Stimulus-dependent spatial patterns of response in SI cortex.
Recently we reported that vibrotactile flutter stimulation of a skin locus at different amplitudes evokes an optical response confined to the same local region of the primary somatosensory cortex (SI), where its overall magnitude varies proportionally to the flutter amplitude. In this report, we characterize the impact of the flutter amplitude on the spatial patterns of activity evoked within the responding SI region. In order to characterize the spatial pattern of activity within the responding SI region, images of the flutter-evoked SI optical response were segmented and analyzed with spatial frequency analysis. The analysis revealed that: (1) dominant spatial frequencies in the optical intrinsic signal emerge within the responding SI region within 3-5 sec of stimulus onset; (2) the stimulus-evoked activity is spatially organized in a form of several roughly parallel, anterior-posteriorly extended waves, spaced 0.4-0.5 mm apart; (3) the waves themselves exhibit spatial periodicities along their long axis; and (4) depending on the flutter stimulus amplitude, these periodicities can range from fine 0.15 mm "ripples" at 50 microm amplitude to well-developed 0.5 mm fluctuations at the amplitude of 400 microm. The observed spatiointensive fractionation on a sub-macrocolumnar scale of the SI response to skin stimulation might be the product of local competitive interactions within the stimulus-activated SI region and may be a feature that could yield novel insights into the functional interactions that take place in SI cortex.


Psychiatric inpatient, outpatient, and medication utilization and costs among privately insured youths, 1997-2000.
The study examined trends in use of inpatient and outpatient mental health services, including pharmacotherapy, among privately insured children and adolescents from 1997 to 2000. Data from a national database of more than 1.7 million privately insured individuals were used in an analysis of inpatient, outpatient, and pharmacy claims of users of mental health care age 17 years and younger (approximately 20,000 patients per year). Annual utilization rates and adjusted costs for services and dispensed psychotropic medications were calculated. Results from 1997 and 2000 were compared across diagnostic and age categories. The proportion of youths with an inpatient psychiatric admission decreased by 23.7% from 1997 to 2000, and annual inpatient and outpatient costs decreased by 1,216 US dollars (18.4%) and 157 US dollars (14.4%), respectively. Decreases were driven by a reduction in inpatient days (20.0%) and by a combination of a reduction in outpatient visits (11.3%) and declining payments per outpatient visit (6.1%). Payment trends across diagnoses varied considerably, with the largest reductions seen in treatment of depression, hyperactivity, adjustment disorders, and anxiety disorders. Over the same period, the proportion of youths receiving medication increased by 4.9%, and mean annual medication-related costs per outpatient increased by 41 US dollars (12.1%). Reductions in inpatient and outpatient mental health service intensity and reimbursements documented in previous research continued through the late 1990s. Declines were accompanied by concurrent increases in the use of and costs associated with psychotropic medications, particularly for youths with mood and anxiety disorders. These results document a shift toward medication-based outpatient treatment modalities.


Evaluation of the effectiveness and safety of photodynamic therapy in the treatment of precancerous diseases of the cervix (neoplasia) associated with the human papillomavirus: a systematic review.
This study provides an overview of the effectiveness and safety of PDT for the treatment of HPV-associated precancerous cervical conditions and contains recent findings from relevant research studies. A comprehensive literature search of MEDLINE/PubMed, Cochrane Central Library, and Google Scholar was conducted, including analytic epidemiological studies, and 11 papers were included. The narrative synthesis approach was used to summarize the results of the included studies. Studies were critically appraised using The Joanna Briggs Institute (JBI) tool for assessing the risk of bias. The results of the study demonstrate that CRR for HPV remission ranges from 66.7% to 92.73%, whereas for CIN1 it fluctuates from 57.1% to 83.3%. The frequency of recurrence of the disease ranged from 3.3% to 8.9% during the follow-up period of up to 2 years. Adverse events were observed in 8 (66%) studies and the most common were cervical stenosis, abdominal pain, vaginal pain, and focal edema. Five types of topical and intravenous applications along with lasers of various wavelengths and intensities were mostly used. However, all studies demonstrated relatively similar results. According to the results, PDT has demonstrated favorable outcomes, but no impressive effect on the treatment of CIN. It should be emphasized, that the effectiveness of PDT for the treatment of HPV-associated CIN may vary depending on some variables, including the kind of PDT agent used, the dosage, duration and frequency of PDT administration, the severity and location of the lesions, and the host immunological response.


Clinical genetic testing and early surgical intervention in patients with multiple endocrine neoplasia type 1 (MEN 1).
We sought to develop a comprehensive program for clinical genetic testing in a large group of extended families with multiple endocrine neoplasia type 1 (MEN 1), with the ultimate aim of early tumor detection and surgical intervention. Germline mutations in the MEN1 tumor suppressor gene are responsible for the MEN 1 syndrome. Direct genetic testing for a disease-associated MEN1 mutation is now possible in selected families. The neuroendocrine tumors of the pancreas/duodenum and the intrathoracic neuroendocrine tumors that occur in MEN 1 carry a malignant potential. Importantly, these tumors arise in otherwise young healthy patients and are complicated by the potential for multifocality and involvement of multiple target tissues. The optimal screening methods and indications for early surgical intervention in genetically positive patients have yet to be defined. Nine MEN 1 kindreds were included in the study. The mutations for each kindred were initially identified in the research laboratory. Subsequently, mutation detection was independently validated in the clinical Molecular Diagnostic Laboratory. Each patient in the study underwent formal genetic counseling before testing. Genetic testing was performed in 56 at-risk patients. Patients were stratified according to risk: Group I (n = 25), 50% risk, younger than 30 years old; Group II (n = 20), 50% risk, 30 years old or older; Group III (n = 11) 25% risk. Seven patients (age, 12 to 42 years; mean, 20.6 +/- 3.8 years) had a positive genetic test. Patients with a novel positive genetic test were in either Group I (n = 6) or Group II (n = 1) and have been followed for 35.8 +/- 2.0 months. Of the 7 genetically positive patients, hypercalcemia was either present at the time of diagnosis or developed during the period of follow-up in 6 patients. Four patients have undergone parathyroidectomy as early as age 16 years. One genetically positive patient has not yet developed hyperparathyroidism. Intensive biochemical screening in this select group of patients identified an elevated pancreatic polypeptide level and pancreatic tail mass lesion in a 15-year-old male who is asymptomatic and currently normocalcemic. Genetic testing identifies patients harboring an MEN1 mutation before the development of clinical signs or symptoms of endocrine disease. When genetically positive patients are carefully studied prospectively, biochemical evidence of neoplasia can be detected an average of 10 years before clinically evident disease, allowing for early surgical intervention. Genetically positive individuals should undergo focused cancer surveillance for early detection of the potentially malignant neuroendocrine tumors that account for most of the disease-related morbidity and mortality.


A recursive ensemble organ segmentation (REOS) framework: application in brain radiotherapy.
The aim of this work is to develop a novel recursive ensemble OARs segmentation (REOS) framework for accurate organs-at-risk (OARs) automatic segmentation. The REOS recursively segment individual OARs by ensembling images features extracted from an organ localization module and a contour detection module. Both modules are based on a 3D U-Net architecture. The organ localization module is trained for rough segmentation to localize a region of interest (ROI) that encompasses the to-be-delineated OAR, while the contour detection module is trained to segment the OAR within the identified ROI. In this study, the developed REOS framework is applied for brain radiotherapy on segmenting six OARs including the eyes, the brainstem (BS), the optical nerves and the chiasm. Eighty T1-weighted magnetic resonance images (MRI) from 80 brain cancer patients' cases with OARs' gold standard contours were collected for training and testing REOS. On 20 testing cases, the REOS achieve a high segmentation accuracy with Dice similarity coefficient (DSC) mean and standard deviation of 93.9% ± 1.4%, 94.5% ± 2.0%, 90.6% ± 2.7%, on the left and right eyes and the BS, respectively. On small and segmentation-challenging organs, the left and right optical nerves and the chiasm, the REOS achieves DSC of 78.0% ± 10.5%, 82.2% ± 5.9% and 71.1% ± 9.1%. The satisfactory performances demonstrated the effectiveness of the REOS in OARs segmentation.


Chronic graft-versus-host disease. Part I: Epidemiology, pathogenesis, and clinical manifestations.
Chronic graft-versus-host disease is a major complication of allogeneic hematopoietic cell transplantation and a leading cause of long-term morbidity, nonrelapse mortality, and impaired health-related quality of life. The skin is commonly affected and presents heterogeneously, making the role of dermatologists critical in both diagnosis and treatment. In addition, new clinical classification and grading schemes inform treatment algorithms, which now include 3 U.S. Food and Drug Administration-approved therapies, and evolving transplant techniques are changing disease epidemiology. Part I reviews the epidemiology, pathogenesis, clinical manifestations, and diagnosis of chronic graft-versus-host disease. Part II discusses disease grading and therapeutic management.


Serologic abnormalities in systemic sclerosis.
Recent evidence has confirmed that sera from most systemic sclerosis (SSc) patients contain one of three mutually exclusive, SSc-associated autoantibodies (anti-RNA polymerase III, anti-topoisomerase I, or anti-centromere antibodies). Each is associated with the presence of particular clinical features and certain human lymphocyte antigen (HLA) alleles. Based on the available data the most likely model is for the existence of three distinct disease processes, each with certain key pathologic features. In turn, each pathologic state is responsible for characteristic symptoms, and leads to the production of a distinctive set of modified autoantigens. Certain cryptic epitopes are consequently produced by antigen-presenting cells, and are effectively presented according to the available HLA molecules, with subsequent HLA-restricted autoantibody production. Thus, while not directly involved in disease pathogenesis, SSc-associated autoantibodies appear to be reliable reporters of disease-specific pathologic phenomena, and may prove valuable pointers toward the etiopathogenesis of the different subtypes of SSc.


