcome measure in scleroderma-related pulmonary arterial hypertension: a systematic literature analysis by the EPOSS group.
To assess the validation status of echocardiography with continuous Doppler (echo-Doppler) as an outcome measure in pulmonary arterial hypertension associated with systemic sclerosis (PAH-SSc). Structured literature review on full-text English articles was performed using the PubMed and Cochrane databases. Assessment of validation of echo-Doppler was based on the OMERACT filter criteria with the domains truth (face, content, construct, and criterion validity), discrimination, and feasibility. Out of 35 studies eligible for analysis, only 5 included well defined PAH-SSc subgroups (World Health Organization criteria). Echo was considered as having face validity based on expert opinion and high number of studies using echo for evaluation of patients with SSc. Echo was considered partially validated with respect to criterion validity based on significant correlations between echo measures and right-heart catheterization in patients with SSc at risk of PAH/PH. However, echo was found to lack specificity (lack of content validity), since measurements of echo pulmonary pressure may be influenced by left-heart disease and interstitial lung disease. Data from general populations of patients with scleroderma indicate that evaluation of pulmonary artery pressure by echo might not be available in all PAH-SSc patients because of technical factors. No studies enabling evaluation of the discriminant capacity over time and treatment of echo in PAH-SSc could be identified. Further studies are needed to fully validate echo-Doppler as an outcome measure in PAH-SSc. These studies would include cross-sectional analysis of baseline measures and longitudinal data of placebo and verum groups in randomized controlled trials of patients with PAH-SSc.


TGF-beta signaling promotes survival and repair in rat alveolar epithelial type 2 cells during recovery after hyperoxic injury.
Hyperoxic rats treated with inosine during oxygen exposure have increased levels of active transforming growth factor (TGF)-beta in the bronchoalveolar lavage (BAL), yet alveolar epithelial type 2 cells (AEC2) isolated from these animals demonstrate less hyperoxia-induced DNA damage and increased expression of active Smad2. To determine whether TGF-beta1 signaling per se protected AEC2 against hyperoxic damage, freshly isolated AEC2 from hyperoxic rats were incubated with TGF-beta1 for 24 h and assayed for DNA damage by fluorescein-activated cell sorter analysis of TdT-mediated dUTP nick end labeling. TGF-beta1 was protective over a concentration range similar to that in BAL of inosine-treated hyperoxic animals (50-5,000 pg/ml). TGF-beta1 also augmented hyperoxia-induced DNA repair activity and cell migration, stimulated autocrine secretion of fibronectin, accelerated closure of a monolayer scratch wound, and restored hyperoxia-depleted VEGF secretion by AEC2 to normoxic levels. The TGF-beta receptor type I activin-like kinase-4, -5, and -7 inhibitor peptide SB-505124 abolished the protective effect of TGF-beta on hyperoxic DNA damage and increased TdT-mediated dUTP nick end labeling in normoxic cells. These data suggest that endogenous TGF-beta-mediated Smad signaling is required for AEC2 homeostasis in vitro, while exogenous TGF-beta1 treatment of hyperoxia-damaged AEC2 results in a cell that is equipped to survive, repair, migrate, secrete matrix, and induce new blood vessel formation more efficiently than AEC2 primed by hyperoxia alone.


A metric method for sex determination using the hipbone and the femur.
Since the earliest descriptions of the pubis length measurement, it has been recognized that the location of the key landmark in the acetabulum has to be estimated. Using samples from the Terry Collection (n = 324) and the Coimbra Collection (n = 232), the purpose of this research is to, first, test the reproducibility of a new alternative to the traditional measurement of the pubis, and second, to use the best measurement of the pubis along with other measurements of the hipbone and femur to develop a metric method that can be used with confidence to determine the sex of individuals of various geographic origins and time periods. In this study, it was found that, first, the alternative pubis measurement, known as the superior pubis ramus length (SPRL), can be collected more reliably with less mean intra-observer error (0.57%) than the more commonly used manner of measuring the pubis (2.7%). Second, a logistic regression sex determination method using the SPRL, along with other measurements of the hipbone and femur, has an allocation accuracy of 90% to 98.5% (depending on the model used and the manner of testing) across independent samples. Third, traditional racial categorization was irrelevant to the accuracy of the method. Fourth, measurement error greater than 2% in the measurement of the pubis can be the difference between a correct and an incorrect allocation of sex, particularly in borderline cases.


