PRISM: recovering cell-type-specific expression profiles from individual composite RNA-seq samples.
A major challenge in analyzing cancer patient transcriptomes is that the tumors are inherently heterogeneous and evolving. We analyzed 214 bulk RNA samples of a longitudinal, prospective ovarian cancer cohort and found that the sample composition changes systematically due to chemotherapy and between the anatomical sites, preventing direct comparison of treatment-naive and treated samples. To overcome this, we developed PRISM, a latent statistical framework to simultaneously extract the sample composition and cell-type-specific whole-transcriptome profiles adapted to each individual sample. Our results indicate that the PRISM-derived composition-free transcriptomic profiles and signatures derived from them predict the patient response better than the composite raw bulk data. We validated our findings in independent ovarian cancer and melanoma cohorts, and verified that PRISM accurately estimates the composition and cell-type-specific expression through whole-genome sequencing and RNA in situ hybridization experiments. https://bitbucket.org/anthakki/prism. Supplementary data are available at Bioinformatics online.


Critical band 3 multiprotein complex interactions establish early during human erythropoiesis.
Band 3, the major anion transport protein of human erythrocytes, forms the core of a multiprotein complex in the erythrocyte membrane. Here we studied the spatiotemporal mechanisms of band 3 multiprotein complex assembly during erythropoiesis. Significant pools of intracellular band 3 and Rh-associated glycoprotein (RhAG) were found in the basophilic erythroblast. These intracellular pools decreased in the polychromatic erythroblast, whereas surface expression increased and were lowest in the orthochromatic erythroblast and reticulocytes. Protease treatment of intact cells to remove extracellular epitopes recognized by antibodies to band 3 and RhAG was used to study surface delivery kinetics and intracellular complex composition from the proerythroblast stage to the enucleated reticulocyte. Newly synthesized band 3 and protein 4.2 interact initially in the early stages of the secretory pathway and are found associated at the plasma membrane from the basophilic stage of erythropoiesis. Although we could successfully coimmunoprecipitate Rh with RhAG from plasma membrane pools at a similar stage, no intracellular interaction between these proteins was detectable. Knockdown of RhAG during early erythropoiesis was accompanied by a concomitant drop in membrane expression of Rh polypeptides. These data are consistent with assembly of major components of the band 3 macrocomplex at an early stage during erythropoiesis.


New markers for minimal residual disease detection in acute lymphoblastic leukemia.
To identify new markers for minimal residual disease (MRD) detection in acute lymphoblastic leukemia (ALL), we compared genome-wide gene expression of lymphoblasts from 270 patients with newly diagnosed childhood ALL to that of normal CD19⁺CD10⁺ B-cell progenitors (n = 4). Expression of 30 genes differentially expressed by ≥ 3-fold in at least 25% of cases of ALL (or 40% of ALL subtypes) was tested by flow cytometry in 200 B-lineage ALL and 61 nonleukemic BM samples, including samples containing hematogones. Of the 30 markers, 22 (CD44, BCL2, HSPB1, CD73, CD24, CD123, CD72, CD86, CD200, CD79b, CD164, CD304, CD97, CD102, CD99, CD300a, CD130, PBX1, CTNNA1, ITGB7, CD69, CD49f) were differentially expressed in up to 81.4% of ALL cases; expression of some markers was associated with the presence of genetic abnormalities. Results of MRD detection by flow cytometry with these markers correlated well with those of molecular testing (52 follow-up samples from 18 patients); sequential studies during treatment and diagnosis-relapse comparisons documented their stability. When incorporated in 6-marker combinations, the new markers afforded the detection of 1 leukemic cell among 10(5) BM cells. These new markers should allow MRD studies in all B-lineage ALL patients, and substantially improve their sensitivity.


[Vaginal intraepithelial carcinoma. Diagnosis and management].
At the Colposcopy Clinic, Hospital "Luis Castelazo Ayala", from January 1990 to May, 1991, 24 cases of vaginal intraepithelial neoplasia, were diagnosed. The average age of the patients was 54.2 years. Twenty had antecedents of previous hysterectomy; seven (29%) with benign pathology, and twelve (50%) with malignant pathology. Only four patients (17%) presented with symptomatology. In all the cases it was suspected by abnormal cytology. Colposcopy was done, as well as directed biopsy, finding that the pointillism and white epithelium, were the most frequent findings, with localization mainly in the vaginal cupule and vaginal upper third. Histopathological correlation showed NIVa I in three cases (13%) NIVa II in six cases (25%), and NIVa III in 15 (62%). Treatment was done with cryotherapy in 10 patients; with 5-fluorouracil in eight; cryotherapy plus 5-fluorouracil in three; radiotherapy in two, and it was not done in one. It was found persistent lesion in two cases treated with cryotherapy, and in one case with radiotherapy; there was a complication in one case after cryotherapy (retrovaginal fistula). Vaginal cytology should be done in every patient after hysterectomy, by benign or malignant pathology. In NIVa the colposcopic study is mandatory for the adequate diagnosis. 5-Fluorouracil showed to be an adequate treatment.


[Geriatrics: the day hospital as a part of comprehensive medical care of elderly patients--also or especially in threatened rationing].
The wrong conclusion of elderly people being the reason for increasing costs of public health is corrected by several differentiated statements. Geriatrics as a comprehensive medicine for the elderly can be realized in an exemplary way, even in a day hospital. An attitude of solidarity and a high level of interpersonal communication play the important and decisive part.


Family history of insomnia in a population-based sample.
To examine the rates of family history of insomnia in a population-based sample composed of self-defined good sleepers and individuals with insomnia and compare individuals with and without family history of insomnia on several characteristics presumably associated with insomnia. Cross-sectional comparisons of self-defined good sleepers and individuals with insomnia selected from a larger epidemiologic study using a randomly selected sample of 2001 adults of the province of Quebec in Canada. Nine hundred fifty-three adults (60.3% women; mean age = 43.9 years) completed several postal questionnaires, including a survey of past and current history of insomnia/sleep disorders for self and first-degree relatives. Participants were classified as good sleepers, individuals with insomnia symptoms, or individuals with an insomnia syndrome. N/A. Of the total sample, 34.9% reported at least 1 first-degree relative with past or current insomnia. The mother was the most frequently afflicted first-degree relative with insomnia (19.7%). Family history rates of insomnia were not significantly different when individuals with current insomnia symptoms or syndrome were compared with self-defined good sleepers. However, significant group differences emerged when good sleepers were subdivided according to the presence or absence of past personal history of insomnia. Individuals with past or current insomnia were significantly more likely to report a family history of insomnia than were good sleepers who had never experienced insomnia in the past (39.1% vs 29.0%). Participants with a family history of insomnia endorsed higher scores on measures of insomnia severity, anxiety symptomatology, and arousal predisposition. These findings provide additional evidence about the potential role of both family and personal history of insomnia as predisposing factors to insomnia. Longitudinal family studies are needed to further examine the relative contribution of genetic and environmental factors in the genesis and heritability of insomnia.


Relationships Between Identity, Well-Being, and Willingness to Sacrifice in Personal and Collective Favorite Places: The Mediating Role of Well-Being.
In line with research indicating positive associations between well-being and personal and collective people-place bonding, and that collectivistic compared to individualistic commitment may have stronger associations with pro-environmental behavior, we investigated relationships between identity, well-being, and willingness to sacrifice (type of pro-environmental behavior) in personal and collective favorite places. A total of 884 respondents, living in three Swedish municipalities, participated in this study. In line with the hypotheses, we showed congruent positive relationships between place-related: (1) personal identity and personal well-being; (2) collective identity and collective well-being, (3) collective identity and collective willingness to sacrifice; and (4) an incongruent positive association between collective identity and personal willingness to sacrifice. Additionally, a significant role of well-being in mediating the identity → willingness to sacrifice relationship was reported, suggesting that our willingness to pay higher taxes and prices and to accept cuts in standard of living in order to protect our personal and collective favorite places might be accounted for partly by how we feel visiting these places.


A biomechanical evaluation of femoroplasty under simulated fall conditions.
To test the hypotheses that, compared with controls: 1) femoroplasty (the injection of bone cement into the proximal femur in an attempt to prevent fragility fracture) increases the yield and ultimate loads, yield and ultimate energies, and stiffness of the proximal osteoporotic femur in a simulated fall model; and 2) the manner in which the cement distributes in the proximal femur affects the extent to which those mechanical properties are altered. In 10 pairs of osteoporotic human cadaveric femora, we injected one femur of each pair with 40 to 50 mL of polymethylmethacrylate bone cement; the noninjected femur served as the control. The filling percentage was calculated in four anatomic regions of the femur: head, neck, trochanter, and subtrochanter. All specimens were biomechanically tested in a configuration that simulated a fall on the greater trochanter. Student t test, linear regression, and multinomial logistic regression statistical analyses were conducted where appropriate with significant difference defined as P < 0.05. Femoroplasty significantly increased yield load (22.0%), ultimate load (37.3%), yield energy (79.6%), and ultimate energy (154%) relative to matched controls but did not significantly change stiffness (-10.9%). There was a strong (r = 0.7) correlation between yield load and filling percentage in the femoral neck. This study showed that 1) femoroplasty significantly increased fracture load and energy to fracture when osteoporotic femora were loaded in simulated fall conditions, and 2) cement filling in the femoral neck may have an important role in the extent to which femoroplasty affects mechanical strength of the proximal femur.