Effect of alpha and beta adrenergic blockade on oxygen transport in rat skeletal muscle and brain.
The effects of phenoxybenzamine HCl and propranolol HCl, 2 mg/kg, on tissue oxygen tension (PO2), perfusion and small vessel blood content of the cerebral cortex and biceps brachii muscle of anesthetized rats were determined. Perfusion and PO2 were measured polarographically and small vessel blood content was measured with 59Fe-siderophilin-labeled blood. Under control conditions PO2, perfusion and small vessel blood content averaged 15.1 mm Hg., 15.6 ml/min/100 g and 0.91 ml/100 g in brain and 15.6 mm Hg, 13.1 ml/min/100 g and 1.63 ml/100 g in muscle. After phenoxybenzamine adminstration, there was a significant increase in muscle perfusion (17.4%) and decrease in cortical PO2 (9.2%). No other factors changed significantly. Propranolol caused no significant changes in any of the above factors. Arteriolar resistance in skeletal muscle decreased after phenoxybenzamine. Small vessel blood content measurements (an estimate of open capillary density) indicate no effects on precapillary sphincters with either agent. Since some changes in metabolism were indicated with these agents, regional oxygen consumption was calculated from this data.


Effects of test method and participant musical training on preference ratings of stimuli with different reverberation times.
Selecting an appropriate listening test design for concert hall research depends on several factors, including listening test method and participant critical-listening experience. Although expert listeners afford more reliable data, their perceptions may not be broadly representative. The present paper contains two studies that examined the validity and reliability of the data obtained from two listening test methods, a successive and a comparative method, and two types of participants, musicians and non-musicians. Participants rated their overall preference of auralizations generated from eight concert hall conditions with a range of reverberation times (0.0-7.2 s). Study 1, with 34 participants, assessed the two methods. The comparative method yielded similar results and reliability as the successive method. Additionally, the comparative method was rated as less difficult and more preferable. For study 2, an additional 37 participants rated the stimuli using the comparative method only. An analysis of variance of the responses from both studies revealed that musicians are better than non-musicians at discerning their preferences across stimuli. This result was confirmed with a k-means clustering analysis on the entire dataset that revealed five preference groups. Four groups exhibited clear preferences to the stimuli, while the fifth group, predominantly comprising non-musicians, demonstrated no clear preference.


Luria's fist-edge-palm test: A small change makes a big difference.
Slight modifications in the instructions or administration of neuropsychological tests could result in noticeable differences in performance. A good example is offered by a test devised by Luria to assess executive functioning in motor planning, the three-step fist-edge-palm (FEP) test, which is still frequently employed in clinical settings and features in several neuropsychological test batteries such as the Frontal Assessment Battery (FAB). While Luria described the orientation of the fist as horizontal to the testing desk (hFEP), recent versions of the task indicate the fist should be vertical to the testing desk (vFEP). The current study examined whether administering the hFEP or the vFEP tests results in different performance in healthy people, and whether one version is better than the other at detecting impairments in a patient population. The hFEP proved more challenging for healthy adults than the vFEP, and people with brain damage committed more errors on the hFEP than the vFEP. Both versions correlated with executive measures but also with several other cognitive variables, indicating that the test is not a specific marker of executive functions. Although performance on the FEP is sensitive to articulatory suppression, faster pace, and the number of sequences performed, none of these conditions fully account for the differences between the hFEP and vFEP. The additional demand of the hFEP appears to be due to the less natural (i.e., automatic) orientation of the horizontal fist. In conclusion, a small change in the administration of the test, eluding Luria's instructions, grossly modified its sensitivity. Clinicians and researchers should be wary of modifying instructions or testing procedures without considering the possible consequences of such modifications.


A controlled quantitative study of facial expression in Parkinson's disease and depression.
A microcomputer-based approach to the quantification of facial expression was used to measure and compare the smiling behavior of a group of Parkinson's disease sufferers, a group of patients with major depression, and a control group of comparable age. Subjects were asked to view a series of amusing slides and their expressions were recorded. The most animated smile for each subject was chosen for analysis and scores on 12 computer-generated measures were obtained using the Facial Expression Measurement program. These measures are end-lip measure, mouth width measure, mouth-opening measure, mid-top measure, mid-lower lip measure, top lip-thickness measure, lower lip-thickness measure, eye-opening measure, top eyelid/iris intersect measure, lower eyelid/iris intersect measure, inner eyebrow measure, and mid-eyebrow measure. The depressed group differed significantly from the other groups, with higher scores on end-lip measure, mid-top lip measure, and mid-eyebrow measure. All subjects completed the Levine-Pilowsky Depression Questionnaire. The depressed patients obtained higher depression scores than the parkinsonian group, who in turn had significantly higher depression scores than the control group. The depression score was correlated with end-lip measure, mouth width measure, mid-top lip measure, eye-opening measure, and mid-eyebrow measure in the population as a whole. A significant negative correlation emerged between the depression score and mid-eyebrow measure in the depressed group. Both the depressed group and the parkinsonian group were found to smile significantly less often during the slide session when compared with the control group. These results are discussed in the light of earlier findings.


An examination of work instability, functional impairment, and disease activity in employed patients with rheumatoid arthritis.
To evaluate the relationship between the Disease Activity Score 28-joint count (DAS28), Health Assessment Questionnaire (HAQ), and Rheumatoid Arthritis-Work Instability Scale (RAWIS); and to define thresholds for clinical assessments associated with moderate to high RA-WIS. Employed patients with RA were evaluated using DAS28, HAQ, and RA-WIS during routine clinics. Relationships between these assessments were evaluated by simple correlation. Multiple linear regression modeling was performed using RA-WIS as an outcome variable and HAQ, DAS28, age, sex, occupation, and disease duration as input variables. Receiver-operating characteristic curves were then formulated to determine optimal DAS28, and HAQ cutoff points for RA-WIS >or= 10, along with the odds ratio (OR). Ninety patients with RA completed the RA-WIS, which was moderately correlated with DAS28 (r =0.53) and HAQ (r = 0.66). Fifty-four percent of RA-WIS was explained by DAS28 (p = 0.002), HAQ (p = 0.001), and sex (p = 0.04). A DAS28 of 3.81 and HAQ of 0.55 were clinically important thresholds. High DAS28 and HAQ were associated with high RA-WIS (OR(DAS) 14.17, OR(HAQ) 25.13, OR(DAS+HAQ) 29.9). Functional impairment and disease activity significantly and independently contributed to patient-perceived work instability risk.


Changing interpretations of the human cortical pattern.
There has been a long historical succession of scientific description of the cerebral cortex, usually accompanied by conflicting speculations on its function. It was noted by Thomas S. Kuhn that scientific descriptions are phrased in terms of the prevailing scientific paradigm and that disagreement about the interpretation of observed phenomena is what drives scientists to formulate new theories. The objectives of this study were to examine how the observation of Kuhn can help to gain insight into historical concepts of brain functioning from contemporary descriptions of the cortical gyrations, to examine how these historical concepts are relevant to neurology today, and to demonstrate how subjective these concepts are because they are based on interpretations that may be wrong. The method used here is examination of historical sources that give descriptions and illustrations of the cerebral cortex and contemporary theories of brain function. I have found that the emphases on cortical description have varied according to the prevailing contemporary paradigm. Debates about and between different paradigms mirror some themes in current neuroscience. In conclusion, the observations of Kuhn help to interpret descriptions to shed light on theories of cerebral cortical functioning, and they demonstrate that a scientific description is necessarily highly subjective (since it is phrased in terms of the current paradigm). The insights that can be gained are relevant to modern neurology and neuroscience research.


Tumor-educated tolerogenic dendritic cells induce CD3epsilon down-regulation and apoptosis of T cells through oxygen-dependent pathways.
Defects in the CD3/TCR complex and impairment of T cell function are necessary for tumor evasion, but the underlying mechanisms are incompletely understood. We found that culture supernatants from several types of solid tumor cell lines drove human monocytes to become tolerogenic semimature dendritic cells (TDCs). Upon encountering T cells, the TDCs triggered rapid down-regulation of CD3epsilon and TCR-alpha/beta and subsequent apoptosis in autologous T cells. Consistent with these results, accumulation of immunosuppressive DCs coincided with CD3epsilon down-regulation and T cell deletion in cancer nests of human tumors. The impaired T cell function was mediated by factor(s) released by live TDCs after direct interaction with lymphocytes. Also, the TDC-induced effect on T cells was markedly reduced by blocking of NADPH oxidase but not by inhibition of arginase, inducible NO synthase (iNOS), IDO, or IFN-gamma. Moreover, we found that hyaluronan fragments constituted a common factor produced by a variety of human tumor cell lines to induce formation of TDCs. These observations indicate that tumor microenvironments, including hyaluronan fragments derived from cancer cells, educate DCs to adopt a semimature phenotype, which in turn aids tumor immune escape by causing defects in the CD3/TCR complex and deletion of T cells.


Endometrial growth and uterine blood flow: a pilot study for improving endometrial thickness in the patients with a thin endometrium.
To examine whether thin endometria can be improved by increasing uterine radial artery (uRA) blood flow. A prospective observational study. University hospital and city general hospital. Sixty-one patients with a thin endometrium (endometrial thickness [EM] <8 mm) and high radial artery-resistance index of uRA (RA-RI >or=0.81). Vitamin E (600 mg/day, n = 25), l-arginine (6 g/day, n = 9), or sildenafil citrate (100 mg/day, intravaginally, n = 12) was given. EM and RA-RI were assessed by transvaginal color-pulsed Doppler ultrasound. Vitamin E improved RA-RI in 18 (72%) out of 25 patients and EM in 13 (52%) out of 25 patients. L-arginine improved RA-RI in eight (89%) out of nine patients and EM in six (67%) patients. Sildenafil citrate improved RA-RI and EM in 11 (92%) out of 12 patients. In the control group (n = 10), who received no medication to increase uRA-blood flow, only one (10%) patient improved in RA-RI and EM. The effect of vitamin E was histologically examined in the endometrium (n = 5). Vitamin E improved the glandular epithelial growth, development of blood vessels, and vascular endothelial growth factor protein expression in the endometrium. Vitamin E, l-arginine, or sildenafil citrate treatment improves RA-RI and EM and may be useful for the patients with a thin endometrium.