Mineral metabolism during prolonged oral calcium substitution after jejuno-ileal bypass for morbid obesity.
The influence of jejuno-ileal bypass surgery on mineral metabolism was studied in patients with morbid obesity before operation, and 2 and 5 years after-wards. When calcium and potassium were orally substituted post-operatively, in serum calcium fractions, parathyroid hormone, phosphate, potassium and the bone mineral content remained unchanged, while serum magnesium decreased. Serum 25-hydroxyvitamin D was already low before bypass operation, and did not change thereafter. Post-operatively, the urinary excretion of oxalate rose into the upper normal range, while that of calcium, magnesium and citrate was markedly reduced. The urinary activity product of calcium oxalate rose slightly, but that of brushite decreased. Since these changes were manifest in the urine of all patients, the reasons for the post-operative formation of renal stones in 4 of 19 patients remain unclear at the moment. We conclude that the recommendation for precise oral calcium substitution after jejuno-ileal bypass operation seems justified in order to avoid serious disturbances of calcium metabolism in the long term, and to reduce intestinal oxalate absorption.


The biomechanical effect of single-level laminectomy and posterior instrumentation on spinal stability in degenerative lumbar scoliosis: a human cadaveric study.
OBJECTIVEDegenerative lumbar scoliosis, or de novo degenerative lumbar scoliosis, can result in spinal canal stenosis, which is often accompanied by disabling symptoms. When surgically treated, a single-level laminectomy is performed and short-segment posterior instrumentation is placed to restore stability. However, the effects of laminectomy on spinal stability and the necessity of placing posterior instrumentation are unknown. Therefore, the aim of this study was to assess the stability of lumbar spines with degenerative scoliosis, characterized by the range of motion (ROM) and neutral zone (NZ) stiffness, after laminectomy and placement of posterior instrumentation.METHODSTen lumbar cadaveric spines (T12-L5) with a Cobb angle ≥ 10° and an apex on L3 were included. Three loading cycles were applied per direction, from -4 Nm to 4 Nm in flexion/extension (FE), lateral bending (LB), and axial rotation (AR). Biomechanical evaluation was performed on the native spines and after subsequent L3 laminectomy and the placement of posterior L2-4 titanium rods and pedicle screws. Nonparametric and parametric tests were used to analyze the effects of laminectomy and posterior instrumentation on NZ stiffness and ROM, respectively, both on an individual segment's motion and on the entire spine section. Spearman's rank correlation coefficient was used to study the correlation between disc degeneration and spinal stability.RESULTSThe laminectomy increased ROM by 9.5% in FE (p = 0.04) and 4.6% in LB (p = 0.01). For NZ stiffness, the laminectomy produced no significant effects. Posterior instrumentation resulted in a decrease in ROM in all loading directions (-22.2%, -24.4%, and -17.6% for FE, LB, and AR, respectively; all p < 0.05) and an increase in NZ stiffness (+44.7%, +51.7%, and +35.2% for FE, LB, and AR, respectively; all p < 0.05). The same changes were seen in the individual segments around the apex, while the adjacent, untreated segments were mostly unaffected. Intervertebral disc degeneration was found to be positively correlated to decreased ROM and increased NZ stiffness.CONCLUSIONSLaminectomy in lumbar spines with degenerative scoliosis did not result in severe spinal instability, whereas posterior instrumentation resulted in a rigid construct. Also, prior to surgery, the spines already had lower ROM and higher NZ stiffness in comparison to values shown in earlier studies on nonscoliotic spines of the same age. Hence, the authors question the clinical need for posterior instrumentation to avoid instability.


FLIM data analysis based on Laguerre polynomial decomposition and machine-learning.
The potential of fluorescence lifetime imaging microscopy (FLIM) is recently being recognized, especially in biological studies. However, FLIM does not directly measure the lifetimes, rather it records the fluorescence decay traces. The lifetimes and/or abundances have to be estimated from these traces during the phase of data processing. To precisely estimate these parameters is challenging and requires a well-designed computer program. Conventionally employed methods, which are based on curve fitting, are computationally expensive and limited in performance especially for highly noisy FLIM data. The graphical analysis, while free of fit, requires calibration samples for a quantitative analysis. We propose to extract the lifetimes and abundances directly from the decay traces through machine learning (ML). The ML-based approach was verified with simulated testing data in which the lifetimes and abundances were known exactly. Thereafter, we compared its performance with the commercial software SPCImage based on datasets measured from biological samples on a time-correlated single photon counting system. We reconstructed the decay traces using the lifetime and abundance values estimated by ML and SPCImage methods and utilized the root-mean-squared-error (RMSE) as marker. The RMSE, which represents the difference between the reconstructed and measured decay traces, was observed to be lower for ML than for SPCImage. In addition, we could demonstrate with a three-component analysis the high potential and flexibility of the ML method to deal with more than two lifetime components. The ML-based approach shows great performance in FLIM data analysis.