Quantitative proteomics of small numbers of closely-related cells: Selection of the optimal method for a clinical setting.
Mass spectrometry (MS)-based proteomics profiling has undoubtedly increased the knowledge about cellular processes and functions. However, its applicability for paucicellular sample analyses is currently limited. Although new approaches have been developed for single-cell studies, most of them have not (yet) been standardized and/or require highly specific (often home-built) devices, thereby limiting their broad implementation, particularly in non-specialized settings. To select an optimal MS-oriented proteomics approach applicable in translational research and clinical settings, we assessed 10 different sample preparation procedures in paucicellular samples of closely-related cell types. Particularly, five cell lysis protocols using different chemistries and mechanical forces were combined with two sample clean-up techniques (C18 filter- and SP3-based), followed by tandem mass tag (TMT)-based protein quantification. The evaluation was structured in three phases: first, cell lines from hematopoietic (THP-1) and non-hematopoietic (HT-29) origins were used to test the approaches showing the combination of a urea-based lysis buffer with the SP3 bead-based clean-up system as the best performer. Parameters such as reproducibility, accessibility, spatial distribution, ease of use, processing time and cost were considered. In the second phase, the performance of the method was tested on maturation-related cell populations: three different monocyte subsets from peripheral blood and, for the first time, macrophages/microglia (MAC) from glioblastoma samples, together with T cells from both tissues. The analysis of 50,000 cells down to only 2,500 cells revealed different protein expression profiles associated with the distinct cell populations. Accordingly, a closer relationship was observed between non-classical monocytes and MAC, with the latter showing the co-expression of M1 and M2 macrophage markers, although pro-tumoral and anti-inflammatory proteins were more represented. In the third phase, the results were validated by high-end spectral flow cytometry on paired monocyte/MAC samples to further determine the sensitivity of the MS approach selected. Finally, the feasibility of the method was proven in 194 additional samples corresponding to 38 different cell types, including cells from different tissue origins, cellular lineages, maturation stages and stimuli. In summary, we selected a reproducible, easy-to-implement sample preparation method for MS-based proteomic characterization of paucicellular samples, also applicable in the setting of functionally closely-related cell populations.


Relation of dopamine receptor 2 binding to pain perception in female fibromyalgia patients with and without depression--A [¹¹C] raclopride PET-study.
Dopamine D2/D3 receptor availability at rest and its association with individual pain perception was investigated using the [(11)C] raclopride PET-method in 24 female Fibromyalgia (FMS) participants with (FMS+, N=11) and without (FMS-, N=13) comorbid depression and in 17 healthy women. Thermal pain thresholds (TPT) and pain responses were assessed outside the scanner. We compared the discriminative capacity, i.e. the individual׳s capacity to discriminate between lower and higher pain intensities and the response criterion, i.e. the subject׳s tendency to report pain during noxious stimulation due to psychological factors. [(11)C] raclopride binding potential (BP), defined as the ratio of specifically bound non-displaceable radioligand at equilibrium (BP(ND)) was used as measure of D2/D3 receptor availability. We found significant group effects of BP(ND) in striatal regions (left ventral striatum, left caudate nucleus and left nucleus accumbens) between FMS+ and FMS- compared to healthy subjects. Correlational analysis showed negative associations between TPT and D2/D3 receptor availability in the left caudate nucleus in FMS-, between TPT and D2/D3 receptor availability in the right caudate nucleus in FMS + and positive associations between TPT and D2/D3 receptor availability in the left putamen and right caudate nucleus in healthy controls. The response criterion was positively associated with D2/D3 receptor availability in the right nucleus accumbens in FMS - and negatively with D2/D3 receptor availability in the left caudate nucleus in healthy controls. Finally, no significant associations between D2/D3 receptor availability and discriminative capacity in any of the groups or regions were determined. These findings provide further support for a disruption of dopaminergic neurotransmission in FMS and implicate DA as important neurochemical moderator of differences in pain perception in FMS patients with and without co-morbid depression.


Atmospheric pollution for trace elements in the remote high-altitude atmosphere in central Asia as recorded in snow from Mt. Qomolangma (Everest) of the Himalayas.
A series of 42 snow samples covering over a one-year period from the fall of 2004 to the summer of 2005 were collected from a 2.1-m snow pit at a high-altitude site on the northeastern slope of Mt. Everest. These samples were analyzed for Al, V, Cr, Mn, Co, Ni, Cu, Zn, As, Rb, Sr, Cd, Sb, Pb, and Bi in order to characterize the relative contributions from anthropogenic and natural sources to the fallout of these elements in central Himalayas. Our data were also considered in the context of monsoon versus non-monsoon seasons. The mean concentrations of the majority of the elements were determined to be at the pg g(-1) level with a strong variation in concentration with snow depth. While the mean concentrations of most of the elements were significantly higher during the non-monsoon season than during the monsoon season, considerable variability in the trace element inputs to the snow was observed during both periods. Cu, Zn, As, Cd, Sb, and Bi displayed high crustal enrichment factors (EFc) in most samples, while Cr, Ni, Rb, and Pb show high EFc values in some of the samples. Our data indicate that anthropogenic inputs are potentially important for these elements in the remote high-altitude atmosphere in the central Himalayas. The relationship between the EFc of each element and the Al concentration indicates that a dominant input of anthropogenic trace elements occurs during both the monsoon and non-monsoon seasons, when crustal contribution is relatively minor. Finally, a comparison of the trace element fallout fluxes calculated in our samples with those recently obtained at Mont Blanc, Greenland, and Antarctica provides direct evidence for a geographical gradient of the atmospheric pollution with trace elements on a global scale.


Individual Patient Data Meta-Analysis of FOLFOXIRI Plus Bevacizumab Versus Doublets Plus Bevacizumab as Initial Therapy of Unresectable Metastatic Colorectal Cancer.
A proper estimation of the magnitude of the overall survival (OS) benefit from infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) plus bevacizumab versus doublets + bevacizumab is lacking because all trials that have investigated this regimen had primary end points other than OS. To test OS with higher power and to explore the interaction of treatment effect with main patient and disease characteristics, we performed an individual patient data (IPD) meta-analysis. IPD from 5 eligible trials were collected: CHARTA (ClinicalTrials.gov identifier: NCT01321957), OLIVIA (ClinicalTrials.gov identifier: NCT00778102), STEAM (ClinicalTrials.gov identifier: NCT01765582), TRIBE (ClinicalTrials.gov identifier: NCT00719797), and TRIBE2 (ClinicalTrials.gov identifier: NCT02339116). The primary end point was OS. Secondary end points were progression-free survival (PFS), objective response rate (ORR), R0 resection rate, grade 3/4 adverse events, and subgroup analyses according to clinical and molecular characteristics. A total of 1,697 patients were randomly assigned to FOLFOXIRI + bevacizumab (n = 846) or doublets + bevacizumab (n = 851). Most (78%) had an Eastern Cooperative Oncology Group performance status of 0, and the median age was 61 years. After a median follow-up of 39.9 months, patients assigned to FOLFOXIRI + bevacizumab had significantly longer OS than those assigned to doublets + bevacizumab (median, 28.9 v 24.5 months; hazard ratio [HR], 0.81; 95% CI, 0.72 to 0.91; P < .001), with no significant heterogeneity among trials (P = .39; I2 = 2%). No significant interaction effect between treatment arm and investigated characteristics was demonstrated. Patients assigned to FOLFOXIRI + bevacizumab had longer PFS (median, 12.2 v 9.9 months; HR, 0.74; 95% CI, 0.67 to 0.82; P < .001), higher ORR (64.5% v 53.6%; P < .001), higher R0 resection rate (16.4% v 11.8%; P = .007), and higher rates of grade 3/4 neutropenia (45.8% v 21.5%; P < .001), febrile neutropenia (6.3% v 3.7%; P = .019), and diarrhea (17.8% v 8.4%; P < .001). FOLFOXIRI + bevacizumab significantly and meaningfully improves survival of patients with metastatic colorectal cancer compared with doublets + bevacizumab and provides advantage in PFS, ORR, and R0 resection rate at the price of a moderate increase in toxicity. No increased benefit is observed among patients with BRAF-mutant tumors.


Suturing Skills for Medical Students: A Systematic Review.
This systematic review aimed to identify all published evidence on teaching suturing skills for medical students. We aimed to outline significant positive teaching outcomes and devise a comprehensive framework for the optimal teaching of suturing skills for medical students. We searched MEDLINE® (via Ovid), EMBASE and SCOPUS databases until July 2019 with no language restriction using predefined 'Population, Intervention, Comparison, Outcome (PICO)' criteria. Data were summarised in discrete thematic axes using a qualitative synthesis approach. Our search yielded a total of 2,562 articles, out of which 25 were included in the final data synthesis. We provide a structured breakdown of educational interventions including participants, instructors and nature of teaching intervention. We also describe discrete means for assessment of performance and retention of suturing skills. Based on those we propose a standardised framework on teaching suturing skills for novices. To our knowledge this is the first systematic review investigating teaching interventions used to teach suturing skills in medical students. After extraction of individual positive teaching outcomes and utilising widely known learning theories and principles, we devised a comprehensive framework for more efficient and cost-effective teaching of suturing skills to medical students in the future.


Effects of nurse home-visiting on maternal life course and child development: age 6 follow-up results of a randomized trial.
To test, with an urban, primarily black sample, the effects of prenatal and infancy home visits by nurses on mothers' fertility and economic self-sufficiency and the academic and behavioral adjustment of their children as the children finished kindergarten, near their sixth birthday. We conducted a randomized, controlled trial of a program of prenatal and infancy home-visiting in a public system of obstetric and pediatric care in Memphis, Tennessee. A total of 743 primarily black women at <29 weeks of gestation, with no previous live births and with > or =2 sociodemographic risk characteristics (unmarried, <12 years of education, or unemployed), were randomly assigned to receive nurse home visits or comparison services. Outcomes consisted of women's number and timing of subsequent pregnancies, months of employment, use of welfare, food stamps, and Medicaid, educational achievement, behavioral problems attributable to the use of substances, rates of marriage and cohabitation, and duration of relationships with partners and their children's behavior problems, responses to story stems, intellectual functioning, receptive language, and academic achievement. In contrast to counterparts assigned to the comparison group, women visited by nurses had fewer subsequent pregnancies and births (1.16 vs 1.38 pregnancies and 1.08 vs 1.28 births, respectively), longer intervals between births of the first and second children (34.28 vs 30.23 months), longer relationships with current partners (54.36 vs 45.00 months), and, since the previous follow-up evaluation at 4.5 years, fewer months of using welfare (7.21 vs 8.96 months) and food stamps (9.67 vs 11.50 months). Nurse-visited children were more likely to have been enrolled in formal out-of-home care between 2 and 4.5 years of age (82.0% vs 74.9%). Children visited by nurses demonstrated higher intellectual functioning and receptive vocabulary scores (scores of 92.34 vs 90.24 and 84.32 vs 82.13, respectively) and fewer behavior problems in the borderline or clinical range (1.8% vs 5.4%). Nurse-visited children born to mothers with low levels of psychologic resources had higher arithmetic achievement test scores (score of 88.61 vs 85.42) and expressed less aggression (score of 98.58 vs 101.10) and incoherence (score of 20.90 vs 29.84) in response to story stems. There were no statistically significant program effects on women's education, duration of employment, rates of marriage, being in a partnered relationship, living with the father of the child, or domestic violence, current partner's educational level, or behavioral problems attributable to the use of alcohol or drugs. This program of prenatal and infancy home-visiting by nurses continued to improve the lives of women and children at child age 6 years, 4 years after the program ended.