Effect of prostaglandin E2 on multidrug resistance transporters in human placental cells.
Prostaglandin (PG) E2, a major product of cyclooxygenase (COX)-2, acts as an immunomodulator at the maternal-fetal interface during pregnancy. It exerts biologic function through interaction with E-prostanoid (EP) receptors localized to the placenta. The activation of the COX-2/PGE2/EP signal pathway can alter the expression of the ATP-binding cassette (ABC) transporters, multidrug resistance protein 1 [P-glycoprotein (Pgp); gene: ABCB1], and breast cancer resistance protein (BCRP; gene: ABCG2), which function to extrude drugs and xenobiotics from cells. In the placenta, PGE2-mediated changes in ABC transporter expression could impact fetal drug exposure. Furthermore, understanding the signaling cascades involved could lead to strategies for the control of Pgp and BCRP expression levels. We sought to determine the impact of PGE2 signaling mechanisms on Pgp and BCRP in human placental cells. The treatment of placental cells with PGE2 up-regulated BCRP expression and resulted in decreased cellular accumulation of the fluorescent substrate Hoechst 33342. Inhibiting the EP1 and EP3 receptors with specific antagonists attenuated the increase in BCRP. EP receptor signaling results in activation of transcription factors, which can affect BCRP expression. Although PGE2 decreased nuclear factor κ-light chain-enhancer of activated B activation and increased activator protein 1, chemical inhibition of these inflammatory transcription factors did not blunt BCRP up-regulation by PGE2. Though PGE2 decreased Pgp mRNA, Pgp expression and function were not significantly altered. Overall, these findings suggest a possible role for PGE2 in the up-regulation of placental BCRP expression via EP1 and EP3 receptor signaling cascades.


Conversion of ethanolamine, monomethylethanolamine and dimethylethanolamine to choline-containing compounds by neurons in culture and by the rat brain.
The incubation of neurons from chick embryos in primary culture with [3H]ethanolamine revealed the conversion of this base into monomethyl, dimethyl and choline derivatives, including the corresponding free bases. Labelling with [methyl-3H]monomethylethanolamine and [methyl-3H]dimethylethanolamine supported the conclusion that in chick neuron cultures, phosphoethanolamine appears to be the preferential substrate for methylation, rather than ethanolamine or phosphatidylethanolamine. The methylation of the latter two compounds, in particular that of phosphatidylethanolamine, was seemingly stopped at the level of their monomethyl derivatives. Fetal rat neurons in primary culture incubated with [3H]ethanolamine showed similar results to those observed with chick neurones. However, phosphoethanolamine and phosphatidylethanolamine and, to a lesser extent, free ethanolamine, appeared to be possible substrates for methylation reactions. The methylation of water-soluble ethanolamine compounds de novo was further confirmed by experiments performed in vivo by intraventricular injection of [3H]ethanolamine. Phosphocholine and the monomethyl and dimethyl derivatives of ethanolamine were detected in the brain 15 min after injection.


Complex life cycles: why refrain from growth before reproduction in the adult niche?
Organisms with complex life cycles occupy distinct niches as larvae and adults. One presumed advantage of this is the ability to exploit different resources successively throughout ontogeny. Various taxa, however, have evolved nonfeeding, nongrowing adult stages. We show theoretically that this counterintuitive no-growth strategy is favored when the optimal larval size is greater than or equal to the optimal adult size for reproduction. We empirically investigated this in a group of parasitic worms (helminths). Helminths are transmitted trophically between hosts before reproducing in large, high-trophic-level hosts, and most undergo considerable growth as adults in their final host. Some well-studied tapeworm species (Schistocephalus, Ligula, and Digramma species) are notable exceptions; they reproduce semelparously without any growth in their final habitat (the gut of piscivorous birds). Using cross-species comparative analyses, we show that these tapeworms that do not grow in their final host (1) attain larval sizes in their last intermediate host (fishes) that are comparable to or larger than the adult sizes reached by tapeworms that do grow in the same adult niche (also piscivorous birds) and (2) are large, even as larvae, relative to the mass of their final hosts. These results are consistent with the idea that a massive larval size can make adult growth superfluous, and we discuss whether this likely applies to other complex life cycle taxa with nonfeeding, nongrowing adults.


Research ethics committees and paternalism.
In this paper the authors argue that research ethics committees (RECs) should not be paternalistic by rejecting research that poses risk to people competent to decide for themselves. However it is important they help to ensure valid consent is sought from potential recruits and protect vulnerable people who cannot look after their own best interests. The authors first describe the tragic deaths of Jesse Gelsinger and Ellen Roche. They then discuss the following claims to support their case: (1) competent individuals are epistemologically and ethically in the best position to say which risks are reasonable for them, so RECs should be no more restrictive than the "normal" constraints on people taking risks with themselves; (2) RECs do not judge individual competence (that is for researchers and psychiatrists); (3) individual liberty is mostly limited by what serves the public interest, and RECs do not determine public interest; (4) RECs may have a paternalistic role in preventing exploitation of competent people vulnerable to the use of incentives, and in protecting the interests of incompetent people; however, (5) the moral and political authority of RECs has not been established in this respect.


Parental substance abuse and the development of children in family foster care.
To determine the impact of parental substance abuse on children, the cognitive skills and behavior ratings of 268 school-age children placed in family foster care were examined. As a group, the children in family foster care presented with low average cognitive skills and made significant improvement in cognitive functioning during placement. The children with prenatal exposure to drugs scored significantly lower in cognitive skills at the beginning of placement but made significantly more progress than the other children during placement. Behavior ratings by the foster parents and teachers revealed that 29% of the children had scores in the significant range, and the children exposed prenatally to drugs had a higher incidence of behavior problems at school compared to family foster care peers. Recommendations for further study of these factors and for enhancing outcomes for children in care are provided.


Pharmacologic inhibition of RGD-binding integrins ameliorates fibrosis and improves function following kidney injury.
Fibrosis is a final common pathway for many causes of progressive chronic kidney disease (CKD). Arginine-glycine-aspartic acid (RGD)-binding integrins are important mediators of the pro-fibrotic response by activating latent TGF-β at sites of injury and by providing myofibroblasts information about the composition and stiffness of the extracellular matrix. Therefore, blockade of RGD-binding integrins may have therapeutic potential for CKD. To test this idea, we used small-molecule peptidomimetics that potently inhibit a subset of RGD-binding integrins in a murine model of kidney fibrosis. Acute kidney injury leading to fibrosis was induced by administration of aristolochic acid. Continuous subcutaneous administration of CWHM-12, an RGD integrin antagonist, for 28 days improved kidney function as measured by serum creatinine. CWHM-12 significantly reduced Collagen 1 (Col1a1) mRNA expression and scar collagen deposition in the kidney. Protein and gene expression markers of activated myofibroblasts, a major source of extracellular matrix deposition in kidney fibrosis, were diminished by treatment. RNA sequencing revealed that inhibition of RGD integrins influenced multiple pathways that determine the outcome of the response to injury and of repair processes. A second RGD integrin antagonist, CWHM-680, administered once daily by oral gavage was also effective in ameliorating fibrosis. We conclude that targeting RGD integrins with such small-molecule antagonists is a promising therapeutic approach in fibrotic kidney disease.


A Meta-analysis of the Association Between Needle Exchange Programs and HIV Seroconversion Among Injection Drug Users.
We assessed the association between different levels of needle exchange program (NEP) use and human immunodeficiency virus (HIV) seroconversion in the injecting drug user (IDU) population using meta-analysis to aggregate risk estimates from any reported cohort studies or randomized controlled trials (RCTs) in the literature. We searched the literature for articles published from January 1990 to August 2014 using Medical Subject Headings and other terms from MEDLINE® (using Ovid), Embase, ProQuest, the International Aids Society Abstract database, and the European AIDS clinical society database, and the European Conferences Abstract Archive. Articles were included if data were reported from an original study; the study was a prospective cohort or RCT design; estimates for seroconversion (hazard ratios [HRs]) for drug-users with different levels of NEP-use, as well as variance data, or the information to calculate these were reported; risk estimates were adjusted for unstable housing, risky sexual behaviors, frequency of injections, cocaine use, and risky needle sharing practices; and the study was published between January 1990 and August 2014. Information abstracted was general study information (i.e., study name, authors, publication year, study site, sample size, length of follow-up, and follow-up intervals, incentives to IDUs for improving compliance/enrollment), outcomes variable measures (seroconversion HR estimates, variance figures, and factors adjusted for), description of the study population (inclusion and exclusion criteria and definitions of comparison groups), type of intervention (NEP program), statistical methods used, and sub-group information. Two prospective cohort studies with a total of 3,172 IDUs were eligible for inclusion. Comparison groups had different levels of NEP-use (e.g., daily use vs. non-daily use and NEP-users vs. non-users) from fixed-site NEPs. Our Q-statistic was insignificant with a p-value of 0.401 while the I2 value was 0.0%. A random-effects model was used to aggregate the estimates, and we found an overall significant positive association between NEP-use and HIV seroconversion with an HR estimate of 1.59 (95% confidence interval [CI]: 1.2 to 2.1). According to our results, higher usage of NEPs is associated with a higher risk of HIV seroconversion in the IDU population. The observed association aligns with previous findings of NEP programs being inadequate for HIV control in IDUs. Further research on the topic needs to be done including studies on different NEP designs and how they can be made more effective by combining with other strategies, including the study of IDU characteristics which make them more likely to use safe syringes when they inject.


Alteration of Mitochondrial Integrity as Upstream Event in the Pathophysiology of SOD1-ALS.
Little is known about the early pathogenic events by which mutant superoxide dismutase 1 (SOD1) causes amyotrophic lateral sclerosis (ALS). This lack of mechanistic understanding is a major barrier to the development and evaluation of efficient therapies. Although protein aggregation is known to be involved, it is not understood how mutant SOD1 causes degeneration of motoneurons (MNs). Previous research has relied heavily on the overexpression of mutant SOD1, but the clinical relevance of SOD1 overexpression models remains questionable. We used a human induced pluripotent stem cell (iPSC) model of spinal MNs and three different endogenous ALS-associated SOD1 mutations (D90Ahom, R115Ghet or A4Vhet) to investigate early cellular disturbances in MNs. Although enhanced misfolding and aggregation of SOD1 was induced by proteasome inhibition, it was not affected by activation of the stress granule pathway. Interestingly, we identified loss of mitochondrial, but not lysosomal, integrity as the earliest common pathological phenotype, which preceded elevated levels of insoluble, aggregated SOD1. A super-elongated mitochondrial morphology with impaired inner mitochondrial membrane potential was a unifying feature in mutant SOD1 iPSC-derived MNs. Impaired mitochondrial integrity was most prominent in mutant D90Ahom MNs, whereas both soluble disordered and detergent-resistant misfolded SOD1 was more prominent in R115Ghet and A4Vhet mutant lines. Taking advantage of patient-specific models of SOD1-ALS in vitro, our data suggest that mitochondrial dysfunction is one of the first crucial steps in the pathogenic cascade that leads to SOD1-ALS and also highlights the need for individualized medical approaches for SOD1-ALS.