How leaders perceive employee deviance: Blaming victims while excusing favorites.
Drawing from theories of attribution and perception, we posit that employees who are victims of rudeness are themselves (inappropriately) evaluated by leaders as being interpersonally deviant. We further theorize that employees who are themselves rude to others at work are evaluated negatively, but not when they have high-quality relationships with leaders or are seen as high performers. We tested our predictions across 4 studies. Our first study included 372 leader-follower pairs. Our second study extended to dyadic interactions among employees by using an employee roster method, resulting in paired data from 149 employees (2,184 dyads) across 5 restaurant locations. Our third and fourth studies utilized a policy-capturing design in which individuals provided performance evaluations for fictitious employees. We find that victims of rudeness are viewed by leaders as deviant, and that leaders are less likely to perceive rude employees as deviant when these perpetrators are seen as having high levels of leader-member exchange (LMX) or performance. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Phospholipid transfer proteins revisited.
Phosphatidylinositol transfer protein (PI-TP) and the non-specific lipid transfer protein (nsL-TP) (identical with sterol carrier protein 2) belong to the large and diverse family of intracellular lipid-binding proteins. Although these two proteins may express a comparable phospholipid transfer activity in vitro, recent studies in yeast and mammalian cells have indicated that they serve completely different functions. PI-TP (identical with yeast SEC14p) plays an important role in vesicle flow both in the budding reaction from the trans-Golgi network and in the fusion reaction with the plasma membrane. In yeast, vesicle budding is linked to PI-TP regulating Golgi phosphatidylcholine (PC) biosynthesis with the apparent purpose of maintaining an optimal PI/PC ratio of the Golgi complex. In mammalian cells, vesicle flow appears to be dependent on PI-TP stimulating phosphatidylinositol 4,5-bisphosphate (PIP2) synthesis. This latter process may also be linked to the ability of PI-TP to reconstitute the receptor-controlled PIP2-specific phospholipase C activity. The nsL-TP is a peroxisomal protein which, by its ability to bind fatty acyl-CoAs, is most likely involved in the beta-oxidation of fatty acids in this organelle. This protein constitutes the N-terminus of the 58 kDa protein which is one of the peroxisomal 3-oxo-acyl-CoA thiolases. Further studies on these and other known phospholipid transfer proteins are bound to reveal new insights in their important role as mediators between lipid metabolism and cell functions.


Malnutrition and iron deficiency in lactating women in urban slum communities from Addis Ababa, Ethiopia.
To determine the status of iron deficiency anaemia (IDA) and malnutrition in lactating women. A cross-sectional study. Six urban slum communities in Teklehaimanot district, Addis Ababa. One thousand and seventeen lactating women were enrolled and assessed for their haemoglobin (Hgb), serum ferritin level and body mass index (BMI) during the month of March 2001. Iron deficiency anaemia was considered when Hgb and serum ferritin concentrations were less than 12gm/dl and 12 microg/l respectively, whereas, a BMI less than 18.5% kg/m2 was considered malnourished. Determinations of haemoglobin, serum ferritin and BMI measurements. The overall prevalence of iron deficiency anaemia (IDA) and protein energy malnutrition in the slum communities was 22.3% and 27.1% respectively. The mean age of mothers (28.4 +/- 6.12 years) indicates that prevalence of malnutrition and iron deficiency anaemia was higher among younger mothers than among older mothers. The prevalence of malnutrition was positively correlated with the serum ferritin concentration status, of the mothers (r=0.12, p=0.2, RR=1.03). It is observed that malnutrition and IDA are major health problems and therefore, an appropriate nutrition intervention package to improve the nutrition situation of the communities is recommended.