Interaction between cardiac chambers and thoracic pressure in intact circulation.
A comprehensive model that describes the interaction between the cardiovascular system (CVS) and the intrathoracic pressure (ITP) based on a lumped parameter vascular representation and a time-varying elastance concept for the four cardiac chambers is presented. Special attention is given to two possible mechanisms of interventricular interaction; the constraining effects of the pericardium and direct interventricular interaction that results from the fact that the two ventricles share a common interventricular septum. The response of the CVS to positive and negative perturbations in the ITP and to injection of fluid into the pericardium was simulated and compared with experimental literature data. The results show that 1) the total heart volume is relatively constant throughout the cycle both for ITP of 0 and +15 mmHg, which is consistent with experimental data in dogs, thus suggesting that intrinsic properties of the cardiac chambers rather than a restricting pericardium is the mechanism for that observation. 2) The pericardium has a major role in modifying the transient and steady-state response to a step decrease in the ITP with a transient decrease in left ventricle (LV) end-diastolic volume followed by gradual increase afterwards. 3) The response to sudden injection of fluid into the pericardial space is a larger transient decrease in right ventricle than LV volume, which is consistent with experimental data. 4) Transmission across the septum has a relatively minor role in modifying the response of the CVS to negative pressure. Thus the model reasonably predicts the effects of intrathoracic and pericardial pressures on the circulation in a reflex-blocked animal and provides a means for placing multiple potential mechanisms in proper hierarchial order with regard to contributions to LV and overall CVS function.


Reconstitution of Rh (D) antigen activity from human erythrocyte membranes solubilized by deoxycholate.
Proteins were selectively solubilized from human erythrocyte membranes with deoxycholate. After ultracentrifugation and preliminary fractionation procedures, the detergent was removed from the soluble membranes by Bio-Beads SM-2 and dialysis against 5 millimolar magnesium chloride. Reaggregation took place with the apparent formation of vesicles which showed serologically specific Rh antigen activity.


Processed antigen binds to newly synthesized MHC class II molecules in antigen-specific B lymphocytes.
We describe the direct detection of radiolabeled antigen fragments bound to class II MHC molecules following immunoglobulin-mediated endocytosis and processing of native antigen in B lymphoblastoid cells. Tris-Tricine SDS gels revealed six distinct iodinated processing products that could be detected on class II MHC 1 hr after antigen endocytosis and persisted for at least 20 hr. These physiological processed antigen-class II complexes were remarkably stable, as judged by the fact that class II alpha beta dimers, which remain associated in SDS, became labeled with the same set of processed peptides. Using a lectin-binding assay, we show that these physiological processing products bind to the newly maturing population of MHC molecules rather than binding to the preexisting cell surface population; in contrast, an exogenous peptide binds predominantly to the latter population. A direct T cell-independent assay for processed peptide-MHC complex formation should facilitate additional studies on the exogenous antigen processing pathway.


Dynamic Metabolic Regulation by a Chromosome Segment from a Wild Relative During Fruit Development in a Tomato Introgression Line, IL8-3.
We performed comparative metabolome and transcriptome analyses throughout fruit development using the tomato cultivar M82 and its near-isogenic line IL8-3, with interesting and useful traits such as a high content of soluble solids. Marked differences between M82 and IL8-3 were found not only in ripe fruits but also at 20 days after flowering (DAF) in the hierarchical clustering analysis of the metabolome, whereas patterns were similar between the two genotypes at 10 and 30 DAF. Our metabolome analysis conclusively showed that 20 DAF is an important stage of fruit metabolism and that the Solanum pennellii introgressed region in IL8-3 plays a key role in metabolic changes at this stage. Carbohydrate and amino acid metabolism were found to be promoted in IL8-3 at 20 DAF and the ripening stage, respectively, whereas transcriptome analysis showed no marked differences between the two genotypes, indicating that dynamic metabolic regulation at 20 DAF and the ripening stage was controlled by relatively few genes. The transcript levels of the cell wall invertase (LIN6) and sucrose synthase (TOMSSF) genes in starch and sucrose metabolic pathway and that of the glutamate synthase (SlGOGAT) gene in the amino acid metabolic pathway in IL8-3 fruit were higher than those in M82, and SlGOGAT expression was enhanced under high-sugar conditions. The results suggest that the promotion of carbohydrate metabolism by LIN6 and TOMSSF in IL8-3 fruit at 20 DAF affects SlGOGAT expression and amino acid accumulation via higher sugar concentration at the late stage of fruit development.


Chick cartilage collagen: a new type of alpha 1 chain not present in bone or skin of the species.
Isolation and chromatography of collagen from chick cartilage revealed an excess of alpha1 relative to alpha2-chains. Characterization of the cyanogen bromide peptides from the alpha1 fraction indicated the presence of two homologous forms of alpha1. The results suggest that cartilage contains two collagens, one identical to the collagen of skin and bone, the other clearly different requiring the expression of an additional structural gene and possibly containing only alpha1-chains.


Reliability of the routine cytological diagnosis in bladder cancer.
To establish the reliability of three cytopathologists for cytological diagnosis of primary bladder tumors. Preoperative voided urine specimens of 71 patients with bladder cancer and 55 noncancer controls were retrospectively and blindly reviewed by 3 independent cytologists, and their results compared. The estimation of the interobserver agreement was calculated using the weighted kappa coefficient. A multivariate analysis was carried out to identify the factors associated with the disagreement between the three observers. The sensitivity and specificity for each of the participants was calculated in order to clearly identify the origin of the disagreement, in terms of the performance of the diagnostic test in the hands of each observer. A comparison of the overall diagnostic performance was made by plotting sensitivity versus 1-specificity. The weighted kappa coefficient among the 3 observers was 0.46. The multivariate analysis did not identify any variable that could have caused such disagreement. Vast differences in sensitivity and specificity were detected between observer 1 (sens. 0.90, spec. 0.45) and observers 2 (sens. 0.67, spec. 0.72) and 3 (sens. 0.71, spec. 0.80), but the overall diagnostic performance (sensitivity vs. 1-specificity) was superimposable in the 3 cases (p = NS). Simple, reproducible and agreed-on-diagnostic criteria should be established to yield reliable results in a group of cytologists. The consideration of individual diagnostic performances can give a false idea of homogeneity between observers. In this field, concordance analysis makes quality control reliable and should be a routine procedure of any pathology department.


Twenty-four-week safety and tolerability of nevirapine vs. abacavir in combination with zidovudine/lamivudine as first-line antiretroviral therapy: a randomized double-blind trial (NORA).
To compare the safety/tolerability of abacavir and nevirapine in HIV-infected adults starting antiretroviral (ARV) therapy in Uganda. Twenty-four-week randomized double-blind trial conducted with 600 symptomatic ARV-naive adults with CD4 <200 cells/mm(3) allocated to zidovudine/lamivudine plus 300 mg abacavir (A) and nevirapine placebo (n = 300) or 200 mg nevirapine (N) and abacavir placebo (n = 300) twice daily. The primary endpoint was any serious adverse event (SAE) definitely/probably or uncertain whether related to blinded nevirapine/abacavir. Secondary endpoints were adverse events leading to permanent discontinuation of blinded nevirapine/abacavir, and grade 4 events. Seventy-two per cent participants were women; 19% had WHO stage 4 disease; the median age was 37 years (range 18-66); the median baseline CD4 count was 99 cells/mm(3) (1-199). Ninety-five per cent completed 24 weeks: 4% died and 1% were lost to follow-up. Thirty-seven SAEs occurred on blinded drug in 36 participants. Twenty events [6 (2.0%) abacavir, 14 (4.7%) nevirapine participants] were considered serious adverse reactions definitely/probably/uncertain whether related to blinded abacavir/nevirapine [HR = 0.42 (95% CI 0.16-1.09) P = 0.06]. Only 2.0% of abacavir participants [six patients (0.7-4.3%)] experienced a suspected hypersensitivity reaction (HSR). In total 14 (4.7%) abacavir and 30 (10.0%) nevirapine participants discontinued blinded abacavir/nevirapine (P = 0.02): because of toxicity (6A, 15N; P = 0.07, all rash/possible HSR and/or hepatotoxicity), anti-tuberculosis therapy (6A, 13N), or for other reasons (2A, 2N). There was a trend towards a lower rate of serious adverse reactions in Ugandan adults with low CD4 starting ARV regimens with abacavir than with nevirapine. This suggests that abacavir could be used more widely in resource-limited settings without major safety concerns.


Therapeutic techniques to enhance nerve gliding in thoracic outlet syndrome and carpal tunnel syndrome.
By studying capabilities inherent in the nerve proper and carefully considering patient complaints and limitations, the surgeon-therapist team may be able to guide patients through a restorative phase via nerve gliding techniques. Nerve symptoms must be heeded when employing rehabilitation techniques. Rather than encouraging the patient to push beyond nerve pain either proximally or distally, the patient is instructed to perform exercises in positions that enhance nerve gliding in a slow, controlled manner. "Tincture of time" is prescribed as the patient advances to a less symptomatic level of function.