Skin cover in extensive hand injuries.
The concept of 'axial-based' flaps has revolutionised the replacement of full-thickness defects of the skin and subcutaneous tissue of the hand. The groin flap provides extensive skin replacement, and has the advantage of allowing considerable mobility of the hand, elbow and should during the period of attachment.


Sound localization, sound lateralization, and binaural masking level differences in young children with normal hearing.
In this study, procedures for measuring sound localization, sound lateralization, and binaural masking level differences (BMLDs) in young children were developed. Sensitivity for these tasks was assessed in large groups of children between 4 and 9 yr of age to investigate potential developmental trends. Sound localization was measured in the sound field, with a broadband bell-ring presented from one of nine loudspeakers positioned in the frontal horizontal field. A group of 33 children between 4 and 6 yr of age and 5 adults took part in this experiment. Sound lateralization based on interaural time differences was measured with headphones in 49 children between 4 and 9 yr of age and 10 adults. A low-frequency stimulus containing harmonics 2 to 5 from a click train with a rate of 160 Hz was used. In the BMLD test, the same filtered click train was presented diotically or dichotically (phase reversed or time delayed) in a broadband (200 to 1000 Hz) frozen noise to 23 children between 4 and 6 yr of age and 10 adults. For comparison with literature, additional measurements with a 500-Hz sinusoid were administered to adults. All tasks were adapted to the interest and attention span of young children. Children of 5 yr of age did not perform significantly different from adults on the sound localization task, but mean absolute errors were larger for the 4-yr-olds. Also on the BMLD task, 5-yr-old children performed at the adult level, whereas the 4-yr-old children obtained significantly less binaural unmasking compared with the adults. Concerning sound lateralization, a small but significant difference between adults and children existed, but no age effects were apparent in the 4- to 9-yr-old group. Overall, the variation was relatively large in the 4-yr-old group, with some of the children performing at adult level, in all three tasks. The results of this study show that the modified procedures are suitable for testing children from the age of 4 to 5 yr. Furthermore, it seems that binaural hearing capacities of the 5-yr-olds are similar to those of adults. Several observations led to the hypothesis that the observed age differences between 4-yr-olds and older subjects on localization and BMLD or between those 4- to 9-yr old and adults on lateralization, were attributable to both a development in binaural hearing and to nonauditory factors, such as task comprehension, attention, and testing conditions. It is possible that the developmental process is more obvious and prolonged in other aspects of binaural hearing, which require more dynamic or more central processing.


Evaluation of the Direct MacConkey Method for Identification of Carbapenem-Resistant Gram-Negative Organisms from Rectal Swabs: Reevaluating Zone Diameter Cutoffs.
The optimal method to screen for gastrointestinal colonization with carbapenem-resistant organisms (CRO) has yet to be established. The direct MacConkey (direct MAC) plate method demonstrates high sensitivity for CRO detection, but established zone diameter (ZD) criteria for ertapenem (≤27 mm) and meropenem (≤32 mm) result in high rates of false positives upon confirmatory testing. To increase specificity, we screened for CRO in two high-risk wards using the direct MAC plate method, recorded ZDs for each sample, and generated receiver operating characteristic (ROC) curves to evaluate the optimal ZD cutoff criteria. Of 6,868 swabs obtained over an 18-month period, 4,766 (69%) had growth on MAC plates, and 2,500 (36%) met criteria for further evaluation based on previously established ZDs around the carbapenem disks. A total of 812 (12%) swabs were confirmed positive for at least one CRO and included 213 (3%) carbapenemase-producing organisms (CPO), resulting in a specificity of 78% for the direct MAC plate method. Reducing the ertapenem and meropenem ZDs to ≤25 mm improved specificity to 83%, decreasing the confirmatory testing workload by 32%. The sensitivities with the lower ZD criteria were 89% for CRO and 94% for CPO, respectively. The direct MAC plate method criteria for CRO testing can be modified to balance the sensitivity and specificity of CRO while reducing the burden on clinical microbiology laboratories. These modifications can be particularly helpful in regions with a low CRO prevalence.


Correcting motion induced fluorescence artifacts in two-channel neural imaging.
Imaging neural activity in a behaving animal presents unique challenges in part because motion from an animal's movement creates artifacts in fluorescence intensity time-series that are difficult to distinguish from neural signals of interest. One approach to mitigating these artifacts is to image two channels simultaneously: one that captures an activity-dependent fluorophore, such as GCaMP, and another that captures an activity-independent fluorophore such as RFP. Because the activity-independent channel contains the same motion artifacts as the activity-dependent channel, but no neural signals, the two together can be used to identify and remove the artifacts. However, existing approaches for this correction, such as taking the ratio of the two channels, do not account for channel-independent noise in the measured fluorescence. Here, we present Two-channel Motion Artifact Correction (TMAC), a method which seeks to remove artifacts by specifying a generative model of the two channel fluorescence that incorporates motion artifact, neural activity, and noise. We use Bayesian inference to infer latent neural activity under this model, thus reducing the motion artifact present in the measured fluorescence traces. We further present a novel method for evaluating ground-truth performance of motion correction algorithms by comparing the decodability of behavior from two types of neural recordings; a recording that had both an activity-dependent fluorophore and an activity-independent fluorophore (GCaMP and RFP) and a recording where both fluorophores were activity-independent (GFP and RFP). A successful motion correction method should decode behavior from the first type of recording, but not the second. We use this metric to systematically compare five models for removing motion artifacts from fluorescent time traces. We decode locomotion from a GCaMP expressing animal 20x more accurately on average than from control when using TMAC inferred activity and outperforms all other methods of motion correction tested, the best of which were ~8x more accurate than control.


Quantifying the effect of experimental perturbations at single-cell resolution.
Current methods for comparing single-cell RNA sequencing datasets collected in multiple conditions focus on discrete regions of the transcriptional state space, such as clusters of cells. Here we quantify the effects of perturbations at the single-cell level using a continuous measure of the effect of a perturbation across the transcriptomic space. We describe this space as a manifold and develop a relative likelihood estimate of observing each cell in each of the experimental conditions using graph signal processing. This likelihood estimate can be used to identify cell populations specifically affected by a perturbation. We also develop vertex frequency clustering to extract populations of affected cells at the level of granularity that matches the perturbation response. The accuracy of our algorithm at identifying clusters of cells that are enriched or depleted in each condition is, on average, 57% higher than the next-best-performing algorithm tested. Gene signatures derived from these clusters are more accurate than those of six alternative algorithms in ground truth comparisons.


Risk factors for adjacent segment disease after lumbar fusion.
The incidence of adjacent segment problems after lumbar fusion has been found to vary, and risk factors for these problems have not been precisely verified, especially based on structural changes determined by magnetic resonance imaging. The purpose of this retrospective clinical study was to describe the incidence and clinical features of adjacent segment disease (ASD) after lumbar fusion and to determine its risk factors. We assessed the incidence of ASD in patients who underwent lumbar or lumbosacral fusions for degenerative conditions between August 1995 and March 2006 with at least a 1-year follow-up. Patients less than 35 years of age at the index spinal fusion, patients with uninstrumented fusion, and patients who had not achieved successful union were excluded. Of the 1069 patients who underwent fusions, 28 (2.62%) needed secondary operations because of ASD and were included in this study. In order to identify the risk factors, we matched a disease group and a control group. The disease group consisted of 26 of the 28 patients with ASD, excluding the 2 patients for whom we did not have initial MRI data. Each patient in the disease group was matched by age, sex, fusion level and follow-up period with a control patient. The assumed risk factors included disc and facet degeneration, instability, listhesis, rotational deformity, and disc wedging. The mean age of the 28 patients with ASD requiring surgical treatment was 58.4 years, which did not differ significantly from that of the population in which ASD did not develop (58.2 years, p = 0.894). Of the 21 patients who underwent floating fusion, only 1 developed distal ASD. Facet degeneration was a significant risk factor (p < 0.01) on logistic regression analysis. The incidence of distal ASD was much lower than that of proximal ASD. Pre-existing facet degeneration may be associated with a high risk of adjacent segment problems following lumbar fusion procedures.


Successful treatment with dabigatran for consumptive coagulopathy associated with extensive vascular malformations.
: Vascular malformation is occasionally complicated by consumptive coagulopathy, known as localized intravascular coagulopathy (LIC), which is characterized by a reduced fibrinogen level, an elevated D-dimer level and a normal platelet count. We report the case of a 17-year-old Japanese girl who presented with LIC secondary to extensive vascular malformations, whose condition had progressed to disseminated intravascular coagulation (DIC). She suddenly presented with severe anaemia, despite the absence of obvious bleeding, and she began to require regular red blood cell (RBC) transfusions. As she was suffering from paroxysmal atrial fibrillation, we treated her with dabigatran, after obtaining informed consent. Immediately after the administration of dabigatran, the results of clotting tests improved dramatically. Seven months later, she has not required any RBC transfusions, and the dabigatran treatment has been well tolerated. The present case report suggests that dabigatran may be a useful treatment option for patients with DIC associated with vascular malformations.


Advances in nonlinear optical microscopy for visualizing dynamic tissue properties in culture.
Optical microscopy encompasses high-resolution imaging techniques that can be used to non-destructively investigate and characterize living biological systems and engineered tissue constructs in culture. In particular, nonlinear optical microscopy (NLOM) is well suited for the visualization and quantification of processes involved in cell-extracellular matrix interactions in vivo. Current NLOM technology enables concomitant molecular imaging and visualization of microstructural organization that could provide a direct link between signal transduction and biological effect at microscopic length scales that culminate into tissue macroscopic properties and function. This review highlights the fundamentals of nonlinear optical interactions between light and tissue and presents a direction for future technology development to better complement quantitative, high-throughput assays of the modern life sciences.