Low rate of initiation and short duration of breastfeeding in a maternal and infant home visiting project targeting rural, Southern, African American women.
Despite the benefits of breastfeeding for both infant and mother, rates in the United States remain below Healthy People 2020 breastfeeding objectives. This paper describes breastfeeding outcomes of the Delta Healthy Sprouts participants during gestational and postnatal periods. Of specific interest was whether breastfeeding intent, knowledge, and beliefs changed from the early to late gestational period. Additionally, analyses were conducted to test for associations between breastfeeding initiation and breastfeeding intent, knowledge and beliefs as well as sociodemographic characteristics and other health measures. Eighty-two pregnant women were enrolled in this project spanning three Mississippi counties. Participants were randomly assigned to one of two treatment groups. Because both groups received information about breastfeeding, breastfeeding outcomes were analyzed without regard to treatment assignment. Hence participants were classified into two groups, those that initiated breastfeeding and those that did not initiate breastfeeding. Generalized linear mixed models were used to test for significant group, time, and group by time effects on breastfeeding outcomes. Breastfeeding knowledge scores increased significantly from baseline to late gestational period for both groups. Across time, breastfeeding belief scores were higher for the group that initiated breastfeeding as compared to the group that did not breastfeed. Only 39% (21 of 54) of participants initiated breastfeeding. Further, only one participant breastfed her infant for at least six months. Breastfeeding intent and beliefs as well as pre-pregnancy weight class significantly predicted breastfeeding initiation. Our findings indicate that increasing knowledge about and addressing barriers for breastfeeding were insufficient to empower rural, Southern, primarily African American women to initiate or continue breastfeeding their infants. Improving breastfeeding outcomes for all socioeconomic groups will require consistent, engaging, culturally relevant education that positively influences beliefs as well as social and environmental supports that make breastfeeding the more accepted, convenient, and economical choice for infant feeding. clinicaltrials.gov NCT01746394. Registered 5 December 2012.


Exploiting Robot Hand Compliance and Environmental Constraints for Edge Grasps.
This paper presents a method to grasp objects that cannot be picked directly from a table, using a soft, underactuated hand. These grasps are achieved by dragging the object to the edge of a table, and grasping it from the protruding part, performing so-called slide-to-edge grasps. This type of approach, which uses the environment to facilitate the grasp, is named Environmental Constraint Exploitation (ECE), and has been shown to improve the robustness of grasps while reducing the planning effort. The paper proposes two strategies, namely Continuous Slide and Grasp and Pivot and Re-Grasp, that are designed to deal with different objects. In the first strategy, the hand is positioned over the object and assumed to stick to it during the sliding until the edge, where the fingers wrap around the object and pick it up. In the second strategy, instead, the sliding motion is performed using pivoting, and thus the object is allowed to rotate with respect to the hand that drags it toward the edge. Then, as soon as the object reaches the desired position, the hand detaches from the object and moves to grasp the object from the side. In both strategies, the hand positioning for grasping the object is implemented using a recently proposed functional model for soft hands, the closure signature, whereas the sliding motion on the table is executed by using a hybrid force-velocity controller. We conducted 320 grasping trials with 16 different objects using a soft hand attached to a collaborative robot arm. Experiments showed that the Continuous Slide and Grasp is more suitable for small objects (e.g., a credit card), whereas the Pivot and Re-Grasp performs better with larger objects (e.g., a big book). The gathered data were used to train a classifier that selects the most suitable strategy to use, according to the object size and weight. Implementing ECE strategies with soft hands is a first step toward their use in real-world scenarios, where the environment should be seen more as a help than as a hindrance.


Clinical management of cystic echinococcosis: state of the art and perspectives.
This review draws attention to patients with cystic echinococcosis migrating from highly endemic to non-endemic countries with limited experience in cystic echinococcosis management, to ultrasound-based cyst staging, and to the WHO cyst classification as a powerful, to date underused tool to triage patients into the four currently available treatment modalities. In non- and low-prevalence countries, cystic echinococcosis is often misclassified. Differential diagnoses, such as simple cysts and other benign and malignant space-occupying lesions, have similar appearances on imaging. Serology is confirmatory but often disappointing due to sensitivity and specificity problems. There is increasing confidence in assigning uncomplicated cystic echinococcosis cysts to the four treatment modalities [drug treatment (benzimidazoles), percutaneous methods, surgery, watch and wait] on the basis of cyst stage (WHO cyst classification), size and location. However, current best practice is still not widely implemented outside cystic echinococcosis treatment centres, and further consolidation is needed by well-designed clinical trials. Recently published long-term follow-up studies have shown that patients with inactive cyst stages CE4 and CE5 benefit, especially since they do not need any treatment at all if they have not received prior benzimidazole or percutaneous therapy. Instead, cysts that have reached cyst stages CE4 and CE5 through drug treatment do need careful follow-up as they often relapse. Surgical procedures in which the cysts are opened and percutaneous approaches require very careful control of cyst content spillage to the peritoneum, pleura and intravascularly to prevent dissemination - a still too often neglected issue with severe consequences for patients. Though a neglected disease with predominantly expert-opinion-based treatment strategies, cystic echinococcosis patients can greatly benefit from interdisciplinary management in cystic echinococcosis treatment centres and cyst-stage-based assignment of treatment modalities. Increased suspicion for cystic echinococcosis in migrants from endemic to non-endemic countries is urgently needed at the current level of global mobility.