Associations between maternal urinary rare earth elements during pregnancy and birth weight-for-gestational age: Roles of cord blood vitamin D levels.
Prenatal exposure to rare earth elements (REEs) may contribute to adverse birth outcomes in previous studies. Cord blood vitamin D has been suggested to modify or mediate the effects of environmental exposures. However, none has investigated these roles of cord blood vitamin D in the associations of prenatal exposure to REEs with fetal growth. Maternal trimester-specific urinary concentrations of 13 REEs, cord serum total 25-hydroxyvitamin D at delivery, and birth weight (BW)-for-gestational age (GA) were determined in 710 mother-newborn pairs from Wuhan, China. Higher maternal average urinary concentrations of europium (Eu), gadolinium (Gd), dysprosium (Dy), holmium (Ho), erbium (Er), and ytterbium (Yb) across three trimesters, either individually or jointly, were significantly associated with lower BW-for-GA Z-scores and higher odds of small for gestational age (SGA) [β = -0.092; 95 % confidence interval (CI): -0.149, -0.035 for BW-for-GA Z-scores, and odds ratio = 1.60; 95 % CI: 1.14, 2.24 for SGA involved in each unit increase in weighted quantile sum index of REEs mixture]. When stratified by cord blood vitamin D levels, the associations mentioned above persisted in participants with relatively low vitamin D levels (<13.94 μg/L, the first tertile of distribution), but not among those with relatively high levels (≥13.94 μg/L) (all p-values for interaction<0.05). The mediation analyses taking account of exposure-mediator interaction showed that the relationships between REEs (as individual and mixture) exposure and lower BW-for-GA were partly mediated through decreasing cord blood vitamin D levels. The proportions mediated by cord blood vitamin D levels were 24.48 % for BW-for-GA Z-scores and 29.05 % for SGA corresponding to the REEs mixture exposure. Conclusively, our study revealed that prenatal exposures to Eu, Gd, Dy, Ho, Er, and Yb were related to fetal growth restriction. Cord blood vitamin D might alleviate toxic effects of these REEs and its reduction might partly mediate REE-induced fetal growth restriction.


Tridimensional architecture of the Golgi apparatus and its components in mucous cells of Brunner's glands of the mouse.
The three-dimensional structure of the Golgi apparatus and its components has been analyzed in thin and thick sections of mucous cells of mouse Brunner's glands by using low- and high-voltage electron microscopes and a stereoscopic approach. In thick sections of glands impregnated with osmium or treated to detect nicotinamide adenine dinucleotide phosphatase (NADPase) or thiamine pyrophosphatase (TPPase) activity, the Golgi apparatus appeared, at low magnification, as a continuous network located in the supranuclear region. At higher magnifications and in thin sections of tissue postfixed with reduced osmium and stained with lead citrate or treated to demonstrate phosphatase activity, the following components were observed: on the cis-face of the Golgi stacks, an osmiophilic tubular network referred to as the cis-element; a cis-saccular-compartment composed of a distended porous saccule slightly reactive for NADPase and three or four underlying NADPase-positive, flattened, poorly fenestrated saccules; a trans-saccular-compartment consisting of four to six TPPase-positive saccules or sacculo-tubular elements, prosecretory granules, and "peeling off" trans-tubular networks. The saccules of the cis-compartment were often perforated by large pores in register. The cavities thus formed in the stacks were called wells and were pan-shaped with a mouth directed toward the cis-face of the stacks and a bottom closed by TPPase-positive saccules. The wells always contained 80-nm vesicles. The saccules of the trans-compartment were involved in the formation of secretory granules according to the following proposed sequence of transformation. The secretion product appeared initially as a granular material evenly distributed throughout a slightly distended, poorly fenestrated saccule. These saccules appeared to transform into fenestrated elements with irregular pores and with parts of them taking on the appearance of a tubular network; they were thus referred to as sacculotubular elements. The secretory material initially distributed throughout these elements accumulated in nodular dilatations randomly distributed along the tubular portions of the elements. The dilatations, considered as prosecretory granules, increased in size as they drained the secretory material from the rest of the sacculotubular elements. Such prosecretory granules, large and irregular in shape, "peeled off" from the stacks of saccules with residual saccular or tubular structures still attached to them, some of the latter forming trans-tubular networks. The prosecretory granules detached from such membranous residues, condensed, and finally transformed into spherical secretion granules.


A new application of monolithic supports: the separation of viruses from one another.
The emergence of next-generation "deep" sequencing has enabled the study of virus populations with much higher resolutions. This new tool increases the possibility of observing mixed infections caused by combinations of plant viruses, which are likely to occur more frequently than previously thought. The biological impact of co-infecting viruses on their host has yet to be determined and fully understood, and the first step towards reaching this goal is the separation and purification of individual species. Ion-exchange monolith chromatography has been used successfully for the purification and concentration of different viruses, and number of them have been separated from plant homogenate or bacterial and eukaryotic lysate. Thus, the question remained as to whether different virus species present in a single sample could be separated. In this study, anion-exchange chromatography using monolithic supports was optimized for fast and efficient partial purification of three model plant viruses: Turnip yellow mosaic virus, Tomato bushy stunt virus, and Tobacco mosaic virus. The virus species, as well as two virus strains, were separated from each other in a single chromatographic experiment from an artificially mixed sample. Based on A260/280 ratios, we were able to attribute specific peaks to a certain viral morphology/structure (icosahedral or rod-shaped). This first separation of individual viruses from an artificially prepared laboratory mixture should encourage new applications of monolithic chromatographic supports in the separation of plant, bacterial, or animal viruses from all kinds of mixed samples.


An Analog-Digital Mixed Measurement Method of Inductive Proximity Sensor.
Inductive proximity sensors (IPSs) are widely used in position detection given their unique advantages. To address the problem of temperature drift, this paper presents an analog-digital mixed measurement method based on the two-dimensional look-up table. The inductance and resistance components can be separated by processing the measurement data, thus reducing temperature drift and generating quantitative outputs. This study establishes and implements a two-dimensional look-up table that reduces the online computational complexity through structural modeling and by conducting an IPS operating principle analysis. This table is effectively compressed by considering the distribution characteristics of the sample data, thus simplifying the processing circuit. Moreover, power consumption is reduced. A real-time, built-in self-test (BIST) function is also designed and achieved by analyzing abnormal sample data. Experiment results show that the proposed method obtains the advantages of both analog and digital measurements, which are stable, reliable, and taken in real time, without the use of floating-point arithmetic and process-control-based components. The quantitative output of displacement measurement accelerates and stabilizes the system control and detection process. The method is particularly suitable for meeting the high-performance requirements of the aviation and aerospace fields.


Usefulness of the Quick-Sepsis Organ Failure Assessment Score in Cardiovascular Intensive Care Unit to Predict Prognosis in Acute Coronary Syndrome.
Triage of patients with acute coronary syndrome (ACS) at high risk of in-hospital complications is essential. In this study, we evaluated the quick sepsis organ failure assessment (qSOFA) score as a tool for predicting the prognosis of 964 patients admitted to the cardiovascular intensive care unit (CICU) with ACS over a 4-year period. In total, out of 964 patients included, with a percentage of 4.6% for 30-day mortality. The risk of 30-day mortality was independently associated with qSOFA ≥ 2 at admission (hazard ratio = 2.76, 95% CI 1.32-5.74, p = 0.007). For MACEs, qSOFA ≥ 2 at admission was a predictive factor with (odds ratio = 2.42, 95% CI 1.37-4.36, p = .002). A qSOFA ≥ 2 on admission had an AUC of 0.729 (95% CI [0.694, 0.762]), with a good specificity of 91.6%. For 30-day mortality, an AUC of 0.759 (95%CI [0.726, 0.792]) for cardiogenic shock with specificity of 92.5%. For MACEs, an AUC of 0.702 (95% CI [0.64, 0.700] with a specificity of 95%. Concerning the different scores tested, we found no significant difference between the Zwolle score and the qSOFA score for predicting prognosis, whereas the CADILLAC score was better than qSOFA for predicting 30-day mortality (AUC = 0.829 and De long test = 0.03). However, there was no difference between qSOFA and CADILLAC scores for predicting cardiogenic shock (De Long test at 0.08). This is the first study to evaluate qSOFA as a predictive score for 30-day mortality and MACEs, and the results are very encouraging, particularly for cardiogenic shock.


Axicon-type test interferometer for cylindrical surfaces: systematic error assessment.
The principle and the alignment aberration functions are described for an axicon-type test interferometer for measuring cylindrical mantle surfaces. Additionally, we show that the derived systematic alignment functions fulfill for reasonably small misalignments the requirements for measurements in the range of approximately 1/100 of a fringe. We verify this with optical path-length calculations, using ray tracing.


Prenatal hypoxia-ischemia alters expression and activity of nitric oxide synthase in the young rat brain and causes learning deficits.
Inhibition of nitric oxide synthase (NOS) is known to possibly impair learning and memory. Our previous studies have demonstrated that prenatal hypoxia-ischemia (HI) decreases NOS expression and NOS activity in the neonatal rat brain. To investigate whether effects of prenatal HI on NOS expression continue and whether prenatal HI affects learning and memory in young rats, NOS expression and NOS activity were determined in the hippocampus of rat brains at 28 days of age following a prenatal HI insult on G17. Performances in the passive avoidance test and the Morris water maze test were also studied in these young rats prior to sampling. Rat fetuses were subjected to either a 30-min prenatal HI insult or a sham operation (SH) on gestation day 17 and rat pups were delivered naturally. Increased locomotor activity was observed in the prenatal HI rats as compared to the SH rats on postnatal days 13 and 15, but not on postnatal days 20 and 30. Prenatal HI affected learning ability in these young rats at 28 days of age, as indicated by a delayed acquisition of passive avoidance and by longer escape latency in the Morris water maze test as compared to the SH group. Prenatal HI did not affect retention of passive avoidance and spatial memory. Concomitant with these learning deficits, expression of neuronal NOS and endothelial NOS mRNAs as well as Ca2(+)-dependent NOS activity in the hippocampus of the prenatal HI rat brain were significantly decreased as compared to the SH group. These results suggest that a 30-min prenatal HI insult on gestation day 17 in rats has long-lasting effects on NOS expression and NOS activity in the offspring brain and on learning ability of these young rats. The learning deficit in offspring is possibly associated with the reduction in expression of NOS mRNA and NOS activity in the hippocampus of these animals.


Sugar nucleotide quantification using multiple reaction monitoring liquid chromatography/tandem mass spectrometry.
Glycosylation of proteins and lipids is reliant on the availability of monosaccharide-activated donors known as sugar nucleotides. They are responsible for glycosylation in cells. Reliable quantification of these sugar nucleotides might provide an insight into their biological roles and attributes. Herein, a method is described for the quantification of sugar nucleotides using ultra high pressure liquid chromatography (UHPLC) tandem mass spectrometry, allowing selective detection of sugar nucleotides in a biological sample. Seven model sugar nucleotide standards commonly associated with lipid and protein glycosylation were separated on a porous graphitic carbon column using an UHPLC system coupled to a triple stage quadrupole mass spectrometer utilizing a multiple reaction monitoring approach. Successful baseline separation of these metabolites was attained in 6 min using an ammonium formate buffer and acetonitrile, circumventing the use of MS-unfriendly pairing reagents. The linear dynamic range of this procedure was established over almost three orders of magnitude from 20 pg to 1 ng (40 pg to 2 ng for the isomers UDP-GlcNAc/GalNAc). The limit of detection ranged from 15 pg to 30 pg while the limit of quantification ranged from 50 pg to 100 pg. Furthermore, viability of this method was tested using three different breast cancer cell lines (MDA-MB-231, MDA-MB-231-BR, and MDA-MB-361) with the successful identification and quantification of all seven targeted sugar nucleotides. The described method permitted the quantitative analysis of sugar nucleotides in 10 min, thus allowing the practical use of this approach in high-throughput settings. The method was also very effective for the quantification of sugar nucleotides derived from three different breast cancer cell lines. The distribution of sugar nucleotides was different among the different cell lines and unique for each cell line.