An In Vitro Assessment of Cariogenic and Erosive Potential of Pediatric Liquid Medicaments on Primary Teeth: A Comparative Study.
To compare the cariogenic and erosive potential of seven commonly prescribed pediatric liquid medicaments (PLMs) by pediatricians in Kempegowda Institute of Medical Sciences, Bengaluru. The selected medicaments are:Syp paracetamol (antipyretic).Syp amoxicillin-clavulanate (antibiotic).Syp cetirizine (antihistamine).Syp dextromethorphan (antitussive).Syp salbutamol (antiasthmatic).Syp phenytoin (anticonvulsant).Syp multivitamin (nutritional supplement). Quantitative endogenous sucrose estimation: Lane-Eynon volumetric copper reduction method was used for the estimation.Endogenous pH estimation: The endogenous pH was measured using a digital pH meter at 10% dilution.Quantification of endogenous erosive potential: few caries and restoration-free, exfoliated or extracted primary teeth were utilized to produce 1-1.5 g of enamel powder. A 50 mg of enamel powder was then added to 1 mL of individual PLM. The mixtures were maintained for three-time intervals, 1 minute, 10 minutes, and 8 hours. The samples were then prepared for the estimation of calcium using Inductively Coupled Plasma Mass Spectrometry. Sucrose was seen in all the PLMs except amoxicillin-clavulanate. Calcium was found to be present in all the PLMs except cetirizine. The highest calcium dissolution was seen within Syp salbutamol and the least with Syp paracetamol. Syp phenytoin can be regarded as medicament with the highest cariogenic potential and Syp salbutamol with the highest erosive potential and Syp paracetamol with the lowest cariogenic and erosive potential among the compared and tested PLMs. Considering syrups that have high cariogenic and erosive potential, greater knowledge about the detrimental effects of these drugs should direct us to evolve effective programs to alert parents to follow proper oral hygiene practices or to search for alternative drugs void of such detrimental effects. Singana T, Suma NK. An In Vitro Assessment of Cariogenic and Erosive Potential of Pediatric Liquid Medicaments on Primary Teeth: A Comparative Study. Int J Clin Pediatr Dent 2020;13(6):595-599.


Screening for inhibitors of chloroplast galactolipid synthesis acting in membrano and in planta.
The knowledge of the membrane lipid metabolism in photosynthetic cells is expected to benefit from the availability of inhibitors acting at the level of specific enzymes like MGD1 (E.C. 126.96.36.199) that catalyzes the synthesis of monogalactosyldiacylglycerol (MGDG) in chloroplasts. MGDG is a major lipid of photosynthetic membrane, interacting with photosystems. It is the precursor of digalactosyldiacylglycerol that serves as a phospholipid surrogate when plants are deprived of phosphate, and it is a source of polyunsaturated fatty acids for jasmonic acid syntheses. MGD1 is activated by phosphatidic acid and thus a coupling point between phospholipid and galactolipid metabolisms. Here we describe a method to screen for inhibitors of MGD1 assayed in liposomes. Selected compounds can therefore reach the core of the biological membranes in which the target sits. We then describe a secondary screen to evaluate the efficiency of developed compounds at the whole plant level. Major issues raised by the screening of inhibitors acting on membrane proteins are discussed and can be useful for similar targets.


Regulating cell death at, on, and in membranes.
Bcl-2 family proteins are central regulators of apoptosis. Various family members are located in the cytoplasm, endoplasmic reticulum, and mitochondrial outer membrane in healthy cells. However during apoptosis most of the interactions between family members that determine the fate of the cell occur at the membranes of intracellular organelles. It has become evident that interactions with membranes play an active role in the regulation of Bcl-2 family protein interactions. Here we provide an overview of various models proposed to explain how the Bcl-2 family regulates apoptosis and discuss how membrane binding affects the structure and function of each of the three categories of Bcl-2 proteins (pro-apoptotic, pore-forming, and anti-apoptotic). We also examine how the Bcl-2 family regulates other aspects of mitochondrial and ER physiology relevant to cell death.


Role of mitogen-activated protein kinase pathways in multifactorial adverse cardiac remodeling associated with metabolic syndrome.
Metabolic syndrome has been widely associated with an increased risk for acute cardiovascular events. Emerging evidence supports metabolic syndrome as a condition favoring an adverse cardiac remodeling, which might evolve towards heart dysfunction and failure. This pathological remodeling has been described to result from the cardiac adaptive response to clinical mechanical conditions (such as hypertension, dyslipidemia, and hyperglycemia), soluble inflammatory molecules (such as cytokines and chemokines), as well as hormones (such as insulin), characterizing the pathophysiology of metabolic syndrome. Moreover, these cardiac processes (resulting in cardiac hypertrophy and fibrosis) are also associated with the modulation of intracellular signalling pathways within cardiomyocytes. Amongst the different intracellular kinases, mitogen-activated protein kinases (MAPKs) were shown to be involved in heart damage in metabolic syndrome. However, their role remains controversial. In this paper, we will discuss and update evidence on MAPK-mediated mechanisms underlying cardiac adverse remodeling associated with metabolic syndrome.


Trends in maternal obesity incidence rates, demographic predictors, and health inequalities in 36,821 women over a 15-year period.
The aim of this study was to identify trends in maternal obesity incidence over time and to identify those women most at risk and potential-associated health inequalities. Longitudinal database study. James Cook University Hospital maternity unit, Middlesbrough, UK. A total of 36 821 women from 1 January 1990 to 31 December 2004. Trends in maternal obesity incidence over time were analysed using chi-square test for trend. Demographic predictor variables were analysed using multivariate logistic regression, adjusting for confounding factors after testing for multicollinearity. National census data were used to place the regional data into the context of the general population. Trends in maternal obesity incidence. Demographic predictor variables included ethnic group, age, parity, marital status, employment and socio-economic disadvantage. The proportion of obese women at the start of pregnancy has increased significantly over time from 9.9 to 16.0% (P<0.01). This is best described by a quadratic model (P<0.01) showing that the rate is accelerating; by 2010, the rate will have increased to 22% of this population if the trend continues. There is also a significant relationship with maternal obesity and mothers' residing in areas of most deprivation (odds ratio [OR]=2.44, 95% CI=1.98, 3.02, P<0.01), with increasing age (OR=1.04, 95% CI=1.04, 1.05, P<0.01), and parity (OR=1.17, 95% CI=1.12, 1.21, P<0.01). The incidence of maternal obesity at the start of pregnancy is increasing and accelerating. Predictors of maternal obesity are associated with health inequalities, particularly socio-economic disadvantage.


Comparisons of serotests with calf inoculations for detection of carriers in anaplasmosis- vaccinated cattle.
Fifteen months after discontinuing vaccination for anaplasmosis in a herd of 131 cattle, 126 of the animals were reactive to the complement-fixation or card-agglutination tests. Inoculation of splenectomized calves proved that 9 animals were carriers and 117 animals were free of anaplasmosis. Anaplasmosis vaccination induced titers detectable by the standard serotests that persisted for at least 15 months.


Selection and validation of reference genes for gene expression analysis in apomictic and sexual Cenchrus ciliaris.
Apomixis is a naturally occurring asexual mode of seed reproduction resulting in offspring genetically identical to the maternal plant. Identifying differential gene expression patterns between apomictic and sexual plants is valuable to help deconstruct the trait. Quantitative RT-PCR (qRT-PCR) is a popular method for analyzing gene expression. Normalizing gene expression data using proper reference genes which show stable expression under investigated conditions is critical in qRT-PCR analysis. We used qRT-PCR to validate expression and stability of six potential reference genes (EF1alpha, EIF4A, UBCE, GAPDH, ACT2 and TUBA) in vegetative and reproductive tissues of B-2S and B-12-9 accessions of C. ciliaris. Among tissue types evaluated, EF1alpha showed the highest level of expression while TUBA showed the lowest. When all tissue types were evaluated and compared between genotypes, EIF4A was the most stable reference gene. Gene expression stability for specific ovary stages of B-2S and B-12-9 was also determined. Except for TUBA, all other tested reference genes could be used for any stage-specific ovary tissue normalization, irrespective of the mode of reproduction. Our gene expression stability assay using six reference genes, in sexual and apomictic accessions of C. ciliaris, suggests that EIF4A is the most stable gene across all tissue types analyzed. All other tested reference genes, with the exception of TUBA, could be used for gene expression comparison studies between sexual and apomictic ovaries over multiple developmental stages. This reference gene validation data in C. ciliaris will serve as an important base for future apomixis-related transcriptome data validation.


Improving communication for learning with students: expectations, feedback and feedforward.
This article was migrated. The article was marked as recommended. The aim of this paper is to draw together numerous strands from within the literature and our own practice to provide advice for improving communication about learning with students in undergraduate medical education. There is an assumption within higher education that assessment drives learning and, as such, assessment forms the focal points for communication between teachers and students. However, a broader approach is required to avoid misunderstandings and maximise the successful engagement with learning of everyone involved. It is important to plan a clear communication strategy that incorporates and enables identification with the unique values of the particular school. Where communication about learning is overtly discussed there are three main areas to consider: (1) management of expectations (sometimes referred to as feed up or feed in) that needs to include not only the use of authentic formative assessments, but also the viewpoints of both teachers and students. (2) Feedback and (3) Feedforward, both need to be considered from the perspectives of student and teacher. All communication needs to be inclusive, it's structures must provide scaffolding for respectful exchanges of information, and this will have clear practical consequences for the activities within the school.


[Use of monoclonal antibodies for the intratypic differentiation of strains of poliomyelitis type I virus].
Six clones of mouse hybridomas producing highly specific antibodies to the vaccine LSc 2ab strain of poliomyelitis virus type I have been derived. The clone 10C5 antibodies were used for intratypic serodifferentiation of 75 poliomyelitis virus type I strains from the collection of the Institute of Poliomyelitis and Viral Encephalitides of the USSR Acad. Med. Sci. which had been isolated in the USSR from children with paralytic poliomyelitis in 1950-1983. General large-scale vaccination campaigns for children using live poliomyelitis vaccine (SLV) had started in 1959. Among 12 strains isolated in 1950-1958, only 2 strains could be neutralized with clone 10C5 antibody. These 2 strains were evidently of the vaccine origin since they had been isolated in 1957 in Leningrad where at that time first large-scale trials of SLV had already been initiated (Smorodintsev, A.A. in: "Live Vaccine against Poliomyelitis", Leningrad, 1960, 42-60). In the period after the beginning of large-scale vaccination campaigns (1959-1983), 11 out of 26 strains and 25 out of 36 strains isolated in areas of the moderate and hot climate, respectively, showed antigenic relationship with the vaccine LSc 2ab strain. The portion of vaccine-like strains isolated in different years beginning since 1959 was sufficiently stable comprising about half of the total number of poliomyelitis virus type I strains examined.