Pseudoaneurysm of the lingual artery after temperature-controlled radiofrequency tongue base reduction: a severe complication.
Temperature-controlled radiofrequency reduction (TCRF) of the tongue base has been developed as an alternative option for the treatment of patients with obstructive sleep apnea syndrome. The technique is propagated as an easy and safe surgical method. The case of a 34-year-old male patient with obstructive sleep apnea syndrome who underwent TCRF is reported. Fourteen days after surgery was performed, heavy bleeding at the base of the tongue occurred. Computed tomography and digital subtraction angiography imaging revealed a pseudoaneurysm of the lingual artery, which was treated endovascularly by detachable and free platinum coils during the same session. The article reports the first case of pseudoaneurysm under TCRF of the tongue base and discusses the diagnostic and therapeutic procedure to handle and avoid life-threatening complications under this method of treatment.


Blood Cultures for the Diagnosis of Infective Endocarditis: What Is the Benefit of Prolonged Incubation?
To assess the need for prolonged incubation of blood culture bottles beyond five days for the diagnosis of infectious endocarditis (IE), we conducted a retrospective cohort study of 6109 sets of two blood culture bottles involving 1211 patients admitted to the Henri Mondor University Hospital for suspicion of IE between 1 January 2016 and 31 December 2019. Among the 322 patients with IE, 194 had positive blood cultures in our centre. Only one patient with a time-to-positivity blood culture of more than 120 h (5 days) was found. The main cause for the 22 patients with positive blood cultures after five days was contamination with Cutibacterium acnes. Our results do not support extending the duration of incubation of blood culture bottles beyond five days for the diagnosis of infectious endocarditis, with the exception of patients with risk factors for C. acnes infection.


Infusion of freshly isolated autologous bone marrow derived mononuclear cells prevents endotoxin-induced lung injury in an ex-vivo perfused swine model.
The acute respiratory distress syndrome (ARDS), affects up to 150,000 patients per year in the United States. We and other groups have demonstrated that bone marrow derived mesenchymal stromal stem cells prevent ARDS induced by systemic and local administration of endotoxin (lipopolysaccharide (LPS)) in mice. A study was undertaken to determine the effects of the diverse populations of bone marrow derived cells on the pathophysiology of ARDS, using a unique ex-vivo swine preparation, in which only the ventilated lung and the liver are perfused with autologous blood. Six experimental groups were designated as: 1) endotoxin alone, 2) endotoxin + total fresh whole bone marrow nuclear cells (BMC), 3) endotoxin + non-hematopoietic bone marrow cells (CD45 neg), 4) endotoxin + hematopoietic bone marrow cells (CD45 positive), 5) endotoxin + buffy coat and 6) endotoxin + in vitro expanded swine CD45 negative adherent allogeneic bone marrow cells (cultured CD45neg). We measured at different levels the biological consequences of the infusion of the different subsets of cells. The measured parameters were: pulmonary vascular resistance (PVR), gas exchange (PO2), lung edema (lung wet/dry weight), gene expression and serum concentrations of the pro-inflammatory cytokines IL-1β, TNF-α and IL-6. Infusion of freshly purified autologous total BMCs, as well as non-hematopoietic CD45(-) bone marrow cells significantly reduced endotoxin-induced pulmonary hypertension and hypoxemia and reduced the lung edema. Also, in the groups that received BMCs and cultured CD45neg we observed a decrease in the levels of IL-1β and TNF-α in plasma. Infusion of hematopoietic CD45(+) bone marrow cells or peripheral blood buffy coat cells did not protect against LPS-induced lung injury. We conclude that infusion of freshly isolated autologous whole bone marrow cells and the subset of non-hematopoietic cells can suppress the acute humoral and physiologic responses induced by endotoxemia by modulating the inflammatory response, mechanisms that do not involve engraftment or trans-differentiation of the cells. These observations may have important implications for the design of future cell therapies for ARDS.


Results in the operative treatment of pelvic endometriosis.
Two hundred and eight patients treated surgically for endometriosis were reviewed one to four years later. The incidence of endometriosis in this survey was 17 per cent of all gynecological laparotomies. After operation, 30 per cent of the patients were symptomless, 60 per cent estimated the alleviation as good or moderate, and only 10 per cent had no benefit from the operation. In the 32 cases where infertility was the main indication for operation and other factors affecting fertility were excluded, 20 pregnancies of 19 women were achieved after operation.


Health care technology in public health institutions in Kenya.
To highlight the role of technology in the practice of medicine and the delivery of health care in public hospitals, the problems encountered and suggested solutions. The article reviews the process of technology planning, acquisition, management and assessment. Analysis of results and observations leads to recommendation and suggestions. Health care technology assessment in hospitals in Kenya and South Africa 1998. INSTITUTIONS: Twenty four hospitals in Kenya and 54 hospitals in South Africa. Technology assessment as a health policy instrument and planning tool has not gained recognition in Kenya; acquisition of health care equipment is not done on the basis of evidence from relative advantage outcome, cost of ownership or returns on investment; tender boards lack the technical expertise to make clinical and technical evaluations of health care equipment and; health care is compromised due to poor equipment acquisition. The planning, deployment, management and assessment of technology should be fully integrated into health policy and planning. Policy guidelines should include the regulation, control and utilisation of health care technologies.


Fracture risk after parathyroidectomy among chronic hemodialysis patients.
The impact of parathyroidectomy (PTX) on the long-term risks for hip and other fractures is unknown. Uncontrolled case series have reported an increase in bone mineral density after PTX. However, very low serum parathyroid hormone levels have been associated with decreased bone mineral density, adynamic bone disease, and fractures. This study compared long-term fracture rates among hemodialysis patients who underwent PTX with a matched control group. Data were obtained from the US Renal Data System. Patients who underwent a first PTX while receiving hemodialysis were matched with up to three control patients by age, race, gender, year of dialysis initiation, primary cause of renal failure, and the dosage of intravenous vitamin D used before PTX. Patients with a history of fracture or renal transplantation were excluded. Study outcomes were incident hip, vertebral, and distal radius-wrist fractures identified using hospitalization codes. Incident hip fracture rates in the PTX and matched control groups were 6.0 and 9.3 fractures per 1000 person-years, respectively. After adjustment, PTX was associated with a significant 32% lower risk for hip fracture (95% confidence interval 0.54 to 0.86; P = 0.001) and a 31% lower risk for any analyzed fracture (95% confidence interval 0.57 to 0.83; P < 0.001) compared with matched control subjects. Fracture risks were lower among hemodialysis patients who underwent PTX compared with matched control subjects. Surgical amelioration of secondary hyperparathyroidism may outweigh the risk of parathyroid hormone oversuppression in terms of bone health.


Inner products and orthogonality in color recording filter design.
We formalize ideas of orthogonality and inner products implicit in the development of a number of figures of merit (FOM) of color recording filters. We show that, in negligible measurement noise, the data dependence of each FOM based on linear color correction is equivalent to a choice of inner product (and hence of orthogonality). Further, we show that optimal sensors with respect to noise sensitivity are simply defined as orthogonal with respect to this inner product. We also develop the idea of a generalized Q-factor by generalizing the Euclidean inner product to include all inner products. Simulations demonstrate the utility of our analytical results.


[Children of the GAZEL Cohort: I--Prevalence of contacts with the medico-educational system for psychological reasons, and associated factors].
An epidemiological survey of French children aged 4 to 16 was conducted in order to estimate the 12-months rates of service utilization for psychological reasons and to assess the factors associated with service use in this community sample. A large sample of 2582 children and adolescents was recruited from the families whose one parent was employed by the national electricity and gaz company (EDF-GDF). Of these employees, 20,000 have volunteered for a long-term prospective cohort study of their health and, since 1989, they have participated to annual surveys and additional ad hoc research programmes. Families with a child aged 4 to 16 in 1991 were selected. Only one child was selected in each family, and the sample was stratified by socio-economic status and family size according to census data. A survey questionnaire comprising a valid measure of child psychopathology (Child Behavior Checklist: CBCL) and an additional questionnaire including questions related to service use was used as a means of data collection. The response rate was 62.2% and factors associated with participation in the survey were analysed. The 12-months prevalence rate of contact for psychological motives were: 42.3% for general practitioners and family doctors, 7.8% for speech and language therapists, 9.5% for educational specialists, and 6.0% for mental health professionals. With the exception of general practitioners, rates of service contact were significantly higher for boys. Logistic regression analysis was used to identify separately factors associated with recent contact for each category of professionals. Results showed that, for all professionals, high scores on the CBCL measure was significantly associated with service use, the strongest association being found for mental health professionals. Family structure was also predictive of the latter, with higher rates of contacts for those children living in families whose parents are divorced, separated or widowed. Some differences for contacts with doctors were found according to the region; otherwise, no effects of socio-economic status, educational level of the parent, or other socio-economic indicators were found to predict service utilization. The implications for services are discussed.