Updating Norman's "Adequate Taxonomy": intelligence and personality dimensions in natural language and in questionnaires.
Research on the dimensions of personality represented in the English language has repeatedly led to the identification of five factors (Norman, 1963). An alternative classification of personality traits, based on analyses of standardized questionnaires, is provided by the NEO (Neuroticism, Extraversion, Openness) model (Costa & McCrae, 1980b). In this study we examined the correspondence between these two systems in order to evaluate their comprehensiveness as models of personality. A sample of 498 men and women, participants in a longitudinal study of aging, completed an instrument containing 80 adjective pairs, which included 40 pairs proposed by Goldberg to measure the five dimensions. Neuroticism and extraversion factors from these items showed substantial correlations with corresponding NEO Inventory scales; however, analyses that included psychometric measures of intelligence suggested that the fifth factor in the Norman structure should be reconceptualized as openness to experience. Convergent correlations above .50 with spouse ratings on the NEO Inventory that were made three years earlier confirmed these relations across time, instrument, and source of data. We discuss the relations among culture, conscientiousness, openness, and intelligence, and we conclude that mental ability is a separate factor, though related to openness to experience.


Effect of replacing calcium salts of palm oil distillate with incremental amounts of conventional or high oleic acid milled rapeseed on milk fatty acid composition in cows fed maize silage-based diets.
Based on potential benefits to human health, there is increasing interest in altering the composition of ruminant-derived foods. Including rapeseeds in the dairy cow diet is an effective strategy for replacing medium-chain saturated fatty acids (SFA) with cis-monounsaturated fatty acids (MUFA) in bovine milk, but there is limited information on the optimum level of supplementation. Decreases in SFA due to plant oils are also accompanied by increases in milk trans fatty acid (FA) content and it is possible that high oleic acid rapeseeds may result in a higher enrichment of cis-9 18:1 and lower increases in trans FAs in milk compared with conventional varieties. Seven multiparous lactating Holstein-Friesian cows were allocated to one of seven treatments in an incomplete Latin square design with five 28-day experimental periods, to evaluate the effect of replacing calcium salts of palm oil distillate (CPO; 41 g/kg diet dry matter, DM) with 128, 168 or 207 g/kg diet DM of conventional (COR) or a high oleic acid (HOR) rapeseed fed as a supplement milled with wheat. Rapeseed variety and inclusion level had no effect (P > 0.05) on DM intake, milk yield and composition. Both rapeseed varieties decreased linearly (P < 0.001) milk fat SFA content, which was partially compensated for by a linear increase (P < 0.001) in cis-9 18:1 concentration. Reductions in milk SFA were also associated with increases (P < 0.05) in trans 18:1 and total trans FA content, with no difference (P > 0.05) between rapeseed varieties. Replacing CPO in the diet with milled rapeseeds had no effect (P > 0.05) on total milk conjugated linoleic acid (CLA) concentration. Relative to a COR, inclusion of a high oleic acid variant in the diet increased (P = 0.01) the ratio of trans-MUFA : trans-polyunsaturated fatty acids in milk that may have implications with respect to cardiovascular disease risk in humans. In conclusion, data indicated that replacing CPO with milled rapeseeds at levels up to 1150 g oil/day could be used as a nutritional strategy to lower milk SFA content without inducing adverse effects on DM intake and milk production. HOR reduced milk fat SFA content to a greater extent than a conventional variety, but did not minimise associated increases in trans FA concentrations. However, the high oleic acid variant did alter the relative abundance of specific trans 18:1, CLA and trans 18:2 isomers compared with conventional rapeseeds.


Adhesive interactions of normal and leukemic human CD34+ myeloid progenitors: role of marrow stromal, fibroblast, and cytomatrix components.
Adhesive interactions between CD34+ myeloid progenitors, cytomatrix components, and marrow fibroblast and stromal monolayers are described and compared to the binding interactions of the CD34+ myeloid leukemic cell lines KG1a and KG1. Both normal precursors and their leukemic counterparts showed adhesion to marrow stroma and fibroblasts. CD34+ myeloid progenitors bound to the extracellular matrices of marrow stromal cell and fibroblast monolayers and to laminin and fibronectin to a lesser extent than to cellular stromal layers. These adhesive interactions were not inhibited by polyclonal antibodies to laminin or fibronectin, nor by 1 mM Arg-Gly-Asp-Ser (RGDS)-containing peptides. Also, although both normal and leukemic cells expressed the CD18 antigen, binding of these cells to stroma was not inhibited by blocking anti-CD18 monoclonal antibodies. Finally, KG1a adhesion was not blocked in the presence of anti-CD54 (ICAM) antibody, nor was it blocked when galactosyl or mannosyl pyranosides were added. KG1a binding was trypsin sensitive and enhanced in the presence of neuraminidase. These studies serve to characterize adhesive properties of normal and leukemic myeloid progenitors and begin to establish interactions important for the lodgement of early progenitor cells in human marrow.


Direct Gas-Phase Derivatization by Employing Tandem μ-Reactor-Gas Chromatography/Mass Spectrometry: Case Study of Trifluoroacetylation of 4,4'-Methylenedianiline.
Pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) is a promising technique allowing the rapid characterization of the polymer structure and additives of microgram-scale plastics. However, the Py-GC/MS analysis of polymers with urethane bonds is challenging because they produce highly reactive pyrolyzates such as amines and isocyanates polymerizing in the GC column, which limits the efforts to elucidate the pyrolysis mechanism and plastic characterization by online GC analysis. Herein, a novel pyrolysis-gas-phase derivatization-GC/MS (Py-GPD-GC/MS) technique was developed, allowing the pyrolysis of polymers and the subsequent direct gas-phase derivatization of pyrolyzates, employing a modified tandem μ-reactor-GC/MS system. This work conducted the gas-phase trifluoroacetylation of 4,4'-methylenedianiline (MDA), which is one of the major polyurethane (PU) pyrolyzates, using N-methyl-bis-trifluoroacetamide (MBTFA) as a derivatization agent. The trifluoroacetylation gas-phase reaction was monitored by in situ GC/MS analysis and the effects of derivatization conditions were investigated. The highest MDA conversion observed was 65.6 area %. Furthermore, the sequential PU pyrolysis and direct trifluoroacetylation of PU pyrolyzates in the first μ-reactor and second μ-reactor, respectively, were successfully operated, achieving the inhibited polymerization and detection of trifluoroacetylated derivatives. Thus, the Py-GPD-GC/MS method has a significant potential to be applied for other combinations of pyrolyzates and derivatization reactions, enabling deeper characterization of plastics producing highly reactive pyrolyzates that cannot be accurately analyzed by conventional Py-GC/MS analysis.


Genome-Wide Identification and Characterization of CDPK Gene Family in Cultivated Peanut (Arachis hypogaea L.) Reveal Their Potential Roles in Response to Ca Deficiency.
This study identified 45 calcium-dependent protein kinase (CDPK) genes in cultivated peanut (Arachis hypogaea L.), which are integral in plant growth, development, and stress responses. These genes, classified into four subgroups based on phylogenetic relationships, are unevenly distributed across all twenty peanut chromosomes. The analysis of the genetic structure of AhCDPKs revealed significant similarity within subgroups, with their expansion primarily driven by whole-genome duplications. The upstream promoter sequences of AhCDPK genes contained 46 cis-acting regulatory elements, associated with various plant responses. Additionally, 13 microRNAs were identified that target 21 AhCDPK genes, suggesting potential post-transcriptional regulation. AhCDPK proteins interacted with respiratory burst oxidase homologs, suggesting their involvement in redox signaling. Gene ontology and KEGG enrichment analyses affirmed AhCDPK genes' roles in calcium ion binding, protein kinase activity, and environmental adaptation. RNA-seq data revealed diverse expression patterns under different stress conditions. Importantly, 26 AhCDPK genes were significantly induced when exposed to Ca deficiency during the pod stage. During the seedling stage, four AhCDPKs (AhCDPK2/-25/-28/-45) in roots peaked after three hours, suggesting early signaling roles in pod Ca nutrition. These findings provide insights into the roles of CDPK genes in plant development and stress responses, offering potential candidates for predicting calcium levels in peanut seeds.


Estimating time preferences for health using discrete choice experiments.
This study is the first to use discrete choice experiments to elicit inter-temporal preferences for health. Inter-temporal preferences with respect to one's own future health are compared with inter-temporal preferences with respect to others' future health. Discrete choice experiments are used to measure the relative importance of the duration of ill-health and how far in the future the ill-health occurs. Data were collected by postal questionnaire in the UK. The median implied rates of discount range from 0.055 to 0.091 for own health, depending on the period of delay, and from 0.078 to 0.147 for others' health. The implied discount rate varies with respect to age, self-rated health, and version of the questionnaire. The implied discount rates are broadly comparable with other published estimates using closed-ended methods. One concern is the large percentage of respondents with dominant preferences. This issue needs to be explored before adopting the approach of discrete choice experiments to elicit inter-temporal preferences.


Effects of Stress and Relaxation on Central Pain Modulation in Chronic Whiplash and Fibromyalgia Patients Compared to Healthy Controls.
Compelling evidence has demonstrated that impaired central pain modulation contributes to persistent pain in patients with chronic whiplash associated disorders (WAD) and fibromyalgia (FM). However, there is limited research concerning the influence of stress and relaxation on central pain modulation in patients with chronic WAD and FM. The present study aims to investigate the effects of acute cognitive stress and relaxation on central pain modulation in chronic WAD and FM patients compared to healthy individuals. A randomized crossover design was employed. The present study took place at the University of Brussels, the University Hospital Brussels, and the University of Antwerp. Fifty-nine participants (16 chronic WAD patients, 21 FM, 22 pain-free controls) were enrolled and subjected to various pain measurements. Temporal summation (TS) of pain and conditioned pain modulation (CPM) were evaluated. Subsequently, participants were randomly allocated to either a group that received progressive relaxation therapy or a group that performed a battery of cognitive tests (= cognitive stressor). Afterwards, all pain measurements were repeated. One week later participant groups were switched. A significant difference was found between the groups in the change in TS in response to relaxation (P = 0.008) and cognitive stress (P = 0.003). TS decreased in response to relaxation and cognitive stress in chronic WAD patients and controls. In contrast, TS increased after both interventions in FM patients. CPM efficacy decreased in all 3 groups in response to relaxation (P = 0.002) and cognitive stress (P = 0.001). The obtained results only apply for a single session of muscle relaxation therapy and cognitive stress, whereby no conclusions can be made for effects on pain perception and modulation of chronic cognitive stress and long-term relaxation therapies. A single relaxation session as well as cognitive stress may have negative acute effects on pain modulation in patients with FM, while cognitive stress and relaxation did not worsen bottom-up sensitization in chronic WAD patients and healthy persons. However, endogenous pain inhibition, assessed using a CPM paradigm, worsened in chronic WAD and FM patients, as well as in healthy people following both interventions.


Phylo-comparative analyses reveal the dual role of drift and selection in reproductive character displacement.
When incipient species meet in secondary contact, natural selection can rapidly reduce costly reproductive interactions by directly targeting reproductive traits. This process, called reproductive character displacement (RCD), leaves a characteristic pattern of geographic variation where divergence of traits between species is greater in sympatry than allopatry. However, because other forces can also cause similar patterns, care must be given in separating pattern from process. Here we show how the phylo-comparative method together with genomic data can be used to evaluate evolutionary processes at the population level in closely related species. Using this framework, we test the role of RCD in speciation of two cricket species endemic to Anatolian mountains by quantifying patterns of character displacement, rates of evolution and adaptive divergence. Our results show differing patterns of character displacement between species for reproductive vs. non-reproductive characters and strong patterns of asymmetric divergence. We demonstrate diversification results from rapid divergence of reproductive traits towards multiple optima under the dual influence of strong drift and selection. These results present the first solid evidence for RCD in Anatolian mountains, quantify the amount of drift and selection necessary for RCD to lead to speciation, and demonstrate the utility of phylo-comparative methods for quantifying evolutionary parameters at the population level.


Genomic Integration of HHV-6 Mimicking Viral Reactivation after Autologous Stem Cell Transplantation.
The monitoring of Human Herpesvirus 6 (HHV-6) after allogeneic stem cell transplantation has proven to be useful in preventing life-threatening complications; however, the pathogenic role of HHV-6 after autologous transplantation is not well-characterized, although viral reactivation might be responsible for significant complications even after this type of transplant. Here we report, for the first time to our knowledge, the case of a patient with chromosomally integrated HHV-6 (ciHHV-6), presenting with high titers of HHV-6 DNA copies after autologous transplantation, mimicking HHV-6 reactivation. The presence of viral DNA in the follicle bulb confirmed the ciHHV-6 and allowed for the discontinuation of the antiviral treatment. Due to the increasing awareness of HHV-6 potential pathogenicity and the fact that ciHHV-6 is expected in 1-2% of the population, such a case might be helpful in recognizing ci HHV-6, thus avoiding unnecessary and potentially toxic antiviral therapy once the viral genomic integration is confirmed.


Lymphocytic esophagitis: a chronic or recurring pattern of esophagitis resembling allergic contact dermatitis.
Lymphocytic esophagitis (LE) is characterized by intraepithelial lymphocytes (IELs) and spongiosis, resembling contact dermatitis. LE has been defined as high numbers of IELs and no or rare granulocytes and was found in young patients and in association with Crohn disease (CD). We reviewed the medical records of 42 LE cases. Cases were divided into severe (IELs in interpapillary and peripapillary fields) and mild (IELs in peripapillary fields) LE. The control group included specimens from 34 consecutive esophageal biopsy cases. Mean ages were similar (LE, 44 years; control subjects, 43 years). CD was present in 5 LE cases (12%) and 1 control case, an insignificant difference. Of patients with LE, 14 (33%) had an allergy; 11 (26%), gastroesophageal reflux disease (GERD); 4 (10%), Helicobacter pylori gastritis; and 18 (43%), dysphagia. No differences were found in clinical features between LE and control cases, except GERD was less common in severe LE (6/30 [20%]) than in control cases (17 [50%]). No patient with LE had celiac disease. No medications were common among LE cases. Patients with LE are statistically no more likely than control subjects to have CD. We found no association between LE and any clinical condition or symptom. Based on sequential biopsies in 7 patients, LE seems to be a chronic disease.


Lipopolysaccharide-mediated inflammatory priming potentiates painful post-traumatic trigeminal neuropathy.
We explored the molecular and behavioral effects of a perineural Lipopolysaccharide (LPS)-mediated inflammatory priming on the development and maintenance of painful post-traumatic trigeminal neuropathy (PPTTN) following infra-orbital nerve chronic constriction injury (CCI-IoN) in rats. Rats were pretreated with repetitive perineural injections in the vicinity of the IoN of either LPS or vehicle (Vhcl) before being submitted to CCI-IoN. Orofacial pain-like behaviors (response to Von Frey Filament testing and spontaneous isolated face grooming) were measured during the period of LPS injections (three weeks) and following CCI-IoN surgery (two weeks). Local LPS administration induced an early pain-like behavior (i.e. an increase in spontaneous pain [SP] or mechanical static allodynia [MSA]) in both conditions, and following CCI-IoN, MSA and SP developed earlier and more severely in LPS-pretreated rats than in the control group. Ipsilateral increases of key neuropathic pain mRNA markers in the IoN parenchyma, trigeminal ganglia (TG) and spinal trigeminal nucleus caudalis (Sp5C) were observed in CCI-IoN injured animals as compared to controls. Although no significant molecular differences could be observed within the IoN parenchyma between LPS and Vhcl-pretreated animals, a significant increase of key inflammatory cytokine Interleukin 1 beta (IL - 1β) could be found in the TG of LPS-pretreated CCI-injured animals versus controls. Finally, a higher increase of inducible nitric oxide synthase (iNOS) in ipsilateral Sp5C of LPS-pretreated animals was observed as compared to Sp5C of Vhcl-pretreated animals. These results suggest a key role of inflammatory priming in the development and maintenance of PPTTN implicating IL-1β/iNOS-dependent central sensitization mechanisms.


Evaluation of various HILIC materials for the fast separation of polar compounds.
In recent years, numerous works have been reported on hydrophilic interaction chromatography (HILIC) columns, but there is a growing demand for fast separations with improved resolution. Such analyses can only be obtained with the new generation of columns and instrumentation. In the present study, HILIC columns packed with porous sub-2 microm particles or with superficially porous particles of 2.7 microm were evaluated. A set of 15 compounds with diverse physicochemical properties was selected. The aim of this study was to compare the chromatographic behavior of three selected columns. Concerning kinetic performance, the fused-core column offers a backpressure two times lower than the sub-2-microm particle columns. However, these superficially porous particles also generated a 30% lower efficiency. The complex mechanism of HILIC was also investigated on bare silica columns, confirming that the mechanism is a mixture of partitioning, adsorption and ion exchange in different proportions according to the nature of the analytes, the composition of the mobile phase and the characteristics of the analytical support. Finally, a rapid separation of three drugs and their corresponding metabolites was carried out. The analysis time was reduced to less than 4 min while maintaining acceptable backpressure and sufficient resolution.


Ethical issues surrounding interprofessional collaboration.
Global healthcare and health disciplines' education policy and position statements contain mandates for education that incorporates interprofessional collaboration. One of the popular educational technologies involves virtual simulation as tools for educating future generations of healthcare professionals. This article discusses potential ethical implications for interprofessional collaboration from a humanbecoming lens of understanding.


Cerebral effects of isovolemic hemodilution with a hypertonic saline solution.
In view of a growing interest in the resuscitative use of hypertonic saline solutions, the authors have examined the cerebral effects of isovolemic hemodilution carried out over 1 hour (hematocrit decreased from 40% to 20%, stable arterial and right arterial pressures), using a hypertonic lactated Ringer's solution (HT-LR: Na+ 252 mEq/liter, osmolality 480 mOsm/liter). Experiments were carried out in anesthetized ventilated rabbits. Measured variables included cerebral blood flow (using the H2 clearance method), intracranial pressure (ICP), the electroencephalogram, spinal cord and skeletal muscle water content (%H2O), and the specific gravity of small (10- to 30-mg) tissue samples taken from different areas of the left hemisphere (including the cortex, thalamus, internal capsule, and hippocampus). The changes produced by HT-LR were compared with those seen in both undiluted control animals and in rabbits hemodiluted with normal saline (Na+ 155 mEq/liter, osmolality 310 mOsm/liter). The results demonstrate that hemodilution with HT-LR leads to the expected increases in serum Na+ and osmolality (158 +/- 6 mEq/liter and 320 +/- 5 mOsm/kg, respectively, mean +/- standard deviation) and that these were accompanied by reductions in the %H2O of all cerebral and extracerebral tissues, increases in the specific gravity of all tissue regions studied, and a decrease in ICP (1.9 +/- 0.7 mm Hg). By contrast, rabbits with hemodilution by normal saline showed no changes in either %H2O or specific gravity, but had significant increases in ICP (3.3 +/- 1.3 mm Hg). Cerebral blood flow increased in all animals hemodiluted with either HT-LR or normal saline by a combined average of +29 ml/100 gm/min. Although these studies were performed in neurologically normal animals, the combination of cerebral changes seen with HT-LR (cerebral dehydration, less peripheral edema, decreased ICP but with increased cerebral blood flow) suggests that this approach may have some advantages over the use of isotonic fluids, and may have some utility in the resuscitation of head-injured patients.


Enteral feeding practices in very preterm infants: an international survey.
To evaluate enteral feeding practices in neonatal units in different countries and on different continents. A web-based survey of 127 tertiary neonatal intensive care units in Australia, Canada, Denmark, Ireland, New Zealand, Norway, Sweden and the UK. 124 units (98%) responded. 59 units (48%) had a breast milk bank or access to donor human milk (Australia/New Zealand 2/27, Canada 6/29, Scandinavia 20/20 and UK/Ireland 31/48). The proportion of units initiating enteral feeding within the first 24 h of life was: 43/124 (35%) if gestational age (GA) <25 weeks, 53/124 (43%) if GA 25-27 weeks and 88/124 (71%) if GA 28-31 weeks. In general, Scandinavian units introduced enteral feeds the earliest, followed by UK/Ireland. Continuous feeding was routinely used for infants below 28 weeks' gestation in almost half of the Scandinavian units and in approximately one sixth of units in UK/Ireland, but rarely in Australia/New Zealand and Canada. Minimal enteral feeding for 4-5 days was common in Canada, but rare in Scandinavia. Target enteral feeding volume in a 'stable' preterm infant was 140-160 ml/kg/day in most Canadian units and 161-180 ml/kg/day or higher in units in the other regions. There were also marked regional differences in criteria for use and timing when human milk fortifier was added. This study highlights areas of uncertainty and demonstrates marked variability in feeding practices. It provides valuable data for planning collaborative feeding trials to optimise outcome in preterm infants.