A PNPase dependent CRISPR System in Listeria.
The human bacterial pathogen Listeria monocytogenes is emerging as a model organism to study RNA-mediated regulation in pathogenic bacteria. A class of non-coding RNAs called CRISPRs (clustered regularly interspaced short palindromic repeats) has been described to confer bacterial resistance against invading bacteriophages and conjugative plasmids. CRISPR function relies on the activity of CRISPR associated (cas) genes that encode a large family of proteins with nuclease or helicase activities and DNA and RNA binding domains. Here, we characterized a CRISPR element (RliB) that is expressed and processed in the L. monocytogenes strain EGD-e, which is completely devoid of cas genes. Structural probing revealed that RliB has an unexpected secondary structure comprising basepair interactions between the repeats and the adjacent spacers in place of canonical hairpins formed by the palindromic repeats. Moreover, in contrast to other CRISPR-Cas systems identified in Listeria, RliB-CRISPR is ubiquitously present among Listeria genomes at the same genomic locus and is never associated with the cas genes. We showed that RliB-CRISPR is a substrate for the endogenously encoded polynucleotide phosphorylase (PNPase) enzyme. The spacers of the different Listeria RliB-CRISPRs share many sequences with temperate and virulent phages. Furthermore, we show that a cas-less RliB-CRISPR lowers the acquisition frequency of a plasmid carrying the matching protospacer, provided that trans encoded cas genes of a second CRISPR-Cas system are present in the genome. Importantly, we show that PNPase is required for RliB-CRISPR mediated DNA interference. Altogether, our data reveal a yet undescribed CRISPR system whose both processing and activity depend on PNPase, highlighting a new and unexpected function for PNPase in "CRISPRology".


Dynamical Systems Modeling to Identify a Cohort of Problem Drinkers with Similar Mechanisms of Behavior Change.
One challenge to understanding mechanisms of behavior change (MOBC) completely among individuals with alcohol use disorder is that processes of change are theorized to be complex, dynamic (time varying), and at times non-linear, and they interact with each other to influence alcohol consumption. We used dynamical systems modeling to better understand MOBC within a cohort of problem drinkers undergoing treatment. We fit a mathematical model to ecological momentary assessment data from individual patients who successfully reduced their drinking by the end of the treatment. The model solutions agreed with the trend of the data reasonably well, suggesting the cohort patients have similar MOBC. This work demonstrates using a personalized approach to psychological research, which complements standard statistical approaches that are often applied at the population level.


Differences in outer membrane proteins of the lymphogranuloma venereum and trachoma biovars of Chlamydia trachomatis.
The lymphogranuloma venereum (LGV) and trachoma biovars of Chlamydia trachomatis exhibit differences in biological properties both in vivo and in vitro. To identify analogous biochemical differences, we studied the molecular charges of chlamydial outer membrane proteins (OMPs) by means of isoelectric focusing and nonequilibrium pH gradient electrophoresis. Analysis of proteins of whole elementary bodies biosynthetically labeled with L-[35S]cysteine revealed that most chlamydial proteins were neutral or acidic. The major OMPs (MOMPs) of all strains tested were acidic and had apparent isoelectric points (pIs) that varied within narrow limits (approximately 5.3 to 5.5) despite differences in molecular mass of up to 3,000 daltons (Da). However, a low-molecular-mass cysteine-rich OMP analogous to that previously described for Chlamydia psittaci varied consistently in molecular mass (12,500 versus 12,000 Da) and pI (5.4 versus 6.9) between LGV strains and trachoma strains, respectively. OMPs with a molecular mass of 60,000 Da in the trachoma biovar strains had pIs in the 7.3 to 7.7 range. However, analogous OMPs in the LGV strains existed as a doublet with a molecular mass of about 60,000 Da. Both members of the doublet were basic (pIs greater than 8.5). Both proteins of this basic doublet in LGV strains and the neutral analog in trachoma strains bound a species-specific monoclonal antibody in an immunoblot assay. These data indicate substantial differences in biochemical characteristics of analogous OMPs in the LGV and trachoma biovars. Such differences are the first structural differences described between LGV and trachoma strains which support their distinction into separate biovars and may be related to some of their biological differences.


Semaphorin3A enhances endocytosis at sites of receptor-F-actin colocalization during growth cone collapse.
Axonal growth cone collapse is accompanied by a reduction in filopodial F-actin. We demonstrate here that semaphorin 3A (Sema3A) induces a coordinated rearrangement of Sema3A receptors and F-actin during growth cone collapse. Differential interference contrast microscopy reveals that some sites of Sema3A-induced F-actin reorganization correlate with discrete vacuoles, structures involved in endocytosis. Endocytosis of FITC-dextran by the growth cone is enhanced during Sema3A treatment, and sites of dextran accumulation colocalize with actin-rich vacuoles and ridges of membrane. Furthermore, the Sema3A receptor proteins, neuropilin-1 and plexin, and the Sema3A signaling molecule, rac1, also reorganize to vacuoles and membrane ridges after Sema3A treatment. These data support a model whereby Sema3A stimulates endocytosis by focal and coordinated rearrangement of receptor and cytoskeletal elements. Dextran accumulation is also increased in retinal ganglion cell (RGC) growth cones, in response to ephrin A5, and in RGC and DRG growth cones, in response to myelin and phorbol-ester. Therefore, enhanced endocytosis may be a general principle of physiologic growth cone collapse. We suggest that growth cone collapse is mediated by both actin filament rearrangements and alterations in membrane dynamics.


Improving Lithium Metal Composite Anodes with Seeding and Pillaring Effects of Silicon Nanoparticles.
Metallic lithium (Li) anodes are crucial for the development of high specific energy batteries yet are plagued by their poor cycling efficiency. Electrode architecture engineering is vital for maintaining a stable anode volume and suppressing Li corrosion during cycling. In this paper, a reduced graphene oxide "host" framework for Li metal anodes is further optimized by embedding silicon (Si) nanoparticles between the graphene layers. They serve as Li nucleation seeds to promote Li deposition within the framework even without prestored Li. Meanwhile, the LixSi alloy particles serve as supporting "pillars" between the graphene layers, enabling a minimized thickness shrinkage after full stripping of metallic Li. Combined with a Li compatible electrolyte, a 99.4% Coulombic efficiency over ∼600 cycles is achieved, and stable cycling of a Li||NMC532 full cell for ∼380 cycles with negligible capacity decay is realized.


Survival of RNA Replicators is much Easier in Protocells than in Surface-Based, Spatial Systems.
In RNA-World scenarios for the origin of life, replication is catalyzed by polymerase ribozymes. Replicating RNA systems are subject to invasion by non-functional parasitic strands. It is well-known that there are two ways to avoid the destruction of the system by parasites: spatial clustering in models with limited diffusion, or group selection in protocells. Here, we compare computational models of replication in spatial models and protocells as closely as possible in order to determine the relative importance of these mechanisms in the RNA World. For the survival of the polymerases, the replication rate must be greater than a minimum threshold value, kmin, and the mutation rate in replication must be less than a maximum value, Mmax, which is known as the error threshold. For the protocell models, we find that kmin is substantially lower and Mmax is substantially higher than for the equivalent spatial models; thus, the survival of polymerases is much easier in protocells than on surfaces. The results depend on the maximum number of strands permitted in one protocell or one lattice site in the spatial model, and on whether replication is limited by the supply of monomers or the population size of protocells. The substantial advantages that are seen in the protocell models relative to the spatial models are robust to changing these details. Thus, cooperative polymerases with limited accuracy would have found it much easier to operate inside lipid compartments, and this suggests that protocells may have been a very early step in the development of life. We consider cases where parasites have an equal replication rate to polymerases, and cases where parasites multiply twice as fast as polymerases. The advantage of protocell models over spatial models is increased when the parasites multiply faster.


Ectomycorrhizal fungal biomass in roots and uptake of P from apatite by Pinus sylvestris seedlings growing in forest soil with and without wood ash amendment.
Forest soil from an experimental Norway spruce forest with four levels of wood ash addition (0, 1, 3 and 6 tonnes ha(-1)) was used to inoculate pine (Pinus sylvestris) seedlings with indigenous ectomycorrhizal (EM) fungi. Uptake of 32P and 86Rb in a root bioassay was used to estimate the demand for P and K by seedlings grown in the different soils. Utilisation of P from apatite was tested in a laboratory system where uptake by the ectomycorrhizal mycelium was separated from uptake by roots. The demand for P and K in the seedlings was similar regardless of the ash treatment. Variation in EM levels, estimated as fungal biomass (ergosterol) in roots, was large in the different soils, but not related to ash addition. Uptake of P from apatite was, on average, 23% of total seedling P and was not related to EM levels. It was concluded that the improved P uptake from apatite by EM fungi found in earlier studies is probably not a general phenomenon among EM fungi. The small effect of ash addition on EM levels and P uptake suggests that addition of granulated wood ash is a forest management treatment that will have only minor influence on ectomycorrhizal symbiosis.


Environmental and physiological controls over oxygen and carbon isotope composition of Tasmanian blue gum, Eucalyptus globulus.
We measured oxygen isotope ratios (delta18O) of xylem sap, phloem sap, leaves, wood and bark of Eucalyptus globulus Labill. growing in southwestern Australia. Carbon isotope ratios (delta13C) were measured in the dry matter of phloem sap, leaves and wood. Results were used to test several aspects of a mechanistic model of 18O enrichment and provided insights into post-photosynthetic variations in dry matter delta13C. Xylem water delta18O varied little within the tree crown, whereas variation at the landscape-level was more pronounced, with plantations near the coast being enriched by up to 3 per thousand compared with plantations less than 100 km inland. Phloem water was significantly enriched in 18O compared with xylem water in two of three sampling campaigns; mean enrichments were 0.5 and 0.8 per thousand. Phloem sap sugars exported from E. globulus leaves closely reflected observed leaf water enrichment when diurnal variation in photosynthesis was taken into account. Photosynthetic rates were higher in the morning than in the afternoon, whereas leaf water 18O enrichment increased to maximum values in the afternoon. A non-steady-state model of leaf water 18O enrichment accurately predicted observed values through a full diel cycle. Mean estimates of the proportion of organic oxygen effectively exchanging with xylem water during cellulose synthesis were close to 0.40 for both leaves and wood. Carbon isotope ratios of nascent xylem tissues did not differ from those of phloem sap sugars collected concurrently, whereas nascent leaf tissues were depleted in 13C by 2 per thousand compared with phloem sap sugars, suggesting that, in E. globulus, 13C enrichment of sink tissues compared with source leaves does not result from an enriching process within the sink tissue.


Burnout among Iranian medical students: Prevalence and its relationship to personality dimensions and physical activity.
Several studies have shown the association between personality traits and academic burnout. But the main goal of the present study was to find out an experimental answer to the following questions: Is there a simple relationship between personality dimensions and academic burnout? Can physical activity affect this relationship?. In this cross-sectional correlational study, 417 medical students were selected from three major cities of Iran through stratified multistage sampling and assessed by demographic information form, Baecke Physical Activity Questionnaire, Temperament and Character Inventory, and Breso's Academic Burnout Questionnaire. Bivariate Pearson correlations and hierarchical linear regression were used to examine the relationships between academic burnout, personality traits, and physical activity. In this study, 400 medical students (39% male and 61% female) filled the questionnaires correctly. The total prevalence of academic burnout was 25.5% (n=102), with heterogeneous levels. Regression analysis indicated that in a multivariate model, being male (β=0.08, p=0.013), higher years of medical school (β=0.18, p˂0.001), and lower scores in novelty seeking (β=-0.53, p=0.006), cooperativeness (β=-0.55, p=0.010), and physical activity (β=-1.22, p˂0.001) could be attributed to higher scores of academic burnout. Furthermore, physical activity had a moderating role in "novelty seeking-academic burnout" (β=-0.47, p=0.044) and "cooperativeness-academic burnout" (β=-0.89, p=0.001) relationships (ΔR2=0.02, p˂0.001). The results suggested that male gender, higher years of medical school, and lower levels of novelty seeking, cooperativeness, and physical activity are associated with higher levels of academic burnout among Iranian medical students. Therefore, paying attention to male gender and individual difference factors, as well as planning for physical education classes during the medicine courses (especially in the last years of medical school), seems essential. However, more extensive investigations need to be carried out in this field through longitudinal studies.


Phylogenetic characterization of episymbiotic bacteria hosted by a hydrothermal vent limpet (lepetodrilidae, vetigastropoda).
Marine invertebrates hosting chemosynthetic bacterial symbionts are known from multiple phyla and represent remarkable diversity in form and function. The deep-sea hydrothermal vent limpet Lepetodrilus fucensis from the Juan de Fuca Ridge complex hosts a gill symbiosis of particular interest because it displays a morphology unique among molluscs: filamentous bacteria are found partially embedded in the host's gill epithelium and extend into the fluids circulating across the lamellae. Our objective was to investigate the phylogenetic affiliation of the limpet's primary gill symbionts for comparison with previously characterized bacteria. Comparative 16S rRNA sequence analysis identified one γ- and three ε-Proteobacteria as candidate symbionts. We used fluorescence in situ hybridization (FISH) to test which of these four candidates occur with the limpet's symbiotic gill bacteria. The γ-proteobacterial probes consistently hybridized to the entire area where symbiotic bacteria were found, but fluorescence signal from the ε-proteobacterial probes was generally absent. Amplification of the γ-proteobacterial 16S rRNA gene using a specific forward primer yielded a sequence similar to that of limpets collected from different ridge sections. In total, direct amplification or FISH identified a single γ-proteobacterial lineage from the gills of 23 specimens from vents separated by a distance up to about 200 km and collected over the course of 2 years, suggesting a highly specific and widespread symbiosis. Thus, we report the first filamentous γ-proteobacterial gill symbiont hosted by a mollusc.


Therapeutic plasma exchange as a nephrological procedure: a single-center experience.
In the United States, therapeutic plasma exchange (TPE) is both performed and requested by a wide range of services, often on an empiric basis (before a diagnosis is established). Whether empiric therapy is beneficial has not been established. Patients were identified from an electronic procedure log that included those patients who received plasmapheresis at Walter Reed Army Medical Center from 1996 to 2003. The clinical indications, referring service, and outcomes (including deaths) that occurred were tabulated. Between March 1997 and August 2003, 568 TPE treatments were performed in 54 patients. The majority of the diagnoses were either neurologic (48%) or hematologic (37%). Thirty-three patients (61%) received TPE for a Category I indication. Twelve cases were performed empirically (without an established diagnosis) at the request of the referring service, most (7) performed for presumed thrombotic thrombocytopenic purpura (TTP). Almost 80% of patients required central venous catheters for treatment. Twelve patients (22%) experienced a major complication including death, and six patients (11%) died. Of the patients who died, 5 (83%) were treated empirically versus one death (17%) among patients not treated empirically, P < 0.001 by Chi Square. Only one of the seven patients treated empirically for TTP died, however. In logistic regression analysis, empiric treatment was the only factor independently associated with death, adjusted odds ratio, 34.2, 95% CI, 3.4, 334.8, P = 0.003. The most common indication for TPE was neurological disease, which also accounted for the highest proportion of complications. With the exception of presumed TTP, performing TPE in the absence of a confirmed diagnosis was not beneficial.


The prior infection with SARS-CoV-2 study (PICOV) in nursing home residents and staff - study protocol description and presentation of preliminary findings on symptoms.
The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has presented itself as one of the most important health concerns of the 2020's, and hit the geriatric population the hardest. The presence of co-morbidities and immune ageing in the elderly lead to an increased susceptibility to COVID-19, as is the case for other influenza-like illnesses (ILI) or acute respiratory tract infections (ARI). However, little is known, about the impact of a previous or current infection on the other in terms of susceptibility, immune response, and clinical course. The aim of the "Prior Infection with SARS-COV-2" (PICOV) study is to compare the time to occurrence of an ILI or ARI between participants with a confirmed past SARS-CoV-2 infection (previously infected) and those without a confirmed past infection (naïve) in residents and staff members of nursing homes. This paper describes the study design and population characteristics at baseline. In 26 Belgian nursing homes, all eligible residents and staff members were invited to participate, resulting in 1,226 participants. They were classified as naïve or previously infected based on the presence of detectable SARS-CoV-2 antibodies and/or a positive RT-qPCR result before participation in the study. Symptoms from a prior SARS-CoV-2 infection between March and August 2020 were compared between previously infected residents and staff members. Infection naïve nursing home residents reported fewer symptoms than previously infected residents: on average 1.9 and 3.1 symptoms, respectively (p = 0.016). The same effect was observed for infection naïve staff members and previously infected staff members (3.1 and 6.1 symptoms, respectively; p <0.0001). Moreover, the antibody development after a SARS-CoV-2 infection differs between residents and staff members, as previously infected residents tend to have a higher rate of asymptomatic cases compared to previously infected staff members (20.5% compared to 12.4%; p <0.0001). We can postulate that COVID-19 disease development and symptomatology are different between a geriatric and younger population. Therefore, the occurrence and severity of a future ILI and/or ARI might vary from resident to staff.


Anchoring protein is required for cAMP-dependent stimulation of L-type Ca(2+) channels in rabbit portal vein.
Stimulation of cardiac L-type Ca(2+) channels by cAMP-dependent protein kinase (PKA) requires anchoring of PKA to a specific subcellular environment by A-kinase anchoring proteins (AKAP). This study evaluated the possible requirement of AKAP in PKA-dependent regulation of L-type Ca(2+) channels in vascular smooth muscle cells using the conventional whole cell patch-clamp technique. Peak Ba(2+) current in freshly isolated rabbit portal vein myocytes was significantly increased by superfusion with either 0.5 microM isoproterenol (131 +/- 3% of the control value, n = 11) or 10 microM 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP; 114 +/- 1%, n = 8). The PKA-induced stimulatory effects of both isoproterenol and 8-BrcAMP were completely abolished by a specific PKA inhibitor KT-5720 (0.2 microM) or by dialyzing cells with Ht 31 (100 microM), a peptide that inhibits the binding of PKA to AKAP. In contrast, Ht 31 did not block the excitatory effect of the catalytic subunit of PKA when dialyzed into the cells. These data suggest that stimulation of Ca(2+) channels in vascular myocytes by endogenous PKA requires localization of PKA through binding to AKAP.


Identification and characterization of a versatile keratinase, KerZJ, from Stenotrophomonas sp. LMY.
Keratinases have drawn increasing attention in recent decades owing to their catalytic versatility and broad applications from agriculture to medicine. In the present study, we isolated a highly keratinolytic and fibrinolytic bacterium from the campus soil and named it Stenotrophomonas sp. LMY based on genetic information. To identify the potential keratinase genes, the genome sequence of the strain was obtained and analyzed. Sequence alignment and comparison revealed that the protein 1_737 (KerZJ) had the highest sequence homology to a reported keratinase KerBL. We recombinantly expressed KerZJ in Escherichia coli Origami™ (DE) pLysS and purified it to homogeneity. KerZJ showed the highest activity at 40 °C and pH 9.0, and metal ions exhibited no significant effects on its activity. Although reducing agents would break the disulfide bonds in KerZJ and reduce its activity, KerZJ still exhibited the ability to hydrolyze feather keratin in the presence of β-ME. KerZJ could efficiently digest human prion proteins. In addition, KerZJ showed fibrinolytic activity on fibrin plates and effectively eliminated blood clots in a thrombosis mouse model without side effects. Our results suggest that KerZJ is a versatile keratinase with significant potential for keratin treatment, decontamination of prions, and fibrinolytic therapy.


Human parvovirus B19 infection during pregnancy.
Human parvovirus B19 (B19) has been implicated as the cause of fifth disease and has been associated with fetal death. We identified pregnant women who were at risk of contracting B19 infection during an outbreak of fifth disease. The sera of 12 women classified at high risk of exposure and 19 classified at low risk were tested during prenatal care, at delivery, or at both times for IgG and IgM antibodies to B19. Four women at high risk but none at low risk were considered infected because they were IgM positive. One IgM-positive woman gave birth to a stillborn hydropic fetus whose tissues were positive for B19 DNA by a nucleic acid hybridization assay. The other three IgM-positive women gave birth to normal offspring, of whom one had IgM-positive cord serum. We conclude that B19 infection during pregnancy can lead to fetal infection with at least two associated outcomes--no adverse effect on the fetus or fetal death.