A new steroid-eluting epicardial lead: experience with atrial and ventricular implantation in the immature swine.
The first study with investigational steroid epicardial leads was carried out in mature canine with prototype leads. Because the demand for epicardial leads is highest in small infants and the prototype steroid-eluting lead has been redesigned, this study was carried out in immature swine to evaluate the newly designed lead. Six immature swine (2 at 5 weeks of age and 4 at 6 weeks) underwent epicardial implantation of four porous platinized tip leads: one steroid and one nonsteroid on the right atrium; one steroid and one nonsteroid on the right ventricle. At implantation, the lead terminals were connected to a percutaneous access device subcutaneously placed in the right lateral neck. This allowed chronic measurements by using an insulated needle connected with a cable to the pacing systems analyzer. Measurements were obtained at implantation and weekly for 3 weeks. Compared to the nonsteroid atrial leads, the steroid atrial leads had lower mean thresholds (P less than 0.01) at 1, 2, and 3 weeks after implantation. The mean threshold values from ventricular steroid leads were also lower and exhibited little increase from implant with the highest mean threshold of only 1.02 V, however, a statistically significant difference between steroid and nonsteroid was not reached. This newly designed steroid epicardial lead provided favorable results for continual human clinical study.


Bcl-xL is an antiapoptotic regulator for postnatal CNS neurons.
Bcl-xL is a death-inhibiting member of the Bcl-2/Ced9 family of proteins which either promote or inhibit apoptosis. Gene targeting has revealed that Bcl-xL is required for neuronal survival during brain development; however, Bcl-xL knock-out mice do not survive past embryonic day 13.5, precluding an analysis of Bcl-xL function at later stages of development. Bcl-xL expression is maintained at a high level postnatally in the CNS, suggesting that it may also regulate neuron survival in the postnatal period. To explore functions of Bcl-xL related to neuron survival in postnatal life, we generated transgenic mice overexpressing human Bcl-xL under the control of a pan-neuronal promoter. A line that showed strong overexpression in brainstem and a line that showed overexpression in hippocampus and cortex were chosen for analysis. We asked whether overexpression of Bcl-xL influences neuronal survival in the postnatal period by studying two injury paradigms that result in massive neuronal apoptosis. In the standard neonatal facial axotomy paradigm, Bcl-xL overexpression had substantial effects, with survival of 65% of the motor neurons 7 d after axotomy, as opposed to only 15% in nontransgenic littermates. To investigate whether Bcl-xL regulates survival of CNS neurons in the forebrain, we used a hypoxia-ischemia paradigm in neonatal mice. We show here that hypoxia-ischemia leads to substantial apoptosis in the hippocampus and cortex of wild-type neonatal mice. Furthermore, we show that overexpression of Bcl-xL is neuroprotective in this paradigm. We conclude that levels of Bcl-xL in postnatal neurons may be a critical determinant of their susceptibility to apoptosis.


[Surgical treatment of severe forms of ischemic heart disease].
Over 400 operations of an indirect revascularization of the myocardium have been performed at the A.I. Bakulev institute of Cardiovascular Surgery of the USSR Academy of Medical Sciences. Since 1970, the direct method have been developed, predominantly those of aorto-coronary bypass. Careful examination of 709 patients was carried out, 445 of them were subjected to selective coronary angiography, 108 were operated on. In 1974, 56 operations were undertaken, among them 36 aorto-coronary bypasses, in 6 of them with a preliminary endarterectomy from the coronary artery, 8 double bypasses, 6 procedures for acute myocardial infarction, 5 combined operations of aorto-coronary bypass and resections of cardiac aneurysms, and 15 resections of postinfarction aneurysms of the heart. Twelve patients died in the postoperative period, mainly due to acute cardiac insufficiency. The high figures of mortality are caused not only by the faults of the surgical procedures but also by the grave initial state of the patients (multiple coronary lesions large focal cardiosclerosis due to preceeding infarctions, high degree of initial cardiac insufficiency). The improvement of the results of surgery for the ischaemic heart disease will depend on the perfection of the surgical technique, on proper selection of the patients, and on the precise determination of the indications for such treatment.


Pain in multiple sclerosis: a clinical and instrumental approach.
Pain is a frequent and disabling symptom in multiple sclerosis (MS) patients. In this study we assess the frequency and intensity of pain, as well as its impact on the quality of life and activities of daily living, in a sample of MS patients. One hundred and twenty eight MS patients underwent a neurological examination, a structured interview designed to assess pain, and a Medical Outcome 36-item Short Form Health Survey. Functional status was assessed by means of the Barthel Index (BI) and Rivermead Mobility Index. We also assessed the presence of depression, by means of the Montgomery and Asberg Depression Rating Scale, and fatigue, by means of the Fatigue Severity Scale. An algometer was used to measure thermal and discomfort thresholds in all of the patients and a group of 61 age- and sex-matched healthy subjects. Pain was present in 61 patients. No differences were found between patients with and those without pain in disease duration, disease form or Expanded Disability Status Scale and its functional systems. Patients with pain had a lower vitality score (p = 0.008), mental health score (p = 0.03) and physical (p < 0.001) and mental composite scores (p = 0.01) than patients without pain. Furthermore, there was a significant difference between patients with and those without pain in the BI (p = 0.04). Both thermal and discomfort thresholds, as assessed by means of the algometer, were statistically lower in MS patients than in controls, whereas no difference was observed between patients with and those without pain. There was a statistically significant improvement in the thermal threshold in patients with pain who were treated pharmacologically when compared with those who were not treated (p = 0.049). The results of this study provide further evidence of the negative impact that the presence of pain has on both the quality of life and activities of daily living in MS patients. The lower thermal and discomfort thresholds observed in our MS patients, compared with controls, may represent a predisposition to develop pain during the course of the disease.


The Effect of Workers' Compensation on Outcome Measurement Methods after Upper Extremity Surgery: A Systematic Review and Meta-Analysis.
Patients who receive workers' compensation often display worse surgical results, such as prolonged pain or reduced functional ability. The outcomes of surgery can be assessed using a variety of surveys, assessments, and measurements. It is unknown whether the confounding effect differs based on how results are measured. The aim of this study was to determine whether these variations exist. A search of full-length articles published between January 1, 1995, and December 31, 2015, was conducted using 3 online databases. The authors performed a systematic review and meta-analysis using unique inclusion criteria for each. A total of 101 articles were included in the systematic review; 62 of them were retained for the meta-analysis. In the systematic review, 70 percent of studies found that patients receiving workers' compensation had significantly worse postoperative results than uncompensated patients, whereas only 42 percent of studies that measured preoperative versus postoperative improvement were influenced by workers' compensation. The meta-analysis found that uncompensated patients were more likely to experience improvement after surgery than patients receiving workers' compensation (summary OR, 3.17; 95 percent CI, 2.47 to 4.08). A subgroup analysis demonstrated that functional measures, such as grip strength or nonunion, were least affected by workers' compensation, compared with other outcome measures such as patient-reported outcomes questionnaires or time off work. Potential bias introduced by workers' compensation can be mitigated by evaluating surgical treatment of work-related upper extremity disorders using preoperative versus postoperative improvement or functional measures.


Chronic lymphocytic leukemia in (Richter's) transformation.
Non-Hodgkin's lymphomas (NHL), Hodgkin's Disease (HD), and multiple myeloma (MM) develop as second malignancies in approximately 3%, 0.5%, and 0.1%, respectively, of chronic lymphocytic leukemia (CLL) patients. The true incidence may be higher, as postmortem examination is not performed in most patients, thus underestimating occult disease. As originally described, the term Richter's syndrome (RS) refers to the development of aggressive NHL during the course of CLL. The onset of RS is usually abrupt with clinical deterioration as manifested by worsening systemic symptoms, rapid tumor growth, and/or extranodal involvement. Diagnosis requires tissue biopsy. The NHL is usually diffuse large cell (LCL) or its immunoblastic variant. It is resistant to current therapies, and the median survival of patients who develop RS is approximately 6 months. The precise relationship between the cells of origin of CLL and LCL in RS patients is unknown with data suggesting either common (60%) or distinct (40%) clonal evolutions for these malignancies in different patients. Gene rearrangement studies and isotype analysis suggest that CLL and LCL in RS patients frequently share identical clonal origins. Purine analog therapy of CLL patients does not seem to affect the incidence or clinical behavior of RS. Despite increasing rates of achievement of complete remission in CLL associated with fludarabine-based regimens, RS still occurs, warranting continued surveillance of all CLL patients regardless of disease status. HD and MM in CLL patients are usually advanced at the time of presentation and have poor response and survival rates.


Rhodamine 101-graphene oxide composites in aqueous solution: the fluorescence quenching process of rhodamine 101.
The interaction of rhodamine 101 (Rh101) with graphene oxide (GO) in aqueous dispersion was examined using advanced spectroscopic techniques. Rh101-GO composites in water were easily prepared by mixing an aqueous solution of both components since GO sheets interacted with the cationic dyes via π-π and electrostatic cooperative interactions. In the composites, the fluorescence of Rh101, which was a well-known laser dye with a high fluorescence quantum yield, could be efficiently quenched by GO. The quenching mechanism of Rh101 by GO sheets was evaluated by the Stern-Volmer (SV) equation and the time-resolved fluorescence studies. The results revealed that the fluorescence quenching of Rh101 by GO in the aqueous dispersion is due to the static quenching mechanism. The formation of the Rh101-GO composites at various pH values was spectroscopically monitored, and the spectroscopic results revealed that the composites were formed at the pH values studied except in the strong acidic media (pH ≈ 2). The interaction of Rh101 with GO in aqueous solution was spectroscopically followed in the presence of SDS (sodium dodecyl sulphate) at the surfactant concentrations above and below the CMC (critical micelle concentration). The fluorescence studies revealed that the fluorescence of Rh101 in the aqueous solution remarkably increased at the surfactant concentration forming the micelle of SDS.