Evaluation of an oral health intervention among mothers of young children: a clustered randomized trial.
Oral health education for the mothers of very young children is important in reducing the risk of early childhood caries. This study aimed to evaluate the impact of an oral health intervention among mothers of 1-2 years old children. This cluster randomized controlled trial (2012) was conducted among ninety mothers of 1-2 year old children. The setting of study was 10 child day-care centers out of 18 in Hamadan, western Iran. Day-care centers were randomly allocated into two groups: an intervention group (5 day-care centers, 45 mothers) and a control group (5 day-care centers, 45 mothers). Intervention consisted of three sessions, a booklet, and mobile phone text-message reminders. The primary outcome was change in cleaning the children' teeth, while the secondary outcomes were changes in Theory of Planned Behavior (TPB) cognitions. Questionnaires at baseline, 10 days, and 3 months assessed intervention effects. Data were analyzed using SPSS v.16. T tests, chi- square, and logistic and linear generalized estimating equations (GEE) regression were used to test intervention impact. At 10-day assessment, mothers in intervention group reported a significant difference in knowledge (P=0.001), attitude (P=0.004), perceived behavioral control (P=0.008), and cleaning of children's teeth (P=0.011). Also, at 3-month assessment compared to control group, the mothers in intervention group significantly improved in scores of knowledge (P=0.001), attitude (P=0.001), perceived behavioral control (P=0.001), and cleaning of children's teeth (P=0.001). However, the effect sizes were small to medium and ranged from 0.1 to 0.4 for all cognitions except knowledge (effect size>0.70). Generalized estimating equations (GEE) showed that score of attitude and perceived behavioral control of intervention group improved between the two post-test assessments. A brief multicomponent theory-based intervention among mothers of 1-2 years old children was effective moderately in improving cognitions and self-reported cleaning children's teeth.


Isoprenoid Fatty acids isolated from the kerogen matrix of the green river formation (eocene).
Demineralized oil shale was oxidized with chromic acid, and C(14) to C(22) isoprenoid fatty acids were isolated and identified. The major components of the branched-chain acid fraction after successive 3-, 6-, and 15-hour oxidations are C(15) and C(16) branched-chain acids; C(17), C(19) (norphytanic acid), and C(20) (phytanic acid) were obtained in lower concentration; no C(18) product was obtained. Separations were effected by column and gas-liquid chromatography, and the structures of individual components were determined by high- and low-resolution mass spectrometry.


The clinical specialist in community health nursing: a solution for the 21st century.
The clinical specialist (CS) in community health nursing (CHN) addresses health problems in populations and communities in ways that are different from and complimentary to strategies used by practitioners of individualized patient care. Four programs based on comprehensive assessments, systematic program planning, deliberate implementation, and both formative and summative evaluation are presented. The programs were developed by graduate students in the CHN clinical specialization major at the Frances Payne Bolton School of Nursing. With expert faculty guidance and a competency-driven program of study, strategies were implemented to promote the health of community-dwelling well elderly people, home health care nurses who provide service to patients with respiratory problems, and high school students in a private religious school. Experienced parish nurses also benefited from a program designed to enhance their skills in theological reflection. This article also describes the curricular design developed to educate this clinician for the 21st century. Lastly, continued attention to the dynamic criteria of the American Nurses Association Standards of Community Health Nursing Practice is recommended as crucial to the further development of this clinical specialization.


[Influence of electrical stimulation of "hunger center" of the lateral hypothalamus and food reinforcements on myoelectrical activity of the gastro-esophageal sphincter and stomach in rabbits under the conditions of hunger and satiation].
To study the combined effect of electrostimulation of "hunger center" of the lateral hypothalamus (LH) and food-obtaining behavior arising from it on myoelectrical activity of gastro-esophageal sphincter (GES) and the stomach in pre-fed and subjected to food deprivation animals . MATERIAL AND METHODS. Registration of myoelectrical GES and the stomach activity was carried out under free-behavior conditions in rabbits subjected to food deprivation or pre-fed before the experiment. It was done by means of chronically implanted electrodes during LH electrostimulation in the presence of food. Simultaneously using the web-camera the animals behavior was recorded. LH stimulation was produced by STM-100C stimulator (USA) with implanted bipolar nichrome electrodes. Analysis of temporal parameters of myoelectrical activity of GES and the stomach were carried out by the program AcqKnowledge (USA), and statistical analysis of the data by the program Statistica 6. Significanse of differences between the samples was assessed by the U-Mann-Whitney test (p < 0.05). Electrostimulation of "hunger center" of the lateral hypothalamus in pre-fed rabbits and the rabbits subjected to daily food deprivation, in the presence of food causes resultant food behavior which is accompanied by regular generations of bursts of peak potentials, frequency of which is essentially different in hungry and satiated animals and depends on intensity of artificially induced and artificially reinforced food motivation. In the process of LH stimulation arising resultant food behavior in satiated animals is accompanied by regular generation of high-amplitude slow electrical waves (SEW) by the muscles of lesser curvature (LC), the body and antrum of the stomach (AS) and this is reflected in the structure of temporal organization of slow electrical activity (SEA) in the form of monomodal distributions of SEW periods, typical of satiation state. Despite the increase in food motivation level, due to LH stimulation, additional entry of food into the stomach of satiated rabbits completely eliminates inhibitory effect of starvational motivational excitation on SEA of the muscles of LC, the body and AS. SEA alterations of the stomach muscles in hungry rabbits in the presence of food and thus arising of food-obtaining behavior during LH stimulation have two-phase character. At the initial stage of food behavior in hungry animals during LH stimulation high extent of scaterring of the values of SEW periods generated by the body and AS muscles is preserved, as evidenced by the bimodal distribution of SEW periods characteristic of the state of hunger. In spite of food entry into the stomach at the 1-st phase of LH stimulation, inhibitory effect of artificially reinforced starvational motivational excitation on pacemaker activity of the stomach is retained. At the 2-nd phase of LH electrostimulation food reinforcement eliminates inhibitory effect of food motivational excitation on myoelectrical activity of pacemaker of the stomach that gives maximal rhythm of SEW generation to the body and AS, monomodal distributions of SEW periods indicate to it. lnteraction of artificially induced and artificially reinforced food motivational excitation with afferentation from food reinforcement on neurons of the central generator of deglutition pattern and dorsal vagal complex due to LH electrostimulation and thereby arising resultant food obtaining behavior is specifically reflected in patterns of myoelectrical activity of GES, LC, the body and AS.


Trauma- and sepsis-induced hepatic ischemia and reperfusion injury: role of angiotensin II.
We hypothesized that angiotensin II, a potent vasoconstrictor, is involved in the occurrence of hepatic ischemia after burn and sepsis, and that administration of angiotensin II antagonist DuP753 would ameliorate this process. Randomized animal study. University laboratory, investigational intensive care unit, University of Texas Medical Branch, Galveston. Female pigs (n = 18, weighing 20-25 kg). All animals were prepared with ultrasonic flow probes on the portal vein and the common hepatic artery. Catheters were inserted in the superior mesenteric and left hepatic veins. After 5 days all animals were anesthetized and 12 of them received 40% total body surface area third-degree burn. Escherichia coli lipopolysaccharide (100 microg/kg) was intravenously administered at 18 hours postburn DuP753 was administered intravenously in a dose of 1 microg/kg to 6 pigs immediately after the burn. All animals were studied for 42 hours. Systemic and hepatic hemodynamics were measured and blood samples were drawn for determinations of arterial, mixed venous, and portal blood gases at baseline and at 14 consecutive time points, starting 1 hour after the burn. Burn caused a 4.6-fold increase in hepatic arterial vascular resistance and a 49% decrease in hepatic arterial blood flow. Postburn administration of angiotensin II receptor blocker DuP753 yielded a significant improvement in the hepatic arterial hemodynamics (only 12% increase in hepatic arterial vascular resistance and 8% decrease in hepatic arterial blood flow, P<.05 vs nontreated group, analysis of variance [ANOVA]). Postlipopolysaccharide hepatic arterial blood flow was significantly reduced (12% of baseline, P<.05, ANOVA), in contrast to DuP753-treated animals (64% of baseline, P<.05 vs nontreated group, ANOVA). Postburn blocking of angiotensin II receptors yielded a significant improvement in postlipopolysaccharide portal venous blood flow (85% of baseline vs 48% of baseline in nontreated animals, P<.05, ANOVA ). Postburn endotoxemia resulted in a significant decrease of hepatic oxygen delivery (22% of baseline) and hepatic oxygen consumption (30% of baseline), while no marked changes were observed in the DuP753-treated group (P<.05 vs nontreated group, ANOVA). Angiotensin II seems to play a pivotal role in burn- and sepsis-induced hepatic ischemia and reperfusion injury. Blocking angiotensin II receptors by DuP753 seems to abrogate this adverse effect of thermal injuries and sepsis on hepatic perfusion and oxygenation.


Psychometric properties of the neck disability index.
To determine if a response set bias existed, to assess the factor structure and internal consistency, and to compare Neck Disability Index (NDI) scores with visual analogue scale (VAS) scores for pain intensity. Although neck pain is a common problem, few instruments exist to assess the disability that accompanies it. The NDI is a 10 item paper-and-pencil measure of disability resulting from neck pain. A cross sectional study evaluating the psychometric properties of the NDI. Seven modified versions of the original NDI were developed to assess the presence or absence of response set bias using a one-way analysis of variance. Internal consistency was measured by a Cronbach alpha, two factor analyses (exploratory and confirmatory) were conducted to examine the structure of the NDI and stepwise regression analysis was used to examine the variables most predictive of VAS scores. Results from 237 neck pain patients show that the responses given on the eight versions of the NDI are a function of the content and not of the format in which the items are presented. The NDI has stable psychometric characteristics, evidenced by high internal consistency (alpha = .92). In both factor analyses, one factor was extracted. The NDI possesses stable psychometric properties and provides an objective means of assessing the disability of patients suffering from neck pain.


[Neurohumoral control of protein biosynthesis during aging].
It has been shown in the experiments on adult (6-8 mo) and old (26-28 mo) Wistar rats that in aging, due to an electrical stimulation of the hypothalamus, the liver induction of thyroxine aminotransferase, tryptophan-pyrrolase, glucose-6-phosphatase and fructose-1, 6-diphosphatase decreases. In old rats, the biosynthesis of RNA fractions gets activated at later periods. In contrast to adult animals, the electrical hypothalamic stimulation did not induce any marked changes in chromatin fractions ratio and transcriptional processes in old rats. With aging, it may happen that the target cells cannot respond to adequate stimulations, while the central (hypothalamic, in particular) mechanisms cannot realize them. In aging, the influence of the hormones (insulin, testosterone, thyroxin and hydrocortisone) on the synthesis of proteins-invertors, regulating plasmatic membrane state Is weakened. Following surgical denervation of the liver in old rats, the less marked changes in RNA and protein synthesis and lesser influences on monooxygenase induction were found in old rats. All these observations indicate an impairment of the neural control over protein biosynthesis in senescence. Also, the axonal transport of proteins is delayed in old rats that may influence the nervous cell aging. Owing to all these shifts, the plastic provision of body integrative reactions is impaired.